Comparison of the Effect of the early initiation of GnRH Antagonist in the Early Follicular Phase in Poor Responder Patients
Design
This study was designed as a single-blinded randomized clinical trial with parallel groups and a sample size of 58 people in each group.
Settings and conduct
The study will be conducted at Arash Women's Hospital on all women undergoing IVF. Patients who signed informed consent will be randomly divided into two groups. The first group will receive the Early protocol, including Recombinant FSH with LH and antagonist started simultaneously on day 2 of the cycle. The second group will receive the Conventional antagonist protocol, which included Recombinant FSH with LH starting on day 2 of the cycle and injection of antagonist when the follicles sizes reach 14-13 mm. In both groups, the final oocyte maturation will be triggered by of HCG injection when at least one 18-mm and two 16-mm follicles were detected on ultrasound. The ovarian puncture will be performed 36 hours after HCG injection. One or two embryos will be transferred, three days after the puncture. The luteal phase support will be performed with 400 mg of Progesterone suppository.
The final outcome of the study will be assessed by a third party who is unaware of the study process. Also, the statistician will be unaware of the study process.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Bologna criteria (described in the relevant section)
Exclusion criteria: Polycystic ovary syndrome, hypothalamic amenorrhea, congenital uterine anomaly, and uterine cavity problems, chronic diseases, more than three times consecutive IVF failure
Intervention groups
Group One: The Early Antagonist Protocol
Group Two: The Conventional Antagonist Protocol
Main outcome variables
Total number of mature oocytes; Total number of embryos
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20110731007165N9
Registration date:2020-02-08, 1398/11/19
Registration timing:registered_while_recruiting
Last update:2020-02-08, 1398/11/19
Update count:0
Registration date
2020-02-08, 1398/11/19
Registrant information
Name
Ladan Kashani
Name of organization / entity
Tehran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 8828 1866
Email address
kashani_ladan@tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2019-10-06, 1398/07/14
Expected recruitment end date
2020-03-19, 1398/12/29
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the Effect of the early initiation of GnRH Antagonist in the Early Follicular Phase in Poor Responder Patients
Public title
Early initiation of GnRH Antagonist in Poor responder Patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age between 18 up to 44 years
History of poor ovarian response (POR) in previous cycle (oocyte less than 3 in a conventional protocol)
Antral follicle count (AFC) less than 5-7 or Anti-Müllerian hormone (AMH) <0.5-1.1
Poor ovarian response after maximal stimulation
Exclusion criteria:
Polycystic Ovarian Syndrome
Hypothalamic amenorrhea
Uterine congenital anomalies and uterine cavity abnormalities (Bicorn uterus, Unicorn uterus, Asherman, Liomyuma, Polyp, etc.)
Repeated IVF failure (more than three consecutive failures)
Age
From 18 years old to 44 years old
Gender
Female
Phase
3
Groups that have been masked
Outcome assessor
Data analyser
Sample size
Target sample size:
116
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization list will be prepared by the statistician. Treatments will be placed in sealed envelopes and will be kept by the out-of-study nurse.
After identification of the eligibility of the patient, the procedure will be explained to her and informed consent will be obtained.
