Ovarian StimulationNCT04549649
The Effect of Dual Trigger for Final Oocyte Maturation on IVF/ICSI Outcomes in Patients With Suboptimal Ovarian Response
A study testing Dual triggering in people with Ovarian Stimulation and Reproductive Techniques, Assisted, run by Royan Institute at 1 site in Iran.
Trial summary
Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ovarian Stimulation, Reproductive Techniques, Assisted
- What is being tested?
- Dual triggering
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteIran
- Study dates
- 1 Nov 2019to 30 Nov 2022
- 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 20 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients with poor ovarian response (POR) diagnosis according to the POSEIDON stratification system (as POSEIDON group 1) with following criteria :
- Women' age under 35 years;
- Previous unexpected poor or suboptimal ovarian response after using conventional protocols (subgroup 1a: < 4 oocytes ) and (subgroup 1b: 4-9 oocytes retrieved)
- Adequate ovarian reserve (antral follicle count ≥5 on menstrual cycle day 2-3; and basal serum AMH ≥ 1.2 ng/ml)
Who cannot join
- Ovarian failure including basal FSH above 20 IU/l or no antral follicle by ultrasound examination;
- Endometriosis grade 3 or higher;
- Severe male infertility (surgical sperm extraction: TESE, PESA)
- Body mass index >30 kg/ m2
- History of uterine surgery as well as sub-mucosal and intramural fibroids greater than 5 cm or uterine polyps
- Treatment cycles with pre-implantation genetic diagnosis, blastocyst and donation embryo transfer indications
- Cigarette and drug addiction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Royan Institute for Reproductive Biomedicine
Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a sub-optimal ovarian response.
Read the detailed description
Ovulation stimulation will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a suboptimal ovarian response.
Controlled Ovulation stimulation (COS) will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. The required number of blocks will be randomly selected according to sample size.
The final ovarian stimulation (oocyte triggering) will be performed in groups A and B as follows:
Group A (Experimental): 0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously.
Group B (Control): Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously.
The COS cycles with less than two follicles will be cancelled s. Ovum pick up is performed 32-34 hours after oocyte triggering, and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.
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).
- Being tested
- Dual triggering
- Keywords
- Poor ovarian response, Dual trigger, GnRH antagonist protocol
- Medical subject headings
- Helping Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual triggeringOther
Adding GnRH agonist (0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) to routine oocyte triggering (two ampoules of Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) is defined as dual triggering.
| Study group | Role | What they receive |
|---|---|---|
| Group A (Experimental oocyte triggering approach) | Experimental | 0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously for final oocyte triggering. Receives: Other: Dual triggering |
| Group B (Routine oocyte triggering approach) | No intervention | Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously for final oocyte triggering. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of retrieved oocytes
In one hour after ovum pick-up, outcome measurement will be possible.
Measured: Day of oocyte pick-up (32-34 hours after hCG administration)
Total number of mature or metaphase II (MII) oocytes
In one hour after ovum pick-up, counting the total number of MII oocytes will be possible.
Measured: Day of oocyte pick-up ( 32-34 hours after hCG administration )
Oocyte recovery ratio
Ratio of the total number of follicles above 18 mm to the total number of retrieved oocytes
Measured: 32-34 hours after oocyte triggering
Secondary outcomes (2)
Fertilization rate
The number of 2 pronucleus (2pn) oocytes per number of injected and/or inseminated MII oocytes
Measured: Day 1 post oocyte retrieval
Quality of obtained embryos: grade
The quality of embryos was graded from 1 to 3 under inverted microscope 3 days after IVF/ICSI procedure. Embryos with even-sized blastomers and/or ≤10% fragments were classified as Grade 1 (Excellent or good quality). Grade 2 embryos (moderate or fair quality) had blastomeres with slightly-moderate size differences and/or 10- 20% fragments. Grade 3 embryos (poor quality) had markedly different-sized blastomers and/or >20% fragments.
Measured: 3 days after in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start1 Nov 2019
- Primary completion30 Nov 2021
- Study completion30 Nov 2022
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 Ovarian StimulationStudies 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Maryam Hafezi, M.D., Principal investigator, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549649
- Sponsor's protocol ID
- Research ID (96000024)
- Status last verified
- Jun 2023
- First submitted
- 5 Aug 2020
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The principle investigator of study can share IPD after finishing the study and publishing the results.
