InfertilityPhase 2/3NCT01798836
Oestradiol Pre-treatment in an Ultrashort Flare GnRH Agonist/GnRH Antagonist Protocol in Poor Responders Undergoing IVF
A Phase 2/3 study testing Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol and GnRH agonist or antagonist protocol without oestradiol pre-treatment in people with Infertility, run by National and Kapodistrian University of Athens at 1 site in Greece.
Trial summary
To evaluate the effect of oestradiol pre-treatment in a combined ultrashort flare GnRH agonist /GnRH antagonist protocol Read more about this study
- Who is it for?
- Ages 25 to 44 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol and GnRH agonist or antagonist protocol without oestradiol pre-treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteGreece
- Study dates
- Feb 2013to Feb 2015
- Phase
- Phase 2/3
- 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 25 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Patients with poor or no response in previous COH for IVF cycles
- Patients with AMH < 1 and/or FSH >12
- Poor quality of embryos in previous cycles
- Age of patients up to 44 years
Who cannot join
- Patients with normal ovarian reserve
- Patients with sonographically detected hydrosalpinges
- Presence of intramural fibroid distorting the endometrial cavity or submucous myoma or Asherman's syndrome
- Women with thrombofilia disorders
Trial locations and contacts
1 site in 1 country.
Greece1 site
Assisted Reproduction Unit, 3rd Department of Obstetrics and Gynecology. Attikon University Hospital
Athens, Attica, 12642
About this study
To evaluate the effect of oestradiol pre-treatment in a combined ultrashort flare GnRH agonist /GnRH antagonist protocol
Read the detailed description
The combined ultrashort flare GnRH agonist /GnRH antagonist protocol during COH cycle resulted in a significantly higher clinical pregnancy rate in patients with poor embryo quality, with repeated IVF failures and in poor responders. This is a protocol combining the effect of the microdose flare on endogenous FSH release with the benefit of an immediate LH suppression of the GnRH antagonist.
A major disadvantage of the use of a GnRH antagonist protocol is the limitation for programming cycles, as the drugs administration is started on day 2 of the menstrual cycle and is strictly followed until the hCG criteria are met.
The purpose of the study is to perform oestradiol pre-treatment with the combined ultrashort flare GnRH agonist /GnRH antagonist protocol aiming to
- better programme an antagonist cycle and
- improve the IVF outcome parameters, from the production of more follicles / oocytes up to the rise in live birth rates.
- Conditions
- Infertility
- Being tested
- Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol, GnRH agonist or antagonist protocol without oestradiol pre-treatment
- Keywords
- IVF/ICSI cycles, poor responders, ultrashort flare protocol, antagonist protocol
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocolProcedure or surgery
GnRH agonist or antagonist protocol without oestradiol pre-treatmentProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Oestradiol and ultrashort GnRH agonist/antagonist protocol | Experimental | Women will begin pretreatment with 4 mg/day of 17 β-estradiol before the combination of GnRH ultashort agonist and antagonist protocol Receives: Procedure: Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol |
| GnRH agonist or antagonist protocol. | Active comparator | Women will undergo either a conventional short or long GnRH agonist or an antagonist protocol during COH for IVF Receives: Procedure: GnRH agonist or antagonist protocol without oestradiol pre-treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
Measured: 2 years
Clinical pregnancy rate
Measured: 2 years
Secondary outcomes (5)
Number of oocytes retrieved
Measured: 2 years
Top embryo quality at day 2
Measured: 2 years
Biochemical pregnancy
Measured: 2 years
Ectopic pregnancy
Measured: 2 years
Miscarriage rate
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionJan 2015
- Study completionFeb 2015
Why it stopped: Obtained results were not good. Protocol was proved ineffective.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by National and Kapodistrian University of AthensThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siristatidis Charalampos, MD, PhD, National and Kapodistrian University of Athens
- Investigators
- George Salamalekis, MD, PhD, Principal investigator, National and Kapodistrian University of AthensCharalampos Siristatidis, Assistant Professor, Principal investigator, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01798836
- Sponsor's protocol ID
- 030675
- Status last verified
- Aug 2015
- First submitted
- 20 Feb 2013
- Last updated
- 6 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Griesinger G, Kolibianakis EM, Venetis C, Diedrich K, Tarlatzis B. Oral contraceptive pretreatment significantly reduces ongoing pregnancy likelihood in gonadotropin-releasing hormone antagonist cycles: an updated meta-analysis. Fertil Steril. 2010 Nov;94(6):2382-4. doi: 10.1016/j.fertnstert.2010.04.025. Epub 2010 May 26.
PubMed 20537631Bosch E. Can we skip weekends in GnRH antagonist cycles without compromising the final outcome? Fertil Steril. 2012 Jun;97(6):1299-300. doi: 10.1016/j.fertnstert.2012.04.024. No abstract available.
PubMed 22656307Orvieto R, Nahum R, Rabinson J, Gemer O, Anteby EY, Meltcer S. Ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist for patients with repeated IVF failures and poor embryo quality. Fertil Steril. 2009 Apr;91(4 Suppl):1398-400. doi: 10.1016/j.fertnstert.2008.04.064. Epub 2008 Aug 3.
PubMed 18675974Cedrin-Durnerin I, Guivarc'h-Leveque A, Hugues JN; Groupe d'Etude en Medecine et Endocrinologie de la Reproduction. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012 Jun;97(6):1359-64.e1. doi: 10.1016/j.fertnstert.2012.02.028. Epub 2012 Mar 28.
