Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Remarkable contamination characteristics, potential hazards and source apportionment of heavy metals in surface dust of kindergartens in a northern megacity of China.

It is essential to understand the impact of heavy metals (HMs) present in the surface dust (SD) of kindergartens on children, who are highly sensitive to contaminated dust in cities in their growth stage. A study was conducted on 11 types of HMs present in the SD of 73 kindergartens in Beijing. This study aims to assess the pollution levels and sources of eleven HMs in Beijing's kindergartens surface dust (KSD), and estimate the potential health risks in different populations and sources. The results indicate that Cd has the highest contamination in the KSD, followed by Pb, Zn, Ni, Ba, Cr, and Cu. The sources of these pollutants are identified as industrial sources (23.7%), natural sources (22.1%), traffic sources (30.4%), and construction sources (23.9%). Cancer risk is higher in children (4.02E-06) than in adults (8.93E-06). Notably, Cr is the priority pollutant in the KSD, and industrial and construction activities are the main sources of pollution that need to be controlled. The pollution in the central and surrounding areas is primarily caused by historical legacy industrial sites, transportation, urban development, and climate conditions. This work provides guidance to manage the pollution caused by HMs in the KSD of Beijing. ENVIRONMENTAL IMPLICATION: Children within urban populations are particularly sensitive to pollutants present in SD. Prolonged exposure to contaminated SD significantly heightens the likelihood of childhood illnesses. The pollution status and potential health risks of HMs within SD from urban kindergartens are comprehensively investigated. Additionally, the contributions from four primary sources are identified and quantified. Furthermore, a pollution-source-oriented assessment is adopted to clearly distinguish the diverse impacts of different sources on health risks, and the priority pollutants and sources are determined. This work holds pivotal importance for risk management, decision-making, and environmental control concerning HMs in KSD.

Mesenchymal stem cells therapy improves ovarian function in premature ovarian failure: a systematic review and meta-analysis based on preclinical studies.

Background: Studies have revealed that the transplantation of mesenchymal stem cells (MSCs) might be a potential star candidate for premature ovarian failure (POF) in animal experiments. However, individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis to explore the potential of using MSCs in the treatment of POF in animals. Methods: Seven databases were searched for studies exploring the effect of the transplantation of MSCs on POF in animal models. The PRISMA guideline was followed, and the methodological quality was ensured using SYRCLE's risk of bias tool. RevMan 5.4 and STATA 12.0 software was performed to meta-analysis. Results: In total, 37 studies involving 1,079 animals were included. Significant associations were found for MSCs with the levels of E2 (SMD 2.69 [95% CI 1.97, 3.41]), FSH (-2.02, [-2.74, -1.30]), primary follicles (2.04, [1.17, 2.92]), secondary follicles (1.93, [1.05, 2.81]), and primordial follicles (2.38, [1.19, 3.57]. Other outcomes, such as AMH, LH, INHB, antral follicles, growing follicles, mature follicles, and early antral were also found to be significant. There was no difference in FSH/LH, corpus leteum, follicles, and estruc cycle. Conclusions: Our meta-analysis result indicated that the transplantation of MSCs might exert therapeutic effects on animal models of POF, and these effects might be associated with improving the disorder of the sexual cycle, modulating serum hormone expressions to a better state, and restoring ovarian function.

Advances in the application of metallic isotopes to the identification of contaminant sources in environmental geochemistry.

The development of the economy and society makes heavy metals (HMs) pollution more and more serious. And, pollution source identification is the primary work of environmental pollution control and land planning. Notably, stable isotope technology has a high ability to distinguish pollution sources, and can better reflect the migration behavior and contribution of HMs from diverse sources, which has become a hot research tool for pollution source identification of HMs. Currently, the rapid development of isotope analysis technology provides a relatively reliable reference for pollution tracking. Based on this background, the fractionation mechanism of stable isotopes and the influence of environmental processes on isotope fractionation are reviewed. Furthermore, the processes and requirements for the measurement of metal stable isotope ratios are summarized, and the calibration methods and detection accuracy of sample measurement are evaluated. Besides, the current commonly used binary model and multi-mixed models in the identification of contaminant sources are also concluded. Moreover, the isotopic changes of different metallic elements under natural and anthropogenic conditions are discussed in detail, and the application prospects of multi-isotope coupling in the traceability of environmental geochemistry are evaluated. This work has some guidance for the application of stable isotopes in the source identification of environmental pollution.

