Comparison of the effect of delayed start GnRH antagonist protocol and usual antagonist protocol on oocyte count and pregnancy rate in ART cycle in poor ovarian responders
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Protocol summary
In the intervention group with delayed protocol: First, like the control group, estradiol valerate 4 mg daily for 10 days starts from the 20th day of the previous menstrual cycle, then 7 days of daily administration of gonadotropin-releasing hormone antagonist (0.25 mg cetrorelix acetate) begins. The ovaries are then stimulated with gonadotropins.
In the control group ovarian stimulation was performed using standard GnRH protocol.
In the intervention group with delayed protocol: First, like the control group, estradiol valerate 4 mg daily for 10 days starts from the 20th day of the previous menstrual cycle, then 7 days of daily administration of gonadotropin-releasing hormone antagonist (0.25 mg cetrorelix acetate) begins. The ovaries are then stimulated with 375 u gonadotropins.
In the control group ovarian stimulation was performed using standard GnRH protocol with 375u gonadotropin.
In the intervention group with delayed protocol: First, like the control group, estradiol valerate 4 mg daily for 10 days starts from the 20th day of the previous menstrual cycle, then 7 days of daily administration of gonadotropin-releasing hormone antagonist (0.25 mg cetrorelix acetate) begins. The ovaries are then stimulated with 375 u gonadotropins. In the control group ovarian stimulation was performed using standard GnRH protocol with 375u gonadotropin.
در گروه مداخله با پروتوکل تاخیری: ابتدا مانند گروه کنترل از روز 20 سیکل قاعدگی قبلی قرص استرادیول والرات 4 میلی گرم روزانه به مدت 10 روز شروع می شود سپس 7 روز تجویز روزانه ی آنتاگونیست هورمون ازاد کننده گونادوتروپین، 0.25 میلی گرم سترورلیکس، شروع می شود. بعد از ان تحریک تخمدان با گونادوتروپین انجام می شود.
در گروه کنترل تحریک با پروتکل معمول GnRH انتاگونیست انجام می شود.
در گروه مداخله با پروتوکل تاخیری: ابتدا مانند گروه کنترل از روز 20 سیکل قاعدگی قبلی قرص استرادیول والرات 4 میلی گرم روزانه به مدت 10 روز شروع می شود سپس 7 روز تجویز روزانه ی آنتاگونیست هورمون ازاد کننده گونادوتروپین، 0.25 میلی گرم سترورلیکس، شروع می شود. بعد از ان تحریک تخمدان با 375 واحد گونادوتروپین انجام می شود.
در گروه کنترل تحریک با پروتکل معمول GnRH انتاگونیست و با 375 واحد گونادوتروپین انجام می شود.
در گروه مداخله با پروتوکل تاخیری: ابتدا مانند گروه کنترل از روز 20 سیکل قاعدگی قبلی قرص استرادیول والرات 4 میلی گرم روزانه به مدت 10 روز شروع می شود سپس 7 روز تجویز روزانه ی آنتاگونیست هورمون ازاد کننده گونادوتروپین، 0.25 میلی گرم سترورلیکس، شروع می شود. بعد از ان تحریک تخمدان با 375 واحد گونادوتروپین انجام می شود. در گروه کنترل تحریک با پروتکل معمول GnRH انتاگونیست و با 375 واحد گونادوتروپین انجام می شود.
