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Background: It is currently inconclusive whether different intracytoplasmic sperm injection (ICSI) timings post oocyte retrieval (POR) lead to altered chance of clinical pregnancy and live birth following in vitro fertilization (IVF) treatment. This study, therefore, aimed to synthesize literature-based evidence for better clinical guidance regarding ICSI practice. Methods: A systematic review and meta-analysis were performed according to PRISMA guidelines. Studies were searched for in PubMed, MEDLINE, EMBASE, and the Cochrane Library. Outcome endpoints included clinical pregnancy and live birth rates (LBRs). Results: A total of 605 records were retrieved in the initial search. After exclusion, 30 articles were included for further screening for eligibility. For meta-analysis, 1 prospective and 5 retrospective cohort studies were included for pooled analysis, from which clinical pregnancy rates (CPRs) were evaluated in 6 studies while LBRs were evaluated in 3 studies. CPRs were comparable when ICSI was performed at (a) [Formula: see text] hours POR (risk ratio or RR = 1.00, [Formula: see text] confidence interval [CI] 0.94–1.08) vs [Formula: see text] hours, (b) [Formula: see text] hours (RR = 1.01, [Formula: see text] CI 0.88–1.16) vs [Formula: see text] hours, (c) [Formula: see text] hours (RR = 0.99, [Formula: see text] CI 0.93–1.05) vs [Formula: see text] hours, (d) [Formula: see text] hours (RR = 0.98, [Formula: see text] CI 0.93–1.02) vs [Formula: see text] hours, and (e) [Formula: see text] hours (RR = 1.05, [Formula: see text] CI 0.90–1.23) vs [Formula: see text] hours. However, LBR was reduced when ICSI was performed [Formula: see text] hours POR vs [Formula: see text] hours (RR = 0.94, [Formula: see text] CI 0.89–0.99), but such reduction disappeared when comparing [Formula: see text] hours POR (RR = 1.09, [Formula: see text] CI 0.85–1.38) vs [Formula: see text] hours. Conclusions: CPRs remain comparable when ICSI is performed at a range of timings up to 6-hour POR. However, LBR may benefit slightly by scheduling ICSI between 5- and 6-hour POR.

Genetic basis and network studies underlying synergistic biomass accumulation of roots and shoots (SBA) are conducive for rational design of high-biomass rice breeding. In this study, association signals for root weight, shoot weight, and the ratio of root-to-shoot mass (R/S) were identified using 666 rice accessions by genome-wide association study, together with their sub-traits, root length, root thickness and shoot length. Most association signals for root weight and shoot weight did not show association with their sub-traits. Based on the results, we proposed a top-to-bottom model for SBA, i.e. root weight, shoot weight and R/S were determined by their highest priority in contributing to biomass in the regulatory pathway, followed by a lower priority pathway for their sub-traits. Owing to 37 enriched clusters with more than two association signals identified, the relationship among the six traits could be also involved in linkage and pleiotropy. Furthermore, a discrimination of pleiotropy and LD at sequencing level using the known gene OsPTR9 for root weight, R/S and root length was provided. The results of given moderate correlation between traits and their corresponding sub-traits, and moderate additive effects between a trait and the accumulation of excellent alleles corresponding to its sub-traits supported a bottom-to-top regulation model for SBA. This model depicted each lowest-order trait (root length, root thickness and shoot length) was determined by its own regulation loci, and competition among different traits, as well as the pleiotropy and LD. All above ensure the coordinated development of each trait and the accumulation of the total biomass, although the predominant genetic basis of SBA is still indistinguishable. The presentation of the above two models and evidence of this study shed light on dissecting the genetic architecture of SBA.

