Diminished Ovarian ReservePhase 4DOS/DORNCT01614067
Delayed Start to Ovarian Stimulation
A Phase 4 study testing Ganirelix acetate in people with Diminished Ovarian Reserve and Infertility, run by University of California, San Francisco at 1 site in United States.
Trial summary
In couples with infertility secondary to Diminished Ovarian Reserve, the investigators hypothesize that a delayed start (7 day) to ovarian stimulation with an GnRH antagonist (Ganirelix) will improve oocyte maturation and quality, and improve pregnancy outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Diminished Ovarian Reserve, Infertility, In Vitro Fertilization
- What is being tested?
- Ganirelix acetate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Sep 2014
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Antral Follicle Count (AFC) less than or equal to 4 as measured by transvaginal ultrasound (TVUS), or
- Cancellation of a prior IVF cycle due to poor ovarian response.
- Patients will receive an antagonist stimulation protocol for IVF, or IVF with Intracytoplasmic Sperm Injection (ICSI).
Who cannot join
- Severe male factor infertility requiring surgical intervention to obtain sperm
- Major uterine abnormality,
- Preimplantation genetic diagnostic (PGD) testing,
- Planned cycles without embryo transfer (for example, freeze-all, donor, or surrogate cycles).
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Center for Reproductive Health
San Francisco, California, 94115
About this study
Official title: Delayed Start to Ovarian Stimulation Improves Oocyte Maturation and Quality: A Randomized Trial
In couples with infertility secondary to Diminished Ovarian Reserve, the investigators hypothesize that a delayed start (7 day) to ovarian stimulation with an GnRH antagonist (Ganirelix) will improve oocyte maturation and quality, and improve pregnancy outcomes.
Read the detailed description
Over the past two decades, the success rate of assisted reproductive technology (ART) has dramatically increased. This increase is attributed to improvements in embryo culture, laboratory conditions, and optimization of ovarian stimulation protocols. Over the past years, there has been more interest in altering the ovarian stimulation protocol to improve outcomes. For example, recently our group found that a modification of ovulation trigger toward a more physiologic process improves oocyte quality and pregnancy outcomes. Others have suggested minimal stimulation improves in vitro fertilization (IVF) outcomes. The investigators propose to further investigate modifying the ovarian stimulation for women who have "decreased" ovarian reserve. The investigators propose that a delayed start to ovarian stimulation will improve oocyte maturation and quality and pregnancy outcomes. No published studies to date have evaluated if a delayed start to ovarian stimulation improves pregnancy outcomes. However, the investigators hypothesize that the use an antagonist for a delayed start of stimulation will work by one of two mechanisms:
- The partial suppression of FSH will allow for further recruitment of early antral follicles.
II. The partial suppression of FSH will allow for further FSH responsiveness in existing follicles to synchronize the primary cohort, thereby increasing the total number of follicles.
- Being tested
- Ganirelix acetate
- Keywords
- DOR, Infertility, IVF, ART, GnRHa, GnRH Antagonist Protocol, Ganirelix
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ganirelix acetateDrug
Also called Ganirelix
Subjects will receive 7 days of pre-treatment with the GnRH antagonist
| Study group | Role | What they receive |
|---|---|---|
| Delayed Start | Experimental | Study subjects will receive 7 days of pre-treatment with a GnRH antagonist (Delayed Start) before standard ovarian stimulation with FSH/LH. Receives: Drug: Ganirelix acetate |
| Conventional Start | Active comparator | Ovarian stimulation with standard antagonist protocols (no delay). Receives: Drug: Ganirelix acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fertilization Proportions
Developmental competence (fertilization of oocytes) through standard in vitro fertilization (estimated time frame to be between 8-24 hours following IVF). This percentage will be calculated as the number of fertilized eggs ( 2PN stage) per total number of eggs collected from the egg retrieval.