General information
65
60
6560
Updating the trial according to the last changes in inclusion and exclusion criteria, actual number of cases, date of recruitment and trial completion
Updating the trial according to the last changes in Actual sample size reached and secondary outcomes
Updating the trial according to the last changes in inclusionActual sample size reached and exclusion criteria, actual number of cases, date of recruitment and trial completionsecondary outcomes
به روز رسانی کارازمایی بالینی بر اساس آخرین تغییرات در معیارهای ورود و خروج، تعداد بیماران، تاریخ نهایی بیمارگیری و پایان مطالعه
به روز رسانی کارازمایی بالینی بر اساس آخرین تغییرات در حجم نمونه تحقق یافته و پیامدهای ثانویه
به روز رسانی کارازمایی بالینی بر اساس آخرین تغییرات در معیارهای ورودحجم نمونه تحقق یافته و خروج، تعداد بیماران، تاریخ نهایی بیمارگیری و پایان مطالعهپیامدهای ثانویه
Secondary outcomes
#1
empty
oocyte maturity rate (MII number /total oocytes number)
oocyte maturity rate (MII number /total oocytes number)
empty
میزان بلوغ اووسیت( اووسیت بالغ بر تعداد اووسیت کل)
میزان بلوغ اووسیت( اووسیت بالغ بر تعداد اووسیت کل)
empty
oocyte retrieval day
oocyte retrieval day
empty
روز برداشت اووسیت
روز برداشت اووسیت
empty
with microscope
with microscope
empty
با میکروسکوپ
با میکروسکوپ
#2
empty
oocyte yield (total oocytes number /antral follicle count [AFC])
oocyte yield (total oocytes number /antral follicle count [AFC])
empty
بازده اووسیت( تعداد کل اووسیت بر تعداد فولیکول انترال)
بازده اووسیت( تعداد کل اووسیت بر تعداد فولیکول انترال)
empty
oocyte retrieval day for oocyte count and before the start of the ivf cycle for antral follicles
oocyte retrieval day for oocyte count and before the start of the ivf cycle for antral follicles
empty
روز تخمک کشی برای تعداد اووسیت و قبل از شروع سیکل لقاح خارج رحمی برای فولیکول انترال
روز تخمک کشی برای تعداد اووسیت و قبل از شروع سیکل لقاح خارج رحمی برای فولیکول انترال
empty
With microscope for oocytes and vaginal ultrasound for antral follicles
With microscope for oocytes and vaginal ultrasound for antral follicles
empty
با میکروسکوپ برای اووسیت و سونوگرافی واژینال برای فولیکول انترال
با میکروسکوپ برای اووسیت و سونوگرافی واژینال برای فولیکول انترال
#3
empty
mature oocyte yield (MII number/AFC)
mature oocyte yield (MII number/AFC)
empty
بازده اووسیت بالغ( تعداد اووسیت بالغ بر تعداد فولیکول انترال)
بازده اووسیت بالغ( تعداد اووسیت بالغ بر تعداد فولیکول انترال)
empty
oocyte retrieval day for mature oocyte count and before the start of the ivf cycle for antral follicles
oocyte retrieval day for mature oocyte count and before the start of the ivf cycle for antral follicles
empty
روز تخمک کشی برای تعداد اووسیت بالغ و قبل از شروع سیکل لقاح خارج رحمی برای فولیکول انترال
روز تخمک کشی برای تعداد اووسیت بالغ و قبل از شروع سیکل لقاح خارج رحمی برای فولیکول انترال
empty
With microscope for mature oocytes and vaginal ultrasound for antral follicles
With microscope for mature oocytes and vaginal ultrasound for antral follicles
empty
با میکروسکوپ برای اووسیت بالغ و سونوگرافی واژینال برای فولیکول انترال
با میکروسکوپ برای اووسیت بالغ و سونوگرافی واژینال برای فولیکول انترال
#4
empty
total dosage of gonadotropin
total dosage of gonadotropin
empty
دوز کلی گونادوتروپین
دوز کلی گونادوتروپین
empty
End of IVF cycle
End of IVF cycle
empty
پایان سیکل لقاح خارج رحمی
پایان سیکل لقاح خارج رحمی
empty
Count the dose of gonadotropin received
Count the dose of gonadotropin received
empty
شمارش دوز گونادوتروپین دریافتی
شمارش دوز گونادوتروپین دریافتی
#5
empty
ovarian stimulation days
ovarian stimulation days
empty
تعداد روزهای تحریک تخمدان
تعداد روزهای تحریک تخمدان
empty
End of IVF cycle
End of IVF cycle
empty
پایان سیکل لقاح خارج رحمی
پایان سیکل لقاح خارج رحمی
empty
Counting the days of ovarian stimulation
Counting the days of ovarian stimulation
empty
شمارش روزهای تحریک تخمدان
شمارش روزهای تحریک تخمدان
#6
empty
fertilization rate (two-pronuclear [2PN]/ MII)
