Infertility, FemaleNCT03134690
GnRh Antagonist Protocol With Delayed Start Stimulation in Patients With Poor Ovarian Response
A study testing delayed start and Conventional in people with Infertility, Female, run by Royan Institute at 1 site in Iran.
Trial summary
The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG trigger and the number of mature (MII) oocytes collected after conventional versus delayed-start ovarian stimulation protocol. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- delayed start and Conventional
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteIran
- Study dates
- Jan 2016to Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Premature ovarian failure (basal follicle stimulating hormone (FSH) above 20 IU/l or no antral follicle in ultrasound examination),
- ِDonor/recipient treatments,
- Metabolic or endocrine disorders including hyperprolactinoma and hypo/hyperthyroidism, endometriosis,
- Body mass index > 30 kg/m2,
- azoospermic male partner.
- A minimum of 2 or more month's interval from the previous ovarian stimulation is considered to prevent any potential source of error.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of a Novel " Delayed Start" Protocol With Gonadotropin-releasing Hormone Antagonist in Poor Responders: A Randomized Clinical Trial Phase 3
The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG trigger and the number of mature (MII) oocytes collected after conventional versus delayed-start ovarian stimulation protocol. Secondary outcome measures are including total number of oocytes retrieved, oocyte maturity rate (number of MII oocytes/total number of oocytes), oocyte yield (total number of oocytes retrieved/ antral follicle count [AFC]), mature oocyte yield (number of mature oocytes retrieved/AFC), total dosage of gonadotropin (recombinant FSH and/or highly purified hMG) needed, number of days needed for ovarian stimulation, quality of obtained embryos, fertilization rate (the proportion of total number of two-pronuclear [2PN] stage zygotes /per total injected MII oocytes), implantation rate (total number of observed gestational sac/ number of transferred embryos) and clinical pregnancy rate (presence of fetal heart beat by transvaginal ultrasound per embryo transfer).
Read the detailed description
One of the principal steps to obtain the favorable success is still related to the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH analogues. In the patients with "poor ovarian response" diagnosis, the limited number of obtained oocytes remains the main obstacle in optimizing the live birth rates. The objective of present study is to evaluate a new procedure to increase a cohort of the growing antral follicles and consequently the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH antagonist. In present study, eligible patients with diagnosis poor ovarian responder based on the Bologna criteria are included. Ovarian stimulation procedure will be performed by antagonist protocol. All the patients will be received two tablets daily of Estradiol valerate (Estraval®, 2 mg, Aburaihan Co., Tehran, Iran) starting a week after LH surge until menses. The hormonal evaluation (serum LH and FSH) and basic vaginal ultrasound will be performed before the starting ovarian stimulation on the 2th or 3th day of the menstrual cycle. On this day, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4.
In the Group A: treatment with GnRH antagonists (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started on the 2th or 3th day of the menstrual cycle and continues until the ninth day. Then, the ovarian stimulation with gonadotropin 300 IU recombinant FSH (Gonal - F®, Serono Laboratories Ltd, Geneva, Switzerland) and 150 IU of hMG (Menopur®; Ferring) will be started from ninth day of menstrual cycle until the day of hCG administration. The monitoring of ovarian stimulation will be done every other day by vaginal ultrasound and whenever at least 1 to 3 follicles larger than 13 mm are observed, the antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of hCG. When at least two follicles greater than 17 to 18 mm is seen, two pre-filled syringes of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered. The patients will undergo puncture operation 32-34 hours after hCG injection.
In the control group (B), as conventional antagonist procedure, the ovarian stimulation with gonadotropin 300 IU recombinant FSH (Gonal - F®, Serono Laboratories Ltd, Geneva, Switzerland) and 150 IU of hMG ( Menopur®; Ferring ) will be started from on the 2th or 3th day of the menstrual cycle. The monitoring of ovarian stimulation will be done every other day by vaginal ultrasound and whenever at least 1 to 3 follicles larger than 13 mm are observed, the antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of rhCG. 32-34 hours after the rhCG injection, the ovum pick up will be performed and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.
