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Study Question: Compared to the 'single biopsy + single vitrification' approach, do 'double biopsy + double vitrification' or 'single biopsy + double vitrification' arrangements compromise subsequent clinical outcomes following euploidy blastocyst transfer?, Summary Answer: Both 'double biopsy + double vitrification' and 'single biopsy + double vitrification' led to reduced live birth/ongoing pregnancy rates and clinical pregnancy rates., What Is Known Already?: It is not uncommon to receive inconclusive results following blastocyst biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Often these blastocysts are warmed for re-test after a second biopsy, experiencing 'double biopsy + double vitrification'. Furthermore, to achieve better workflow, IVF laboratories may choose to routinely vitrify all blastocysts and schedule biopsy at a preferred timing, involving 'single biopsy + double vitrification'. However, in the current literature, there is a lack of systematic evaluation of both arrangements regarding their potential clinical risks in reference to the most common 'single biopsy + single vitrification' approach., Study Design, Size, Duration: A systematic review and meta-analysis were performed, with the protocol registered in PROSPERO (CRD42023469143). A search in PUBMED, EMBASE, and the Cochrane Library for relevant studies was carried out on 30 August 2023, using the keywords 'biopsy' and 'vitrification' and associated variations respectively. Only studies involving frozen transfers of PGT-A tested euploid blastocysts were included, with those involving PGT-M or PGT-SR excluded., Participants/materials, Setting, Methods: Study groups included blastocysts having undergone 'double biopsy + double vitrification' or 'single biopsy + double vitrification', with a 'single biopsy + single vitrification' group used as control. The primary outcome was clinical pregnancy, while secondary outcomes included live birth/ongoing pregnancy, miscarriage, and post-warming survival rates. Random effects meta-analysis was performed with risk ratios (RR) and 95% CIs were used to present outcome comparisons., Main Results and the Role of Chance: A total of 607 records were identified through the initial search and nine studies (six full articles and three abstracts) were eventually included. Compared to 'single biopsy + single vitrification', 'double biopsy + double vitrification' was associated with reduced clinical pregnancy rates (six studies, n = 18 754; RR = 0.80, 95% CI = 0.71-0.89; I2 = 0%) and live birth/ongoing pregnancy rates (seven studies, n = 20 964; RR = 0.72, 95% CI = 0.63-0.82; I2 = 0%). However, no significant changes were seen in miscarriage rates (seven studies, n = 22 332; RR = 1.40, 95% CI = 0.92-2.11; I2 = 53%) and post-warming survival rates (three studies, n = 13 562; RR = 1.00, 95% CI = 0.99-1.01; I2 = 0%) following 'double biopsy + double vitrification'. Furthermore, 'single biopsy + double vitrification' was also linked with decreased clinical pregnancy rates (six studies, n = 13 284; RR = 0.84, 95% CI = 0.76-0.92; I2 = 39%) and live birth/ongoing pregnancy rates (seven studies, n = 16 800; RR = 0.79, 95% CI = 0.69-0.91; I2 = 70%), and increased miscarriage rates (five studies, n = 15 781; RR = 1.48, 95% CI = 1.31-1.67; I2 = 0%), but post-warming survival rates were not affected (three studies, n = 12 452; RR = 0.99, 95% CI = 0.97-1.01; I2 = 71%) by 'single biopsy + double vitrification'., Limitations, Reasons for Caution: All studies included in this meta-analysis were retrospective with varying levels of heterogeneity for different outcomes. Not all studies had accounted for potential confounding factors. Only one study reported neonatal outcomes., Wider Implications of the Findings: Our data indicated adverse impacts of 'double biopsy + double vitrification' and 'single biopsy + double vitrification' on clinical outcomes following euploid blastocyst transfers. Patients should be carefully consulted about the risks when offered such approaches. The biopsy process should be carried out as carefully and competently as possible to minimize an inconclusive diagnosis., Study Funding/competing Interest(s): R.W. is supported by a National Health and Medical Research Council Emerging Leadership Investigator Grant (2009767). There is no other external funding to report. All authors report no conflict of interest., Registration Number: CRD42023469143., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: To explore the pregnancy outcomes of women who couldn't obtain effective results from noninvasive prenatal testing (NIPT) and examine the factors leading to test failure., Methods: From April 2017 to December 2019, 120,041 pregnant women enrolled for voluntary NIPT. The case group comprised of 274 (274/120,041) women who failed to obtain effective NIPT results, and the control group ( n = 540) was from the same population who obtained effective NIPT results and matched by age at a 1:2 ratio. Abnormal pregnancy rates between the two groups were analyzed using Chi-square analysis. NIPT failure risk factors were analyzed using logistic regression analysis., Results: Logistic regression analysis showed that increased maternal age (OR = 0.988; 95% CI = 0.982-0.994), increased pregnancy age (OR = 0.989; 95%CI = 0.988-0.991), and decreased cell-free fetal DNA concentration (OR = 1.050; 95%CI = 1.043-1.058) were independent risk factors for NIPT failure. Fifteen cases showed fetus loss in cases of NIPT failure. There was a significant difference in abnormal pregnancy rate between the NIPT success and failure groups (χ2 = 50.943, P < 0.05)., Expert Commentary: The specific interventions, guidance, and precautions are needed for pregnant women who have no effective NIPT results.

