Search

Rationale: If one of the partners is having balanced autosomal translocation, it is usually observed that the offspring inherit either normal chromosomes, balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation. Concern: A unique case presented with history of 8 miscarriages for genetic counseling. The last abortus material evaluation showed monosomy of chromosome X (Turner syndrome) in all the analysed cells. There was a history of infertility and also repeated second trimester abortions on the paternal side. On the maternal side, there was a history of intellectual disability. Diagnose: History of repeated abnormal pregnancy outcomes. Wife’s karyotype is normal; however, husband shows translocation between chromosome 4 and 22. Intervention: Peripheral blood sample around 3 mL was collected for karyotype. Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing. Outcomes: Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22. Surprisingly, the entire pregnancy outcome including embryo screening has different, complete or partial aneuploidies of chromosomes other than chromosome 4 and 22. Main lesson: Though the translocation in one of the parent is balanced, we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division. Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.

Background: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell‐free DNA screening results. Methods: In this study, we retrospectively examined 523 prenatal and 319 products‐of‐conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. Results. In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. Conclusion: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory. [ABSTRACT FROM AUTHOR]

Background A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023.

Abstract Background Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell‐free DNA screening results. Methods In this study, we retrospectively examined 523 prenatal and 319 products‐of‐conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. Results. In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. Conclusion Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

الملخص: أهداف البحث: يعتقد بأن عملية الحمل تمثل إحدى التحديات التي تواجهها النساء اللاتي يقطن الأماكن شديدة الارتفاع عن سطح البحر، وذلك نظرا لصعوبة التأقلم مع معضلة نقص الأكسجين. من خلال هذا البحث تم دراسة مجموعة من الخصائص المرضية النسيجية (الباثولوجية) لبعض اضطرابات الحمل التي تتضمن فقدان الحمل (الإجهاض) بين النساء الحوامل اللائي يقطن منطقة مرتفعة عن سطح البحر بحوالي 2200 متر بالمملكة العربية السعودية. طرق البحث: دراسة مقطعية تم خلالها جمع البيانات بأثر رجعي من مستشفى واحد واقع في منطقة مرتفعة وذلك خلال عامي 2018-2020 . النتائج: أسفرت النتائج عن أن نسبة تقدر بحوالي 55% من النساء اللاتي حدث عندهن حمل غير مكتمل (إجهاض أو حمل العنقودي أو حمل خارج الرحم) كانت أعارهن تقل عن 35 عامًا. وقد دلت الإحصائية على أن نسبة الحمل خارج الرحم وصلت إلى 6.8% من تلك الاضطرابات. وقد بلغ معدل الإجهاض 19% من إجمالي عدد حالات الحمل التي تمت دراستها الاستنتاجات: توصي الدراسة الباحثين باستكمال وتواصل الدراسات في هذا الشأن وأن تشتمل دراساتهم المستقبلية على عدد أكبر من السيدات الحوامل في تلك المناطق شديدة الارتفاع عن سطح الأرض مستعينين بالتحليلات الجينية وغيرها من الوسائل التي تساعد على التوصل إلى نتائج أكثر دقة والتعرف على الأسباب وطرق الوقاية من تلك الاضطرابات، إضافة إلى الحاجة إلى المزيد من الدراسات المماثلة بمناطق تقع على مستوى سطح البحر. Abstract: Objectives: Pregnancy at high altitudes is relatively challenging because of hypobaric hypoxia, which is associated with a smaller uterine artery diameter and diminished blood flow. Here, we investigated the histopathological characteristics of early pregnancy disorders among pregnant women living in a high-altitude region (approximately 2200 m above sea level). Methods: This cross-sectional study used retrospective data collection from a single tertiary hospital in a high-altitude region in KSA. Age and histopathology were analyzed in 495 women diagnosed with early pregnancy disorders (mainly miscarriage) in 2018–2020. Results: Approximately one-fifth of pregnancies in this high-altitude region were lost before 24 weeks’ gestation, whereas 1150/6044 experienced miscarriage; 495 samples from those participants were sent for histopathological analysis. A total of 269 (54.34%) patients were younger than 35 years. Missed miscarriages accounted for 49.3% of miscarriages, followed by inevitable miscarriages (34.2%), which had a relatively higher frequency among mothers older than 35 years. The correlation between age and inevitable miscarriage was significant; ectopic pregnancy was diagnosed in 6.8%, molar pregnancy was detected in 6.26%, and blighted ovum was observed in 3.4%. Conclusion: The miscarriage rate in this high-altitude region was 19% of all pregnancies. Approximately half of the affected women were in their 30s. Missed miscarriage cases were relatively high in this region. The percentage of molar pregnancy was higher than those reported in prior studies, thus suggesting a need for monitoring and genetic workup practices. Furthermore, studies involving a larger population at high altitudes will be crucial for further risk assessment in addition to national studies on women living at sea level.

