Dynamic peripheral blood microRNA expression landscape during the peri-implantation stage in women with successful pregnancy achieved by single frozen-thawed blastocyst transfer.

STUDY QUESTION: What are the dynamic expression features of plasma microRNAs (miRNAs) during the peri-implantation period in women with successful pregnancy via single frozen-thawed blastocyst transfer? SUMMARY ANSWER: There is a significant change in the plasma miRNA expression profile before and after blastocyst transfer, during the window of implantation. WHAT IS KNOWN ALREADY: The expression of miRNAs in peripheral blood has indicative functions during the peri-implantation period. Nevertheless, the dynamic expression profile of circulating miRNAs during the peri-implantation stage in women with a successful pregnancy has not been studied. STUDY DESIGN SIZE DURATION: Seventy-six women treated for infertility with a single frozen-thawed blastocyst transfer in a natural cycle were included in this study. Among them, 57 women had implantation success and a live birth, while 19 patients experienced implantation failure. Peripheral blood samples were collected at five different time points throughout the peri-implantation period, including D0 (ovulation day), D3, D5, D7, and D9 in this cycle of embryo transfer. The plasma miRNAs in women with blastocyst transfer were isolated, sequenced, and analyzed. PARTICIPANTS/MATERIALS SETTING METHODS: Peripheral blood samples were collected in EDTA tubes and stored at -80°C until further use. miRNAs were isolated from blood, cDNA libraries were constructed, and the resulting sequences were mapped to the human genome. The plasma miRNAs were initially analyzed in a screening cohort (n = 34) with successful pregnancy. Trajectory analysis, including a global test and pairwise comparisons, was performed to detect dynamic differentially expressed (DE) miRNAs. Fuzzy c-means clustering was conducted for all dynamic DE miRNAs. The correlation between DE miRNAs and clinical characteristics of patients was investigated using a linear mixed model. Target genes of the miRNAs were predicted, and functional annotation analysis was performed. The expression of DE miRNAs was also identified in a validation set consisting of women with successful (n = 23) and unsuccessful (n = 19) pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: Following small RNA sequencing, a total of 2656 miRNAs were determined as valid read values. After trajectory analysis, 26 DE miRNAs (false discovery rate < 0.05) were identified by the global test, while pairwise comparisons in addition identified 20 DE miRNAs. A total of seven distinct clusters representing different temporal patterns of miRNA expression were discovered. Nineteen DE miRNAs were further identified to be associated with at least one clinical trait. Endometrium thickness and progesterone level showed a correlation with multiple DE miRNAs (including two of the same miRNAs, hsa-miR-1-3p and hsa-miR-6741-3p). Moreover, the 19 DE miRNAs were predicted to have 403 gene targets, and there were 51 (12.7%) predicted genes likely involved in both decidualization and embryo implantation. Functional annotation for predicted targets of those clinically related DE miRNAs suggested the involvement of vascular endothelial growth factor and Wnt signaling pathways, as well as responses to hormones, immune responses, and cell adhesion-related signaling pathways during the peri-implantation stage. LARGE SCALE DATA: The raw miRNA sequence data reported in this article have been deposited in the Genome Sequence Archive (GSA-Human: HRA005227) and are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/browse/HRA005227. LIMITATIONS REASONS FOR CAUTION: Although the RNA sequencing results revealed the global dynamic changes of miRNA expression, further experiments examining the clinical significance of the identified DE miRNAs in embryo implantation outcome and the relevant regulatory mechanisms involved are warranted. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the dynamic landscape of the miRNA transcriptome could shed light on the physiological mechanisms involved from ovulation to the post-implantation stage, as well as identifying biomarkers that characterize stage-related biological process. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Major clinical research project of Tangdu Hospital (2021LCYJ004) and the Discipline Platform Improvement Plan of Tangdu Hospital (2020XKPT003). The funders had no influence on the study design, data collection, and analysis, decision to publish, or preparation of the article. There are no conflicts of interest to declare.

Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention.

Introduction: A systematic review analysis was used to assess the profile of mitochondrial involvement in adipose tissue regulation and potential reagents to intervene in obesity through the mitochondrial pathway. Methods: Three databases, PubMed, Web of Science, and Embase, were searched online for literature associated with mitochondria, obesity, white adipose tissue, and brown adipose tissue published from the time of their creation until June 22, 2022, and each paper was screened. Results: 568 papers were identified, of which 134 papers met the initial selection criteria, 76 were selected after full-text review, and 6 were identified after additional searches. A full-text review of the included 82 papers was performed. Conclusion: Mitochondria play a key role in adipose tissue metabolism and energy homeostasis, including as potential therapeutic agents for obesity.