fertilization rate (two-pronuclear [2PN]/ MII)
empty
میزان لقاح( 2 پره نوکلیوس بر اووسیت بالغ)
میزان لقاح( 2 پره نوکلیوس بر اووسیت بالغ)
empty
16 hr after Intra-cytoplasmic sperm injection
16 hr after Intra-cytoplasmic sperm injection
empty
16 ساعت بعد از تزریق اسپرم به سیتوپلاسم تخمک
16 ساعت بعد از تزریق اسپرم به سیتوپلاسم تخمک
empty
With microscope
With microscope
empty
با میکروسکوپ
با میکروسکوپ
#7
empty
Implantation rate (the number of gestational sacs divided/the number of transferred embryos)
Implantation rate (the number of gestational sacs divided/the number of transferred embryos)
empty
میزان لانه گزینی(تعداد ساک بارداری بر تعداد جنین منتقل شده)
میزان لانه گزینی(تعداد ساک بارداری بر تعداد جنین منتقل شده)
empty
3 week after positive serum βhCG
3 week after positive serum βhCG
empty
3 هفته بعد از مثبت شدن تست حاملگی
3 هفته بعد از مثبت شدن تست حاملگی
empty
Vaginal ultrasonography
Vaginal ultrasonography
empty
سونوگرافی واژینال
سونوگرافی واژینال
#8
empty
Ongoing pregnancy rate
Ongoing pregnancy rate
empty
حاملگی ادامه دار
حاملگی ادامه دار
empty
after 12 week gestation
after 12 week gestation
empty
بعد از 12 هفته
بعد از 12 هفته
empty
ultrasound
ultrasound
empty
سونوگرافی
سونوگرافی
#9
empty
miscarriage rate
miscarriage rate
empty
میزان سقط
میزان سقط
empty
miscarriages before 20 weeks gestation
miscarriages before 20 weeks gestation
empty
از دست رفتن بارداری قبل از هفته 20
از دست رفتن بارداری قبل از هفته 20
empty
ultrasound
ultrasound
empty
سونوگرافی
سونوگرافی
Intervention groups
#1
In intervention group 0/25 mg/vial cetrorelix( GNRH antagonist), one vial daily, subcutaneous, for 7 days, before starting COH
In intervention group 0/25 mg/vial cetrorelix( GNRH antagonist), one vial daily, subcutaneous, for 7 days, before starting COH. Then start ovarian stimulation with 375 units of gonadotropin
In intervention group 0/25 mg/vial cetrorelix( GNRH antagonist), one vial daily, subcutaneous, for 7 days, before starting COH. Then start ovarian stimulation with 375 units of gonadotropin
در گروه مداخله امپول سترورلیکس استفاده می شود. هر ویال حاوی 0/25 میلی گرم انتاگونیست هورمون ازاد کننده گونادوتروپین است. دوز و نحوه مصرف: یک ویال، یک بار در روز، بصورت زیر جلدی قبل از شروع تحریک تخمدان، به مدت 7 روز
در گروه مداخله امپول سترورلیکس استفاده می شود. هر ویال حاوی 0/25 میلی گرم انتاگونیست هورمون ازاد کننده گونادوتروپین است. دوز و نحوه مصرف: یک ویال، یک بار در روز، بصورت زیر جلدی قبل از شروع تحریک تخمدان، به مدت 7 روز. سپس شروع تحریک تخمدان با 375 واحد گونادوتروپین
در گروه مداخله امپول سترورلیکس استفاده می شود. هر ویال حاوی 0/25 میلی گرم انتاگونیست هورمون ازاد کننده گونادوتروپین است. دوز و نحوه مصرف: یک ویال، یک بار در روز، بصورت زیر جلدی قبل از شروع تحریک تخمدان، به مدت 7 روز. سپس شروع تحریک تخمدان با 375 واحد گونادوتروپین
#2
in control group patients treated with antagonist protocol without GNRH antagonist pretreatment.
in control group patients treated with antagonist protocol with 375 units of gonadotropin, without GNRH antagonist pretreatment.
in control group patients treated with antagonist protocol with 375 units of gonadotropin, without GNRH antagonist pretreatment.
در گروه کنترل 30 بیمار تحت درمان با پروتوکل معمول انتاگونیست بدون پیش درمانی با انتاگونیست هورمون ازاد کننده گونادوتروپین قرار می گیرند
در گروه کنترل 30 بیمار تحت درمان با پروتوکل معمول انتاگونیست با 375 واحد گونادوتروپین، بدون پیش درمانی با انتاگونیست هورمون ازاد کننده گونادوتروپین قرار می گیرند
در گروه کنترل 30 بیمار تحت درمان با پروتوکل معمول انتاگونیست با 375 واحد گونادوتروپین، بدون پیش درمانی با انتاگونیست هورمون ازاد کننده گونادوتروپین قرار می گیرند
Protocol summary
Study aim
Effect of delayed start GnRH protocol in ovarian poor responders
Design
Interventional clinical trial with control and parallel groups, non-blind, randomized, phase 2 was performed on 72 patients. Randomization was performed using random number table.
