Poor RespondersPhase 4NCT02201914
Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
A Phase 4 study testing Clomiphene citrate, Daily FSH and LH plus Cetrorelix and Triptorelin plus daily FSH anh LH in people with Poor Responders and IVF, run by Bioroma at 1 site in Italy.
Trial summary
Poor ovarian response to stimulation in IVF cycles is a challenging and frustrating condition, due to its poor prognosis in terms of chances of pregnancy and live births. Various ovarian stimulation regimens have been tried to overcome these obstacles. Read more about this study
- Who is it for?
- Ages 25 to 44 years, women only
- Conditions the study is for
- Poor Responders, IVF, Clomiphene Citrate
- What is being tested?
- Clomiphene citrate, Daily FSH and LH plus Cetrorelix and Triptorelin plus daily FSH anh LH
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2014to Nov 2014
- 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 25 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- poor responders in a previous IVF cycle at least 3 months before at our center and undergoing a new IVF attempt with at least two of the following criteria : I) age > 40 years old; II) basal follicular stimulation hormone (FSH) > 12 mIU/ml; III) three or fewer oocytes retrieved in the previous IVF cycle; IV) low estradiol levels on the day of human chorionic gonadotropin (hCG) administration (< 1500 pmol/ml).
Who cannot join
- body mass index > 30
- biochemical and ultrasound evidence of polycystic ovary syndrome
- stage III-IV endometriosis
- inflammatory or autoimmune disorders
- metabolic disease
- infertility medications within the past two months
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Bioroma
Rome, Rome, 00197
Mauro Schimberni, MD, +39063334266, bioroma@bioroma.net
About this study
Official title: Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF: a Randomized Study
Poor ovarian response to stimulation in IVF cycles is a challenging and frustrating condition, due to its poor prognosis in terms of chances of pregnancy and live births. Various ovarian stimulation regimens have been tried to overcome these obstacles. A simple approach is increase the dose of the gonadotropin administration, but the results in terms of pregnancy rate are very low Another commonly used stimulation regimen is the microdose GnRH agonist protocol, which takes advantage of the initial rise in endogenous gonadotropins that follows the agonist administration in the early follicular phase and subsequently prevents a premature LH surge, with fewer cycle cancellations. However, their application in poor responders, even if in small doses and for a limited period, has been questioned as they may cause oversuppression of ovarian function, leading to a prolonged cycle and increased treatment costs without improving the outcomes.
Recently, GnRH antagonists were introduced in ART treatment. They are effective in preventing a premature LH surge and allow for a more natural recruitment of follicles in the follicular phase in a non-suppressed ovary, offering a potential alternative in the treatment of these patients. However, randomized studies evaluating the efficacy of this regimen in poor responders did not show any improvements in pregnancy rates. Current approach have included the addition of oral agents such us clomiphene citrate (CC) to gonadotropins. Some authors have investigated the role of CC in addition to low dose of gonadotropins in mild stimulation regimen, demonstrating that, despite a small number of retrieved oocytes, good quality embryos were produced with a subsequent improvement in the fertilization rate, clinical pregnancy rate and live birth rate. The only study that evaluate the efficacy of CC in addition to high doses of gonadotropins in poor responders showed improving in number of retrieved oocytes, transferred embryos and biochemical pregnancy; however, clinical pregnancy rate and live birth rate remained low and showed no measurable increase.
The aim of this study was to compare the efficacy of the CC as an adjunctive to a high dose of gonadotropins in cycles with antagonist protocols with the microdose GnRH agonist and flexible antagonist protocols in women who responded poorly to ovarian stimulation, to determine whether this protocol may improve IVF outcomes, offering a valid alternative in poor responder patients treatment.
- Conditions
- Poor Responders, IVF, Clomiphene Citrate, GnRH Agonist, GnRH Antagonist
- Being tested
- Clomiphene citrate, Daily FSH and LH plus Cetrorelix, Triptorelin plus daily FSH anh LH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomiphene citrateDrug
patients receive clomiphene citrate 100 mg daily starting on day 2 for 5 days and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 5; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection
Daily FSH and LH plus CetrorelixDrug
Women receive an initial daily dose of 450 IU recombinant FSH and 225 IU recombinant LH starting on day 3; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection.
Triptorelin plus daily FSH anh LHDrug
women receive short-acting Triptorelin 0,05 mg daily starting on day 1 until the hCG injection and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 2.
| Study group | Role | What they receive |
|---|---|---|
| Clomiphene citrate | Experimental | Not described Receives: Drug: Clomiphene citrate |
| Daily FSH and LH plus Cetrorelix | Experimental | Not described Receives: Drug: Daily FSH and LH plus Cetrorelix |
| Triptorelin plus daily FSH and LH | Experimental | Not described Receives: Drug: Triptorelin plus daily FSH anh LH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
Measured: Time Frame: until 12th gestational week
Secondary outcomes (1)
implantation rate
Measured: Time Frame: until 12th gestational week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startJan 2014
- Primary completionOct 2014 (estimated)
- Study completionNov 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Poor RespondersStudies 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bioroma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201914
- Sponsor's protocol ID
- BRM003
- Status last verified
- Jul 2014
- First submitted
- 22 Jul 2014
- Last updated
- 28 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF: a Randomized Study
- ClinicalTrials.gov ID
- NCT02201914
- Acronym / sponsor ID
- BRM003
- Conditions
- Poor Responders, IVF, Clomiphene Citrate, GnRH Agonist, GnRH Antagonist
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- BioromaUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Oct 2014 (estimated)
- Study completion
- Nov 2014 (estimated)
- First posted
- 28 Jul 2014 (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.
