Chromosome Abnormality and Female Age 染色体异常和年龄之间的关系

分类:医学文献 38 0

The most relevant and recent evidences suggest that failed implantation due to embryo aneuploidy rather than failed conception is the primary cause of low human fertility. Some of the earlier studies underestimate chromosome abnormalities in spontaneous miscarriage because conventional karyotyping requires tissue culture, which is prone to maternal contamination.


The most significant variable related to the production of aneuploid embryos is the age of the female partner. It is well known that the female age is associated with an increase in aneuploidy rate, correlated with a reduced implantation and a higher abortion rates. Direct cytogenetic analysis of human oocytes demonstrates that oocyte aneuploidy rates could reach even 50 percent for women over 40 years of age and that almost all chromosomes are involved in meiotic errors albeit with different frequencies. (1-2)


Oocyte derived factors play a critical role in maintaining chromosome stability and euploidy in early-cleavage embryogenesis. An age-related defective cytoplasmic maturation during the antral follicle growth in older women could probably induce an alteration in spindle assembly, chromosome alignment and spindle assembly checkpoint (SAC) in a transcriptionally quiescence state of embryonic genome and in the absence of strong cell cycle control mechanisms. Since standard FISH probes combination can detect 72-83 percent of the chromosomally abnormal fetuses routinely detected by karyotyping in women of advanced maternal age it was proposed that PGD-AS should eliminate close to 80 percent of all chromosomally abnormal embryos at risk of causing a miscarriage. These data are supported by oocyte donation programs showing that older women failing to conceive with their own oocytes may conceive by using donor oocytes from younger women. Therefore,advanced-female reproductive age (ARA) (cut off varies between 35 and 40 years of age,depending on the center) was the primary indication proposed for PGD-AS in order to improve IVF outcomes and reduce chromosomal syndromes as an alternative to PND. (3-4)



1. Gutiérrez-Mateo C, Benet J, Wells D, et al. Aneuploidy study ofhuman oocytes first polar body comparative genomic hybrid.ization and metaphase Il fluorescence in situ hybridizationanalysis. Hum Reprod 2004; 19: 2859-68.

2. Fragouli E, Wells D, Thornhill A, Serhal P, Faed MJ, Harper JC,Delhanty ID. Comparative genomic hybridization analysis ofhuman oocytes and polar bodies. Hum Reprod 2006;21:2319-28.

3. Munne S, Alikani M, Tomkin G, et al. Embryo morphology,developmental rates, and maternal age are correlated withchromosome abnormalities. Fertil Steril 1995; 64: 382-91.

4. Zheng P, Dean J. Role of Filia, a maternal effect gene, in main-taining euploidy during cleavage-stage mouse embryogenesis.PNAS 2009; 18: 7473-8.

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