Blinding (investigator's opinion)
Single blinded
Blinding description
Completion of the final information is up to the person who is unaware of the type of treatment and also the specialist will be blind.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics Committee of Tehran University of Medical Sciences
Street address
Qods St, Keshavarz Blvd, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2019-10-05, 1398/07/13
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1398.544
Health conditions studied
1
Description of health condition studied
Poor Ovarian Response
ICD-10 code
N98
ICD-10 code description
Complications associated with artificial fertilization
Primary outcomes
1
Description
Number of Mature Retrieved Oocytes
Timepoint
At the end of the study
Method of measurement
Embryology Report
2
Description
Embryos
Timepoint
At the end of the study
Method of measurement
Embryology Report
3
Description
Total Gonadotropins used
Timepoint
At the end of the study
Method of measurement
Checklist
4
Description
Total Antagonist used
Timepoint
At the end of the study
Method of measurement
Checklist
5
Description
Total Days of Induction of ovulation
Timepoint
At the end of the study
Method of measurement
Checklist
6
Description
Total Number of Retrieved Oocytes
Timepoint
At the end of the study
Method of measurement
Embryology Report
Secondary outcomes
1
Description
Clinical Pregnancy
Timepoint
At the end of the study
Method of measurement
Pregnancy confirmed by both high levels of hCG and presence of gestational sac with positive heart beats in ultrasound
2
Description
Ongoing pregnancy
Timepoint
At the end of the study
Method of measurement
Pregnancy had continued more than 12 weeks of gestation
3
Description
Chemical Pregnancy
Timepoint
At the end of the study
Method of measurement
A very early pregnancy loss in the first few weeks
4
Description
Luteinizing Hormone (LH) Level
Timepoint
In the second day of the cycle and then one time in trigger day
Method of measurement
Blood Test
5
Description
Progestrone Level
Timepoint
In the second day of the cycle and then one time in trigger day
Method of measurement
Blood Test
6
Description
Estradiol Level
Timepoint
In the second day of the cycle and then one time in trigger day
Method of measurement
Blood Test
7
Description
Implantation Rate
Timepoint
At the end of the study
Method of measurement
The percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period.
8
Description
Fertilization rate
Timepoint
At the end of the study
Method of measurement
Percentage of transformation of micro injected oocytes into two pronuclei
Intervention groups
1
Description
Intervention group: Early antagonist protocol: Recombinant FSH (150-225 IU) and GnRH Antagonist (Cetrotid 0.25 mg) will be started simultaneously on the second day of the cycle. Final oocyte maturation will be triggered with 5000 units of HCG when at least one 18-mm and two 16-mm follicles were detected on ultrasound. The ovarian puncture will be performed 36 hours after HCG injection. One or two embryos will be transferred three days after the ovarian puncture. The luteal phase support will be performed by the use of 100 mg of Progesterone.
Category
Treatment - Drugs
2
Description
Control group: Conventional antagonist protocol: Recombinant FSH (150-225 IU) will be started on day 2 of the cycle and the Antagonist (Cetrotid 0.25 mg) will be injected when follicle size reaches to 13-14 mmHg. Final oocyte maturation will be triggered with 5000 units of HCG when at least one 18-mm and two 16-mm follicles were detected on ultrasound. The ovarian puncture will be performed 36 hours after HCG injection. One or two embryos will be transferred three days after the ovarian puncture. The luteal phase support will be performed by the use of 100 mg of Progesterone.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Arash women's hospital
Full name of responsible person
Dr.Ladan Kashani
Street address
No. 162 َAlley (Abdul Majid), Shahid Baghdarnia Street (North Rashid), Shahid Bagheri Highway, Resalat Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1653915981
Phone
+98 21 7788 3283
Fax
+98 21 7788 3196
Email
Kashani_ladan@tums.ac.ir
Web page address
http://arash.tums.ac.ir/
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Mohammad Ali Sahraian
Street address
Qods St, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 8163 3619
Fax
+98 21 8163 3611
Email
rmo@tums.ac.ir
Web page address
http://vcr.tums.ac.ir/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran 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
Tehran University of Medical Sciences
Full name of responsible person
Dr. Tayebeh Esfidani
Position
Fellowship
Latest degree
Subspecialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
No. 162 َAlley (Abdul Majid), Shahid Baghdarnia Street (North Rashid), Shahid Bagheri Highway, Resalat Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1653915981
Phone
+98 21 7788 3195
Fax
Email
esfidani.tayebeh@gmail.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Ladan Kashani
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
No. 162 َAlley (Abdul Majid), Shahid Baghdarnia Street (North Rashid), Shahid Bagheri Highway, Resalat Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1653915981
Phone
+98 21 7788 3195
Fax
Email
Kashani_ladan@tums.ac.ir
Web page address
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Ladan Kashani
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
No. 162 َAlley (Abdul Majid), Shahid Baghdarnia Street (North Rashid), Shahid Bagheri Highway, Resalat Highway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1653915981
Phone
+98 21 7788 3195
Fax
Email
Kashani_ladan@tums.ac.ir
Web page address
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
Undecided - It is not yet known if there will be 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