IVFNCT05924048
Effect of Reducing the Oxygen Concentration From 5% to 2% on ICSI Outcome
A study testing Reducing the Oxygen Concentration From 5% to 2% in people with IVF, run by International Islamic Center for Population Studies and Research at 1 site in Egypt.
Trial summary
To assess the effect of reducing the oxygen concentration from 5% to 2% on Intracytoplasmic sperm injection (ICSI) outcome. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- IVF
- What is being tested?
- Reducing the Oxygen Concentration From 5% to 2%
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2023to 25 Mar 2024
- 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 20 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female age 20-35 years. Oocytes with normal morphology.
Who cannot join
- Embryo number less than 5. Male factor.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
International Islamic Center
Cairo, 11511
Amira Badereldin Mehaney, 01226629235, amiraamirabader@hotmail.com
About this study
Official title: Effect of Reducing the Oxygen Concentration From 5% to 2% on Intracytoplasmic Sperm Injection (ICSI) Outcome
To assess the effect of reducing the oxygen concentration from 5% to 2% on Intracytoplasmic sperm injection (ICSI) outcome.
Read the detailed description
Oxygen level plays a critical role in reducing the high level of detrimental reactive oxygen species within cells, influences embryonic gene expression, helps with embryo metabolism of glucose, and enhances embryo development from 2PN to the blastocyst stage, the oxygen concentration in the incubator is an important determinant of the in vitro environment that an embryo encounters. The preimplantation embryo consumes oxygen at a relatively constant level from the one-cell through the morula stage, while at the blastocyst stage the consumption is considerably increased. Oxygen plays a role in energy production, but in too high concentrations it may have a toxic effect by the formation of reactive oxygen species. While in vivo oxygen levels range from 1.5 to 8.7% in the fallopian tubes and uterus of several species, in most laboratories in vitro culture of human embryos was traditionally performed under atmospheric oxygen concentrations (~20%) . In mammals, the oxygen (O2) tension in the uterus is lower (2%) than the oviduct (5-7%). This fits with a shift in the metabolic strategy of the embryo after compaction and may have implications for EC in clinical IVF. Indeed, in a recent study utilizing discarded human embryos, blastulation rates were superior when cultured in 2% compared to 5% after day day 3. However, it is exceedingly difficult to control for the myriad factors impacting blastulation when employing discarded material . The technologies available in the early days of IVF, and most likely also for financial reasons, led to the widespread implementation of incubators that used atmospheric air (i.e. 20% oxygen) . Around the turn of the last century, more advanced incubators capable of creating an environment of 5% oxygen, which better resembles the natural
environment for oocytes and embryos, were developed. Currently, in around 60% of the IVF cycles performed worldwide, the embryos are cultured under 5% oxygen . Kaser et al. add to the long history of experimental data evaluating different oxygen levels in embryo culture. They evaluated the impact of a sequential oxygen tension system (5% oxygen from day 1 to day 3; 2% oxygen from day 3 to day 5) in extended culture . The effect of oxygen level during embryo culture on pregnancy and live birth rates is less straightforward. Although most studies found an improvement in embryo quality when culturing embryos under 5% oxygen . This discrepancy is partly explained by lack of power due to small sample sizes in some studies. When data are pooled in meta-analyses, the overall effect favours culture under 5% oxygen . Another explanation for the inconsistent results among the studies could be due to the differences in duration of exposure, until cleavage or blastocyst stage. When data in the meta-analyses were stratified for duration of culture, there was no effect of oxygen on pregnancy or live birth rates after 2-3 days of culture. After culture to the blastocyst stage, however, culture under 5% oxygen resulted in improved ongoing pregnancy. In the previous studies reported that culture under 5% O2 results in significantly more human surplus embryos reaching the blastocyst stage, as well as a higher proportion of blastocysts consisting of a normal number of cells.
in the human, indirect evidence exists that a low O2 tension of 5% appears to enhance the blastulation rate of surplus embryos .
A reduction in oxygen tension from atmospheric to more physiologic levels is beneficial for the mammalian blastocyst, in terms of a higher cell number and decreased apoptosis, less DNA fragmentation and less oxidative stress. During this highly metabolically active period of growth of the embryo and differentiation into trophectoderm (TE) and inner cell mass (ICM), this decrease in oxygen may protect against oxidative stress .