Settings and conduct
The objective of this study is evaluating the effect of delayed start protocol in ovarian poor responders. Study population: Infertile women with poor ovarian response candidate for IVF. Study groups: Intervention and control groups. Sample size: 72 poor responder women. This is a randomized not blinded trial, in one center, in phase 2 study. Setting and conduct: Ovarian poor responders after obtaining informed consent randomized into intervention and control groups.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Patient with Bologna criteria for ovarian poor responders
Exclusion criteria: History of endocrine disorders, severe endometriosis, azoospermia.
Intervention groups
In the intervention group with delayed protocol: First, like the control group, estradiol valerate 4 mg daily for 10 days starts from the 20th day of the previous menstrual cycle, then 7 days of daily administration of gonadotropin-releasing hormone antagonist (0.25 mg cetrorelix acetate) begins. The ovaries are then stimulated with 375 u gonadotropins.
In the control group ovarian stimulation was performed using standard GnRH protocol with 375u gonadotropin.
Main outcome variables
Number of mature oocytes (MII) and total number of oocytes
General information
Reason for update
Updating the trial according to the last changes in Actual sample size reached and secondary outcomes
Acronym
IRCT registration information
IRCT registration number:IRCT2015100424335N1
Registration date:2016-01-18, 1394/10/28
Registration timing:retrospective
Last update:2021-08-10, 1400/05/19
Update count:3
Registration date
2016-01-18, 1394/10/28
Registrant information
Name
robabe hoseinisadat
Name of organization / entity
infertility institute center of shahid sadughi
Country
Iran (Islamic Republic of)
Phone
+98 35 3824 7085
Email address
robabehoseini@ssu.ac.ir
Recruitment status
Recruitment complete
Funding source
Shahid Sadoughi University of Medical Sciences
Expected recruitment start date
2015-03-01, 1393/12/10
Expected recruitment end date
2015-09-30, 1394/07/08
Actual recruitment start date
2015-03-01, 1393/12/10
Actual recruitment end date
2015-09-30, 1394/07/08
Trial completion date
2016-03-30, 1395/01/11
Scientific title
Comparison of the effect of delayed start GnRH antagonist protocol and usual antagonist protocol on oocyte count and pregnancy rate in ART cycle in poor ovarian responders
Public title
Effect of delayed start protocol in outcome of ART cycle in poor ovarian responders
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Poor ovarian responders according to Bologna criteria. At least two of the following three features must be present:
Advanced maternal age (≥40 years) or any other risk factor for poor ovarian response;
A previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol);
An abnormal ovarian reserve test (i.e. AFC <5–7 follicles or AMH <1.1 ng/ml).
Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder.
Exclusion criteria:
History of endocrine and metabolic disorders
endometriosis
azoospermia
Age
From 18 years old to 45 years old
Gender
Female
Phase
2
Groups that have been masked
No information
Sample size
Target sample size:
72
Actual sample size reached:
60
Randomization (investigator's opinion)
Randomized
Randomization description
In this trial,72 infertile women with poor ovarian response were informed about the research design and signed a written consent form. All women were randomly divided into two groups. Randomization was simple, individual, not blinded, using a random number table.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Randomized with enveloped pocket method
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Shahid Sadoughi University of Medical Sciences
Street address
Research and Clinical Center for Infertility, Bouali, Timsar Fallahy, Safayeh, Yazd
City
Yazd
Province
Yazd
Postal code
8916877391
Approval date
2015-06-07, 1394/03/17
Ethics committee reference number
148
Health conditions studied
1
Description of health condition studied
Infertility
ICD-10 code
N98.9
ICD-10 code description
Complication associated with artificial fertilization, unspecified
Primary outcomes
1
Description
Mature oocytes count
Timepoint
Oocyte retrieval day
Method of measurement
Counting number of mature oocytes with microscope
2
Description
Total oocytes count
Timepoint
Oocyte retrieval day
Method of measurement
Counting number of total oocytes with microscope
Secondary outcomes
1
Description
Number of embryo
Timepoint
On the 2nd day after ICSI
Method of measurement
Observation with microscope
2
Description
Chemical pregnancy
Timepoint
14 days after embryo transfer
Method of measurement
Serum βhCG
3
Description
Clinical pregnancy
Timepoint
3 weeks after positive serum βhCG
Method of measurement
Vaginal ultrasonography
4
Description
oocyte maturity rate (MII number /total oocytes number)
Timepoint
oocyte retrieval day
Method of measurement
with microscope
5
Description
oocyte yield (total oocytes number /antral follicle count [AFC])
Timepoint
