39. CLINICAL INTERPRETATION OF NON-STANDARD PGT-A RESULTS

Abstract

Introduction Preimplantation genetic testing for chromosome anomalies has been used to improve reproductive outcomes for nearly 20 years. But in some cases, the effectiveness of Preimplantation genetic testing for aneuploidies (PGT-A) may be reduced. Sources of errors during PGT-A are low sensitivity or specificity of either method or interpretation. The threshold value that separates normal result from pathological is not fully formalized for current methods of PGT-A (aCGH, NGS). The decision on the status of the sample is taken by the interpreter (the expert). Can preimplantation genetic testing for aneuploidies reduce IVF efficiency? Yes, if euploid embryo is defined as abnormal or if abnormal embryo is recommended for transfer. To estimate how much the interpretation of the same PGT-A data may differ between the readers we designed the project «Many men, many minds». Materials & Methods We compared the experts’ interpretation with some arbitrary reference. The references are the clinical reports, created in Genetico Laboratory, based on the joined decision after discussion of program data between the clinical geneticist, laboratory geneticist and biologist. Participants of the study were 10 readers, 2 of which are outside Russia. We included 50 samples analyzed by aCGH (Cytochip 24sure, Illumina) and 50 samples analyzed by NGS (Veriseq, Illumina) in our project. The samples for interpretation were not representative of routine samples of Genetico Laboratory (not typical samples were chosen for interpretation, but rather most hard to read ones). The experts received data which include chromosome profiles, QC metrics, and chromosome imbalances which automatically determined by the BlueFuse Multi program (Illumina). We asked experts to provide an answer containing molecular karyotype for each sample and clinical recommendations for embryo transfer. Results Interpretation of PGT-A results depends of expert's “school of thought” – at the same lab opinions tend to be more concordant. And interpretation of chromosome profiles by another expert can lead to a change in the clinical fate of the embryo. It is advisable to discuss PGT-A results between specialists before clinical report making. Interpretation of hard to read data of PGT-A is difficult and the role of the human factor very big. The “low specificity” of an expert may led to samples being recognized as aneuploid, although another expert using the same data will give an estimate of “norm” (or vice versa). Reanalysis of PGT-A data may lead to significant changes in clinical decisions regarding the fate of embryos. And after several months we tested if one interpreter could have two different opinions regarding the same sample. The participants of this additional experiment became 5 experts from initial list of participants. We asked them about the interpretation of 10 samples from the initial list. We did not reveal that these samples were same the experts interpreted several months before. We saw that the same expert may have different opinions on the same sample. Conclusions PGT-A allows to increase IVF efficiency, however, we have room for improvement. It is possible to work on improving the process of data interpretation.