A Giant Urachal Accessory Spleen: Case Report.

Accessory spleen (AS) refers to single or multiple splenic tissues which appear outside the relative normal spleen position results from embryonic dysplasia similar in structure and function to the spleen. AS is frequently observed in the splenic hilus and or adjacent to the tail of pancreas, and only a few cases occurred in the pelvic cavity. We present an extremely rare AS case in urachus, which was initially considered as an urachal neoplasm revealed on CT images with big mass. However, the postoperative pathology confirmed it was an AS that had not been reported at urachal before. Urachal AS can be misdiagnosed as a tumor, so it is vital to make an accurate imaging preoperative diagnosis to avoid unnecessary biopsy and surgery.

A Case-Control Study on Factors of HPV Vaccination for Mother and Daughter in China.

(1) Background: To explore the influencing factors of human papillomavirus (HPV) vaccination among mothers and daughters so as to provide evidence and strategies for improving the HPV vaccination rate of 9-18-years-old girls. (2) A questionnaire survey was conducted among the mothers of 9-18-year-old girls from June to August 2022. The participants were divided into the mother and daughter vaccinated group (M1D1), the mother-only vaccinated group (M1D0), and the unvaccinated group (M0D0). Univariate tests, the logistic regression model, and the Health Belief Model (HBM) were employed to explore the influencing factors. (3) Results: A total of 3004 valid questionnaires were collected. According to the regions, Totally 102, 204, and 408 mothers and daughters were selected from the M1D1, M1D0, and M0D0 groups, respectively. The mother having given her daughter sex education (OR = 3.64; 95%CI 1.70, 7.80), the mother's high perception of disease severity (OR = 1.79; 95%CI 1.02, 3.17), and the mother's high level of trust in formal information (OR = 2.18; 95%CI 1.26, 3.78) were all protective factors for both the mother and her daughter's vaccination. The mother's rural residence (OR = 0.51; 95%CI 0.28, 0.92) was a risk factor for vaccination of both mother and daughter. The mother's education of high school or above (OR = 2.12; 95%CI 1.06, 4.22), the mother's high level of HPV and HPV vaccine knowledge (OR = 1.72; 95%CI 1.14, 2.58), and the mother's high level of trust in formal information (OR = 1.72; 95%CI 1.15, 2.57) were protective factors of mother-only vaccination. The older the mother (OR = 0.95; 95%CI 0.91, 0.99) was classed as a risk factor for mother-only vaccination. "Waiting until the daughters are older to receive the 9-valent vaccine" is the main reason why the daughters of M1D0 and M0D0 are not vaccinated". (4) Chinese mothers had a high willingness to vaccinate their daughters with the HPV vaccine. The higher education level of the mother, giving sex education to the daughter, the older ages of mothers and daughters, the mother's high level of HPV and HPV vaccine knowledge, a high level of perception of the disease severity, and a high level of trust in formal information were promoting factors of HPV vaccination for mother and daughter, and rural residence was a risk factor to vaccination. To promote HPV vaccination in girls from 9-18 years old, communities could provide health education to rural mothers with low education levels; the government could advocate for HPV vaccination through issuing policy documents; and doctors and the CDC could popularize the optimal age for HPV vaccination to encourage mothers to vaccinate their daughters at the age of 9-14 years old.

Preliminary investigation of soil organic carbon distribution and turnover patterns, and potential pollution sources in and around a typical coking plant in North China.

The variation characteristics of soil organic carbon (SOC) in and around the coking plant area are still unclear. In this work, the concentration and stable carbon isotope composition of SOC in coke plant soils were investigated to preliminarily identify the sources of SOC in and around the plant area, and to characterize soil carbon turnover. Meanwhile, the carbon isotopic technique was used to initially identify the soil pollution processes and sources in and around the coking plant area. The results demonstrate that the SOC content (12.76 mg g-1) of the surface soil in the coking plant is about 6 times higher than that outside the coking plant (2.05 mg g-1), and the variation range of δ13C value of the surface soil in the plant (-24.63～-18.55‰) is larger than that of the soil outside the plant (-24.92～-20.22‰). The SOC concentration decreases gradually from the center of the plant outward with increasing distance, and the δ13C in the middle and north of the plant tends to be positive compared with the δ13C in the west and southeast of the plant. As the increase of soil depth, the SOC content and δ13C value in the plant increases. On the contrary, δ13C value and SOC content outside the plant decreases, with a minor variation. Based on the carbon isotope method, the SOC in and around the coking plant area is mainly from industrial activities (e.g., coal burning and coking), and partly from C3 plants. Notably, organic waste gases containing heavy hydrocarbons, light oils, and organic compounds accumulated in the northern and northeastern areas outside the plant due to south and southwest winds, which may pose an environmental health risk.

