Incidence Of Chromosomal Aberrations Research Articles

Detection of chromosome aberrations in 17 054 individuals with fertility problems and their subsequent assisted reproductive technology treatments in Central China.

How do the types and frequency of chromosome aberrations in couples in central China affect fertility and ART treatment? Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility, and couples affected by reciprocal translocations had a lower pregnancy rate compared with other chromosome aberrations. Karyotyping is crucial for patients affected by infertility as chromosome aberrations play an important role in the etiology of male infertility. However, the influence of chromosome aberrations and polymorphisms on sperm motility and morphology remains controversial. Data on ART treatment outcomes in infertile couples affected by chromosome aberrations are insufficient. We conducted a retrospective study involving 17 054 patients affected by infertility who underwent karyotyping in our center between January 2020 and May 2022. Karyotyping was performed on 17 054 patients with reproductive failure. All patients were from the central regions of China. The following data were collected from a medical records system using patient identification numbers: couples' ages, history of pregnancy and childbirth, type of infertility, years of infertility, cause of infertility, chromosome karyotypes, semen analysis results, assisted reproductive techniques performed, and treatment outcomes of ART. The incidence of chromosome aberrations was 2.04%; 2.49% in men and 1.57% in women. By analyzing the relationships between chromosome aberrations/polymorphisms and abnormal semen parameters, we found that there were significantly higher rates of asthenozoospermia, oligospermia, and teratozoospermia among men with Robertsonian translocations and sex chromosomal structural aberrations compared with those with normal karyotypes. Higher rates of asthenozoospermia and teratozoospermia were also observed among men with autosomal reciprocal translocations. The incidence of chromosome aberrations in azoospermic men (13.75%), and in men with cryptozoospermia or severe oligospermia (6.97%) was significantly higher than that in men with mild oligospermia or normospermia (0.88-2.12%). In addition, we found that the progressive movement of sperm is impaired in men with Chromosome 21 polymorphisms compared with men with normal karyotypes (39.46% ± 20.51% vs 48.61% ± 18.76%, P = 0.026). The percentage of morphologically normal forms was lower in the chromosomal polymorphism group than in the normal karyotype group (5.01% ± 2.41% vs 5.59% ± 2.14%, P = 0.001), especially in men with polymorphisms on Chromosome 9 (enlarged Chromosome 9 heterochromatin [9qh+]: 4.48% ± 2.22% vs 5.59% ± 2.14%, P = 0.006; pericentric inversion of Chromosome 9 [inv(9)]: 5.09% ± 3.11% vs 5.59% ± 2.14%, P = 0.008). ART treatment was successful in 36.00% of couples affected by chromosome aberrations. However, couples affected by reciprocal translocations achieved a lower pregnancy rate (24.07%), which may be due to the lower euploidy rates (27.31%) when compared with that in other chromosome aberrations. First, although the initial cohort was large, chromosome aberrations were identified in a small number of patients. Second, the observational nature of the study design is limiting. Third, the couples affected by infertility in this study were all outpatients that did not undergo identical comprehensive examinations except for karyotyping, leading to the incomplete collection of medical records. Also, the population included in this study mainly focused on couples affected by infertility, which may not be included in the European Association of Urology (EAU) recommendation on male infertility. Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility. Constitutional chromosome analysis is recommended for men affected by infertility and severe oligospermia or azoospermia to facilitate early and appropriate guidance for the most suitable treatment. Carriers of chromosome aberrations can achieve acceptable pregnancy outcomes through IVF. However, couples affected by reciprocal translocations have lower pregnancy rates, and more treatment cycles are needed before a successful pregnancy. A possible explanation may be the fewer euploid embryos obtained. This work was supported by Grant 2021YFC2700603 from the National Key Research & Development Program of China. The authors declare no conflicts of interest. N/A.

Pregnancy outcomes and genetic analysis for fetal ventriculomegaly.

