Rate Of Chromosomal Abnormalities Research Articles

Clinical Utility and the Yield of Single Nucleotide Polymorphism Array in Prenatal Diagnosis of Fetal Central Nervous System Abnormalities.

Applying single nucleotide polymorphism (SNP) array to identify the etiology of fetal central nervous system (CNS) abnormality, and exploring its association with chromosomal abnormalities, copy number variations, and obstetrical outcome. 535 fetuses with CNS abnormalities were analyzed using karyotype analysis and SNP array. Among the 535 fetuses with CNS abnormalities, chromosomal abnormalities were detected in 36 (6.7%) of the fetuses, which were consistent with karyotype analysis. Further, additional 41 fetuses with abnormal copy number variations (CNVs) were detected using SNP array (the detection rate of additional abnormal CNVs was 7.7%). The rate of chromosomal abnormalities, but not that of pathogenic CNVs in CNS abnormalities with other ultrasound abnormalities was significantly higher than that in isolated CNS abnormalities. The rates of chromosomal abnormalities and pathogenic CNVs in fetuses with spine malformation (50%), encephalocele (50%), subependymal cyst (20%), and microcephaly (16.7%) were higher than those with other isolated CNS abnormalities. The pregnancies for 36 cases with chromosomal abnormalities, 18 cases with pathogenic CNVs, and three cases with VUS CNVs were terminated. SNP array should be used in the prenatal diagnosis of fetuses with CNS abnormalities, which can enable better prenatal assessment and genetic counseling, and affect obstetrical outcomes.

Structure and signifi cance of cytogenetic abnormalities in patients with multiple myeloma

Introduction. Cytogenetic and genomic traits of tumour cells are considered the key mediating factors in multiple myeloma (MM). Selected chromosomal abnormalities are prognostic of therapeutic response and patient survival in MM.Aim — to assess of the diversity and rate of chromosomal abnormalities in MM patients and their association with the disease course.Materials and methods. The study enrolled 134 MM patients with pre-treatment bone marrow FISH assay screening for chromosomal abnormalities: t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), hyperdiploidy, del13q14/-13, del17p13/TP53, amp1q21, t(8q24)/cMYC. The studied criteria at the MM onset were: hemogram, lactate dehydrogenase (LDH) activity, calcium, β2-microglobulin and creatinine concentrations, punctate cytology, bone marrow trephine biopsy and/or soft tissue biopsy histology, bone X-ray, immunochemical variant of MM, disease staging. A median follow-up was 20 months (3.2–77.4).Results. The primary chromosomal abnormality rate was 82.9 %, among them t(14q32)/IGH — 29.1 %, multiple trisomies — 46.3 % and their combination — 7.5 %. The rates of particular t(14q32)/IGH): t(11;14) — 16.4 %, t(4;14) — 12.7 %, t(14;16) and t(14;20) — 3.7 and 2.2 %, respectively. The secondary chromosomal abnormality rate was 69.4 %, among them del13q14/-13 — 40.3 %, amp1q21 — 39.6 %, t(8q24)/cMYC — 17.2 %, del17p13/TP53 — 12.7 %, del1p32 — 2.2 %. Analyses of the primary–secondary abnormality combinations showed that del13q14/-13 is more frequently combined with t(4;14) and less frequently with trisomies (p < 0.05). Amp1q21 occurs more frequently with t(4;14) and less — with t(11;14) (p<0.05). Patients with t(4;14) more frequently (p < 0.05) had anemia at a hemoglobin level<100 g/L, and the presence of amp1q21 and del17p13/TP53-enhanced serum LDH activity (p < 0.05). Abnormality t(8q24)/cMYC more often co-occurred with higher serum β2-microglobulin concentrations (p < 0.05). A three-year overall survival (OS) in del17p13/TP53-positive patients was 35.5 vs. 71.3 % in the negative (p = 0.002) and 50.8 vs. 67 % — in t(8q24)/cMYC-positive and negative patients, respectively (p = 0.001). Patients without amp1q21, with one, with two or more additional 1q21 copies had a five-year OS 79.4, 67.3 and 20.9 %, respectively (p = 0.0016), and a two-year progression-free survival (PFS) 83, 50 and 0 %, respectively (p = 0.005).Conclusion. We establish a negative impact of del17p13/TP53 and t(8q24)/cMYC on patients’ OS in MM, as well as unfavourable effect of amp1q21 on OS and PFS in the presence of two or more additional copies of 1q21 loci.

