How common is germinal mosaicism that leads to premeiotic aneuploidy in the female?

PURPOSE: Molecular cytogenetic analysis has confirmed that a proportion of apparently meiotic aneuploidy may be present in the germ cells prior to the onset of meiosis, but there is no clear perception of its frequency. The aim of this review is to assess the evidence for premeiotic aneuploidy from a variety of sources to arrive at an estimate of its overall contribution to oocyte aneuploidy in humans. METHODS: Relevant scientific literature was covered from 1985 to 2018 by searching PubMed databases with search terms: gonadal/germinal mosaicism, ovarian mosaicism, premeiotic aneuploidy, meiosis and trisomy 21. Additionally, a key reference from 1966 was included. RESULTS: Data from over 9000 cases of Down syndrome showed a bimodal maternal age distribution curve, indicating two overlapping distributions. One of these matched the pattern for the control population, with a peak at about 28 years and included all cases that had occurred independently of maternal age, including those due to germinal mosaicism, about 40% of the cohort. The first cytological proof of germinal mosaicism was obtained by fluorescence in situ hybridisation analysis. Comparative genomic hybridisation analysis of oocyte chromosomes suggests an incidence of up to 15% in premeiotic oocytes. Direct investigation of fetal ovarian cells led to variable results for chromosome 21 mosaicism. CONCLUSIONS: Oocytes with premeiotic errors will significantly contribute to the high level of preimplantation and prenatal death. Data so far available suggests that, depending upon the maternal age, up to 40% of aneuploidy that is present in oocytes at the end of meiosis I may be due to germinal mosaicism.