Commentary on two recently published formal guidelines on management of “mosaic” embryos after preimplantation genetic testing for aneuploidy (PGT-A)

Abstract

Two professional societies recently published opinions on the clinical management of “mosaic” results from preimplantation genetic testing for aneuploidy (PGT-A) in human blastocyst-stage embryos in associations with in vitro fertilization (IVF). We here point out three principal shortcomings: (i) Though a most recent societal opinion states that it should not be understood as an endorsement of the use of PGT-A, any discussion of how PGT-A should be clinically interpreted for all practical purposes does offer such an endorsement. (ii) The same guideline derived much of its opinion from a preceding guidance in favor of utilization of PGT-A that did not follow even minimal professional requirements for establishment of practice guidelines. (iii) Published guidelines on so-called “mosaic” embryos from both societies contradict basic biological characteristics of human preimplantation-stage embryos. They, furthermore, are clinically unvalidated and interpret results of a test, increasingly seen as harmful to IVF outcomes for many infertile women. Qualified professional organizations, therefore, should finally offer transparent guidelines about the utilization of PGT-A in association with IVF in general.

From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

“…A Preimplantation Genetic Diagnosis International Society (PGDIS) Position Statement on chromosome mosaicism in PGS has suggested a guideline to prioritize mosaic embryos for transfer based on the level of mosaicism and the specific chromosome involved [90]. There are also other recommendations and clarifications of principles for the transfer of mosaic embryos [91,92]. Nevertheless, information about the mechanism of aneuploidy formation may decrease the probability of PGT-A error when determining the fate of embryos with chromosomal mosaicism.…”

The Disputable Discourse on Accuracy and Effectiveness of PGT-A in Light of Advancements in Genetic Tools

“…Despite these developments, researchers have not yet been able to experimentally or clinically validate the effectiveness of these techniques. On the contrary, there is growing evidence that the effectiveness of these procedures is being questioned due to biological characteristics of early human embryos at pre-implantation stage ( 1 ).…”

“…Regarding mosaicism detection in embryos, three conditions can be reported for trophectoderm biopsy and PGT-A results at blastocyst stage: ( 1 ) the reported euploid embryos may be 100% euploid or contain aneuploid cells elsewhere in the trophectoderm or inner cell mass. The actual explanation is that this embryo is not completely aneuploid, may be fully euploid or mosaic; ( 2 ) the reported aneuploidy embryos may actually be 100% aneuploid or may be mosaic due to presence of euploid cells elsewhere in the trophectoderm and inner cell mass.…”

“…The actual explanation is that this embryo is not completely aneuploid, may be fully euploid or mosaic; ( 2 ) the reported aneuploidy embryos may actually be 100% aneuploid or may be mosaic due to presence of euploid cells elsewhere in the trophectoderm and inner cell mass. In fact, this embryo is not completely euploid; ( 3 ) the reported mosaic embryo is certainly mosaic, although it is not possible to reliably determine the true percentage of euploidy and aneuploidy through few cells collected from trophectoderm ( 1 ).…”

“…Currently, the maximum time for culturing and maintaining early embryos outside the uterus is 6 days, after which the embryos should be frozen or transferred into the uterus. Therefore, if the advancement of science and technology lays the ground for longer in vitro culture of human embryos without interfering with implantation rate, it will be possible to select more euploid embryos for transfer into the uterus and considerably enhance the success rate of infertility treatment ( 1 , 4 ).…”