Preimplantation genetic diagnosis of chromosome abnormalities: implications from the outcome for couples with chromosomal rearrangements

Abstract

Biopsy and analysis of two blastomeres, where possible, reduced the risk of misdiagnosis in cases of balanced/aneuploid mosaics. The three live births achieved for the eight couples treated in this series, despite the poor history in almost all cases, is further proof that a policy of biopsying two cells from embryos consisting of six or more cells and a single cell from four- or five-cell embryos is compatible with a positive outcome.

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

“…The median number of eggs collected was 13 (range 4-39) and the median number of embryos biopsied was 6 (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In our study the number of oocytes was not an important predictor for a live-birth pregnancy (OR 1.0, 95% CI 0.92-1.10, P ¼ 0.960).…”

“…5,6 Some approaches allow discrimination between normal and heterozygote chromosome complements, as well as detecting abnormal copy number for the translocation segments. [7][8][9] However, the most commonly used methodology of locus-specific probes applied to interphase nuclei from cleavage stage blastomeres, [10][11][12][13][14][15][16] or cells sampled from the trophectoderm, 17 will not differentiate between normal and heterozygote chromosome complements unless probes are designed to flank closely or span the breakpoints. 18 Guy's and St Thomas' Centre for PGD has undertaken 319 biopsy cycles with genetic testing for 171 couples with reciprocal translocations, which has resulted in the delivery of 85 live-born offspring.…”

Preimplantation genetic diagnosis: present and future

“…Chromosome imbalance due to segregation of translocated chromosomes was detected by both of these schemes. However, the relative simplicity of the "flanking probe" approach, along with the commercial availability of sub-telomeric probes specific for each chromosome arm, has made it the most popular strategy for PGD of reciprocal translocations [23][24][25][26][27][28].…”

“…The generated sticky ends reunite as a ring Isochromosome Loss of one chromosome arm and duplication of the other resulting embryos [22,28,29,33]. Several published reports have identified highly abnormal chromosome complements in 70-100% of embryos generated from some patients with poor reproductive histories attributed to a structural rearrangement (reviewed in [34]).…”

Errors in Chromosome Segregation During Oogenesis and Early Embryogenesis

“…However, from the data gathered on the outcome of this type of specific PGD, it is apparent that the level of abnormality detected far exceeds that expected due to parental meiotic segregation errors alone. Much of the abnormality is chaotic in nature (affecting multiple chromosomes) and clearly post-zygotic in origin ( [46][47][48][49]. The frequency of abnormality in the embryos from these cycles approaches 75%, adding weight to the suggestion that these particular couples are afflicted by two pathologies, the increased risk of parental meiotic segregation errors, compounded by additional factors that result in above normal rates of post-zygotic anomalies.…”