Article

Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing.

Reproductive Genetics Institute, 2825 N Halsted St., Chicago, IL 60614, United States.
Reproductive biomedicine online (Impact Factor: 2.68). 01/2011; 22(1):2-8. DOI: 10.1016/j.rbmo.2010.08.014
Source: PubMed

ABSTRACT This study presents the world’s largest series of over 20,000 oocytes tested for aneuploidies, involving chromosomes 13,16, 18, 21 and 22, providing the data on the rates and types of aneuploidies and their origin. Almost every second oocyte (46.8%) is abnormal, with predominance of extra chromatid errors predicting predominance of trisomies (53%) over monosomies (26%) in the resulting embryos (2:1), which is opposite to monosomy predominance observed in embryo testing. Of the detected anomalies in oocytes, 40% are complex, so testing for a few most prevalent chromosome errors may allow detection of the majority of abnormal embryos. Chromosome 21 and 22 errors are more prevalent, while two different patterns of error origin were observed for different chromosomes: chromosome 16 and 22 errors originate predominantly from meiosis II, compared with chromosome 13, 18 and 21 errors originating from meiosis I. This provides the first evidence for the differences in the aneuploid embryo survival depending on the meiotic origin. Considering the problem of mosaicism, which is the major limitation of the cleavage-stage testing, the direct oocyte aneuploidy testing by polar body analysis may be of obvious practical value in improving accuracy and reliability of avoiding aneuploid embryos for transfer.

0 Bookmarks
 · 
66 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian female gametes frequently suffer from numerical chromosomal aberrations, the main cause of miscarriages and severe developmental defects. The underlying mechanisms responsible for the development of aneuploidy in oocytes are still not completely understood and remain a subject of extensive research. From studies focused on prevalence of aneuploidy in mouse oocytes, it has become obvious that reported rates of aneuploidy are strongly dependent on the method used for chromosome counting. In addition, it seems likely that differences between mouse strains could influence the frequency of aneuploidy as well; however, up till now, such a comparison has not been available. Therefore, in our study, we measured the levels of aneuploidy which has resulted from missegregation in meiosis I, in oocytes of three commonly used mouse strains-CD-1, C3H/HeJ, and C57BL/6. Our results revealed that, although the overall chromosomal numerical aberration rates were similar in all three strains, a different number of oocytes in each strain contained prematurely segregated sister chromatids (PSSC). This indicates that a predisposition for this type of chromosome segregation error in oocyte meiosis I is dependent on genetic background.
    Chromosome Research 06/2014; 22(3). · 2.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chromosome aneuploidies commonly arise in embryos produced by assisted reproductive technologies and represent a major cause of implantation failure and miscarriage. Currently, pre-implantation genetic diagnosis (PGD) is performed by array-based methods to identify euploid embryos for transfer to the patient. We speculated that a combination of next generation sequencing technologies and sophisticated bioinformatics would deliver a more comprehensive and accurate methodology to improve the overall efficacy of embryo testing. To meet this challenge, we developed a high-resolution copy number variation (CNV) sequencing pipeline suitable for single cell analysis. In validation studies, we showed that CNV-Seq was highly sensitive and specific for detection of euploidy, aneuploidy and segmental imbalances in 24 WGA samples from PGD embryos that were originally diagnosed by gold standard array CGH. In addition, CNV-Seq was capable of detecting, mapping and accurately quantifying terminal chromosome imbalances down to 1 Mb in size originating from abnormal segregation of translocation chromosomes. These validation studies indicate that CNV-Seq displays the hallmarks of an accurate and reliable embryo test with the potential to further improve the overall efficacy of PGD.
    Biology of Reproduction 06/2014; · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any one single assay to detect the monogenic disorder in question or the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach (‘karyomapping’) was designed to circumvent this problem. In this example, karyomapping was used to confirm an existing PGD case detecting both chromosomal and a monogenic disorder (Smith–Lemli–Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and polar body and cleavage stage biopsy were carried out. Array comparative genomic hybridization and minisequencing were simultaneously used to diagnosis SLO status and chromosome abnormality. This was confirmed, at the same time, by karyomapping. Unlike standard PGD performed alongside it, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD.
    Reproductive biomedicine online 11/2014; · 2.68 Impact Factor