- Conditions
- Infertility, Female
- Being tested
- delayed start, Conventional
- Keywords
- Poor ovarian response gonadotropins antagonist
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
delayed startProcedure or surgery
In this protocol, ovarian stimulation will be started from ninth day of menstrual cycle .
ConventionalProcedure or surgery
In this protocol, ovarian stimulation will be started from the 2th or 3th day of the menstrual cycle.
| Study group | Role | What they receive |
|---|---|---|
| delayed start antagonist | Experimental | 60 women with poor ovarian responses undergo ovarian stimulation with delayed start antagonist. Receives: Procedure: delayed start |
| conventional antagonist | Experimental | 60 women with diagnose of poor ovarian response will have undergone ovarian stimulation with conventional antagonist protocol. Receives: Procedure: Conventional |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of dominant follicles (≥13 mm)
The number of dominant follicles (≥13 mm) on the day of hCG trigger
Measured: 24h after rhCG injection
Total number of oocytes
the number of mature oocytes collected after conventional versus delayed-start ovarian stimulation protocol
Measured: 32-34 hours after rhCG
Secondary outcomes (2)
Total number of retrieved oocytes
Total number of retrieved oocytes 32-34 hours after rhCG injection .
Measured: 32-34 hours after rhCG injection
Quality of obtained embryos
we score embryo quality according to the following quality criteria: Excellent (Day 3: 6-8 even size blastomeres with ≤10% fragmentation), Good (Day 3: 6-8 even or uneven size blastomeres with 10%-20% fragmentation), Poor (Uneven and few blastomeres with >20% fragmentation)
Measured: on the third day after oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study startJan 2016
- Primary completionApr 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Hamid Gourabi, PhD, Study chair, Head of Royan InstituteMahnaz Ashrafi, MD, Study director, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, IranMandana Hemmat, MD, Principal investigator, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, IranArezoo Arabipour, MSc, Principal investigator, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, Iran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03134690
- Sponsor's protocol ID
- Royan-Emb-028
- Status last verified
- Feb 2023
- First submitted
- 19 Dec 2016
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ashrafi M, Arabipoor A, Yahyaei A, Zolfaghari Z, Ghaffari F. Does the "delayed start" protocol with gonadotropin-releasing hormone antagonist improve the pregnancy outcome in Bologna poor responders? a randomized clinical trial. Reprod Biol Endocrinol. 2018 Dec 28;16(1):124. doi: 10.1186/s12958-018-0442-y.
PubMed 30593268
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Novel " Delayed Start" Protocol With Gonadotropin-releasing Hormone Antagonist in Poor Responders: A Randomized Clinical Trial Phase 3
- ClinicalTrials.gov ID
- NCT03134690
- Acronym / sponsor ID
- Royan-Emb-028
- Conditions
- Infertility, Female
- Keywords
- Poor ovarian response gonadotropins antagonist
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Royan InstituteOther government
- Study start
- Jan 2016
- Primary completion
- Apr 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG trigger and the number of mature (MII) oocytes collected after conventional versus delayed-start ovarian stimulation protocol. Secondary outcome measures are including total number of oocytes retrieved, oocyte maturity rate (number of MII oocytes/total number of oocytes), oocyte yield (total number of oocytes retrieved/ antral follicle count [AFC]), mature oocyte yield (number of mature oocytes retrieved/AFC), total dosage of gonadotropin (recombinant FSH and/or highly purified hMG) needed, number of days needed for ovarian stimulation, quality of obtained embryos, fertilization rate (the proportion of total number of two-pronuclear [2PN] stage zygotes /per total injected MII oocytes), implantation rate (total number of observed gestational sac/ number of transferred embryos) and clinical pregnancy rate (presence of fetal heart beat by transvaginal ultrasound per embryo transfer).