OBJECTIVE: To report a live birth from a patient with complete zona-free oocytes due to abnormal zona production and to reveal full time-lapse blastocyst development footage of its originating embryo. METHODS: A 34-year-old woman presented with a history of failed fertilization via standard in vitro fertilization insemination and a potential absence of zona pellucida. A total of 3 intracytoplasmic sperm injection cycles were undertaken with all oocytes collected being zona-free. Embryos created in the initial 2 cycles were cultured in the G1+/G2+ sequential media in a benchtop incubator. During the final successful cycle, the culture strategy was shifted to single step media (G-TL) in an Embryoscope+ incubator. RESULTS: The first 2 attempts led to a biochemical pregnancy or no blastocyst available for transfer. In the third cycle, 13 out of 24 collected oocytes were subjected to injection, with 4 being normally fertilized. Two blastocysts were subsequently formed, in which one was cryopreserved and the other transferred. A live baby girl (1570g) was subsequently delivered at 34 weeks of gestation by cesarean section. CONCLUSION: Live birth can be achieved for patients with zona production deficiency. Adjustment in ovarian stimulation and subsequent embryo culture strategies may have potentially contributed to the success of the 3rd cycle. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02114-3.

Background The speciation and fast global domestication of bread wheat have made a great impact on three subgenomes of bread wheat. DNA base composition is an essential genome feature, which follows the individual-strand base equality rule and [AT]-increase pattern at the genome, chromosome, and polymorphic site levels among thousands of species. Systematic analyses on base compositions of bread wheat and its wild progenitors could facilitate further understanding of the evolutionary pattern of genome/subgenome-wide base composition of allopolyploid species and its potential causes. Results Genome/subgenome-wide base-composition patterns were investigated by using the data of polymorphic site in 93 accessions from worldwide populations of bread wheat, its diploid and tetraploid progenitors, and their corresponding reference genome sequences. Individual-strand base equality rule and [AT]-increase pattern remain in recently formed hexaploid species bread wheat at the genome, subgenome, chromosome, and polymorphic site levels. However, D subgenome showed the fastest [AT]-increase across polymorphic site from Aegilops tauschii to bread wheat than that on A and B subgenomes from wild emmer to bread wheat. The fastest [AT]-increase could be detected almost all chromosome windows on D subgenome, suggesting different mechanisms between D and other two subgenomes. Interestingly, the [AT]-increase is mainly contributed by intergenic regions at non-selective sweeps, especially the fastest [AT]-increase of D subgenome. Further transition frequency and sequence context analysis indicated that three subgenomes shared same mutation type, but D subgenome owns the highest mutation rate on high-frequency mutation type. The highest mutation rate on D subgenome was further confirmed by using a bread-wheat-private SNP set. The exploration of loci/genes related to the [AT] value of D subgenome suggests the fastest [AT]-increase of D subgenome could be involved in DNA repair systems distributed on three subgenomes of bread wheat. Conclusions The highest mutation rate is detected on D subgenome of bread wheat during domestication after allopolyploidization, leading to the fastest [AT]-increase pattern of D subgenome. The phenomenon may come from the joint action of multiple repair systems inherited from its wild progenitors.

Objective: To investigate morphokinetic characteristics of embryos displaying either reverse cleavage or direct cleavage during the first, second or third cleavage cycle. Methods: A total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (35.0±4.6) years] were included for reverse cleavage analysis, and a total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (33.8 ±4.3) years] were included for direct cleavage analysis in this study. Using a sibling-embryo design, morphokinetic profiles (both before and after the onset of abnormal event) of embryos displaying reverse cleavage (n=241) or direct cleavage (n=244) were compared with their unaffected siblings (the controls) in the first, second and third cell cycles (n=32, n=142, n=562; n=195, n=412, n=205, respectively), at different developmental stages up to day 3. Results: Direct cleavage embryos demonstrated significantly delayed cleavage rates prior to the event regardless of developmental stage of the occurrence, while reverse cleavage embryos showed similar cleavage rates to their unaffected siblings. Post event, direct cleavage embryos sped up cleavage rates while reverse cleavage embryos slowed down. Conclusions: Altered morphokinetic profiles are displayed by direct cleavage embryos both before and after their occurrence and reverse cleavage embryos after the occurrence, which could potentially confound morphokinetic comparisons if not separated from their unaffected sibling embryos. Further study is warranted in order to fully understand the biological mechanisms of such events.