Poor ovarian response to stimulation in IVF cycles is a challenging and frustrating condition, due to its poor prognosis in terms of chances of pregnancy and live births. Various ovarian stimulation regimens have been tried to overcome these obstacles. A simple approach is increase the dose of the gonadotropin administration, but the results in terms of pregnancy rate are very low Another commonly used stimulation regimen is the microdose GnRH agonist protocol, which takes advantage of the initial rise in endogenous gonadotropins that follows the agonist administration in the early follicular phase and subsequently prevents a premature LH surge, with fewer cycle cancellations. However, their application in poor responders, even if in small doses and for a limited period, has been questioned as they may cause oversuppression of ovarian function, leading to a prolonged cycle and increased treatment costs without improving the outcomes.
Recently, GnRH antagonists were introduced in ART treatment. They are effective in preventing a premature LH surge and allow for a more natural recruitment of follicles in the follicular phase in a non-suppressed ovary, offering a potential alternative in the treatment of these patients. However, randomized studies evaluating the efficacy of this regimen in poor responders did not show any improvements in pregnancy rates. Current approach have included the addition of oral agents such us clomiphene citrate (CC) to gonadotropins. Some authors have investigated the role of CC in addition to low dose of gonadotropins in mild stimulation regimen, demonstrating that, despite a small number of retrieved oocytes, good quality embryos were produced with a subsequent improvement in the fertilization rate, clinical pregnancy rate and live birth rate. The only study that evaluate the efficacy of CC in addition to high doses of gonadotropins in poor responders showed improving in number of retrieved oocytes, transferred embryos and biochemical pregnancy; however, clinical pregnancy rate and live birth rate remained low and showed no measurable increase.
The aim of this study was to compare the efficacy of the CC as an adjunctive to a high dose of gonadotropins in cycles with antagonist protocols with the microdose GnRH agonist and flexible antagonist protocols in women who responded poorly to ovarian stimulation, to determine whether this protocol may improve IVF outcomes, offering a valid alternative in poor responder patients treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Clomiphene citrate | Experimental | Drug: Clomiphene citrate |
| Daily FSH and LH plus Cetrorelix | Experimental | Drug: Daily FSH and LH plus Cetrorelix |
| Triptorelin plus daily FSH and LH | Experimental | Drug: Triptorelin plus daily FSH anh LH |
Who may qualify
- Ages
- 25 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- poor responders in a previous IVF cycle at least 3 months before at our center and undergoing a new IVF attempt with at least two of the following criteria : I) age > 40 years old; II) basal follicular stimulation hormone (FSH) > 12 mIU/ml; III) three or fewer oocytes retrieved in the previous IVF cycle; IV) low estradiol levels on the day of human chorionic gonadotropin (hCG) administration (< 1500 pmol/ml).
Key exclusion criteria (6 listed)
- body mass index > 30
- biochemical and ultrasound evidence of polycystic ovary syndrome
- stage III-IV endometriosis
- inflammatory or autoimmune disorders
- metabolic disease
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 |
|---|---|---|
| Clomiphene citratepatients receive clomiphene citrate 100 mg daily starting on day 2 for 5 days and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 5; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection | Drug | Clomiphene citrate |
| Daily FSH and LH plus CetrorelixWomen receive an initial daily dose of 450 IU recombinant FSH and 225 IU recombinant LH starting on day 3; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection. | Drug | Daily FSH and LH plus Cetrorelix |
| Triptorelin plus daily FSH anh LHwomen receive short-acting Triptorelin 0,05 mg daily starting on day 1 until the hCG injection and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 2. | Drug | Triptorelin plus daily FSH and LH |
Primary outcome
Clinical pregnancy rate
Time frame: Time Frame: until 12th gestational week
1 secondary outcome
implantation rate
Time frame: Time Frame: until 12th gestational week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2014.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clomiphene citrate, Daily FSH and LH plus Cetrorelix and Triptorelin plus daily FSH anh LH in people with Poor Responders and IVF, run by Bioroma at 1 site in Italy.
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 6 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: status not confirmed, as of the sponsor's last update on 28 Jul 2014. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mauro Schimberni, MD (+39063334266, bioroma@bioroma.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate (time frame: Time Frame: until 12th gestational week). 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 28 Jul 2014.