The objective of this study was to characterize the relationship between embryonic chromosomal errors in the products of conception (POC) and maternal age, gestational age (GA) of pregnancy loss, and findings on routine recurrent pregnancy loss (RPL) workup. This is a retrospective cohort study of women with a history of ≥ 2 pregnancy losses and who underwent cytogenetic testing on the POC of a subsequent pregnancy loss at an academic tertiary RPL referral center. The association between the odds of embryonic chromosomal errors in POC and maternal age, GA of pregnancy loss, as well as RPL work up findings was investigated. A total of 1107 miscarriages were analyzed from 741 women. There was an overall linear relationship between embryonic chromosomal errors and maternal age, with a nearly twofold increase in the odds of chromosomal error with every 5-year increase in maternal age (P < 0.0001). The association between chromosomal errors and GA was also linear (P = 0.0001), with most losses having no chromosomal errors after 13 weeks' gestation. Women with ≥ 1 positive findings on routine RPL diagnostic workup had lower odds of embryonic chromosomal errors compared to those with a normal workup [OR 0.57 (95% CI = 0.41–0.80)]. Notably, the estimated prevalence of chromosomal error remained high (> 60%) in women ≥ 35 years old irrespective of findings on routine evaluation. While embryonic chromosomal errors were associated with advanced maternal age, early GA of loss, and a negative routine RPL evaluation, the prevalence of chromosomal errors remained high in all subpopulations. These findings suggest that primary cytogenetic testing on POCs should be offered at the time of second and subsequent pregnancy losses in all RPL patients. [ABSTRACT FROM AUTHOR]

Abstract Background Whole-exome sequencing (WES) is an effective method in the prenatal setting for identification of the underlying genetic etiology of fetal ultrasound abnormalities. To investigate the diagnostic value of WES in fetuses with ultrasound abnormalities that resulted in fetal demise or pregnancy termination. Methods 61 deceased fetuses with ultrasound abnormalities and normal copy number variation Sequencing were retrospectively collected. Proband-only or trio-WES were performed on the products of conception. Result Collectively, 28 cases were positive with 39 variants (10 pathogenic, 22 likely pathogenic and 7 variants of uncertain significance) of 18 genes, and the overall diagnostic rate was 45.9% (28/61), of which 39.2% (11/28) were de novo variants. In addition, 21 variants in 11 genes among the positive cases had not been previously reported. The diagnostic yield for definitive findings for trio analysis was 55.9% (19/34) compared to 33.3% (9/27) for singletons. The most common ultrasound abnormalities were skeletal system abnormalities 39.2% (11/28), followed by multiple system abnormalities (17.9%, 5/28) and genitourinary abnormalities (17.9%, 5/28). Conclusion Our results support the use of WES to identify genetic etiologies of ultrasound abnormalities and improve understanding of pathogenic variants. The identification of disease-related variants provided information for subsequent genetic counseling of recurrence risk and management of subsequent pregnancies.

Background: Chromosomal abnormalities are a major cause of early pregnancy loss. However, models synthesizing existing genetic technologies to improve pregnancy outcomes are lacking. We aim to provide an integrated laboratory algorithm for the genetic etiology of couples who experienced pregnancy loss. Methods: Over a 6-year period, 3,634 products of conception (POCs) following early pregnancy loss were collected. The clinical outcomes from a laboratory algorithm based on single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and parental chromosomal karyotyping assays were comprehensively evaluated. Results: In total, 3,445 of 3,634 (94.8%) POCs had no maternal-cell contamination. Of those POCs, the detection rate of abnormal results was 65.2% (2,247/3,445), of which 91.2% (2,050/2,247) had numerical chromosomal abnormalities, 2.7% (60/2,247) had copy-number variations (CNVs) =10 Mb, 2.7% (61/2,247) had CNVs of terminal deletion and duplication, 2.8% (62/2,247) had CNVs <10 Mb, and 0.6% (14/2,247) had uniparental disomy. Furthermore, FISH confirmed 7 of the 60 POCs with mosaic aneuploids below 30% based on the SNP array results as tetraploid. Of the 52 POCs with CNVs of terminal deletion and duplication, 29 couples had balanced rearrangements based on chromosomal karyotyping. Conclusion: The integrated SNP array-based algorithm combined with optional FISH and parental chromosomal karyotyping is an effective laboratory testing strategy, providing a comprehensive and reliable genetic investigation for the etiology of miscarriage, regardless of the number of miscarriages and the method of conception. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics. Method: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher's exact test and logistic regression. Results: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41–2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79–4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84–2.94; 3 times: OR, 1.59; 95% CI, 1.23–2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15–1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87–8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00–12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics. Conclusion: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Whole-exome sequencing (WES) is an effective method in the prenatal setting for identification of the underlying genetic etiology of fetal ultrasound abnormalities. To investigate the diagnostic value of WES in fetuses with ultrasound abnormalities that resulted in fetal demise or pregnancy termination. Methods: 61 deceased fetuses with ultrasound abnormalities and normal copy number variation Sequencing were retrospectively collected. Proband-only or trio-WES were performed on the products of conception. Result: Collectively, 28 cases were positive with 39 variants (10 pathogenic, 22 likely pathogenic and 7 variants of uncertain significance) of 18 genes, and the overall diagnostic rate was 45.9% (28/61), of which 39.2% (11/28) were de novo variants. In addition, 21 variants in 11 genes among the positive cases had not been previously reported. The diagnostic yield for definitive findings for trio analysis was 55.9% (19/34) compared to 33.3% (9/27) for singletons. The most common ultrasound abnormalities were skeletal system abnormalities 39.2% (11/28), followed by multiple system abnormalities (17.9%, 5/28) and genitourinary abnormalities (17.9%, 5/28). Conclusion: Our results support the use of WES to identify genetic etiologies of ultrasound abnormalities and improve understanding of pathogenic variants. The identification of disease-related variants provided information for subsequent genetic counseling of recurrence risk and management of subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Abstract Background Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation based on etiology analysis are critical for reducing anxiety and distress. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods A retrospective study was conducted according to cytogenetic findings of 1252 POC from spontaneous pregnancy loss over 11 years. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal ages, previous miscarriage history, normal live birth history, and different modes of conception. Results A total of 667 (53.2%) chromosomal abnormalities were observed, including 592 (47.3%) cases of numerical abnormalities, 38 (3.0%) cases of structural abnormalities, and 37 (3.0%) cases of mosaic aberrations. In women above 40 years of age, the rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in women with ≤ 29, 30–34, and 35–39 years of age (p 0.05); viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages than women with 0.05), respectively; monosomy X was more frequently detected in women with natural conception than assisted conception. Conclusion The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including maternal age, previous miscarriage, live birth history, and mode of conception. Cytogenetic analysis of POC should be recommended to women with a first miscarriage and women with normal live birth history.