Introduction: Fetal ventriculomegaly (VM) is associated with neurodevelopmental disorders, partly caused by genetic factor. Methods: To systematically investigate the genetic etiology of fetal VM and related pregnancy outcomes in different subgroups: IVM (isolated VM) and NIVM (non-isolated VM); unilateral and bilateral VM; mild, moderate, and severe VM, a retrospective study including 131 fetuses with VM was carried out from April 2017 to August 2022. Results: 82 cases underwent amniocentesis or cordocentesis, of whom 8 cases (9.8%) were found chromosomal abnormalities by karyotyping. Meanwhile, additional 8 cases (15.7%) with copy number variations (CNVs) were detected by copy number variation sequencing (CNV-seq). The detection rate (DR) of chromosomal abnormalities was higher in NIVM, bilateral VM and severe VM groups. And CNVs frequently occurred in NIVM, bilateral VM and moderate VM groups. In the NIVM group, the incidence of chromosomal aberrations and CNVs in multiple system anomalies (19.0%, 35.7%) was higher than that in single system anomalies (10.0%, 21.1%). After dynamic ultrasound follow-up, 124 cases were available in our cohort. 12 cases were further found other structural abnormalities, and lateral ventricular width was found increased in 8 cases and decreased in 15 cases. Meanwhile, 82 cases underwent fetal brain MRI, 10 cases of brain lesions and 11 cases of progression were additionally identified. With the involvement of a multidisciplinary team, 45 cases opted for termination of pregnancy (TOP) and 79 cases were delivered with live births. One infant death and one with developmental retardation were finally found during postnatal follow-ups. Discussion: CNV-seq combined with karyotyping could effectively improve the diagnostic rate in fetuses with VM. Meanwhile, dynamic ultrasound screening and multidisciplinary evaluation are also essential for assessing the possible outcomes of fetuses with VM.

Gender pecularity of the material of reproductive losses

Aim. The prognosis of the reproductive function of women with pregnancy loss is complex and partly based on the results of karyotyping of material of reproductive loss. According to the literature, during conception are formed the same number of male and female fetuses, but more boys are born. The purpose of this study was to evaluate the gender ratio and incidence of chromosomal anomalies in the products of conception (POC). Methods. Banding cytogenetic and interphase mFISH with the centromeric probe panel for chromosomes 13, 14, 15, 16, 17, 18, 21, 22, X and Y were used. Results. Were examined 497 cases of material POC. Among all samples, female karyotype was established in 273 cases (54.9 %), and male karyotype in 224 cases (45.1 %). Gender ratio of female to male in the POC, regardless of presence or absence of chromosomal anomalies, is 1.22:1. Conclusions. Depending on presence or absence of chromosomal anomalies in POC, the gender ratio differs: with a normal karyotype, female-to-male ratio is 1.09:1, and with an abnormal karyotype, it is 1.6:1, respectively

Chromosomal aberrations in the peripheral blood lymphocytes of Dental Radiographers who exposed to diagnostic X-ray in Erbil city / Iraqi Kurdistan region

Radiographic examination is one of the principal diagnostic methods used in all fields of medical and dental services. The incidence of chromosomal aberrations was evaluated in the peripheral blood lymphocytes of 50 individuals who worked in different dental colleges and clinics in Erbil City. This research was donning between March to September 2016. Blood samples were collected also from 20 individuals as control group, that were not exposed to any diagnostic radiations. An attempt was done to find the relationship between the frequency of chromosomal aberrations and smoking habit. The radiographers showed a significant increase of chromosomal aberrations as compared to control group at both probability level (P< 0.01, P< 0.05), but significant decreases in mitotic index were shown. The highest value of chromosomal aberrations was chromatid gap and lowest value of mitotic index were found both observed in dental radiographers who were smoker with duration of exposure for more than 10 yrs.

Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study and meta-analysis.

