scholarly journals Aneuploidy in human spermatozoa: FISH analysis in men with constitutional chromosomal abnormalities, and in infertile men

Reproduction ◽  
2001 ◽  
pp. 655-666 ◽  
Author(s):  
Q Shi ◽  
RH Martin
Keyword(s):  
Chromosomal Abnormalities ◽  
Sperm Concentration ◽  
Normal Karyotype ◽  
Semen Parameters ◽  
Fish Analysis ◽  
Reciprocal Translocations ◽  
Interchromosomal Effect ◽  
Infertile Men ◽  
Sperm Aneuploidy ◽  
Increased Risk

Reproductive difficulties are associated intimately with cytogenetic abnormalities. This article reviews multicolour fluorescence in situ hybridization studies on spermatozoa from men with constitutional chromosomal abnormalities and the consequences for spermatozoa, and on chromosomal abnormalities in the spermatozoa of infertile men who have normal somatic karyotypes. In 47,XYY men, the frequencies of 24,XY and 24,YY spermatozoa appear to be < or = 1%. Klinefelter (47,XXY) and mosaic Klinefelter patients had sperm aneuploidy frequencies of 2-25% and 1.5-7.0%, respectively. Robertsonian translocation carriers had 3-27% spermatozoa unbalanced for the chromosomes involved in the translocation, with a possible modest interchromosomal effect, but none of the increased frequencies of chromosomal disomy approached 1%. The frequency of chromosomally unbalanced spermatozoa in reciprocal translocations averages 50%, is strongly dependent on the chromosomes involved in the individual translocation, and may be slightly increased as a result of a small interchromosomal effect. Infertile men with a normal karyotype and low sperm concentration or certain types of morphologically abnormal spermatozoa have a significantly increased risk of producing aneuploid spermatozoa, particularly for the sex chromosomes. An increased risk of sperm aneuploidy was not observed in infertile men with poor sperm motility or in those with a normal karyotype and normal semen parameters.

scholarly journals Prevalence of Chromosomal Abnormalities in Infertile Couples in Romania

2015 ◽  
Vol 18 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Dana Mierla ◽  
M. Malageanu ◽  
R. Tulin ◽  
D. Albu
Keyword(s):  
Retrospective Study ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Control Group ◽  
Chromosomal Anomalies ◽  
Exact Test ◽  
Infertile Women ◽  
Infertile Men ◽  
Significant Statistical Association

AbstractThe purpose of this study was to establish a correlation between the presence of chromosomal abnormalities in one of the partners and infertility. This retrospective study was performed at the Department of Reproductive Medicine, Life Memorial Hospital, Bucharest, Romania, between August 2007 to December 2011. Two thousand, one hundred and ninety-five patients with reproductive problems were investigated, and the frequency of chromosomal abnormalities was calculated. The control group consisting of 87 fertile persons who had two or more children, was investigated in this retrospective study. All the patients of this study were investigated by cytogenetic techniques and the results of the two groups were compared by a two-tailed Fisher’s exact test. In this study, 94.99% patients had a normal karyotype and 5.01% had chromosomal abnormalities (numerical and structural chromosomal abnormalities). In the study group, numerical chromosomal abnormalities were detected in 1.14% of infertile men and 0.62% of infertile women, and structural chromosomal abnormalities were detected in 1.38% of infertile men and 1.87% of infertile women, respectively. The correlation between the incidence of chromosomal anomalies in the two sexes in couple with reproductive problems was not statistically significant. Recently, a possible association between infertility and chromosomal abnormalities with a significant statistical association has been reported. Our study shows that there is no association between chromosomal abnormalities and infertility, but this study needs to be confirmed with further investigations and a larger control group to establish the role of chromosomal abnormalities in the etiology of infertility.

scholarly journals Semen quality pattern and age threshold: a retrospective cross-sectional study of 71,623 infertile men in China, between 2011 and 2017

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
W. N. Li ◽  
M. M. Jia ◽  
Y. Q. Peng ◽  
R. Ding ◽  
L. Q. Fan ◽  
...  
Keyword(s):  
Semen Quality ◽  
Sperm Count ◽  
Sperm Concentration ◽  
Cross Sectional Study ◽  
Semen Parameters ◽  
Sectional Study ◽  
Joinpoint Regression ◽  
Cross Sectional ◽  
Progressive Motility ◽  
Infertile Men