- Conditions
- IVF
- Being tested
- Reducing the Oxygen Concentration From 5% to 2%
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reducing the Oxygen Concentration From 5% to 2%Other
Effect of Reducing the Oxygen Concentration From 5% to 2% in arm 1.
| Study group | Role | What they receive |
|---|---|---|
| Group of 2% oxygen concentration. | Experimental | Incubate human embryo at 2% oxygen concentration. Receives: Other: Reducing the Oxygen Concentration From 5% to 2% |
| Group of 5% oxygen concentration. | No intervention | Incubate human embryo at 5% oxygen concentration. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and grad of embryos which exposed to oxygen concentration 2% .
Evaluate embryo quality at day 5
Measured: 1.3 year
Secondary outcomes (1)
Clinical pregnancy rate for examined subject.
Compare the two arms in clinical pregnancy.
Measured: 1.5 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start1 Jan 2023
- Primary completion27 Jan 2024 (estimated)
- Study completion25 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for IVFStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Islamic Center for Population Studies and Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed EL-Sayed Sabry Metwally, International Islamic Center for Population Studies and Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05924048
- Sponsor's protocol ID
- O2 level in human embryo
- Status last verified
- Jun 2023
- First submitted
- 18 Jun 2023
- Last updated
- 11 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bahceci M, Ciray HN, Karagenc L, Ulug U, Bener F. Effect of oxygen concentration during the incubation of embryos of women undergoing ICSI and embryo transfer: a prospective randomized study. Reprod Biomed Online. 2005 Oct;11(4):438-43. doi: 10.1016/s1472-6483(10)61136-4.
PubMed 16274603Bontekoe S, Mantikou E, van Wely M, Seshadri S, Repping S, Mastenbroek S. Low oxygen concentrations for embryo culture in assisted reproductive technologies. Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD008950. doi: 10.1002/14651858.CD008950.pub2.
PubMed 22786519Christianson MS, Zhao Y, Shoham G, Granot I, Safran A, Khafagy A, Leong M, Shoham Z. Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey. J Assist Reprod Genet. 2014 Aug;31(8):1029-36. doi: 10.1007/s10815-014-0250-z. Epub 2014 Jun 10.
PubMed 24913025Gomes Sobrinho DB, Oliveira JB, Petersen CG, Mauri AL, Silva LF, Massaro FC, Baruffi RL, Cavagna M, Franco JG Jr. IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis. Reprod Biol Endocrinol. 2011 Nov 1;9:143. doi: 10.1186/1477-7827-9-143.
PubMed 22044493Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001 Mar-Apr;7(2):175-89. doi: 10.1093/humupd/7.2.175.
PubMed 11284661Dumoulin JC, Meijers CJ, Bras M, Coonen E, Geraedts JP, Evers JL. Effect of oxygen concentration on human in-vitro fertilization and embryo culture. Hum Reprod. 1999 Feb;14(2):465-9. doi: 10.1093/humrep/14.2.465.
PubMed 10099995Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6):1030-1037.e2. doi: 10.1016/j.fertnstert.2018.02.119.
PubMed 29935641Kea B, Gebhardt J, Watt J, Westphal LM, Lathi RB, Milki AA, Behr B. Effect of reduced oxygen concentrations on the outcome of in vitro fertilization. Fertil Steril. 2007 Jan;87(1):213-6. doi: 10.1016/j.fertnstert.2006.05.066. Epub 2006 Nov 1.
PubMed 17081523Kovacic B, Sajko MC, Vlaisavljevic V. A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles. Fertil Steril. 2010 Jul;94(2):511-9. doi: 10.1016/j.fertnstert.2009.03.077. Epub 2009 May 5.
PubMed 19409544Meintjes M, Chantilis SJ, Douglas JD, Rodriguez AJ, Guerami AR, Bookout DM, Barnett BD, Madden JD. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Hum Reprod. 2009 Feb;24(2):300-7. doi: 10.1093/humrep/den368. Epub 2008 Oct 16.
PubMed 18927130Nastri CO, Nobrega BN, Teixeira DM, Amorim J, Diniz LMM, Barbosa MWP, Giorgi VSI, Pileggi VN, Martins WP. Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertil Steril. 2016 Jul;106(1):95-104.e17. doi: 10.1016/j.fertnstert.2016.02.037. Epub 2016 Mar 21.
