History
# Registration date Revision Id
5 2019-12-31, 1398/10/10 126723
4 2019-10-17, 1398/07/25 116770
3 2019-10-17, 1398/07/25 112243
2 2019-05-26, 1398/03/05 92781
1 2018-08-21, 1397/05/30 57042
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  • Protocol summary

    Improvement of ovarian function and fertility in patients with diminished ovarian reserve using stem cells derived from menstrual blood
    Improvement of ovarian function and fertility in patients with poor ovarian response using stem cells derived from menstrual blood
    افزایش عملکرد تخمدان و قدرت باروری در بیماران مبتلا به کاهش ذخیره تخمدان با استفاده از سلولهاي بنيادين مشتق شده از خون قاعدگي
    افزایش عملکرد تخمدان و قدرت باروری در بیماران مبتلا به نارسایی زودرس تخمدان با استفاده از سلولهاي بنيادين مشتق شده از خون قاعدگي
    Inclusion criteria: married woman;having previous cycles of ovarian stimulation with oocyte number of up to 3;anti-muller hormone below 1.1 ng/ml; antral follicle below5; up to 40 years Sperm analysis: 15 million per ml; normal morphology with the strict criterion of at least 2%;25% of sperm motility Conditions of non compliance: Thyroid dysfunction; Immune system disease; History of cancer; Hepatitis B and C and HIV; Endometriosis; Ovarian surgery; Diabetes; Liver dysfunction
    Inclusion criteria: married woman;having previous cycles of ovarian stimulation with oocyte number of up to 3;anti-muller hormone below 1.1 ng/ml; antral follicle below 5; up to 40 years Sperm analysis:more than 5 million per ml; normal morphology with the strict criterion of at least 1%;25% of sperm motility Exclusion criteria: Thyroid dysfunction; Immune system disease; History of cancer; Hepatitis B and C and HIV; Endometriosis; Ovarian surgery; Diabetes; Liver dysfunction
    شرایط ورود: زن متاهل؛داشتن سیکل قبلی تحریک تخمدان با تعداد تخمک تا 3 عدد؛هورمون ضد مولرین زیر 1.1 نانوگرم در هر میلی لیتر؛فولیکول آنترال زير 5عدد؛تا 40 سال آنالیز اسپرم همسر:15 میلیون در میلی لیتر،مورفولوژی نرمال با معیار استریکت حداقل 2%،25% اسپرم متحرک شرایط عدم ورود:نقص عملکرد تیروئید؛بیماری سیستم ایمنی؛سابقه سرطان؛مبتلا به هپاتیت بی و سی و ایدز؛آندومتریوز؛جراحی تخمدان؛دیابت؛اختلال تستهای کبدی
    شرایط ورود: زن متاهل؛داشتن سیکل قبلی تحریک تخمدان با تعداد تخمک تا 3 عدد؛هورمون ضد مولرین زیر 1.1 نانوگرم در هر میلی لیتر؛فولیکول آنترال زير 5عدد؛تا 40 سال آنالیز اسپرم همسر:حداقل 5 میلیون در میلی لیتر،مورفولوژی نرمال با معیار استریکت حداقل 1%،25% اسپرم متحرک شرایط عدم ورود:نقص عملکرد تیروئید؛بیماری سیستم ایمنی؛سابقه سرطان؛مبتلا به هپاتیت بی و سی و ایدز؛آندومتریوز؛جراحی تخمدان؛دیابت؛اختلال تستهای کبدی
    Number and volume of antral follicles The amount of FSH and LH AMH levels Ovarian volume Number of follicles in the treatment cycle The number of oocytes in the treatment cycle Quality of oocytes, the quality of the embryos Occurrence of pregnancy
    Number of antral follicles, Anti Mullerian hormone levels, Number and quality of oocytes in the treatment cycle, Number and quality of the embryos, Spontaneous pregnancy, Clinical pregnancy, Implantation rate, Live birth rate
    تعداد و حجم فولیکول های آنترال میزان هورمون محرک فولیکول و هورمون لوتئینه کننده میزان هورمون آنتی مولرین حجم تخمدان تعداد فولیکولها در سیکل درمانی تعداد تخمکهای بدست امده در سیکل درمانی کیفیت تخمکها، کیفیت جنینها وقوع بارداری
    تعداد فولیکول های آنترال، میزان هورمون آنتی مولرین ، تعداد و کیفیت تخمکهای بدست امده در سیکل درمانی، کیفیت و تعداد جنینها، بارداری خودبخودی، بارداری کلینیکال، میزان کاشت جنین، میزان تولد زنده
  • General information