Chromosomal Aneuploidy Associated With Clinical Characteristics of Pregnancy Loss.

ObjectiveEmbryonic aneuploidy is found in about half of sporadic pregnancy losses and the associations between the chromosomal aneuploidy and clinical characteristics of pregnancy loss remain unclear. The aims of this study were to evaluate the associations between chromosomal aneuploidy of products of conception (POC) and clinical features of pregnancy loss.MethodsWe conducted a retrospective cohort study including 1,102 women experienced singleton pregnancy loss and underwent chromosomal microarray analysis (CMA) detection of POC in our hospital. The results of molecular karyotypes and clinical features including maternal age, history of pregnancy loss, gestational age, vaginal bleeding and ultrasonographic findings were extracted from the medical records. χ2 test was used to compare categorical data between groups.Results631 (57.26%) POC specimens were detected to be chromosomal aneuploidy. Aneuploid rates were significantly higher in women >35 years (P < 0.001) and pregnancy loss <11 gestational weeks (P = 0.044), but the rates of sex chromosome abnormalities and triploid were significantly higher in women ≤35 years (P < 0.001, P = 0.002) and the rates of viable autosomal trisomy and sex chromosome abnormalities were significantly high in those women with pregnancy loss ≥11 weeks (P < 0.001, P < 0.001). Aneuploid rate was overall similar between the sporadic and the recurrent pregnancy loss (RPL) (P = 0.404), but the rate of sex chromosome abnormalities was higher in women with sporadic pregnancy loss (P = 0.03). Aneuploid rates were higher in subjects with yolk sac or embryo than in those without (P < 0.001 and P = 0.001).ConclusionAdvanced maternal age is mainly associated with autosomal trisomy, while sex chromosome abnormalities and triploid might be more likely to occur in younger women. Aneuploidy rates might be no association with previous pregnancy loss except for sex chromosome abnormalities. Pregnancy loss without yolk sac or embryo might be less related to embryonic aneuploidy, and other factors should be emphasized.

Chromosomal analysis for embryos from balanced chromosomal rearrangement carriers using next generation sequencing.

We aimed to use next generation sequencing (NGS) to investigate chromosomal abnormalities in blastocyst trophectoderm (TE) samples, and reproductive outcomes with the different types of chromosomal rearrangements (CR) and for each sex of CR carrier. A total of 1189 blastocyst TE samples were evaluated using NGS to detect chromosomal unbalanced translocations as well as aneuploidy, including blastocytes from 637 blastocysts from carriers of balanced CRand 552 blastocysts from carriers of normal chromosomes. The optimal embryos had lower chromosomal abnormality rates compared to the poor-quality embryos. The experimental group had significantly reduced rates of normal embryos and euploidy, and higher rates of total abnormalities, aneuploidy and unbalanced chromosomal aberrations. Carriers of reciprocal translocationshad a reduced rate of normal embryos and an increased percentage of embryos with total abnormalities and unbalanced chromosomal aberrations compared with carriers of Robertsonian translocations. Couples with female carriers of chromosomal abnormalities had significantly reduced rates of normal embryos and euploidy, and a higher percentage of embryos with total abnormalities, aneuploidy, and unbalanced chromosomal aberrations compared with couples of male carriers. Our preimplantation genetic testing (PGT) study identified higher rates of chromosomal abnormalities, including chromosomal unbalanced translocations and aneuploidy, in blastocysts from CR carriers, especially from the female carriers, in a Chinese population. The PGT cycles successfully improved clinical outcomes by increasing the fertilization rate and reducing the early spontaneous abortion rate compared with the in vitro fertilization and intracytoplasmic sperm injection cycles, especially for CR carriers.

Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China.

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

Prenatal diagnosis of 913 fetuses samples using copy number variation sequencing.

