InfertilityPhase 4XpectNCT00778999
Predictive Factors for Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH (Study 142003)(P05696)
A Phase 4 study testing Marvelon in people with Infertility, run by Organon and Co.
Trial summary
The success of assisted reproductive technologies (ART) is critically dependent on optimizing protocols for controlled ovarian stimulation to provide adequate numbers of good quality oocytes and embryos. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- Marvelon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 442 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2006to 24 Jul 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Females of couples with an indication for In Vitro Fertilization (IVF) and/or Intracytoplasmic Sperm Injection (ICSI) scheduled for their first COS treatment cycle
- Females >18 and <=39 years of age at the time of signing informed consent
- Body Mass Index (BMI) <= 32 kg/m^2
- Normal menstrual cycle length; 24-35 days
- Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed)
- Willing and able to sign informed consent
Who cannot join
- History of/or any current endocrine abnormality
- Less than 2 ovaries or any other ovarian abnormality (inc.>10mm endometrioma)
- Presence of unilateral or bilateral hydrosalpinx
- Presence of any clinically relevant pathology affecting the uterine cavity or fibroids >= 5cm
- History of recurrent miscarriage (3 or more, even when unexplained)
- FSH or LH > 12 IU/L as measured by a local laboratory (sample taken during the early follicular phase: menstrual day 2-5)
Show all 15Show fewer
- Any clinically relevant abnormal laboratory value (FSH, LH, estradiol (E2), Progesterone (P), total Testosterone (T), prolactin, Thyroid Stimulating Hormone (TSH), blood biochemistry, hematology and urinalysis) based on a sample during the screening phase.
- Contraindications for the use of gonadotropins (tumors, pregnancy, lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts)
- Contraindications for the use of oral contraceptive pills (history of (h/o) thromboembolism, breast cancer, undiagnosed vaginal bleeding)
- Recent history of/or current epilepsy, Human Immunodeficiency Virus (HIV) infection, diabetes, cardiovascular, gastrointestinal, hepatic, renal or pulmonary disease
- Abnormal karyotyping of the patient or her partner (if karyotyping is performed)
- History or presence of alcohol or drug abuse within 12 months of signing the consent
- Use of hormonal preparations within one month prior to randomization
- Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol
- Administration of investigational drugs within three months prior to signing the informed consent
About this study
Official title: A Randomized, Open-Label Clinical Trial to Identify Predictive Factors for Controlled Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH in GnRH Antagonist Regimen With or Without Oral Contraceptive Scheduling
The success of assisted reproductive technologies (ART) is critically dependent on optimizing protocols for controlled ovarian stimulation to provide adequate numbers of good quality oocytes and embryos. This optimization is mainly valuable to a group of infertility patients (9%-24%) who respond poorly to Controlled Ovarian Stimulation(COS). It is also important for an additional 2.6% of the infertility patients who manifest a high response to gonadotropin and are at risk for hyperstimulation syndrome, a life-threatening situation. Extensive research was carried out and led to the introduction of GnRH antagonist, as an alternative to Gonadotropin Releasing Hormone (GnRH) agonist, for the prevention of premature Luteinizing Hormone (LH) surges. Further research to optimize the GnRH antagonist regimen concluded that a daily treatment with 200 IU of recombinant Follicle Stimulating Hormone (recFSH) in a GnRH antagonist regimen is safe, well tolerated and results in a good clinical outcome. This protocol is now frequently applied in the US and Europe.
Predicting a woman's response (based on the assessment of ovarian reserve) to COS is useful in determining individualized clinical management strategies for low and high responders and thus avoiding cancellation. Such prediction when based on reliable scientific evidence is valuable in consulting patients about their chances of success. A large number of studies have been performed, which used certain clinical, ultrasonographic and hormonal markers (called predictive factors), to try to optimize a COS protocol for patients who were down-regulated with a long GnRH agonist protocol. Prospective trials of predictive models have also been used to adjust the starting dose of FSH to prevent a too low or too high ovarian response. To date, however, none have been performed for women undergoing ovarian stimulation with a GnRH antagonist protocol.
The primary objective of this randomized, open-label, multicenter clinical trial was to identify one or more factors capable of predicting ovarian response in women treated with a daily dose of 200 IU recFSH in a GnRH antagonist protocol. Since many ART centers now use oral contraceptives as a means to schedule patients stimulated with recFSH and a GnRH antagonist for assisted reproduction, the trial evaluated also whether intervention with oral contraceptives affects the accuracy of predictive models for ovarian response.
- Conditions
- Infertility
- Being tested
- Marvelon
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MarvelonDrug
oral contraceptive 1 tablet daily for 14 to 21 days
| Study group | Role | What they receive |
|---|---|---|
| Oral Contraceptive | Active comparator | Use of oral contraceptive pills prior to controlled ovarian stimulation Receives: Drug: Marvelon |
| Non-Oral Contraceptive | No intervention | No use of oral contraceptive pills prior to controlled ovarian stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Oocytes
The total number of oocytes on the Day of oocyte pick-up is an indication of ovarian response
Measured: 12 weeks
Secondary outcomes (5)
Number of Mature Oocytes
This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Measured: 12 weeks
Number of Follicles on Stimulation Day 8
This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Measured: 12 weeks
Number of Follicles on Day of hCG
This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Measured: 12 weeks
Number of Fertilized (2PN) Oocytes
This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Measured: 12 weeks
Number of Good Quality Embryos
This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study start1 Oct 2006
- Primary completion24 Jul 2008
- Study completion24 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)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
- 442 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00778999
- Sponsor's protocol ID
- P05696
- Other IDs
- 142003
- Acronym
- Xpect
- Status last verified
- Feb 2022
- First submitted
- 23 Oct 2008
- Last updated
- 4 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Broekmans FJ, Verweij PJ, Eijkemans MJ, Mannaerts BM, Witjes H. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2014 Aug;29(8):1688-97. doi: 10.1093/humrep/deu090. Epub 2014 Jun 5.
