InfertilityNCT05737381
Quality of Human Embryos in IVF, Culturing in Differentiated Oxygen
A study testing Differential oxygen tension in people with Infertility and IVF, run by Odense University Hospital at 1 site in Denmark.
Trial summary
The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts. Read more about this study
- Who is it for?
- Ages 18 to 41 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, IVF, Embryo
- What is being tested?
- Differential oxygen tension
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Sep 2022to Dec 2025
- 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 18 to 41 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles.
- Women age 18 - 41 years and BMI 18 - 35 kg/m2 (both inclusive) with ≥ 8 oocytes.
- Patients will be included no later than at oocyte pick-up.
Who cannot join
- Patients with sperm from testes biopsy, congenital uterine abnormalities, presence of fibromas or polyps, or suspected hydro salpinges. Oocytes from donors.
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Odense University Hospital
Odense, 5000
Tilde Eskildsen, +4565412324, tilde.veng.eskildsen@rsyd.dk
Kirsten Simonsen, +4586101388, ks@maigaard.dk
About this study
Official title: Can a Differentiated Oxygen Setup Improve Embryo Quality and Increase the Number of Usable Embryos After in Vitro Fertilization (IVF)?
The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.
This is a prospective, interventional multicenter study using sibling embryos.
Read more
Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART) can be included in the study.
Patients included in the project will follow standard IVF protocol and treatment.
By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study.
According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2.After 3 days of cultivation, the dishes with the study-embryos will be transferred to an incubator with 2% O2. The control embryos will remain in the conventional 5% O2 incubator.
On the fifth day, the embryos will be evaluated, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.
Value for public Health:
If our hypothesis is confirmed, we will be able to optimize the developmental conditions and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.
Read the detailed description
The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.
This is a prospective, interventional multicenter study using sibling embryos.
Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles can be included in the study.
Patients included in the project will follow standard IVF protocol and treatment including hormonal injections, oocyte pick-up, embryo transfer and blastocyst cryopreservation. No further examinations or deviation from standard treatment is necessary in order to participate in the project.
By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study. The minimum number of 8 oocytes has been determined to ensure an average of two blastocysts. The oocytes, will be divided into 2 groups. The first part of the collected oocytes will be included as controls, whereas the second part of the collected oocytes will be included as study group.
According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2. From time-lapse videos, observations of fertilization and cleavage after 20 hours ± 1h and 44 hours ± 1h, respectively will be annotated. After 3 days of cultivation (68h± 1h), the dishes with the study-embryos will be transferred to a time-lapse incubator with ultralow O2 tension (2%). The control embryos will remain in the conventional 5% O2 time-lapse incubator.
On the fifth day, the embryos will be evaluated by a trained embryologist, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.
Primary outcome:
- Improved morphokinetics parameters; decreased time difference from 5-cell (t5) to blastocyst stage (tB) in the embryos cultured in differential O2 tensions.
As secondary outcomes:
- Decreased ROS-activity in spent media from the developing blastocysts cultivated in differential O2 tensions.
- Number of transferable/vitrified blastocyst in both study and test groups
- Verification of clinical pregnancy, using ultrasound scanning around week 7. All pregnancies or miscarriage will be registered for all patients if possible.
Value for public Health:
If our hypothesis is confirmed as expected, we will be able to optimize the developmental conditions i.e. faster developmental rate from t5 to tB and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.
- Conditions
- Infertility, IVF, Embryo
- Being tested
- Differential oxygen tension
- Keywords
- Oxygen, Blastocyst, Time lapse, ROS, Embryology
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Differential oxygen tensionOther
By culturing the embryos in a differential O2 set-up, changing the O2 tension from reduced (5% O2) to ultralow (2% O2) from day 3 to day 5 of embryo development in vitro, we mimic the physiological differential changes in O2 as the embryo migrate from the oviduct to the uterus and develops in vivo.
