The challenge of embryonic mosaicism in preimplantation genetic screening

Richard T. Scott Jr., M.D., Daniela Galliano, M.D.

Volume 105, Issue 5, Pages 1150-1152


The availability of reliable 24 chromosome aneuploidy screening platforms has provided clinicians and scientists with a powerful new diagnostic tool in the embryology laboratory. Class I data demonstrate increased implantation and delivery rates and reduced multiple gestation rates by empowering more effective single ET after preimplantation genetic screening (PGS) is performed on trophectoderm biopsies (1, 2). Sustained implantation rates of 60% or higher are routinely being attained in multiple programs after synchronous transfer of euploid blastocysts—even in women in their early forties.

  • Essam Othman

    I see most advocats of PGS describe a higher implantation rate with the use of the technique. Any information about improving live birth rate?
    Another point: It is my understanding on Mosaicism in trophoectoderm biopsy that we identify different cell lines in the trophoectoderm cells, however that does not give information about nature of cells in the inner cell mass!

  • Richard Scott

    When using technologies which have well done non-selection studies I do not think we need to save all embryos. The reality is that if a good study shows that embryos which were biopsied and transferred who analysis ultimately showed aneuploidy have exceedingly low chances of delivery, then it is unlikely that we need to save these abnormal embryos. One problem comes when we apply technologies without doing those studies. For SNP array, the error rate is about 4%. With qPCR, the rate is lower and is a little under 2%. The sample size is quite small with NextGen following directed amplifcation (not WGA), but the rate has been zero so far.

    In the end, patients, embryologist, and clinicians will need to decide if it is worth saving and transferring an embryo with < 2% chance of delivering.

    There is a great deal of important work remaining to be done here. This is a exciting but confusing time for the issue of mosaicism. Hopefully the field will see methodical valiadations so we can all decide how best to manage the 5% of embryos which are designated mosaic (ref Greco NEJM)

  • Richard Scott


    A few opinions – not enough data to be definitive.

    Most important is the need to validate the results seen with Next Gen and other platforms to see how often the diagnosis of “mosaicism” is real. We certainly do not have sufficient data to date.

    The concept of rebiopsy is complex. Biopsies only samples a few percent of the cells. Even if absent in an additional biopsy is clearly euploid it does not mean that an aneuploid cell line is present elsewhere in the embryos. Clinically that is a problem since we have two results from two samples and no real basis for selecting which one we believe. Clearly we need to know more and it may come down to a large multi-center prospective study to assess the outcomes including the risk of abnormal gestation. Recruitment will be quite challenging.

    We are not certain when mosaicism occurs, but there are some data to suggest that it occurs prior to compaction.

    Day 3 biopsy of a single cell would eliminate the problem because there is no possible way to detect mosaicism – even if present. However, we probably want to know so simply hiding the result by limiting sampling is not optimal. Beyond that, the detrimental impact of day 3 biopsy would likely preclude any perceived benefits anyway. Collecting two cells on day 3 might allow some mosaicism to be detected by the impact is even more detrimental and probably does not represent a realistic option.

    • wonderful paper Richard. Do you think we have reached the point where we have to reassess the policy of discarding abnormal PGS embryos as “abnormal” …this is a very complex counseling situation and I can see where we would need to discuss the potential for mosicism with couples (I already do this) but consider if some might in that situation want to continue to store the embryo for the possibility of better assay techniques in the future. I am concerned re: the pandora’s box of centers keeping vast stores of what we believe are likely abnormal embryos

  • mperloe

    1. Would a multi-center clinical IRB approved trial that looks at transfer or re-biopsy of these embryos yield helpful information?
    2. Is there data available to suggest when mosaicism occurs?

    3. Would the diagnosis of true mosaicism by greater with day 3 biopsy? Would this warrant reconsideration of D3 biopsy?

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