InfertilityPhase 4KvLNCT00756028
Short Versus Long Protocol for IVF and IVF+ICSI
A Phase 4 study testing Patients receiving short protocol IVF/ICSI-treatment. and Long protocol in people with Infertility and Ovarian Hyperstimulation Syndrome, run by Peter Hornnes, MD, DMSc at 2 sites in Denmark.
Trial summary
Purpose: Comparing a GnRH agonist and an antagonist protocol for IVF/ICSI with regard to 1. frequency of ovarian hyperstimulation syndrome (OHSS) (1. outcome measure) 2. quality of life (2. outcome measure) 3. live birth rate (2. outcome measure) 4. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Infertility, Ovarian Hyperstimulation Syndrome, Quality of Life
- What is being tested?
- Patients receiving short protocol IVF/ICSI-treatment. and Long protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,099 participants
- Where
- 2 sitesDenmark
- Study dates
- Jan 2009to Dec 2015
- Phase
- Phase 4
- 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 18 to 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- All patients referred for infertility receiving their first IVF or IVF+ICSI treatment
Who cannot join
- Previous IVF or IVF+ICSI-treatment
- Uterine anomalies
- It is necessary to perform direct sperm aspiration from husband's/partner's testicles
- Allergy to one of the intervention products
- Patient is 40 years or above
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Dronninglund Fertility Clinic
Dronninglund, 9330
Fertility Clinic, Hvidovre Hospital
Hvidovre, 2650
About this study
Official title: Short Versus Long IVF-treatment. A Prospective, Consecutive and Randomized Comparative Study
Purpose: Comparing a GnRH agonist and an antagonist protocol for IVF/ICSI with regard to
- frequency of ovarian hyperstimulation syndrome (OHSS) (1. outcome measure)
- quality of life (2. outcome measure)
- live birth rate (2. outcome measure)
- gene expression profiles of granulosa and cumulus cells, and concentrations of estradiol and vascular endothelial growth factor in follicular fluid(not only compared between GnRH agonist and antagonist protocol, but also between patients with OHSS and no OHSS and patients becoming pregnant and not becoming pregnant (2. outcome measure), and
- number of oocytes removed per treatment, number of embryo transfers per treatment and number of spontaneous abortions per treatment (these three parameters are tertiary outcome measures).
In addition to the above mentioned efficacy outcome measures the safety outcome measure "frequency of known side-effects" will be compared between the two protocols.
Read the detailed description
Patients: 1100 patients are randomized prospectively to either treatment. Stratification: =<36 y/>36 y, IVF/ICSI, and treatment centre.
Methods: OHSS is quantified by consecutive measurements of weight, abdominal diameter, ultrasound measurements of ascites and ovarian volume, paraclinical parameters, and by a systematic patient questionnaire. Furthermore it is registered if the patients have been hospitalized and/or have had ascites drainage performed due to OHSS. Data from the first 100 patients are used together with Golans OHSS-classification, to make a more precise definition of OHSS. This definition is applied prospectively on data from the remaining patients.
Quality of life is gauged by a questionnaire. Child birth rate is ascertained by a pregnancy response questionnaire and by obtaining data from the Danish National Birth Registry.
Statistics: The study is designed to be able to show a 50% reduction of OHSS comparing short to long protocol.
- Being tested
- Patients receiving short protocol IVF/ICSI-treatment., Long protocol
- Keywords
- OHSS, quality of life, IVF, ICSI, GnRH-agonist, GnRH-antagonist
- Medical subject headings
- Infertility, Ovarian Hyperstimulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients receiving short protocol IVF/ICSI-treatment.Drug
Injection s.c. Orgalutran® (Ganirelix)0.25 mg once daily from day 5 of FSH-stimulation until HCG-day
Long protocolDrug
Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®:Nafarelin)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients receiving short protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-antagonist (Orgalutran®: Ganirelix) Receives: Drug: Patients receiving short protocol IVF/ICSI-treatment. |
| 2 | Active comparator | Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®: Nafarelin) Receives: Drug: Long protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Ovarian Hyperstimulation Syndrome (OHSS)
Measured: 3 years
Secondary outcomes (4)
Quality of life during treatment
Measured: 3 years
Live births
Measured: 3 years
Gene expression profiles of granulosa and cumulus cells
Measured: 3 years
Estradiol and vascular endothelial growth factor concentrations in follicular fluid.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2008 (estimated)
- Study startJan 2009
- Primary completionDec 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,099 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peter Hornnes, MD, DMSc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Peter Hornnes, MD, DMSc, Hvidovre University Hospital
- Investigators
- Thue Bryndorf, Study chair, Hvidovre University HospitalHelle Meinertz, Study chair, Hvidovre University HospitalPeter Hornnes, Principal investigator, Hvidovre University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00756028
- Sponsor's protocol ID
- KvL
- Acronym
- KvL
- Status last verified
- Jan 2016
- First submitted
- 18 Sep 2008
- Last updated
- 13 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Toftager M, Sylvest R, Schmidt L, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Pinborg A. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril. 2018 Jan;109(1):154-164. doi: 10.1016/j.fertnstert.2017.09.020. Epub 2017 Nov 23.