    POR
    Not randomized
    Randomized
    N/A
    1-2
    30
    36
    Title correction based on ethical committee approval
    Methodology revision during project implementation
    تغییر عنوان بر اساس تاییدیه کمیته اخلاق
    اصلاح روش کار طی مراحل انجام پروژه
    Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with diminished ovarian reserve.
    Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with poor ovarian response.
    ارزیابی ایمنی و اثربخشی تزریق سلولهاي بنيادين مشتق شده از خون قاعدگی به داخل بافت تخمدان زنان مبتلا به کاهش شدید ذخیره تخمدانی
    ارزیابی ایمنی و اثربخشی تزریق سلولهاي بنيادين مشتق شده از خون قاعدگی به داخل بافت تخمدان زنان مبتلا به پاسخ ضعیف تخمدان ها.
    Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with diminished ovarian reserve
    Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with poor ovarian response.
    ارزیابی ایمنی و اثربخشی تزریق سلولهاي بنيادين مشتق شده از خون قاعدگی به داخل بافت تخمدان زنان مبتلا به کاهش شدید ذخیره تخمدانی
    ارزیابی ایمنی و اثربخشی تزریق سلولهاي بنيادين مشتق شده از خون قاعدگی به داخل بافت تخمدان زنان مبتلا به پاسخ ضعیف تخمدان ها.
    Got married woman
    Picked up less than 3 oocytes in last ovarian stimulation
    Anti mullerian hormone; less than 1.1 ng/ml
    Upper age limit: 40
    Spermogram: more than 15 million/ml, normal morphology more than 2%, sperm motility (A+B) more than 25%
    Anteral follicles: less than 5-7
    Got married woman
    Picked up less than 3 oocytes in last ovarian stimulation
    Anti mullerian hormone; less than 1.1 ng/ml
    Upper age limit: 40
    Spermogram: more than 5 million/ml, normal morphology more than 1, sperm motility (A+B) more than 25%
    Anteral follicles: less than 5-7
    زن متاهل
    داشتن سیکل قبلی تحریک تخمدان با تعداد تخمک برابر یا زیر 3 عدد
    مقدار هورمون ضد مولرین زیر 1.1 ng/ml
    برابر یا زیر 40 سال
    آنالیز اسپرم همسر (حداقل 15میلیون در میلی لیتر اسپرم با موفولوژی نرمال حدافل 2 درصد با معیار strict و اسپرمهای متحرک (A+B) بالای 25 درصد)
    تعداد فولیکول های آنترال زير 5 تا 7 عدد
    زن متاهل
    داشتن سیکل قبلی تحریک تخمدان با تعداد تخمک برابر یا زیر 3 عدد
    مقدار هورمون ضد مولرین زیر 1.1 ng/ml
    برابر یا زیر 40 سال
    آنالیز اسپرم همسر (حداقل 5 میلیون در میلی لیتر اسپرم با موفولوژی نرمال بیشتر 1 درصد با معیار strict و اسپرمهای متحرک (A+B) بالای 25 درصد)
    تعداد فولیکول های آنترال زير 5 تا 7 عدد
    Block randomization: In order to randomly assign 36 subjects in treatment group or control group, 6 blocks including 6 subjects each will be defined using "https://app.studyrandomizer.com". Treatment group and control group will be identified by codes A and B, respectively. In each block, number of treatment group and control group is equal and situation of each block with other block is different.
    تصادفی سازی بلوکی: به منظور اختصاص دهی تصادفی 36 فرد در گروه درمان یا گروه کنترل، 6 بلوك 6 تایی با استفاده از اپ استادی رندومایزر ایجاد می شود. گروه درمان و گروه کنترل به ترتیب با کد A و با کد B تعریف می شود. داخل هر بلوک توازن بین گروه اصلی و کنترل یکسان بوده و حالت هر بلوک با بلوک بعدی متفاوت می باشد.
  • Ethics committees

    #1
    IR.ACECR.REC.1397.002
    IR.ACECR.REC.1397.001
  • Health conditions studied

    #1
    Diminished ovarian reserve
    Poor ovarian response
    کاهش ذخیره تخمدان
    پاسخ ضعیف تخمدان
  • Primary outcomes

