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PURPOSE: To assess the association between maternal education level and live birth after in vitro fertilization (IVF). METHODS: We studied women who underwent the first cycle of fresh or frozen-thawed embryo transfer between 2014 and 2019. Women were divided into four educational categories according to the level of education received (elementary school graduate or less, middle school graduate, high school graduate, college graduate or higher). The live birth rate was compared between different education level groups. We used logistic regression to analyze the association between maternal education level and live birth after IVF. RESULTS: We studied 41,546 women, who were grouped by maternal educational level: elementary school graduate or less (n = 1590), middle school graduate (n = 10,996), high school graduate (n = 8354), and college graduate or higher (n = 20,606). In multivariable logistic regression analysis, we did not demonstrate a statistically significant relationship between educational level and live birth in middle school graduate (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.84–1.09), high school graduate (AOR 1.01; 95% CI, 0.87–1.14) or college graduate or higher (AOR 1.01; 95% CI, 0.88–1.14) patients, with elementary school graduate or less as the reference group. CONCLUSIONS: Maternal educational level was not associated with the likelihood of live birth in patients undergoing fresh or frozen embryo transfer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02345-4.

We aimed to explore the effect of three pro-nuclei (3PN) incidence on laboratory and clinical outcomes after early rescue intracytoplasmic sperm injection (rescue-ICSI).This study included 509 early rescue-ICSI cycles from February 2014 to February 2019. The patients were divided into 3PN = 0% (394 cycles) and 3PN 0% (115 cycles) group. Main outcomes compared were good quality embryo, available embryo, implantation (IR), clinical pregnancy (CPR), abortion (AR) and live birth rates (LBR).There were no significant differences in the basal characteristics between two groups (3PN incidence made negative effects on the clinical outcomes after early rescue-ICSI.

BackgroundAlthough immunotherapy can induce durable anti-tumor response in multiple cancers, immune checkpoint blockade (ICB) therapy resistance in ovarian cancer and melanoma remains problematic. Here, we report that tumor cell-intrinsic mTORC1 regulates ICB response through mTORC1 defining subunit Raptor (Rptor) by modulating interferon-gamma (IFNg) resistance and tumor-initiating cell (TIC) virulence.MethodsWe knocked down two distinct mTORC1 signaling components: Rptor (Rptorlo, aids in mTORC1 assembly) and Lamtor1 (Ltor1lo, docks mTORC1 on lysosomes) in murine ovarian cancer ID8agg and melanoma B16 cells. PD-L1 was CRISPR knocked out in B16 and human ovarian cancer line ES2. Mice with tumors were treated with a-PD-L1± a-CD8 antibody. TICs were estimated by flow-cytometry.1ResultsRptorlo B16 and ID8agg, but not Ltor1lo B16 tumors grew slower and were a-PD-L1 responsive unlike control (ctrl) in WT mice. We noted that ctrl and Rptorlo B16 and ID8agg cells expressed similar surface PD-L1 in vitro. Thus, Rptor suppresses a-PD-L1 response in ICB-resistant tumors. Tumor immune analysis revealed increased CD8+ T cell% and a trend to increased IFNg+CD8+ T cells in a-PD-L1 treated Rptorlo, but not ctrl B16. Rptorlo a-PD-L1 efficacy was lost with a-CD8 and in IFNg knockout mice. In vitro, IFNg suppressed Rptorlo ID8agg proliferation, unlike ctrl. These data suggested that lack of Rptor makes tumors ICB responsive, possibly by making tumors IFNg-sensitive and increasing IFNg+CD8+ T cells. Further, tumor and draining lymph node (DLN) TCF1+PD-1+ T cell stem cells (critical for aPD-L1/PD-1 success2 3) were significantly higher in a-PD-L1 treated Rptorlo tumors. Thus, tumor Rptor status could regulate tumor microenvironment and distal DLN immune landscape on a-PD-L1 treatment.We previously published that mTORC1 promotes PD-L1-dependent tumor proliferation, TIC virulence1 4 PD-L1KO B16 and ES2 cells expressed similar total Rptor protein. However, lower levels of Rptor were loaded in mTOR complex in absence of PD-L1, as assessed by a-mTOR immunoprecipitation, suggesting that pro-tumorigenic Rptor functions were downstream of, and dependent on PD-L1. Successful Rptorlo aPD-L1 treatment reduced TIC in vivo, an effect reversed in absence of CD8+ T cells or host IFNg. Inhibiting ID8agg mTORC1 with rapamycin reduced stemness genes oct4, nanog expression by QPCR. Further, ID8agg Rptorlo TIC formed significantly smaller tumors versus ctrl TIC in immune-compromised NSG mice, confirming their reduced virulence. Rptor, but not Ltor1, expression inversely correlated with tumor CD8+ infiltrate in IMvigor210 trial, and strongly with TIC gene signature in ovarian cancer patients.5 6ConclusionsTumor-cell intrinsic Rptor modulates ICB resistance, IFNg responsiveness, immune microenvironment, and TIC virulence.AcknowledgementsN/ATrial RegistrationN/AReferencesGupta HB, et al. Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer. Signal Transduct Target Ther 2016;1,Article number:16030.Im SJ, et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 2016;537:417–421.Dammeijer F, et al. The PD-1/PD-L1-checkpoint restrains T cell immunity in tumor-draining lymph nodes. Cancer Cell 2020;38:685–700.Clark CA, et al. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis, and autophagy in ovarian cancer and melanoma. Cancer Res 2016;76:6964–6974.Smith BA, et al. A human adult stem cell signature marks aggressive variants across epithelial cancers. Cell Rep 2018;24:3353–3366.Hoffman-Censits JH, et al. IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). J Clin Oncol 2016;34, no.2_suppl:355–355.