Publications
Hafezi M, Arabipoor A, Zareei M, Vesali S, Mostafaei P, Zameni N. The Effect of Dual Trigger on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes in Patients with Suboptimal Ovarian Response (POSEIDON Classification Group I): A Randomized Clinical Trial. Int J Fertil Steril. 2025 May 14;19(3):251-258. doi: 10.22074/ijfs.2025.2027114.1669.
PubMed 40590283
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Royan Institute for Reproductive Biomedicine
- ClinicalTrials.gov ID
- NCT04549649
- Acronym / sponsor ID
- Research ID (96000024)
- Keywords
- Poor ovarian response, Dual trigger, GnRH antagonist protocol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Royan InstituteOther government
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 30 Nov 2022 (actual)
- First posted
- 16 Sep 2020 (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.
Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a sub-optimal ovarian response.
Detailed description
Ovulation stimulation will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a suboptimal ovarian response.
Controlled Ovulation stimulation (COS) will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. The required number of blocks will be randomly selected according to sample size.
The final ovarian stimulation (oocyte triggering) will be performed in groups A and B as follows:
Group A (Experimental): 0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously.
Group B (Control): Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously.
The COS cycles with less than two follicles will be cancelled s. Ovum pick up is performed 32-34 hours after oocyte triggering, and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (Experimental oocyte triggering approach) | Experimental | Other: Dual triggering0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously for final oocyte triggering. |
| Group B (Routine oocyte triggering approach) | No intervention | –Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously for final oocyte triggering. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Patients with poor ovarian response (POR) diagnosis according to the POSEIDON stratification system (as POSEIDON group 1) with following criteria :
- Women' age under 35 years;
- Previous unexpected poor or suboptimal ovarian response after using conventional protocols (subgroup 1a: < 4 oocytes ) and (subgroup 1b: 4-9 oocytes retrieved)
- Adequate ovarian reserve (antral follicle count ≥5 on menstrual cycle day 2-3; and basal serum AMH ≥ 1.2 ng/ml)
Key exclusion criteria (7 listed)
- Ovarian failure including basal FSH above 20 IU/l or no antral follicle by ultrasound examination;
- Endometriosis grade 3 or higher;
- Severe male infertility (surgical sperm extraction: TESE, PESA)
- Body mass index >30 kg/ m2
- History of uterine surgery as well as sub-mucosal and intramural fibroids greater than 5 cm or uterine polyps
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 |
|---|---|---|
| Dual triggeringAdding GnRH agonist (0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) to routine oocyte triggering (two ampoules of Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) is defined as dual triggering. | Other | Group A (Experimental oocyte triggering approach) |
Primary outcome
Total number of retrieved oocytes
Time frame: Day of oocyte pick-up (32-34 hours after hCG administration)
In one hour after ovum pick-up, outcome measurement will be possible.
Total number of mature or metaphase II (MII) oocytes
Time frame: Day of oocyte pick-up ( 32-34 hours after hCG administration )
In one hour after ovum pick-up, counting the total number of MII oocytes will be possible.
Oocyte recovery ratio
Time frame: 32-34 hours after oocyte triggering
Ratio of the total number of follicles above 18 mm to the total number of retrieved oocytes
2 secondary outcomes
Fertilization rate
Time frame: Day 1 post oocyte retrieval
Quality of obtained embryos: grade
Time frame: 3 days after in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) procedure
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 15 Jun 2023.
- Derived from this study: PubMed 40590283Hafezi M, Arabipoor A, Zareei M, Vesali S, Mostafaei P, Zameni N. The Effect of Dual Trigger on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes in Patients with Suboptimal Ovarian Response (POSEIDON Classification Group I): A Randomized Clinical Trial. Int J Fertil Steril. 2025 May 14;19(3):251-258. doi: 10.22074/ijfs.2025.2027114.1669.
- Individual participant dataSharing planned: Yes. The principle investigator of study can share IPD after finishing the study and publishing the results.
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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.
Maryam Hafezi, M.D. principal investigator
Royan Institute for Reproductive Biomedicine, 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 Dual triggering in people with Ovarian Stimulation and Reproductive Techniques, Assisted, 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 4 inclusion and 7 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 15 Jun 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?
Total number of retrieved oocytes (time frame: Day of oocyte pick-up (32-34 hours after hCG administration)). The study lists 3 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 NCT04549649, 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 15 Jun 2023.