Integrative bioinformatics analysis to identify novel biomarkers associated with non-obstructive azoospermia.

Aim: This study aimed to identify autophagy-related genes (ARGs) associated with non-obstructive azoospermia and explore the underlying molecular mechanisms. Methods: Two datasets associated with azoospermia were downloaded from the Gene Expression Omnibus database, and ARGs were obtained from the Human Autophagy-dedicated Database. Autophagy-related differentially expressed genes were identified in the azoospermia and control groups. These genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction (PPI) network, and functional similarity analyses. After identifying the hub genes, immune infiltration and hub gene-RNA-binding protein (RBP)-transcription factor (TF)-miRNA-drug interactions were analyzed. Results: A total 46 differentially expressed ARGs were identified between the azoospermia and control groups. These genes were enriched in autophagy-associated functions and pathways. Eight hub genes were selected from the PPI network. Functional similarity analysis revealed that HSPA5 may play a key role in azoospermia. Immune cell infiltration analysis revealed that activated dendritic cells were significantly decreased in the azoospermia group compared to those in the control groups. Hub genes, especially ATG3, KIAA0652, MAPK1, and EGFR were strongly correlated with immune cell infiltration. Finally, a hub gene-miRNA-TF-RBP-drug network was constructed. Conclusion: The eight hub genes, including EGFR, HSPA5, ATG3, KIAA0652, and MAPK1, may serve as biomarkers for the diagnosis and treatment of azoospermia. The study findings suggest potential targets and mechanisms for the occurrence and development of this disease.

Programmed frozen embryo transfer cycle increased risk of hypertensive disorders of pregnancy: a multicenter cohort study in ovulatory women.

BACKGROUND: Although live birth rates were comparable between programmed and natural frozen-thawed embryo transfer cycles, recent data showed that pregnancies after programmed cycle were associated with an increased risk of adverse perinatal outcomes, such as hypertensive disorders of pregnancy. Such a difference might be attributed to selection bias because patients with ovulation disorders are more likely to receive programmed endometrial preparation protocol than natural cycle. OBJECTIVE: This study aimed to analyze whether programmed endometrial preparation protocol is associated with an increased risk of adverse perinatal outcomes compared with natural cycle during frozen embryo transfer in ovulatory women. STUDY DESIGN: This regional multicenter retrospective cohort study was conducted in 5 reproductive medical centers in Southeast China. Patients with regular cycles (21-35 days), who underwent either programmed or natural cycle blastocyst frozen embryo transfer and delivered singleton live birth babies after 28 weeks of gestation between 2016 and 2019 were analyzed. Each patient only contributed 1 cycle per cohort. The patients' frozen embryo transfer treatment cycles were linked to their obstetrical medication record, and a comprehensive medical record review was conducted to compare the maternal and neonatal outcomes between natural cycle and programmed cycle. Crude and adjusted odds ratios with 95% confidence intervals were calculated, and adjustment was made for relevant confounders. RESULTS: Study samples included 499 natural cycle frozen embryo transfer cases and 900 programmed frozen embryo transfer cases. Pregnancies after programmed cycle were associated with increased odds of hypertensive disorders of pregnancy (adjusted odds ratio, 2.71; 95% confidence interval, 1.59-4.91) and preeclampsia (adjusted odds ratio, 2.71; 95% confidence interval, 1.17-6.23) compared with pregnancies after natural cycle. No significant difference was detected regarding other adverse perinatal outcomes between the 2 endometrial protocols. In subgroup analysis, both the subgroups of hormone replacement therapy and hormone replacement therapy with gonadotrophin-releasing hormone analogue pretreatment had increased odds of developing hypertensive disorders of pregnancy than the natural cycle group. The risk of developing preeclampsia was higher in the hormone replacement therapy with gonadotrophin-releasing hormone analogue pretreatment subgroup than in the other 2 groups (adjusted odds ratio, 4.99; 95% confidence interval, 1.94-12.82) (aOR, 2.47; 95% CI, 1.17-5.18). CONCLUSION: Pregnancies after programmed frozen embryo transfer were associated with higher risks of hypertensive disorders of pregnancy in ovulatory women. The hormone replacement therapy with gonadotrophin-releasing hormone analogue pretreatment cycle led to the highest risk of preeclampsia among the 3 protocols.

