PGT for structural rearrangements (PGT-SR)

Abstract

Background Patients with structural chromosome rearrangements encounter a variety of reproductive obstacles as a result of the high frequency of unbalanced gametes in these individuals, including low pregnancy rates, increase in spontaneous abortion (SAB) rate and an increased risk for unbalanced, genetically abnormal offspring1. The most common structural chromosome abnormality is the reciprocal translocation, seen in about 0.16% of the general population. A reciprocal translocation is the exchange of genetic material between two chromosomes; it is estimated that approximately 70% of embryos generated by a parent with a reciprocal translocation are abnormal. The next two most common structural chromosome abnormalities are Robertsonian translocations (0.1% of the general population) and inversions (0.02% of the general population). Other cases of structural chromosome abnormalities are less common, more complex, and supposedly precipitate the chances to have a successful outcome. Due to the scarcity of these cases these structural abnormalities have been poorly studied. For this study we include the chromosomal structural abnormalities classified as insertions and complex chromosome rearrangements (CCRs). Insertions are the relocation of a region of a chromosome to another location of the genome (whether the same chromosome or other chromosome), and CCRs are structural chromosome abnormalities involving three or more chromosomes. This study aims to determine the proportion of unbalanced embryos and reproductive risk to patients carrying insertions or CCR. Materials and methods This study collects data from insertion and CCR cases analyzed by PGD techniques available at the time the case was processed. These techniques are fluorescence in situ hybridization (FISH), array comparative genome hybridization (aCGH), and next generation sequencing (NGS). CCR cases were classified further depending of the type of abnormalities of which the CCR is compounded (Table 1).Table 1: Types of abnormalities for this studyStructural abnormalityAcronymNumber of patientsNumber of cyclesInsertionINS812Reciprocal translocation and deletionREC + DEL11Reciprocal translocation and insertionREC + INS14Reciprocal translocation and inversionREC + INV57Reciprocal translocation and Robertsonian translocationREC + ROB38Male carrier reciprocal translocation and Female carrier of reciprocal translocationREC XX + REC XY23Two reciprocal translocation in one carrierRECx237Robertsonian translocation and inversionROB + INV11Three way translocationTWT815Total3258 32 patients were included in this studies, from which 58 cycles were performed, and 517 embryos were analyzed Results The overall results are summarized in table 2. ConclusionsTable 2a: Number of embryos and type of embryosN of embsN/BUNBABNNRINS681532192REC + DEL60312REC + INS6836005REC + INV96206736REC + ROB10459900REC XX + REC XY1641020RECx23412265ROB + INV85120TWT117158967Total517683833927