Analysis of molecular cytogenetic features and PGT-SR for two infertile patients with small supernumerary marker chromosomes

Can preimplantation genetic testing for structural rearrangement (PGT-SR) with next-generation sequencing (NGS) be used to infertile patients carrying small supernumerary marker chromosomes (sSMCs)?

In this study, two infertile patients carrying ring sSMCs were recruited. Different molecular cytogenetic techniques were performed to identify the features of the two sSMCs, followed by clinical PGT-SR cycles.

The results of G-banding and FISH showed that patient 1’s sSMC originated from the 8p23-p10 region, with a resulting karyotype of [ 47,XY, del(8)(p23p10), +r(8)(p23p10).ish del(8)(CEP8+,subtle 8p+,subtle 8q+),r(8)(CEP8+,subtle 8p-,subtle 8q-)[55/60].arr(1-22) ×2,(X,Y)×1]. The sSMC of patient 2 was derived from chromosome 3 and further microdissection with next-generation sequencing (MicroSeq) revealed it contained the region of chromosome 3 between 93,504,855 and 103,839,892 bp (GRCh37), which involved 52 known genes. So the karyotype of patient 2 was 47,XX, +mar.ish der(3)(CEP3+,subtle 3p-,subtle 3q-)[49/60].arr[GRCh37] 3q11.2q13.1(93,500,001_103,839,892) ×3(0.5). PGT-SR with NGS was performed to provide reproductive guidance for the two patients. For patient 1, four balanced euploid embryos and four embryos with partial trisomy/monosomy of (8p23.1-8p11.21) were obtained, and a balanced euploid embryo was successfully implanted and had resulted in a healthy baby. For patient 2, an embryo with monosomy of sex chromosomes and another embryo with a duplication at (3q11-q13.1), neither of which was available for implantation.

The identification of the origins and structural characteristics of rare sSMCs should rely on different molecular cytogenetic techniques. PGT-SR is an alternative fertility treatment for these patients carrying sSMCs. This study may provide directions for the assisted reproductive therapy for infertile patients with sSMC.