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | The oocytes from a patient, retrieving more than 8 oocytes will be divided into 2 sibling groups. The control group and the study group. The first part of the collected oocytes, will be included as controls. If an unequal numbers of oocytes are collected, the extra oocyte will be included into the control group. Control oocytes are, after fertilization, placed in conventional 5% O2 incubators and cultured herein for 5 days. |
| Study group | Experimental | The second part of the collected oocytes, from a patient retrieving more than 8 oocytes, will be included as study group.
Study oocytes, are after fertilization, placed and cultured in conventional 5% O2 incubators for the first 3 days. At day 3, the embryos are moved to an incubator with 2% O2 tension and cultured until day 5. Receives: Other: Differential oxygen tension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improved morphokinetics parameters
Decreased time difference from 5-cell (t5) to full blastocyst stage (tB) in the embryos cultured in differential O2 tensions. This will be analysed using timelapse systems and specific annotation strategies.
Measured: Analysis of morphokinetic, will be finalised approximately 12 months after last intervention.
Secondary outcomes (3)
Decreased ROS-activity
Decreased ROS-activity in spent media from the developing blastocysts cultivated in differential O2 tensions. Developing embryos in this project are cultured in seperat wells, allowing for individual analysis of spent media from each unique embryos. After transfer or freezing of embryos, the media is collected and stored for analysis.
Measured: Analysis of ROS will be finalised approximately 12 months after interventions have been completed.
Number of transferable/frozen blastocyst
Number of transferable/frozen blastocyst in both control and study group
Measured: Number count of transferable/vitrified blastocysts will be finalised approximately 6 months after interventions have been complete
Clinical pregnancy (CP)
Number of Clinical pregnancies in both control and study group
Measured: Data of CP from fresh transfers can be finalised 12 months after last intervention. Data of CP from frozen blastocyst can be finalized either within the project or if not used within the following year, in a followup project.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start15 Sep 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Sibling study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Odense Patient Data Explorative Network, University of Southern Denmark
- Responsible party
- Sponsor
- Investigators
- Tilde Eskildsen, Principal investigator, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737381
- Sponsor's protocol ID
- S-20210143
- Status last verified
- Feb 2023
- First submitted
- 10 Feb 2023
- Last updated
- 27 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can a Differentiated Oxygen Setup Improve Embryo Quality and Increase the Number of Usable Embryos After in Vitro Fertilization (IVF)?
- ClinicalTrials.gov ID
- NCT05737381
- Acronym / sponsor ID
- S-20210143
- Conditions
- Infertility, IVF, Embryo
- Keywords
- Oxygen, Blastocyst, Time lapse, ROS, Embryology
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Odense Patient Data Explorative Network, University of Southern Denmark
- Study start
- 15 Sep 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 21 Feb 2023 (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 goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.
This is a prospective, interventional multicenter study using sibling embryos.
Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART) can be included in the study.
Patients included in the project will follow standard IVF protocol and treatment.
By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study.
According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2.After 3 days of cultivation, the dishes with the study-embryos will be transferred to an incubator with 2% O2. The control embryos will remain in the conventional 5% O2 incubator.
On the fifth day, the embryos will be evaluated, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.
Value for public Health:
If our hypothesis is confirmed, we will be able to optimize the developmental conditions and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.
Detailed description
The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.
This is a prospective, interventional multicenter study using sibling embryos.
Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles can be included in the study.
Patients included in the project will follow standard IVF protocol and treatment including hormonal injections, oocyte pick-up, embryo transfer and blastocyst cryopreservation. No further examinations or deviation from standard treatment is necessary in order to participate in the project.
By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study. The minimum number of 8 oocytes has been determined to ensure an average of two blastocysts. The oocytes, will be divided into 2 groups. The first part of the collected oocytes will be included as controls, whereas the second part of the collected oocytes will be included as study group.
