History
# Registration date Revision Id
5 2024-01-22, 1402/11/02 292763
4 2023-11-08, 1402/08/17 287340
3 2023-09-27, 1402/07/05 281898
2 2022-06-11, 1401/03/21 229581
1 2021-07-12, 1400/04/21 189969
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  • Protocol summary

    Inclusion criteria: age 20-40 years, BMI less than 25 kg/m2, good response to previous ovulation stimulation, at least two embryos with good grade in the current cycle, normal uterus. Inclusion criteria: Women with submucosal myoma, congenital anomalies, intramural and subserosal myoma, endometrioma, and hydrosalpinx. Less than 2 available embryos, use of specific drugs. history of diabetes, thyroid disease, or any endocrine, genetic, infection, or autoimmune disorder. Severe male factor infertility, previous uterine or ovarian surgery, abnormal results of pre-implantation genetic testing (PGT)
    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
    معیار ورود: سن 20 تا 40 سال،BMI کمتر از 25 کیلوگرم بر متر مربع، پاسخ خوب به تحریک تخمک گذاری قبلی، حداقل دو جنین با گرید خوب در سیکل فعلی، رحم نرمال. معیار عدم ورود: زنان مبتلا به میوم ساب موکوزال، ناهنجاری های مادرزادی، میوم اینترامورال و ساب سروزال، آندومتریوما، هیدروسالپنکس. تعداد جنین در دسترس کمتر از 2 عدد در سیکل فعلی، مصرف داروي خاص. سابقه دیابت، بیماری تیروئید، هر گونه اختلال غدد درون ریز، ژنتیکی، عفونت یا خودایمنی، ناباروری شدید با عامل مردانه،جراحی رحم یا تخمدان قبلی، نتایج غیرطبیعی آزمایش ژنتیکی قبل از لانه گزینی (PGT)
    معیار ورود: زنان با شکست مکرر در لانه گزینی با علت نامشخص(uRIF)، سن 20 تا 40 سال،شاخص توده بدنی (BMI) کمتر از 25 ، پاسخ خوب به تحریک تخمک گذاری قبلی، حداقل دو جنین با گرید خوب در سیکل فعلی، رحم نرمال.معیار عدم ورود: ضخامت آندومتر کمتر از 7 میلی متر،ناهنجاری های مادرزادی، میوم، آندومتریوما، چسبندگی ها، هیدروسالپنکس، جراحی رحم یا تخمدان قبلی، ناباروری شدید با عامل مردانه، تعداد جنین در دسترس کمتر از 2 در سیکل فعلی، دیابت، بیماری تیروئید، هر گونه اختلال غدد درون ریز، ژنتیکی، عفونت یا خودایمنی
  • General information

