the Number of Mature OocytesNCT03740880
Trigger Time in Advanced Maternal Age Patients With Low AMH
A study testing Dual trigger in people with the Number of Mature Oocytes, run by ART Fertility Clinics LLC at 1 site in United Arab Emirates.
Trial summary
The investigators want to verify if advanced maternal age patients with a low Anti-Müllerian hormone (AMH) level may benefit from an early trigger time (compared to a late trigger). Read more about this study
- Who is it for?
- Ages 40 to 48 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- the Number of Mature Oocytes
- What is being tested?
- Dual trigger
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited Arab Emirates
- Study dates
- 7 Jan 2019to 30 Mar 2020
- Phase
- Interventional
- 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 40 to 48 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- • POR defined according to the Bologna criteria:
- AMA: ≥40 years and AMH <1.1 ng/ml
- Previous poor ovarian response with maximum 3 cumulus oocyte complexes retrieved after conventional stimulation
- Antral follicle count < 5-7
- Cycling patients
- Fresh ejaculates
Show all 23Show fewer
- ICSI
- BMI 19-32 kg/m2
- Ovarian stimulation protocol: Antagonist HMG 450 IU to ensure all receptors are covered and to ensure maximum recruitment. Dose adjustments can be made after 5 days of stimulation
- Type of trigger for final oocyte maturation: dual trigger: 10.000 IU hCG i.m. and 0.3 mg Deca
- Couples requesting preimplantation genetic testing (for aneuploidies) of their embryos
- Follicular measurements should be performed at IVI RMA Fertility, Abu Dhabi, UAE: a single operator will perform the ultrasound for the final measurement before trigger. Recruitment can be done by all physicians
- Only patients with an oral contraceptive pill (OCP) pretreatment to synchronize follicular development:
- 2 weeks OCP followed by
- a wash out of 5 days (without OCP) followed by
- o start stimulation
- Basal hormone profile (FSH, LH, E2, P4) measured between day 1-3 at IVIRMA Fertility, Abu Dhabi, UAE
- FSH <15 IU
- E2 <50 pg/ml
- P <1ng/ml
- Only the Arab population
- Oocyte retrieval: 36 hours after trigger
- PGT-A
Who cannot join
- If follicular measurement before randomization shows a leading follicle ≥ 13mm
- IVF
- History of:
- Endometriosis AFS>2
- Chemotherapy/radiotherapy
- Ovarian surgery (iatrogenic)
Show all 14Show fewer
- Cyst puncture in the last three months
- Sonographic finding of:
- Hydrosalpinx
- Ovarian cyst
- Testicular samples and frozen ejaculates
- If patients are pre-screened at the start of stimulation but no follicular development is observed, patients will not be randomized
- Asynchronized follicular development at the moment of randomization: if the leading follicle is >3 mm lager than the smaller follicles.
- All other hormonal pretreatments (except OCP) and all patients without hormonal pretreatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study: Optimal Trigger Time in Advanced Maternal Age Patients With Low AMH
The investigators want to verify if advanced maternal age patients with a low Anti-Müllerian hormone (AMH) level may benefit from an early trigger time (compared to a late trigger).
Read the detailed description
During assisted reproduction, patients are stimulated in order to achieve a multifollicular development. The final step in this stimulation process is "the trigger" that will induce the final maturation of the oocytes. This timing is historically put once at least one follicle of 16-17 mm is obtained.
When looking at poor ovarian responder (POR) patients (characterized by a low AMH), the investigators observe shorter menstrual cycles and thus it is thought that the oocyte selected for ovulation, will also mature faster. This observation may indicate that POR patients potentially do not benefit from a trigger performed once a leading follicle of 17 mm is present, but rather from an earlier trigger.
The main objective is to analyse if an early trigger (leading follicle of 14 mm) results in the same maturation rate in POR patient as compared to a late trigger (17 mm). As the embryos will be cultured in a time lapse imaging system, annotations on the developmental kinetics can be made and the differences in fertilization rate and embryo development can be analysed as secondary outcome parameter. On top of this, patients will undergo a genetic testing of their embryos and this genetic analysis , together with the mtDNA copy number will also be compared between patients with early or late trigger. Euploid blastocysts will be transferred in subsequent frozen embryo transfer (FET) cycles and give an indication on the clinical outcome between IVF and ICSI.
- Conditions
- the Number of Mature Oocytes
- Being tested
- Dual trigger
- Keywords
- ICSI, early trigger, poor ovarian responders, low AMH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual triggerOther
dual trigger: 10.000 IU hCG i.m. and 0.3 mg Deca
| Study group | Role | What they receive |
|---|---|---|
| Late trigger | Active comparator | dual trigger (10.000 IU hCG i.m. and 0.3 mg Deca) once the leading follicle is 17 mm Receives: Other: Dual trigger |
| Early trigger | Experimental | dual trigger (10.000 IU hCG i.m. and 0.3 mg Deca) once the leading follicle is 14 mm Receives: Other: Dual trigger |
What is being measured
The primary outcome is the main question the study is designed to answer.
the number of mature oocytes
A mature oocyte is defined as an oocyte that has extruded his first polar body and this mature oocyte is ready to be fertilized by the participants sperm.