To evaluate the postnatal outcome of children with a prenatal diagnosis of apparently isolated agenesis of the septum pellucidum (ASP). A retrospective cohort study of cases of prenatally diagnosed ASP followed in two tertiary centers and a meta-analysis combining data from the cohort study with data from published studies identified in a systematic review were carried out. Only cases with apparently isolated ASP on antenatal ultrasound and/or magnetic resonance imaging and with available postnatal follow-up data were considered eligible for inclusion. The following outcomes were analyzed: incidence of chromosomal anomalies, agreement between antenatal and postnatal findings, overall incidence of septo-optic dysplasia (SOD) and incidence of major neurological disability (motor, language, coordination or behavioral disorder or epilepsy) in non-SOD children. The incidence of SOD in infants with apparently normal optic pathways on antenatal imaging was also evaluated. Fifteen cases of isolated ASP, with median postnatal follow-up of 36 months (range, 12-60 months), were selected from the two centers. Six previously published studies met the inclusion criteria for the systematic review and a total of 78 cases were eligible for the analysis, including the 15 cases from our series. Genetic tests were carried out antenatally in 30 fetuses, of which two had an abnormal result (pooled proportion, 9.0% (95% CI, 1.8-20.7%); I2 = 0%). Additional or discordant imaging findings were noted postnatally in 9/70 (pooled proportion, 13.7% (95% CI, 3.5-29.0%); I2 = 63.9%) cases. Of all 78 neonates with available follow-up, SOD was diagnosed postnatally in 14 (pooled proportion, 19.4% (95% CI, 8.6-33.2%); I2 = 51.2%). In 60 cases, the optic pathways were considered to be normal on antenatal imaging, and six of these (pooled proportion, 9.1% (95% CI, 1.1-24.0%); I2 = 62.0%) were diagnosed postnatally with SOD. Of the 46 infants with available neurological follow-up who were not affected by SOD, a major neurological disability was diagnosed in three (pooled proportion, 6.5% (95% CI, 0.5-18.6%); I2 = 40.1%). In the vast majority of cases with a prenatal diagnosis of apparently isolated ASP, the prognosis is favorable. However, an additional anomaly is detected after birth in about 14% of cases and has a negative impact on clinical outcome. Detailed antenatal assessment of the brain and optic pathways is strongly recommended in order to identify the presence of associated anomalies. Antenatal visualization of apparently normal optic pathways does not rule out SOD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of Single Umbilical Artery (Isolated and non-isolated) and Its Correlation with Birth Defects and Premature Death

Background: The single umbilical artery (SUA) is linked to congenital abnormalities in almost every organ system, however published findings have been inconsistent. Although It has been proposed that inherited and long-term environmental factors do play a role, there is a need for further investigations on the same. The goal is to look into the possibility of a link between a single umbilical artery (SUA) in the incidence of chromosomal anomalies in the second trimester of pregnancy and their collective occurrence.
 Methods: The exclusion of any one of the two umbilical artery and a present umbilical vein was considered as a single umbilical artery for the purpose of this research. A single umbilical artery was established by gross or histologic investigation of the placenta, neonatal evaluation, or autopsy. As a direct consequence, a newborn who did not have a single umbilical artery documented in these records was presumed to have an umbilical cord consisting of three vessels.
 Results: SUA was identified in 0.46 percent of our population (4241/918 933). SUA risk factors included pregestational diabetes in the mother, consistently high blood pressure, prior Cesarean delivery. Some other factors include smoking, epilepsy, and conception via assisted reproductive technology. SUA was associated with gastrointestinal atresia or stenosis in the neonate, esophageal and anorectal atresia or stenosis followed renal agenesis. SUA was linked to an elevated risk of congenital cardiac abnormalities by up to 7–8 times. There was a link between microcephaly, congenital hydrocephalus. There was a link established between other congenital brain and spinal cord anomalies as well. SUA displayed a lesser relationship with hernia associated with the diaphragm, limb reduction defect. It also showed a smaller relation to cleft lip or cleft palate. The risks of trisomy 13 and 21 were both increased, while the risk of trisomy 18 was maximum. Fetuses diagnosed with SUA, whether or not accompanied with a deformity, had two times the higher potential possibility of SUA in a future pregnancy.
 Conclusion: Single Umbilical Artery is closely linked to gastrointestinal atresia or stenosis, implying the same developmental processes. The higher likelihood of reappearance of Single Umbilical Artery implies that inheritable and/or long-term environmental variables play a role. SUA was shown to have high correlations with trisomies 13 and 18.

