Clinical outcomes in carriers of insertional translocation: a retrospective analysis of comprehensive chromosome screening results

Abstract

Objective: To evaluate the clinical outcomes in the carriers of insertional translocation (IT).

Design: Retrospective case series.

Setting: University-affiliated reproductive medical center.

Patients: Twenty-three couples with ITs.

Intervention: No direct interventions were involved; however, this study included patients who underwent preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR).

Main outcome measure: Outcome of preimplantation genetic testing for structural chromosomal rearrangements and percentage of blastocysts available for transfer.

Results: Among 23 IT carriers, 15 were simple interchromosome ITs (type A), 3 were intrachromosome IT carriers (type B), and 5 were interchromosome IT carriers combined with other translocations (type C). A total of 190 blastocysts from 30 cycles were biopsied, 187 embryos were tested successfully, and only 57 blastocysts (30.5%) from 21 patients were available for transfer (normal or balanced). The unbalanced rearrangement rate of type C was 79.2% (42/53), and the proportion of type A was 50.0% (57/114), which was significantly higher than that of type B (5%, 1/20). In type A, the probability of embryos harboring unbalanced rearrangement in female carriers was 56.0% (51/91), which was higher than that in male carriers (26.1%, 6/23). Furthermore, the haploid autosomal length value of the inserted fragment was correlated linearly with the incidence of abnormal embryos. In type A gametes, most gametes produced by 2:2 separation without crossover, and no 3:1 separation gamete was observed.

Conclusions: The chance of identifying normal or balanced and mosaic blastocysts per mature oocytes in patients with ITs are 16.6% (67/404). Greater IT complexity results in fewer transferable embryos. For simple interchromosome ITs, female carriers and those with higher haploid autosomal length values have a higher risk of producing embryos with unbalanced rearrangement.

Keywords: Insertional translocation; next-generation sequencing (NGS); preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR).

Figure 1

The proportion of insertional translocation (IT) types and incidence of ITs on different chromosomes. (A) The proportion of three different types of IT carriers in our study. (B) The proportion of three different types of IT carriers in the literature. (C) The relative incidence of ITs on different chromosomes in our study. (D) The relative incidence of ITs on different chromosomes in the literature. The arrows indicate the chromosomes with a higher incidence of translocation.

Figure 2

The pattern of gametogenesis in insertional translocation identified in blastocysts. (A) Four types of gametes produced after 2:2 separation without crossover. (B–D) Three types of gametes produced after 2:2 separation with crossover. (B) The first type of break occurred at the insert site of the recipient chromosome (13q33.3) and near the centromeric site of the donor chromosome (5q12.1). (C) The second type of break occurred at the insert site of the recipient chromosome (13q33.3) and at the far centromeres of the donor chromosome (5q34). (D) The third type of breakage occurred in the donor chromosome twice (5q31.2 and 5q34), resulting in the loss of a small fragment. The detailed PGT-SR results are shown in Supplemental Table 2 and Supplemental Figure 3.