Ovarian stimulation protocols for poor ovarian responders: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of manifold ovarian stimulation protocols for patients with poor ovarian response. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched until February 14, 2021. Primary outcomes included clinical pregnancy rate per initiating cycle and low risk of cycle cancellation. Secondary outcomes included number of oocytes retrieved, number of metaphase II (MII) oocytes, number of embryos obtained, number of transferred embryos, endometrial thickness on triggering day and estradiol (E2) level on triggering day. The network plot, league table, rank probabilities and forest plot of each outcome measure were drawn. Therapeutic effects were displayed as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: This network meta-analysis included 15 trials on 2173 participants with poor ovarian response. Delayed start GnRH antagonist was the best regimen in terms of clinical pregnancy rate per initiating cycle (74.04% probability of being the optimal), low risk of cycle cancellation (75.30%), number of oocytes retrieved (68.67%), number of metaphase II (MII) oocytes (97.98%) and endometrial thickness on triggering day (81.97%), while for E2 level on triggering day, microdose GnRH agonist (99.25%) was the most preferred. Regarding number of embryos obtained and number of transferred embryos, no statistical significances were found between different ovarian stimulation protocols. CONCLUSION: Delayed start GnRH antagonist and microdose GnRH agonist were the two superior regimens in the treatment of poor ovarian response, providing favorable clinical outcomes. Future investigation is needed to confirm and enrich our findings.

Epigallocatechin-3-gallate (EGCG) attenuates inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced endometritis via silent information regulator transcript-1 (SIRT1)/nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) pathway.

The protective effects of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl-2, cleaved caspase-3, silent information regulator transcript-1 (SIRT1), nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase1 was detected by Western blot and real-time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS-induced uterine histopathological changes, MPO activity, pro-inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.

Clinical pregnancy outcomes prediction in vitro fertilization women based on random forest prediction model: A nested case-control study.

The present study aimed to analyze the risk factors influencing the in vitro fertilization embryo transfer (IVF-ET) pregnancy and to construct a prediction model for clinical pregnancy outcome in patients receiving IVF-ET based on the predictors. In this nested case-control study, the data of 369 women receiving IVF-ET were enrolled. Univariate and multivariate Logistic regression analyses were conducted to identify the potential predictors. Ten-fold cross validation method was used to validate the random forest model for predicting the clinical pregnancy. The receiver operating characteristic curve was drawn to evaluate the prediction ability of the model. The importance of variables was shown according to Mean Decrease Gini. The data delineated that age (odds ratio [OR]= 1.093, 95% confidence interval [CI]: 1.036-1.156, P = .0010), body mass index (BMI) (OR = 1.094, 95%CI: 1.021-1.176, P = .012), 3 cycles (OR = 0.144, 95%CI: 0.028-0.534, P = .008), hematocrit (HCT) (OR = 0.865, 95% CI: 0.791-0.943, P = .001), luteinizing hormone (LH) (OR = 0.678, 95%CI: 0.549-0.823, P < .001), progesterone (P) (OR = 2.126, 95%CI: 1.112-4.141, P = .024), endometrial thickness (OR = 0.132, 95%CI: 0.034-0.496, P = .003) and FSH (OR = 1.151, 95%CI: 1.043-1.275, P = .006) were predictors associated with the clinical pregnancy outcome of patients receiving IVF-ET. The results might provide a novel method to identify patients receiving IVF-ET with a high risk of poor pregnancy outcomes and provide interventions in those patients to prevent the occurrence of poor pregnancy outcomes.

A research on quality of life score (QOLS) of patients with trigeminal neuralgia (TN).

BACKGROUND: To evaluate the clinic effect of treatment of trigeminal neuralgia (TN). METHODS: The current study aims to develop a multiple-scale characteristics quality of life (QOL) for patients with TN. After interview, the individual questionnaire was acquired. indicating the QOL has a good responsiveness and surveying effects of the dynamic state of health on TN patients. CONCLUSION: It is feasible to form multiple-scale characteristics QOL for patients with TN.