    #1
    Before intervention and 3 months, 6 months and one year after cell administration
    Before intervention, 3 months and 6 months after cell administration
    قبل از شروع مطالعه و 3، 6 ماه و یک سال پس از پیوند
    قبل از شروع مطالعه و 3، 6 ماه پس از پیوند
    #2
    FSH level in blood serum
    Anti Mullerian hormone level in blood serum
    میزان هورمون محرک فولیکول در سرم خون
    میزان هورمون ضد مولرین در سرم خون
    Before intervention and 3 months, 6 months and one year after cell administration
    Before intervention, 3 months, 6 months and one year after cell administration
    قبل از شروع مطالعه و 3، 6 ماه و یک سال پس از پیوند
    قبل از شروع مطالعه، 3، 6 ماه و یک سال پس از پیوند
    Biochemical assay
    biochemical assay
    #3
    Anti Mullerian hormone level in blood serum
    number and quality of oocytes in intra-cytoplasmic sperm injection cycle
    میزان هورمون ضد مولرین در سرم خون
    تعدادو کیفیت تخمکهای بدست آمده در سیکل درمانی تزریق داخل سیتوپلاسمی اسپرم
    Before intervention and 3 months, 6 months and one year after cell administration
    first intra-cytoplasmic sperm injection cycle after intervention
    قبل از شروع مطالعه و 3، 6 ماه و یک سال پس از پیوند
    اولین سیکل درمانی تزریق داخل سیتوپلاسمی اسپرم بعد از مداخله
    biochemical assay
    embryologic evaluation
    اندازه گیری بیوشیمی
    ارزیابی جنین شناسی
    #4
    number and quality of oocytes in ICSI cylcle
    spontaneous pregnancy
    تعدادو کیفیت تخمکهای بدست آمده در سیکل درمانی ICSI
    بارداری خود بخودی
    Before and 3-6 moths after intervention
    up to 3 months after intervention
    قبل و 3 الی 6 ماه بعد از مداخله
    طی 3 ماه بعد از شروع مداخله
    embryologic evaluation
    beta-HCG assay
    ارزیابی جنین شناسی
    اندازه گیری بتا -اچ سی جی
    #5
    number and quality ofembryoes in ICSI cylcle
    empty
    تعدادو کیفیت جنینهای بدست آمده در سیکل درمانی ICSI
    empty
    Before and 3-6 moths after intervention
    empty
    قبل و 3 الی 6 ماه بعد از مداخله
    empty
    embryologic evaluation
    empty
    ارزیابی جنین شناسی
    empty
  • Secondary outcomes

    #1
    3,6 months and 1 year after intervention
    in new intra-cytoplasmic sperm injection cycle after intervention
    3،6 ماه و یکسال بعد از مداخله
    در سیکل جدید تزریق داخل سیتوپلاسمی اسپرم پس از مداخله
    #2
    3,6 months and 1 year after intervention
    6-8 weeks after last menstrual period
    3،6 ماه و یکسال بعد از مداخله
    6-8 هفته پس از اولین روز آخرین پریود
    #3
    periodic cycle
    live birth
    سیکلهای قاعدگی
    تولد زنده
    Before and 3,6 months and 1 year after intervention
    9 months after pregnancy
    قبل و 3،6 و یکسال بعد از مداخله
    9 ماه پس از وقوع بارداری
    Description of patient
    delivery report based on gynecologist comment
    شرح حال بیمار
    گزارش زایمان زنده بر اساس نظر پزشک متخصص زنان
    #4
    empty
    embryo quality and number
    empty
    تعداد و کیفیت جنین
    empty
    in new intra-cytoplasmic sperm injection cycle after intervention
    empty
    در سیکل جدید تزریق داخل سیتوپلاسمی اسپرم پس از مداخله
    empty
    embryology report
    empty
    بررسی جنین شناسی
  • Intervention groups

