ABSTRACT
Structural chromosomal rearrangements cause infertility, with balanced translocations and inversions usually resulting in no phenotypic change but a high risk of producing unbalanced gametes and embryos due to abnormal meiotic segregations leading to miscarriage and repeated implantation failures. Preimplantation genetic testing for structural rearrangements (PGT-SR) aims to select normal/balanced embryos, maximizing a couple's chances of having an unaffected pregnancy. Like PGT-A, there are various sampling methods and diagnostic techniques to facilitate PGT-SR, including fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), single-nucleotide polymorphism (SNP)-arrays, karyomapping, and next-generation sequencing (NGS). Trophectoderm biopsy is the most common sampling approach, although non/minimally invasive methods have recently found clinical use. The biggest limiting factor is the availability of normal/balanced embryo(s) for transfer, which is affected by the type of rearrangement, the chromosomes involved, and the sex of the carrier. PGT-SR differs from PGT-A as it aims primarily to eliminate inherited abnormalities in embryos; nevertheless, de novo aneuploidy is also common in embryos obtained from rearrangement carriers. This became more evident through the use of modern PGT-A methods and, at least for some types of rearrangement, an interchromosomal effect has been suggested. Maternal age does not have any impact on segregation patterns per se, but the possibility of reaching an embryo transfer decreases in cases of older women due to higher rates of de novo aneuploidies. Evolution from FISH on cleavage stage biopsies to comprehensive chromosome screening on trophectoderm has yielded better clinical outcomes. Although heterogenous, PGT-SR cases provide an invaluable dataset helping clinicians and genetic counselors to give more realistic information on individual reproductive risks of carrier patients.