According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2. From time-lapse videos, observations of fertilization and cleavage after 20 hours ± 1h and 44 hours ± 1h, respectively will be annotated. After 3 days of cultivation (68h± 1h), the dishes with the study-embryos will be transferred to a time-lapse incubator with ultralow O2 tension (2%). The control embryos will remain in the conventional 5% O2 time-lapse incubator.
On the fifth day, the embryos will be evaluated by a trained embryologist, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.
Primary outcome:
- Improved morphokinetics parameters; decreased time difference from 5-cell (t5) to blastocyst stage (tB) in the embryos cultured in differential O2 tensions.
As secondary outcomes:
- Decreased ROS-activity in spent media from the developing blastocysts cultivated in differential O2 tensions.
- Number of transferable/vitrified blastocyst in both study and test groups
- Verification of clinical pregnancy, using ultrasound scanning around week 7. All pregnancies or miscarriage will be registered for all patients if possible.
Value for public Health:
If our hypothesis is confirmed as expected, we will be able to optimize the developmental conditions i.e. faster developmental rate from t5 to tB and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Sibling study
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –The oocytes from a patient, retrieving more than 8 oocytes will be divided into 2 sibling groups. The control group and the study group. The first part of the collected oocytes, will be included as controls. If an unequal numbers of oocytes are collected, the extra oocyte will be included into the control group. Control oocytes are, after fertilization, placed in conventional 5% O2 incubators and cultured herein for 5 days. |
| Study group | Experimental | Other: Differential oxygen tensionThe second part of the collected oocytes, from a patient retrieving more than 8 oocytes, will be included as study group. Study oocytes, are after fertilization, placed and cultured in conventional 5% O2 incubators for the first 3 days. At day 3, the embryos are moved to an incubator with 2% O2 tension and cultured until day 5. |
Who may qualify
- Ages
- 18 to 41 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patients undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles.
- Women age 18 - 41 years and BMI 18 - 35 kg/m2 (both inclusive) with ≥ 8 oocytes.
- Patients will be included no later than at oocyte pick-up.
Key exclusion criteria (1 listed)
- Patients with sperm from testes biopsy, congenital uterine abnormalities, presence of fibromas or polyps, or suspected hydro salpinges. Oocytes from donors.
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 |
|---|---|---|
| Differential oxygen tensionBy culturing the embryos in a differential O2 set-up, changing the O2 tension from reduced (5% O2) to ultralow (2% O2) from day 3 to day 5 of embryo development in vitro, we mimic the physiological differential changes in O2 as the embryo migrate from the oviduct to the uterus and develops in vivo. | Other | Study group |
Primary outcome
Improved morphokinetics parameters
Time frame: Analysis of morphokinetic, will be finalised approximately 12 months after last intervention.
Decreased time difference from 5-cell (t5) to full blastocyst stage (tB) in the embryos cultured in differential O2 tensions. This will be analysed using timelapse systems and specific annotation strategies.
3 secondary outcomes
Decreased ROS-activity
Time frame: Analysis of ROS will be finalised approximately 12 months after interventions have been completed.
Number of transferable/frozen blastocyst
Time frame: Number count of transferable/vitrified blastocysts will be finalised approximately 6 months after interventions have been complete
Clinical pregnancy (CP)
Time frame: Data of CP from fresh transfers can be finalised 12 months after last intervention. Data of CP from frozen blastocyst can be finalized either within the project or if not used within the following year, in a followup project.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Individual participant dataSharing planned: Undecided
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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.
Tilde Eskildsen principal investigator
Odense University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Differential oxygen tension in people with Infertility and IVF, run by Odense University Hospital at 1 site 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 3 inclusion and 1 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 27 Feb 2023. 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 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.
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 Tilde Eskildsen (+4565412324, tilde.veng.eskildsen@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improved morphokinetics parameters (time frame: Analysis of morphokinetic, will be finalised approximately 12 months after last intervention.). 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 27 Feb 2023.