Safety assessment of β-fructofuranosidase from Aspergillus brunneoviolaceus

β-Fructofuranosidase (β-D-fructofuranoside fructohydrolase; EC 3.2.1.26) is used in the production of fructo-oligosaccharides that are commonly used by the food industry as prebiotics for their purported health benefits. The β-fructofuranosidase discussed herein is obtained from a novel source organism that is a non-genetically modified strain of Aspergillus brunneoviolaceus, which phylogenetically belongs to the Aspergillus section Nigri. The safety of β-fructofuranosidase was evaluated in a series of toxicology studies as prescribed by Tier 1 toxicity testing by the European Food Safety Authority, including an evaluation of the mutagenicity and genotoxicity potential using the in vitro bacterial reverse mutation and mammalian chromosomal aberration assays, as well as systemic toxicity in a 90-day oral subchronic toxicity study in Sprague-Dawley rats. β-Fructofuranosidase was demonstrated to lack mutagenic or genotoxic potential based on the results of the in vitro assays due to absence of increased revertant colonies in the bacterial reverse mutation test and incidence of chromosome aberrations in the chromosomal aberration assay. Administration of β-fructofuranosidase by gavage at doses up to 1200 mg total organic solids (TOS)/kg body weight/day for 90 days did not elicit any systemic toxic effects in rats based on a lack of adverse effect in any study parameter, and therefore the no-observed-adverse-effect level of β-fructofuranosidase was concluded to be 1200 mg TOS/kg body weight/day, the highest dose tested. The results of the toxicology studies on β-fructofuranosidase from A. brunneoviolaceus demonstrate this species to be a safe and suitable source of enzymes for use by the food industry.

Associated Chromosomal Abnormalities in Fetuses Diagnosed Prenatally with Right Aortic Arch.

Right aortic arch (RAA) is an abnormal embryologic development of the aorta characterized by its descendance on the right side of the trachea. This anomaly is accompanied often by other intracardiac and extracardiac anomalies and it is also known for potential association with genetic aberrations, most common being 22q11.2 deletion. The aim of the study was to evaluate the incidence of chromosomal anomalies and in particular 22q11.2 deletion in RAA. Moreover, we assessed the prognosis of fetuses with isolated RAA. Our second objective was to evaluate the prevalence of hypoplastic or absent thymus in RAA fetuses diagnosed with 22q11.2 deletion. We conducted a retrospective study of all fetuses with RAA over a period of 10 years diagnosed prenatally in a tertiary referral center in Romania. A detailed ultrasound was obtained in each case. We extracted the cases that were investigated genetically and selected the cases positive for 22q11.2 deletion. These fetuses were followed up until pregnancy termination or birth to confirm the ultrasound findings. Deletion 22q11.2 was present in 23.52% (4/17) cases. The incidence was particularly high when the fetuses presented a small thymus. In conclusion, we believe that all cases of RAA, including when isolated, should be referred for genetic testing and especially 22q11.2 deletion exclusion. Also, we suggest considering hypoplastic thymus to be a soft marker for this deletion.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in foetuses with ventriculomegaly

Ventriculomegaly is considered to be linked to abnormal neurodevelopment outcome. The aim of this retrospective study was to investigate the current applications of chromosomal microarray analysis (CMA) in foetuses with ventriculomegaly. A total of 548 foetuses with ventriculomegaly detected by prenatal ultrasound underwent single nucleotide polymorphism (SNP) array testing and were subjected to long-term follow-up. The overall prevalence of chromosomal aberrations was 7.30% (40/548), including 4.20% (23/548) with pathogenic/likely pathogenic copy number variants. The incidence of chromosomal aberrations was significantly higher in foetuses with bilateral ventriculomegaly than in those with unilateral ventriculomegaly (10.56% vs. 5.71%, P = 0.040), in foetuses with non-isolated ventriculomegaly than in those with isolated ventriculomegaly (12.99% vs. 2.38%, P < 0.0001), and in foetuses with severe ventriculomegaly than in those with mild-to-moderate ventriculomegaly (23.08% vs. 6.51%, P = 0.005). The outcome in foetuses with mild ventriculomegaly was significantly better than in those with moderate ventriculomegaly (95.60% vs. 84.00%, P = 0.003). Thus, CMA should be regarded as the first-tier test for prenatal diagnosis of foetal ventriculomegaly, especially in foetuses with bilateral or non-isolated ventriculomegaly. The outcome of foetuses with mild ventriculomegaly is favourable; however, there is an increased risk of neurodevelopmental disabilities in foetuses with moderate ventriculomegaly.

