OBJECTIVE: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb?
METHODS: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed.
RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage.
CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.

Infertility affects ∼15% of couples globally and half of cases are related to genetic disorders. Despite growing data and unprecedented improvements in high-throughput sequencing technologies, accumulated fertility-related issues concerning genetic diagnosis and potential treatment are urgent to be solved. However, there is a lack of comprehensive platforms that characterise various infertility-related records to provide research applications for exploring infertility in-depth and genetic counselling of infertility couple. To solve this problem, we provide IDDB Xtra by further integrating phenotypic manifestations, genomic datasets, epigenetics, modulators in collaboration with numerous interactive tools into our previous infertility database, IDDB. IDDB Xtra houses manually-curated 2369 genes of human and nine model organisms, 273 chromosomal abnormalities, 884 phenotypes, 60 genomic datasets, 464 epigenetic records, 1144 modulators relevant to infertility diagnosis and treatment. Additionally, IDDB Xtra incorporated customized graphical applications for researchers and clinicians to decipher in-depth disease mechanisms from the perspectives of developmental atlas, mutation effects, and clinical manifestations. Users can browse genes across developmental stages of human and mouse, filter candidate genes, mine potential variants and retrieve infertility biomedical network in an intuitive web interface. In summary, IDDB Xtra not only captures valuable research and data, but also provides useful applications to facilitate the genetic counselling and drug discovery of infertility. IDDB Xtra is freely available at https://mdl.shsmu.edu.cn/IDDB/and http://www.allostery.net/IDDB.

OBJECTIVE: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies.
METHODS: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth.
RESULTS: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period.
CONCLUSIONS: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors.

Chromosome abnormalities have certain impacts on the disease mechanism in patients with gastrointestinal Behçet\'s disease-like syndrome (GIBS) and myelodysplastic syndrome (MDS). This study aimed to investigate the clinical characteristics and long-term outcomes of patients with GIBS-MDS and the potential role(s) played by trisomy 8 from a gastroenterology perspective.
A retrospective cohort of 18 patients with GIBS-MDS in China was analysed, and 97 reported cases with individual data from the literature were reviewed in total. The primary outcome was overall survival (OS). Cox regression analysis was performed on the influencing factors of OS.
Of the 115 patients included in the study, with a majority from East Asia (92.2%), there were 66 (57.4%) female patients and 76 (66.7%) patients with GIBS onset before MDS, and the ileocecum (45, 48.9%) was the most common location of gastrointestinal (GI) involvement. In addition, 91 (79.1%) patients had the chromosome abnormality of trisomy 8, and 32 (33.7%) patients died. Cox regression analysis demonstrated that a region of origin of East Asia (HR [hazard ratio]: 0.36, 95% CI [confidence interval]: 0.14 to 0.96, p = 0.041) rather than trisomy 8 (HR: 0.71, 95% CI: 0.30 to 1.68, p = 0.428) was identified as an independent protective factor for survival.
Compared to patients without trisomy 8, GIBS-MDS patients with trisomy 8 showed unique clinical characteristics but an unfavorable OS. The region of origin rather than trisomy 8 syndrome played a more important role in the prognosis of GIBS-MDS patients.

Precise segmentation of chromosome in the real image achieved by a microscope is significant for karyotype analysis. The segmentation of image is usually achieved by a pixel-level classification task, which considers different instances as different classes. Many instance segmentation methods predict the Intersection over Union (IoU) through the head branch to correct the classification confidence. Their effectiveness is based on the correlation between branch tasks. However, none of these methods consider the correlation between input and output in branch tasks. Herein, we propose a chromosome instance segmentation network based on regression correction. First, we adopt two head branches to predict two confidences that are more related to localization accuracy and segmentation accuracy to correct the classification confidence, which reduce the omission of predicted boxes in NMS. Furthermore, a NMS algorithm is further designed to screen the target segmentation mask with the IoU of the overlapping instance, which reduces the omission of predicted masks in NMS. Moreover, given the fact that the original IoU loss function is not sensitive to the wrong segmentation, K-IoU loss function is defined to strengthen the penalty of the wrong segmentation, which rationalizes the loss of mis-segmentation and effectively prevents wrong segmentation. Finally, an ablation experiment is designed to evaluate the effectiveness of the chromosome instance segmentation network based on regression correction, which shows that our proposed method can effectively enhance the performance in automatic chromosome segmentation tasks and provide a guarantee for end-to-end karyotype analysis.