BackgroundThe present study aimed to explore the etiological relationship between fetal abnormalities and copy number variations (CNVs) with the aim of intervening and preventing the birth of children with birth defects in time.MethodsSamples of 913 fetuses with puncture indications were collected from January 2017 to December 2019. Karyotype analysis and CNV sequencing (CNV‐seq) testing was performed for fetuses with ultrasonic abnormalities, a high risk of Down’s syndrome and an adverse birth history. All cases were followed up.ResultsIn total, 123 cases (13.47%) had abnormal karyotypes, including 109 cases with chromosome number abnormalities and 14 cases of chromosomal structural abnormalities. Thirty‐seven (4.05%) cases with pathogenic CNVs were detected. The detection rate of pathogenicity CNVs was 12.82% for mixed indications, followed by 7.5% for an adverse birth history, 5.88% at high risk of non‐invasive prenatal testing, 5.00% with an abnormal ultrasonic marker, 1.89% at high risk of screening for Down's syndrome and 1.45% with advanced maternal age. There were 12 (1.31%) cases with microduplications and 25 (2.74%) cases with microdeletions. Trisomy 21 (39.02%), trisomy 18 (13.82%) and Turner syndrome (9.76%) were the top three chromosome abnormalities. There were 104, 746 and 63 cases in the 11–13 weeks, 14–27 weeks 28–38 weeks gestational ages, respectively. The abnormal rates of fetal chromosome aneuploidy and the rate of pathogenic CNVs were decreased and increased with the increase of gestational age (p < 0.05), respectively.ConclusionsCompared with karyotype analysis, CNV‐seq can improve the detection rate of chromosomal abnormalities. CNV‐seq combined karyotype analysis should be performed simultaneously in fetuses with puncture indications.

Analysis of Copy Number Variations by Low-Depth Whole-Genome Sequencing in Fetuses with Congenital Cardiovascular Malformations

Congenital cardiovascular malformations (CVMs) due to genomic mutations bring a greater risk of morbidity and comorbidity and increase the risks related to heart surgery. However, reports on CVMs induced by genomic mutations based on actual clinical data are still limited. In this study, 181 fetuses were screened by fetal echocardiography for prenatal diagnosis of congenital heart disease, including 146 cases without ultrasound extracardiac findings (Group A) and 35 cases with ultrasound extracardiac findings (Group B). All cases were analyzed by clinical data, karyotyping, and low-depth whole-genome sequencing. The rates of chromosomal abnormalities in Groups A and B were 4.8% (7/146) and 37.1% (13/35), respectively. There was a significant difference in the incidence of chromosomal abnormalities between Groups A and B (p < 0.001). In Group A, CNV-seq identified copy number variations (CNVs) in an additional 9.6% (14/146) of cases with normal karyotypes, including 7 pathogenic CNVs and 7 variations of uncertain clinical significance. In Group B, one pathogenic CNV was identified in a case with normal karyotype. Chromosomal abnormality is one of the most common causes of CVM with extracardiac defects. Low-depth whole-genome sequencing could effectively become a first approach for CNV diagnosis in fetuses with CVMs.

Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down's Syndrome

To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.

430 Prenatal findings and associated survival rates in fetal ventriculomegaly: a prospective observational study

The aim was to present the antenatal experience of fetal ventriculomegaly in a large European center in relation to; 1.Grade of ventriculomegaly; 2.Additional chromosomal/structural abnormalities and 3.Perinatal survival rates. This was a prospective observational study of patients referred with fetal ventriculomegaly to the National Maternity Hospital, Dublin, from January 2010 through July 2020 (with Institutional Review Board Approval). Data was obtained from the hospital database and categorized as mild (10-12mm), moderate (13-15 mm) or severe ventriculomegaly (>15mm), as per SMFM recommendations. Data was analyzed and statistical analysis performed using the Chi-Square test. 213 were included for analysis. The mean maternal age was 31.6 years, the mean gestation at diagnosis was 25+6 weeks (17 to 38+5 weeks) and the mean gestation at delivery was 38+3 weeks (33 -41+7 weeks). There was bilateral and unilateral ventriculomegaly in 186/213 (87.3%) and 27/213 (12.7%) cases respectively. Ventriculomegaly was mild in 92/213 (43.2%), moderate in 25/213 (11.7%) and severe in 96/213 (45.1%). 114/213 (53.5%) had additional structural abnormalities on ultrasound (US), of which 43/213 (20.2%) had intracranial findings only. 27/213 (12.7%) had underlying chromosomal abnormalities (21 diagnosed antenatally, 6 postnatally). No difference was observed in the rate of chromosomal abnormalities between the groups, though those with mild ventriculomegaly and additional US features had higher rates of chromosomal abnormalities than those with isolated ventriculomegaly (IVM), 12/49 (24.5%) vs 4/43 (9.3%), P<0.05 (Table 1). 28/213 (13.1%) had termination of pregnancy and 18/213 (8.5%) had a subsequent neonatal death. The overall survival was 167/213 (78.4%) . No difference was observed in the survival rates between the groups, though those with additional US findings in the mild and the severe groups had worse survival rates of 61.2% and 67.31% (P<0.05)(Table 1). In this cohort, fetuses with IVM had survival rates greater than 90% and chromosomal abnormalities under 10% in all groups.

