Mixed probiotics modulated gut microbiota to improve spermatogenesis in bisphenol A-exposed male mice.

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.

The effect of embryo selection using time-lapse monitoring on IVF/ICSI outcomes: A systematic review and meta-analysis.

AIM: To explore the effect of embryo selection using the time-lapse monitoring (TLM) system compared with conventional morphological selection (CMS) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. METHODS: We searched PubMed, Ovid-Embase, and The Cochrane Library for the following studies: At Comparison 1, embryo selection using TLM images in a TLM incubator based on morphology versus embryo selection using CMS in a conventional incubator based on morphology; at Comparison 2, embryo selection using TLM based on morphokinetics versus embryo selection using CMS based on morphology. The primary outcomes were the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), and implantation rate (IR), and the secondary outcome was the miscarriage rate (MR). RESULTS: A total of 14 randomized control trials (RCTs) were included. Both based on morphology, TLM incubators increased the IR (risk ratio [RR]: 1.10; 95% confidence interval [CI]: 1.01, 1.18; I2 = 0%, moderate-quality evidence) compared to conventional incubators. Low- to moderate-quality evidence suggests that TLM incubators did not improve LBR, OPR, CPR, and MR compared to conventional incubators. In addition, low- to moderate-quality evidence indicates that embryo selection using TLM based on morphokinetics did not improve LBR, OPR, CPR, IR, or MR compared to CMS based on morphology. CONCLUSIONS: Low- to moderate-quality evidence suggests that neither TLM incubators nor embryo selection using TLM based on morphokinetics improved clinical outcomes (LBR, OPR, CPR, and MR) compared with CMS based on morphology. TLM is still an investigational procedure for IVF/ICSI practice.

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases.

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials.

IMPORTANCE: The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation. OBJECTIVE: To investigate the effect of progesterone supplementation for LPS on the reproductive outcomes of patients undergoing NC-FET cycles. DATA SOURCES: The PubMed, Ovid-Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM were electronically searched. The search time frame was from inception up to September 2022. STUDY SELECTION AND SYNTHESIS: Randomized controlled trials (RCTs) that used progesterone for LPS in NC-FET cycles, including true NC-FET cycles (tNC-FET) and modified NC-FET cycles (mNC-FET), were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI). MAIN OUTCOME MEASURES: The primary outcomes were the live birth rate (LBR) and the clinical pregnancy rate (CPR), and the secondary outcome was the miscarriage rate. RESULTS: Four RCTs were included, which involved 1116 participants. The results of the meta-analysis showed that progesterone supplementation was associated with increased LBR (RR, 1.42; 95% CI, 1.15-1.75; I2 = 0%, moderate-quality evidence) and CPR (RR, 1.30, 95% CI, 1.07-1.57; I2 = 0%, moderate-quality evidence) in patients undergoing NC-FET cycles. Subgroup analysis showed that progesterone supplementation was associated with higher LBR and CPR in tNC-FET cycles. However, no association was found between increased LBR and CPR in mNC-FET cycles. In addition, only one RCT reported that oral dydrogesterone had similar CPR and miscarriage rate compared with vaginal progesterone in mNC-FET cycles. CONCLUSION(S): Overall, moderate-quality evidence suggested that progesterone supplementation for LPS was associated with increased LBR and CPR in NC-FET cycles. Progesterone supplementation was associated with a higher LBR and CPR in tNC-FET cycles. However, the effectiveness of progesterone supplementation in mNC-FET cycles should be further verified by larger RCTs. Low to very low-quality evidence indicated that oral dydrogesterone and vaginal progesterone have similar reproductive outcomes in mNC-FET cycles, which requires further study, especially in tNC-FET cycles. REGISTRATION NUMBER: PROSPERO CRD42022355550 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355550) was registered on September 3, 2022.

Reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with a septate uterus: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to analyze the reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility. DATA SOURCES: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, and Chinese Biomedical Literature Database (CBM) databases were electronically searched. The search time frame was from inception up to July 2021. The English search terms were (arcuate* and uter*), (sept* and uter*), (subseptate* and uter*), metroplast*, septoplast*, and resect*. STUDY ELIGIBILITY CRITERIA: Selection criteria included randomized controlled trials, cohort studies, and case series that explored reproductive outcomes after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility with or without a control group. METHODS: The primary outcomes were the live birth rate and eventual postoperative live birth rate after hysteroscopic septum resection. The secondary outcomes were the clinical pregnancy rate, preterm birth rate, and miscarriage rate. Study-level proportions of outcomes were transformed using the Freeman-Tukey double-arcsine transformation to calculate pooled values for the postoperative rates; the counted data were analyzed using relative risk as the effect analysis statistic, and each effect size was provided with its 95% confidence interval. Heterogeneity between the results of the included studies was analyzed using the I2 test. RESULTS: Overall, 5 cohort studies and 22 case series involving 1506 patients were included. In patients with a septate uterus and recurrent miscarriage, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 1.77; 95% confidence interval, 1.26-2.49; P=.001; I2=0%), resulting in a postoperative live birth rate of 66% (95% confidence interval, 59-72), and septum resection was associated with a reduced preterm birth rate (relative risk, 0.15; 95% confidence interval, 0.04-0.53; P=.003; I2=0%) and miscarriage rate (relative risk, 0.36; 95% confidence interval, 0.20-0.66; P=.0009; I2=0%). In patients with a septate uterus and primary infertility, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 4.12; 95% confidence interval, 1.19-14.29; P=.03; I2=0%) and clinical pregnancy rate (relative risk, 2.28; 95% confidence interval, 1.04-4.98; P=.04; I2=0%). The postoperative live birth rate was 37% (95% confidence interval, 30-44), and the miscarriage rate of patients with primary infertility was reduced (relative risk, 0.19; 95% confidence interval, 0.06-0.56; P=.003). The efficacy of hysteroscopic septum resection in patients with secondary infertility was unclear. However, their postoperative live birth rate was found to be 41% (95% confidence interval, 2-88). CONCLUSION: Hysteroscopic septum resection is associated with an increased live birth rate and a reduced miscarriage rate in patients with recurrent miscarriage or primary infertility, indicating that septum resection may improve the reproductive outcomes of these patients. The effectiveness of septum resection was unclear for patients with secondary infertility. These findings are limited by the quality of the included studies, warranting further randomized controlled trials, including only patients with recurrent miscarriage or primary infertility.

Independent value of serum ß-human chorionic gonadotropin in predicting early pregnancy loss risks in IVF/ICSI cycles.

Background: Early pregnancy loss (EPL) is the most prevalent complication, particularly in couples undergoing assisted reproductive technology treatment. The present study aimed to determine whether the serum ß-human chorionic gonadotropin (ß-hCG) level after 14 days of embryo transfer, either alone or in conjunction with other parameters in IVF/ICSI cycles, could be used to predict subsequent EPL. Methods: This was a retrospective cohort study of all couples who received clinical pregnancy and underwent fresh IVF/ICSI cycles at a single large reproductive medical center between January 2013 and June 2020. The research involved a total of 6600 cycles. For risk variables, we conducted the least absolute shrinkage and selection operator (LASSO) analysis, and for risk scoring, we used logistic regression coefficients. To analyze relevant risk factors for EPL, univariate and multivariate logistic regression analyses were employed. Areas under the curve (AUC) were determined and compared between ß-hCG and other factors using receiver operating characteristic (ROC) curves. Results: ß-hCG level was considerably lower in women who had EPL than in those who were ongoing pregnancy (564.03 ± 838.16 vs 1139.04 ± 1048.72 IU/L, p< 0.001). Univariable and multivariable logistic regression revealed that ß-hCG levels were significantly correlated with the probability of EPL, independent of other risk factors. More importantly, the ß-hCG level could independently predict the occurrence of EPL and was comparable to the model that combined other risk factors. The optimal serum ß-hCG cut-off value for predicting EPL was 542.45 IU/L. Conclusions: Our results suggest that the serum ß-hCG level has a strong independent predictive value for EPL occurrence in fresh IVF/ICSI cycles.

