Body mass index modified the effectiveness of low dose aspirin treatment on frozen-thawed embryo transfer outcome: a propensity score-matched study.

Background: Low-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI). Methods: A retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders. Results: The clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (<18.5 kg/m2) in either unmatched (46.4% versus 59.8%, RR:1.29, 95%CI:1.07-1.55) or matched cohort (44% versus 59.8%, RR: 1.36, 95%CI: 1.01-1.83) but not in patients with higher BMI categories. With the interaction analysis, less association between aspirin and live birth appeared in patients with normal BMI (Ratio of OR:0.49, 95%CI: 0.29-0.81) and high BMI (Ratio of OR:0.57, 95%CI: 0.27-1.2) compared with patients with low BMI. Conclusion: BMI may be considered when evaluating aspirin's effect in FET cycles.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

Predicting the unexpected total fertilization failure in conventional in vitro fertilization cycles: What is the role of semen quality?

Background: Male and female gametes factors might contribute to the total fertilization failure (TFF). In first in vitro fertilization (IVF) cycles, decision-making of insemination protocol was mainly based on semen quality for the contribution of female clinical characteristics to TFF remained obscure. The purpose of the study was to evaluate the role of semen quality in predicting unexpected TFF. Methods: A single-center retrospective cohort analysis was performed on 19539 cycles between 2013 and 2021. Two algorithms, a Least Absolute Shrinkage and Selection Operator (LASSO) and an Extreme Gradient Boosting (Xgboost) were used to create models with cycle characteristics parameters. By including semen parameters or not, the contribution of semen parameters to the performance of the models was evaluated. The area under the curve (AUC), the calibration, and the net reclassification index (NRI) were used to evaluate the performance of the models. Results: The prevalence of TFF were .07 (95%CI:0.07-0.08), and .08 (95%CI:0.07-0.09) respectively in the development and validation group. Including all characteristics, with the models of LASSO and Xgboost, TFF was predicted with the AUCs of .74 (95%CI:0.72-0.77) and .75 (95%CI:0.72-0.77) in the validation group. The AUCs with models of LASSO and Xgboost without semen parameters were .72 (95%CI:0.69-0.74) and .73 (95%CI:0.7-0.75). The models of LASSO and Xgboost with semen parameters only gave the AUCs of .58 (95%CI:0.55-0.61) and .57 (95%CI:0.55-0.6). For the overall validation cohort, the event NRI values were -5.20 for the LASSO model and -.71 for the Xgboost while the non-event NRI values were 10.40 for LASSO model and 0.64 for Xgboost. In the subgroup of poor responders, the prevalence was .21 (95%CI:0.18-0.24). With refitted models of LASSO and Xgboost, the AUCs were .72 (95%CI:0.67-0.77) and .69 (95%CI:0.65-0.74) respectively. Conclusion: In unselected patients, semen parameters contribute to limited value in predicting TFF. However, oocyte yield is an important predictor for TFF and the prevalence of TFF in poor responders was high. Because reasonable predicting power for TFF could be achieved in poor responders, it may warrant further study to prevent TFF in these patients.

Does conventional morphological evaluation still play a role in predicting blastocyst formation?

BACKGROUND: Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation. METHODS: Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles. RESULTS: Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77-0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771-0.789) and 0.754(95%CI: 0.745-0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911-0.94). CONCLUSION: The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.

Regulation of the Two-Component Regulator CpxR on Aminoglycosides and ß-lactams Resistance in Salmonella enterica serovar Typhimurium.