OBJECTIVE: To investigate the incidence of the single umbilical artery (SUA) malformation and postpartum outcomes in a retrospective analysis of 781 fetuses.
METHODS: This retrospective analysis included 781 pregnant women carrying singleton fetuses diagnosed with SUA at Gansu Provincial Maternal and Child-care Hospital between 2013 and 2019. Detailed data on maternal and fetal characteristics and postpartum outcomes were obtained.
RESULTS: In total, 624 (79.9 %) fetuses were diagnosed with isolated SUA and 157 (20.1 %) fetuses had SUA together with other structural and/or chromosome abnormalities. The highest incidence of malformation was found in the urinary system, followed by the cardiovascular system and digestive system. The incidence of SUA was 59.1 % on the right side and 40.9 % on the left side. Fetuses with SUA and other abnormalities tended to have a lower mean birth weight (3061 g vs 3201 g, p < 0.01), but no difference in the rate of preterm delivery was noted.
CONCLUSIONS: After a diagnosis of SUA, structural observation of the fetus is required. The urinary, cardiovascular and digestive systems should be the focus of observation. If relevant malformations are found, then genetic testing must be performed. With isolated SUA, dynamic monitoring of biological indicators is recommended for lower birth weight, but genetic testing is not recommended.

Chromosome 1p36 deletion is the most common subtelomeric deletion syndrome characterized by variable features including unique facial appearance, intellectual disability, developmental delay, cardiac defects, seizures and hypotonia. Here, we report a patient with developmental delay, dilated cardiomyopathy, seizures, hirsutism and cutis laxa who was diagnosed with 1p36 deletion syndrome by chromosome microarray analysis. This patient is the first reported case of 1p36 deletion syndrome associated with cutis laxa and our results suggest that the 1p36 region contains one or more genes relevant to cutis laxa. This case also indicates the importance of considering chromosome abnormalities (microdeletion/microduplication syndromes) in patients presenting skin disorders combined with unexplained developmental delay, intellectual disability or multiple congenital abnormalities.

Few studies have examined the value of cytogenetic studies with flow cytometry (FC) in lymph node/extranodal tissue biopsies with suspected lymphoma. To evaluate this, G-banded karyotyping and/or fluorescence in situ hybridization (FISH) with FC immunophenotyping were performed on 185 lymph node or extranodal tissue biopsy specimens with suspected lymphoma. Complete cytogenetic analysis of lymph node/extranodal tissue was successful in 174 cases (94.1%) and 57.5% demonstrated chromosomal abnormalities. In 116 malignant lymphoma cases, 83.8% showed abnormalities. In 74 B cell lymphomas (B-NHL), abnormalities were more frequent in lymph node/extranodal tissues than in bone marrow by conventional cytogenetics (CC, 97.2 vs 26.1%), FISH (70.6 vs 17.6%), and FC (98.6 vs 28.4%). Three B-NHL diagnoses were confirmed by re-biopsy of lymph nodes due to the presence of abnormalities in the first biopsy, but no evidence of malignancy in pathological, FC, or IgH/TCR gene rearrangement analyses. In 29 T cell lymphomas (T-NHL), abnormalities were more frequent in lymph nodes than in bone marrow by CC (67.9 vs 21.4%) and FC (75.9 vs 27.6%) analyses. As expected, in 13 Hodgkin lymphoma cases, abnormalities were more frequent in lymph nodes than bone marrow by CC (41.7 vs 16.7%) and FC (30.8 vs 7.7%) analyses. In 56 reactive lymphoid hyperplasias (RLH), 7.1% had conventional clonal cytogenetic abnormalities. Two of these patients died of disease progression and two had their pathological diagnosis revised after the second review. These findings indicate that cytogenetic analysis combined with FC in lymph node/extranodal tissue biopsies can provide critical information in the auxiliary diagnosis of lymphoma.

