No abstract

Previous studies assessing the relationship between embryo development, maternal age and chromosome abnormalities were either small or analysed mostly embryos not suitable for replacement. The present study includes >6000 embryos, including many suitable for replacement. Embryos with the best morphology and development were 44% euploid in patients younger than 35, decreasing to 21% in patients 41 and older. The worst morphology group had only 30% normal embryos from patients younger than 35, and 12% in embryos from patients 41 and older. Thus morphological analysis was able to improve the population of normal embryos only from 30 to 44% in the best of cases. Regarding specific abnormalities, 20% of embryos were aneuploid, 32% aneuploid plus other abnormalities, and the rest had post-meiotic abnormalities. Of those, only aneuploidy increased with maternal age. There were no big differences in the frequency of chromosome abnormalities depending on patient indication, within a similar age group. In summary, previous trends detected in suboptimal embryos were also confirmed in the best embryos for replacement. Although dysmorphism and advanced maternal age are both related to chromosome abnormalities, these parameters can yield at most <50% euploid embryos, and other techniques such as preimplantation diagnosis are required to ensure that only euploid embryos are replaced.

This study examines the relationship between common morphological anomalies of cleaving embryos and their ability to form apparently normal blastocysts in vitro. The impact of cleavage rate, fragmentation, and multinucleation on compaction, cavitation, along with inner cell mass and trophectoderm formation has been assessed. The study population consisted of 102 patients who elected or were selected to have a day 5 embryo transfer. Clinical pregnancy and implantation rates were 66.7 and 49% respectively. Slow and fast cleavage had a significant negative association with normal blastocyst formation. Only 13.8% (67/484) of embryos with <7 cells and 27.5% (25/91) of those with >9 cells on day 3 formed blastocysts with apparently normal morphology, compared to 41.9% (252/602) with 7-9 cells on day 3 (P < 0.001). Fragmentation had a negative impact on normal blastocyst formation. Embryos with >15% fragmentation formed normal blastocysts at a significantly lower rate (46/279; 16.5%) than embryos with 0-15% fragmentation (311/935; 33.3%) (P < 0. 001). Furthermore, the pattern of fragmentation was associated with blastocyst formation. Type IV fragmentation led to a significant reduction in blastocyst formation (25/170 or 14.7%), compared to types I, II and III which performed much better (38.6, 32.9 and 32.4% respectively). Only 15.9% (22/138) of embryos with one or more multinucleate cells on day 2 and/or 3 formed normal blastocysts compared with 31.9% (335/1051) (P < 0.001) of those without multinucleation. Collectively, the data suggest that cleavage anomalies, some of which do not preclude development after short-term culture, may reduce the developmental competence of embryos after prolonged culture.

No abstract

The correlation between human zygote morphology and chromosomal anomalies after cleavage has not been well characterised. Commonly observed morphological qualities at the zygote stage have provided little insight into further development, and therefore selection for cryopreservation or transfer appears to be less specific than that at later stages of preimplantation development. The purpose of this work was to evaluate the relationship between aberrant pronuclear morphology and chromosomal anomalies after cleavage. Monospermic zygotes exhibiting two pronuclei where diameters differed by at least 4 μm were found to arrest at a significantly higher rate than zygotes with pronuclear diameters differing by less than 4 µm. In addition, a higher incidence of day 2 multinucleation was observed. Embryos deriving from zygotes with dysmorphic pronuclei that were not replaced or cryopreserved by day 3 of development were separated and fixed for fluorescence in situ hybridisation analysis of chromosomes X, Y, 13, 18 and 21. A significantly higher incidence of mosaicism was found in this group compared with others that had developed from zygotes with normal pronuclear morphology. Although the mechanism leading to this form of divergent pronuclear morphology is unclear, results suggest a correlation with oocyte cyto-plasmic immaturity.