    2023-01-21, 1401/11/01
    2022-04-15, 1401/01/26
    In the previous report, we had reported the entry of the last person in the study as the end of sampling, but according to the evaluation of the rate of clinical pregnancy (5 weeks after embryo transfer) and live birth (9 months of pregnancy) in people participating in the project, so The final completion time increases. In addition to the clinical pregnancy criteria, the embryo implantation rate was also investigated in the study as one of the secondary objectives. The time of scraping and sampling has not changed in terms of time, but it is better to specify it as a time frame. On the other hand, the inclusion and exclusion criteria of people in the study were applied more strictly. Also, in addition to angiogenic factors, anti-angiogenic factors were also evaluated in the study.
    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.
    در گزارش قبلی ورود آخرین فرد در مطالعه را به عنوان زمان پایان نمونه گیری گزارش کرده بودیم اما با توجه به بررسی میزان حاملگی بالینی (5 هفته بعد از انتقال جنین)و تولد زنده (9 ماه حاملگی) در افراد شرکت کننده در طرح، زمان نهایی پایان کار افزایش می یابد. علاوه بر معیار حاملگی بالینی میزان لانه گزینی جنین نیز در مطالعه جز اهداف ثانویه مورد بررسی قرار گرفت.زمان انجام خراش و نمونه گیری نیز از نظرز زمانی هیچ تغییری نکرده است ولی بهتر است به صورت بازه زمانی مشخص گردد. از طرفی معیارهای ورود و خروج افراد در مطالعه سختگیرانه تر اعمال گردید. هم چنین علاوه بر فاکتورهای آنژیوژنیک فاکتورهای آنتی آنژیوژنیک نیز در مطالعه ارزیابی گردید.
    طبق گزارش قبلی تاریخ پایان بیمارگیری تحقق یافته همان تاریخ 1401/01/26 صحیح می باشد و تنها تاریخ اتمام کارآزمایی با توجه به بررسی میزان حاملگی بالینی (5 هفته بعد از انتقال جنین) و تولد زنده (9 ماه حاملگی) در افراد شرکت کننده در طرح، افزایش یافته است. علاوه بر این با توجه به ارزیابی متغیرهای ثانویه میزان لانه گزینی و حاملگی بالینی، متغیرهای مرتبط با آن ها که مورد ارزیابی قرار می گیرند اضافه می گردند. کمی تغییر نگارشی در نحوه بیان معیارهای ورود و خروج نیز انجام شده است.
    Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors expression in unexplained repeated implantation failure (RIF) patients
    Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors expression in unexplained repeated implantation failure (uRIF) patients
    بررسی تاثیر خراش اندومتر بر میزان بیان فاکتورهای رشد آنژیوژنیک و آنتی آنژیوژنیک در نمونه اندومتر بیماران دچار شکست مکرر لانه گزینی با علت نامشخص
    بررسی تاثیر خراش اندومتر بر میزان بیان فاکتورهای رشد آنژیوژنیک و آنتی آنژیوژنیک در نمونه اندومتر بیماران دچار شکست مکرر لانه گزینی با علت نامشخص(uRIF)
    Infertile women with unexplained repeated implantation failure who have implantation failure after three or more cycles of embryo transfer (ET) using high-quality transferred embryos
    BMI less than 25 kg/m2
    Age range of 20 to 40 years
    Good response to stimulation of previous ovulation
    Having at least two embryos with good grade
    The uterus is normal on hysterosalpingography examination or ultrasound or hysteroscopy
    Patient consent is required to participate in the study and to complete the consent form
    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
    زنان نابارور با شکست مکرر در لانه گزینی با علت نامشخص که پس از سه یا چند چرخه انتقال جنین (ET) با استفاده از جنین های انتقال یافته با کیفیت بالا، شکست در لانه گزینی داشته باشند
    BMI کمتر از 25 کیلوگرم بر متر مربع
    محدوده سنی 20 تا 40 سال
    بیماران به تحریک تخمک گذاری قبلی خوب پاسخ داده اند
    بیماران حداقل دو جنین با گرید خوب داشته باشند
    رحم در بررسی هیستروسالپنگوگرافی یا سونوگرافی یا هیستروسکوپی نرمال باشد
