Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oxygen Tension on Human Embryonic Development (EmbryOx)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03964805
Recruitment Status : Completed
First Posted : May 28, 2019
Last Update Posted : May 28, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 28, 2019
Last Update Posted Date May 28, 2019
Actual Study Start Date  ICMJE September 1, 2016
Actual Primary Completion Date September 6, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
  • Embryo quality at Day 2 between groups A and B. [ Time Frame: Day 2 ]
    Embryo morphology is qualified as the number of blastomeres, degree of cytoplasmic fragmentation, regularity of the cells and presence/absence of multinucleated blastomeres. Day 2 top-quality embryos are defined as 4 regular blastomeres, <20% cytoplasmic fragmentation, no multinucleations.mbryos are defined as 4/8 regular blastomeres, <20% cytoplasmic fragmentation, no multinucleations.
  • Embryo quality at Day 3 between groups A and B. [ Time Frame: Day 3 ]
    Embryo morphology is qualified as the number of blastomeres, degree of cytoplasmic fragmentation, regularity of the cells and presence/absence of multinucleated blastomeres. Day 3 top-quality embryos are defined as 8 regular blastomeres, <20% cytoplasmic fragmentation, no multinucleations.
  • Embryo quality at blastocyst stage (Day 5) between groups A, B and C. [ Time Frame: Day 5 ]
    Blastocyst morphology is assessed according to Gardner and Schoolcraft's classification: degree of blastocele expansion (graded from B1 to B6), inner cell mass and trophectoderm morphology (both graded A, B or C). Day 5 top quality blastocyst are defined as ≥B4AA/AB/BA.
  • Embryo quality at blastocyst stage (Day 6) between groups A, B and C. [ Time Frame: Day 6 ]
    Blastocyst morphology is assessed according to Gardner and Schoolcraft's classification: degree of blastocele expansion (graded from B1 to B6), inner cell mass and trophectoderm morphology (both graded A, B or C). Day 5 top quality blastocyst are defined as ≥B4AA/AB/BA.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
  • Fertilization rate [ Time Frame: Days 1 ]
    Percentage of oocytes fertilized per oocyte inseminated, assessed at Day 1
  • Early cleavage rate [ Time Frame: 25 hours after insemination ]
    Percentage of embryos at the 2-cell stage per oocyte fertilized, assessed 25 hours after insemination
  • Useable embryo rate [ Time Frame: Days 2/3; 5/6 ]
    Percentage of embryos transferred and/or frozen per embryo
  • Implantation rate [ Time Frame: 4-5 weeks after transfer ]
    Number of gestational sacs with fetal heart beat detected per embryo transferred
  • Clinical pregnancy rate [ Time Frame: 4-5 weeks after transfer ]
    Percentage of pregnancies diagnosed by ultrasonographic visualization of at least one gestational sac with fetal heart beat per embryo transfer
  • Miscarriage rate [ Time Frame: 4-5 weeks after transfer ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oxygen Tension on Human Embryonic Development
Official Title  ICMJE Impact of Low Versus Atmospheric Oxygen Tension on Human Embryo Development : A Prospective Randomized Study
Brief Summary In mammals, uterine environment is at low oxygen concentration (2-8% O2). Thus, human embryo culture under low O2 tension (5%) is now recommended by European Society of Human Reproduction and Embryology (ESHRE) revised guidelines for good practices in in vitro fertilization (IVF) labs. Indeed, hypoxia seems to improve embryo quality at cleavage and blastocyst stages, presumably by reducing damages of oxidative stress (OS). Nevertheless, recent meta-analyses concluded only with a low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Furthermore, a study on mouse embryos suggested a negative impact of OS only at cleavage stage. The aim of the present prospective randomized study was to investigate this hypothesis for the first time in human embryos.
Detailed Description

In mammals, uterine environment is at low oxygen tension, between 2 and 8% O2 . However, most IVF labs perform embryo culture at atmospheric tension (around 20% O2). Several randomized studies in human embryos have reported the superiority of hypoxia (5%) in terms of embryo quality and blastulation rates. This fact might be explained by a more physiological environment, probably inducing a decrease in oxidative stress (OS), which has a harmful impact on embryo development. Other studies have also suggested that before compaction, OS damages might be irreversible.

Wale et Gardner have investigated this impact of oxygen tension on mouse embryo development, by comparing four culture conditions: (i) group 1: culture exclusively at 5% O2 ; (ii) group 2: culture at 5% from Day 0 to Day 2, then at 20% from Day 2 to Day 4; (iii) group 3: at 20% then at 5% from Day 2; (iv) and group 4: culture exclusively at 20% Interestingly, no difference in terms of blastulation had been reported between groups 1 and 2, suggesting the OS might impact only at cleavage stage, and that switching culture under atmospheric conditions from Day 2/3 might not influence embryo development thereafter.

Hence, all those investigations suggest that embryo culture using trigas incubators (5% O2, 6% CO2 and 89% N2) would be preferable. However, this system is very expensive, notably due to a high N2 consumption, and requires a more complicated logistics (e.g. N2 levels monitoring). Yet, Wale and Gardner's results imply that sequential culture conditions (trigas from Day 0 to Day 2/3, then conventional incubator at 20% O2 until blastocyst stage) could be an valuable option, reducing the costs and, essentially, without any detrimental impact on embryo development.

The present study has two main objectives: (i) to confirm the improvement in embryo quality under low oxygen tension and (ii) to demonstrate the negative impact of OS only at cleavage stage in human embryos, as assumed by Wale and Gardner. For that purpose, we designed an original prospective randomized study comparing three culture conditions: (i) culture excusively at 20% O2 (Day 0 to Day 6) (Group A); (ii) culture exclusively at 5% O2 (Day 0 to Day 6) (Group B); (iii) culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6) (Group C). Inclusion criteria and outcome measures are detailed in the following sections.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Infertility
  • Embryo Culture
  • Hypoxia
Intervention  ICMJE
  • Other: 20% oxygen
    culture excusively at 20% O2 (Day 0 to Day 6)
    Other Name: culture at 20% O2
  • Other: 5% oxygen
    culture excusively at 5% O2 (Day 0 to Day 6)
    Other Name: culture at 5% O2
  • Other: 20 % and 5 % oxygen
    culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6)
    Other Name: culture at 20 % and at 5%O2
Study Arms  ICMJE
  • Active Comparator: group A
    Embryo culture at 20% O2
    Intervention: Other: 20% oxygen
  • Active Comparator: group B
    Embryo culture at 5% O2
    Intervention: Other: 5% oxygen
  • Active Comparator: group C
    Embryo culture at 5% O2 and at 20% O2
    Intervention: Other: 20 % and 5 % oxygen
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 24, 2019)
773
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 1, 2018
Actual Primary Completion Date September 6, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age: 18 - 39 years
  • IVF / ICSI Attempt with Ejaculated Sperm Sperm (Fresh or Frozen)
  • At least 8 oocytes retrieved in total
  • Good understanding of the protocol by the patient
  • Informed and consentment signed of the couple

Exclusion Criteria:

  • - Hydrosalpinx
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 39 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03964805
Other Study ID Numbers  ICMJE 2015-A02019-40
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christophe Sifer AP-HP_Hôpital Jean Verdier
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP