Study of the interchromosomal effect in carriers of balanced structural chromosomal rearrangements by PGT-SR

Abstract

Introduction: Carriers of balanced structural rearrangements, despite being phenotypically normal, they have a signifi- cantly decreased reproductive competence compared to the general population. The reason is because, during gametoge- nesis, depending on how the chromosomal alteration is segregated in meiosis I, normal, balanced, or unbalanced gametes will be generated in greater proportion than in carriers of normal karyotypes. This is the main cause of the higher rate of abortions and offspring with alterations that carriers of inversions, reciprocal translocations or Robertsonian translocations present. Another possible source of aneuploid gametes and/or embryos is the so-called interchromosomal effect (ICE), which consists of an interference produced by a structural chromosomal alteration on the proper disjunction and segregation of other chromosomes not involved in the rearrangement.

Material and methods: A total of 40 couples were included in the study, of which 31 belonged to the study group: fourteen Robertsonian translocations, thirteen reciprocal translocations and four pericentric inversions. As for the affected parent, in nineteen of the cases the woman was the carrier of the chromosomal alteration and in the remaining twelve it was the man who was affected. Nine couples with a normal karyotype, carriers of a mutation responsible for monogenic disease, were included in the control group. 57 cycles of PGT-SR and PGT-M+PGT-A were performed using NGS-based techni- ques, and 180 embryos were analyzed.

Results: It was observed that the rate and the number of aneuploid embryos were higher in the study group than in the control group (62.76% vs. 31.43%, p = 0.011). Among the different types of balanced rearrangements, the percentage of aneuploid embryos was higher in reciprocal translocations, the percentage of euploid embryos was higher in Robertsonian translocations, and the number and rate of undiagnosed embryos was higher in pericentric inversions. These differences reached statistical significance. No significant differences were found in the interchromosomal effect between rearrange- ment carriers or compared to the control group. The chromosomes most frequently involved in aneuploidies were 16, 22 and 21.