    رضایت بیمار جهت شرکت در مطالعه و پر نمودن رضایت نامه ضروری می باشد
    زنان نابارور با شکست مکرر در لانه گزینی (با علت نامشخص که موجب شکست مکرر در آن ها می شود) که پس از سه یا چند چرخه انتقال جنین با استفاده از جنین های انتقال یافته با کیفیت بالا (حداقل یک انتقال جنین بلاستوسیست داشته اند) شکست داشته باشند
    سن 20 تا 40 سال
    شاخص توده بدنی (BMI) کمتر از 25 کیلوگرم بر متر مربع
    پاسخ خوب به تحریک تخمک گذاری قبلی
    بیماران حداقل دو جنین با گرید خوب داشته باشند
    رحم در بررسی هیستروسالپنگوگرافی (HSG) یا هیستروسکوپی نرمال باشد
    رضایت شرکت کننده برای شرکت در مطالعه و تکمیل فرم رضایت نامه الزامی می باشد
    The thickness of the endometrium on the day of Human chorionic gonadotropin hormone injection is less than 7 mm.
    Women with sub mucosal myoma
    Women with congenital anomalies, intramural and subserosal myomas( larger than 4 cm)
    Women with endometrioma larger than or equal to 3 cm
    Women with hydrosalpinx
    If the number of available embryos is less than 2 in the current cycle
    Women with endometrial tuberculosis and those undergoing tuberculosis treatment
    Patients with any specific medication
    Patients who have a history of diabetes, thyroid disease, any endocrine, genetic, infection or autoimmune disorder
    Failure to return the patient to prepare an endometrial sample
    Inability to obtain tissue samples from patients due to severe pain or the possibility of infection
    Severe male factor infertility (sperm extraction from the testis, sperm freezing, sperm DNA fragmentation index equal to or above 16%)
    Have previous uterine or ovarian surgery
    Abnormal Pre-implantation Genetic Test (PGT) Results
    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
    ضخامت آندومتردر روز تزریق هورمون گنادوتروپین جفتی انسان (HCG)کمتر از 7 میلی متر باشد.
    زنان مبتلا به میوم ساب موکوزال
    زنان با ناهنجاری های مادرزادی، میوم اینترامورال و ساب سروزال (بیشتر از 4 سانتی متر)
    زنان مبتلا به آندومتریوما بزرگتر یا مساوی 3 سانتی متر
    زنان مبتلا به هیدروسالپنکس
    اگر تعداد جنین در دسترس کمتر از 2 عدد در سیکل فعلی باشد.
    زنان مبتلا به سل اندومتر و کسانیکه تحت درمان سل هستند.
    بيمارانی که هر گونه مصرف داروي خاص داشته باشند.
    بیمارانی که سابقه دیابت، بیماری تیروئید، هر گونه اختلال غدد درون ریز، ژنتیکی، عفونت یا خودایمنی داشته باشند
    عدم مراجعه مجدد بیمار جهت تهیه نمونه آندومتر
    عدم امکان تهیه نمونه بافتی از بیماران به دلیل درد شدید یا احتمال عفونت
    ناباروری شدید با عامل مردانه (استخراج اسپرم از بیضه، اسپرم فریز، شاخص شکست DNA اسپرم مساوی یا بالای 16% داشته باشند)
    جراحی رحم یا تخمدان قبلی داشته باشند
    نتایج غیرطبیعی آزمایش ژنتیکی قبل از لانه گزینی (PGT)
    ضخامت آندومتردر روز تزریق هورمون گنادوتروپین جفتی انسان کمتر از 7 میلی متر باشد
    زنان با ناهنجاری های مادرزادی، میوم اینترامورال و ساب سروزال (بیشتر از 5 سانتی متر)
    میوم ساب موکوزال
    زنان مبتلا به آندومتریوما بزرگتر یا مساوی 3 سانتی متر
    مبتلا به چسبندگی ها
    مبتلا به هیدروسالپنکس
    جراحی رحم یا تخمدان قبلی داشته باشند
    ناباروری شدید با عامل مردانه (استخراج اسپرم از بیضه، اسپرم فریز، شاخص شکست DNA اسپرم مساوی یا بالای 16% داشته باشند)
    اگر تعداد جنین در دسترس کمتر از 2 عدد در سیکل فعلی باشد
    زنان مبتلا به سل اندومتر و کسانیکه تحت درمان سل هستند
    سابقه دیابت، بیماری تیروئید، هر گونه اختلال غدد درون ریز، ژنتیکی، عفونت یا خودایمنی داشته باشند
    نتایج غیرطبیعی آزمایش ژنتیکی قبل از لانه گزینی (PGT)
    مصرف هر داروی خاص
    عدم مراجعه بیمار به تهیه نمونه آندومتر
    زنان با درد شدید در حین تهیه نمونه بافت و یا احتمال عفونت
  • Secondary outcomes