Risk factors related to early pregnancy loss in fresh IVF/ICSI: An analysis of 954 embryo transfer cycles.

Early pregnancy loss (EPL) is a common complication of assisted reproductive technology treatment; however, the exact factors involved in EPL are not fully understood. This study aimed to evaluate the risk factors for EPL in fresh in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. This retrospective cohort study was conducted on all couples who underwent clinical pregnancy in fresh IVF/ICSI cycles from January to December 2019 at a single large reproductive medical center. In total, 954 cycles were included in this study. Univariate and multivariate logistic regression analyses were performed to evaluate relevant risk factors for EPL. Curve fitting and threshold analyses were used to explore the association between risk factors and EPL. Compared with women with a normal total antral follicle count (AFC) (≥10, <15), those with a low AFC (<10) had a higher risk of EPL (odds ratio 2.97, 95% confidence interval: 1.38-6.38, P < .05). Patients with an estradiol/progesterone ratio (E2/P) ≥ 1.1 had significantly lower odds of EPL than women with E2/P < 1.1 (odds ratio 0.51, 95% confidence interval 0.28-0.91, P < .05). E2/P and serum human chorionic gonadotropin (hCG) levels negatively correlated with EPL. By using a 2-piecewise regression model, the inflection point of serum hCG level was 599.9 IU/L. Our results showed that lower AFC, E2/P, and serum hCG levels were associated with a higher EPL risk in fresh IVF/ICSI cycles.

Animal Models of Rotator Cuff Injury and Repair: A Systematic Review.

There are a large number of animal studies on rotator cuff injury and repair, but a lack of detailed research and evaluation on the animal models. This systematic review aims to provide a framework for animal studies and repair patches for rotator cuff injury. Four hundred nine animal studies were included, of which the most common animal model of rotator cuff injury is rat (53.56%), the most common site of rotator cuff injury is the supraspinatus tendon (62.10%), and the most common injury type (degree) is acute tear (full thickness) (48.41%). The most common research purpose is to evaluate the repair effect of the patch (24.94%), followed by the observation of pathophysiological changes after rotator cuff injury (20.87%). Among the five types of repair patch materials including nondegradable and degradable synthetic materials, autologous and allogeneic tissues, and naturally derived biomaterial, the last one is the mostly used (52.74%). For different animal models, the rodent models (rat and mouse) are the most commonly used and probably the most suitable species for preliminary studies of rotator cuff injury; the rabbit, canine, sheep, and goat models are more suitable for biomechanical performance testing, rehabilitation training, and validation of surgical methods; and the nonhuman primate models (monkey and baboon) are the closest to human, but it is more difficult to carry out the animal studies on them because of ethical issues, high feeding cost, and management difficulties.

Evaluation of patches for rotator cuff repair: A systematic review and meta-analysis based on animal studies.

Based on the published animal studies, we systematically evaluated the outcomes of various materials for rotator cuff repair in animal models and the potentials of their clinical translation. 74 animal studies were finally included, of which naturally derived biomaterials were applied the most widely (50.0%), rats were the most commonly used animal model (47.0%), and autologous tissue demonstrated the best outcomes in all animal models. The biomechanical properties of naturally derived biomaterials (maximum failure load: WMD 18.68 [95%CI 7.71-29.66]; P = 0.001, and stiffness: WMD 1.30 [95%CI 0.01-2.60]; P = 0.048) was statistically significant in the rabbit model. The rabbit model showed better outcomes even though the injury was severer compared with the rat model.

Mechanisms and Advances in Anti-Ovarian Cancer with Natural Plants Component.