PubMed 29175067Toftager M, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Nilas L, Pinborg A. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017 Mar 1;32(3):556-567. doi: 10.1093/humrep/dew358.
PubMed 28130435Toftager M, Bogstad J, Bryndorf T, Lossl K, Roskaer J, Holland T, Praetorius L, Zedeler A, Nilas L, Pinborg A. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016 Jun;31(6):1253-64. doi: 10.1093/humrep/dew051. Epub 2016 Apr 8.
PubMed 27060174
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Versus Long IVF-treatment. A Prospective, Consecutive and Randomized Comparative Study
- ClinicalTrials.gov ID
- NCT00756028
- Acronym / sponsor ID
- KvL / KvL
- Keywords
- OHSS, quality of life, IVF, ICSI, GnRH-agonist, GnRH-antagonist
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,099 participants (actual)
- Lead sponsor
- Peter Hornnes, MD, DMScUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 19 Sep 2008 (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.
Purpose: Comparing a GnRH agonist and an antagonist protocol for IVF/ICSI with regard to
- frequency of ovarian hyperstimulation syndrome (OHSS) (1. outcome measure)
- quality of life (2. outcome measure)
- live birth rate (2. outcome measure)
- gene expression profiles of granulosa and cumulus cells, and concentrations of estradiol and vascular endothelial growth factor in follicular fluid(not only compared between GnRH agonist and antagonist protocol, but also between patients with OHSS and no OHSS and patients becoming pregnant and not becoming pregnant (2. outcome measure), and
- number of oocytes removed per treatment, number of embryo transfers per treatment and number of spontaneous abortions per treatment (these three parameters are tertiary outcome measures).
In addition to the above mentioned efficacy outcome measures the safety outcome measure "frequency of known side-effects" will be compared between the two protocols.
Detailed description
Patients: 1100 patients are randomized prospectively to either treatment. Stratification: =<36 y/>36 y, IVF/ICSI, and treatment centre.
Methods: OHSS is quantified by consecutive measurements of weight, abdominal diameter, ultrasound measurements of ascites and ovarian volume, paraclinical parameters, and by a systematic patient questionnaire. Furthermore it is registered if the patients have been hospitalized and/or have had ascites drainage performed due to OHSS. Data from the first 100 patients are used together with Golans OHSS-classification, to make a more precise definition of OHSS. This definition is applied prospectively on data from the remaining patients.
Quality of life is gauged by a questionnaire. Child birth rate is ascertained by a pregnancy response questionnaire and by obtaining data from the Danish National Birth Registry.
Statistics: The study is designed to be able to show a 50% reduction of OHSS comparing short to long protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Patients receiving short protocol IVF/ICSI-treatment.Patients receiving short protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-antagonist (Orgalutran®: Ganirelix) |
| 2 | Active comparator | Drug: Long protocolPatients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®: Nafarelin) |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- All patients referred for infertility receiving their first IVF or IVF+ICSI treatment
Key exclusion criteria (5 listed)
- Previous IVF or IVF+ICSI-treatment
- Uterine anomalies
- It is necessary to perform direct sperm aspiration from husband's/partner's testicles
- Allergy to one of the intervention products
- Patient is 40 years or above
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 |
|---|---|---|
| Patients receiving short protocol IVF/ICSI-treatment.Injection s.c. Orgalutran® (Ganirelix)0.25 mg once daily from day 5 of FSH-stimulation until HCG-day | Drug | 1 |
| Long protocolPatients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®:Nafarelin) | Drug | 2 |
Primary outcome
Frequency of Ovarian Hyperstimulation Syndrome (OHSS)
Time frame: 3 years
4 secondary outcomes
Quality of life during treatment
Time frame: 3 years
Live births
Time frame: 3 years
Gene expression profiles of granulosa and cumulus cells
Time frame: 3 years
Estradiol and vascular endothelial growth factor concentrations in follicular fluid.
Time frame: 3 years
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 13 Jan 2016.
- Derived from this study: PubMed 29175067Toftager M, Sylvest R, Schmidt L, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Pinborg A. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril. 2018 Jan;109(1):154-164. doi: 10.1016/j.fertnstert.2017.09.020. Epub 2017 Nov 23.
- Derived from this study: PubMed 28130435Toftager M, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Nilas L, Pinborg A. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017 Mar 1;32(3):556-567. doi: 10.1093/humrep/dew358.
- Derived from this study: PubMed 27060174Toftager M, Bogstad J, Bryndorf T, Lossl K, Roskaer J, Holland T, Praetorius L, Zedeler A, Nilas L, Pinborg A. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016 Jun;31(6):1253-64. doi: 10.1093/humrep/dew051. Epub 2016 Apr 8.
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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.
Thue Bryndorf study chair
Hvidovre University Hospital
Helle Meinertz study chair
Hvidovre University Hospital
Peter Hornnes principal investigator
Hvidovre University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Patients receiving short protocol IVF/ICSI-treatment. and Long protocol in people with Infertility and Ovarian Hyperstimulation Syndrome, run by Peter Hornnes, MD, DMSc at 2 sites in Denmark.
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 1 inclusion and 5 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 13 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Frequency of Ovarian Hyperstimulation Syndrome (OHSS) (time frame: 3 years). 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 NCT00756028, which also lists 3 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 13 Jan 2016.