Measured: 8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilization
Number of Oocytes Retrieved
The egg retrieval procedure will be performed 36 hours after the ovulation trigger. The procedure is estimated to take up to 1 hour at study visit as part of routine care. The number of retrieved eggs will be counted
Measured: up to 1 hour after oocytes retrieved
Secondary outcomes (5)
Embryo Quality
Embryo quality will be assessed by the embryologist on days 2 or 3 (Cleavage stage) following IVF using standard embryo grading criteria. Embryos grading is based on three criteria: the number of blastomere cells present in the embryo, the degree of observed cell fragmentation and the degree of observed symmetry of the cells.
Measured: One hour on day 2 or 3 (following IVF procedure)
Pregnancy Rates
Beta HCG levels will be assessed at 2 weeks and 3 weeks after embryo transfer. A positive pregnancy is defined as two positive beta HCG levels (a value > 5 mIU/ml ) observed over the time frame.
Measured: 2 to 3 weeks following embryo transfer
Stages of Oocyte Nuclear Maturation
Quality of oocytes will be assessed for developmental stages (Germinal Vesicles, Meiosis I, or Meiosis II)
Measured: average of 1 to 2 hours on the Day of Retrieval
Number of Mature Follicles
Maturation of follicles will be assessed by measuring the size of follicles (mature > 13mm) prior to (or at the time of) oocytes retrieval.
Measured: up to 1 hour (during the Transvaginal Ultrasound before Retrieval of Oocytes)
Oocyte Recovery Rate
The number of oocytes recovered at the time of oocyte retrieval following ovarian stimulation.
Measured: up to 1 hours after oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2012 (estimated)
- Study startMay 2012
- Primary completionJul 2014
- Study completionSep 2014
Why it stopped: Slow enrollment resulted in withdraw of funding
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 (1)Papers the sponsor has linked to this study.
- Other trials for Diminished Ovarian ReserveStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Mitchell Rosen, MD, Principal investigator, UCSF Center for Reproductive Health and Fertility Preservation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01614067
- Sponsor's protocol ID
- UCSF 11-07259
- Acronym
- DOS/DOR
- Status last verified
- May 2021
- First submitted
- 2 May 2012
- Last updated
- 15 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
Blockeel C, Riva A, De Vos M, Haentjens P, Devroey P. Administration of a gonadotropin-releasing hormone antagonist during the 3 days before the initiation of the in vitro fertilization/intracytoplasmic sperm injection treatment cycle: impact on ovarian stimulation. A pilot study. Fertil Steril. 2011 Apr;95(5):1714-9.e1-2. doi: 10.1016/j.fertnstert.2011.01.028.
PubMed 21300334
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delayed Start to Ovarian Stimulation Improves Oocyte Maturation and Quality: A Randomized Trial
- ClinicalTrials.gov ID
- NCT01614067
- Acronym / sponsor ID
- DOS/DOR / UCSF 11-07259
- Keywords
- DOR, Infertility, IVF, ART, GnRHa, GnRH Antagonist Protocol, Ganirelix
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment resulted in withdraw of funding
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- May 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 7 Jun 2012 (estimated)
- Results
- Posted 15 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In couples with infertility secondary to Diminished Ovarian Reserve, the investigators hypothesize that a delayed start (7 day) to ovarian stimulation with an GnRH antagonist (Ganirelix) will improve oocyte maturation and quality, and improve pregnancy outcomes.
Detailed description
Over the past two decades, the success rate of assisted reproductive technology (ART) has dramatically increased. This increase is attributed to improvements in embryo culture, laboratory conditions, and optimization of ovarian stimulation protocols. Over the past years, there has been more interest in altering the ovarian stimulation protocol to improve outcomes. For example, recently our group found that a modification of ovulation trigger toward a more physiologic process improves oocyte quality and pregnancy outcomes. Others have suggested minimal stimulation improves in vitro fertilization (IVF) outcomes. The investigators propose to further investigate modifying the ovarian stimulation for women who have "decreased" ovarian reserve. The investigators propose that a delayed start to ovarian stimulation will improve oocyte maturation and quality and pregnancy outcomes. No published studies to date have evaluated if a delayed start to ovarian stimulation improves pregnancy outcomes. However, the investigators hypothesize that the use an antagonist for a delayed start of stimulation will work by one of two mechanisms:
- The partial suppression of FSH will allow for further recruitment of early antral follicles.