From November 1988 to December 1994, a total of 567 female volunteers were enrolled in Norplant implant studies at the National Taiwan University Hospital. After a median follow-up of 29 months, only 3 of the 529 available cases became pregnant (a cumulative rate of 1.2 pregnancies per 100 users over 5 years). Chromosome analysis of 2 of the 3 abortuses revealed 46,XX/46,XX,inv(3) and 46,XX. Menstrual problems were the most common adverse effects and were also the main reason for discontinuation (65%, 108/166). The continuation rate was 90%, 78%, 70%, 61%, and 42% at the end of 1, 2, 3, 4, and 5 years after insertion, respectively. In the 21 patients who wished to become pregnant, fertility recurred soon after removal of the Norplant implants. The data suggested that the Norplant implants system is a highly effective, safe, and long-acting method of reversible contraception. It would be worthwhile to introduce this contraceptive system to Taiwan\'s family planning program.
Between November 1988 and December 1994 health providers at the National Taiwan University Hospital enrolled 567 women aged 17-47 in the Norplant implant studies that aimed to evaluate the benefits and side effects of Norplant as another contraceptive method choice. They followed the women for a median of 29 months. 38 cases were lost to follow-up. The 5-year contraceptive effectiveness rate was 98.8%. The 3 pregnancies (2 intrauterine and 1 ectopic) occurred during the 24th, 45th, and 47th months of use. None of the women who became pregnant weighed more than 70 kg. Two of the aborted fetuses had chromosomal abnormalities (46,XX/46,XX,inv(3) and 46,XX). 29.9% of the Norplant users had menstrual problems. Even though irregular bleeding occurred to 19.7% of Norplant users, hemoglobin levels increased after Norplant use (p 0.05). Triglycerides and total cholesterol levels decreased (p 0.05). None of the women developed thromboembolism. The Norplant continuation rate was 89.7% at 1 year, 78% at 2 years, 70% at 3 years, 61% at 4 years, and 42.4% at 5 years. The leading reason for implant removal was menstrual problems (108). The implants were removed during one sitting without x-ray or ultrasound identification in all 166 women who stopped using Norplant before 5 years and the 16 women who stopped using it at the end of 5 years. 78% of women who discontinued Norplant to become pregnant were pregnant within one year following removal. All their infants were normal. These findings suggest that Norplant is a safe, effective, and acceptable contraceptive method and that the family planning program should introduce Norplant to its contraceptive mix.

Chromosome breakage can lead to teratology and neoplasia, although mutagenicity is not identical with carcinogenicity. The human chorionic villus micronucleus (CVMN) test was first developed in 1987 to study the mutagenicity of smoking, drinking, and contraceptives on offspring. 507 couples were studied, and human chorionic villi were taken from abortion material of women aged 18-43 with gestation of 10 weeks. None of these women drank; however, among their husbands there were 172 smokers (2-40 cigarettes/day for 2-20 years), 15 who drank (.5-3 liters of liquor/month for 2-20 years), 107 smoked and drank (1-40 cigarettes/day for 2-10 years and .5-3 liters of liquor/month for 2-15 years), and 115 nondrinking and nonsmoking controls. Micronuclei (MN) were scored according to Countryman\'s standard, and 2000 interphase was observed in each subject of CVMN frequency. 1,014,000 interphase cells were scored. There was no correlation between CVMN frequency and maternal age. The difference of the correlation coefficient between CVMN frequency and pregnancy was not statistically significant. 105 women had aborted before, 9 had had spontaneous abortion, and 113 had neither. There were no statistical differences between these women and no correlation with CVMN frequency. The gestation ranged from 32 days to 79 days; again, no correlation was found. The mean frequency of CVMN was significantly higher in those with smoking husbands than in nonsmokers and nondrinkers. The CVMN frequency of women with drinking husbands was also high but without statistical significance. The group with husbands who both smoked and drank had the highest CVMN frequency, but this did not differ significantly from controls. The mutagens and carcinogens of cigarettes linger in the smoke. In addition to effect on the function and MN frequency in the sperm of smokers, the ova and embryo of passive smokers may be affected as damage in the DNA and spindle apparatus of chorionic villi increases the frequency of MN.