Proportion Of Aneuploidy Research Articles

A Chinese multicenter retrospective study of isolated increased nuchal translucency associated chromosome anomaly and prenatal diagnostic suggestions

Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.

Proportion of aneuploidy does not impact live birth rate or pregnancy loss rate in patients with recurrent pregnancy loss (RPL) undergoing comprehensive chromosome screening

There is limited evidence that aneuploidy disproportionately effects outcomes in patients with RPL as compared to the general infertility population. In an effort to investigate the potential that patients with RPL without balanced translocations have a biologic mechanism related to aneuploidy behind their poor pregnancy outcomes, we sought to evaluate if the proportion of aneuploidy within a cohort of embryos impacts pregnancy outcomes. If an intrinsic biologic deficit exists, we suspect that patients with high aneuploidyrates in the RPL population would be disproportionately helped by CCS.

Repeat ccs cycles will typically result in some euploid blastocysts for transfer in women of advanced maternal age

The aim of this study was to evaluate whether the proportion of aneuploid blastocysts in repeat comprehensive chromosome screening (CCS) cycles is consistent. Retrospective study. Inclusion criteria for this study included patients (n = 67) with normal ovarian reserve and normal responders, who underwent repeat CCS cycles (range 2-4). For all cycles (n = 153), embryos were cultured to the blastocyst stage with a trophectoderm (TE) biopsy performed prior to vitrification. CCS analysis was performed by qPCR technology or SNP microarray (RMA-NJ). Half of the patients (50.7%; n = 34) who underwent repeat CCS cycles had some euploid blastocysts in each cycle (Group A), with no significant differences observed in the proportion of aneuploidy between each CCS cycle. Close to a third of the patients (35.8%; n = 24) experienced an ‘all aneuploid’ blastocyst CCS cycle followed by some euploid blastocysts in a repeat CCS cycle (Group B). Only 13.4% of patients (n = 9) who underwent repeat CCS cycles always produced ‘all aneuploid’ blastocysts (Group C). Not surprisingly a significant difference in the proportion of aneuploid blastocysts per CCS cycle was observed across the groups (A = 49.7%, B = 74%, C = 100%; P<0.01). The mean maternal age was also significantly different, with the oldest patients in Group C (A = 38.4 ± 3.2, B = 40.6 ± 2.6, C = 41.3 ± 4.2 years; P<0.01). In addition, a lower number of blastocysts were available for biopsy in Groups B & C as would be anticipated (A = 4.45 ± 2.5, B = 3.65 ± 3.3, C = 3.33 ± 1.9; ns), even though the number of oocytes retrieved was similar across groups (A = 18.8 ± 8.7, B = 17.4 ± 8.6, C = 18.3 ± 6.1; ns). Only a small percentage of normal responder patients produced ‘all aneuploid’ blastocysts in repeat CCS cycles, and these women were typically in their forties. For patients who produced ‘all aneuploid’ blastocysts in a CCS cycle (Groups B & C) there was a high probability that in a repeat CCS cycle they would produce some euploid blastocysts for transfer.

A genome-wide association scan identifies several maternal susceptbility loci for embryo aneuploidy

OBJECTIVE: To locate genetic variation which may be significantly associated with the proportion of embryo aneuploidy in a cohort of female IVF patients. DESIGN: Prospective observational. Caucasian female IVF patients were genotyped by microarray. Genome-wide association analysis was performed for genotypes against the proportion of aneuploid embryos obtained during a single cycle. MATERIALS AND METHODS: Female Caucasian IVF patients (n1⁄458) were selected for age ( 2, mean1⁄410). The proportion of aneuploid embryos in a single cycle was used as the dependent variable (mean1⁄438.5%). All subjects were genotyped using Affymetrix 250K Nsp arrays. SNPs were filtered using standard QC criteria (HWE p>0.001, MAF>0.03, CR>0.85). Stratification was corrected by principal component analysis. Genomewide regression models of genotypic association were calculated (additive, recessive, and dominant). Resulting regression p-values were adjusted for multiple testing (Bonferroni). RESULTS: After regression analysis and MT correction, 13 SNPs remained significantly associated (p<0.05) with the proportion of aneuploidy in female IVF patient embryos: 5 in additive, 2 in recessive and 6 in dominant models. Of the 13, 2 SNPs (rs1535208, chr20q12, and rs2506350, chr9q31.1) had corrected p<0.01, and nearby genes included some known as important to mitotic function such as topoisomerase 1 (TOP1) and structural maintenance of chromosomes 2 (SMC2). Genes near the other SNPs (<5MB) include SMC5, CENPN, BMI1, POT1, PTTG1, DBF4, and MAP1B, all which may have roles in maintaining chromosomal integrity, sister chromatid separation, and overall mitotic function. CONCLUSION: This is the first study to show a genetic predisposition to the maternal contribution to embryonic aneuploidy. Genes near associated SNPs may add biological context and provide avenues for future study. Ongoing accrual of data will increase power and provide an opportunity to replicate and refine these statistical associations.