    #1
    Only once; 5 weeks after embryo transfer
    5 weeks after embryo transfer
    فقط یکبار؛ 5 هفته پس از انتقال جنین
    5 هفته پس از انتقال جنین
    Vaginal ultrasound (gestational sac observation and cardiac activity/fetal heartbeats)
    Vaginal ultrasonography (observing the gestational sac and fetal heart rate)
    سونوگرافی واژینال (مشاهده ساک حاملگی و فعالیت قلبی / ضربان قلب جنین)
    سونوگرافی واژینال (مشاهده ساک حاملگی و ضربان قلب جنین)
    #2
    empty
    Age
    empty
    سن
    empty
    At the time of entering the study
    empty
    در زمان ورود به مطالعه
    empty
    Based on the person's birth certificate and the information contained in the file
    empty
    بر اساس شناسنامه فرد و اطلاعات مندرج در پرونده
    #3
    empty
    Duration of infertility (years)
    empty
    مدت زمان ناباروری (سال)
    empty
    At the time of entering the study
    empty
    در زمان ورود به مطالعه
    empty
    According to the history taken by the infertility specialist at the time of filing the case (trying to get pregnant despite regular intercourse)
    empty
    طبق شرح حال اخذ شده توسط متخصص ناباروری در زمان تشکیل پرونده (تلاش جهت بارداری با وجود نزدیکی منظم)
    #4
    empty
    Body mass index
    empty
    شاخص توده بدنی
    empty
    At the time of entering the study
    empty
    در زمان ورود به مطالعه
    empty
    Weight divided by the square of height in meters
    empty
    وزن تقسیم بر مجذور قد به متر
    #5
    empty
    Luteinizing hormone (LH )
    empty
    هورمون لوتئینه کننده (LH)
    empty
    On the third day of menstruation
    empty
    در روز سوم قاعدگی
    empty
    LH titer in blood serum using ELISA method (IU/L)
    empty
    تیتر LH در سرم خون با استفاده از روش الایزا (واحد بین المللی بر لیتر)
    #6
    empty
    Follicle-Stimulating Hormone (FSH)
    empty
    هورمون تحریک کننده فولیکول (FSH)
    empty
    On the third day of menstruation
    empty
    در روز سوم قاعدگی
    empty
    FSH titer in blood serum using ELISA method (IU/L)
    empty
    تیتر FSH در سرم خون با استفاده از روش الایزا (واحد بین المللی بر لیتر)
    #7
    empty
    Anti Mullerian Hormone (AMH)
    empty
    هورمون آنتی مولرین (AMH)
    empty
    On the third day of menstruation
    empty
    در روز سوم قاعدگی
    empty
    AMH titer in blood serum using ELISA method (ng/ml)
    empty
    تیتر AMH در سرم خون با استفاده از روش الایزا (واحد نانوگرم بر میلی لیتر)
    #8
    empty
    Total dose of gonadotropin (IU)
    empty
    دوز کلی گنادوتروپین (واحد بین الملل)
    empty
    From ovarian stimulation to human chorionic gonadotropin (hCG) injection
    empty
    از شروع تحریک تخمدان تا تزریق هورمون گنادوتروپین جفتی انسان (hCG)
    empty
    The number of international units (IU) received during the ovarian stimulation cycle
    empty
    تعداد واحد بین الملل (IU) دریافت شده در طول سیکل تحریک تخمدان
    #9
    empty
    Duration of ovarian stimulation (day)
    empty
    مدت زمان تحریک تخمدان (روز)
    empty
    From the start of gonadotropin administration to human chorionic gonadotropin (hCG) injection
    empty
    از شروع تجویز گنادوتروپین تا تزریق گنادوتروپین جفتی انسان(hCG)
    empty
    According to the patient's monitoring ultrasound chart (number of days receiving the medicine)
    empty
    طبق چارت سونوگرافی مانیتورینگ بیمار (تعداد روز دریافت دارو)
    #10
    empty
    Number of retrieved oocytes
    empty
    تعداد تخمک‌های به‌دست آمده
    empty
    On the day of oocyte pick-up