Abstract Background The aim of this study was to provide information on the semen quality pattern of infertile men and age thresholds for semen parameters in China. Methods This was a retrospective cross-sectional study investigating 71,623 infertile men from the Reproductive and Genetic Hospital of CITIC Xiangya in Hunan, China, from 2011 to 2017. The Kruskal-Wallis test, Mann-Kendall test, linear regression model and joinpoint regression were used. Results Although erratic changes were observed in the median semen parameters (sperm concentration 40.1–52.1 × 106/ml, total sperm count 117.8–153.1 × 106, sperm progressive motility 33.4–38.1%) during the 7 years of observation, no significant decrease in semen quality was found, and 47.88% of infertile men showed normal semen parameters according to the World Health Organization (WHO) criteria. According to the joinpoint regression analysis, sperm progressive motility appeared to decrease earlier than the sperm concentration and total sperm count (at 28, 58, and 42 years of age, respectively). Conclusions There is no evidence of a deterioration in semen quality among infertile men in Hunan, China. Semen parameters decreased with increasing age, with turning points noted at different ages. Semen parameters are not absolute evidence for the assessment of male fertility potential. Therefore, we believe that, among semen parameters, the sperm concentration is the best predictor of fertility for ART, followed by motility. Decreased sperm motility may affect natural pregnancy, but it is not necessary for successful IVF.

scholarly journals Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center

2020 ◽  
Vol 35 (9) ◽  
pp. 2149-2162
Author(s):  
F Belva ◽  
M Bonduelle ◽  
A Buysse ◽  
A Van den Bogaert ◽  
F Hes ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Maternal Age ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Semen Quality ◽  
Sperm Concentration ◽  
Prenatal Testing ◽  
Semen Parameters ◽  
Chromosomal Anomalies ◽  
Single Center

Abstract STUDY QUESTION Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father’s semen parameters? SUMMARY ANSWER The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers’ sperm parameters. WHAT IS KNOWN ALREADY Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. STUDY DESIGN, SIZE, DURATION We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. MAIN RESULTS AND THE ROLE OF CHANCE An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7–4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3–4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96–1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm. Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6–1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm. The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04–1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration &lt;15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14–3.78), sperm concentration &lt;5 million/ml (AOR 1.9; 95% CI 1.05–3.45) and total sperm count &lt;10 million (AOR 1.97; 95% CI 1.04–3.74). LIMITATIONS, REASONS FOR CAUTION We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing. The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. TRIAL REGISTRATION NUMBER N/A

Chromosomal Abnormalities in MDS Are Linked to Dysregulation of CDC20 and CEP55 Genes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Mayara Magna de Lima Melo ◽  
Daniela de Paula Borges ◽  
Antônio Wesley Araújo Dos Santos ◽  
Gabrielle Melo Cavalcante ◽  
Leticia Rodrigues Sampaio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Mitotic Arrest ◽  
Complex Karyotype ◽  
Increased Risk

Myelodysplastic syndrome (MDS) is a clonal hematopoietic disorder characterized by cytopenias and an increased risk of progression to acute myeloid leukemia (AML). Its pathogenesis is strictly linked to chromosomal instability, which in turn provides a valuable prognostic marker. Malignant cells develop alternative routes to escape mitosis checkpoints, overcoming the mitotic arrest imposed by Spindle Assembly Checkpoint (SAC), a process dependent on CDC20 inactivation. Abnormal levels of CDC20 can inhibit mitotic arrest, promoting premature exit from mitosis. Overexpression of CEP55 also facilitates the mitotic exit, resulting in polyploidy (an event called Mitotic Slippage). Since chromosomal abnormalities are one of the most important prognostic factors for patients with MDS, this study aimed to analyze the possible link between chromosomal abnormalities and CDC20 and CEP55 mRNA expression in MDS. We evaluated the bone marrow cells from 45 patients diagnosed as MDS according to 2016 WHO-classification (1 MDS-SLD, 15 MDS-RS-MLD, 5 MDS-MLD, 1 t-MDS, and 23 MDS-EB) and 5 bone marrow of healthy controls. Conventional Karyotyping was performed by G-banding of 20 metaphases whenever possible. TaqMan expression assays for CDC20 (Hs00426680_mH) and CEP55 (Hs01070181_m1) were performed in duplicate and the expression ratios were calculated using the 2−ΔCq method. Normality was evaluated by Shapiro-Wilk test. Outliers were removed. The Student's t-test or one-way ANOVA with Tukey/Games Howell post-hoc test was used to analyze the influence of relative expression regarding variables. Patients with MDS showed increased expression of CDC20 and CEP55 compared to healthy individuals (p&lt;0.0001 and p&lt;0.0001). Regarding karyotype, there was the overexpression of CDC20 and CEP55 in patients with altered karyotype and aneuploid karyotype when compared to patients with normal karyotype (p &lt;0.0001 and p =0.001; p = 0.013 and p = 0.022, respectively) (Figure 1A-D). CDC20 and CEP55 have fundamental functions in controlling the progression of metaphase to anaphase and both, when upregulated, induce chromosomal instability. Additionally, patients with del(7q) and complex karyotype showed hyperexpression of CEP55 when compared with patients with normal karyotype (p = 0.005 and p = 0.019) (Figure 1E-F), while patients with deletion (5q) had an increased expression of CDC20 when compared with patients with normal karyotype (p &lt;0.0001). Our group previously demonstrate that high CDC20 protein expression is associated with complex karyotype in MDS patients. Thus, we hypothesized that the deregulation of CDC20 and CEP55 expression induces chromosomal changes, each one in its way. Both can cause disturbances in crucial phases of mitosis (anaphase and cytokinesis, respectively). Finally, we detected a strong correlation between CDC20 and CEP55 (r = 0.646; p &lt;0.0001), suggesting both genes may play a synergistic role during chromosomal abnormalities in MDS, creating possible new targets to be evaluated in MDS. Our data suggest CDC20 and CEP55 as possible new therapeutic targets in MDS. There is a need for further studies, validations and urgent in-depth investigations in cell lines/primary samples or murine models. Disclosures No relevant conflicts of interest to declare.

