Chromosome analysis of preovulatory human oocytes and oocytes failing to cleave following insemination in vitro.

Abstract

These investigations were carried out within a clinical in vitro fertilization and egg replacement program. A gradual fixation method for chromosome preparations of animal oocytes, when modified and applied to human oocytes, gave numerical analyzability in about 80%. Of preovulatory oocytes recovered in stimulated cycles, 53% of oocytes with numbers of chromosomes in the haploid range had an apparently normal set of 23 chromosomes. Oocytes with a very low number of chromosomes or in first meiosis were also found. In a separate investigation the chromosome constitution of oocytes not showing clinical signs of fertilization 48 hours after insemination in vitro was also studied. Of the oocytes with numbers of chromosomes in the haploid range, 50% had a normal 23,X karyotype. A different distribution of abnormal chromosome preparations was found, compared with the preovulatory oocytes. Twelve oocytes (16%) carrying between 10 and 18 chromosomes were found among the inseminated oocytes, but none in the other study. Moreover, 15 preparations displayed no chromosomes in the inseminated oocytes, whereas in the uninseminated group, none lacked chromosomes completely. These results may indicate how unfertilized human oocytes in vitro undergo chromosome loss and degeneration and could represent different stages of degeneration. Among both preovulatory and unfertilized oocytes the distribution between hyper- and hypohaploid oocytes was of particular interest in that hypohaploid chromosome complements were in excess. This finding supports the hypothesis that aberration in the number of chromosomes in an oocyte is caused not only by nondisjunction but also by anaphase lag, since nondisjunction alone would result in a 1: 1 ratio between hyper- and hypohaploid complements. In conclusion, human oocytes recovered for in vitro fertilization seem to have an incidence of numerical chromosome abnormalities in the region of 40-50%. This is close to the figures estimated on the basis of observations made in spontaneous abortions and could be a major explanation for the low developmental potential of human cleavage stage ova.