Chromosome analysis in human oocytes unfertilized in vitro: a mathematical model for the estimation of the first meiotic non-disjunction frequency.

The results of cytogenetic analysis of unfertilized human oocytes in an in-vitro fertilization programme are to a large extent influenced by the methodology used. Exact conclusions cannot be drawn due to technical and interpretational errors. A mathematical model was constructed, therefore, to estimate the weight of these errors and to calculate the exact frequency of first meiotic non-disjunction in IVF oocytes. Of 246 prepared oocytes only 105 could be karyotyped exactly. Using the classical method of calculation, an aneuploidy frequency of 39% was obtained. By applying the maximum likelihood method a correlation between the frequency of first meiotic non-disjunction and the interpretational error level was found. Loss of chromosomes by anaphase lagging seemed to be undetectable, but the probability of chromosome loss due to fixation and unhomogeneous spreading was found to be 20%. Accepting an error level of 10-20%, the true non-disjunction frequency expected should range between 20 and 40%. This model yields a standard curve which can offer a basis for comparison of results obtained in different studies.