Health Risk Assessment of Inhalation Exposure to Airborne Particle-Bound Nitrated Polycyclic Aromatic Hydrocarbons in Urban and Suburban Areas of South China.

Airborne particulates (PM2.5 and TSP) were collected from outdoor and indoor areas at urban (Haizhu District) and suburban (Huadu District) sites from 2019 to 2020 in Guangzhou. Three nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) in the airborne particulates were identified by a gas chromatograph equipped with a triple-quadrupole mass spectrometer. In the Haizhu District and Huadu District, the nitro-PAH concentrations in PM2.5 and TSP did not show a significant decrease from winter to summer. From 2019 to 2020, the difference in the average concentration of nitro-PAHs in PM2.5 and TSP in Guangzhou was relatively low and had no statistical significance. The diagnostic ratios of 2-nitrofluorene (2-NF)/1-nitropyrene (1-NP) in TSP are less than five, while for 2-NF/1-NP in outdoor PM2.5 in the summer of 2019 and 2020 are more than five, which indicates that nitro-PAHs in the atmospheric PM2.5 in Guangzhou during summer mainly originated from the secondary formation of atmospheric photochemical reactions between parent PAHs and oxidants (·OH, NO3, and O3). 9-Nitroanthracene (9-NT) made the most significant contribution to the total nitro-PAH concentration. The incremental lifetime cancer risks (ILCRs) of nitro-PAHs in PM2.5 and TSP by inhalation exposure indicated low potential health risks in the urban-suburban of Guangzhou.

Distribution, source, and health risk assessment of polycyclic aromatic hydrocarbons in the soils from a typical petroleum refinery area in south China.

The ubiquity of polycyclic aromatic hydrocarbons (PAHs) in soils in petroleum refining areas is an important problem affecting human and ecological safety. In this study, 103 topsoil (0-0.50 m) samples were collected from a retired petroleum refinery area in Guangdong province, south China. The PAHs concentrations were determined by ultrasonic extraction and gas chromatography-mass spectrometry detection methods. Twelve PAHs controlled priority listed by the US Environmental Protection Agency (USEPA) were investigated. The results revealed that the concentration of Æ©12PAHs ranged from 2100 to 5200 µg kg-1, with a mean value of 3741.66 µg kg-1. The site was dominated by high rings PAHs (4-, 5-, and 6-ring), contributing 81.96% to Æ©12PAHs. The concentrations of 9 kinds of PAHs exceeded the Dutch soil quality standard. Besides, the PAHs were primarily distributed in the storage tank area and with high levels of contamination. The results of hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicated that coal combustion was the source of PAHs in topsoil, followed by petroleum dripping and traffic emissions. The incremental lifetime cancer risk (ILCR) modeling illustrated that soil ingestion was the major pathway of PAH exposure for both adults and children. Notably, the total noncarcinogenic human health risk due to PAHs was within the limit of 1, while the carcinogenic risks alone caused by benzo(a)pyrene via soil ingestion to adults and children were obviously beyond the USEPA limit (1.00E -06). Therefore, PAHs in the petroleum refinery areas have potential carcinogenic hazards to human health, the area should be remediated before reuse.

Ovarian Hyperresponse Following the Sole Administration of GnRH Agonist.

BACKGROUND: The gonadotrophin-releasing hormone agonist (GnRHa) has gained widespread popularity in achieving pituitary suppression before ovarian stimulation with exogenous gonadotropins in assisted reproductive technology protocols. However, a very small part of patients may develop ovarian hyper response after the sole administration of GnRHa without gonadotropins. CASE REPORT: A 32-year-old female diagnosed with polycystic ovary syndrome presented for her second IVF cycle in our reproductive center. Twenty-eight days after 3.75mg triptorelin was administrated on day 2 of her menstrual cycle, bilateral ovaries were significantly enlarged and presented multiple cystic masses. The hormone profile was as follows: E24870pg/ml, P 13.19ng/ml, FSH 14IU/L, and LH 10.77IU/L. The patient felt symptoms of mild ovarian hyperstimulation syndrome. In the subsequent IVF treatment cycle, antagonist protocol was performed. It showed that follicles developed slowly and exogenous gonadotropins were used for 13 days. Finally, seven oocytes were obtained, and only one blastocyst graded 4BC formed. CONCLUSION: Ovarian hyperstimulation following the sole administration of GnRHa can occur, but the mechanism is still not yet clear. Antagonist protocol may be an alternative fertility strategy, but the risk of poor embryo quality and low pregnancy rate of transplantation should be warned.