    empty
    در روز تخمک‌کشی
    empty
    The number of retrieved oocytes reported in the embryology chart
    empty
    تعداد تخمک های به دست آمده گزارش شده در چارت جنین شناسی
    #11
    empty
    Metaphase II oocytes
    empty
    تخمک‌های متافاز II
    empty
    On the day of oocyte pick-up
    empty
    در روز تخمک‌کشی
    empty
    Based on the presence of the polar body reported by the embryologist
    empty
    براساس وجود گویچه قطبی گزارش شده توسط جنین شناس
    #12
    empty
    Number of embryos
    empty
    تعداد جنین
    empty
    Three or five days after oocyte pick-up
    empty
    سه یا پنج روز پس از تخمک‌کشی
    empty
    The number of cleavage embryos reported by the embryologist
    empty
    تعداد جنین‌های تسهیم شده گزارش شده توسط جنین شناس
    #13
    empty
    Embryo transfer cancelation
    empty
    انتقال جنین کنسل شده
    empty
    Three or five days after oocyte pick-up
    empty
    سه یا پنج روز پس از تخمک‌کشی
    empty
    Participants with no embryo transfer
    empty
    شرکت کنندگان با عدم انتقال جنین
    #14
    empty
    Chemical pregnancy rate/Embryo transfer
    empty
    حاملگی شیمیایی به ازای انتقال جنین
    empty
    2 weeks after embryo transfer
    empty
    2هفته بعد از انتقال جنین
    empty
    Beta human chorionic gonadotropin (beta hCG) titer in blood serum by ELISA method
    empty
    تیتر هورمون بتا گنادوتروپین انسانی در سرم خون با روش الایزا
    #15
    empty
    Blighted ovum/Embryo transfer
    empty
    حاملگی پوچ به ازای انتقال جنین
    empty
    5 weeks after embryo transfer
    empty
    5 هفته بعد از انتقال جنین
    empty
    Absence of fetus in gestational sac according to ultrasound report
    empty
    عدم وجود جنین در ساک حاملگی طبق گزارش سونوگرافی
    #16
    empty
    Ectopic pregnancy/Embryo transfer
    empty
    حاملگی خارج از رحم به ازای انتقال جنین
    empty
    5 weeks after embryo transfer
    empty
    5 هفته بعد از انتقال جنین
    empty
    According to the ultrasound report, there is a gestational sac outside the uterus with a positive Beta hCG titer
    empty
    طبق گزارش سونوگرافی مبنی بر وجود ساک حاملگی در خارج از رحم با وجود تیتر Beta hCG مثبت
    #17
    empty
    Miscarriage rate/Embryo transfer
    empty
    نرخ سقط به ازای سیکل انتقال جنین
    empty
    Pregnancy loss before 20 weeks
    empty
    از دست دادن حاملگی قبل از هفته 20
    empty
    Excretion of pregnancy remnants with vaginal bleeding (absence of heartbeat according to ultrasound report)
    empty
    دفع بقایای حاملگی همراه با خونریزی واژینال (عدم ضربان قلب طبق گزارش سونوگرافی)
    #18
    empty
    Multiple Pregnancy (Twin)
    empty
    حاملگی چند قلویی (دو قلویی)
    empty
    5 weeks after embryo transfer
    empty
    5 هفته بعد از انتقال جنین
    empty
    Ultrasound report based on the number of gestational sacs with embryo
    empty
    گزارش سونوگرافی مبنی بر تعداد ساک حاملگی با جنین
    #19
    empty
    Live birth rate/Embryo transfer
    empty
    تولد زنده به ازای انتقال جنین
    empty
    Time of delivery
    empty
    زمان زایمان
    empty
    Birth of a live baby
    empty
    تولد نوزاد زنده
    #20
    empty
    Fertilization rate
    empty
    نرخ لقاح
    empty
    The day after the sperm injection
    empty
    روز بعد از تزریق اسپرم
    empty
    number of oocytes with two pronuclei (2PN) divided by the number of injected oocytes
    empty
    تعداد تخمک های با دو پیش هسته (2PN) تقسیم بر تعداد تخمک های تزریق شده