The two-component signal transduction system CpxAR is especially widespread in Gram-negative bacteria. It has been reported that CpxAR contributes to the multidrug resistance (MDR) in Escherichia coli. CpxR is a response regulator in the two-component CpxAR system. The aim of this study was to explore the role of cpxR in the MDR of S. enterica serovar Typhimurium. The minimal inhibitory concentrations (MICs) of various antibiotics commonly used in veterinary medicine for strains JS (a multidrug-susceptible standard strain of S. enterica serovar Typhimurium), JSΔcpxR, JSΔcpxR/pcpxR, JSΔcpxR/pcpxR (*), JSΔcpxRΔacrB, JSΔcpxRΔacrB/pcpxR, JSΔcpxRΔacrB/pcpxR (*), 9 S. enterica serovar Typhimurium isolates (SH1-9), and SH1-9ΔcpxR were determined by the 2-fold broth microdilution method. The relative mRNA expression levels of ompF, ompC, ompW, ompD, tolC, acrB, acrD, acrF, mdtA, marA, and soxS in strains JS, JSΔcpxR, and JSΔcpxR/pcpxR were detected by real-time PCR. The results showed 2- to 4-fold decreases in the MICs of amikacin (AMK), gentamycin (GEN), apramycin (APR), neomycin (NEO), ceftriaxone (CRO), ceftiofur (CEF), and cefquinome (CEQ) for strain JSΔcpxR, as compared to those for the parental strain JS. Likewise, SH1-9ΔcpxR were found to have 2- to 8-fold reduction in resistance to the above antibiotics, except for NEO, as compared to their parental strains SH1-9. Furthermore, 2- to 4-fold further decreases in the MICs of AMK, GEN, APR, and CEF for strain JSΔcpxRΔacrB were observed, as compared to those for strain JSΔacrB. In addition, CpxR overproduction in strain JSΔcpxR led to significant decreases in the mRNA expression levels of ompF, ompC, ompW, ompD, tolC, acrB, marA, and soxS, and significant increases in those of stm3031 and stm1530. Notably, after all strains were induced simultaneously by GEN to the 15th passage at subinhibitory concentrations, strain JSΔcpxR/pcpxR showed significant increases in mRNA expression levels of the efflux pump acrD and mdtA genes, as compared to strain JSΔcpxR. Our results indicate that the two-component regulator CpxR contributes to resistance of S. enterica serovar Typhimurium to aminoglycosides and ß-lactams by influencing the expression level of the MDR-related genes.

Equity of the essential public health service in rural china: evidence from a nationwide survey of hypertensive patients.

OBJECTIVES: To explore healthcare disparities in rural China two years after the implementation of the Essential Public Health Service (EPHS) reform in 2009. METHODS: A cross-sectional study was conducted by surveying 930 hypertension patients (HPs) from different regions in rural China in 2011. The percentages of patients using recommended four or more follow-up visits in a year were calculated by patient socio-demographic characteristics and statistically examined using chi-square and logistic regression to uncover disparities and correlated factors in EPHS use. RESULTS: The rates were not significantly different by age, gender, education, insurance status or income, but significantly different by region and hypertension history (p<0.01). Higher rates were also observed on patients who sought actively follow-up service at clinics, making appointment for the next follow-up with doctors, awareness of the need of follow-up, more satisfied with the follow-up services, and better medication adherence (p<0.01). CONCLUSIONS: There were no disparities observed among HPs in the use of follow-up services, suggesting that the reform has to some extent achieved its goal in ensuring equal access to EPHS. In this regard, regional implementation of the national policies and improvement of EPHS management at local level should be further improved.

Genome-wide identification of micro-ribonucleic acids associated with human endometrial receptivity in natural and stimulated cycles by deep sequencing.

OBJECTIVE: To identify microRNAs (miRNAs) associated with endometrial receptivity. DESIGN: Observational study. SETTING: Medical center. PATIENT(S): Healthy, regularly cycling women undergoing IVF treatment. INTERVENTION(S): Gonadotropin stimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S): Quantification of miRNA expression profiles by deep sequencing. RESULT(S): The miRNA expression profiles in human endometrium on days LH+2 and LH+7 (LH = 0 is the day of the LH surge) in natural cycles as well as on days hCG+4 and hCG+7 (hCG = 0 is the day of hCG injection) in stimulated cycles were determined by deep sequencing. In natural cycles, there were 20 significantly changed miRNAs in human endometrium on LH+7 compared with LH+2. These miRNAs were predicted to target a large set of genes with different functions, including cell cycle, transport, cell adhesion, cell death, and metabolism. In stimulated cycles, 22 miRNAs were significantly dysregulated on hCG+7 in comparison with LH+7, 11 of which exhibited putative estrogen response elements or P response elements in the promoters. Additionally, unsupervised hierarchical clustering analysis demonstrated that the miRNA expression profile on hCG+4 was similar to that on LH+7, suggesting that ovarian stimulation may alter the window of endometrial receptivity. CONCLUSION(S): MiRNAs may be novel biomarkers for human endometrial receptivity and may help optimize the protocol for IVF treatment.