Clinical Value of Mosaicism Diagnosis on the Trophectoderm Biopsies
Condition: Aneuploidy; Chromosome Abnormality
MeSH terms: Chromosome Disorders; Aneuploidy; Chromosome Aberrations
Study type: Observational

Summary: 
      Mosaicism within an embryo is defined as the presence of two or more cell populations with
      different genotypes. Blastocysts classified as mosaic by Preimplamtation Genetic Testing for
      Aneuploidy (PGT-A) have been reported to implant less and miscarry more frequently than
      embryos classified as euploid. Because of the unknown impact of mosaicism on embryo
      development, these embryos are given low priority and are discarded for transfer. However,
      recent papers on the transfer of human embryos classified by PGT-A as mosaic suggest that
      embryos with a low fraction of abnormal cells resulting in viable, chromosomally normal
      ongoing pregnancies, and high-level mosaics resulting in fewer viable pregnancies, but so far
      none producing mosaic babies.

      The apparent presence of mosaicism in an embryo is used as a selection criteria for embryo
      transfer (ET), introducing a strong bias in terms of patient prognosis and embryo quality.
      Additionally, it is also possible that some embryos are incorrectly classified as "mosaic"
      due to technical variability derived from the processing of a uniform aneuploid embryo.

      The aims of this study is to provide evidences about the clinical significance of chromosomal
      mosaicism in PGT-A cycles by a prospective non-selection based methodology.
    

Detailed description: 
      One of the most common reasons why in vitro fertilization (IVF) is unsuccessful, or why
      miscarriages occur, is because of chromosomal abnormalities in the embryo. Embryos with less
      than 20% aneuploidy are considered as euploid, while those between 20-80% are reported as
      mosaic, and those over 80% as aneuploid. Embryos with the correct number of chromosomes
      (euploid) have a higher chance of leading to a successful pregnancy than those with the
      incorrect number of chromosomes (aneuploid) or mosaics.

      Mosaicism within an embryo is defined as the presence of two or more cell populations with
      different genotypes. Preliminary data suggested that embryos identified as mosaic by
      Preimplamtation Genetic Testing for Aneuploidy (PGT-A) may have a reduced chance of
      implantation compared with euploid and may play a significant role in pregnancy loss.

      Because of the unknown impact of mosaicism on embryo development, these embryos are given low
      priority and are discarded for transfer. They are transferred mostly in poor prognosis
      patients, explaining the reported lower clinical performances. However, other recent data
      regarding the transfer of embryos diagnosed as mosaic has shown that embryos with a low
      fraction of abnormal cells may result in viable, chromosomally normal ongoing pregnancies.

      The apparent presence of mosaicism in an embryo is used as a selection criteria for embryo
      transfer (ET), introducing a strong bias in terms of patient prognosis and embryo quality.
      Additionally, it is also possible that some embryos are incorrectly classified as mosaic due
      to technical variability derived from the processing of a uniform aneuploid embryo. Thus,
      there is an urgent need to understand how to appropriately select and counsel patients
      regarding such embryos.

      This study aims to provide evidences about the clinical significance of chromosomal mosaicism
      in PGT-A cycles by a prospective non-selection based methodology.

      The objectives are to investigate the clinical predictive value for intermediate copy number
      results consistent with the presence of low mosaicism in TE biopsies, and to validate the
      thresholds for the classification of embryos in relation with their reproductive potential,
      providing comprehensive data for clinicians and patients. To demonstrate these objectives, a
      total of 878 participants are expected to be recruited in 18 months. As the datapoints
      required for comparison concern embryo transfers rather than participants, this number could
      be lower depending on the number of embryo transfers received by each participant.
    

Intervention name(s): PGT-A
Intervention type(s): Diagnostic Test
Intervention description(s): PGT-A will be carried out following the usual clinical practice: Trophectoderm biopsy samples from blastocysts are analyzed by NGS to screen for numerical chromosomal abnormalities.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Embryos from In Vitro Fertilization (IVF) patients up to 44 years old (also included) with
        medical indication of PGT-A and own oocytes.
      
Biospecimen description: 
      DNA analysis of each patient's embryos
    
Keywords: Mosaicism; PGT-A; Blastocyst biopsy; Aneuploidy testing; Preimplantation genetics