Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

Synthetic Phenolic Antioxidants and Their Metabolites in Follicular Fluid and Association with Diminished Ovarian Reserve: A Case-Control Study.

BACKGROUND: Diminished/decreased ovarian reserve (DOR) is a disorder of ovarian function, which severely affects women's reproductive health. Accumulating evidence has found that adverse environmental factors can affect ovarian function. However, whether synthetic phenolic antioxidants (SPAs) exposure is associated with DOR is still unknown. OBJECTIVES: We explored whether concentrations of SPAs and their metabolites are associated with DOR. METHODS: A case-control study was conducted from January 2019 to January 2020 in China. One hundred eighty-one women 20-44 years of age, with (case group, n=63) and without DOR (control group, n=118) were included in our study. The follicular fluid concentrations of typical SPAs and their metabolites were measured, including butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), butylated hydroxytoluene (BHT), and five BHT metabolites [3,5-di-tert-butyl-4-hydroxy-benzylalcohol (BHT-OH), 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), and 2,6-di-tert-butyl-4-hydroxy-4-methylcyclohexa-2,5-dien-1-one (BHT-quinol)]. Information about serum basal concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) and the basal antral follicle count (AFC) was collected. RESULTS: The measured frequencies of BHA, TBHQ, BHT, BHT-OH, BHT-CHO, BHT-COOH, BHT-Q, and BHT-quinol in follicular fluid were 1.7%, 2.2%, 40.3%, 46.4%, 57.5%, 100%, 64.6%, and 49.2%, respectively. The concentrations of BHT-CHO (0.49 ng/mL vs. 0.12 ng/mL, p=0.041), BHT-COOH (0.45 ng/mL vs. 0.28 ng/mL, p<0.001), BHT-Q (0.70 ng/mL vs. 0.13 ng/mL, p<0.001), and the sum of five BHT metabolites (Σ5metabolites; 1.79 ng/mL vs. 1.0 ng/mL, p<0.001) in the case group were significantly higher than those in the control group. The risk of DOR was further analyzed according to the tertiles of chemical concentration. Compared with the low levels of BHT metabolites, the adjusted odds ratios (ORs) for DOR were significantly increased in the high levels of BHT-CHO [OR=3.19, 95% confidence interval (CI): 1.22, 8.31, p=0.018], BHT-COOH [OR=4.73 (95% CI: 1.63, 13.71), p=0.004], and BHT-Q [OR=4.48 (95% CI: 1.69, 11.86), p=0.003] after adjusting for age, body mass index, education, infertility type, triglycerides, and total cholesterol. Moreover, compared with the low level of Σ5metabolites, increased adjusted ORs for DOR were found both in the middle level [OR=4.11 (95% CI: 1.44, 11.75), p=0.008] and high level [OR=5.51 (95% CI: 1.81, 16.77), p=0.003], showing an obvious dose-response relationship (pTrend=0.003). CONCLUSION: In this study, we report the measured frequency and concentrations of BHA, TBHQ, BHT, and their metabolites in follicular fluid. Moreover, we found the concentrations of BHT metabolites, especially BHT-CHO, BHT-COOH, and BHT-Q, are positively associated with the increased risk of DOR. https://doi.org/10.1289/EHP11309.

Mixed and single effects of endocrine disrupting chemicals in follicular fluid on likelihood of diminished ovarian reserve: A case-control study.

Endocrine-disrupting chemicals (EDCs) are a group of the most widely spread pollutants. Their impacts on reproductive health have become public concerns. Diminished ovarian reserve (DOR) is a disorder of ovarian function. Associations between EDC and DOR have been inconsistent. Very little research investigated the joint effects of multiple EDCs. Here, we performed a case-control study among 64 DOR women and 86 controls. Twenty-one EDC chemicals were assessed in follicular fluid, including parabens, phenols, phthalates and poly-fluoroalkyl substances. Both mixed and single effects of EDCs on DOR were evaluated and validated with a Bayesian kernel machine and logistic regressions. We found that the likelihood of DOR significantly increased with rising levels of the 21-EDC mixture, with an odds ratio (OR) and 95% confidence interval (CI) of 2.12 (1.17-3.83) for the 75th percentile compared to its median level. The overall effect was higher than effects of each subgroup. BP4, MECPP, and PFHxA were driving the association to the mixture, and their single effects were validated, with individual ORs of 8.25 (95%CI:3.45-12.21), 1.92 (95%CI:1.02-4.09), and 1.84 (95%CI:1.08-3.86), respectively. In conclusion, we provided new pollutant markers for DOR and emphasized the importance of the effects of EDC mixtures on female reproductive health.

A Bayesian network model for prediction of low or failed fertilization in assisted reproductive technology based on a large clinical real-world data.

