Ovarian StimulationPhase 1/2NCT00823004
Antagonist/Letrozole in Poor Responders
A Phase 1/2 study testing letrozole, oral contraceptive (Marvelone) and GnRH agonist (buserelin) in people with Ovarian Stimulation, run by Yazd Research & Clinical Center for Infertility at 1 site in Iran.
Trial summary
Failure to respond to controlled ovarian hyperstimulation (COH) is still a major concern in assisted reproduction and there is no consensus on the ovarian stimulation choice regime for poor responders. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ovarian Stimulation
- What is being tested?
- letrozole, oral contraceptive (Marvelone) and GnRH agonist (buserelin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteIran
- Study dates
- Jun 2008to Oct 2009
- Phase
- Phase 1/2
- 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
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- at least one previous failed IVF cycle in which three or fewer follicles with a mean diameter of 16 mm were achieved, and/or
- serum E2 level measured on the day of hCG administration was ≤500 pg/ml
Who cannot join
- day 3 serum FSH level ≥12 mIU/mL
- there is no age limit
Trial locations and contacts
1 site in 1 country.
Iran1 site
Research and clinical center for infertility
Yazd, Yazd Province, 8916877391
About this study
Official title: GnRH Antagonist /Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing in Vitro Fertilization
Failure to respond to controlled ovarian hyperstimulation (COH) is still a major concern in assisted reproduction and there is no consensus on the ovarian stimulation choice regime for poor responders.
Aim: To evaluate and compare the efficacy of a microdose GnRH agonist flare (MF) and a GnRH antagonist/letrozole (A/L) protocols in poor responders undergoing in vitro fertilization (IVF).
Methods: One hundred eighty poor responder patients will be randomized to an ovarian stimulation protocol with either a MF or a letrozole and high dose FSH/hMG and flexible GnRH antagonist protocol.
Read the detailed description
All women receive 21 days of an oral contraceptive. A MF protocol will be used for ovarian stimulation in 90 patients. Three days after the last pill, a GnRH-agonist buserelin (Suprefact, Aventis Pharma, Frankfurt, Germany) 50 µg SC twice daily will be initiated and two days after that, recombinant FSH (Gonal-F, Serono, Aubonne, Switzerland) or hMG (Merional, IBSA, Lugano, Switzerland) 300-450 IU/day will be administered. Ninetyty patients will be assigned to an A/L protocol. After oral contraceptive withdrawal bleeding on day 3 of cycle, recombinant FSH or hMG 300-450 IU/day will be initiated and letrozole (Femara, Novartis, East Hanover, NJ) 5 mg/day will be administered for 5 days. When the dominant follicle reached 14 mm in mean diameter, ganirelix acetate (Antagon, Organon, West Orange, NJ) 0.25 mg SC daily will be started.
Patients weill be monitored by serial vaginal ultrasonography and measurement of serum E2 level. When at least two follicles with a mean diameter of 18 mm will be achieved hCG (Pregnyl, Organon, Oss, the Netherlands) 10000 IU will be administered. Cycle cancellation will be considered when fewer than two follicles with normal growth pattern weill be noted.
Oocyte retrieval will be performed 34-36 hours after hCG administration. Conventional IVF or intracytoplasmic sperm injection (ICSI) will be performed as appropriate. Embryos with 4-6 equally sized blastomers on day 2 with ≤ 20% fragmentation and no multinucleation will be considered top quality embryos. Embryos with 2-6 equally or unequally blastomers with ≤20% fragmentation and no multinucleation will be considered good quality embryos. Embryos will be transferred on day 2 or 3 under ultrasound guidance, with a C.C.D. embryo transfer catheter ( Laboratoire C.C.D., Paris, France). Luteal support with progesterone in oil (Progesterone, Aburaihan Co., Tehran, Iran) 100 mg daily IM will be started on the day of oocyte retrieval.
Serum β-hCG level will be measured 14 days after embryo transfer and a transvaginal ultrasonography will be performed 3 weeks after positive β-hCG for documentation of gestational sac and fetal heart activity. Clinical pregnancy will be considered as the presence of a gestational sac with fetal heart activity.
- Conditions
- Ovarian Stimulation
- Being tested
- letrozole, oral contraceptive (Marvelone), GnRH agonist (buserelin), recombinant FSH or hMG, ganirelix acetate
- Keywords
- controlled ovarian hyperstimulation, pregnancy rate, Poor responders, GnRH antagonist, GnRH agonist, letrozole, in vitro fertilization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Also called letrozole (Femara, Novartis, East Hanover, NJ)
letrozole 5mg/day from day 3 to day 7 of menstrual cycle
oral contraceptive (Marvelone)Drug
Also called Marvelon
oral contraceptive, first 21 days
GnRH agonist (buserelin)Drug
Also called suprefact
50 µg SC twice daily
recombinant FSH or hMGDrug
Also called Gonal F, Merional
recombinant FSH or hMG 300-450 IU/day
ganirelix acetateDrug
Also called Antagon
GnRH antagonist (ganirelix acetate) when a leading follicle reaches a mean diameter of 14 mm, 0.25 mg per day (Antagon, Organon, West Orange, NJ)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation Receives: Drug: letrozole; Drug: oral contraceptive (Marvelone); Drug: recombinant FSH or hMG; Drug: ganirelix acetate |
| 2 | Active comparator | MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol Receives: Drug: oral contraceptive (Marvelone); Drug: GnRH agonist (buserelin); Drug: recombinant FSH or hMG |
What is being measured
The primary outcome is the main question the study is designed to answer.
pregnancy rate
Measured: 5 weeks
Secondary outcomes (1)
stimulation outcomes
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2009 (estimated)
- Study startJun 2008
- Primary completionFeb 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yazd Research & Clinical Center for Infertility
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, homa oskouian, Yazd Research & Clinical Center for Infertility
- Investigators
- homa oskouian, M.D., Principal investigator, Research and clinical center for infertilityrobab davar, MD, Principal investigator, Research and clinical center for infertility
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00823004
- Sponsor's protocol ID
- 1969yazdRCCI
- Status last verified
- Dec 2013
- First submitted
- 14 Jan 2009
- Last updated
- 23 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GnRH Antagonist /Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing in Vitro Fertilization
- ClinicalTrials.gov ID
- NCT00823004
- Acronym / sponsor ID
- 1969yazdRCCI
- Conditions
- Ovarian Stimulation
- Keywords
- controlled ovarian hyperstimulation, pregnancy rate, Poor responders, GnRH antagonist, GnRH agonist, letrozole, in vitro fertilization
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Yazd Research & Clinical Center for InfertilityUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 15 Jan 2009 (estimated)
- 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.
Failure to respond to controlled ovarian hyperstimulation (COH) is still a major concern in assisted reproduction and there is no consensus on the ovarian stimulation choice regime for poor responders.
Aim: To evaluate and compare the efficacy of a microdose GnRH agonist flare (MF) and a GnRH antagonist/letrozole (A/L) protocols in poor responders undergoing in vitro fertilization (IVF).
Methods: One hundred eighty poor responder patients will be randomized to an ovarian stimulation protocol with either a MF or a letrozole and high dose FSH/hMG and flexible GnRH antagonist protocol.
Detailed description
All women receive 21 days of an oral contraceptive. A MF protocol will be used for ovarian stimulation in 90 patients. Three days after the last pill, a GnRH-agonist buserelin (Suprefact, Aventis Pharma, Frankfurt, Germany) 50 µg SC twice daily will be initiated and two days after that, recombinant FSH (Gonal-F, Serono, Aubonne, Switzerland) or hMG (Merional, IBSA, Lugano, Switzerland) 300-450 IU/day will be administered. Ninetyty patients will be assigned to an A/L protocol. After oral contraceptive withdrawal bleeding on day 3 of cycle, recombinant FSH or hMG 300-450 IU/day will be initiated and letrozole (Femara, Novartis, East Hanover, NJ) 5 mg/day will be administered for 5 days. When the dominant follicle reached 14 mm in mean diameter, ganirelix acetate (Antagon, Organon, West Orange, NJ) 0.25 mg SC daily will be started.