Purpose: This study aims to investigate genomic imbalance in euploid products of conceptions (POCs) detected by chromosomal microarray analysis (CMA) and its association with clinical characteristics. Methods: In a retrospective cohort study where all women with singleton pregnancy losses underwent CMA detection of POCs, only patients with euploid POCs were included in the analysis. The clinical features were compared between those with and without a copy number variant (CNV). The pathogenic CNVs and the variant of uncertain significance (VOUS) were analyzed, and the common pathogenic CNVs and uniparental disomy (UPD) were investigated. Results: A total of 610 POCs were detected as chromosomal euploid, of which 176 were euploid with CNVs and 434 were euploid without CNVs. Regarding maternal age, gestational age, and history of pregnancy loss, no significant differences were found between the two groups. Furthermore, 104 pathogenic CNVs were identified in 93 POCs, and the deletion of 8p23.3 was found in 10 subjects. All CNVs greater than 3 Mb and 39.5% of CNVs ranging from 1 to 2 Mb were pathogenic, and only 3 CNVs < 1 Mb were pathogenic. UPD was detected in 12 POCs. Conclusion: Besides aneuploidy, 15.24% pregnancy loss might have an association with pathogenic genomic imbalance, and the occurrence of genomic imbalance is not related to clinical characteristics. CNVs greater than 3 Mb in pregnancy losses have a high probability to be pathogenic, and approximately 40% of CNVs ranging from 1 to 2 Mb are pathogenic. The deletion of 8p23.3 is the most common pathogenic CVN in POCs of Chinese-Han women. The clinical significance of UPD in pregnancy loss needs further study. [ABSTRACT FROM AUTHOR]

The first trimester placenta is very rarely investigated for placental vascular formation in developmental or diseased contexts. Defects in placental formation can cause heart defects in the fetus, and vice versa. Determining the causality is therefore difficult as both organs develop concurrently and express many of the same genes. Here, we performed a systematic review to determine feto-placental and coronary endothelial genes implicated in miscarriages, stillbirth and congenital heart defects (CHD) from human genome wide screening studies. 4 single cell RNAseq datasets from human first/early second trimester cardiac and placental samples were queried to generate a list of 1187 endothelial genes. This broad list was cross-referenced with genes implicated in the pregnancy disorders above. 39 papers reported feto-placental and cardiac coronary endothelial genes, totalling 612 variants. Vascular gene variants were attributed to the incidence of miscarriage (8 %), CHD (4 %) and stillbirth (3 %). The most common genes for CHD (NOTCH, DST, FBN1, JAG1, CHD4), miscarriage (COL1A1, HERC1), and stillbirth (AKAP9, MYLK), were involved in blood vessel and cardiac valve formation, with roles in endothelial differentiation, angiogenesis, extracellular matrix signaling, growth factor binding and cell adhesion. NOTCH1, AKAP12, CHD4, LAMC1 and SOS1 showed greater relative risk ratios with CHD. Many of the vascular genes identified were expressed highly in both placental and heart EC populations. Both feto-placental and cardiac vascular genes are likely to result in poor endothelial cell development and function during human pregnancy that leads to higher risk of miscarriage, congenital heart disease and stillbirth., Competing Interests: Declaration of competing interest The authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract Background Retained products of conception (POC) following uterine evacuation can lead to adverse sequelae, including hemorrhage, endometritis, intrauterine adhesions, and reoperation. Use of procedural transvaginal sonography (TVUS) in the operating room has been proposed to help decrease retained POC. Methods A retrospective review of all first trimester uterine evacuation procedures from 1/2015 to 2/2017 was performed, noting use of transabdominal ultrasonography, retained products of conception, and complications. A practice change was implemented in May 2018, in which routine intra-procedural TVUS use was initiated. A second retrospective chart review was conducted to assess for post-implementation incidence of retained POC, re-operation, and associated complications. Results Prior to intra-procedural TVUS implementation, 130 eligible procedures were performed during the specified timeframe, with 9/130 (6.9%) incidence of retained products of conception. TAUS was performed in 59/130 (45.4%) of procedures, and 4/9 (44.4%) of those with retained products. There were eight re-operative procedures in seven patients, and two patients were treated with misoprostol. Complications included hemorrhage, Asherman’s syndrome and endometritis. Following implementation, 95 first trimester procedures were performed with transvaginal sonography, with 0 (0%) cases of retained POC (p = 0.01), no incidences of re-operation (p = 0.02), and one case of Asherman’s syndrome. TVUS findings led to additional focused suction curettage in 20/95 (21.0%) of procedures. The endometrium was measured on procedure completion in 64 procedures, with a mean thickness of 5.5 mm (1–12 mm). Conclusion Implementation of routine TVUS during uterine evacuation may reduce the incidence of retained POC and associated reoperation rates. Further multi-center trials are needed to confirm this finding.

