38. CASE STUDY: PREGNANCY WITH MOSAIC OF TRISOMY / MONOSOMY 18 AFTER TRANSFER OF AN APPARENTLY EUPLOID BLASTOCYST TESTED BY ACGH

Abstract

Introduction It is already known that accuracy of preimplantation genetic testing for aneuploidy (PGT-A) might be compromised by relatively high frequency of mosaics in human preimplantation embryos, even in the blastocyst stage. Giving into account low number of cells which may be removed from embryo for analysis, the fact that all the cells are biopsied in a cluster from one locus of trophectoderm (TE) and that TE represents not foetal but future placental tissue, PGT-A should not be considered as a diagnostic examination but only as a screening test that may contribute to a better assessment of embryonal viability. Material & methods We present a case of a couple with multiple recurrent miscarriages in the first trimester after spontaneous conceptions. In 2016 the couple decided to undergo IVF/ICSI treatment with PGT-A by array comparative genome hybridization (aCGH) on TE samples (24sure, Bluegnome /Illumina). All (8) analyzed blastocysts were shown to be euploid. The first (double) embryotransfer resulted in pregnancy and the patient gave birth to a healthy girl (2017). After two subsequent (single) embryo transfers in 2018 patient got pregnant but the pregnancy resulted in a missed abortion in 10th week of pregnancy. Results Analysis of aborted tissue by quantitative fluorescent polymerase chain reaction (QF-PCR; Devyser Complete v2/ Devyser 18 v2, Devyser AB) showed aneuploidy of chromosome 18 in a form not conflicting with trisomy of mitotic origin (all short tandem repeats (STR) markers were in 2:1 ratio). aCGH (SurePrint G3, ISCA v2, 8x60K, Agilent Technologies) confirmed trisomy 18 corresponding with 75% representation of the trisomic cell line. Re-analysis of stored amplified TE sample by next generation sequencing (NGS) method (VeriSeq, Illumina) revealed, by aCGH unrecognized, monosomy 18 at the level corresponding with 20% of monosomic cells. Both trophectoderm and aborted tissue samples showed origin from the same individual (Devyser 18 v2, Devyser AB). Conclusions The presented case clearly documents limitation of PGT-A, and caution which should be taken when the test is offered to patients and particularly when doing interpretation of the results. It also supports the opinion that embryos with proven mosaic monosomy of chromosomes 13, 18, 21 should be always avoided from the transfer.