A critical review and meta-analysis of epidemiology studies of occupationally exposed styrene workers evaluated for chromosomal aberration incidence

Chromosome aberrations in the peripheral blood lymphocytes of styrene exposed workers have been suggested as a potential early marker for cancer risk. We performed a critical review and abstracted data from all studies using current chromosome aberration scoring criteria and providing at least a mean and standard deviation or standard error for the exposed and comparison groups. Using these data, we conducted a meta-analysis of occupational styrene exposed workers and incidence of chromosome aberrations. Our meta-analysis used the standardized mean difference as the summary statistic since all studies assess the same outcome but use different comparison populations. The primary meta-analysis of the 20 comparisons of 505 styrene exposed workers to 532 comparison workers found a meta-mean difference of 0.361 (95 % CI −0.084 to 0.807, random effects model), but there was substantial lack of consistency across studies (I2 of 90.11, p-value <0.001, fixed effect model). Studies with higher styrene exposures had lower mean standard differences compared to studies with lower styrene exposures. While studies of styrene workers overall had a slight increase in chromosomal aberrations relative to comparison groups, the lack of consistency across studies and the absence of an exposure response and other limitations of the reviewed studies including inadequate exposure assessment, small numbers of participants per study, and poorly matched exposed and comparison workers, we find insufficient evidence to support a conclusion that styrene exposure increases chromosome aberration frequencies in styrene workers.

Perinatal outcome of fetuses with echogenic intracardiac focus

Objective: Echogenic intracardiacs focus (EIF), a microcalcification of the papillary muscles in either or both ventricles of the fetal heart, is one of the more common ultrasonographic soft markers of trisomy 21. This study aimed to determine the relationship of EIF with trisomies in the presence of various ultrasonographic findings. Materials and Methods: A retrospective study of second-trimester obstetric sonograms (18-24 weeks) was conducted at a tertiary care center over a two-year period. The patients were divided into three groups: isolated EIF (group 1), EIF with at least one soft marker (group 2), and EIF with structural anomalies (group 3). All the groups were divided into subgroups on the basis of a screening test (maternal age ≥ 35, positive combined-triple-quadruple tests). The incidence of chromosome anomalies was evaluated. Results: The authors examined 8,300 patients during the study period and found 170 fetuses with isolated EIF (group 1), 26 fetuses with EIF and soft markers (group 2), and 37 fetuses with EIF and structural anomalies (group 3). Thirteen (8%) patients underwent fetal karyotyping in group 1, 10 (38%) in group 2, and 22 (60%) in group 3. The rate of the invasive test was higher in fetuses exhibiting EIF accompanied by at least one of the soft markers. No trisomy was detected in group 1 or 2. Conclusion: The risk of aneuploidy did not increase in either isolated EIF or in cases with other soft markers but only in cases with structural anomalies.

Incidence of chromosomal anomalies in fetuses with isolated right aortic arch: A meta-analysis.