II. The partial suppression of FSH will allow for further FSH responsiveness in existing follicles to synchronize the primary cohort, thereby increasing the total number of follicles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Delayed Start | Experimental | Drug: Ganirelix acetateStudy subjects will receive 7 days of pre-treatment with a GnRH antagonist (Delayed Start) before standard ovarian stimulation with FSH/LH. |
| Conventional Start | Active comparator | Drug: Ganirelix acetateOvarian stimulation with standard antagonist protocols (no delay). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Antral Follicle Count (AFC) less than or equal to 4 as measured by transvaginal ultrasound (TVUS), or
- Cancellation of a prior IVF cycle due to poor ovarian response.
- Patients will receive an antagonist stimulation protocol for IVF, or IVF with Intracytoplasmic Sperm Injection (ICSI).
Key exclusion criteria (4 listed)
- Severe male factor infertility requiring surgical intervention to obtain sperm
- Major uterine abnormality,
- Preimplantation genetic diagnostic (PGD) testing,
- Planned cycles without embryo transfer (for example, freeze-all, donor, or surrogate cycles).
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 |
|---|---|---|
| Ganirelix acetateAlso: GanirelixSubjects will receive 7 days of pre-treatment with the GnRH antagonist | Drug | Conventional Start, Delayed Start |
Primary outcome
Fertilization Proportions
Time frame: 8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilization
Developmental competence (fertilization of oocytes) through standard in vitro fertilization (estimated time frame to be between 8-24 hours following IVF). This percentage will be calculated as the number of fertilized eggs ( 2PN stage) per total number of eggs collected from the egg retrieval.
Number of Oocytes Retrieved
Time frame: up to 1 hour after oocytes retrieved
The egg retrieval procedure will be performed 36 hours after the ovulation trigger. The procedure is estimated to take up to 1 hour at study visit as part of routine care. The number of retrieved eggs will be counted
5 secondary outcomes
Embryo Quality
Time frame: One hour on day 2 or 3 (following IVF procedure)
Pregnancy Rates
Time frame: 2 to 3 weeks following embryo transfer
Stages of Oocyte Nuclear Maturation
Time frame: average of 1 to 2 hours on the Day of Retrieval
Number of Mature Follicles
Time frame: up to 1 hour (during the Transvaginal Ultrasound before Retrieval of Oocytes)
Oocyte Recovery Rate
Time frame: up to 1 hours after oocyte retrieval
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21300334Blockeel C, Riva A, De Vos M, Haentjens P, Devroey P. Administration of a gonadotropin-releasing hormone antagonist during the 3 days before the initiation of the in vitro fertilization/intracytoplasmic sperm injection treatment cycle: impact on ovarian stimulation. A pilot study. Fertil Steril. 2011 Apr;95(5):1714-9.e1-2. doi: 10.1016/j.fertnstert.2011.01.028.
- Individual participant dataSharing planned: No
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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.
Mitchell Rosen, MD principal investigator
UCSF Center for Reproductive Health and Fertility Preservation
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 Ganirelix acetate in people with Diminished Ovarian Reserve and Infertility, run by University of California, San Francisco at 1 site in United States.
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 3 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 15 Jun 2021. 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 United States. 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?
Yes. Results are posted in the registry (first posted 15 Jun 2021). 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?
Fertilization Proportions (time frame: 8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilization). 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 NCT01614067, which also lists 1 linked publication.
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 15 Jun 2021.