PURPOSE: To study the morphometric and morphokinetic profiles of pronuclei (PN) between male and female human zygotes. METHOD(S): This retrospective cohort study included 94 consecutive autologous single day 5 transfer cycles leading to a singleton live birth. All oocytes were placed in the EmbryoScope + incubator post-sperm injection with all annotations performed retrospectively by one embryologist (L-SO). Timing parameters included 2nd polar body extrusion (tPB2), sperm-originated PN (tSPNa) or oocyte-originated PN (tOPNa) appearance, and PN fading (tPNF). Morphometrics were evaluated at 8 (stage 1), 4 (stage 2), and 0 h before PNF (stage 3), measuring PN area (um(2)), PN juxtaposition, and nucleolar precursor bodies (NPB) arrangement. RESULTS: Male zygotes had longer time intervals of tPB2_tSPNa than female zygotes (4.8 ± 0.2 vs 4.2 ± 0.1 h, OR = 1.442, 95% CI 1.009–2.061, p = 0.044). SPN increased in size from stage 1 through 2 to 3 (435.3 ± 7.2, 506.7 ± 8.0, and 556.3 ± 8.9 um(2), p = 0.000) and OPN did similarly (399.0 ± 6.1, 464.3 ± 6.7, and 513.8 ± 6.5 um(2), p = 0.000), with SPN being significantly larger than OPN at each stage (p

Refereed/Peer-reviewed Research question: Does variation in day 5 assessment timing confound live birth prediction using snapshot blastocyst morphology and is it possible to develop a numerical prediction algorithm? Design: Retrospective multicentre cohort study including 4851 autologous oocyte single day 5 fresh embryo transfers performed at 11 Monash IVF clinics between 2016 and 2020. Repeat cycles of the same patients were excluded to avoid clustering effects in regression analysis. Results: Hours post insemination (HPI) at day 5 assessment (115.9 ± 2.6 h) significantly correlated with blastocyst developmental stage (r = 0.118, P < 0.001). Independent association (expressed as adjusted odds ratio [aOR] and 95% confidence interval [CI]) was identified between live birth and HPI (aOR 0.950, 95% CI 0.925–0.976, P < 0.001) after accounting for blastocyst morphology and a range of patient/cycle characteristics. Algorithms were constructed using four significant live birth predictors: HPI at day 5 assessment, blastocyst developmental stage (aOR 1.347, 95% CI 1.217–1.491, P < 0.001), morphological grade (aOR 1.314, 95% 1.197–1.443, P < 0.001) and maternal age (aOR 0.922, 95% CI 0.907–0.936, P < 0.001). Receiver operating characteristic (ROC) analysis showed consistent predicting performance of algorithms via five-fold cross-validation, with similar area under the ROC curve (AUC 0.718, 0.715, 0.720, 0.712, 0.726, P < 0.001, respectively, in development subsets; and AUC 0.718, 0.731, 0.709, 0.741, 0.684, P < 0.001, respectively, in validation subsets). A score (ranging from 0.1 to 4.7) calculator based on the final algorithm was subsequently created. Conclusions: Day 5 assessment timing is a confounding factor for live birth prediction using snapshot blastocyst morphology. A numerical algorithm incorporating day 5 assessment HPI, blastocyst morphology and maternal age can be developed for live birth prediction.