Detailed description
One of the principal steps to obtain the favorable success is still related to the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH analogues. In the patients with "poor ovarian response" diagnosis, the limited number of obtained oocytes remains the main obstacle in optimizing the live birth rates. The objective of present study is to evaluate a new procedure to increase a cohort of the growing antral follicles and consequently the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH antagonist. In present study, eligible patients with diagnosis poor ovarian responder based on the Bologna criteria are included. Ovarian stimulation procedure will be performed by antagonist protocol. All the patients will be received two tablets daily of Estradiol valerate (Estraval®, 2 mg, Aburaihan Co., Tehran, Iran) starting a week after LH surge until menses. The hormonal evaluation (serum LH and FSH) and basic vaginal ultrasound will be performed before the starting ovarian stimulation on the 2th or 3th day of the menstrual cycle. On this day, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4.
In the Group A: treatment with GnRH antagonists (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started on the 2th or 3th day of the menstrual cycle and continues until the ninth day. Then, the ovarian stimulation with gonadotropin 300 IU recombinant FSH (Gonal - F®, Serono Laboratories Ltd, Geneva, Switzerland) and 150 IU of hMG (Menopur®; Ferring) will be started from ninth day of menstrual cycle until the day of hCG administration. The monitoring of ovarian stimulation will be done every other day by vaginal ultrasound and whenever at least 1 to 3 follicles larger than 13 mm are observed, the antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of hCG. When at least two follicles greater than 17 to 18 mm is seen, two pre-filled syringes of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered. The patients will undergo puncture operation 32-34 hours after hCG injection.
In the control group (B), as conventional antagonist procedure, the ovarian stimulation with gonadotropin 300 IU recombinant FSH (Gonal - F®, Serono Laboratories Ltd, Geneva, Switzerland) and 150 IU of hMG ( Menopur®; Ferring ) will be started from on the 2th or 3th day of the menstrual cycle. The monitoring of ovarian stimulation will be done every other day by vaginal ultrasound and whenever at least 1 to 3 follicles larger than 13 mm are observed, the antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of rhCG. 32-34 hours after the rhCG injection, the ovum pick up will be performed and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| delayed start antagonist | Experimental | Procedure: delayed start60 women with poor ovarian responses undergo ovarian stimulation with delayed start antagonist. |
| conventional antagonist | Experimental | Procedure: Conventional60 women with diagnose of poor ovarian response will have undergone ovarian stimulation with conventional antagonist protocol. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Premature ovarian failure (basal follicle stimulating hormone (FSH) above 20 IU/l or no antral follicle in ultrasound examination),
- ِDonor/recipient treatments,
- Metabolic or endocrine disorders including hyperprolactinoma and hypo/hyperthyroidism, endometriosis,
- Body mass index > 30 kg/m2,
- azoospermic male partner.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| delayed startIn this protocol, ovarian stimulation will be started from ninth day of menstrual cycle . | Procedure or surgery | delayed start antagonist |
| ConventionalIn this protocol, ovarian stimulation will be started from the 2th or 3th day of the menstrual cycle. | Procedure or surgery | conventional antagonist |
Primary outcome
number of dominant follicles (≥13 mm)
Time frame: 24h after rhCG injection
The number of dominant follicles (≥13 mm) on the day of hCG trigger
Total number of oocytes
Time frame: 32-34 hours after rhCG
the number of mature oocytes collected after conventional versus delayed-start ovarian stimulation protocol
2 secondary outcomes
Total number of retrieved oocytes
Time frame: 32-34 hours after rhCG injection
Quality of obtained embryos
Time frame: on the third day after oocyte retrieval
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Derived from this study: PubMed 30593268Ashrafi M, Arabipoor A, Yahyaei A, Zolfaghari Z, Ghaffari F. Does the "delayed start" protocol with gonadotropin-releasing hormone antagonist improve the pregnancy outcome in Bologna poor responders? a randomized clinical trial. Reprod Biol Endocrinol. 2018 Dec 28;16(1):124. doi: 10.1186/s12958-018-0442-y.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hamid Gourabi, PhD study chair
Head of Royan Institute
Mahnaz Ashrafi, MD study director
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, Iran
Mandana Hemmat, MD principal investigator
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, Iran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing delayed start and Conventional in people with Infertility, Female, run by Royan Institute at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of dominant follicles (≥13 mm) (time frame: 24h after rhCG injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03134690, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.