Background: The optimal means to prepare the endometrial preparation for PCOS patients is a topic of ongoing controversy. Our objective was to compare the clinical outcomes of frozen-thawed embryo transfer (FET) with and without pretreatment gonadotropin-releasing hormone agonist (GnRHa) in polycystic ovary syndrome (PCOS) patients. Methods: In this retrospective cohort study, we evaluated 1638 consecutive cycles between June 2014 and December 2017 in the Assisted Reproduction Center of Northwest Women’s and Children’s Hospital. The patients who underwent FET were assigned to two groups as follows: hormone replacement treatment (HRT) group, comprising 1115 cycles; HRT with GnRHa pretreatment (GnRHa + HRT), comprising 523 cycles. Patients using GnRHa + HRT (n=519) were matched with 519 patients using HRT. Results: The live birth rate was higher in the GnRHa + HRT group compared with the HRT group with no significant difference (60.4% vs 55.5%, p=0.062). The clinical pregnancy rate (72.74% vs 75.33%), miscarriage rate (14.26% vs 13.96%) and ectopic pregnancy rate (0.36% vs 0.38%) were similar between the two groups. The preterm birth rate in HRT was lower than GnRHa + HRT (14.08% vs 20.08%). There were no significant interactions in any of the subgroups (p>0.05 for all comparisons). In the unadjusted model and adjusted model, the live birth rate was comparable between GnRHa + HRT and HRT group (OR 1.22, 95%CI, 0.99-1.51, p=0.062; aOR 1.56, 95%CI, 1.001-2.41, p=0.048). Similar results were obtained after propensity score matching in the entire cohort. Conclusions: GnRHa pretreatment could not improve the live birth rate in women with PCOS.

To compare the clinical outcome of fresh embryo transfer with frozen-thawed embryo transfer in subsequent cycle of GnRH antagonist protocol. Totally, 1430 women were enrolled from the cases of our Assisted Reproduction Center from January 2015 to January 2019 for this retrospective cohort study. The inclusion criteria of the subjects included women with ages under 40 years, 3–10 oocytes retrieved, good embryo quality according to gardener score, GnRH antagonist protocol, underwent first cycle of fresh embryo transfer or freeze-all strategy and transferred in subsequent cycle. However, the patients with endometriosis, PGD/PGS cycles, history of recurrent pregnancy loss and uterine pathology were excluded. 495 women of group I underwent fresh embryo transfer in first cycle and 935 patients of group II received frozen-thawed transfer in subsequent cycle. The primary outcome was clinical pregnancy rate. A logistic regression analysis was performed to determine the variables that could be independently associated with clinical pregnancy rate. Models were adjusted for covariates including patients’ age, fertilization type, infertility type, infertility duration, the number of oocytes retrieved, the number of embryos transferred and type of embryo transferred. Clinical pregnancy rate was significantly higher in frozen-thawed embryo transfer than in fresh embryo transfer (63.70% vs. 54.50%, p

Objective To investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients. Design We conducted a retrospective cohort analysis. Setting The study was conducted at an IVF clinic in a public hospital. Patients A total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria. Interventions None. Main outcome measure The primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI). Results The FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose. Conclusion Ovarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred.