Artificial intelligence (AI) techniques are starting to be used in IVF, in particular for selecting which embryos to transfer to the woman. AI has the potential to process complex data sets, to be better at identifying subtle but important patterns, and to be more objective than humans when evaluating embryos. However, a current review of the literature shows much work is still needed before AI can be ethically implemented for this purpose. No randomized controlled trials (RCTs) have been published, and the efficacy studies which exist demonstrate that algorithms can broadly differentiate well between ‘good-’ and ‘poor-’ quality embryos but not necessarily between embryos of similar quality, which is the actual clinical need. Almost universally, the AI models were opaque (‘black-box’) in that at least some part of the process was uninterpretable. This gives rise to a number of epistemic and ethical concerns, including problems with trust, the possibility of using algorithms that generalize poorly to different populations, adverse economic implications for IVF clinics, potential misrepresentation of patient values, broader societal implications, a responsibility gap in the case of poor selection choices and introduction of a more paternalistic decision-making process. Use of interpretable models, which are constrained so that a human can easily understand and explain them, could overcome these concerns. The contribution of AI to IVF is potentially significant, but we recommend that AI models used in this field should be interpretable, and rigorously evaluated with RCTs before implementation. We also recommend long-term follow-up of children born after AI for embryo selection, regulatory oversight for implementation, and public availability of data and code to enable research teams to independently reproduce and validate existing models.

Prefrontal cortex (PFC) is the cognitive center that integrates and regulates global brain activity. However, the whole-brain organization of PFC axon projections remains poorly understood. Using single-neuron reconstruction of 6,357 mouse PFC projection neurons, we identified 64 projectome-defined subtypes. Each of four previously known major cortico-cortical subnetworks was targeted by a distinct group of PFC subtypes defined by their first-order axon collaterals. Further analysis unraveled topographic rules of soma distribution within PFC, first-order collateral branch point-dependent target selection and terminal arbor distribution-dependent target subdivision. Furthermore, we obtained a high-precision hierarchical map within PFC and three distinct functionally related PFC modules, each enriched with internal recurrent connectivity. Finally, we showed that each transcriptome subtype corresponds to multiple projectome subtypes found in different PFC subregions. Thus, whole-brain single-neuron projectome analysis reveals organization principles of axon projections within and outside PFC and provides the essential basis for elucidating neuronal connectivity underlying diverse PFC functions.

Study question Does variation in day 5 observation timing confound embryo-morphology-based live birth prediction, and is it possible to develop a robust comprehensive numerical prediction model. Summary answer Day 5 observation timing confounds embryo-morphology-based live birth prediction. A robust comprehensive numerical prediction model can be developed after considering a number of contributing variables. What is known already Embryo development is a dynamic process, and therefore the widely used static observations potentially lead to biased prediction of live birth outcomes. So far, little is known in regard to potential confounding impact of day 5 assessment timing on the static-morphology-based live birth prediction. In addition, the inter-observer variation in morphology-based embryo assessment requires a more robust system to improve consistency of selection. Study design, size, duration This retrospective multi-center cohort study included 8866 autologous oocyte in vitro fertilisation treatment cycles performed at 14 associated clinics within the same network during 2012–2018. Only fresh cycles with single day 5 embryo transfers were included for analysis with all pregnancies followed up until birth. Repeat cycles of same patients were excluded to avoid clustering effect in statistical analysis. Participants/materials, setting, methods Dataset was randomly split into two subsets at 60:40 ratio, with one (n = 5274) used for regression analysis and model development and the other (n = 3592) used for model testing. Multiple logistic regression was performed to evaluate live birth predicting power of several potential contributors, expressed by odds ratio (OR) and 95% confidence interval (CI). A comprehensive prediction model was subsequently developed based on calculated weights of contributing factors, then tested via receiver operating characteristics (ROC) analysis. Main results and the role of chance The timings of day 5 observation of 8866 included embryos, measured by hours post insemination (HPI), distributed in a bell shape ranging from 112.0 to 120.0 h (mean±SD 115.7±1.7 h). After taking into account female age at egg collection (grouped as Limitations, reasons for caution The retrospective design does not allow for controlling of unknown confounders. HPI was based on static observations in this study so future time-lapse study may bring more insights with more accurate observation and measurement. Wider implications of the findings: The varying HPIs at day 5 observation were alarming as this could confound live birth prediction using embryology parameters. It is important to standardise the timing of embryo observations. The inclusion of HPI into a comprehensive numerical scoring system for live birth prediction may potentially improve its robustness Trial registration number Not applicable