The assosiation between preimplantation embryo morphology and the incidence of chromosome aneuploidy

OBJECTIVE: To evaluate the association between preimplantation embryo morphology and proportion of aneuploidy on day 3 and 4 after oocyte retrieval. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Preimplantation genetic screening (PGS) was performed in 64 IVF cycles of 58 patients because of history of repeated pregnancy loss, repeated implantation failure and advanced maternal age. The chromosomes 13, 16, 18, 21, X and Y were assessed in blastomeres biopysed from day 3 embryos by fluorescence in situ hybridization (FISH). A total of 614 embryos were analyzed. The incidence of chromosome aneuploidy was compared depending on the cell number, cellular fragment, and blastomere evenness of embryos. Data were analyzed by chi-square analysis. RESULTS: One hundred seventy-nine embryos (29.2%) were chromosomally normal and the others were aneuploid for one or more chromosomes. The incidence of aneuploidy was lower in normal-cleaving embryos (7- ∼ 9-cell stage) compared to slow-cleaving (≤ 6-cell stage) or fast-cleaving embryos (≥ 10-cell stage) at day 3 after oocytes retrieval. The incidence of aneuploidy was significantly higher (P<0.001) in slow-cleaving embryos (79.2%) than normal-cleaving embryos (62.0%). Aneuploidy of fast-cleaving embryos (78.6%) was higher than normal-cleaving embryos but there was no significant difference. The incidence of aneuploidy was significantly lower in normal-cleaving embryos (compaction ∼ morula stage, 58.9%) compared to arrested embryos (≤6-cell stage, 82.1%) or slow-cleaving embryos (7- ∼ 9-cell stage, 75.6%) at day 4 after oocytes retrieval. Aneuplody of moderately slow-cleaving embryos (10- ∼ 14-cell stage, 64.9%) was higher than normal-cleaving embryos but there was no significant. The incidence of chromosome aneuploidy was significantly increased (P<0.01) in embryos with cellular fragments more than 25% of embryo compared to embryos with cellular fragment less than 25% of embryo. Embryo with uneven blastomeres (73.7%) had a higher proportion of chromosome aneuploidy compared to those with even blastomeres (62.3%; P<0.01). CONCLUSIONS: The proportion of chromosome aneuploidy was significantly higher in slow-cleaving embryos compared to normal-cleaving embryos at day 3 and day4, respectively. The increase of cellular fragment and uneven blastomeres were associated with an increased incidence of chromosome abnormalities.

A prospective correlation of Laurén's histological classification of stomach cancer with clinicopathological findings including DNA flow cytometry.

Between November 1990 and December 1992, 217 patients with stomach cancer were enrolled in a prospective study evaluating the prognostic value of DNA flow cytometry. Laurén's histological type was evaluated in 216 cases, of which 102 (47%) were of the diffuse type, 74 (34%) were of the intestinal type, and 40 (19%) were mixed type tumors. Laurén's histological type showed a significant correlation with age (p = 0.028), sex (p = 0.004), tumor size (p = 0.002), T stage (p = 0.006), overall TNM stage (p = 0.008), histological grade (p < 0.001), and tumor ploidy (p < 0.001). Intestinal type stomach cancer showed a significantly higher proportion of aneuploidy [diffuse vs. intestinal type; 41/102 (40%) vs. 52/74 (70%)]. After a median follow-up of 66.1 months (range, 29.6-78.1), 110 of 216 patients (51%) survived. Patients with intestinal type stomach cancer had a significantly better survival than did those with diffuse type stomach cancer (64% vs. 42% of patients surviving, p = 0.020). Our study suggests that there are biological differences between the two subtypes of Laurén's classification of stomach cancer in addition to the morphological differences. Laurén's classification should remain valid in future studies investigating the pathogenetic and clinical aspects of stomach cancer.

DNA ploidy and proliferative activity in bcl-2 expressed non-small cell lung cancer.

ObjectivesThe expressions of bcl-2 have been reported recently in non-small cell lung carcinoma (NSCLC*). As oncogensis is believed to involve a number of genetic alterations, there can be differences in DNA ploidy or proliferative activity even in bcl-2 positive cases according to the superimposed genetic events.Subjects and MethodsOn the assumption that we might further discern the biologic behavior of bcl-2 positive NSCLC according to the status of DNA ploidy and proliferative activity, we conducted a study for bcl-2 expression with immunohistochemical staining and DNA analysis on 52 surgical specimens of NSCLC.ResultsThe bcl-2 was positive in 52% (27/52) of specimens, According to the status of bcl-2 expression, there were no significant differences in tumor stages, performance status score and survival time. Among bcl-2 positive NSCLC, aneuploidy and high proliferative activity were noted in 40% and 44%, respectively. In cases with squamous cell carcinoma (SQC**), the proportion of aneuploidy was significantly higher in bcl-2 positive group compared to bcl-2 negative group (p<0.01), which could not be explained with the sole effect of bcl-2. In bcl-2 positive NSCLC, there was no significant survival difference by the status of DNA analysis results. With a Coxproportional hazard model, only T stage was an independent prognostic factor.ConclusionIn bcl-2 expressed NSCLC, proliferative activity and DNA ploidy were not homogeneous, suggesting other genetic alterations. This may explain our results which showed no differences in survival according to the status of the bcl-2 expression.

Does in vitro colony formation and chemosensitivity relate to DNA ploidy and S-phase fractions?

In vitro colony formation and chemosensitivity were analyzed in 65 human solid tumors and compared to proliferation parameters simultaneously obtained by DNA flow cytometry of the same tumor specimens. Colony growth in the human tumor colony assay was enhanced in aneuploid tumors (39/65) in comparison to diploid tumors (26/65, P less than 0.05). In addition, there was a relationship between % S-phase and colony growth. The existence of polyploid sublines (23/65) improved in vitro growth even in tumors with a diploid main G0/1-peak or with a low % S-phase. Metastases exhibited a higher proportion of aneuploidy and showed slightly better growth in vitro than primary tumors. Sensitivity testing in 34 of the 65 tumors showed no convincing relation between DNA parameters and the inhibition of colony formation by five standard anticancer agents with different mechanisms of action. This indicates additional factors other than the proliferative activity of the tumor to be responsible for drug sensitivity or resistance.