    #1
    Intervention group includes 15 patients with poor ovarian response that will be treated by stem cell injection.
    Intervention group: includes 18 patients with poor ovarian response that will be treated by once injection of autologous menstrual blood stem cells. After cells isolation, culture and qualification in GMP grade- clean room of STERCO (Tehran, Iran), they will be intravaginally injected by vaginal ultrasonography into left ovary of patients after receiving general anesthesia.
    گروه مداخله: شامل 15 بیمار مبتلا به کاهش ذخیره تخمدان که به وسیله تزریق سلولهای بنیادی تحت درمان قرار میگیرند.
    گروه مداخله: شامل 18 بیمار مبتلا به کاهش ذخیره تخمدان که به وسیله یکبار تزریق اتولوگ سلولهای بنیادی مشتق از خون قاعدگی تحت درمان قرار میگیرند. سلولها پس از جداسازی، کشت و تستهای کنترل کیفی در اتاق تمیز تحت GMP شرکت زیست مهندسی سینا التیام به صورت سوسپانسون به غلظت 20 میلیون در میلی لیتر آماده سازی شده و 150 میکرولیتر ازآن به داخل تخمدان چپ بیماران تحت بیهوشی از طریق واژن با گاید سونوگرافی واژینال تزریق خواهد شد.
    #2
    Control group: includes 15 patients with poor ovarian response that will not receive any intervention and their biochemical parameters, sonographic and embryologic data will be compared with intervention group.
    Control group: includes 18 patients with poor ovarian response that will not receive any intervention and their biochemical parameters, sonographic and embryologic data will be compared with intervention group.
    گروه کنترل: شامل 15 بیمار مبتلا به کاهش ذخیره تخمدان که مداخله درمانی در مورد آنها انجام نمی گیرد و صرفا وضعیت آنها از لحاظ داده های سونوگرافی، بیوشیمیایی و جنین شناسی با گروه مداخله مقایسه می شود.
    گروه کنترل: شامل 18 بیمار مبتلا به کاهش ذخیره تخمدان که مداخله درمانی در مورد آنها انجام نمی گیرد و صرفا وضعیت آنها از لحاظ داده های سونوگرافی، بیوشیمیایی و جنین شناسی با گروه مداخله مقایسه می شود.

Protocol summary

Study aim
Improvement of ovarian function and fertility in patients with poor ovarian response using stem cells derived from menstrual blood
Design
Clinical trial including control group, two arm parallel group, randomised trial
Settings and conduct
The entire population is selected according to the inclusion and exclusion criteria and all patients must sign the informed consent. The subjects are randomly divided into intervention and control groups. Menstrual blood is collected from the patients of the intervention group at days 1 or 2 of their menstruation cycle using menstrual cups. Stem cells are isolated from collected menstrual blood and cultured in vitro. Cultured cells are evaluated for phenotyping and non-contamination. Autologous cells are administered to the ovary of patients in Avicenna Infertility Treatment Center.
Participants/Inclusion and exclusion criteria
Inclusion criteria: married woman;having previous cycles of ovarian stimulation with oocyte number of up to 3;anti-muller hormone below 1.1 ng/ml; antral follicle below 5; up to 40 years Sperm analysis:more than 5 million per ml; normal morphology with the strict criterion of at least 1%;25% of sperm motility Exclusion criteria: Thyroid dysfunction; Immune system disease; History of cancer; Hepatitis B and C and HIV; Endometriosis; Ovarian surgery; Diabetes; Liver dysfunction
Intervention groups
Intervention group: patients with reduced ovarian function are treated by stem cell infusion Control group: patients with reduced ovarian function are considered with no intervention only to compare their status with the intervention group
Main outcome variables
Number of antral follicles, Anti Mullerian hormone levels, Number and quality of oocytes in the treatment cycle, Number and quality of the embryos, Spontaneous pregnancy, Clinical pregnancy, Implantation rate, Live birth rate

General information

Reason for update
Methodology revision during project implementation
Acronym
IRCT registration information
IRCT registration number: IRCT20180619040147N2
Registration date: 2018-08-21, 1397/05/30
Registration timing: registered_while_recruiting

Last update: 2020-03-25, 1399/01/06
Update count: 4
Registration date
2018-08-21, 1397/05/30
Registrant information
Name
Maryam Darzi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2243 2020
Email address
m.darzi@ari.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-08-06, 1397/05/15
Expected recruitment end date
2019-10-07, 1398/07/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with poor ovarian response.
Public title
Evaluation of the safety and feasibility of intra ovarian injection of menstrual blood derived stem cells (MenSCs) in women with poor ovarian response.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Got married woman Picked up less than 3 oocytes in last ovarian stimulation Anti mullerian hormone; less than 1.1 ng/ml Upper age limit: 40 Spermogram: more than 5 million/ml, normal morphology more than 1, sperm motility (A+B) more than 25% Anteral follicles: less than 5-7
Exclusion criteria:
Thyroid dysfunction Immune disorders History of cancer, chemotherapy and radiotherapy Infected by hepatitis B,C or HIV Severe endometriosis History of ovarian surgery Diabetes Dysfunction of electrolyte or liver tests Psychological problem like depression, high stress an anxiety
Age
From 25 years old to 40 years old
Gender
Female
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size: 36
Randomization (investigator's opinion)
Randomized
Randomization description
Block randomization: In order to randomly assign 36 subjects in treatment group or control group, 6 blocks including 6 subjects each will be defined using "https://app.studyrandomizer.com". Treatment group and control group will be identified by codes A and B, respectively. In each block, number of treatment group and control group is equal and situation of each block with other block is different.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Academic Center for Education, Culture and Research (ACECR)- Biomedical Research Ethics Committee
Street address
1270, Secretariat of the Ethics Committee of ACECR,Deputy Director of Research and Technology, Headquarters of ACECR, Opposite the main door of Tehran University, Enghelab Street, Tehran
City
Tehran
Province
Tehran
Postal code
1936773493
Approval date
2018-05-06, 1397/02/16
Ethics committee reference number
IR.ACECR.REC.1397.001

