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: 3.02). 01/2011; 22(1):2-8. DOI: 10.1016/j.rbmo.2010.08.014
Source: PubMed


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.

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    • "Thus, in human IVF clinics, a significant higher pregnancy rate from single embryo transfer is obtained if embryos are screened for euploidy compared with embryos assessed only by morphology (Yang et al. 2012). In particular, aneuploidy is commonly seen in oocytes from women of advanced reproductive age, suggesting it is a major cause of declining fertility with maternal aging (Savva et al. 2010; Kuliev et al. 2011; Jones and Lane 2013). A similar age-associated increased aneuploidy rate is observed in mice (Merriman et al. 2012). "
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    ABSTRACT: Oocyte quality is a critical factor limiting the efficiency of assisted reproductive technologies (ART) and pregnancy success in farm animals and humans. ART success is diminished with increased maternal age, suggesting a close link between poor oocyte quality and ovarian aging. However, the regulation of oocyte quality remains poorly understood. Oocyte quality is functionally linked to ART success because the maternal-to-embryonic transition (MET) is dependent on stored maternal factors, which are accumulated in oocytes during oocyte development and growth. The MET consists of critical developmental processes, including maternal RNA depletion and embryonic genome activation. In recent years, key maternal proteins encoded by maternal-effect genes have been determined, primarily using genetically modified mouse models. These proteins are implicated in various aspects of early embryonic development, including maternal mRNA degradation, epigenetic reprogramming, signal transduction, protein translation and initiation of embryonic genome activation. Species differences exist in the number of cell divisions encompassing the MET and maternal-effect genes controlling this developmental window. Perturbations of maternal control, some of which are associated with ovarian aging, result in decreased oocyte quality.
    Reproduction Fertility and Development 02/2015; 27(6). DOI:10.1071/RD14441 · 2.40 Impact Factor
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    • "Our observations are consistent with human studies that have shown a prevalence of pre-division in eggs from older women (Angell, 1997; Kuliev et al., 2011), but suggest that they result from errors that manifest themselves in MII, despite having origins in MI. This conclusion agrees with recent work on human oocytes, which has extensively screened both polar bodies and suggested that a large component of the maternal age effect is due to segregation errors arising in MII (Fragouli et al., 2011). "
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    ABSTRACT: As women get older their oocytes become susceptible to chromosome mis-segregation. This generates aneuploid embryos, leading to increased infertility and birth defects. Here we examined the provenance of aneuploidy by tracking chromosomes and their kinetochores in oocytes from young and aged mice. Changes consistent with chromosome cohesion deterioration were found with age, including increased interkinetochore distance and loss of the centromeric protector of cohesion SGO2 in metaphase II arrested (metII) eggs, as well as a rise in the number of weakly attached bivalents in meiosis I (MI) and lagging chromosomes at anaphase I. However, there were no MI errors in congression or biorientation. Instead, premature separation of dyads in meiosis II was the major segregation defect in aged eggs and these were associated with very low levels of SGO2. These data show that although considerable cohesion loss occurs during MI, its consequences are observed during meiosis II, when centromeric cohesion is needed to maintain dyad integrity.
    Development 01/2014; 141(1):199-208. DOI:10.1242/dev.100206 · 6.46 Impact Factor
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    • " detected in polar bodies using fluorescence in - situ hybridization for chromosomes 13 , 16 , 18 , 21 and 22 . Despite assessing only five chromosomes , almost every second oocyte ( 46 . 8% ) was abnormal : most errors involved chromatid loss , predicting predominance of trisomies ( 53% ) over monosomies ( 26% ) in the resulting embryos ( 2 : 1 ; Kuliev et al . , 2011 ) . Of the detected anomalies in oocytes , 40% were complex ."
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    ABSTRACT: The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children. Assisted reproduction treatment is a general term used to describe methods of achieving pregnancy by artificial means and includes IVF and sperm implantation. The effect of assisted reproduction treatment on the health of children born using these artificial methods is not fully understood. In April 2011, fertility research experts met to give presentations based on research in this area and to look carefully at the evidence for the effects of assisted reproduction treatment on children’s health. The purpose of this review was to reach an agreement on whether there are differences in the health of assisted-conception children with naturally conceived children. The researchers discovered no increased risk in birth defects in assisted-conception children compared with naturally conceived children. They found that IVF-conceived children have lower birth weights and higher fat under the skin, higher blood pressure and higher fasting glucose concentrations than naturally conceived children; however, growth, development and cognitive function are similar between groups. A very low risk of disorders of genetic control was observed in assisted-conception children. Overall, there did not appear to be a direct link between assisted reproduction treatment and children’s health. The researchers concluded that the cause of some differences in the health of children conceived using assisted reproduction treatment may be due to the age of the woman receiving treatment. Large-scale, research studies are needed to study the long-term health of children conceived using assisted reproduction treatment.
    Reproductive biomedicine online 01/2013; 28(2). DOI:10.1016/j.rbmo.2013.10.013 · 3.02 Impact Factor
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