Ralph S Papas,1 William H Kutteh2,3 1Department of Obstetrics and Gynecology, Saint George Hospital - University Medical Center, Beirut, Lebanon; 2Department of Obstetrics and Gynecology, Baptist Memorial Hospital, Memphis, TN, USA; 3Recurrent Pregnancy Loss Center, Fertility Associates of Memphis, Memphis, TN, USACorrespondence: William H KuttehRecurrent Pregnancy Loss Center, Fertility Associates of Memphis, 80 Humphreys Center, Suite 307, Memphis, TN, 38139, USATel +1 901-747-2229Fax +1 901-747-4446Email wkutteh@fertilitymemphis.comAbstract: Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of “truly unexplained RPL” would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.Keywords: karyotype, products of conception, chromosomal microarray analysis, aneuploidy, pre-implantation genetic testing, recurrent pregnancy loss

Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, as well as microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination). However, a high percentage of MCC impedes a definitive diagnosis, which can be addressed by an additional pre-analytical quality control step that includes histological assessment of H&E stained slides from formalin-fixed paraffin embedded (FFPE) tissue with macro-dissection for chorionic villi to enrich fetal tissue component for single nucleotide polymorphism microarray (SNPM) analysis. To improve the diagnostic yield, an integrated workflow was devised that included MCC characterization of POC tissue, followed by OGM for MCC-negative cases or SNPM with histological assessment for MCC-positive cases. A result was obtained in 93% (29/31) of cases with a diagnostic yield of 45.1% (14/31) with the proposed workflow, compared to 9.6% (3/31) and 6.4% (2/31) with routine workflow, respectively. The integrated workflow with these technologies demonstrates the clinical utility and higher diagnostic yield in evaluating POC specimens. [ABSTRACT FROM AUTHOR]

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death. Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1.10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12.0. Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs. Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of chromosomal abnormalities detected in products of conception (POCs) between recurrent pregnancy loss and sporadic pregnancy loss. Methods: A systematic search was performed in the PubMed and Embase databases from inception to December 31, 2020. Relevant studies analysing the association between the number of pregnancy losses and the incidence of chromosomal abnormalities were included. Independent data extraction was conducted and study quality was assessed. Meta-analyses were carried out to calculate odds ratios by using fixed- or random-effects models according to statistical homogeneity. Results: A total of 8320 POCs in 19 studies were identified for the meta-analyses. The incidence of chromosomal abnormalities in sporadic pregnancy loss was significantly higher than that in recurrent pregnancy loss. In subgroup analyses, the following studies reported a high incidence of abnormal outcomes of sporadic pregnancy loss: studies with ≥ 300 samples, studies published before 2014, studies conducted in European and American countries, and studies with analyses using conventional karyotype techniques. Moreover, the incidence of chromosomal abnormalities in women with two pregnancy losses was significantly higher than that in women with three or more pregnancy losses. However, there was no difference in the distribution of abnormal types between sporadic and recurrent pregnancy loss or between two and three or more pregnancy losses. Conclusions: The prevalence of chromosomal abnormalities detected in POCs was lower in recurrent pregnancy loss than in sporadic pregnancy loss, and decreased with an increasing number of pregnancy losses. [ABSTRACT FROM AUTHOR]

