Microarray analysis reveals abnormal chromosomal complements in over 70% of 14 normally developing human embryos

Mertzanidou, Afroditi; Wilton, Leeanda; Cheng, Jun‐Hu; Spits, Claudia; Vanneste, Evelyne; Moreau, Yves; Vermeesch, Joris Robert; Sermon, Karen

doi:10.1093/humrep/des362

Cited by 179 publications

(121 citation statements)

References 33 publications

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“…Where studied, most pregnancy losses are related to aneuploidy or other severe genetic conditions that are incompatible with extrauterine life (Boue et al 1975a,b;De Braekeleer and Dao 1990). For example, apparently healthy 2-d-old embryos have .70% aneuploidy (Mertzanidou et al 2013) and congenital heart disease is identified in 10% of stillbirths (Hoffman 1995 In 2011, there were 3,952,841 births in the United States Martin et al 2013). Approximately 10% of all newborns born in the United States are admitted to a NICU secondary to either a birth defect, prematurity or a complication of delivery (Schwartz et al 2000;Bettegowda et al 2010).…”

Section: Impact and Incidence Of Monogenic Diseasesmentioning

confidence: 99%

Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Smith

Willig

Kingsmore

2015

Cold Spring Harb Perspect Med

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Section: Impact and Incidence Of Monogenic Diseasesmentioning

confidence: 99%

Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Smith

Willig

Kingsmore

2015

Cold Spring Harb Perspect Med

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“…It has been previously shown that almost 50% of the embryos created by ARTs are mosaic, containing both normal (diploid) and abnormal (non-diploid) cells. [12][13][14][15] With respect to FP results, the contribution of mosaicism to the FP rate (FP ¼ 19.1%) in the overall data, reaches 54%. FP diagnosis is characterized as more benign as it does not lead to the initiation of an affected pregnancy, although it may decrease the number of genetically transferable embryos, hence reducing the probability of achieving a pregnancy.…”

Section: Discussionmentioning

confidence: 91%

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

et al. 2013

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Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P ¼ 0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P ¼ 0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P ¼ 0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.

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“…During the first mitotic divisions in human preimplantation development, improper segregation of chromosomes might occur, causing high rates of aneuploidy and mosaicism [11]. Several studies showed that a majority of preimplantation embryos are diploid-aneuploid mosaic [12][13][14]. Chow et al [14] applied array comparative genomic hybridization to analyze high percentage of blastomeres from good quality day 3 embryos of young patients (with no known indication for PGD).…”

Section: Resultsmentioning

confidence: 99%

“…These embryos showed a high degree of mosaicism and less than 20 % euploidy. It is likely that mosaic embryos with a low number of abnormal blastomeres have self-correction mechanisms that enable normal implantation [13,14]. It has been shown that abnormal cells can be forced away from the embryonic inner cell mass leading to a viable euploid embryo [11].…”

Section: Resultsmentioning

confidence: 99%

Irregular cleavage of early preimplantation human embryos: characteristics of patients and pregnancy outcomes

Almagor

Fieldust

et al. 2015

J Assist Reprod Genet

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Purpose This is a retrospective analysis of the morphokinetics, prevalence, and implantation potential of embryos with irregular first and second cleavages as identified by time-lapse microscopy. Methods The study included 253 women who underwent 387 assisted reproduction treatments with intracytoplasmic sperm injection (ICSI). Each patient was assigned to one of three groups based on embryo cleavage results. In group I, one to two embryos per cycle showed irregular cleavage; group II, at least three embryos with abnormal cleavage; and in group III (the control group), all embryos cleaved normally. The number of embryos that cleaved from 1 to ≥3 cells or from 2 to ≥5 cells for each patient was recorded. Their prevalence and association with women's characteristics and pregnancy outcome were evaluated. Results The prevalence of irregular cleavage was 15.6 % among 1772 ICSI embryos. In 101 cycles, 1-2 embryos per cycle showed irregular cleavage (group I). In 32 cycles, at least 3 embryos showed abnormal cleavage (group II). In 254 cycles, all embryos cleaved normally (group III). The average age of the women in group II was significantly lower in comparison with groups I and III (32.5±4.2 vs. 35.1±4.9 and 35.5±5.1, respectively, p<0.02). In comparison of groups I and II, the odds ratio for ≥3 embryos with irregular cleavage in women younger than 35 was 3.48 (95 % CI, 1.28 to 9.46). Embryos with irregular cleavage were transferred in 16 women. Three live births were achieved following the transfer of single blastocysts derived from embryos with irregular cleavage from two to five cells. Conclusions Early embryos with irregular cleavage are significantly more prevalent in younger women. When these embryos develop to the blastocyst stage, they may have normal implantation potential, leading to the birth of healthy babies.

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Microarray analysis reveals abnormal chromosomal complements in over 70% of 14 normally developing human embryos

Abstract: This research was supported by the Instituut voor de aanmoediging van innovatie door Wetenschap en Technologie in Vlaanderen (IWT-Vlaanderen). A.M. is a PhD student at the IWT-Vlaanderen. C.S. is a postdoctoral fellow at the FWO Vlaanderen. There are no competing interests.

Cited by 179 publications

References 33 publications

Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

Irregular cleavage of early preimplantation human embryos: characteristics of patients and pregnancy outcomes

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