Study question What is the live birth rate after single, low-grade blastocyst (LGB) transfer? Summary answer The live birth rate for LGBs is 28%, ranging between 15–31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. What is known already Live birth rates following LGB transfer are varied and have been reported to be in the range of 5–39%. However, these estimates are inaccurate as studies investigating live birth rates following LGB transfer are inherently limited by sample size (n = 10–440 for LGB transfers) due to LGBs being ranked last for transfer. Further, these studies are heterogenous with varied LGB definitions and design. Collating LGB live birth data from multiple clinics is warranted to obtain sufficient numbers of LGB transfers to establish reliable live birth rates, and to allow for delineation of different LGB subgroups, including blastocyst age and female age. Study design, size, duration We performed a multicentre, multinational retrospective cohort study in 9 IVF centres in China and New Zealand from 2012 to 2019. We studied the outcome of 6966 single blastocyst transfer cycles on days 5–7 (fresh and frozen) according to blastocyst grade, including 875 transfers from LGBs ( Participants/materials, setting, methods The main outcome measured was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n = 3849, aa, ab and ba), moderate-grade blastocysts (MGBs; n = 2242, bb) and LGBs (n = 875, ac, ca, bc, cb and cc) and live birth rates compared using the Pearson Chi-squared test. A logistic regression analysis explored the relationship between blastocyst grade and live birth after adjustment for the confounders: clinic, female age, expansion stage, and blastocyst age. Main results and the role of chance The live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p Limitations, reasons for caution Despite the large multicentre design of the study, analyses of transfers occurring within the smallest subsets of the LGB group were limited by sample size. The study was not randomised and had a retrospective character. Wider implications of the findings: LGBs maintain satisfactory live birth rates (averaging 28%) in the general IVF population. Even those in the lowest grading tier maintain modest live birth rates (15%; cc). It is recommended that LGBs not be universally discarded, and instead considered for subsequent frozen embryo transfer to maximize cumulative live birth rates. Trial registration number Not applicable

Study question Do morphometric and morphokinetic profiles of pronuclei (PN) following intracytoplasmic sperm injection (ICSI) vary between male and female human zygotes? Summary answer Male and female zygotes displayed different PN morphometrics and morphokinetics. Additionally, variations were identified between sperm-originated (SPN) and oocyte-originated (OPN) pronuclei. What is known already Previous studies have investigated the use of PN-associated parameters via static observations as indicators of zygote viability, including size equality or juxtaposition. However, recent clinical application of time-lapse videography (TLV) provides a novel opportunity to assess these pronuclear events with greater accuracy and precision of morphometric and morphokinetic measurement. A number of recent TLV studies have also investigated potential live birth prediction by such PN associated measures, however whether or not there are gender associated differences in such measures which could in turn confound live birth prediction is unknown. Study design, size, duration: This retrospective cohort study included 94 consecutive autologous single day 5 transfer cycles (either fresh or frozen) performed between January 2019 and March 2020. Only ICSI cycles (maternal age Participants/materials, setting, methods Timings included 2nd polar body extrusion (tPb2), SPN(tSPNa)/OPN(tOPNa) appearance (differentiated by proximity to Pb2) and PN fading (tPNF). Morphometrics were evaluated at 8 (stage 1), 4 (stage 2) and 0 hour before PNF (stage 3), measuring PN area (um2), PN juxtaposition, and nucleolus precursor body (NPB) arrangement. Means ± standard deviation were compared using student t test or logistic regression as odds ratio (OR) and 95% confidence interval (CI), and proportional data by chi-squared analysis. Main results and the role of chance Logistic regression indicated that male zygotes had longer time intervals of tPb2_tSPNa than female zygotes (4.8±1.5 vs 4.2±1.0 h, OR = 1.442, 95% CI 1.009–2.061, p = 0.044), but not tPb2_tOPNa (4.7±1.8 vs 4.5±1.3 h, OR = 1.224, 95% CI 0.868–1.728, p = 0.250) and tPb2_tPNF (19.9±2.8 vs 19.1±2.3 h, OR = 1.136, 95% CI 0.957–1.347, p = 0.144). SPN increased in size from stage 1 through 2 to 3 (435.3±70.2, 506.7±77.3, and 556.3±86.4 um2, p = 0.000) and OPN did similarly (399.0±59.4, 464.3±65.2, and 513.8±63.5 um2, p = 0.000), with SPN being significantly larger than OPN at each stage (p 0.05 respectively). Limitations, reasons for caution The retrospective design does not allow for control of unknown confounders. Sample size is considered relatively small. PN area measurement may not truly represent volume as PN may not be perfectly spherical. Findings were based on women Wider implications of the findings: These findings augment and extend previous studies investigating PN parameters via static observations. The reported variations between male and female embryos may confound live birth prediction when using pronuclei morphometrics and morphokinetics. Larger scaled studies are warranted to verify these findings. Trial registration number Not applicable

