Inheritance of imbalances in recurrent chromosomal translocation t(11;22): clarification by PGT-SR and sperm-FISH analysis

Reprod Biomed Online. 2019 Jul;39(1):40-48. doi: 10.1016/j.rbmo.2019.02.010. Epub 2019 Mar 12.

Abstract

Research question: To analyse why unbalanced viable offspring are derived mainly from the 3:1 segregation mode in t(11;22)(q23;q11.2) reciprocal translocation.

Design: Retrospective analysis of 24 pre-implantation genetic testing for chromosomal structural re-arrangements (PGT-SR) cycles was performed on seven male and five female carriers of t(11;22) translocation. Sperm analysis was performed on each male carrier. These patients were directed to the study centre after several years of miscarriages and/or abortions, primary infertility for male carriers or birth of an affected child.

Results: Twenty-four PGT-SR cycles were performed to exclude imbalances in both male and female carriers. The unbalanced embryos derived from the adjacent-1 segregation mode were the most represented in both male and female carriers (68.4% and 50%, respectively). These results were positively related with meiotic segregation analysis of reciprocal translocation in spermatozoa. A thorough analysis of the unbalanced embryo karyotypes determined that the expected viable +der22 karyotype resulting from 3:1 malsegregation was less represented at 5.3%.

Conclusions: These findings highlight the divergence that may exist between meiotic segregation and post-zygotic selection. Post-zygotic selection would be responsible for the elimination of unbalanced embryos derived from the adjacent-1 segregation mode. The combined action of several factors occurs at the beginning of post-zygotic selection. Genetic counselling must consider the risk of a birth related to the adjacent-1 segregation mode, irrespective of the sex of the translocation carrier. These results will allow deeper understanding of the PGT results of t(11;22) carriers, which often include a high number of aneuploid embryos.

Keywords: Embryo development; Implantation; Meiosis; Pre-implantation genetic testing for chromosomal Structural re-arrangements; Reciprocal translocation t(11;22); Viability.

MeSH terms

  • Adult
  • Chromosome Mapping / methods
  • Chromosome Mapping / statistics & numerical data
  • Chromosomes, Human, Pair 11 / genetics*
  • Chromosomes, Human, Pair 22 / genetics*
  • Female
  • Gene Frequency
  • Genetic Carrier Screening / methods
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • In Situ Hybridization, Fluorescence / statistics & numerical data
  • Inheritance Patterns / genetics*
  • Karyotyping
  • Male
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Preimplantation Diagnosis / statistics & numerical data
  • Retrospective Studies
  • Semen Analysis / methods
  • Semen Analysis / statistics & numerical data
  • Translocation, Genetic* / genetics