Ovarian cancer ranks seventh in the most common malignant tumors among female disease, which seriously threatens female reproductive health. It is characterized by hidden pathogenesis, missed diagnosis, high reoccurrence rate, and poor prognosis. In clinic, the first-line treatment prioritized debulking surgery with paclitaxel-based chemotherapy. The harsh truth is that female patients are prone to relapse due to the dissemination of tumor cells and drug resistance. In these circumstances, the development of new therapy strategies combined with traditional approaches is conductive to improving the quality of treatment. Among numerous drug resources, botanical compounds have unique advantages due to their potentials in multitarget functions, long application history, and wide availability. Previous studies have revealed the therapeutic effects of bioactive plant components in ovarian cancer. These natural ingredients act as part of the initial treatment or an auxiliary option for maintenance therapy, further reducing the tumor and metastatic burden. In this review, we summarized the functions and mechanisms of natural botanical components applied in human ovarian cancer. We focused on the molecular mechanisms of cell apoptosis, autophagy, RNA and DNA lesion, ROS damage, and the multiple-drug resistance. We aim to provide a theoretical reference for in-depth drug research so as to manage ovarian cancer better in clinic.

Therapeutic Effects of Stem Cells From Different Source on Renal Ischemia- Reperfusion Injury: A Systematic Review and Network Meta-analysis of Animal Studies.

Objective: Although stem cell therapy for renal ischemia-reperfusion injury (RIRI) has made immense progress in animal studies, conflicting results have been reported by the investigators. Therefore, we aimed to systematically evaluate the effects of different stem cells on renal function of animals with ischemia-reperfusion injury and to compare the efficacies of stem cells from various sources. Methods: PubMed, Web of Science, Embase, Cochrane, CNKI, VIP, CBM, and WanFang Data were searched for records until April 2021. Two researchers independently conducted literature screening, data extraction, and literature quality evaluation. Results and conclusion: Seventy-two animal studies were included for data analysis. Different stem cells significantly reduced serum creatinine and blood urea nitrogen levels in the early and middle stages (1 and 7 days) compared to the negative control group, however there was no significant difference in the late stage among all groups (14 days); In the early stage (1 day), the renal histopathological score in the stem cell group was significantly lower than that in the negative control group, and there was no significant difference among these stem cells. In addition, there was no significant difference between stem cell and negative control in proliferation of resident cells, however, significantly less apoptosis of resident cells than negative control. In conclusion, the results showed that stem cells from diverse sources could improve the renal function of RIRI animals. ADMSCs and MDMSCs were the most-researched stem cells, and they possibly hold the highest therapeutic potential. However, the quality of evidence included in this study is low, and there are many risks of bias. The exact efficacy of the stem cells and the requirement for further clinical studies remain unclear.

Biodegradable metals for bone defect repair: A systematic review and meta-analysis based on animal studies.

Biodegradable metals are promising candidates for bone defect repair. With an evidence-based approach, this study investigated and analyzed the performance and degradation properties of biodegradable metals in animal models for bone defect repair to explore their potential clinical translation. Animal studies on bone defect repair with biodegradable metals in comparison with other traditional biomaterials were reviewed. Data was carefully collected after identification of population, intervention, comparison, outcome, and study design (PICOS), and following the inclusion criteria of biodegradable metals in animal studies. 30 publications on pure Mg, Mg alloys, pure Zn and Zn alloys were finally included after extraction from a collected database of 2543 publications. A qualitative systematic review and a quantitative meta-analysis were performed. Given the heterogeneity in animal model, anatomical site and critical size defect (CSD), biodegradable metals exhibited mixed effects on bone defect repair and degradation in animal studies in comparison with traditional non-degradable metals, biodegradable polymers, bioceramics, and autogenous bone grafts. The results indicated that there were limitations in the experimental design of the included studies, and quality of the evidence presented by the studies was very low. To enhance clinical translation of biodegradable metals, evidence-based research with data validity is needed. Future studies should adopt standardized experimental protocols in investigating the effects of biodegradable metals on bone defect repair with animal models.

Biodegradable metals for bone fracture repair in animal models: a systematic review.