Right aortic arch (RAA) can be associated with chromosomal anomalies. However, the incidence of chromosomal anomalies when RAA is isolated (iRAA), ie, not associated with intracardiac anomalies, varies between different studies (0%-28.5%). We have performed a meta-analysis to allow a more accurate prenatal counselling. We searched PubMed, Embase, and Web of Science for articles related to chromosomal anomalies among iRAA fetuses until April 2019. A total of 22 relevant studies, including 670 fetuses, were selected in the final meta-analysis. The results revealed that the overall rates of chromosomal anomalies and 22q11.2 deletion in iRAA fetuses were 7.5% (95% confidence interval [CI], 4.7%-10.8%) and 4.3% (95% CI, 2.6%-6.4%), respectively, while the rates were lower in iRAA without extracardiac anomalies, 4.7% (95% CI, 1.1%-10.8%) and 2.4% (95% CI, 0.5%-5.7%). The rate of chromosomal or copy number variants including 22q11.2 deletion identified by chromosomal microarray analysis (CMA) in iRAA fetuses was 8.2% (95% CI, 5.0%-12.1%) and 3.7% (95% CI, 1.7%-6.6%), respectively, compared with 5.1% (95% CI, 2.5%-8.4%) and 2.4% (95% CI, 0.7%-5.1%) identified by traditional karyotyping. A considerable proportion of iRAA cases have associated chromosomal anomalies and prevalence of associated 22q11.2 deletion, and CMA is recommended if invasive prenatal testing is performed.

Toxicity Studies of Lactobacillus plantarum PS128TM Isolated from Spontaneously Fermented Mustard Greens.

Probiotics are extensively available to consumers; however, the use of probiotics may not always be safe, and there are few reports on their side effects, including those of Lactobacillus. Lactobacillus plantarum strain PS128TM isolated from spontaneously fermented mustard greens in Taiwan was recently reported to exhibit probiotic properties. In this study, we aimed to assess the safety of strain PS128TM for use in humans via examining genotoxic and oral toxic effects using in vitro and in vivo testing. Five strains of Salmonella typhimurium were evaluated by the Ames test; no signs of increased reverse mutation were observed following exposure to PS128TM. Additional testing of Chinese hamster ovary (CHO) cells exposed to PS128TM revealed that the incidence of chromosomal aberrations in CHO cells had not increased. PS128TM treatment also did not affect the proportion of immature to total erythrocytes or the number of micronuclei in the immature erythrocytes of ICR mice. Moreover, following a 28 day study involving repeated oral dose toxicity tests (2400, 400, and 40 mg/kg body weight) utilizing an ICR mouse model, no observable adverse level (NOAEL) was found at any of the doses. PS128TM was sensitive to antibiotics; however, genes related to the production of biogenic amines were absent. While further research is required, these toxicological assessments suggest that PS128TM could be safe for human consumption.

Outcome of non-visualization of fetal gallbladder on second-trimester ultrasound: cohort study and systematic review of literature.

To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB. NVFGB was defined as non-visualization of the gallbladder on two targeted ultrasound examinations performed within a 1-week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9-year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non-isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed. Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non-isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks. In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work-up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cytogenetic Study of Spontaneous Abortions in the Western part of Romania

Regarding the rate of chromosomal abnormalities in spontaneous abortions, the data varies between 50 and 80% for first trimester miscarriages but there are several factors that may influence the rate of chromosomal aberrations as the selection bias of the cases for which cytogenetic analysis is done, the gestational age distribution, the maternal age distribution, the tissue samples analyzed, the expertise in cytogenetic methods. The aim of the research is to establish the incidence of chromosomal aberration in our study lot for the patients from the Western part of Romania, as there are no studies available for this specific population. In the present study, patients were included with pregnancy loss between 4 to 14 weeks of gestation for whom cytogenetic evaluation of the fetus was done in the University of Medicine and Pharmacy Timisoara. Of all results, 48.57% (34 out of 70) aborted fetuses had an abnormal karyotype. The gestational age of the aborted fetuses varied between 5 and 14 weeks of gestation, with a mean of 8.95 weeks of gestation. A higher incidence of chromosomal anomalies was observed in the group including patients � 35 years as compared with the group patients aged under 35 years old (55.5% vs 45.5%). The results of cytogenetic analysis of first trimester miscarriage is an important tool that can enhance diagnostic evaluation, and represent a critical information for counselling infertile couples. Post-miscarriage genetic and psychological counselling and appropriate treatment are crucial for the prevention of high psychological distress, psychiatric symptoms and psychopathology in these patients.