STUDY QUESTION: To construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment. A BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. WHAT IS KNOWN ALREADY: The prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China's largest reproductive health centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model. MAIN RESULTS AND THE ROLE OF CHANCE: All twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%. LIMITATIONS, REASON FOR CAUTION: First, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model. WIDER IMPLICATIONS OF THE FINDINGS: Based on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S): Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

STUDY QUESTION: What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? SUMMARY ANSWER: Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. WHAT IS KNOWN ALREADY: Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. LIMITATIONS REASONS FOR CAUTION: Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

RNA sequencing and integrative analysis reveal pathways and hub genes associated with TGFß1 stimulation on prostatic stromal cells.

Objective: Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. The transforming growth factor beta 1 (TGFß1) plays an important role in the proliferation and differentiation of BPH stroma. However, it is not clear yet which important pathways and key genes are the downstream of TGFß1 acting on prostatic stromal cells. Methods: GSE132714 is currently the newer, available, and best high-throughput sequencing data set for BPH disease and includes the largest number of BPH cases. We examined the TGFß1 expression level in BPH and normal prostate (NP) by analyzing the GSE132714 data set as well as carrying out immunohistochemistry of 15 BPH and 15 NP samples. Primary prostatic stromal cells (PrSCs) were isolated from five fresh BPH tissues. RNA sequencing and bioinformatics analysis were used to reveal important pathways and hub genes associated with TGFß1 stimulation on PrSCs. Results: TGFß1 was upregulated in BPH stroma compared to NP stroma. A total of 497 genes (244 upregulated and 253 downregulated) were differentially expressed in PrSCs with and without TGFß1 stimulation. The Gene Ontology revealed that differentially expressed genes (DEGs) were mainly enriched in progesterone secretion, interleukin-7 receptor binding, and CSF1-CSF1R complex. The Wnt signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, and Hippo signaling pathway were screened based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. FN1, SMAD3, CXCL12, VCAM1, and ICAM1 were selected as hub genes according to the degree of connection from the protein-protein interaction (PPI) network. Conclusion: This study sheds some new insights into the role of TGFß1 in BPH stroma and provides some clues for the identification of potential downstream mechanisms and targets.

Prognosis of Congenital Anomalies in Conceptions Following In Vitro Fertilization: A Multicenter Retrospective Cohort Study in China.

Background: Conceptions following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have an increased risk of congenital anomalies. Few studies have explored the prognosis of fetuses with congenital anomalies. This study aimed to investigate the prevalence and prognosis of congenital anomalies in IVF/ICSI pregnancies, and to analyze the influencing factors contributing to poor prognosis. Methods: In this multicenter retrospective cohort study, we followed 405,473 embryo transfer cycles at 15 reproductive centers between January 2010 and December 2019 and enrolled 2,006 intrauterine pregnancies with congenital anomalies. The relatively positive prognosis group with one or more live births and neonatal survival for more than 7 days was compared with the poor prognosis group with poorer outcomes. Results: Among the 168,270 ongoing intrauterine pregnancy cycles, the prevalence of congenital anomalies was 1.19%, wherein the malformation rates of cycles with late abortion and delivery were 2.37% (716/30,202) and 0.93% (1,290/138,068), respectively. Among all IVF/ICSI cycles with congenital anomalies, the relatively positive prognosis rate was 61.39%. Moreover, the fertilization failure rate (2 pro-nuclei rate < 25%) in the poor prognosis group was significantly higher than that in the relatively positive prognosis group (10.89% vs. 5.09%, p < 0.001). Multivariate logistic regression analysis revealed no significant differences in the relatively positive prognosis rate among the various IVF/ICSI protocols. The relatively positive prognosis rate of fertilization failure cycles was 0.180 times that of normal fertilization cycles. Conclusion: Poor fertilization rates during IVF/ICSI treatments are more likely to have poor prognosis in fetuses or neonates with congenital anomalies, and obstetric management should be strengthened in pregnant women, with which pregnant women should be recommended to strengthen obstetric management.

Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey.

BACKGROUND: Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application. OBJECTIVE: This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age. STUDY DESIGN: A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values. RESULTS: A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (<0.01 to 3.40), and 0.04 (<0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age >35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve. CONCLUSION: This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

Changes in the prevalence of polycystic ovary syndrome in China over the past decade.

Background: Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly. Methods: We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years. Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility. Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data. Funding: National Key R&D Program of China and the National Natural Science Foundation of China.

Prediction of Fertilization Disorders in the In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Retrospective Study of 106,728 Treatment Cycles.