BackgroundProgrammed cell death ligand-1 (PD-L1) overexpression in tumor cells inhibits T cells activity and delivers pathologic intracellular signals that can reduce cancer treatment responses in pre-clinicalmodels.1 2MethodsTo reduce tumor intracellular PD-L1-mediated pathology, we performed a drug screen that identified chlorambucil as a tumor cell PD-L1 depletion drug.ResultsChlorambucil depletes basal tumor PD-L1 expression through the ubiquitination proteasome pathway. In the tumor microenvironment, high chlorambucil doses treated orthotopic B16 melanoma and ID8agg ovarian cancer. Chlorambucil treatment efficacy was lost or reduced in PD-L1lo ID8agg and PD-L1KO B16 tumors, corroborated with in vitro data. These data suggest that chlorambucil anti-tumor activity of CAMB requires tumor PD-L1 expression, confirmed in PD-L1KO host challenge with CTRL tumor, which chlorambucil treated effectively. Chlorambucil rendered αPD-L1 resistant CTRL ID8agg and PD-L1lo B16 tumors αPD-L1 sensitive, preliminarily possibly due to tumor STING activation, and associated with enhanced tumor NK cell infiltration and central memory T cell generation. Chlorambucil also phenocopied genetic PD-L1KO by reducing tumor cell mTORC1 signals and stem cell content,3 suggesting additional treatment potential.ConclusionsChlorambucil could be a useful strategy to reprogram tumor PD-L1 signals and boost immune-based therapies especially for anti-PD-L1-resistant tumors.ReferencesClark CA et al. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis, and autophagy in ovarian cancer and melanoma. Cancer Res 2016;76:6964–6974.Juneja VR et al. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med 2017;214:895–904.Gupta HB et al. Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer. Signal Transduct Target Ther 2016;1:2095–9907.Ethics ApprovalWe received approval from the UT Health San Antonio Institutional Animal Care and Use Committee (IACUC) for each procedure that used mice. We conducted each experiment per the standards required by the UT Health San Antonio Department of Laboratory Animal Resources.

The purpose of this study is to assess the impact of a newly developed modules, Interactive Web-Based Visualization Tools for Gluing Undergraduate Fuel Cell Systems Courses system (IGLU), on learning motivations of engineering students using two samples (n1=144 and n2=135) from senior engineering classes. The multivariate analysis results revealed that the participants had a significant increase in their learning motivation after the treatment with the IGLU modules. This result was cross-validated with the two samples, in which the motivation mean posttest scores are significantly higher than the mean pretest scores, systematically (Sample 1: the mean score is increased by 2.09 [.32, 3.87] points, p = .021; Sample 2: the mean score is increased by 1.38 [.14, 2.61] points, p = .029). With the use of instructional technology prevailing in current university courses, the education initiative of the IGLU system and the assessment of its impact on student learning motivation provide us information to improve the modules to serve a more diverse student body. It will greatly help the development of engineering educational curriculum. With regards to the statistical inference, it is desirable to conduct further studies with a quasi-experiment control group design to assess the program effect focusing on student learning and its associations with student learning motivations and learning styles.

To investigate the clinical efficacy of growth hormone (GH) in normal response patients with poor embryo quality in previous in vitro fertilization cycles. A total of 1562 infertile women w...

The ectopic pregnancy (EP) rate after in vitro fertilization-embryo transfer (IVF-ET) is higher than after spontaneous conception. The reason for the increased risk of EP is not clear. We aimed to determine the risk factors associated with EP in patients undergoing IVF-ET.This was a 1:4 matched case-control study that enrolled 225 EP patients and 900 matched intrauterine pregnancy patients from the ART center of Northwest Women's and Children's Hospital from January 2014 to April 2018. Conditional logistic regression was used to analyze the association between risk factors and EP, and a receiver-operating characteristic (ROC) curve was generated for the predictors of EP.Our findings showed that tubal factor (OR 1.61; 95% CI 1.12-2.31) and pelvic surgery other than cesarean section (OR 2.04; 95% CI 1.26-3.29) were associated with a higher risk of EP (p = 0.001). An endometrial thickness 12 mm prior to embryo transfer (OR 0.27; 95% CI 0.13-0.56) and the number of transferable embryos (OR 0.71; 95% CI 0.65-0.78) were protective factors against EP (p 0.001). The other factors did not have a significant effect on the probability of developing ectopic pregnancy. The area under the curve of the endometrial thickness and the number of transferable embryos for EP prediction were higher than those for tubal factor and pelvic surgery other than cesarean section.An endometrial thickness 12 mm is a strong protective factor against ectopic pregnancy. Attention should be paid to women with specific characteristics who have undergone IVF-ET.