Study question Does slow development of fresh transferred day 5 embryos lead to decreased implantation potential and birthweight? Summary answer Slow day 5 development was associated with reduced implantation potential when transferred fresh but the subsequent birthweight of the resulting baby was not impacted. What is known already Slow development of in vitro cultured cleavage stage embryos is associated with reduced blastocyst development and implantation rates. There is no current consensus regarding whether to transfer fresh slow developing day 5 embryos or to extend culture for a subsequent day with potential for cryopreservation. It is therefore important to understand the true prognosis of fresh transferred day 5 embryos at less advanced developmental stages. This would provide evidence based guidelines for the decision making process in regard to embryo transfer. Study design, size, duration This is a retrospective multi-center cohort study, including 1213 consecutive patients undergoing autologous oocyte in vitro fertilization (IVF) treatment during 2016-2019,with fresh transfer of a single day 5 embryo (selection based on developmental stage and inner cell mass and trophectoderm morphology if blastocyst was at the ≥expanding stage). Cycle data were collected from 4 associated private clinics, with repeat cycles of same patients excluded to avoid clustering effect at statistical analysis. Participants/materials, setting, methods Live birth and birthweight were followed up in all 1213 fresh day 5 SETs. Multiple regression (logistic or linear) was performed to investigate association between slow day 5 development (defined as ≤ early blastocyst) and (a)live birth, (b) birthweight, and (c) gestation-adjusted birthweight (Z score) to account for gestational age, gender and compared to embryos at ≥ expanded stage. Results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI)or coefficients (β). Main results and the role of chance No implantation was achieved following single fresh transfer of day 5 embryos that failed to reach early blastocyst stage (n = 76) and were transferred as ≤ morula stage. Live birth rate was significantly lower following single day 5 fresh transfer of an early blastocyst (n = 237, 16%), in comparison to expanding (n = 329, 27%, P = 0.001), expanded(n = 392, 41%, P = 0.000), and hatching/hatched blastocysts (n = 169, 44%, P = 0.000). After adjusting for potential confounding factors including; maternal age, hours post insemination at day 5 assessment, number of oocytes collected, number of 2PN embryos, and number of embryos frozen; multiple logistic regression showed significantly reduced likelihood of live birth resulting from early blastocysts in reference to those at the expanding (aOR=0.584, 0.371-0.917, P = 0.020), expanded (aOR=0.322, 0.208-0.501, P = 0.000), or hatching/hatched stages (aOR=0.255, 0.147-0.443, P = 0.000). However, multivariate linear regression indicated that early blastocysts resulting in a live birth (n = 39) did not lead to altered birthweight (β=-9.091, P = 0.904; β=-34.960, P = 0.343; β=-26.074, P = 0.414; respectively) or Z score (β = 0.045, P = 0.706; β=-0.051, P = 0.426; β=-0.028, P = 0.506; respectively) in reference to the expanding (n = 90), expanded (n = 160), or hatching/hatched stages (n = 75). Limitations, reasons for caution The retrospective nature of this study does not allow controlling of unknown confounders. The 4 participating clinics are associated within the same network with shared protocols, therefore, results may not be generalized to other clinics with different settings. Wider implications of the findings The findings suggest no clinical value of fresh day 5 transfer of embryos ≤morula stage. Although early blastocysts implant at reduced rate, assuring birthweight outcomes suggest clinical value. Future studies intend to investigate slow growing day 5 fresh transfers versus embryos that were slow growing but transferred after day 6. Trial registration number NA