Biodegradable metals hold promises for bone fracture repair. Their clinical translation requires pre-clinical evaluations including animal studies, which demonstrate the safety and performance of such materials prior to clinical trials. This evidence-based study investigates and analyzes the performance of bone fractures repair as well as degradation properties of biodegradable metals in animal models. Data were carefully collected after identification of population, interventions, comparisons, outcomes and study design, as well as inclusion criteria combining biodegradable metals and animal study. Twelve publications on pure Mg, Mg alloys and Zn alloys were finally included and reviewed after extraction from a collected database of 2122 publications. Compared to controls of traditional non-degradable metals or resorbable polymers, biodegradable metals showed mixed or contradictory outcomes of fracture repair and degradation in animal models. Although quantitative meta-analysis cannot be conducted because of the data heterogeneity, this systematic review revealed that the quality of evidence for biodegradable metals to repair bone fractures in animal models is 'very low'. Recommendations to standardize the animal studies of biodegradable metals were proposed. Evidence-based biomaterials research could help to both identify reliable scientific evidence and ensure future clinical translation of biodegradable metals for bone fracture repair.

Association between Frailty and Mortality, Falls, and Hospitalization among Patients with Hypertension: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chronological age alone does not adequately reflect the difference in health status of a patient with hypertension. Frailty is closely associated with biological age, and its assessment is clinically useful in addressing the heterogeneity of health status. The purpose of our study is to comprehensively examine the predictive value of frailty for negative health outcomes in hypertensive patients through a systematic review and meta-analysis. METHODS: Multiple English and Chinese databases were searched from inception to 04.11.2020. All cross-sectional and longitudinal studies that examined the association between frailty and relevant clinical outcomes among hypertensive patients were included. The NOS was used to assess the risk of bias of studies included in the analysis. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were pooled for outcomes associated with frailty. RESULTS: Six longitudinal studies and one cross-sectional study involving 17403 patients with hypertension were included in the meta-analysis. The risk of bias of all included studies was rated as low or moderate. The pooled HR of frailty related to mortality was 2.45 (95% CI: 2.08-2.88). The pooled HR of prefrailty and frailty-related injurious falls was 1.07 (95% CI: 0.83-1.37) and 1.89 (95% CI: 1.56-2.27), respectively. The pooled HR of prefrailty and frailty-related hospitalization was 1.54 (95% CI: 1.38-1.71) and 1.94 (95% CI: 1.17-3.24), respectively. CONCLUSIONS: This systematic review suggests that frailty was a strong predictor of mortality, hospitalization, and injurious falls among patients with hypertension. Our findings indicate that assessment of frailty in patients with hypertension to guide their management may be necessary in clinical setting. However, our finding was based on very limited amount studies; thus, future studies are required to further validate the role of frailty in prediction of negative health outcomes in hypertensive patients as well as pay more attention to the following knowledge gaps: (1) the association between frailty and hypertension-related outcomes, (2) the significance of the association between different frailty models and relevant clinical outcomes, and (3) the predictive value of prefrailty for the negative health outcomes in people with hypertension.

Quality of interventional animal experiments in Chinese journals: compliance with ARRIVE guidelines.

BACKGROUND: In view of the inadequacy and incompleteness of currently-reported animal experiments and their overall poor quality, we retrospectively evaluated the reporting quality of animal experiments published in Chinese journals adhering to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. RESULTS: The databases CNKI, WanFang, VIP, and CBM were searched from inception until July 2018. Two appropriately-trained reviewers screened and extracted articles independently. The ARRIVE guidelines were used to assess the quality of the published reports of animal experiments. The compliance rate of every item was analyzed relative to their date of publication. A total of 4342 studies were included, of which 73.0% had been cited ≤5 times. Only 29.0% (1261/4342) were published in journals listed in the Chinese Science Citation Database. The results indicate that the compliance rate of approximately half of the sub-items (51.3%, 20/39) was less than 50%, of which 65.0% (13/20) was even less than 10%. CONCLUSIONS: The reporting quality of animal experiments in Chinese journals is not at a high level. Following publication of the ARRIVE guidelines in 2010, the compliance rate of the majority of its requirements has improved to some extent. However, less attention has been paid to the ethics and welfare of experimental animals, and a number of specific items in the Methods, Results, and Discussion sections continue to not be reported in sufficient detail. Therefore, it is necessary to popularize the ARRIVE guidelines, advocate researchers to adhere to them in the future, and in particular promote the use of the guidelines in specialized journals in order that the design, implementation, and reporting of animal experiments is promoted, to ultimately improve their quality.