Protocol summary

Study aim
Determining the effect of endometrial scratching on the expression of angiogenic and anti-angiogenic growth factors
Design
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.
Settings and conduct
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.
Participants/Inclusion and exclusion criteria
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
Intervention groups
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.
Main outcome variables
Determination of angiogenic and anti-angiogenic growth factor gene expression in endometrial specimens in the intervention group compared with the control group

General information

Reason for update
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.
Acronym
IRCT registration information
IRCT registration number: IRCT20210316050723N1
Registration date: 2021-07-12, 1400/04/21
Registration timing: registered_while_recruiting

Last update: 2023-12-04, 1402/09/13
Update count: 4
Registration date
2021-07-12, 1400/04/21
Registrant information
Name
Samaneh Aghajanpour
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2356 2727
Email address
aghajanpour.s@iums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-06-20, 1400/03/30
Expected recruitment end date
2023-06-20, 1402/03/30
Actual recruitment start date
2021-06-20, 1400/03/30
Actual recruitment end date
2022-04-15, 1401/01/26
Trial completion date
2023-01-21, 1401/11/01
Scientific title
Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors expression in unexplained repeated implantation failure (uRIF) patients
Public title
Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors
Purpose
Other
Inclusion/Exclusion criteria
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
Age
From 20 years old to 40 years old
Gender
Female
Phase
2
Groups that have been masked
  • Participant
  • Investigator
Sample size
Target sample size: 20
Actual sample size reached: 20
Randomization (investigator's opinion)
Randomized
Randomization description
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.
Blinding (investigator's opinion)
Double blinded
Blinding description
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).
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Research Ethics Committees of school of medicine
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Approval date
2021-06-12, 1400/03/22
Ethics committee reference number
IR.IUMS.FMD.REC.1400.147

Health conditions studied

1

Description of health condition studied
Unexplained repeated implantation failure (uRIF)
ICD-10 code
N97.9
ICD-10 code description
Female infertility, unspecified

Primary outcomes

1

Description
Evaluation of gene expression
Timepoint
In the endometrial sample obtained in the luteal phase during days 19-23
Method of measurement
Using PCR Array method and based on the copy number

Secondary outcomes

1

Description
Clinical pregnancy
Timepoint
5 weeks after embryo transfer
Method of measurement
Vaginal ultrasonography (observing the gestational sac and fetal heart rate)

2

Description
Implantation
Timepoint
5 weeks after embryo transfer
Method of measurement
The number of observed sacs divided by the number of transferred embryos

3

Description
Age
Timepoint
At the time of entering the study
Method of measurement
Based on the person's birth certificate and the information contained in the file

4

Description
Duration of infertility (years)
Timepoint
At the time of entering the study
Method of measurement
According to the history taken by the infertility specialist at the time of filing the case (trying to get pregnant despite regular intercourse)

5

Description
Body mass index
Timepoint
At the time of entering the study
Method of measurement
Weight divided by the square of height in meters

6

Description
Luteinizing hormone (LH )
Timepoint
On the third day of menstruation
Method of measurement
LH titer in blood serum using ELISA method (IU/L)

7

Description
Follicle-Stimulating Hormone (FSH)
Timepoint
On the third day of menstruation
Method of measurement
FSH titer in blood serum using ELISA method (IU/L)

8

Description
Anti Mullerian Hormone (AMH)
Timepoint
On the third day of menstruation
Method of measurement
AMH titer in blood serum using ELISA method (ng/ml)

