Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR)

J Assist Reprod Genet. 2019 Dec;36(12):2547-2555. doi: 10.1007/s10815-019-01593-9. Epub 2019 Nov 6.

Abstract

Purpose: Balanced carriers of structural rearrangements have an increased risk of unbalanced embryos mainly due to the production of unbalanced gametes during meiosis. Aneuploidy for other chromosomes not involved in the rearrangements has also been described. The purpose of this work is to know if the incidence of unbalanced embryos, interchromosomal effect (ICE) and clinical outcomes differ in carriers of different structural rearrangements.

Methods: Cohort retrospective study including 359 preimplantation genetic testing cycles for structural rearrangements from 304 couples was performed. Comparative genomic hybridisation arrays were used for chromosomal analysis. The results were stratified and compared according to female age and carrier sex. The impact of different cytogenetic features of chromosomal rearrangements was evaluated.

Results: In carriers of translocations, we observed a higher percentage of abnormal embryos from day 3 biopsies compared with day 5/6 biopsies and for reciprocal translocations compared with other rearrangements. We observed a high percentage of embryos with aneuploidies for chromosomes not involved in the rearrangement that could be attributed to total ICE (aneuploid balanced and unbalanced embryos). No significant differences were observed in these percentages between types of rearrangements. Pure ICE (aneuploid balanced embyos) was independent of female age only for Robertsonian translocations, and significantly increased in day 3 biopsies for all types of abnormalities. Furthermore, total ICE for carriers of Robertsonian translocations and biopsy on day 3 was independent of female age too. High ongoing pregnancy rates were observed for all studied groups, with higher pregnancy rate for male carriers.

Conclusion: We observed a higher percentage of abnormal embryos for reciprocal translocations. No significant differences for total ICE was found among the different types of rearrangements, with higher pure ICE only for Robertsonian translocations. There was a sex effect for clinical outcome for carriers of translocations, with higher pregnancy rate for male carriers. The higher incidence of unbalanced and aneuploid embryos should be considered for reproductive counselling in carriers of structural rearrangements.

Keywords: Aneuploid unbalanced embryo; Biopsy; Interchromosomal effect; PGT-SR; Structural rearrangement.

MeSH terms

  • Adult
  • Aneuploidy*
  • Biopsy
  • Blastocyst / pathology
  • Chromosome Inversion / genetics*
  • Comparative Genomic Hybridization
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Heterozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Pregnancy
  • Pregnancy Rate
  • Preimplantation Diagnosis*
  • Translocation, Genetic / genetics*