Association between chromosomal translocation imbalances and aneuploidies in PGT-SR in reciprocal translocation carriers

Introduction Reciprocal translocation carriers are known to be at high risk of conceiving genetically unbalanced embryos, which may result in miscarriage or an affected neonate. Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR), a method for embryonic chromosomal analysis, can detect not only translocation chromosome imbalance but also aneuploidy via comprehensive chromosomal analysis with whole-genome amplification (WGA), thereby potentially decreasing miscarriage rate. In this study, we aimed to investigate the relationship between chromosomal abnormalities derived from translocation chromosomes and aneuploidies and the frequency of chromosomal abnormalities among stimulation cycles in reciprocal translocation carriers receiving multiple PGT-SR cycles. Material and Method Between 2013 and 2017, we assessed 20 cycles of 8 couples (reciprocal translocation carriers in 5 females and 3 males; mean women's age, 35.1 years) who received 2 or more PGT-SR cycles at our clinic.Ovarian stimulation was primarily controlled, and when chromosomally normal embryos could not be obtained, a different protocol for ovarian stimulation was adapted. All oocytes were fertilized via intracytoplasmic sperm injection (ICSI). All embryos were cultured to the blastocyst stage. Approximately 5-10 trophectoderm (TE) cells were subjected to a biopsy using a laser system. Chromosomal analysis was performed using the microarray-based comparative genomic hybridization method or next-generation sequencing with whole-genome amplification. Result In all 20 cycles, the number of oocytes retrieved was 432 and the number of blastocysts subjected to biopsy was 90. Among 88 analyzable blastocysts, 19 had normal chromosomes (21.6%) and 69 had abnormal chromosomes (78.4%). Fifty-six embryos (81.2%) contained chromosomal imbalances derived from reciprocal translocation chromosomes and 37 embryos (53.6%) had aneuploidy, 24 embryos (34.8%) had both types of abnormalities. The incidence of chromosomal translocation-derived chromosomal imbalance was 60.0% (12/20) for male carriers and 64.7% (44/68) for female carriers, with no significant difference.The incidence of chromosomally normal embryos per cycle was 0–67%. Normal embryos were not obtained in 9 cycles (45%); however, they were obtained at different stimulation cycles. In 9 PGT-SR cycles with three or more embryos of female carriers subjected to biopsy, there was no correlation between the incidence of the abnormality due to chromosome translocation and aneuploidy. Conclusion There is no association between the incidence of translocation chromosome imbalance and aneuploidy. However, approximately 80% of embryos with chromosomal translocation-derived chromosomal imbalance include aneuploidy. The incidence of chromosomal aberrations in embryos has a large difference among the PGT-SR cycles even in the same carrier. In translocation carriers without normal embryos, performing different ovarian stimulation methods enhances the possibility of obtaining normal embryos.

OC27.06: Non‐visualisation of the fetal gallbladder (NVFGB) at prenatal ultrasound: cohort study and systematic review of the literature on postnatal outcome

i) to investigate the ultrasound characteristics and outcome in fetuses with NVFGB followed in our tertiary university hospital, ii) to provide a comprehensive review of literature on NVFGB. NVFGB was defined as non-visualisation of the gallbladder at two targeted US examination within a 1-week period. Cases of NVFGB managed in our centre were revised and a systematic review of literature was performed. The incidence of chromosomal anomalies, later visualisation of gallbladder, gallbladder agenesis, cystic fibrosis (CF) and Biliary Atresia (BA) in fetuses were assessed isolated and non-isolated NVFGB. 16 cases of NVFGB were followed in our centre, 10 being isolated (62.5%). There was an incidence of 12.5% of BA and 12.5% of gallbladder agenesis while no case of CF was reported. Gallbladder was visualised later in pregnancy or postnatally in 43.8% and 31.3% of cases, respectively. A total of 5 additional studies for a total of 227 cases met inclusion criteria for the systematic review. Overall, 22.0% of fetuses had associated US anomalies, the incidence of chromosomal anomalies in this group was 18.0%, while that of severe conditions (CF or BA) was 39.0% in cases with normal karyotype. Table 1 summarised the results of our review. In case of persistent NVFGB the risk of a severe postnatal condition should be considered. This study provides important information for prenatal counselling. N of studies (n) Fetuses (n/N) I2 (%) Raw % (95% CI) Pooled % (95% CI) 1.3 (0.2-4.7) 1.9 (0.2-5.2) 69.4 (61.9-76.2) 70.4 (61.0-79.0) 24.7 (18.4-31.7) 25.2 (19.0-32.0) 2.4 (0.6-5.9) 3.1 (1.0-6.2) 3.5 (1.3-7.5) 4.8 (2.1-8.4)