Health conditions studied

1

Description of health condition studied
Poor ovarian response
ICD-10 code
E89.40
ICD-10 code description
Asymptomatic postprocedural ovarian failure

Primary outcomes

1

Description
Number of antral follicles in ovary
Timepoint
Before intervention, 3 months and 6 months after cell administration
Method of measurement
Vaginal sonography

2

Description
Anti Mullerian hormone level in blood serum
Timepoint
Before intervention, 3 months, 6 months and one year after cell administration
Method of measurement
biochemical assay

3

Description
number and quality of oocytes in intra-cytoplasmic sperm injection cycle
Timepoint
first intra-cytoplasmic sperm injection cycle after intervention
Method of measurement
embryologic evaluation

4

Description
spontaneous pregnancy
Timepoint
up to 3 months after intervention
Method of measurement
beta-HCG assay

Secondary outcomes

1

Description
Implantation rate
Timepoint
in new intra-cytoplasmic sperm injection cycle after intervention
Method of measurement
Vaginal sonography

2

Description
Clinical pregnancy
Timepoint
6-8 weeks after last menstrual period
Method of measurement
Vaginal sonography

3

Description
live birth
Timepoint
9 months after pregnancy
Method of measurement
delivery report based on gynecologist comment

4

Description
embryo quality and number
Timepoint
in new intra-cytoplasmic sperm injection cycle after intervention
Method of measurement
embryology report

Intervention groups

1

Description
Intervention group: includes 18 patients with poor ovarian response that will be treated by once injection of autologous menstrual blood stem cells. After cells isolation, culture and qualification in GMP grade- clean room of STERCO (Tehran, Iran), they will be intravaginally injected by vaginal ultrasonography into left ovary of patients after receiving general anesthesia.
Category
Treatment - Other

2

Description
Control group: includes 18 patients with poor ovarian response that will not receive any intervention and their biochemical parameters, sonographic and embryologic data will be compared with intervention group.
Category
Treatment - Other

Recruitment centers

1

Recruitment center
Name of recruitment center
Avicenna Infertility Clinic
Full name of responsible person
Somaieh Kazemnejad
Street address
No 97, Beginning of Yakhchal Street, Shariati Ave.
City
Tehran
Province
Tehran
Postal code
1936773493
Phone
+98 21 23519
Email
kazemnejad_s@yahoo.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Iranian Academic Center for Education Culture and Research
Full name of responsible person
Mohammad-Reza Sadeghi
Street address
Avicenna Research Institute, Shahid Beheshti University, Shahid Chamran Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1936772493
Phone
+98 21 2243 2020
Email
sadeghi@ari.ir
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
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other

Person responsible for general inquiries

Contact
Name of organization / entity
Iranian Academic Center for Education Culture and Research
Full name of responsible person
Somaieh Kazemnejad
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biochemistry
Street address
Avicenna Research Institute, Shahid Beheshti University, Shahid Chamran Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1936773493
Phone
+98 21 2243 2020
Email
kazemnejad_s@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Iranian Academic Center for Education Culture and Research
Full name of responsible person
Somaieh Kazemnejad
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biochemistry
Street address
Avicenna Research Institute, Shahid Beheshti University, Shahid Chamran Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1936773493
Phone
+98 21 2243 2020
Email
kazemnejad_s@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Iranian Academic Center for Education Culture and Research
Full name of responsible person
Somaieh Kazemnejad
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biochemistry
Street address
Avicenna Research Institute, Shahid Beheshti University, Shahid Chamran Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1936773493
Phone
+98 21 2243 2020
Email
kazemnejad_s@yahoo.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
No - There is not 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
Not applicable
Data Dictionary
Not applicable
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