The recent clinical introduction of time-lapse videography into in vitro fertilization laboratories has offered a novel opportunity for embryologists to explore improved methods for embryo selectio...

Embryo quality is a key determinant of the success of IVF. Although the focus has been on selecting the best embryo for transfer, the classification of low-grade blastocysts (LGB) in existing scoring systems has received less attention. This is worrisome; embryo freezing allows optimal use of all created embryos, thus maximizing the cumulative live birth rate, which is arguably the most important outcome for infertile couples. A PubMed search was conducted in August 2020, using '((('poor-quality' OR 'poor quality') OR ('low-grade' OR 'low grade')) AND ('embryo' OR 'blastocyst')) AND ('pregnancy' OR 'live birth')'. This scoping review shows that LGB have similar euploidy and pregnancy success rates after implantation and have no adverse effects on pregnancy or perinatal outcomes. Evidence for pregnancy outcomes is lacking for different grades of LGB, with most studies clustering all LQB as one to compare with optimal blastocysts.

Background Colorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism. Methods The expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo. Results Hsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo. Conclusion Hsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.

Fungal disease meets its matchFusariumhead blight (FHB), caused by a fungus, reduces wheat crop yield and introduces toxins into the harvest. From the assembly of the genome ofThinopyrum elongatum, a wild relative of wheat used in breeding programs to improve cultivated wheat, Wanget al.cloned a gene that can address both problems (see the Perspective by Wulff and Jones). The encoded glutathioneS-transferase detoxifies the trichothecene toxin and, when expressed in wheat, confers resistance to FHB.Science, this issue p.eaba5435; see also p.822

This study investigated the efficacy of four published day 3 embryo time-lapse algorithms based on different types of datasets (known implantation data [KID] and single embryo transfer [SET]), and the confounding effect of female age and conventional embryo morphology. Four algorithms were retrospectively applied to three types of datasets generated at Fertility North between February 2013 and December 2014: (a) KID dataset (

PURPOSE: To investigate the between-laboratory reproducibility of embryo selection/deselection effectiveness using qualitative and quantitative time-lapse parameters. METHODS: A systematic search was performed on MEDLINE, EMBASE, and the Cochrane Library (up to February 2020) without restriction on date, language, document type, and publication status. Measuring outcomes included implantation, blastulation, good-quality blastocyst formation, and euploid blastocyst. RESULTS: We detected 6 retrospective cohort studies externally validating the first clinical time-lapse model (Meseguer) emphasizing quantitative parameters, of which 3 (including one involving 2 independent centers) were included for the pooled analysis. Receiver operating characteristics analysis showed reduced predictive power of the model when either including or not including sister clinic validation. Fifteen cohort studies evaluating qualitative parameters were included for meta-analysis, and the mean Newcastle-Ottawa Scale was 5.3. Overall, meta-analysis showed significantly adverse association between the presence of ≥ 1 cleavage abnormalities and embryo implantation rates (11 studies, n = 7266; RR = 0.39[0.28, 0.55](95% CI); I(2) = 57%). Further analysis showed adverse impacts of direct cleavage (7 studies, n = 7065; RR = 0.28 [0.15, 0.54] (95% CI); I(2) = 46%), reverse cleavage (2 studies, n = 3622; RR = 0.16 [0.03, 0.75] (95% CI); I(2) = 0%), chaotic cleavage (2 studies, n = 3643; RR = 0.11 [0.02, 0.69] (95% CI); I(2) = 24%), and multinucleation (5 studies, n = 2576; RR = 0.59 [0.50, 0.69] (95% CI); I(2) = 0%), but not the