PubMed 27012651
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Reducing the Oxygen Concentration From 5% to 2% on Intracytoplasmic Sperm Injection (ICSI) Outcome
- ClinicalTrials.gov ID
- NCT05924048
- Acronym / sponsor ID
- O2 level in human embryo
- Conditions
- IVF
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- International Islamic Center for Population Studies and ResearchUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 27 Jan 2024 (estimated)
- Study completion
- 25 Mar 2024 (estimated)
- First posted
- 29 Jun 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.
To assess the effect of reducing the oxygen concentration from 5% to 2% on Intracytoplasmic sperm injection (ICSI) outcome.
Detailed description
Oxygen level plays a critical role in reducing the high level of detrimental reactive oxygen species within cells, influences embryonic gene expression, helps with embryo metabolism of glucose, and enhances embryo development from 2PN to the blastocyst stage, the oxygen concentration in the incubator is an important determinant of the in vitro environment that an embryo encounters. The preimplantation embryo consumes oxygen at a relatively constant level from the one-cell through the morula stage, while at the blastocyst stage the consumption is considerably increased. Oxygen plays a role in energy production, but in too high concentrations it may have a toxic effect by the formation of reactive oxygen species. While in vivo oxygen levels range from 1.5 to 8.7% in the fallopian tubes and uterus of several species, in most laboratories in vitro culture of human embryos was traditionally performed under atmospheric oxygen concentrations (~20%) . In mammals, the oxygen (O2) tension in the uterus is lower (2%) than the oviduct (5-7%). This fits with a shift in the metabolic strategy of the embryo after compaction and may have implications for EC in clinical IVF. Indeed, in a recent study utilizing discarded human embryos, blastulation rates were superior when cultured in 2% compared to 5% after day day 3. However, it is exceedingly difficult to control for the myriad factors impacting blastulation when employing discarded material . The technologies available in the early days of IVF, and most likely also for financial reasons, led to the widespread implementation of incubators that used atmospheric air (i.e. 20% oxygen) . Around the turn of the last century, more advanced incubators capable of creating an environment of 5% oxygen, which better resembles the natural
environment for oocytes and embryos, were developed. Currently, in around 60% of the IVF cycles performed worldwide, the embryos are cultured under 5% oxygen . Kaser et al. add to the long history of experimental data evaluating different oxygen levels in embryo culture. They evaluated the impact of a sequential oxygen tension system (5% oxygen from day 1 to day 3; 2% oxygen from day 3 to day 5) in extended culture . The effect of oxygen level during embryo culture on pregnancy and live birth rates is less straightforward. Although most studies found an improvement in embryo quality when culturing embryos under 5% oxygen . This discrepancy is partly explained by lack of power due to small sample sizes in some studies. When data are pooled in meta-analyses, the overall effect favours culture under 5% oxygen . Another explanation for the inconsistent results among the studies could be due to the differences in duration of exposure, until cleavage or blastocyst stage. When data in the meta-analyses were stratified for duration of culture, there was no effect of oxygen on pregnancy or live birth rates after 2-3 days of culture. After culture to the blastocyst stage, however, culture under 5% oxygen resulted in improved ongoing pregnancy. In the previous studies reported that culture under 5% O2 results in significantly more human surplus embryos reaching the blastocyst stage, as well as a higher proportion of blastocysts consisting of a normal number of cells.
in the human, indirect evidence exists that a low O2 tension of 5% appears to enhance the blastulation rate of surplus embryos .
A reduction in oxygen tension from atmospheric to more physiologic levels is beneficial for the mammalian blastocyst, in terms of a higher cell number and decreased apoptosis, less DNA fragmentation and less oxidative stress. During this highly metabolically active period of growth of the embryo and differentiation into trophectoderm (TE) and inner cell mass (ICM), this decrease in oxygen may protect against oxidative stress .
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group of 2% oxygen concentration. | Experimental | Other: Reducing the Oxygen Concentration From 5% to 2%Incubate human embryo at 2% oxygen concentration. |
| Group of 5% oxygen concentration. | No intervention | –Incubate human embryo at 5% oxygen concentration. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Female age 20-35 years. Oocytes with normal morphology.