oocyte retrieval day for oocyte count and before the start of the ivf cycle for antral follicles
Method of measurement
With microscope for oocytes and vaginal ultrasound for antral follicles
6
Description
mature oocyte yield (MII number/AFC)
Timepoint
oocyte retrieval day for mature oocyte count and before the start of the ivf cycle for antral follicles
Method of measurement
With microscope for mature oocytes and vaginal ultrasound for antral follicles
7
Description
total dosage of gonadotropin
Timepoint
End of IVF cycle
Method of measurement
Count the dose of gonadotropin received
8
Description
ovarian stimulation days
Timepoint
End of IVF cycle
Method of measurement
Counting the days of ovarian stimulation
9
Description
fertilization rate (two-pronuclear [2PN]/ MII)
Timepoint
16 hr after Intra-cytoplasmic sperm injection
Method of measurement
With microscope
10
Description
Implantation rate (the number of gestational sacs divided/the number of transferred embryos)
Timepoint
3 week after positive serum βhCG
Method of measurement
Vaginal ultrasonography
11
Description
Ongoing pregnancy rate
Timepoint
after 12 week gestation
Method of measurement
ultrasound
12
Description
miscarriage rate
Timepoint
miscarriages before 20 weeks gestation
Method of measurement
ultrasound
Intervention groups
1
Description
In intervention group 0/25 mg/vial cetrorelix( GNRH antagonist), one vial daily, subcutaneous, for 7 days, before starting COH. Then start ovarian stimulation with 375 units of gonadotropin
Category
Treatment - Drugs
2
Description
in control group patients treated with antagonist protocol with 375 units of gonadotropin, without GNRH antagonist pretreatment.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences
Full name of responsible person
Robabe Hosseinisadat
Street address
Research and Clinical Center for Infertility, Bouali, Timsar Fallahy, Safayeh, Yazd
City
Yazd
Province
Yazd
Postal code
8916877391
Phone
+98 35 3824 7085
Fax
+98 35 3824 7087
Email
robabehosseinisadat@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Vice Chancellor for research of Shahid Sadoughi University of Medical Sciences
Full name of responsible person
Masoud Mirzaei
Street address
Bahonar Square, Yazd
City
Yazd
Province
Yazd
Postal code
8916978477
Phone
+98 35 3724 0171
Email
dvc.research@ssu.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Vice Chancellor for research of Shahid Sadoughi 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
Kerman University of Medical Sciences
Full name of responsible person
Robabe Hosseinisadat
Position
Assistant Professor
Latest degree
Medical doctor
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Imam Khomeini Highway, Afzalipour Infertility center
City
Kerman
Province
Kerman
Postal code
8916877391
Phone
+98 35 3824 7085
Fax
+98 35 3824 7087
Email
robabehosseinisadat@yahoo.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Sadoughi University of Medical Sciences
Full name of responsible person
Abbas Aflatoonian
Position
Professor
Latest degree
Medical doctor
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Research and Clinical Center for Infertility, Bouali, Timsar Fallahy, Safayeh, Yazd
City
Yazd
Province
Yazd
Postal code
8916877391
Phone
+98 35 3824 7085
Fax
+98 35 3824 7087
Email
abbas_aflatoonian@yahoo.com
Web page address
Person responsible for updating data
Contact
Name of organization / entity
Kerman University of Medical Sciences
Full name of responsible person
Robabe Hosseinisadat
Position
Assistant Professor
Latest degree
Medical doctor
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Imam Khomeini Highway, Afzalipour Infertility center
City
Kerman
Province
Kerman
Postal code
8916877391
Phone
+98 35 3824 7085
Fax
+98 35 3824 7087
Email
robabehosseinisadat@yahoo.com
Web page address
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
The final result of the study will be published and there is no need to share individual participants' data
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
No - There is not a plan to make this available
Clinical Study Report
No - There is not a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
No - There is not a plan to make this available
Title and more details about the data/document
The final result of the study will be published and there is no need to share individual participants' data
When the data will become available and for how long
The final result of the study will be published and there is no need to share individual participants' data
To whom data/document is available
The final result of the study will be published and there is no need to share individual participants' data
Under which criteria data/document could be used
The final result of the study will be published and there is no need to share individual participants' data
From where data/document is obtainable
The final result of the study will be published and there is no need to share individual participants' data
What processes are involved for a request to access data/document
The final result of the study will be published and there is no need to share individual participants' data