Since the first report on the study of meiosis in human oocytes [18], numerous publications have described the cytogenetic analysis of inseminated oocytes that failed to fertilize in vitro. Data on 2,434 oocytes, reported by 12 groups, have shown that the incidence of chromosome anomalies ranges from 8 to 54% with an average of 27%. The latter figure can be subdivided as follows: 13% hypo­haploidy, 8% hyperhaploidy, 2% structural abnormalities and 4% diploidy [19]. In another study of 400 oocytes showing no sign of fertilization or cleavage, 124 were unanalyzable and 79 were normal haploid [20]. The re­maining oocytes were abnormal, but no instance of hyper­haploidy was noted. An increase in maternal age resulted in an increased embryonic aneuploidy rate and in an in­creased frequency of spontaneous abortion. Both increases result from non disjunction that gives rise to autosomal trisomy. For all chromosomes except the largest, the non disjunction rate increased with age [21]. On the other hand, monosomy X showed an inverse maternal age effect. The maternal age effect on aneuploidy that holds in spon­taneous abortions and liveborns has also been demon­strated in morphologically and developmentally normal pre implantation embryos [22]. Oocyte meiosis is very sensitive to endogenous or exogenous factors, that could lead to chromosomally abnormal oocytes and thus to ab­normal zygotes [23].

The difference in age-related aneuploidy between oocytes and miscarried embryos might be explained on the basis of pre implantation or early post implantation loss. For chromosomes 13, 18 and 21, aneuploidy in clinically recognized pregnancies increases from 1.3% in the 35-39 age group to 4.3% in the 40-45 age group. However, in cleavage stage embryos, it has been observed by that the aneuploidy rates for chromosomes X, Y, 13, 18 and 21 increased from 5 and 10% in the 20-34 and 35-39 age groups, respectively, to 28% in the 40-45 age group [22]. If only normally developing embryos are considered, the differences are even greater, increasing from 4% in the 20-34 age group to 37.2% in the 40-45 age group.

There seems to be no effect of maternal age on tri­ploidy and tetraploidy, which originate at fertilization and during pre implantation development, respectively. This confirms that maternal age is a factor that only influences meiosis. The cause of non disjunction in oocytes of older women is largely unknown. Although an increase in mater­nal age is accompanied by a reduction in chiasma fre­quency of all chromosomes, the distribution of the meiotic errors is not identical for every chromosome. For example, trisomy 16 always show a maternal meiosis-I (M-I) error. Trisomy 18, on the other hand, results predominantly from meiosis-II (M-II) errors [24].

Premature centromere division at M-I has been sug­gested as an alternative mechanism for trisomy formation [25,26]. Unfertilized oocytes obtained following ovarian stimulation for in vitro fertilization (IVF) were studied during M-II for M-I errors. None of the chromosome com­plements studied had an extra whole chromosome. This finding was not in line with the theory of non disjunction which proposes that both chromosomes of the bivalent fail to disjoin at M-I so that both move to one pole, and result in an additional whole chromosome at M-II metaphase. The only abnormality found in the M-II oocytes was that single chromatids (half chromosomes) replaced whole chromosomes. Analysis of the chromosomally abnormal oocytes revealed a close correlation with results on tri­somies in spontaneous abortions, with respect to chromo­some distribution, frequency, and maternal age, and indi­cated the likelihood of the chromatid abnormalities being the M-I non disjunction products that led to trisomy for­mation after fertilization. In light of the data which show that altered recombination patterns of the affected chro­mosomes are a key feature of most M-I origin trisomies, the oocyte data obtained by Angell [25,26] imply that the vulnerable meiotic configurations arising from altered recombination patterns are processed as functional uni­valents in older women.