431 Severe ventriculomegaly: fetal morbidity and mortality and cesarean delivery rates

The aim is to describe the morbidity and mortality associated with severe fetal ventriculomegaly and cesarean delivery rates and to compare two clinical groups. Those with a fetal measurement of the posterior horn of the lateral ventricle (Vp) < 20mm with those Vp>20mm . This is a prospective observational study of fetuses diagnosed with severe ventriculomegaly in a large tertiary center in Ireland from January 2010 through July 2020 (with Institutional Ethical Board Approval). Severe ventriculomegaly was defined as a Vp >15mm. Data was analyzed and statistical analysis performed using the Chi-Square test. Severe ventriculomegaly was diagnosed in 96 fetuses. The average maternal age was 31.7 years and the average BMI was 26.4 kg/m2. The average gestation at diagnosis was 26+3 weeks (range 17–37 weeks) and the average gestation at delivery was 38+2 weeks (range 30 –41+6 weeks). There were 41 with a Vp 20mm (mean 30.5mm). The differences between the two groups are presented in Table 1. The overall rate of chromosomal abnormalities was 9/96(9.4%), with additional intracranial ultrasound(US) and extracranial US findings observed in 23/96(24%) and 29/96(30.2%) respectively, NS. Those in the Vp>20mm group were more likely to have head circumference > 95th centile than those in the Vp < 20mm group, 35/55(63.6%) > vs 14/41(34%), P < 0.05. Delivery information was available for 66. The overall rate of fetal and neonatal loss in this cohort was high at 20.8% (20/96) and the cesarean delivery(CD) rate was 57.6% (38/66). No difference was observed between the groups with regards to rates of termination of pregnancy, neonatal death rate or mode of delivery. This study highlights the significant morbidity and mortality rates associated with fetuses presenting with severe ventriculomegaly. Counselling should include not only the high rates of fetal morbidity and mortality but also the significant maternal morbidity in relation to CD rates of 57.6% in this cohort.

Application of the BACs-on-Beads assay for the prenatal diagnosis of chromosomal abnormalities in Quanzhou, China

BackgroundAn increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China.MethodsA total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings.ResultsIn this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%).ConclusionsBoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers

BackgroundSome ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers.MethodsAmong 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis.ResultsAmong 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups.ConclusionsGenetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.

Kadın Cinsiyet Disforisinin Nadir Bir Nedeni: Düşük Yüzdeli Turner Mozaisizmli Üç Olgu Raporu

Gender dysphoria is a condition caused by a mismatch between the gender assigned at birth and gender identity. Gender development disorders include situations where congenital chromosomal, gonadal, or anatomically gender-related physical features are atypical. In the studies conducted mostly by karyotype analysis, it is reported that the rate of chromosomal abnormality is very low in people with gender dysphoria. In Turner mosaicism, gender dysphoria is not a common finding. In this case series, we examined the phenotype and genotype characteristics of the three cases identified as Turner mosaicism, who applied with gender dysphoria. The patients’ complaints were feeling like a male, negative thoughts about being a female, being uncomfortable with feminine body image, wanting to have a male body. None of our 3 cases had Turner stigmata however their chromosomal or FISH analyses showed that one of them was 45,X/46 XX/47,XXX and two of them were 45 X/46 XX karyotype.

