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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

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.

Condition or disease Intervention/treatment Phase
Infertility Embryo Culture Hypoxia Other: 20% oxygen Other: 5% oxygen Other: 20 % and 5 % oxygen Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 773 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Low Versus Atmospheric Oxygen Tension on Human Embryo Development : A Prospective Randomized Study
Actual Study Start Date : September 1, 2016
Actual Primary Completion Date : September 6, 2018
Actual Study Completion Date : December 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Oxygen Therapy

Arm Intervention/treatment
Active Comparator: group A
Embryo culture at 20% O2
Other: 20% oxygen
culture excusively at 20% O2 (Day 0 to Day 6)
Other Name: culture at 20% O2

Active Comparator: group B
Embryo culture at 5% O2
Other: 5% oxygen
culture excusively at 5% O2 (Day 0 to Day 6)
Other Name: culture at 5% O2

Active Comparator: group C
Embryo culture at 5% O2 and at 20% 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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. Fertilization rate [ Time Frame: Days 1 ]
    Percentage of oocytes fertilized per oocyte inseminated, assessed at Day 1

  2. 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

  3. Useable embryo rate [ Time Frame: Days 2/3; 5/6 ]
    Percentage of embryos transferred and/or frozen per embryo

  4. Implantation rate [ Time Frame: 4-5 weeks after transfer ]
    Number of gestational sacs with fetal heart beat detected per embryo transferred

  5. 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

  6. Miscarriage rate [ Time Frame: 4-5 weeks after transfer ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03964805


Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Christophe Sifer AP-HP_Hôpital Jean Verdier
Publications:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03964805    
Other Study ID Numbers: 2015-A02019-40
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: May 28, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Embryo culture
oxygen tension,
embryo quality,
extended culture
Additional relevant MeSH terms:
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Infertility
Hypoxia
Signs and Symptoms, Respiratory