Patients weill be monitored by serial vaginal ultrasonography and measurement of serum E2 level. When at least two follicles with a mean diameter of 18 mm will be achieved hCG (Pregnyl, Organon, Oss, the Netherlands) 10000 IU will be administered. Cycle cancellation will be considered when fewer than two follicles with normal growth pattern weill be noted.
Oocyte retrieval will be performed 34-36 hours after hCG administration. Conventional IVF or intracytoplasmic sperm injection (ICSI) will be performed as appropriate. Embryos with 4-6 equally sized blastomers on day 2 with ≤ 20% fragmentation and no multinucleation will be considered top quality embryos. Embryos with 2-6 equally or unequally blastomers with ≤20% fragmentation and no multinucleation will be considered good quality embryos. Embryos will be transferred on day 2 or 3 under ultrasound guidance, with a C.C.D. embryo transfer catheter ( Laboratoire C.C.D., Paris, France). Luteal support with progesterone in oil (Progesterone, Aburaihan Co., Tehran, Iran) 100 mg daily IM will be started on the day of oocyte retrieval.
Serum β-hCG level will be measured 14 days after embryo transfer and a transvaginal ultrasonography will be performed 3 weeks after positive β-hCG for documentation of gestational sac and fetal heart activity. Clinical pregnancy will be considered as the presence of a gestational sac with fetal heart activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: letrozole, Drug: oral contraceptive (Marvelone), Drug: recombinant FSH or hMG, Drug: ganirelix acetateA/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation |
| 2 | Active comparator | Drug: oral contraceptive (Marvelone), Drug: GnRH agonist (buserelin), Drug: recombinant FSH or hMGMF: In this arm poor responders are treated by microdose GnRH agonist flare protocol |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- at least one previous failed IVF cycle in which three or fewer follicles with a mean diameter of 16 mm were achieved, and/or
- serum E2 level measured on the day of hCG administration was ≤500 pg/ml
Key exclusion criteria (2 listed)
- day 3 serum FSH level ≥12 mIU/mL
- there is no age limit
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 |
|---|---|---|
| letrozoleAlso: letrozole (Femara, Novartis, East Hanover, NJ)letrozole 5mg/day from day 3 to day 7 of menstrual cycle | Drug | 1 |
| oral contraceptive (Marvelone)Also: Marvelonoral contraceptive, first 21 days | Drug | 1, 2 |
| GnRH agonist (buserelin)Also: suprefact50 µg SC twice daily | Drug | 2 |
| recombinant FSH or hMGAlso: Gonal F, Merionalrecombinant FSH or hMG 300-450 IU/day | Drug | 1, 2 |
| ganirelix acetateAlso: AntagonGnRH antagonist (ganirelix acetate) when a leading follicle reaches a mean diameter of 14 mm, 0.25 mg per day (Antagon, Organon, West Orange, NJ) | Drug | 1 |
Primary outcome
pregnancy rate
Time frame: 5 weeks
1 secondary outcome
stimulation outcomes
Time frame: 2 weeks
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 23 Dec 2013.
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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.
homa oskouian, M.D. principal investigator
Research and clinical center for infertility
robab davar, MD principal investigator
Research and clinical center for infertility
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing letrozole, oral contraceptive (Marvelone) and GnRH agonist (buserelin) in people with Ovarian Stimulation, run by Yazd Research & Clinical Center for Infertility 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 2 inclusion and 2 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 23 Dec 2013. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
pregnancy rate (time frame: 5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Dec 2013.