Background: The management of retained products of conception (RPOC) is not well standardised due to a lack of evidence‐based guidelines. Hysteroscopic resection has been proven to be safe and is hypothesised to have lower risk than dilation and curettage, but data comparing the two directly are limited. Aim: The aim of this study is to evaluate the outcomes for hysteroscopic resection for the management of RPOC in comparison to current standard management techniques. Methods: A literature search was conducted in September 2019 using MEDLINE, Scopus, The Cochrane Library and Web of Science. The key search terms were 'hysteroscopy'/'hysteroscopic resection' and 'retained products of conception'/'RPOC'. Both prospective and retrospective studies were included. A total of 19 studies were included (n = 2314). Due to a critical risk of bias in all studies with a comparison arm, a meta‐analysis was not performed. Meta‐analysis techniques were still used to provide summary estimates for primary and secondary outcomes, including conception rate, time to conception, live birth rate, intrauterine adhesions (IUAs), surgical complications and future pregnancy complications. Results: The overall conception rate for hysteroscopic resection was 81.1% (live birth rate 87.3%) compared to 65.4% for non‐hysteroscopic management (live birth rate 93.8%). After hysteroscopic resection the overall complication rate was 1.9% and the IUA rate was 6.8%. Conclusions: Due to the poor quality and overall scarcity of comparative data, the question whether hysteroscopic resection is superior to traditional curettage for the management of RPOC remains unanswered. This review provides summary data, which will enable the design of adequately powered future studies. [ABSTRACT FROM AUTHOR]

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death.Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1.10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12.0.Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs.Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss.

Background: Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation based on etiology analysis are critical for reducing anxiety and distress. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods: A retrospective study was conducted according to cytogenetic findings of 1252 POC from spontaneous pregnancy loss over 11 years. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal ages, previous miscarriage history, normal live birth history, and different modes of conception. Results: A total of 667 (53.2%) chromosomal abnormalities were observed, including 592 (47.3%) cases of numerical abnormalities, 38 (3.0%) cases of structural abnormalities, and 37 (3.0%) cases of mosaic aberrations. In women above 40 years of age, the rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in women with ≤ 29, 30–34, and 35–39 years of age (p < 0.05). The frequency of abnormal karyotype in women with normal live birth history was 61.1%, significantly higher than 52.5% in women without normal live birth history (p < 0.05). There was no significant differences among women without, with 1–2, and ≥ 3 previous miscarriages regarding the rate of abnormal karyotype (p > 0.05); viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages than women with < 3 miscarriages. The frequency of chromosomal abnormalities was 49.0% and 55.0% in women with assisted conception and natural conception (p > 0.05), respectively; monosomy X was more frequently detected in women with natural conception than assisted conception. Conclusion: The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including maternal age, previous miscarriage, live birth history, and mode of conception. Cytogenetic analysis of POC should be recommended to women with a first miscarriage and women with normal live birth history. [ABSTRACT FROM AUTHOR]

In this retrospective study, the effect of preimplantation genetic testing for aneuploidy (PGT-A) was evaluated in women younger than 38 years with a history of one prior miscarriage and embryonic chromosomal abnormalities were detected in previous products of conception (POCs). Abnormal karyotypes were detected in POCs at our center between January 2014 and December 2017. Of the women included in this analysis, 124 continued with conventional in vitro fertilization/intracytoplasmic sperm injection cycles (non-PGT-A group) and 93 chose PGT-A cycles (PGT-A group), and the pregnancy outcomes in both groups were compared. Although the clinical pregnancy rate per embryo transfer was significantly higher in the PGT-A group (67.23% vs. 51.85%, p-adj = 0.01), no between-group differences were found in the live birth rate or miscarriage rate (45.38% vs. 40.74%, p-adj = 0.59; 16.25% vs. 14.29%, p-adj = 0.15). Women in both groups had comparative cumulative live birth rates (PGT-A vs. non-PGT-A, 58.06% vs. 53.23%, p = 0.48). The main results of this study suggest that PGT-A is not associated with an increased likelihood of a live birth or a decreased rate of miscarriage among women younger than 38 years without recurrent pregnancy loss and with a history of POCs with embryonic chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Background: Retained products of conception (POC) following uterine evacuation can lead to adverse sequelae, including hemorrhage, endometritis, intrauterine adhesions, and reoperation. Use of procedural transvaginal sonography (TVUS) in the operating room has been proposed to help decrease retained POC.Methods: A retrospective review of all first trimester uterine evacuation procedures from 1/2015 to 2/2017 was performed, noting use of transabdominal ultrasonography, retained products of conception, and complications. A practice change was implemented in May 2018, in which routine intra-procedural TVUS use was initiated. A second retrospective chart review was conducted to assess for post-implementation incidence of retained POC, re-operation, and associated complications.Results: Prior to intra-procedural TVUS implementation, 130 eligible procedures were performed during the specified timeframe, with 9/130 (6.9%) incidence of retained products of conception. TAUS was performed in 59/130 (45.4%) of procedures, and 4/9 (44.4%) of those with retained products. There were eight re-operative procedures in seven patients, and two patients were treated with misoprostol. Complications included hemorrhage, Asherman's syndrome and endometritis. Following implementation, 95 first trimester procedures were performed with transvaginal sonography, with 0 (0%) cases of retained POC (p = 0.01), no incidences of re-operation (p = 0.02), and one case of Asherman's syndrome. TVUS findings led to additional focused suction curettage in 20/95 (21.0%) of procedures. The endometrium was measured on procedure completion in 64 procedures, with a mean thickness of 5.5 mm (1-12 mm).Conclusion: Implementation of routine TVUS during uterine evacuation may reduce the incidence of retained POC and associated reoperation rates. Further multi-center trials are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Genetic testing of products of conception (POC) has been proposed as a tool to be used in the evaluation of patients with recurrent pregnancy loss (RPL). Following a complete RPL evaluation, POC results may reveal an aneuploidy and provide an explanation for the miscarriage in more than 55% of cases. When the cytogenetic result of the pregnancy loss reveals a euploid pregnancy, management should be directed towards the identification of treatable abnormalities. Furthermore, the results of POC testing might better define a subgroup of patients with unexplained RPL who may benefit from expectant management versus preimplantation genetics (aneuploid unexplained RPL) or investigational therapy (euploid unexplained RPL). [ABSTRACT FROM AUTHOR]

