Preimplantation Genetic Diagnosis of Chromosomal Rearrangements

Preimplantation genetic diagnosis (PGD) of chromosomal rearrangements is a specialised application of assisted reproduction designed to identify structural chromosome abnormalities in embryos before uterine transfer. Carriers of balanced translocations or inversions face elevated risks of infertility, miscarriage and congenital anomalies owing to the production of unbalanced gametes. PGD combines in vitro fertilisation (IVF) with comprehensive chromosome screening of trophectoderm biopsies, enabling selection of embryos with a normal or balanced karyotype. Advances in high-resolution methods—such as single nucleotide polymorphism arrays, next-generation sequencing and long-read platforms—have improved detection of segmental aneuploidies and precise breakpoint localisation. Clinical practice now integrates haplotype linkage analysis to distinguish between truly normal embryos and those carrying balanced rearrangements. This approach has global significance for reducing pregnancy loss, optimising live birth rates and informing genetic counselling in couples worldwide.

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Preimplantation Genetic Diagnosis of Chromosomal Rearrangements publication trend

The graph below shows the total number of articles in preimplantation genetic diagnosis of chromosomal rearrangements across all publications each year (not limited to Nature Index journals).

Technical terms

Preimplantation Genetic Diagnosis (PGD): Testing of embryos prior to uterine transfer to detect specific genetic abnormalities and guide embryo selection.

Balanced Translocation: Exchange of chromosomal segments between nonhomologous chromosomes without net gain or loss of genetic material, often asymptomatic in carriers.

Robertsonian Translocation: Fusion of two acrocentric chromosomes at the centromere, forming a single chromosome that may lead to unbalanced gametes.

Haplotype: A set of contiguous genetic markers inherited together, used to trace parental origin of chromosomal segments in embryos.

Trophectoderm Biopsy: Removal of a few cells from the outer layer of a blastocyst for genetic analysis, minimising impact on embryonic development.

T2T-CHM13 Reference Genome: A fully assembled human genome sequence that resolves previously intractable repetitive regions, facilitating precise breakpoint mapping.

References

1. Nanopore sequencing with T2T‐CHM13 for accurate detection and preventing the transmission of structural rearrangements in highly repetitive heterochromatin regions in human embryos. Clinical and Translational Medicine (2024).
2. Which factors affect the live birth outcome of the first single euploid frozen-thawed blastocyst transfer in couples with balanced chromosomal translocations?. Frontiers in Endocrinology (2024).
3. Chromosome segregation of human nonhomologous Robertsonian translocations: insights from preimplantation genetic testing. European Journal of Human Genetics (2024).
4. SNP array-based analyses of unbalanced embryos as a reference to distinguish between balanced translocation carrier and normal blastocysts. Journal of Assisted Reproduction and Genetics (2016).
5. Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing. GigaScience (2014).
6. Location of Balanced Chromosome-Translocation Breakpoints by Long-Read Sequencing on the Oxford Nanopore Platform. Frontiers in Genetics (2020).
7. The establishment and application of preimplantation genetic haplotyping in embryo diagnosis for reciprocal and Robertsonian translocation carriers. BMC Medical Genomics (2017).
8. Methods for comprehensive chromosome screening of oocytes and embryos: capabilities, limitations, and evidence of validity. Journal of Assisted Reproduction and Genetics (2012).