Lower chromosomal abnormality frequencies in miscarried conceptuses from frozen blastocyst transfers in ART.

Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)? Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC. Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge. This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed. This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA. The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05). This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy. To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients. This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests. N/A.

Reanalysis of discarded blastocysts for autosomal aneuploidy after sex selection in cleavage-stage embryos.

ObjectiveThe goal of the present study was to investigate the rate of chromosomal aneuploidies in surplus embryos after sex determination at the cleavage stage. Then, the same chromosomal aneuploidies were evaluated in blastocysts after extended culture.MethodsSixty-eight surplus embryos were biopsied at the cleavage stage and incubated for an additional 3 days to allow them to reach the blastocyst stage. The embryos were reanalyzed via fluorescence in situ hybridization (FISH) to examine eight chromosomes (13, 15, 16, 18, 21, 22, X, and Y) in both cleavage-stage embryos and blastocysts.ResultsAlthough the total abnormality rate was lower in blastocysts (32.35%) than in cleavage-stage embryos (45.58%), the difference was not significant (p=0.113). However, when we restricted the analysis to autosomal abnormalities, we observed a significant difference in the abnormality rate between the cleavage-stage embryos (44.11%) and the blastocysts (17.64%, p=0.008). A higher rate of sex chromosomal abnormalities was also observed in cleavage-stage embryos (29.4%) than in blastocysts (14.70%, p=0.038).ConclusionThe data indicated that embryo biopsy should be conducted at the blastocyst stage rather than the cleavage stage. The results also emphasized that examination of common chromosomal aneuploidies apart from sex selection cycles can be conducted in the blastocyst stage with the FISH method.

Application of chromosome microarray analysis in prenatal diagnosis

BackgroundTo explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis.MethodsThe results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared.ResultsAbnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05).ConclusionsThe detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

Evaluation of extracellular vesicles and gDNA from culture medium as a possible indicator of developmental competence in human embryos.

Human embryos generated in vitro have a high incidence of chromosomal abnormalities that negatively affect pregnancy rate. Embryos generated in vitro secrete extracellular vesicles (EVs) into the culture medium that could be used potentially as indicators of embryo competence. This research aimed to evaluate the concentration and size of EVs and their gDNA content as an indicator of developmental competence in human embryos. Human embryos generated by intracytoplasmic sperm injection (ICSI) were classified morphologically as of either TOP, FAIR or POOR quality. Culture medium and developmentally arrested embryos (which were not able to be used for embryo transfer) were collected. Microvesicles, exosomes (MV/Exo) and apoptotic bodies (ABs) were isolated from culture medium. Nanoparticle tracking analysis (NTA) and array comparative genomic hybridization (aCGH) analysis were performed to evaluate EVs and their gDNA content. From NTA, the diameter (mean) of MVs/Exo from TOP quality embryos was higher (112.17 nm) compared with that of FAIR (108.02) and POOR quality embryos (102.78 nm) (P < 0.05). aCGH analysis indicated that MVs/Exo and ABs carried gDNA with the presence of 23 chromosome pairs. However, when arrested embryos were compared with their respective MVs/Exo and ABs, the latter had an increased rate of chromosomal abnormalities (24.9%) compared with embryos (8.7%) (P < 0.05). In conclusion, the size of EVs from culture medium might be an alternative for evaluating competence of human embryos, however more studies are needed to validate the use of gDNA from EVs as an indicator of embryo competence.