9

Description
Total dose of gonadotropin (IU)
Timepoint
From ovarian stimulation to human chorionic gonadotropin (hCG) injection
Method of measurement
The number of international units (IU) received during the ovarian stimulation cycle

10

Description
Duration of ovarian stimulation (day)
Timepoint
From the start of gonadotropin administration to human chorionic gonadotropin (hCG) injection
Method of measurement
According to the patient's monitoring ultrasound chart (number of days receiving the medicine)

11

Description
Number of retrieved oocytes
Timepoint
On the day of oocyte pick-up
Method of measurement
The number of retrieved oocytes reported in the embryology chart

12

Description
Metaphase II oocytes
Timepoint
On the day of oocyte pick-up
Method of measurement
Based on the presence of the polar body reported by the embryologist

13

Description
Number of embryos
Timepoint
Three or five days after oocyte pick-up
Method of measurement
The number of cleavage embryos reported by the embryologist

14

Description
Embryo transfer cancelation
Timepoint
Three or five days after oocyte pick-up
Method of measurement
Participants with no embryo transfer

15

Description
Chemical pregnancy rate/Embryo transfer
Timepoint
2 weeks after embryo transfer
Method of measurement
Beta human chorionic gonadotropin (beta hCG) titer in blood serum by ELISA method

16

Description
Blighted ovum/Embryo transfer
Timepoint
5 weeks after embryo transfer
Method of measurement
Absence of fetus in gestational sac according to ultrasound report

17

Description
Ectopic pregnancy/Embryo transfer
Timepoint
5 weeks after embryo transfer
Method of measurement
According to the ultrasound report, there is a gestational sac outside the uterus with a positive Beta hCG titer

18

Description
Miscarriage rate/Embryo transfer
Timepoint
Pregnancy loss before 20 weeks
Method of measurement
Excretion of pregnancy remnants with vaginal bleeding (absence of heartbeat according to ultrasound report)

19

Description
Multiple Pregnancy (Twin)
Timepoint
5 weeks after embryo transfer
Method of measurement
Ultrasound report based on the number of gestational sacs with embryo

20

Description
Live birth rate/Embryo transfer
Timepoint
Time of delivery
Method of measurement
Birth of a live baby

21

Description
Fertilization rate
Timepoint
The day after the sperm injection
Method of measurement
number of oocytes with two pronuclei (2PN) divided by the number of injected oocytes

Intervention groups

1

Description
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.
Category
Treatment - Other

2

Description
Control group: In the control group endometrial sampling will be done only in the luteal phase of the cycle preceding the embryo transfer cycle.
Category
Treatment - Other

Recruitment centers

1

Recruitment center
Name of recruitment center
Laleh Hospital
Full name of responsible person
Mehrdad Bakhtiyari
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Phone
+98 21 8670 4567
Email
Mehr_bakhtiyari@yahoo.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Mehrdad Bakhtiyari
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Phone
+98 21 8670 4567
Email
Mehr_bakhtiyari@yahoo.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Iran 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
Iran University of Medical Sciences
Full name of responsible person
Mehrdad Bakhtiyari
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Phone
+98 21 8670 4567
Email
mehr_bakhtiyari@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Mehrdad Bakhtiyari
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Phone
+98 21 8670 4567
Email
Mehr_bakhtiyari@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Mehrdad Bakhtiyari
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Tehran, Hemmat Highway next to Milad Tower, Iran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Phone
+98 21 8670 4567
Email
Mehr_bakhtiyari@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
Yes - There is 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
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
Clinical study report (published article)
When the data will become available and for how long
After the publication of the article
To whom data/document is available
Available to the public
Under which criteria data/document could be used
Scientific use by citing the source
From where data/document is obtainable
Dr. Mehrdad Bakhtiyari
What processes are involved for a request to access data/document
Request via e-mail
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