Microblog has become a popular social media because of its short text and timely release, and its impact on society has gradually increased. In order to study the behaviour of microblog users, this paper introduced two algorithms for microblog network community division, which were community discovery algorithm based on density peak clustering and community discovery algorithm based on similarity. Then the two algorithms were simulated using MATLAB software. The data used in the experiment included the artificial network generated by LFR tool and the following information data of different users collected by taking the API interface of the microblog of a student from Computer School of Jining Normal University as the starting point by crawlers. The results demonstrated that the normalised mutual information (NMI) and the density of the community structure obtained by the two algorithms decreased, and the conductivity increased with the expansion of the scale of microblog network, and the community structure obtained by the similarity-based algorithm had higher NMI and density and lower conductivity under the same scale of micrblog network. In conclusion, the similarity-based algorithm can divide microblog network better.

This study investigated the effects of economic status and the educational expectations of significant others on early university aspirations and actual university attainment. The study analyzed two-wave longitudinal data collected from 1,595 Taiwanese students in their 9th grade in middle school and in their freshman year at universities. The results revealed that economic status affected neither university aspirations nor university attainment. Among the significant others studied, parental expectations fundamentally affected university aspirations and teacher expectations consistently affected university aspirations and attainment. After considering economic status and educational expectations, early university aspirations remained strongly related to actual university attainment. Future research directions and practical educational approaches are recommended based on the aforementioned results.

Background Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility. Methods In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer. Results The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, o...

The present study utilizes a multilevel approach to assess the effects of four different types of intervention on college student retention, focusing on the interaction effects between the student characteristics and the types of intervention. The program effects on a 3-year trend are also explored. The findings of the present study reveal that the social integration programs improved the first-year retention rates for female students, the advising programs and the social integration programs worked better in the first year for students from more selective colleges within the university, and the first-year experience programs had a significant lasting effect across the 3 years on retention for elder students and male students. It is also found that the advising programs were significantly more effective on the first-year retention rates than the general orientation programs. This study provides empirical evidence for researchers and administrators in higher education to improve the effectiveness of intervention programs for students with specific characteristics.

The Drug Abuse Resistance Education (D.A.R.E.) program is a widespread but controversial school-based drug prevention program in the United States as well as in many other countries. The present multivariate meta-analysis reviewed 20 studies that assessed the effectiveness of the D.A.R.E. program in the United States. The results showed that the effects of the D.A.R.E. program on drug use did not vary across the studies with a less than small overall effect while the effects on psychosocial behavior varied with still a less than small overall effect. In addition, the characteristics of the studies significantly explained the variation of the heterogeneous effects on psychosocial behavior, which provides empirical evidence for improving the school-based drug prevention program.

Piperlongumine (PPLGM), an alkaloid isolated from the long pepper (Piper longum L.), can selectively trigger cancer cell death in colorectal cancer cells. The present study investigated whether the c-Jun NH2-terminal kinase (JNK) signaling pathway is involved in PPLGM-induced apoptosis in the human colorectal cancer HCT116 cell line. The results demonstrated that PPLGM reduced the cell viability and induced cell apoptosis in a time- and concentration-dependent manner, without a significant effect on cell cycle distribution. Meanwhile, treatment with 10 µM PPLGM resulted in JNK activation within 1 h, and a marked and sustained increase in c-Jun phosphorylation in the HCT116 cells. In addition, SP600125, a general inhibitor of JNK, inhibited PPLGM-induced apoptosis in the HCT116 cells by inhibiting PPLGM-induced c-Jun phosphorylation. Altogether, it can be concluded that the JNK signaling pathway, at least in part, is involved in PPLGM-mediated apoptosis in HCT116 cells.