Introduction: To evaluate the effect of repeating test failures using an automated, non-sequencing based non-invasive prenatal testing test on a general-risk population in Finland., Material and Methods: A total of 545 samples from women who represent the average-risk population in Oulu, Finland were analyzed with Vanadis ® non-invasive prenatal testing. Repeat testing of test failures was performed using a second sample. Results before and after repeat testing were compared with the reference outcome, as determined by clinical examination of neonates., Results: There were eight test failures after first-pass analysis, representing 1.5% of samples (95% CI 0.6%-2.9%). Seven out of eight failures could be resolved by analysis of a second sample, thereby reducing the test failure rate from 1.5% to 0.2% (95% CI 0.0%-1.0%)., Conclusions: Repeating test failures with a second plasma sample could significantly reduce the effective failure rate, thereby providing a way to effectively minimize test failures and further improving clinical utility and test performance., (© 2021 Vanadis Diagnostics AB. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Our aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS)., Methods: A retrospective analysis was performed on pregnant women who had failed NIPS tests., Results: Among the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively., Conclusion: Prenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liu, Liu, Bai, Jing, Xia, Deng, Liu, Cheng, Wei, Xing, Luo, Zhou and Zhu.)

Objective: The constant deterioration of the physical fitness of college students has been a popular topic in China, thus this research analyzes the potential health risk of inadequate physical activity among college students. Participants/methods: During the national student fitness test (NSFT) in 2012, 1500 students from Tsinghua University were recruited and asked to complete the international physical activity questionnaire. Finally, 1414 (94.3%) students completed the study. Results/conclusions: Compared with those students who actively participate in exercise, the risk of obesity in college students lacking exercise was 1.25 times higher. Likewise, the probability of failure in the grip strength test and the standing long jump was also higher, with increases of 2.39 fold and 1.39 fold, respectively. Moreover, the total score of physical fitness test was the same. Consequently, this study suggests that college students should exercise regularly to increase their physical fitness.

Background: Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA (cffDNA) has rapidly been applied into clinic. However, the reliability of this method largely depends on the concentration of cffDNA in the maternal plasma. The chance of test failure results or false negative results would increase when cffDNA fraction is low. In this study, we set out to develop a method to enrich the cffDNA for NIPS based on the size difference between cell-free DNA (cfDNA) of fetal origin and maternal origin, and to evaluate whether the new NIPS method can improve the test quality., Methods: We utilized 10,000 previous NIPS data to optimize a size-selection strategy for enrichment. Then, we retrospectively performed our new NIPS method with cffDNA enrichment on the 1415 NIPS samples, including 1404 routine cases and 11 false negative cases, and compared the results to the original NIPS results., Results: The 10,000 NIPS data revealed the fetal fraction in short cfDNA fragments (< 160 bp) is significantly higher. By using our new NIPS strategy on the 1404 routine cases, the fetal fraction increased from 11.3 ± 4.2 to 22.6 ± 6.6%, and the new method performed a significant decrease of test-failure rate (0.1% vs 0.7%, P < 0.01). Moreover, in 45.5% (5/11) of the false negative cases, fetal trisomies were successfully detected by our new NIPS method., Conclusions: We developed an effective method to enrich cffDNA for NIPS, which shows an increased success rate and a reduced chance of false negative comparing to the ordinary NIPS method.

ABSTRACTObjectives:Bedside tests of attention and organized thinking were performed in patients with cognitive impairment or dementia but without delirium, to provide estimates of false positive rates for detecting delirium superimposed on dementia (DSD)., Design and Setting: This cross-sectional study was conducted in outpatients and institutionalized patients without delirium representing a wide spectrum of severity of cognitive impairments., Participants: Patients with dementia or a cognitive disorder according to DSM IV criteria, after exclusion of (suspected) delirium according to DSM IV criteria., Measurements: Tests for inattention and disorganized thinking from the CAM-ICU were assessed., Results: The sample included 163 patients (mean age 83 years (SD 6; 64% women)), with Alzheimer's disease as most prevalent (45%) diagnosis and a mean MMSE-score of 16.8 (SD 7.5). False positive rates of the test of attention varied from 0.04 in patients with normal to borderline cognitive function to 0.8 in those with severe dementia. The false positive rate of the test of disorganized thinking was zero in the normal to borderline group, increasing to 0.67 in patients with severe dementia. When combining test results false positive rates decreased to 0.03 in patients with MMSE scores above 9., Conclusion: Use of simple bedside tests of attention and organized thinking for the clinical diagnosis of DSD will result in high rates of false positive observations if used regardless of the severity of dementia. However, if test results are combined they may be useful to exclude DSD in patients with minimal to moderate degrees of dementia, but not in the severe group.

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed., (© 2018 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.)