In recent years, digital signal processing (DSP) has been widely investigated for the applications in future next generation passive optical networks (PONs). In this paper, we compare four transmission technologies based on DSP with frequency domain equalization (FDE) for PON transmission with double-side band (DSB) intensity modulation and direct detection. These schemes include orthogonal frequency division multiplexing (OFDM), single-carrier frequency domain equalization (SCFDE), discrete Fourier transform spread orthogonal frequency division multiplexing (DFT-S-OFDM) and interleaved frequency division multiplexing (IFDM). We analyze their computational complexity and flexibility in PON applications, and compare their transmission performance by experiments. Based on above work, we propose and experimentally demonstrate a hybrid DSP-enhanced PON architecture with downstream OFDM modulation and upstream SCFDE modulation.

Objective: To investigate the relationship between elevated serum progesterone levels (EP) on the day of ovulatory trigger, live birth rates, and the growth of resulting embryos. Methods: A total of 836 in vitro fertilization (IVF) cycles with 4 478 embryos in conventional culture were retrospectively analyzed, together with an additional 90 IVF cycles producing 618 embryos from culture and assessment using the Embryoscope™ time-lapse system. Results: In cycles using conventional culture, serum progesterone per follicle ≥14 mm (median 0.42 nmol/L/follicle, range 0.05-3.50 nmol/L/follicle) was a significant negative predictor of live-birth (ROC AUC = 0.395, 95% CI 0.345-0.445; P=0.000) as were progesterone/estradiol ratio (0.442, 0.391-0.494; P=0.027) and progesterone per oocyte (0.374, 0.326-0.421; P=0.000) but not progesterone alone (0.470, 0.419-0.521; P>0.05). Women with an EP/follicle (>0.42 nmol/L/follicle) had reduced live birth rates if they were ≥35 yrs (14.4% vs. 24.2%, P0.42 nmol/L/follicle) adversely affects embryo implantation in women aged ≥35 years, but not

This study evaluated the effect of sperm selection and intracytoplasmic sperm injection (ICSI) on subsequent fertilization and embryo development using the hyaluronic acid-based SpermSlow™ (HA-ICSI) compared to injection with polyvinylpyrrolidone (PVP-ICSI). A total of 206 metaphase II oocytes were collected from 21 prospectively enrolled ICSI cycles at Fertility North between July 2014 and March 2015. Sibling oocytes were randomized into HA-ICSI and PVP-ICSI (n = 103 per group). Subsequent fertilization outcomes and embryo development in terms of qualitative and quantitative time-lapse measures following three-day culture in the Embryoscope™ were compared. HA-ICSI resulted in significantly lower abnormal fertilization rates (1.9% vs 9.7%, p = 0.017), and a trend towards increased normal fertilization rates (73.8% vs 62.1%, p = 0.073) with increased injection time (2.5 vs 2.1 min, p = 0.001). No differences between HA-ICSI and PVP-ICSI were observed in (a) the proportion of good conventional morphology embryos (50% vs 53.1%, p = 0.712), (b) time-lapse qualitative measures (p 0.05) and (c) time-lapse quantitative measures (p 0.05). In conclusion, HA-ICSI improves fertilization outcomes although sperm injection takes longer to complete. Subsequent embryo development up to day 3 is not affected.