Source tracing of potentially toxic elements in soils around a typical coking plant in an industrial area in northern China.

Coking plants are a substantial source of potentially toxic elements (PTEs) in soil. In this study, we examined the concentration of PTEs, the soil physicochemical properties, and the Pb isotopes in the soil inside and around a coking plant in an industrial city in northern China. We analyzed the spatial distribution of PTEs and the pollution risk areas by Igeo index, the enrichment factor (EF), and the Nemerow index, and we quantitatively identified the contribution of PTE pollution sources in the soil on a small- and medium-scale (plant and work section). Our results indicated that the Hg concentration inside the plant and the Cd concentration in the agricultural land around the plant were both relatively high. A comprehensive analysis of the soil in the study area was performed using the positive matrix factorization model and Pb isotope (206/207Pb, 208/206Pb) tracing method, based on the MixSIAR model, this analysis indicated that burning coal was the main source of Pb both inside (46.8%) and outside (26.3%) the coking plant. The pollution emission sources with significant influence on the soil outside the coking plant were diesel vehicles (12.5%), gas tanks (12.4%), and coke ovens (11.5%), while the sources inside the plant were quenching sections (11.1%), atmospheric deposition (11.0%), coke oven sections (9.6%), and diesel vehicles (6.1%). The results of PTE pollution risk zoning and Pb isotope tracing indicated that pollution is more serious in the western part of the plant, which is the area where coking and gas production takes place, and the most serious pollution outside the plant is mainly distributed to the southeast. This study provides theoretical and practical data indicating the contribution of industrial enterprises to soil pollution, and will help identify pollution responsibility and the management of pollution sources.

Can Inhibin B Reflect Ovarian Reserve of Healthy Reproductive Age Women Effectively?

Objective: The reference range and potential value of inhibin B are still unclear and controversial. This study aimed to define the variation trend of inhibin B in healthy women with age and explore its value in the reflection of ovarian reserve. Methods: A total of 2524 healthy reproductive age women from eight medical institutes nationwide were recruited. The variation tendency of inhibin B with age was primarily established in the first group of 948 women and validated in another 605. We evaluated the relationship between inhibin B and classic ovarian reserve and function markers. The potency of inhibin B in predicting AFC <5-7 was also estimated and compared with FSH. Results: The nomogram showed that serum levels of inhibin B rapidly decreased after the age of 40. Inhibin B was positively correlated with AMH (R = 0.57, P < 0.001), AFC (R = 0.34, P < 0.001) and testosterone (R = 0.10, P = 0.002), and negatively correlated with FSH (R = -0.41, P < 0.001) and LH (R = -0.20, P < 0.001) and FSH/LH (R=-0.18, P < 0.001), while no correlation was found with PRL. Unexpectedly, Inhibin B (AUC = 0.74, P < 0.001 for the establishment population; AUC = 0.78, P < 0.001 for the validation population) had a slightly higher value than FSH (AUC = 0.71, P < 0.001 for the establishment population; AUC = 0.72, P < 0.001 for the validation population) in diagnosing AFC <5-7. Conclusions: For healthy reproductive age women, the decline of inhibin B can reflect decreased ovarian reserve effectively, having a good consistency with AMH and AFC. More importantly, inhibin B had an advantage in predicting AFC <5-7 compared with FSH, which suggested the potential of inhibin B in predicting ovarian response. These results will be helpful to the clinical application of inhibin B in the evaluation of female ovarian reserve and the assessment of their reproductive capacity. Trial registration: http://clinicaltrials.gov; NCT02294500.

PAI-1 4G/4G Genotype Is Associated with Recurrent Implantation Failure: a Systematic Review and Meta-analysis.