Measured: 1 day
Secondary outcomes (9)
Maturation rate
The maturation rate is defined as the number of mature oocytes obtained per cumulus complex retrieved for the participants.A mature oocyte is defined as an oocyte that has extruded his first polar body and this mature oocyte is ready to be fertilized by the participants sperm.
Measured: 1 day
Fertilization rate
Fertilization is calculated on all mature oocytes or on all complexes obtained after oocyte retrieval. The fertilization rate is assessed by the presence of a male and a female pronucleus 16-20 hours post fertilization. If the oocyte is fertilized, the outcome is positive, if the oocyte is not fertilized, the outcome is negative.
Measured: 1 day
Embryo development up to day 3
For all normally fertilized oocytes the further development will be assessed as the embryos are cultured in a time lapse system. This system takes pictures of the embryos every 20 minutes which shows the development of the embryo like a movie: every time that a cell divides, the hour at which it divides will be registered in the time lapse system. For each cell division, specific time frames have been described that link the embryo to develop into a blastocyst or that increases the chance of implantation. The embryo will be evaluated on day 3 and will receive an embryo score that is based on the number of cells, the appearance of the cells, fragmentation and embryo dysmorphisms. These will divide the embryo quality into 4 categories with category 1 being the highest quality and category 4 being the lowest quality. The more fragmentation and the higher the degree of dysmorphisms, the more the quality will shift to category 4
Measured: 3 days
Blastulation rate
A blastocyst is an embryo in which a cavity is visible on day 5 of the embryo development. If the cavity is present the outcome is positive, if the cavity is absent, the outcome is negative The complete process in which the development of one embryo is followed from the day of injection up until day 7 is called the preimplantation development
Measured: 7 days
Embryo development up to day 5
On day 5 of development, a score is given to every embryo. This is based on the presence or absence of a cavity, the number of cells and how tight the cells are packed. The more cells, the higher the grade, if less cells are present, the grade is lower. Based on these parameters, a final grade is calculated (3 grades) with grade 1 being the highest score.
Measured: 7 days
Morphokinetic development
As embryos are cultured in a time lapse imaging system, pictures will be taken every 20 minutes to follow the development. Each time that the embryos divides, the timing will be registered in the database. Like this, every division made by every embryo is recorded: the time the embryo needs to go from 1 cell to 2 cells, from 2 cells to 3 cells and so on.
Measured: 7 days
Ploidy state: euploid or aneuploid
Trophectoderm biopsy performed between day 5-7 of preimplantation development. These cells will be genetically tested to see if the correct number of chromosomes are present. Euploid embryos can be used for the patient, aneuploid embryos cannot be used for the patient.
Measured: 7 days
Mitoscore value: ranges from 10-1500
The trophectoderm biopsy sample is used to calculate a value indicating the mitochondrial DNA present in the biopt. Lower values are known to be linked to higher implantation rates of the corresponding blastocyst. Higher values have been correlated to aneuploidy.
Measured: 7 days
Pregnancy outcome
Pregnancy outcomes from the frozen embryo transfers: blood samples will be taken and the level of beta-hCG will be measured to define a pregnancy or no pregnancy. A pregnancy is defined as the best oucome. In case a pregnancy is obtained, the patient will come for an ultrasound scan between week 7-12 to checke the presence of a gestational sac and the presence of a fetal heart beat. The presence of a fetal heart beat is defined as a positive outcome, the absence is defined as a negative outcome.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start7 Jan 2019
- Primary completion12 Mar 2020
- Study completion30 Mar 2020
Why it stopped: insufficient data
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 the Number of Mature OocytesStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two groups: 1 groups of patients receiving an early trigger (14mm), the other group receiving a late trigger (17mm)
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- ART Fertility Clinics LLC
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Neelke De Munck, PhD, Principal investigator, IVIRMA Abu Dhabi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03740880
- Sponsor's protocol ID
- 1810-ABU-067-HF
- Status last verified
- Feb 2022
- First submitted
- 12 Nov 2018
- Last updated
- 4 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Information regarding primary and secondary outcome measures will only be shared with researchers from the clinic, involved in the study.
Publications
Haahr T, Esteves SC, Humaidan P. Individualized controlled ovarian stimulation in expected poor-responders: an update. Reprod Biol Endocrinol. 2018 Mar 9;16(1):20. doi: 10.1186/s12958-018-0342-1.
PubMed 29523204Oudendijk JF, Yarde F, Eijkemans MJ, Broekmans FJ, Broer SL. The poor responder in IVF: is the prognosis always poor?: a systematic review. Hum Reprod Update. 2012 Jan-Feb;18(1):1-11. doi: 10.1093/humupd/dmr037. Epub 2011 Oct 10.
PubMed 21987525Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
PubMed 21505041Beckers NG, Macklon NS, Eijkemans MJ, Fauser BC. Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging. Fertil Steril. 2002 Aug;78(2):291-7. doi: 10.1016/s0015-0282(02)03227-2.