Purpose: This study aimed to develop a risk prediction of fertilization disorders during the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: A retrospective study was performed with 106,728 fresh embryo IVF/ICSI cycles from 2009 to 2019. Basic characteristics of patients, clinical treatment data, and laboratory parameters were involved. The associations between the selected variables and risks for low fertilization rate (LFR) and total fertilization failure (TFF) were investigated. Ordinal logistic regression and the receiver operating characteristic curves (ROCs) were used to construct and evaluate the prediction models. Results: A total of 97,181 controls, 4,343 LFR and 5,204 TFF cases were involved in this study. The model based on clinical characteristics (the ages of the couples, women's BMI, types of infertility, ART failure history, the diminished ovarian reserve, sperm quality, insemination method, and the number of oocytes retrieved) had an AUC of 0.743 for TFF. The laboratory model showed that primary infertility, ART failure history, minimal-stimulation cycle/natural cycle, numbers of oocyte retrieved < 5, IVF, and Anti-Mullerian hormone (AMH) level < 1.1ng/ml are predictors of TFF, with an AUC of 0.742. Conclusion: We established a clinical and a laboratory prediction model for LFR/TFF. Both of the models showed relatively high AUCs.

Maternal and neonatal outcomes following blastocyst biopsy for PGT in single vitrified-warmed embryo transfer cycles.

RESEARCH QUESTION: Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? STUDY DESIGN: Retrospective cohort study of 5097 single vitrified-warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. RESULTS: The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52-0.91, P = 0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38-0.83, P = 0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. CONCLUSION: Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term.

Impact of Androgen Suppression Therapy on the Risk and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the incidence or clinical outcomes of bladder cancer. METHODS: We systematically searched the PubMed and Embase databases from inception to June 20, 2021 to identify all observational studies examining the incidence or clinical outcomes of bladder cancer in patients who received AST. AST is defined as the use of 5-alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT). RESULTS: A total of 18 observational studies were included. Our results showed that AST was not significantly associated with a reduced risk of BCa incidence (OR: 0.92, 95% CI: 0.68-1.24) compared with the lack of AST. The subgroup analysis revealed that finasteride use was significantly associated with a reduction in the risk of BCa incidence (OR: 0.75, 95% CI: 0.64-0.88). Recurrence-free survival (RFS) was improved among AST users compared with nonusers (HR: 0.68, 95% CI: 0.48-0.95), while no significant difference between AST users versus nonusers was identified for cancer-specific survival (CSS), overall survival (OS) or progression-free survival (PFS). CONCLUSION: Current evidence indicates that therapy with finasteride may represent a potential strategy aimed at reducing BCa incidence. Moreover, AST has a beneficial effect on the recurrence of bladder cancer. Further well-designed randomized trials or cohort studies with better characterized study populations are needed to validate our preliminary findings. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews database [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42021261685.

Identification of key genes in benign prostatic hyperplasia using bioinformatics analysis.

PURPOSE: This study aimed to identify differentially expressed genes (DEGs) and pathways in benign prostatic hyperplasia (BPH) by comprehensive bioinformatics analysis. METHODS: Data of the gene expression microarray (GSE6099) were downloaded from GEO database. DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction network was constructed through STRING. Anterior gradient 2 (ARG2) and lumican (LUM) staining in paraffin-embedded specimens from BPH and normal prostate (NP) were detected by immunohistochemistry (IHC). Differences between groups were analyzed by the Student's t test. RESULTS: A total of 24 epithelial DEGs and 39 stromal DEGs were determined. The GO analysis results showed that epithelial DEGs between BPH and NP were enriched in biological processes of glucose metabolic process, glucose homeostasis and negative regulation of Rho protein signal transduction. For DEGs in stroma, enriched biological processes included response to ischemia, antigen processing and presentation, cartilage development, T cell costimulation and energy reserve metabolic process. ARG2, as one of the epithelial DEGs, was mainly located in epithelial cells of prostate. In addition, LUM is primarily expressed in the stroma. We further confirmed that compared with NP, the BPH have the lower ARG2 protein level (p = 0.029) and higher LUM protein level (p = 0.003) using IHC. CONCLUSIONS: Our study indicated that there are possible differentially expressed genes in epithelial and stromal cells, such as ARG2 and LUM, which may provide a novel insight for the pathogenesis of BPH.