To detect the association between PAI-1 -675 4G/5G polymorphism and recurrent implantation failure (RIF). We performed this meta-analysis by searching databases of PubMed, EMBASE, OVID, and CNKI (China National Knowledge Infrastructure) for case-control studies that evaluated the association between PAI 4G/5G polymorphism and RIF. Meta-analysis was performed using the random-effects model. The odds ratios (ORs) with 95% confidence intervals (CIs) were reported to evaluate the association. Meta-regression and subgroup analysis were performed to explore the source of heterogeneity. Sensitivity analysis and trim-and-fill analysis were performed to explore the robustness of the meta-analysis. Eight case-control studies consisted of 1273 women were included in this meta-analysis (including 697 RIF patients and 576 control participants). The combined results showed that the homozygous genotype of PAI-1 -675 4G/4G was significantly associated with RIF (OR 2.79, 95%CI 1.53-5.08, P-value = 0.0008). Meta-regression and subgroup analysis showed that sample origin is the primary source of heterogeneity (P-value for meta-regression: 0.005). Study quality also explains some heterogeneity (P-value for meta-regression: 0.03). Sensitivity analysis showed that the result was not significantly changed after excluding one study each time. Trim-and-fill analysis showed that the result was not significantly changed after filled with three studies. PAI -675 4G/4G genotype may serve as one of the predisposing factors of RIF. Women with PAI-1 4G/4G genotype were at higher risk of RIF. However, more high-quality studies are needed to confirm the conclusion.

Polymorphisms of vascular endothelial growth factor and recurrent implantation failure: a systematic review and meta-analysis.

PURPOSE: To investigate the associations between polymorphisms of vascular endothelial growth factor (VEGF) with recurrent implantation failure (RIF). METHODS: We performed the systematic review and meta-analysis by searching databases of PubMed, EMBASE, OVID, and CNKI (China National Knowledge Infrastructure) for studies that evaluated the associations between VEGF polymorphisms with RIF. Meta-analysis was performed if the polymorphism was studied by more than two case-control studies. Data were analyzed using R software. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported to assess the associations. RESULTS: Nine VEGF polymorphisms (-1154G > A, -460T > C, +405G > C, -7C > T, -634C > G, -2578C > A, +936C > T, 5C > T, -583C > T) were systematically reviewed. Meta-analysis was performed on VEGF -1154 G > A polymorphism. Three case-control studies consisted of 683 women were included in the quantitative meta-analysis (305 RIF patients and 378 controls). Results showed that VEGF -1154A allele was significantly associated with RIF (OR 1.39, 95% CI 1.08-1.78, P-value = 0.01). The dominant genetic model showed that VEGF 1154AA plus VEGF 1154AG genotypes were more frequent in RIF patients than VEGF 1154GG genotype (OR 1.56, 95% CI 1.10-2.20, P-value = 0.01). However, the result under the recessive genetic model showed no significant difference (OR 1.67, 95% CI 0.92-3.03, P-value = 0.09). CONCLUSION: VEGF -1154A allele may serve as one of the predisposing factors of RIF. Women with VEGF 1154 AA/GA genotypes were at higher risk of RIF. However, we should consider the haplotype effect of VEGF polymorphisms in future studies.

Transcriptional Inhibition of lncRNA gadd7 by CRISPR/dCas9-KRAB Protects Spermatocyte Viability.

Our previous study found that lncRNA gadd7 was up-regulated in the semen of varicocele patients, and could promote the apoptosis of mouse spermatocytes and inhibit their proliferation. Therefore, we further explored whether down-regulation of Gadd seven expression could protect the viability of spermatocytes. Here we designed specific sgRNAs targeting the ORF region of gadd7, and constructed a CRISPR-dCas9-KRAB system that effectively inhibits gadd7 at the transcriptional level. The CRISPRi system can effectively prevent the apoptosis of spermatocytes and enhance their proliferation, which is expected to provide a potentially effective molecular intervention method for the treatment of male infertility caused by varicocele.

[Impact of sperm DNA fragmentation on the outcome of frozen-thawed blastocyst transfer in in vitro fertilization and embryo transfer].

