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Infertility has become the third largest human disease in the world. With the wide application of in vitro fertilization (IVF), millions of people solve the problem of infertility by IVF every year. However, many patients experience recurrent IVF failures, displaying abnormal reproductive phenotypes (such as gamete development abnormalities, fertilization disorders, and early embryonic discontinuation). With the development of gene sequencing technology and the deepening of reproductive genetics research, more and more pathogenic genetic factors have been discovered. Genetic testing for these reproductive phenotypes can help patients make an early diagnosis and avoid repeated ineffective attempts. However, the treatment of the patients with recurrent IVF failures after genetic testing has become a new focus of attention. In this paper, the genetic factors, the treatment and potential intervention strategies of recurrent IVF failures in recent years are summarized to provide a reference for individualized diagnosis and treatment.

BackgroundThe treatment scheme for papillary thyroid carcinoma (PTC) patients is related to whether lymph node metastasis is prevalent or not. The routine ultrasound indicator used alone has proven to have a low sensitivity to predict the presence of lymph node metastasis in PTC.ObjectiveTo explore the value of combined use of ultrasonographic indicators in predicting central lymph node metastasis in PTC.MethodsClinical data of PTC patients (n=446) with thyroid surgery and central neck dissection were collected retrospectively from the First Affiliated Hospital of Shihezi University School of Medicine from March 2013 to May 2020, involving sex, age, and ultrasonographic features 〔diameter of nodule, number of nodules, location of single and multiple nodules, internal composition, internal echo, boundary, margin, micro calcification, anteroposterior and transverse diameter (A/T) ratio, posterior echo attenuation, capsular invasion〕. Postoperative pathological results confirmed that 159 cases (35.65%) with central lymph node metastasis and other 287 (64.35%) without. Unconditional stepwise binary Logistic regression was used to explore the factors associated with central lymph node metastasis. Receiver operating characteristic (ROC) analysis was performed to estimate the predictive value of each indicator for central lymph node metastasis.ResultsPatients with and without central lymph node metastasis had significant differences in sex ratio, distribution of age, thyroid nodule diameter, margin conditions, and A/T ratio, as well as prevalence of micro calcification and capsular invasion (P10 mm 〔OR=2.385, 95%CI (1.544, 3.684) 〕, and capsular invasion 〔OR=1.773, 95%CI (1.153, 2.724) 〕 were independently associated with increased risk of central lymph node metastasis (P10 mm, and capsular invasion were independent risk factors for central lymph node metastasis in PTC, and the value of combined use of them had a higher predictive value for central lymph node metastasis.

Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene-based burden test and identified a candidate gene, karyopherin subunit [alpha]7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. [Kpna2.sup.-/-] female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of [Kpna2.sup.-/-] mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in [Kpna2.sup.-/-] mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients., Introduction Successful human reproduction requires normal embryonic development. Preimplantation embryo arrest (PREMBA) is a common reason for recurrent failure of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and [...]

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).

To date, it has become more and more important to design and synthesize energetic materials that have a good balance between energy and safety. In this study, a new nitrogen-rich energetic compound with high energy and low sensitivity is designed and synthesized. The target compound dihydrazinium 3,3′-azo-5,5′-diazido-1,2,4-triazol (DHADAT) shows a very high nitrogen content (81.27%) and high enthalpy of formation (1405 kJ mol−1). Furthermore, DHADAT not only exhibits a detonation velocity (D = 9122 m s−1) comparable to HMX, but also has a much lower impact sensitivity (IS = 23 J) than HMX (D = 9144 m s−1, IS = 7.4 J). Additionally, a calculation based on dispersion-corrected density functional theory (DFT-D) has been performed to examine the electronic and mechanical properties of DHADAT. And the analysis of the density of states and the Hirshfeld surface indicates that the N–H⋯N hydrogen bonding interaction plays a vital role in stabilizing the whole system. And it is discovered through the analysis of the mechanical properties that this compound exhibits a better ductility, resistance to deformation and stiffness than HMX. The systematic research on DHADAT by combining experiment and theory ensures that DHADAT could be an extremely promising insensitive high-energy material. [ABSTRACT FROM AUTHOR]