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Genotoxic Effects of the Anti-Cancer Drug Doxorubicin (Dxr) in the Bone Marrow Cells of Swiss Albino Mice (Mus musculus)

The antineoplastic chemotherapeutic agent doxorubicin (DXR) is probably the most utilized drug for treating many human cancers. In the current study we aimed to evaluate the genotoxic effects of doxorubicin Swiss mice bone marrow cells using the toxicological endpoints chromosomal aberrations, mitotic index and micronuclei formation. Twelve male animals, aged 6-8 weeks and weighing 24±2g were divided into four groups. One group served as control was intraperitoneally injected only with distilled water. The three remaining groups were injected intraperitoneally with single doses of doxorubicin (0.2, 0.4 and 0.8 mg/g body weight) for two consecutive days. 24 hours later, animals were anaesthetized and killed by cervical dislocation. Colchicine (0.05 %) was injected to animals 90 minutes before sacrifice. After sacrificing the animals, both femurs were dissected out and the bone marrow cells obtained. All treatments with doxorubicin caused an increased significance in the incidence of chromosomal aberrations (CA) and micronuclei formation in polychromatic erythrocytes (PCEs) cells. Meanwhile, there was a gradual repression in the mitotic index (MI) percentages of the treated groups compared to that of the control. Different types of chromosomal aberrations (structural and numerical) were induced as a result of doxorubicin treatments. These includes: gaps, breaks, fragments, rings, centric fusions (CF) and polyploidy. The mean percentages of total chromosomal aberrations increased from 3.33 ± 0.28 in the control group to 12.67 ± 2.42, 29.00 ± 4.27 and 38.67 ± 2.82 for doses 0.2, 0.4 and 0.8 mg/kg B.W. respectively. The numbers of micronucleated PCEs observed in mice cells treated with doxorubicin were increased from 4.67±0.48 for the control group to 7.00±1.02, 10.67±2.10 and 17.67 for the three doses respectively. Meanwhile, the PCE / (PCE+NCE) ratio calculated in treated animals were 0.85 ± 0.02, 0.63 ± 0.08 and 0.54 ± 0.10 compared to 0.94 ± 0.12 for the control. Our results indicated that doxorubicin has genotoxic as well as cytotoxic effects in mice bone marrow cells.

Oxidative DNA damage and RUNX1-RUNX1T1 translocation induced by cigarette smoking as a potential risk factor for leukemogenesis

Background Cigarette smoking, one of the main causes of avertible morbidity and mortality, has a multitude of well-known side effects. Cigarette smoking contains large amounts of reactive oxygen species that induce oxidative DNA damage and increase the incidence of chromosomal aberrations and thus increases the incidence of oncogenesis. Aim The aim of this work is to study the hematological effects of smoking and its ability to induce DNA damage and specific RUNX1-RUNX1T1 gene translocation. Patients and methods The hematological studies and measurement of plasma concentration of 8-hydroxy-2’-deoxyguanosine (8-OHDG) (using enzyme-linked immunosorbent assay) and RUNX1-RUNX1T1 translocation t(8;21) (using reverse transcription-PCR) were conducted on two groups of participants one smoking and the other is a nonsmoking control group. Results Smokers group showed a highly significant (P≤0.001) increase in plasma 8-OHDG and with a significant correlation between 8-OHDG and hemoglobin concentrations. In addition, the incidence of translocation(8;21) was 8.3% in the smokers’ group with obvious myelodysplasia of peripheral white blood cells was detected in 29.2% of smoking persons.