Correlation between Immunoglobulin Gene Rearrangements and Chromosomal Abnormalities in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4771-4771
Author(s):  
Giovanna Piras ◽  
Maria Monne ◽  
Antonella Uras ◽  
Laura Pilo ◽  
Luciana Arca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Fish Analysis ◽  
Immunoglobulin Gene ◽  
Cytogenetic Aberrations ◽  
Oncogenic Pathways ◽  
Clonality Analysis ◽  
Conventional Cytogenetics ◽  
Clonogenic Cell

Abstract Background: Multiple Myeloma (MM) is characterized by frequent and complex genetic abnormalities that contribute to the pathogenesis and its prognostic eterogeneity. There is evidence for two oncogenic pathways in the early development of clonal plasma cell disorder: i) non-hyperdiploid carring translocation of the immunoglobulin heavy-chain locus and various oncogenes ii) hyperdiploid tumors with infrequent IgH translocation. The MM clonogenic cell is positively selected during the development and reaction of the germinal center. The immunoglobulin gene (IG) repertoire in MM follows a pattern similar to that of the normal repertoire. However, available data from analysis of IGH and IGK/L genes according to cytogenetic aberrations are limited. In the present study we investigated the frequency and characteristics of IGK and incomplete DJH as well as complete VDJH rearrangements in parallel with chromosomal abnormalities in a series of untreated MM patients. Materials and Methods. Bone marrow aspirates were collected from 53 MM patients with a mean age of 69.6 (range 48–84) between 2003–2007. The serum monoclonal component was IgG and IgA in the 77% and 22% patients respectively; 1 patient presented with IgD k MM. Cytogenetics and FISH analysis were performed simultaneously in 37 MM. In 18 (50.5%) samples kariotype analysis was successful. Interphase FISH analysis was perfomed using a set of probes specific for RB-1 (13q14), D13S319 (13q14.3), IgH (14q32), and p53 (17p13.1) loci, t(4;14), t(14;16), t(11;14) and a multicolor probe set for detection of aneuploidy (Vysis, Downers Grove, IL, USA). Genomic DNA was isolated for clonality analysis. IGHV-J, IGHD-J, IGKV-J, IGKV-KDE, IGKJ-C-INTRON-KDE rearrangements were amplified by PCR and analyzed following the BIOMED-2 protocol. Results: Conventional cytogenetics allowed to detect 16 patients with a normal kariotype, 1 hyperdiploid kariotype with monosomy 13, 1 hyperdiploid kariotype with 3q21 deletion. FISH panel analysis resulted in 4 patients with hyperdiploid kariotype and 7 with abnormalities for RB-1 and/or D13S319. IGH rearrangements were detected in 3 patients and the t (4;14) was found in 1 case. The p53 deletion, t(11;14) and t(14;16) were not detected. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 90%. We found a high frequency (71.7%) of DJH rearrangements with DH3 segment under represented (4%). The DH7 segment was rearranged in the 15% of MM. Incomplete DJH and complete VDJH rearrangements were present at frequencies of 20% and 29.5%, respectively. IGK locus rearrangements were detected in 38 out of 53 MM and the 60% presented the non-productive IGKV-KDE and IGKJ-C-INTRON-KDE rearrangements. Parallel analysis of clonality pattern and chromosomal abnormalities showed that complete VDJH rearrangements were present in all hyperdiploid MM and in a small proportion (4/16) of the MM with normal karyotype. Conclusions: Our results confirm previous estimations about IgH repertoire usage. Despite the small numbers, our findings indicate that complete Ig rearrangements might be correlated with hyperdiploid MM. Combining cytogenetics and IgH clonality studies might help to identify distinct subgroups of MM and provide a framework for dissection of disease prognosis and clinical management. Research funded by Regione Autonoma Sardegna.

Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and Normal Karyotype

2015 ◽  
Vol 146 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Laetitia Gouas ◽  
Stéphan Kémény ◽  
Anne-Marie Beaufrère ◽  
Eléonore Eymard-Pierre ◽  
Céline Pebrel-Richard ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Diagnostic Yield ◽  
Normal Karyotype ◽  
Nuchal Translucency ◽  
Genetic Syndromes ◽  
Pathogenic Variants ◽  
Genome Wide ◽  
Increased Risk ◽  
Structural Abnormalities ◽  
Increased Nuchal Translucency

Fetuses with increased nuchal translucency thickness (NT) are at increased risk for chromosomal abnormalities. In case of a normal karyotype, a minority of them may present with structural abnormalities or genetic syndromes, which may be related to submicroscopic chromosomal imbalances. The objective of this study was to evaluate whether MLPA screening of 21 syndromic and subtelomeric regions could improve the detection rate of small chromosomal aberrations in fetuses with increased NT and a normal karyotype. A total of 106 prenatal samples from fetuses with NT ≥99th centile and normal R- and G-banding were analyzed by MLPA for subtelomeric imbalances (SALSA P036 and P070) and 21 syndromic regions (SALSA P245). One sample showed a benign CNV (dup(8)pter, FBXO25 gene), and 1 patient was found to have a loss of 18qter and a gain of 5pter as a result of an unbalanced translocation. The incidence of cryptic pathogenic variants was <1% or 2.7% when only fetuses with other ultrasound abnormalities were taken into account. Submicroscopic imbalances in fetuses with increased NT may be individually rare, and genome-wide screening seems more likely to improve the diagnostic yield in these fetuses.

Human sperm aneuploidy: FISH analysis in fertile and infertile men

2011 ◽  
Vol 6 (6) ◽  
pp. 609-627 ◽  
Author(s):  
Laura Gambera ◽  
Giuseppe Morgante ◽  
Francesca Serafini ◽  
Anita Stendardi ◽  
Raoul Orvieto ◽  
...  
Keyword(s):  
Human Sperm ◽  
Fish Analysis ◽  
Infertile Men ◽  
Sperm Aneuploidy

Body mass index and human sperm quality: neither one extreme nor the other

2017 ◽  
Vol 29 (4) ◽  
pp. 731 ◽  
Author(s):  
E. M. Luque ◽  
A. Tissera ◽  
M. P. Gaggino ◽  
R. I. Molina ◽  
A. Mangeaud ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Sperm Quality ◽  
Sperm Count ◽  
Sperm Concentration ◽  
Normal Weight ◽  
Semen Parameters ◽  
Morbidly Obese ◽  
Epididymal Maturation ◽  
Increased Risk

The aim of the present study was to investigate the still contentious association between body mass index (BMI) and seminal quality. To this end, 4860 male patients (aged 18–65 years; non-smokers and non-drinkers), were classified according to BMI as either underweight (UW; BMI <20 kg m–2; n = 45), normal weight (NW; BMI 20–24.9 kg m–2; n = 1330), overweight (OW; BMI 25–29.9 kg m–2; n = 2493), obese (OB; BMI 30–39.9 kg m–2; n = 926) or morbidly obese (MOB; BMI ≥40 kg m–2; n = 57). Conventional semen parameters and seminal concentrations of fructose, citric acid and neutral α-glucosidase (NAG) were evaluated. The four parameters that reflect epididymal maturation were significantly lower in the UW and MOB groups compared with NW, OW and OB groups: sperm concentration, total sperm count (103.3 ± 11.4 and 121.5 ± 20.6 and vs 157.9 ± 3.6, 152.4 ± 2.7 or 142.1 ± 4.3 spermatozoa ejaculate–1 respectively, P < 0.05), motility (41.8 ± 2.5 and 42.6 ± 2.6 vs 47.8 ± 0.5, 48.0 ± 0.4 or 46.3 ± 0.6 % of motile spermatozoa respectively, P < 0.05) and NAG (45.2 ± 6.6 and 60.1 ± 7.9 vs 71.5 ± 1.9, 64.7 ± 1.3 or 63.1 ± 2.1 mU ejaculate-1 respectively, P < 0.05). Moreover, the percentage of morphologically normal spermatozoa was decreased in the MOB group compared with the UW, NW, OW and OB groups (4.8 ± 0.6% vs 6.0 ± 0.8%, 6.9 ± 0.1%, 6.8 ± 0.1 and 6.4 ± 0.2%, respectively; P < 0.05). In addition, men in the MOB group had an increased risk (2.3- to 4.9-fold greater) of suffering oligospermia and teratospermia (P < 0.05). Both morbid obesity and being underweight have a negative effect on sperm quality, particularly epididymal maturation. These results show the importance of an adequate or normal bodyweight as the natural best option for fertility, with both extremes of the BMI scale as negative prognostic factors.

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