Exposure to Perfluorinated Compounds and Human Sperm Aneuploidy

Exposure to Perfluorinated Compounds and Human Sperm AneuploidyBackground: Sperm chromosomal abnormalities linked to infertility may be caused by environmental endocrine disrupting chemicals such as perfluoroalkyl and polyfluoroalkyl substances (PFASs). Relatively few studies have investigated the potential effects of PFAS exposure on male reproductive function, although some studies suggest effects on semen quality and concentration as well as reproductive hormone levels.Aim: We examined whether concurrent exposure to PFASs or blood concentrations measured at birth, ages 7, 14, 22, and 28 predicted sperm chromosomal abnormalities in adulthood.Methods: Serum and semen samples were obtained from 146 Faroese men. Serum concentrations included major PFASs (perfluorooctanoic acid (PFOA), perfluorhexane sulfonic acid (PFHxS), pefluorononanoic acide (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctane sulfonate (PFOS)) measured at ages 7, 14, 22, and 28. PFOA concentrations were measured in cord blood. Incidence rate ratios (IRR) measured associations between exposure tertiles and the risk of an extra X or Y chromosome (XX18, YY18 or XY18) in adult sperm as modeled by Poisson regression. Results: Higher tertiles of exposure at ages 7 and adulthood were strongly associated with increased rates of sperm chromosomal abnormalities (IRR ranging from 1.09-2.12; p-trend &lt;0.001) for most of the measured PFASs. However, higher levels of PFOA, PFDA, and PFOS at age 14 were associated with significantly reduced risk of diosmy (ranging from 13-37%). Exposure to PFOS in cord blood showed a significantly increased risk of disomy in the second tertile and a significantly decreased risk in the third tertile.Conclusions: The relationship between exposure to PFAS and sperm disomy appears to be complex with the possibility of risk varying by age of exposure. This suggests that the impactsof these widespread and persistent pollutants on testicular maturation and function need additional investigation.

Comparison of chromosomal instability of human amniocytes in primary and long-term cultures in AmnioMAX II and DMEM media: A cross-sectional study.

BackgroundThe genomic stability of stem cells to be used in cell therapy and other clinical applications is absolutely critical. In this regard, the relationship between in vitro expansion and the chromosomal instability (CIN), especially in human amniotic fluid cells (hAFCs) has not yet been completely elucidated.ObjectiveTo investigate the CIN of hAFCs in primary and long-term cultures and two different culture mediums.Materials and Methods After completing prenatal genetic diagnoses (PND) using karyotype technique and chromosomal analysis, a total of 15 samples of hAFCs from 650 samples were randomly selected and cultured in two different mediums as AmnioMAX II and DMEM. Then, proliferative cells were fixed on the slide to be used in standard chromosome G-banding analysis. Also, the senescent cells were screened for aneuploidy considering 8 chromosomes by FISH technique using two probe sets including PID I (X-13-18-21) & PID II (Y-15-16-22).Results Karyotype and interphase fluorescence in situ hybridization (iFISH) results from 650 patients who were referred for prenatal genetic diagnosis showed that only 6 out of them had culture- derived CIN as polyploidy, including mosaic diploid-triploid and diploid-tetraploid. Moreover, the investigation of aneuploidies in senesced hAFCs demonstrated the rate of total chromosomal abnormalities as 4.3% and 9.9% in AmnioMAX- and DMEM-cultured hAFCs, respectively.ConclusionhAFCs showed a low rate of CIN in two AmnioMAX II and DMEM mediums and also in the proliferative and senescent phases. Therefore, they could be considered as an attractive stem cell source with therapeutic potential in regenerative medicine.

Chromosomal copy number analysis of products of conception by conventional karyotyping and next-generation sequencing.

PurposeChromosomal abnormalities are a major cause of spontaneous abortion, and conventional G‐banded karyotyping (G‐banding) is mainly utilized for chromosomal analysis. Recently, next‐generation sequencing (NGS) has been introduced for chromosomal analysis. Here, we aimed to investigate the applicability and utility of NGS‐based chromosomal analysis of products of conception (POC) on chorionic villus samples from spontaneous abortion.MethodsThe results of chromosomal analysis of 7 chorionic villus samples from spontaneous abortion were compared between conventional G‐banding and NGS‐based chromosomal copy number analysis. Age dependency and frequency of each chromosomal aneuploidy were evaluated for 279 cases analyzed by NGS.ResultsExcluding two cases (culture failure and maternal cell contamination), the results were consistent between G‐banding and NGS. For cases analyzed by NGS, the rate of chromosomal abnormality increased in a maternal age‐dependent manner. The frequency of each chromosomal aneuploidy detected by NGS was almost the same as that previously reported. Finally, NGS analysis was possible for difficult cases by G‐banding analysis, such as culture failure, maternal cell contamination, long‐term storage cases, and low cell number.ConclusionsChromosome analysis using NGS not only obtains comparable results to conventional G‐banding, but also can analyze POC more accurately and efficiently.