Embryo Culture Under Constant 5% vs Gradient 8%, 5%, 2% Oxygen Concentration
Condition: Embryonic Development; Embryo Morphokinetics; Embryo Morphometry
Study type: Interventional

Summary: 
      The purpose of this study is to investigate the development of human embryos in vitro under
      two different oxygen concentrations; a static 5% during all five days of culture or under an
      oxygen gradient, starting with 8% from day-0 to day-3, continuing with 5% on day-3 and
      following with 2% of oxygen from the end of day-3 to day-5.
    

Detailed description: 
      Several studies have shown that embryonic morphological parameters improved when the oxygen
      concentration in embryo culture was reduced from 20% to 5%. Early mammalian embryos developed
      faster, had shorter cell cycles, a higher blastocyst formation rate and a better integrity of
      the inner cell mass (ICM) compared to embryos cultured at 20% oxygen concentration.

      Recent studies have shown that the oxygen concentration in the female reproductive tract is
      not static. In the fallopian tubes of higher mammals it is at around 8%, while in the uterus,
      at the time of embryo implantation, the oxygen concentration is almost anoxic (2%).

      Mimicking such physiological conditions that better reflect the in vivo environment in the
      human reproductive tract is the goal of assisted reproductive technology (ART).

      The aim of this study is to assess whether changing the static 5% oxygen during five days of
      in vitro embryo culture to the gradient of oxygen, starting with 8% from day-0 to day-3,
      continuing with 5% on day-3 and following with 2% of oxygen from the end of day-3 to day-5,
      better reflects conditions found within the human reproductive tract and improves embryo
      developmental characteristics.
    

Intervention name(s): Experimental intervention: 8-5-2% oxygen gradient concentration in the incubator
Intervention type(s): Other
Intervention description(s): After oocyte retrieval and insemination, half of a given patient's embryos will be randomly allocated in an incubator set at a gradient of oxygen tension (8-5-2%). The embryos will remain in the incubator until their developmental assessments on day 5.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 496 sibling oocytes will be randomly allocated for culture either at low oxygen tension (5% O2) (n = 248 oocytes) or a more physiological oxygen gradient (8-5-2% O2) (n = 248 oocytes) for the next 5 days. Immediately after allocation, the oocytes will be inseminated through Intracytoplasmic Sperm Injection (ICSI). The sibling oocytes will always be injected by the same embryologist.
Under standard (5%) oxygen concentration, which is currently being used in the cultivating incubators, approximately 15% of all embryos manage to reach a morphological optimal blastocyst, in a patient group younger than 35 years (see Inclusion Criteria). According to the hypothesis that cultivating embryos under a more physiological atmosphere (gradient from 8% to 2%) improves the blastulation rate of embryos to 25%, a sample size of 496 Injected oocytes (248 in each arm), will be needed. Whereby a statistical strength of 80% and α = 0.05 is considered (calculated using power analysis).
Masking: Single (Investigator)
Primary purpose: Other
Keywords: Embryo culture, reduced oxygen, time-lapse, blastocyst