Highly abnormal cleavage divisions in preimplantation embryos from translocation carriers

Abstract

We have developed preimplantation genetic diagnosis (PGD) for carriers of chromosomal abnormalities using fluorescent in situ hybridisation (FISH). Here we present the detailed analysis of 64 biopsied, normally developing embryos obtained from four Robertsonian and three reciprocal translocation carriers in 11 treatment cycles of which four resulted in normal pregnancies (three simplex, one duplex). In order to investigate the degree of mosaicism and segregation mode in the embryos, the primary analysis of the biopsied cells was extended with the analysis of all cells from the non‐transferred embryos. The analysis also included a second hybridisation with two additional probes, not involved in the translocation (chromosomes 1 and 9), in order to investigate the overall degree of mosaicism. Seventeen out of 64 analysed embryos were balanced for the chromosomes involved in the translocation and 14 of these were transferred. Forty‐seven out of 64 embryos (73%) were mosaic regarding the chromosomes involved in the translocation and alternate segregation mode was the most common mode of segregation. Moreover, we have found a higher degree of mosaicism for the chromosomes involved in translocations as compared to control chromosomes. This difference was more pronounced for the embryos from reciprocal translocation carriers. The results, mechanisms, significance and implications of our findings are discussed. Copyright © 2000 John Wiley & Sons, Ltd.

Estimation of chromosomal imbalances in preimplantation embryos from preimplantation genetic diagnosis cycles of reciprocal translocations with or without acrocentric chromosomes

“…However, the frequency of adjacent-2 and 3:1 segregation may be different between genders of carrier (29). It suggested that the frequency of segregation mode may be related to the types of translocation and female age (26)(27)(28). Interchromosomal effect and mosaicism were also reported as one reason for aneuploidy of embryos and poor pregnancy outcome of natural pregnancies in translocation carriers (20,30).…”

“…Previous studies reported that reciprocal translocations produce similar frequencies of alternate products for transferable embryos and vary from 20% to 50% in male and female carriers (26)(27)(28). However, the frequency of adjacent-2 and 3:1 segregation may be different between genders of carrier (29).…”

Interindividual differences and alterations in the topology of chromosomes in human sperm nuclei of fertile donors and carriers of reciprocal translocations

“…PGD has revealed an increased level of aneuploidy of chromosomes (involved or not directly involved in the translocation) in blastomeres derived from a parent with a balanced translocation. Moreover, the degree of chromosome mosaicism (involved or not involved in the translocation) was higher than would be expected from sperm segregation studies (Iwarsson et al 2000, Munne 2005, Pujol et al 2006. The degree of mosaicism within the embryo differed between the chromosomes involved in the translocation and the control group.…”

“…The degree of mosaicism within the embryo differed between the chromosomes involved in the translocation and the control group. It has been suggested that there are unknown factors involved in the abnormal cleavage divisions leading to mosaic/ chaotic embryos that may differ from one carrier to another (Iwarsson et al 2000). We can only speculate that one of these factors may be the disturbed topology of chromosomes within sperm nuclei.…”

Detection of unbalanced chromosome segregations in preimplantation genetic diagnosis of translocations by short comparative genomic hibridization

“…This phenomenon has been named interchromosomal effect (3,4). On this basis, and to detect other possible postzygotic chromosome errors, aneuploidy screening simultaneous to the PGD of translocations has been recommended (5)(6)(7). A comprehensive cytogenetic analysis of not only the chromosomes involved in the rearrangement but also the whole chromosome complement with the use of metaphase short CGH would be very useful (8,9).…”