• Even in samples with MCC, CNV-seq can still detect abnormalities in some samples that can explain the cause of miscarriage. • Initial CNV-seq followed by QF-PCR if needed was an efficient and cost-effective strategy for the genetic analysis of POCs. Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. We propose an initial CNV-seq followed by QF-PCR if needed—an efficient and cost-effective strategy for the genetic analysis of POCs. [ABSTRACT FROM AUTHOR]

Abstract Background Fetal chromosomal abnormalities was the most frequent cause of miscarriage, and the traditional testing method G-banded karyotyping has limitations. Then high-throughput ligation-dependent probe amplification (HLPA) and single nucleotide polymorphism array (SNP-array) were introduced for genetic analysis on products of conception (POC). Methods HLPA and SNP-array analysis were combined. POC samples were initially tested using HLPA, followed by SNP-array analysis on samples that were found to be normal by HLPA. Results Of the 326 POC samples tested, the overall abnormality rate was 54.6% (178/326), including 44.8% (146/326) chromosomal abnormalities identified by HLPA and 9.8% (32/326) additional chromosomal abnormalities further detected by SNP-array. Conclusions The combination of HLPA and SNP-array analysis is an efficient and cost-effective strategy for genetic analysis of POC.

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

Objective: Embryonic 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. Methods: We 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. Results: 631 (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). Conclusion: Advanced 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. [ABSTRACT FROM AUTHOR]

Objective: To explore the use of a new molecular work-up based on the stepwise use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array) in chorionic villi obtained by chorionic villi sampling (CVS) offered to women experiencing an early pregnancy loss.Methods: During a 3-year period (January 2016–December 2018), CVS was offered to women experiencing an early pregnancy loss before the evacuation of the products of conception (POC) to retrieve chorionic villi, irrespective of the number of previous losses. A new molecular work-up was prospectively assayed encompassing a first QF-PCR round (with the 21, 18, 13, 7, X, and Y chromosomes), a second QF-PCR round (with the 15, 16, and 22 chromosomes), and a high resolution SNP-array in those cases with normal QF-PCR results. A control group in which POC were collected after surgical uterine evacuation was used to be compared with the intervention group.Results: Around 459 women were enrolled in the intervention group (CVS) and 185 in the control group (POC after uterine evacuation). The QF-PCR testing success rates were significantly higher in the intervention group (98.5%: 452/459) as compared to the control group (74%: 109/147; p < 0.001), while the chromosomal anomaly rate at the two QF-PCR rounds was similar between the two groups: 52% (234/452) in the intervention and 42% (46/109) in the control group (p = 0.073). The SNP-array was performed in 202 QF-PCR normal samples of the intervention group and revealed 67 (33%) atypical chromosomal anomalies (>10 Mb), 5 (2.5%) submicroscopic pathogenic copy number variants, and 2 (1%) variant of uncertain significance (VOUS).Conclusion: Eighty-two percent of women experiencing an early pregnancy loss opted for a CVS. The testing success rates were higher in the intervention group (CVS; 98%) as compared to the control group (POC; 74%). The overall yields were 52% by QF-PCR (including three complete hydatiform moles), and 16% by SNP-array, including 15% atypical chromosomal anomalies and 1.1% submicroscopic pathogenic copy number variants.

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied.Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer.Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi.Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.

Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, as well as microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination). However, a high percentage of MCC impedes a definitive diagnosis, which can be addressed by an additional pre-analytical quality control step that includes histological assessment of H&E stained slides from formalin-fixed paraffin embedded (FFPE) tissue with macro-dissection for chorionic villi to enrich fetal tissue component for single nucleotide polymorphism microarray (SNPM) analysis. To improve the diagnostic yield, an integrated workflow was devised that included MCC characterization of POC tissue, followed by OGM for MCC-negative cases or SNPM with histological assessment for MCC-positive cases. A result was obtained in 93% (29/31) of cases with a diagnostic yield of 45.1% (14/31) with the proposed workflow, compared to 9.6% (3/31) and 6.4% (2/31) with routine workflow, respectively. The integrated workflow with these technologies demonstrates the clinical utility and higher diagnostic yield in evaluating POC specimens.

