Oxygen Tension on Human Embryonic Development
Condition: Infertility; Embryo Culture; Hypoxia
MeSH terms: Infertility; Hypoxia
Study type: Interventional

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.
    

Intervention name(s): 20% oxygen; 5% oxygen; 20 % and 5 % oxygen
Intervention type(s): Other; Other; Other
Intervention description(s): culture excusively at 20% O2 (Day 0 to Day 6); culture excusively at 5% O2 (Day 0 to Day 6); culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6)
Other intervention name(s): culture at 20% O2; culture at 5% O2; culture at 20 % and at 5%O2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Embryo culture; oxygen tension,; embryo quality,; extended culture