Key exclusion criteria (1 listed)
- Embryo number less than 5. Male factor.
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 |
|---|---|---|
| Reducing the Oxygen Concentration From 5% to 2%Effect of Reducing the Oxygen Concentration From 5% to 2% in arm 1. | Other | Group of 2% oxygen concentration. |
Primary outcome
Number and grad of embryos which exposed to oxygen concentration 2% .
Time frame: 1.3 year
Evaluate embryo quality at day 5
1 secondary outcome
Clinical pregnancy rate for examined subject.
Time frame: 1.5 Year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2023.
- Results publication: PubMed 16274603Bahceci M, Ciray HN, Karagenc L, Ulug U, Bener F. Effect of oxygen concentration during the incubation of embryos of women undergoing ICSI and embryo transfer: a prospective randomized study. Reprod Biomed Online. 2005 Oct;11(4):438-43. doi: 10.1016/s1472-6483(10)61136-4.
- Results publication: PubMed 22786519Bontekoe S, Mantikou E, van Wely M, Seshadri S, Repping S, Mastenbroek S. Low oxygen concentrations for embryo culture in assisted reproductive technologies. Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD008950. doi: 10.1002/14651858.CD008950.pub2.
- Results publication: PubMed 24913025Christianson MS, Zhao Y, Shoham G, Granot I, Safran A, Khafagy A, Leong M, Shoham Z. Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey. J Assist Reprod Genet. 2014 Aug;31(8):1029-36. doi: 10.1007/s10815-014-0250-z. Epub 2014 Jun 10.
- Results publication: PubMed 22044493Gomes Sobrinho DB, Oliveira JB, Petersen CG, Mauri AL, Silva LF, Massaro FC, Baruffi RL, Cavagna M, Franco JG Jr. IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis. Reprod Biol Endocrinol. 2011 Nov 1;9:143. doi: 10.1186/1477-7827-9-143.
- Results publication: PubMed 11284661Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001 Mar-Apr;7(2):175-89. doi: 10.1093/humupd/7.2.175.
- Results publication: PubMed 10099995Dumoulin JC, Meijers CJ, Bras M, Coonen E, Geraedts JP, Evers JL. Effect of oxygen concentration on human in-vitro fertilization and embryo culture. Hum Reprod. 1999 Feb;14(2):465-9. doi: 10.1093/humrep/14.2.465.
- Results publication: PubMed 29935641Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6):1030-1037.e2. doi: 10.1016/j.fertnstert.2018.02.119.
- Results publication: PubMed 17081523Kea B, Gebhardt J, Watt J, Westphal LM, Lathi RB, Milki AA, Behr B. Effect of reduced oxygen concentrations on the outcome of in vitro fertilization. Fertil Steril. 2007 Jan;87(1):213-6. doi: 10.1016/j.fertnstert.2006.05.066. Epub 2006 Nov 1.
- Results publication: PubMed 19409544Kovacic B, Sajko MC, Vlaisavljevic V. A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles. Fertil Steril. 2010 Jul;94(2):511-9. doi: 10.1016/j.fertnstert.2009.03.077. Epub 2009 May 5.
- Results publication: PubMed 18927130Meintjes M, Chantilis SJ, Douglas JD, Rodriguez AJ, Guerami AR, Bookout DM, Barnett BD, Madden JD. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Hum Reprod. 2009 Feb;24(2):300-7. doi: 10.1093/humrep/den368. Epub 2008 Oct 16.
- Results publication: PubMed 27012651Nastri CO, Nobrega BN, Teixeira DM, Amorim J, Diniz LMM, Barbosa MWP, Giorgi VSI, Pileggi VN, Martins WP. Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertil Steril. 2016 Jul;106(1):95-104.e17. doi: 10.1016/j.fertnstert.2016.02.037. Epub 2016 Mar 21.
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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 study testing Reducing the Oxygen Concentration From 5% to 2% in people with IVF, run by International Islamic Center for Population Studies and Research at 1 site in Egypt.
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 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 11 Jul 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 Egypt. 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 Ahmed El Sayed Sabry (01098609545, ahmedsabry7787@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and grad of embryos which exposed to oxygen concentration 2% . (time frame: 1.3 year). 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 NCT05924048, which also lists 11 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 11 Jul 2023.