PubMed 12137865
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study: Optimal Trigger Time in Advanced Maternal Age Patients With Low AMH
- ClinicalTrials.gov ID
- NCT03740880
- Acronym / sponsor ID
- 1810-ABU-067-HF
- Conditions
- the Number of Mature Oocytes
- Keywords
- ICSI, early trigger, poor ovarian responders, low AMH
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient data
- Enrolment
- 1 participants (actual)
- Lead sponsor
- ART Fertility Clinics LLCUniversity, hospital or other
- Study start
- 7 Jan 2019 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 14 Nov 2018 (actual)
- 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.
The investigators want to verify if advanced maternal age patients with a low Anti-Müllerian hormone (AMH) level may benefit from an early trigger time (compared to a late trigger).
Detailed description
During assisted reproduction, patients are stimulated in order to achieve a multifollicular development. The final step in this stimulation process is "the trigger" that will induce the final maturation of the oocytes. This timing is historically put once at least one follicle of 16-17 mm is obtained.
When looking at poor ovarian responder (POR) patients (characterized by a low AMH), the investigators observe shorter menstrual cycles and thus it is thought that the oocyte selected for ovulation, will also mature faster. This observation may indicate that POR patients potentially do not benefit from a trigger performed once a leading follicle of 17 mm is present, but rather from an earlier trigger.
The main objective is to analyse if an early trigger (leading follicle of 14 mm) results in the same maturation rate in POR patient as compared to a late trigger (17 mm). As the embryos will be cultured in a time lapse imaging system, annotations on the developmental kinetics can be made and the differences in fertilization rate and embryo development can be analysed as secondary outcome parameter. On top of this, patients will undergo a genetic testing of their embryos and this genetic analysis , together with the mtDNA copy number will also be compared between patients with early or late trigger. Euploid blastocysts will be transferred in subsequent frozen embryo transfer (FET) cycles and give an indication on the clinical outcome between IVF and ICSI.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two groups: 1 groups of patients receiving an early trigger (14mm), the other group receiving a late trigger (17mm)
| Arm | Type | Receives |
|---|---|---|
| Late trigger | Active comparator | Other: Dual triggerdual trigger (10.000 IU hCG i.m. and 0.3 mg Deca) once the leading follicle is 17 mm |
| Early trigger | Experimental | Other: Dual triggerdual trigger (10.000 IU hCG i.m. and 0.3 mg Deca) once the leading follicle is 14 mm |
Who may qualify
- Ages
- 40 to 48 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- • POR defined according to the Bologna criteria:
Key exclusion criteria (14 listed)
- If follicular measurement before randomization shows a leading follicle ≥ 13mm
- IVF
- History of:
- Sonographic finding of:
- Testicular samples and frozen ejaculates
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 |
|---|---|---|
| Dual triggerdual trigger: 10.000 IU hCG i.m. and 0.3 mg Deca | Other | Early trigger, Late trigger |
Primary outcome
the number of mature oocytes
Time frame: 1 day
A mature oocyte is defined as an oocyte that has extruded his first polar body and this mature oocyte is ready to be fertilized by the participants sperm.
9 secondary outcomes
Maturation rate
Time frame: 1 day
Fertilization rate
Time frame: 1 day
Embryo development up to day 3
Time frame: 3 days
Blastulation rate
Time frame: 7 days
Embryo development up to day 5
Time frame: 7 days
Morphokinetic development
Time frame: 7 days
Ploidy state: euploid or aneuploid
Time frame: 7 days
Mitoscore value: ranges from 10-1500
Time frame: 7 days
Pregnancy outcome
Time frame: 3 months
Results and safety
The study was stopped early (reason given: insufficient data). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2022.
- Results publication: PubMed 29523204Haahr T, Esteves SC, Humaidan P. Individualized controlled ovarian stimulation in expected poor-responders: an update. Reprod Biol Endocrinol. 2018 Mar 9;16(1):20. doi: 10.1186/s12958-018-0342-1.
- Results publication: PubMed 21987525Oudendijk JF, Yarde F, Eijkemans MJ, Broekmans FJ, Broer SL. The poor responder in IVF: is the prognosis always poor?: a systematic review. Hum Reprod Update. 2012 Jan-Feb;18(1):1-11. doi: 10.1093/humupd/dmr037. Epub 2011 Oct 10.
- Results publication: PubMed 21505041Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
- Results publication: PubMed 12137865Beckers NG, Macklon NS, Eijkemans MJ, Fauser BC. Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging. Fertil Steril. 2002 Aug;78(2):291-7. doi: 10.1016/s0015-0282(02)03227-2.
- Individual participant dataSharing planned: Undecided. Information regarding primary and secondary outcome measures will only be shared with researchers from the clinic, involved in the study.
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.
Neelke De Munck, PhD principal investigator
IVIRMA Abu Dhabi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dual trigger in people with the Number of Mature Oocytes, run by ART Fertility Clinics LLC at 1 site in United Arab Emirates.
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 23 inclusion and 14 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 4 Mar 2022. 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 Arab Emirates. 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.
Are results available for this study?
The study was stopped early (reason given: insufficient data). 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?
the number of mature oocytes (time frame: 1 day). 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 NCT03740880, 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 4 Mar 2022.