PubMed 24903202Andersen AN, Witjes H, Gordon K, Mannaerts B; Xpect investigators. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod. 2011 Dec;26(12):3413-23. doi: 10.1093/humrep/der318. Epub 2011 Sep 27.
PubMed 21954280
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Clinical Trial to Identify Predictive Factors for Controlled Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH in GnRH Antagonist Regimen With or Without Oral Contraceptive Scheduling
- ClinicalTrials.gov ID
- NCT00778999
- Acronym / sponsor ID
- Xpect / P05696
- Conditions
- Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 442 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2006 (actual)
- Primary completion
- 24 Jul 2008 (actual)
- Study completion
- 24 Jul 2008 (actual)
- First posted
- 24 Oct 2008 (estimated)
- Results
- Posted 12 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The success of assisted reproductive technologies (ART) is critically dependent on optimizing protocols for controlled ovarian stimulation to provide adequate numbers of good quality oocytes and embryos. This optimization is mainly valuable to a group of infertility patients (9%-24%) who respond poorly to Controlled Ovarian Stimulation(COS). It is also important for an additional 2.6% of the infertility patients who manifest a high response to gonadotropin and are at risk for hyperstimulation syndrome, a life-threatening situation. Extensive research was carried out and led to the introduction of GnRH antagonist, as an alternative to Gonadotropin Releasing Hormone (GnRH) agonist, for the prevention of premature Luteinizing Hormone (LH) surges. Further research to optimize the GnRH antagonist regimen concluded that a daily treatment with 200 IU of recombinant Follicle Stimulating Hormone (recFSH) in a GnRH antagonist regimen is safe, well tolerated and results in a good clinical outcome. This protocol is now frequently applied in the US and Europe.
Predicting a woman's response (based on the assessment of ovarian reserve) to COS is useful in determining individualized clinical management strategies for low and high responders and thus avoiding cancellation. Such prediction when based on reliable scientific evidence is valuable in consulting patients about their chances of success. A large number of studies have been performed, which used certain clinical, ultrasonographic and hormonal markers (called predictive factors), to try to optimize a COS protocol for patients who were down-regulated with a long GnRH agonist protocol. Prospective trials of predictive models have also been used to adjust the starting dose of FSH to prevent a too low or too high ovarian response. To date, however, none have been performed for women undergoing ovarian stimulation with a GnRH antagonist protocol.
The primary objective of this randomized, open-label, multicenter clinical trial was to identify one or more factors capable of predicting ovarian response in women treated with a daily dose of 200 IU recFSH in a GnRH antagonist protocol. Since many ART centers now use oral contraceptives as a means to schedule patients stimulated with recFSH and a GnRH antagonist for assisted reproduction, the trial evaluated also whether intervention with oral contraceptives affects the accuracy of predictive models for ovarian response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Contraceptive | Active comparator | Drug: MarvelonUse of oral contraceptive pills prior to controlled ovarian stimulation |
| Non-Oral Contraceptive | No intervention | –No use of oral contraceptive pills prior to controlled ovarian stimulation |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Females of couples with an indication for In Vitro Fertilization (IVF) and/or Intracytoplasmic Sperm Injection (ICSI) scheduled for their first COS treatment cycle
- Females >18 and <=39 years of age at the time of signing informed consent
- Body Mass Index (BMI) <= 32 kg/m^2
- Normal menstrual cycle length; 24-35 days
- Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed)
Key exclusion criteria (15 listed)
- History of/or any current endocrine abnormality
- Less than 2 ovaries or any other ovarian abnormality (inc.>10mm endometrioma)
- Presence of unilateral or bilateral hydrosalpinx
- Presence of any clinically relevant pathology affecting the uterine cavity or fibroids >= 5cm
- History of recurrent miscarriage (3 or more, even when unexplained)
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 |
|---|---|---|
| Marvelonoral contraceptive 1 tablet daily for 14 to 21 days | Drug | Oral Contraceptive |
Primary outcome
Total Number of Oocytes
Time frame: 12 weeks
The total number of oocytes on the Day of oocyte pick-up is an indication of ovarian response
5 secondary outcomes
Number of Mature Oocytes
Time frame: 12 weeks
Number of Follicles on Stimulation Day 8
Time frame: 12 weeks
Number of Follicles on Day of hCG
Time frame: 12 weeks
Number of Fertilized (2PN) Oocytes
Time frame: 12 weeks
Number of Good Quality Embryos
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24903202Broekmans FJ, Verweij PJ, Eijkemans MJ, Mannaerts BM, Witjes H. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2014 Aug;29(8):1688-97. doi: 10.1093/humrep/deu090. Epub 2014 Jun 5.
- Derived from this study: PubMed 21954280Andersen AN, Witjes H, Gordon K, Mannaerts B; Xpect investigators. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod. 2011 Dec;26(12):3413-23. doi: 10.1093/humrep/der318. Epub 2011 Sep 27.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Marvelon in people with Infertility, run by Organon and Co.
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 6 inclusion and 15 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 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 12 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Oocytes (time frame: 12 weeks). 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 NCT00778999, which also lists 2 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 4 Feb 2022.