The effect of maternal age on the incidence of chromosomal abnormalities was investigated on a large sample of 3,042 in vitro unfertilized human oocytes II obtained from 792 women aged 19-46 years and participating in an in vitro fertilization program for various indications. The chromosomal analysis combined a gradual fixation of oocytes and an adapted R-banding technique. A total of 1,397 interpretable karyotypes were obtained. Various types of numerical aberration were observed, involving conventional chromosome nondisjunction (3.5%), single-chromatid nondisjunction (5.9%), complex (0.8%) or extreme aneuploidy (0.5%), diploidy (5.4%), and set of single chromatids (3.8%). No significant difference was found in the mean age of women according to the various types of chromosomal abnormalities. A positive relationship was found between maternal age and the global rate of aneuploidy, in agreement with the findings of epidemiological studies. The incidence of both whole-chromosome nondisjunction and precocious chromatid separation were correlated to maternal aging but the most significant correlation was found between maternal aging and singlechromatid nondisjunction. The rate of diploidy was also correlated to a slight extent to maternal aging, whereas no correlation was found between maternal age and the rate of single-chromatid sets. These data reveal that singlechromatid malsegregation is an essential factor in the agedependent occurrence of nondisjunction in human oocytes. Disturbance in sister-chromatid cohesion might be a causal mechanism predisposing to premature chromatid separation and subsequently to nondisjunction in female meiosis.

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Based on the analysis of the most frequent mutations responsible for cystic fibrosis (CF), a higher than expected frequency of CF mutations was recently reported in men with infertility due to reduced sperm quality. To further document whether this condition is associated with severe or mild abnormalities of cystic fibrosis transmembrane conductance regulator (CFTR) functions, we carried out a complete scanning of CFTR sequences using a strategy that detects almost all 850 mutations and 150 polymorphisms reported to date in the CFTR gene. We have investigated a cohort of 56 patients with severe oligoasthenoteratozoospermia (OAT) and 50 controls from southern France for CFTR gene mutations and variations. The frequencies of CF-causing mutations and CFTR variations identified in this OAT sample did not differ significantly from the frequencies found in the normal population. However, we observed a 1.7-fold increase in the proportion of homozygotes for a specific CFTR haplotype (TG11-T7-G1540) in the OAT group (P = 0.025). Our results do not confirm a link between CF mutations and reduced sperm quality. Further studies are needed to substantiate the hypothesis that a combination of variants affecting expression and function of the CFTR protein is associated with male infertility.

During in-vitro fertilization (IVF) procedures, human preimplantation embryos were classified into four grades according to their morphological appearance under light microscopy. The grade IV group included poor quality embryos. In our IVF programme, these embryos were never transferred or frozen, and were thus available for cytogenetic analysis. Cytogenetic analysis was performed on 411 grade IV embryos from 327 couples participating in the IVF programme. A total of 118 embryos were successfully karyotyped using at least one metaphase. Normal diploid chromosomes were found in only 12 embryos, containing a total of 19 metaphases. All others (90%) showed abnormal or aberrant chromosome complements; 48 were aneuploid and six cases of single chromatids were noted; 14 embryos (11.8%) contained haploid complements, while the remaining 44 exhibited mosaics (2n/3n, n/2n, n/3n) or fragmented chromosome sets. Also, several structural aberrations and rearrangements were observed. These results indicate that the large majority of grade IV human embryos are chromosomally abnormal. This confirms the morphological assessment of the poor quality of these embryos and demonstrates the uselessness of both the transfer and the cryopreservation of grade IV embryos.