Use of Time-lapse Morphological Kinetics in the Selection of Blastocysts
Condition: Viability
Study type: Interventional

Summary: 
      This is a randomized controlled observational trial to determine if data obtained from the
      embryoscope is helpful in determining which blastocysts to transfer.
    

Detailed description: 
      Materials and Methods:

      Patient Selection:

      Patients undergoing an IVF cycle at the Cleveland Clinic Reproductive Endocrinology and
      Infertility clinic with the plan for transfer of embryo(s) will be offered the opportunity to
      participate in this study. We would like a total enrollment 300 patients with 150 in each
      group. The only patients excluded will be those undergoing pre-implantation genetic testing
      and/or chromosome screening.

      Study Design This will be a prospective randomized controlled trial where all patients who
      agree to participate will be randomized to having embryo selection for transfer based solely
      on conventional criteria or alternatively conventional criteria in conjunction with
      morphokinetic criteria.

      Enrollment:

      Patients will be enrolled at the Beachwood IVF center by the REI physicians at the time of
      the IVF consultation. They will sign the informed consent for the study at the time that they
      sign the consent for IVF treatment, which is done by the IVF nurses. Informed consent for the
      study will be kept in the patient chart in the Beachwood IVF center along with the IVF
      consent.

      Randomization:

      Patients will be randomized 1:1 to Conventional embryo selection vs. Embryoscope selection
      using a computer generated random number sequence. Group assignment will be written on a
      piece of paper and placed in consecutively numbered opaque envelopes by research personnel
      not involved in embryo selection. Each patient randomized will be assigned the next
      consecutive number and the embryo selection criteria will be revealed at time of oocyte
      retrieval. Patients, REI physicians and staff, and sonographers will be blinded as to how
      embryos are selected. Only the embryologist and the lab staff will be aware of which group
      the patients are randomized into. This will be ensured by not placing the group in the
      computerized medical record or the clinical chart, but only in the laboratory chart and the
      research database.

      Sample Size Justification Little published data is available on time-lapse imaging and human
      embryo selection for transfer. No publications of randomized controlled trials are available
      on the EmbryoScope. Statistician Benjamin Nutter was consulted for sample size estimation.
      Initially, based on the 2012 outcomes there was a pregnancy rate of 49%. For a power of 80%,
      in order to detect an increase to 55% pregnancy rates under the new selection guidelines, we
      would need to randomize 1088 patients. To see an increase to 60% pregnancy rates, we would
      need to randomize 320 patients.

      In this study, we will be focusing on those patients who have blastocysts available for
      transfer since blastocysts are the embryos that we need the most assistance with selection.
      The pregnancy rate in this subset of patients is currently 70% and to detect an increase to
      80% would require randomization of 231 patients. Based on these numbers we feel it is
      reasonable to start with a goal of 300 patients in this study as there will be some patients
      that do not make it to retrieval, some that have no fertilization and some that have no
      embryos progress to transfer. Starting with a goal of 300 patients will hopefully give us a
      large enough sampling to do a preliminary analysis of embryos resulting in a clinically
      evident pregnancy as defined by positive fetal heart rate.

      Given that the outcome of this study is pregnancy rate we will assess the data collected
      after six months to evaluate if there is a clear difference between groups. If there is a
      significant difference at that time, the study may be terminated to allow for all patients to
      have the benefit of the superior method.

      Research Procedure The basic IVF laboratory protocols utilized will be the same as that used
      for all patients. Oocytes will be recovered by transvaginal aspiration of follicles under
      ultrasound guidance. Oocytes will be inseminated by intracytoplasmic sperm injection or
      co-incubation with sperm. The next morning, normally fertilized oocytes will be identified
      and moved to individual wells in a slide chamber and placed in the EmbryoScope.

      Those randomized to classic evaluation will have their embryos graded based on conventional
      daily evaluation at specified daily time points. These criteria encompass timely development
      to specific benchmarks at 20, 26, 44, 68, 92, 116 and 140 hours post-insemination.

      The images will be from the EmbryoScope, but will be static in time and will not span across
      a time range. Embryos will be graded and selected for transfer according to the laboratory's
      conventional criteria. Those randomized to classic evaluation plus morphokinetic parameters
      will have embryo evaluation performed at the same defined intervals but using the data
      analysis software and the captured time-lapse images to include timing of mitotic intervals,
      cleavage planes, timing of compaction and cavitation in embryos leading to blastocyst
      formation.

      Patients electing not to participate in the study would still have their embryos cultured in
      the EmbryoScope and conventional embryo selection criteria would be applied to identify
      embryos fro transfer.
    

Intervention name(s): Embryoscope; Conventional Criteria
Intervention type(s): Device; Other
Intervention description(s): The embryoscope is a microscope that allows for continuous time-lapse monitoring.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment