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Background: The blastocyst morphology provided valuable roles for predicting pregnancy and live birth, but was still not fully understood for evaluating miscarriage. The aim of this study was to explore the association between blastocyst morphologic evaluation and first trimester miscarriage combined with karyotype of miscarried conceptus., Methods: This retrospective cohort study included a total of 2873 clinical pregnancy cycles with single blastocyst transfer performed from January 2013 to April 2019. Chromosome karyotype of miscarried conceptus was analyzed via single nucleotide polymorphism array analysis. Miscarriage and karyotype of miscarried conceptus associated with blastocyst morphology were analyzed by chi-square and logistic regression analysis., Results: A total of 354 (12.3%) cycles resulted in first trimester miscarriage. Miscarriage rates increased with trophectoderm (TE) grade from A to C (P = 0.012), while three morphologic parameters (blastocoele expansion degree, inner cell mass (ICM) and TE) showed no statistical significance with miscarriage after multivariable analysis. The rate of aneuploidy was 47.7% (83 of 174) in total miscarried conceptuses. For euploid miscarriages, the grade B of ICM occupied a higher proportion compared with aneuploidy, with OR of 2.474, (95% CI, 1.311-4.699), P = 0.005., Conclusions: Chromosomal aberration of embryo is an important genetic factor for first trimester miscarriage, and the quality of ICM is a potential indicator for euploid miscarriage. Blastocysts with grade A of ICM should be given priority during single blastocyst transfer to reduce potential miscarriage.

Background: Balanced complex chromosome rearrangements (BCCR) are balanced chromosomal structural aberrations that involve two or more chromosomes and at least three breakpoints. It is very rare in the population. The objective is to explore the difference of influence of three types of BCCR on early embryonic development and molecular karyotype., Results: Twelve couples were recruited including four couples of three-way rearrangements carriers (group A), three couples of double two-way translocations carriers (group B) and five couples of exceptional CCR carriers (group C). A total of 243 oocytes were retrievedin the seventeen preimplantation genetic testing (PGT) cycles, and 207 of these were available for fertilization. After intracytoplasmic sperm injection, 181oocytes normally fertilized. The rates of embryos forming on day3 in three groups were 87.88, 97.78 and77.14%, which was significantly different (P = 0.01). Compared with group B, the rate of embryo formation was statistically significantly lower in group C (P = 0.01). Furthermore, the rates of high-quality blastocysts in three group were 14.71, 48.15 and 62.96%, respectively, which was significantly different (P = 0.00). Compared with group B andC, the rate of high-quality blastocysts in group A was statistically significantly lower (P = 0.00;P = 0.00). Comprehensive chromosome analysis was performed on 83 embryos, including 75 trophectodermcellsand 8 blastomeres. Except 7 embryos failed to amplify, 9.01%embryos were diagnosed as euploidy, and 90.91% were diagnosed as abnormal. As for group A, the euploid embryo rate was 10.71%and the abnormal embryo rate was 89.29%. In group B,the euploid embryo rate was 3.85%, the abnormal embryo rate was 96.15%. The euploid embryo rate was 13.04%, the abnormal embryo rate was 86.96% in group C. There were no significant differences among the three groups (P = 0.55)., Conclusions: The lowest rate of high quality blastocysts has been for three-way rearrangements and the lowest rate of euploidy has been for double two-way translocations, although no significant difference. Different types of BCCR maybe have little effect on the embryonic molecular karyotype. The difference of influence of BCCR on early embryonic developmentandmolecular karyotypeshould be further studied.

Surface property that strongly affects physical and chemical performances of inorganic nanocrystals (NCs) is a key enabler for NCs applications. Here, we report a facile, versatile and general strategy for reactive removal of NCs surface ligands based on electrophilic substitution reaction, in which an electrophile directly reacts with the electron-rich coordinating headgroup of surface-tethered ligands to form a non-coordinating product. This process leads to the break of NC-ligand bond, thereby achieving reactive removal of surface ligands. Based on this strategy, various hydrophobic NCs with different compositions and morphologies can be transferred into polar and hydrophilic media while preserving their size and shape. More importantly, the treated NCs present a great improvement in catalytic and biological performances in comparison with the untreated counterparts. This work not only provides a versatile ligand removal strategy for NCs surface modification but also opens up more opportunities for applications in the fields of electronics, catalysis and biotechnology.

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development 1 . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) 2 . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing 3-5 . Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population., Competing Interests: Conflict of interest statement: S.L. and X.S.X. are cofounders and shareholders of Yikon Genomics Company, Ltd. Z.Z., Y. Gao, W.L., S.B., M.H., and J.R. receive research funding from Yikon Genomics Company, Ltd.

Purpose: We reviewed the influence of dehydroepiandrosterone (DHEA) supplementation in patients with poor ovarian response (POR) undergoing in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI)., Methods: We searched Embase, MEDLINE, PubMed, and the Cochrane Library (1980-2015) for relevant papers and used the Newcastle-Ottawa Scale scoring system to evaluate study quality. Dichotomous data were expressed as pooled relative risk (RR) estimates with fixed or random effect models. Continuous variables were expressed as the weighted mean difference (WMD). All data were analyzed using Revman Software v. 5 and are shown with 95 % confidence intervals (CI)., Results: Twenty-one studies met the inclusion criteria. DHEA pretreatment increased the clinical pregnancy rate (RR 1.53, 95 % CI 1.25-1.86), live birth rate (RR 1.87, 95 % CI 1.22-2.88), implantation rate (RR 1.56, 95 % CI 1.20-2.01), and antral follicle count (WMD 0.4, 95 % CI 0.14 to 0.66) while reducing miscarriages (RR 0.50, 95 % CI 0.27-0.90). After subgroup analysis, oocyte numbers and anti-Müllerian hormone levels were also enhanced after DHEA treatment. However, the endometrial thickness and estradiol levels on the day of injecting hCG to induce ovulation were similar between the DHEA supplementation groups and controls., Conclusions: Based on the limited available evidence, DHEA supplementation seems to improve ovarian reserves and IVF/ICSI outcome in patients with POR. Further research is required to clarify the effect of DHEA exposure in assisted reproduction technology.