OBJECTIVE: To study the impact of sperm DNA fragmentation (DF) on the outcome of frozen-thawed blastocyst transfer in in vitro fertilization and embryo transfer (IVF-ET). METHODS: We retrospectively analyzed 308 cases of routine IVF-ET performed at our Center of Reproductive Medicine from January 2016 to January 2018. According to the sperm DNA fragmentation index (DFI), we divided the patients into a normal DFI (DFI ≤ 15%, n = 114), a moderate DFI (15% < DFI ≤ 30%, n = 103), and a high DFI group (DFI > 30 %, n = 91), and compared the development of embryos and clinical outcomes among the three groups. RESULTS: The blastocyst formation rate was remarkably higher in the normal and moderate DFI groups than in the high DFI group (68.9% and 66.2% vs 58.3%, P < 0.05) but the percentage of available blastocysts exhibited no statistically significant difference between the former two and the latter group (88.1% and 84.0% vs 81.2%, P > 0.05). There were statistically significant differences among the normal, moderate and high DFI groups in the percentage of high-quality blastocysts (80.3% vs 68.8% vs 59.7%, P < 0.05). The implantation rate was dramatically lower in the high DFI group than in the normal and moderate DFI groups (30.4% vs 43.1% and 41.0%, P < 0.05), and so was the clinical pregnancy rate (33.6% vs 43.2% and 40.2%, P < 0.05), but the abortion rate markedly higher in the former than in the latter two groups (16.2% vs 10.0% and 9.8%, P < 0.05). CONCLUSIONS: High sperm DFI can not only significantly reduce the rates of blastocyst formation, available blastocysts and high-quality blastocysts, but also decrease the rates of implantation and clinical pregnancy and increase that of abortion after frozen-thawed blastocyst transfer.

Non spontaneous vaginal delivery was associated with lower probability of subsequent fertility.

OBJECTIVE: Previous systematic reviews have reported that cesarean birth is associated with reduced rate of subsequent fertility. However, other common mode of delivery was poorly understood. The aim of this study was to systematically investigate the subsequent fertility in patients having different modes of non-spontaneous vaginal delivery, if compared to normal vaginal delivery. STUDY DESIGNS: Medline (via PubMed), Web of Science, Embase (via Dialog), CENTRAL (via Cochrane Library), ScienceDirect (via Elsevier) and ClinicalTrial.gov were searched up to October 2019, without language restrictions in this systematic review and meta-analysis. Articles assessing the mode of delivery and subsequent fertility were included. Quality assessment was evaluated using the nine-point Newcastle Ottawa Scale by two independent reviewers. RESULTS: Twenty-one articles, including 4,423,544 women of reproductive age, were included. Results showed that women had a 9% (RR: 0.91 [95 %CI 0.88, 0.94]) lower probability of subsequent fertility in primary cesarean birth group, compared with spontaneous vaginal delivery. Further analysis discovered that a 13 % (0.87, [0.85, 0.90]) lower probability of subsequent fertility was observed in women delivered by emergency cesarean birth, a 14 % (0.86, [0.82, 0.91) lower probability by elective cesarean birth, a 39 % (0.61, [0.57, 0.66]) by maternal-requested cesarean birth, and a 2% (0.98, [0.97, 1.00]) by instrumental vaginal delivery. CONCLUSIONS: Non-spontaneous vaginal delivery may be associated with lower probability of subsequent fertility. Decision makers and obstetricians should be cautious when choosing the mode of delivery.

Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells.

In aortic endothelial cells, the TGFß signaling pathway is involved in the regulation of vascular endothelial growth factor (VEGF), which encodes a potent angiogenic factor crucial for the development of ovarian hyperstimulation syndrome. Growth differentiation factor 9 (GDF9) is a member of the TGFß family and its effect on VEGF expression in human granulosa cells is unknown. In this study, human granulosa cells were collected from patients during the course of oocyte retrieval for in vitro fertilization and were cultured in vitro. After the first 48 h of culture, cells were treated with GDF9 with or without SB431542 (an ALK5 inhibitor) at various doses. The medium was then collected to determine the concentration of VEGF by ELISA. Cellular RNA was collected and extracted for quantification by real-time quantitative fluorescence PCR. Our study showed that GDF9 suppressed VEGF release from human granulosa cells in a dose-dependent manner and also downregulated VEGF mRNA levels in these cells. Furthermore, SB431542 antagonized the suppression of VEGF mRNA by GDF9 and diminished the inhibitory effect of GDF9 on VEGF release by human granulosa cells. Our results indicated that GDF9 can inhibit VEGF expression in human granulosa cells and ALK5 might mediate this process.