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Irregular cleavage divisions are expected to produce chromosomally deviant embryos. We investigated whether embryos from irregular cleavages could develop into euploid blastocysts, and, if so, whether any evidence existed of a self-correction mechanism of the embryo. We also investigated the role of different dynamic aspects of morula compaction in this process. A total of 791 embryos from 141 patients undergoing pre-implantation genetic screening were retrospectively analysed using a time-lapse imaging system, and multiple cell divisions were evaluated. A total of 276 embryos developed into blastocysts suitable for biopsy and chromosome screening through array-comparative genomic hybridization. As well as testing trophectoderm biopsy specimens for aneuploidy, excluded cells of 18 blastocysts, which developed from partially compacted morulas, were also analysed. Unique data on the developmental fate of embryos with cleavage abnormalities are presented, and a potential mechanism of ‘aneuploidy rescue’ is postulated through which mosaic embryos may form partially compacted morulas to exclude aneuploid cells. In addition, this process seems to be less efficient in older women. The data obtained also provide further evidence that excluded cells should not be used to infer the cytogenetic status of the embryo. [ABSTRACT FROM AUTHOR]

Objective: The detection in peripheral blood of cell lines at low frequency with mosaicism of gonosomes could expose the affected individual to a high reproductive risk if the gonads are involved in the production of aneuploid cell lines. Therefore, preimplantation genetic diagnosis (PGD) for aneuploidy has been performed in embryos generated by carriers of gonosomal mosaicism with the aim of verifying (i) the percentage of chromosomally abnormal embryos; (ii) the frequency of aneuploidy referred to sex chromosomes; and (iii) the clinical outcome associated with the selection of euploid embryos. Materials/Methods: From September 1996 to December 2001, 35 patients underwent 54 PGD cycles. The indication for PGD was the presence of gonosomal mosaicism in one of the partners. The mean maternal age was 34.6 ± 3.5 years; 26 couples were having their first assisted reproduction attempt. and 17 required intracystoplasmic sperm injection because of severe oligoaesthenoteratozoospermia of the sperm sample: of the remaining 18 patients, eight had experienced repeated abortions. Fluorescence in-situ hybridization (FISH) analysis was performed on a single cell: 54 embryos from nine cycles were analysed for chromosomes XY, 13, 16, 18 and 21, while the remaining 244 embryos from 45 cycles were also screened for chromosomes 15 and 22. Results: A FISH diagnosis was achieved for 295 of the 298 biopsied embryos: 109 were chromosomally normal (37%) and yielded 19 clinical pregnancies in 39 transferred cycles, corresponding to a pregnancy rate of 35% per oocyte retrieval. An average of 2.2 ± 0.8 euploid embryos were replaced, yielding an implantation rate of 33.7%, Sixteen pregnancies have resulted in 23 healthy babies, and three are past the second trimester (conventional prenatal diagnosis gave confirmation of the PGD results). Analysis of the detected chromosomal abnormalities did not show any increase in the incidence of gonosomal aneuploidy: nevertheless, 41% of total abnormalities were represented by monosomy and trisomy. Conclusions: Carriers of gonosomal mosaicism generate a relevant proportion of chromosomally abnormal embryos that is in the same range as patients with advanced maternal age as an indication for PGD. No increase was observed in the proportion of X- and Y-related aneuploidy, which could suggest a predisposition in these patients to generate aneuploid cell lines in which compatibility with a normal pregnancy is mainly related to mosaicism of sex chromosomes. Consequently, as suggested by genetic counselling, these patients are probably exposed to an increased risk of spontaneous abortion and trisomic pregnancies. In view of these considerations. PGD could be considered as an option in the general framework of prevention in reproductive medicine. [ABSTRACT FROM AUTHOR]