Chromosome mosaicism in cleavage-stage human embryos: evidence of a maternal age effect

Munné, Santiago; Sandalinas, M.; Escudero, T.; Márquez, Carmen; Cohen, Jacques

doi:10.1016/s1472-6483(10)61810-x

Cited by 184 publications

(110 citation statements)

References 43 publications

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“…However, in many of these embryos other cell lines are also present including polyploid, haploid and chaotic types. The available evidence suggests that aneuploid mosaicism detected at the cleavage stage is generated during one of the first three divisions, typically at the first or second division (Delhanty et al, 1997;Munné et al, 2002;Katz-Jaffe et al, 2004). Data from the 5-day-old embryos in the study by Daphnis et al, (2004) suggest that if the aneuploid cells arose during cleavage they are at a selective disadvantage compared with the diploid cells which have outgrown them.…”

Section: The Stage In Embryonic Development When Errors Leading To Anmentioning

confidence: 97%

Mechanisms of aneuploidy induction in human oogenesis and early embryogenesis

Delhanty¹

2005

Cytogenet Genome Res

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The mechanisms of aneuploidy induction in human oogenesis mainly involve nondisjunction arising during the first and second meiotic divisions. Nondisjunction equally affects both whole chromosomes and chromatids, in the latter case it is facilitated by “predivision” or precocious centromere division. Karyotyping and CGH studies show an excess of hypohaploidy, which is confirmed in studies of preimplantation embryos, providing evidence in favour of anaphase lag as a mechanism. Preferential involvement of the smaller autosomes has been clearly shown but the largest chromosomes are also abnormal in many cases. Overall, the rate of chromosomal imbalance in oocytes from women aged between 30 and 35 has been estimated at 11% from recent karyotyping data but accruing CGH results suggest that the true figure should be considerably higher. Clear evidence has been obtained in favour of germinal or gonadal mosaicism as a predisposing factor. Constitutional aneuploidy in embryos is most frequent for chromosomes 22, 16, 21 and 15; least frequently involved are chromosomes 14, X and Y, and 6. However, embryos of women under 37 are far more likely to be affected by mosaic aneuploidy, which is present in over 50% of 3-day-old embryos. There are two main types, diploid/aneuploid and chaotic mosaics. Chaotic mosaics arise independently of maternal age and may be related to centrosome anomalies and hence of male origin. Aneuploid mosaics most commonly arise by chromosome loss, followed by chromosome gain and least frequently by mitotic nondisjunction. All may be related to maternal age as well as to lack of specific gene products in the embryo. Partial aneuploidy as a result of chromosome breakage affects a minimum of 10% of embryos.

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Section: The Stage In Embryonic Development When Errors Leading To Anmentioning

confidence: 97%

Mechanisms of aneuploidy induction in human oogenesis and early embryogenesis

Delhanty¹

2005

Cytogenet Genome Res

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“…It has been found that PGS especially benefits patients of advanced maternal ages, recurrent miscarriage and previous spontaneous miscarriage, as aneuploidy is the main reason for unsuccessful embryo implantation in these populations of patients [5,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Assessment of aneuploidy formation in human blastocysts resulting from donated eggs and the necessity of the embryos for aneuploidy screening

Haddad

Deng

Wang

et al. 2015

J Assist Reprod Genet

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Purpose To examine the prevalence of aneuploidy in human blastocysts resulting from donated eggs and embryo implantation after transfer of normal euploid embryos. Also, to assess the necessity of preimplantation genetic screening (PGS) for embryos produced with donor eggs. Methods Blastocysts from donor-recipient cycles were biopsied for PGS (PGS group) and the samples were analyzed with DNA microarray. Euploid blastocysts were transferred to the recipients, and both clinical pregnancy and embryo implantation were examined and compared with embryos without PGS (control group). Results After PGS, 39.1 % of blastocysts were abnormal, including aneuploidy and euploid with partial chromosome deletion and/or duplication. Transfer of normal euploid blastocysts brought about 72.4 % of clinical pregnancy, 65.5 % of ongoing/delivery and 54.9 % of embryo implantation rates; these rates were slightly higher than those in the control group (66.7, 54.0 and 47.8 %, respectively), but there was no statistical difference between the two groups. By contrast, the miscarriage rate was higher in the control group (19.2 %) than in the PGS group (9.5 %), but no statistical difference was observed. Transfer of two or more embryos did not significantly increase the ongoing/delivery rates in both groups, but significantly increased the twin pregnancy rates (50.0 % in the PGS group and 43.8 % in the control group). Conclusion(s) High proportions of human blastocysts derived from donor eggs are aneuploid. Although pregnancy and embryo implantation rates were increased, and miscarriage rates were reduced by transfer of embryos selected by PGS, the efficiency was not significantly different as compared to the control, suggesting that PGS may be necessary only in some specific situations, such as single embryo transfer.

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“…PGD using polymerase chain reaction (PCR) can test for an increasing number of single gene disorders (Sermon et al, 2004) while PGD using fluorescence in situ hybridization (FISH) is used to determine gender in the case of Xlinked conditions or test for aneuploidy (Griffin et al, 1992;Delhanty et al, 1993). PGD for aneuploidy screening (PGDManuscript received 13 March 2006; accepted in revised form for publication by T. Liehr, 18 April 2006. having an increased number of aneuploid oocytes (Marquez et al, 2000;Munne et al, 2002;Wilton, 2002). PGD-AS represents an early form of prenatal diagnosis allowing identification and preferential transfer of chromosomally normal embryos.…”

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confidence: 99%

A retrospective study of preimplantation embryos diagnosed with monosomy by fluorescence in situ hybridization (FISH)

Cooper

Darilek²,

Wun³

et al. 2006

Cytogenet Genome Res

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This report is a retrospective study of preimplantation embryos diagnosed with monosomy for chromosomes 13, 15, 16, 18, 21, 22, X and Y on day 3 to determine the rate of true positives, false positives and/or mosaicism and to assess if these embryos are suitable for in vitro fertilization (IVF) transfer. In a one year period, 80 patients went through preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). Monosomy was diagnosed in 51 embryos. Fluorescence in situ hybridization (FISH) was then performed on the blastomeres at day 5–7 with commercially available probes using the same probe set that initially identified monosomy for chromosomes 13, 16, 21 and 22 or chromosomes 15, 18, X and Y. Based on FISH analysis, the monosomy diagnosed during routine PGD-AS analysis was confirmed in 17 of the 51 embryos. A euploid result for the specific chromosomes tested was observed in 16 of the 51 embryos while mosaicism was found in the remaining 18 embryos. This results in an estimated false positive rate of 3.8% for a diagnosis of monosomy. Reanalysis of these embryos demonstrates that the majority of monosomy diagnoses represents true monosomy or mosaicism and should be excluded for transfer in IVF. Furthermore, improved understanding from recent emerging data regarding the fate of oocytes in women with advanced maternal age undergoing IVF to the development of early embryos may provide a valuable insight into the mechanism of chromosome mosaicism.

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Chromosome mosaicism in cleavage-stage human embryos: evidence of a maternal age effect

Cited by 184 publications

References 43 publications

Mechanisms of aneuploidy induction in human oogenesis and early embryogenesis

Mechanisms of aneuploidy induction in human oogenesis and early embryogenesis

Assessment of aneuploidy formation in human blastocysts resulting from donated eggs and the necessity of the embryos for aneuploidy screening

A retrospective study of preimplantation embryos diagnosed with monosomy by fluorescence in situ hybridization (FISH)

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