Embryo HypoxiaNCT04424784
Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
A study testing 5% O2 in people with Embryo Hypoxia, run by The University of Hong Kong-Shenzhen Hospital at 1 site in China.
Trial summary
Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex vivo culture conditions comparable to those in vivo. Various culturing condition such as temperature and pH parameters have been adjusted according to in vivo values in order to improve in-vitro fertilization (IVF) outcomes. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Embryo Hypoxia
- What is being tested?
- 5% O2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,160 participants
- Where
- 1 siteChina
- Study dates
- 22 Mar 2021to Jun 2023
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- all the couples undergoing conventional IVF cycle in the reproductive medicine center of the University of Hong Kong-Shenzhen Hospital
Who cannot join
- Intracytoplasmic sperm injection (ICSI) cycle
- Preimplantation genetic testing (PGT) cycle
- cycle with fertilization failure ≥3
- cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE) or cryopreserved sperm
- cycle using cryopreserved oocyte
- cycle with no oocyte retrieved
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Reproductive medicine center
Shenzhen
QIAN PENG, PHD, qianpeng_77@hotmail.com
About this study
Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex vivo culture conditions comparable to those in vivo. Various culturing condition such as temperature and pH parameters have been adjusted according to in vivo values in order to improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes should be kept in a low oxygen environment during manipulation in assisted reproduction treatment.
Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories. However, there are still laboratory procedures when the oocytes/embryos are exposed to atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric oxygen concentration. Oocyte is very sensitive to environmental changes, for instance, transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte retrieval has detrimental effect on embryo development and IVF outcomes is unknown.
Read more
Previous studies showed that low oxygen tension during embryo culture improved implantation rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo quality was improved but overall pregnancy was not affected. The reason for the discrepancies could be because the oxygen tension during oocyte/embryo manipulation was not under well control. For instance, oocyte retrieval, fertilization check and embryo grading were performed under atmospheric oxygen. It is difficult to predict how these factors negatively impact the IVF outcomes.
In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo manipulation improves IVF outcomes.
Read the detailed description
In the experimental group, oocyte pickup will be performed in a lower oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in a special workstation with reduced oxygen tension environment while fertilization check and embryo grading will be performed in conventional and time lapse embryo culture system. The time lapse culture system can provide a constant lower oxygen tension culture environment to the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will be performed in atmospheric oxygen environment. Under this arrangement, the difference between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The investigators believe that a solid conclusion can be drawn about whether lower oxygen tension environment can benefit IVF outcomes.
- Conditions
- Embryo Hypoxia
- Being tested
- 5% O2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5% O2Biological
5% oxygen will be used during oocyte retrieval, fertilization check and embryo grading
| Study group | Role | What they receive |
|---|---|---|
| 20% O2 | No intervention | In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide). |
| 5% O2 | Experimental | In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment. Receives: Biological: 5% O2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
live birth rate
delivery of a live birth beyond 24 weeks of gestation
Measured: 4 years
Secondary outcomes (4)
clinical pregnancy rate
presence of at least one gestational sac on ultrasound of 6 weeks
Measured: 3 years
ongoing pregnancy rate
presence of at least heart pulsation on ultrasound beyond 20 weeks
Measured: 3 years
fertilization rate
No. of fertilized oocyte divided by No. of inseminated cumulus-oocyte complexes (COCs)
Measured: 3 years
cleavage rate
No. of cleaved embryo divided by No. of fertilized oocyte
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start22 Mar 2021
- Primary completionJun 2023 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Embryo HypoxiaStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 1,160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong-Shenzhen Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shubiu Yeung, PhD, Principal investigator, The University of Hong Kong-Shenzhen Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424784
- Sponsor's protocol ID
- HKUSZH201902022
- Status last verified
- May 2021
- First submitted
- 28 May 2020
- Last updated
- 25 May 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
PubMed 8107053Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.
PubMed 18681997Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.
PubMed 18554591
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
- ClinicalTrials.gov ID
- NCT04424784
- Acronym / sponsor ID
- HKUSZH201902022
- Conditions
- Embryo Hypoxia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,160 participants (estimated)
- Lead sponsor
- The University of Hong Kong-Shenzhen HospitalUniversity, hospital or other
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 11 Jun 2020 (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.
Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex vivo culture conditions comparable to those in vivo. Various culturing condition such as temperature and pH parameters have been adjusted according to in vivo values in order to improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes should be kept in a low oxygen environment during manipulation in assisted reproduction treatment.
Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories. However, there are still laboratory procedures when the oocytes/embryos are exposed to atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric oxygen concentration. Oocyte is very sensitive to environmental changes, for instance, transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte retrieval has detrimental effect on embryo development and IVF outcomes is unknown.
Previous studies showed that low oxygen tension during embryo culture improved implantation rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo quality was improved but overall pregnancy was not affected. The reason for the discrepancies could be because the oxygen tension during oocyte/embryo manipulation was not under well control. For instance, oocyte retrieval, fertilization check and embryo grading were performed under atmospheric oxygen. It is difficult to predict how these factors negatively impact the IVF outcomes.
In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo manipulation improves IVF outcomes.
Detailed description
In the experimental group, oocyte pickup will be performed in a lower oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in a special workstation with reduced oxygen tension environment while fertilization check and embryo grading will be performed in conventional and time lapse embryo culture system. The time lapse culture system can provide a constant lower oxygen tension culture environment to the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will be performed in atmospheric oxygen environment. Under this arrangement, the difference between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The investigators believe that a solid conclusion can be drawn about whether lower oxygen tension environment can benefit IVF outcomes.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 20% O2 | No intervention | –In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide). |
| 5% O2 | Experimental | Biological: 5% O2In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- all the couples undergoing conventional IVF cycle in the reproductive medicine center of the University of Hong Kong-Shenzhen Hospital
Key exclusion criteria (6 listed)
- Intracytoplasmic sperm injection (ICSI) cycle
- Preimplantation genetic testing (PGT) cycle
- cycle with fertilization failure ≥3
- cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE) or cryopreserved sperm
- cycle using cryopreserved oocyte
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 |
|---|---|---|
| 5% O25% oxygen will be used during oocyte retrieval, fertilization check and embryo grading | Biological | 5% O2 |
Primary outcome
live birth rate
Time frame: 4 years
delivery of a live birth beyond 24 weeks of gestation
4 secondary outcomes
clinical pregnancy rate
Time frame: 3 years
ongoing pregnancy rate
Time frame: 3 years
fertilization rate
Time frame: 3 years
cleavage rate
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Background: PubMed 8107053Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
- Background: PubMed 18681997Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.
- Background: PubMed 18554591Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.
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.
Shubiu Yeung, PhD principal investigator
The University of Hong Kong-Shenzhen 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 5% O2 in people with Embryo Hypoxia, run by The University of Hong Kong-Shenzhen Hospital at 1 site in China.
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 25 May 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 China. 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 Qian Peng, PhD (8675586917836, qianpeng_77@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
live birth rate (time frame: 4 years). 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 NCT04424784, which also lists 3 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 25 May 2021.