Objective: To explore the use of a new molecular work-up based on the stepwise use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array) in chorionic villi obtained by chorionic villi sampling (CVS) offered to women experiencing an early pregnancy loss. Methods: During a 3-year period (January 2016–December 2018), CVS was offered to women experiencing an early pregnancy loss before the evacuation of the products of conception (POC) to retrieve chorionic villi, irrespective of the number of previous losses. A new molecular work-up was prospectively assayed encompassing a first QF-PCR round (with the 21, 18, 13, 7, X, and Y chromosomes), a second QF-PCR round (with the 15, 16, and 22 chromosomes), and a high resolution SNP-array in those cases with normal QF-PCR results. A control group in which POC were collected after surgical uterine evacuation was used to be compared with the intervention group. Results: Around 459 women were enrolled in the intervention group (CVS) and 185 in the control group (POC after uterine evacuation). The QF-PCR testing success rates were significantly higher in the intervention group (98.5%: 452/459) as compared to the control group (74%: 109/147; p < 0.001), while the chromosomal anomaly rate at the two QF-PCR rounds was similar between the two groups: 52% (234/452) in the intervention and 42% (46/109) in the control group (p = 0.073). The SNP-array was performed in 202 QF-PCR normal samples of the intervention group and revealed 67 (33%) atypical chromosomal anomalies (>10 Mb), 5 (2.5%) submicroscopic pathogenic copy number variants, and 2 (1%) variant of uncertain significance (VOUS). Conclusion: Eighty-two percent of women experiencing an early pregnancy loss opted for a CVS. The testing success rates were higher in the intervention group (CVS; 98%) as compared to the control group (POC; 74%). The overall yields were 52% by QF-PCR (including three complete hydatiform moles), and 16% by SNP-array, including 15% atypical chromosomal anomalies and 1.1% submicroscopic pathogenic copy number variants. [ABSTRACT FROM AUTHOR]

Purpose: Chromosomal 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. Methods: The 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. Results: Excluding 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. Conclusions: Chromosome analysis using NGS not only obtains comparable results to conventional G‐banding, but also can analyze POC more accurately and efficiently. [ABSTRACT FROM AUTHOR]

Background  A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. Results  This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. Conclusions  A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied. Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer. Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother's age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi. Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy. [ABSTRACT FROM AUTHOR]

Abortion providers’ approaches to patient-centred pregnancy tissue viewing (PCV) – when a patient requests to see their products of conception – is understudied in abortion care. This mixed-method study aimed to identify: (1) if, when, and how PCV is facilitated at US independent abortion clinics; (2) how staff are trained to offer viewing; and (3) provider experiences facilitating PCV. We surveyed administrators from 22 independent abortion clinics affiliated with the Abortion Care Network about their PCV practices and then completed in-depth semi-structured interviews with 25 providers to better understand their experiences facilitating PCV. Results indicate that most of the clinics that provide PCV do so by patient request. A variety of providers facilitate viewing, including counsellors, educators, physicians, nurses, and medical assistants. Timing, viewing location, and staff training vary by facility. Benefits of and barriers to PCV emerged through three themes: (1) patient-centred care; (2) misinformation about fetal tissue; and (3) personal navigations as providers. Providers and administrators report PCV aligns with their patient-centred clinic missions and offers patients opportunities for choice, closure, and access to information. Yet, anti-abortion misinformation about fetal tissue impacts the ways providers must navigate complex conversations about PCV professionally and personally. Clinic resources and concern about adverse patient reactions to identifiable fetal parts present barriers to offering viewing. Understanding providers’ experiences and approaches to PCV is an important first step to developing quality practices that can be shared across clinics. The findings of this study support the need for more research and training on PCV in abortion care.

Abstract Background Chromosome translocations are rare but frequently associated with infertility. The objective of this study is to investigate the feasibility of using chromosomal microarray analysis (CMA) on products of conception (POC) samples as an indicator of parental balanced translocation. From January 2011 to December 2016, CMA using Affymetrix Cytoscan™750K array was performed on 1294 POC samples in our hospital. Karyotyping and fluorescence in situ hybridization (FISH) using parental blood samples were performed to validate the origin of subchromosomal copy number variations (CNVs). Results In the 1294 cases of POCs, we detected CNVs of terminal duplication and deletion that imply unbalanced translocation derivatives in 16 cases, and accurate diagnosis with the parental study was made in all the cases by karyotyping and/or FISH. In 10/16 (62.5%) of these cases, CNVs were inherited from one carrier parent of balanced translocation (Cases 1 to 10), while 6/16 (37.5%) cases occurred de novo (Cases 11 to 16). Conclusion This study clearly illustrated the importance of the utilization of CMA on POC, followed by parental karyotyping and FISH to better characterize CNVs. This approach is especially useful for couples in whom one partner carries a cryptic/submicroscopic balanced translocation but has an apparently normal karyotype.