Efficacy and safety of prostatic artery embolization for benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy and safety of prostatic artery embolization (PAE) vs. transurethral resection of the prostate (TURP) in patients affected by benign prostatic hyperplasia (BPH). We also reviewed mean changes from baseline in PAE at selected follow-up points. METHODS: PubMed, Web of Science, and Embase were searched up to May 1, 2020. Randomized controlled trials on PAE were collected according to specific inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3, STATA 14, and GraphPad Prism 8. Pooled patient-reported scores and functional outcomes were calculated by using a fixed or random-effect model. RESULTS: Eleven articles met our selection criteria and ten independent patient series were included in the final analysis. Pooled estimates suggested no significant difference between TURP and PAE for patient-reported outcomes including International Prostate Symptom Score (2.32 (- 0.44 to 5.09)) and quality of life (0.18 (- 0.41 to 0.77)) at 12 months. PAE was less effective regarding improvements in most functional outcomes such as maximum flow rate, prostate volume, and prostate-specific antigen. Moreover, PAE may be associated with relatively fewer complications, lower cost, and shorter hospitalization. After the PAE procedure, the overall weighted mean differences for all outcomes except sexual health scores were significantly improved from baseline during follow-up to 24 months. CONCLUSION: PAE is non-inferior to TURP with regard to improving patient-reported outcomes, though most functional parameters undergo more changes after TURP than after PAE. Moreover, PAE can significantly continue to relieve symptoms for 24 months without causing serious complications. KEY POINTS: • PAE is as effective as TURP in improving subjective symptom scores, with fewer complications and shorter hospitalization times. • PAE is inferior to TURP in the improvement of most functional outcomes. • Improvements due to PAE are durable during follow-up to 24 months.

Low KLOTHO level related to aging is associated with diminished ovarian reserve.

OBJECTIVE: To explore the relationship between KLOTHO expression and diminished ovarian reserve (DOR). DESIGN: A case-control study. SETTING: Reproductive medicine center. PATIENT(S): A total of 157 patients with DOR and 159 control women were recruited from the Centre of Reproductive Medicine, Peking University Third Hospital. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The granulosa cells were isolated from follicular fluid after oocyte retrieval, and the KLOTHO level of granulosa cell was measured using a modified quantitative polymerase chain reaction technique. The serum KLOTHO level was measured by solid-phase sandwich enzyme-linked immunosorbent assay. RESULT(S): In both granulosa cells and serum derived from women with DOR, KLOTHO expressions were significantly lower compared with normal ovarian reserve controls. Moreover, KLOTHO expression diminished with advancing age. CONCLUSION(S): Diminished KLOTHO expression was associated with DOR. Further longitudinal studies in a similar population accompanying disease progression and mechanism exploration are needed to substantiate the rules of KLOTHO in reproductive aging.

Maternal serum level of manganese, single nucleotide polymorphisms, and risk of spontaneous preterm birth: A nested case-control study in China.

Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4-22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma-mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60-3.43), 2.42 (95%CI: 1.06-5.55) and 2.46 (95%CI: 1.08-5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57-25.71) and AG (3.04, 95%CI: 1.59-5.80) of rs2758352, with CC (2.34, 95%CI: 1.31-4.18) of rs699473, and with GG (2.26, 95%CI: 1.22-4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.

Potential risks of SARS-CoV-2 infection on reproductive health.

The outbreak of 2019 novel coronavirus disease (COVID-19) has become a major pandemic threat worldwide. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focuses on its potential risks for reproductive health, including the reproductive system and its functioning, as well as gamete and embryo development, which could be affected by the virus itself, drug treatments, chemical disinfectants and psychological effects related to panic during the COVID-19 outbreak.

A Systematic Review and Meta-analysis of Prostatic Urethral Lift for Male Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

CONTEXT: Recently, prostatic urethral lift (PUL) is being used to treat lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Although preliminary clinical studies on PUL are increasing, the long-term efficacy and safety of this procedure are still not well evaluated. OBJECTIVE: The objective of our study is to synthesize the existing literature evidence, and make a comprehensive and long-term systematic review for the PUL procedure. EVIDENCE ACQUISITION: A systematic search was performed from the electronic databases including PubMed, Embase, and OVID. The search period was up to January 1, 2020. Comprehensive retrospective and prospective studies on PUL were collected in accordance with specific inclusion and exclusion criteria. Pooled prostatic symptom scores, sexual health scores, and functional outcomes were calculated by using a fixed or random-effect model. EVIDENCE SYNTHESIS: Nineteen articles meet our determined inclusion and exclusion criteria, and 11 independent patient series were included in the final analysis. Meta-analysis results indicated improvement after the PUL procedure, including International Prostate Symptom Score improvement of 9.73-12.16 points, BPH Impact Index improvement of 3.74-4.50 points, maximum flow rate improvement of 3.44-4.26 ml/s, and quality of life improvement of 2.20-2.55 points. Postvoid residual volume at most of the intervals was not significantly variable. Data regarding sexual function remained stable or improved slightly during the 24-mo follow-up period. Pooled estimates were largely heterogeneous except for sexual function. CONCLUSIONS: PUL can continue to relieve prostatic symptoms for 24 mo without causing serious complications. The extremely important advantage of the PUL procedure is that it can preserve or slightly improve sexual function. Longer-term and more comprehensive clinical trials are still needed to further clarify the functional outcomes and cost effectiveness of PUL. PATIENT SUMMARY: Prostatic urethral lift is an attractive option for selected patients who seek rapid and durable relief of lower urinary tract symptoms with complete preservation of sexual function.