PubMed 22464760
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oestradiol Pre-treatment in an Ultrashort Flare GnRH Agonist/GnRH Antagonist Protocol in Poor Responders Undergoing IVF
- ClinicalTrials.gov ID
- NCT01798836
- Acronym / sponsor ID
- 030675
- Conditions
- Infertility
- Keywords
- IVF/ICSI cycles, poor responders, ultrashort flare protocol, antagonist protocol
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Obtained results were not good. Protocol was proved ineffective.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 26 Feb 2013 (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.
To evaluate the effect of oestradiol pre-treatment in a combined ultrashort flare GnRH agonist /GnRH antagonist protocol
Detailed description
The combined ultrashort flare GnRH agonist /GnRH antagonist protocol during COH cycle resulted in a significantly higher clinical pregnancy rate in patients with poor embryo quality, with repeated IVF failures and in poor responders. This is a protocol combining the effect of the microdose flare on endogenous FSH release with the benefit of an immediate LH suppression of the GnRH antagonist.
A major disadvantage of the use of a GnRH antagonist protocol is the limitation for programming cycles, as the drugs administration is started on day 2 of the menstrual cycle and is strictly followed until the hCG criteria are met.
The purpose of the study is to perform oestradiol pre-treatment with the combined ultrashort flare GnRH agonist /GnRH antagonist protocol aiming to
- better programme an antagonist cycle and
- improve the IVF outcome parameters, from the production of more follicles / oocytes up to the rise in live birth rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oestradiol and ultrashort GnRH agonist/antagonist protocol | Experimental | Procedure: Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocolWomen will begin pretreatment with 4 mg/day of 17 β-estradiol before the combination of GnRH ultashort agonist and antagonist protocol |
| GnRH agonist or antagonist protocol. | Active comparator | Procedure: GnRH agonist or antagonist protocol without oestradiol pre-treatmentWomen will undergo either a conventional short or long GnRH agonist or an antagonist protocol during COH for IVF |
Who may qualify
- Ages
- 25 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Patients with poor or no response in previous COH for IVF cycles
- Patients with AMH < 1 and/or FSH >12
- Poor quality of embryos in previous cycles
- Age of patients up to 44 years
Key exclusion criteria (4 listed)
- Patients with normal ovarian reserve
- Patients with sonographically detected hydrosalpinges
- Presence of intramural fibroid distorting the endometrial cavity or submucous myoma or Asherman's syndrome
- Women with thrombofilia disorders
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 |
|---|---|---|
| Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol | Procedure or surgery | Oestradiol and ultrashort GnRH agonist/antagonist protocol |
| GnRH agonist or antagonist protocol without oestradiol pre-treatment | Procedure or surgery | GnRH agonist or antagonist protocol. |
Primary outcome
Live birth rate
Time frame: 2 years
Clinical pregnancy rate
Time frame: 2 years
5 secondary outcomes
Number of oocytes retrieved
Time frame: 2 years
Top embryo quality at day 2
Time frame: 2 years
Biochemical pregnancy
Time frame: 2 years
Ectopic pregnancy
Time frame: 2 years
Miscarriage rate
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Obtained results were not good. Protocol was proved ineffective.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2015.
- Background: PubMed 20537631Griesinger G, Kolibianakis EM, Venetis C, Diedrich K, Tarlatzis B. Oral contraceptive pretreatment significantly reduces ongoing pregnancy likelihood in gonadotropin-releasing hormone antagonist cycles: an updated meta-analysis. Fertil Steril. 2010 Nov;94(6):2382-4. doi: 10.1016/j.fertnstert.2010.04.025. Epub 2010 May 26.
- Background: PubMed 22656307Bosch E. Can we skip weekends in GnRH antagonist cycles without compromising the final outcome? Fertil Steril. 2012 Jun;97(6):1299-300. doi: 10.1016/j.fertnstert.2012.04.024. No abstract available.
- Results publication: PubMed 18675974Orvieto R, Nahum R, Rabinson J, Gemer O, Anteby EY, Meltcer S. Ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist for patients with repeated IVF failures and poor embryo quality. Fertil Steril. 2009 Apr;91(4 Suppl):1398-400. doi: 10.1016/j.fertnstert.2008.04.064. Epub 2008 Aug 3.
- Results publication: PubMed 22464760Cedrin-Durnerin I, Guivarc'h-Leveque A, Hugues JN; Groupe d'Etude en Medecine et Endocrinologie de la Reproduction. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012 Jun;97(6):1359-64.e1. doi: 10.1016/j.fertnstert.2012.02.028. Epub 2012 Mar 28.
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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.
George Salamalekis, MD, PhD principal investigator
National and Kapodistrian University of Athens
Charalampos Siristatidis, Assistant Professor principal investigator
National and Kapodistrian University of Athens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Oestradiol pre-treatment and combination of GnRH agonist/antagonist protocol and GnRH agonist or antagonist protocol without oestradiol pre-treatment in people with Infertility, run by National and Kapodistrian University of Athens at 1 site in Greece.
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 4 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: stopped early, as of the sponsor's last update on 6 Aug 2015. 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 Greece. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Obtained results were not good. Protocol was proved ineffective.). Results are not available in the source record.
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?
Live birth rate (time frame: 2 years). 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 NCT01798836, which also lists 4 linked publications.
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 6 Aug 2015.