Background: Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. Methods: A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. Results: In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. Conclusions: Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Abortion providers' approaches to patient-centred pregnancy tissue viewing (PCV) – when a patient requests to see their products of conception – is understudied in abortion care. This mixed-method study aimed to identify: (1) if, when, and how PCV is facilitated at US independent abortion clinics; (2) how staff are trained to offer viewing; and (3) provider experiences facilitating PCV. We surveyed administrators from 22 independent abortion clinics affiliated with the Abortion Care Network about their PCV practices and then completed in-depth semi-structured interviews with 25 providers to better understand their experiences facilitating PCV. Results indicate that most of the clinics that provide PCV do so by patient request. A variety of providers facilitate viewing, including counsellors, educators, physicians, nurses, and medical assistants. Timing, viewing location, and staff training vary by facility. Benefits of and barriers to PCV emerged through three themes: (1) patient-centred care; (2) misinformation about fetal tissue; and (3) personal navigations as providers. Providers and administrators report PCV aligns with their patient-centred clinic missions and offers patients opportunities for choice, closure, and access to information. Yet, anti-abortion misinformation about fetal tissue impacts the ways providers must navigate complex conversations about PCV professionally and personally. Clinic resources and concern about adverse patient reactions to identifiable fetal parts present barriers to offering viewing. Understanding providers' experiences and approaches to PCV is an important first step to developing quality practices that can be shared across clinics. The findings of this study support the need for more research and training on PCV in abortion care. [ABSTRACT FROM AUTHOR]

Abstract Background Traditional testing of miscarriage products involved culture of tissue followed by G-banded chromosome analysis; this approach has a high failure rate, is labour intensive and has a resolution of around 10 Mb. G-banded chromosome analysis has been replaced by molecular techniques in some laboratories; we previously introduced a QF-PCR/MLPA testing strategy in 2007. To improve diagnostic yield and efficiency we have now updated our testing strategy to a more comprehensive QF-PCR assay followed by array CGH. Here we describe the results from the last 5 years of service. Methods Fetal tissue samples and products of conception were tested using QF-PCR which will detect aneuploidy for chromosomes 13, 14, 15, 16, 18, 21, 22, X and Y. Samples that were normal were then tested by aCGH and all imbalance >1Mb and fully penetrant clinically significant imbalance

Aim: Chromosome analysis of prenatal samples and products of conception (POC) has conventionally been done by karyotyping (KT). Shortcomings of KT like high turnaround time and culture failure led to technology innovations, such as the bacterial artificial chromosomes (BAC)s‐on‐Beads (BoBs)‐based tests, Prenatal BoBs (prenatal samples) and KaryoLite BoBs (POC samples). In the present study, we validated and evaluated the utility of each test on prenatal, POC and blood samples. Methods: Study A (n = 305; 259 prenatal + 46 blood/POC) and Study B (n = 176; 146 POC/chorionic vill + 30 blood/amniotic fluid) samples were analyzed using Prenatal and KaryoLite BoBs kits, respectively. KT, array‐based Comparative Genomic Hybridization (arrayCGH) and fluorescence in situ hybridization (FISH) were used for comparison of results. Ability of KaryoLite BoBs to identify ring chromosomes was tested. Results: Prenatal BoBs had zero test failure rate and results of all samples were concordant with KT results. Totally four microdeletions were identified by Prenatal BoBs but not by KT. In Study B, all but two POC samples (one triploid and one tetraploid) were concordant with KT and arrayCGH. Partial chromosomal imbalance detection rate was ~64% and KaryoLite BoBs indicated the presence of a ring chromosome in all four cases. The failure rate of KaryoLite BoBs was 3%. Conclusion: We conclude that Prenatal BoBs (common aneuploidies and nine microdeletions) together with KT constitutes more comprehensive prenatal testing compared to FISH and KT. KaryoLite BoBs for aneuploidies of all chromosomes is highly successful in POC analysis and the ability to indicate presence of ring chromosomes improves its clinical sensitivity. Both tests are robust and could also be used for different specimens. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore the cause of miscarriage, providing risk assessment to guide the next pregnancy.Methods: Four hundred eighty-four products-of-conception (POC) samples were analyzed by single nucleotide polymorphism (SNP) array, and peripheral blood samples of couples were collected for karyotyping or fluorescence in situ hybridization (FISH) analysis.Results: Four hundred sixty-eight of the 484 (96.7%) fresh POC samples were successfully analyzed using SNP-array. The rate of clinically significant chromosomal abnormalities were 58.3% (274/468), in which rates of aneuploidy, polyploidy, partial aneuploidy, uniparental isodisomy (isoUPD), and pathogenic microdeletion/microduplication were 43.4% (203/468), 8.8% (41/468), 3.6% (17/468), 1.9% (9/48), and 0.9% (4/468), respectively. The percentage of embryonic chromosomal abnormalities significantly increased with maternal age of patients older than 35 years old. Among 468 couples, 12 major chromosomal rearrangements were detected by G-banding, including nine reciprocal translocations, two Robertsonian translocations, and one superfemale.Conclusions: Chromosome abnormality is the main causes of early miscarriage, and aneuploidies are the most common type of chromosomal abnormalities. Application of SNP array and karyotyping in early miscarriage can provide more genetic information about miscarriage, providing risk assessment to guide the next pregnancy. [ABSTRACT FROM AUTHOR]