A global perspective: characteristics of infertility-related randomized clinical trials.

BACKGROUND: Infertility is a prevalent global condition, and emerging reproductive technologies may enhance its evaluation and treatment. Understanding the current features of randomized clinical trials in infertility is crucial for improving study design and ensuring the translation of results for patient benefits. OBJECTIVES: To investigate the primary characteristics of randomized clinical trials related to infertility and areas where require improvement. MATERIALS AND METHODS: We conducted a search on the International Clinical Trials Registry platform for eligible infertility trials between 2003 and 2022. The distribution ratio of various characteristics uploaded by infertility-related studies on the platform was analyzed and compared according to sex and registration year. RESULTS: Out of the total trials, 85.3% (1,906) included only women, 8.6% (192) included only men, and 6.1% (136) included couples. The majority of retrieved trials followed a parallel arm design (91.0%) and were non-industry-funded (92.2%), with a median planned sample size of 131 patients (interquartile range 75-270). Among these trials, 54.5% (1,217) were conducted in Asia. The most common primary purpose of infertility-related trials was treatment (88.8%), with over half of the investigated interventions focusing on medication (57.9%). DISCUSSION: Asia is the leading region for research, and the drug therapy is still widely used and updated. However, support care for infertile couples has also received some preference. Areas that require improvement and promotion include addressing male infertility and focusing on underserved regions like Africa. The results also highlight deficiencies in trial registration and masking methods, emphasizing the need for better regulation and facilitation of infertility trials in the post-COVID-19 era. CONCLUSION: Based on the current status of infertility RCT studies, greater attention should be paid to infertile men and populations in underdeveloped regions like Africa in future studies, together with a standardized registration and implementation procedures.

Potential of crop straw incorporation for replacing chemical fertilizer and reducing nutrient loss in Sichuan Province, China.

Sichuan Province is rich in crop straw, yet little is known about its spatial distribution pattern, potential in replacing chemical fertilizer and mitigating nutrient loss. Based on the statistical data and literature review, the spatial distribution and potential of nutrient resources in crop straw for replacing chemical fertilizers was evaluated in this study. The nutrient loss with both crop incorporation and chemical fertilizer application were examined using a nutrient release coefficient method and compared. Results showed that Chengdu Plain, Northeast and South Sichuan produced more than 95% of the total straw nutrient resources during the period of 2016-2020. The potential of crop straw to substitute potassium (K), nitrogen (N) and phosphorus (P) fertilizer were K2O 33.08-285.95 kg hm-2, N 9.52-82.32 kg hm-2 and P2O5 4.91-28.71 kg hm-2, respectively. If chemical fertilizer was substituted by all the available straw nutrient resources, N and P loss can be decreased by 55.12% and 65.84% in average in Sichuan Province. 343.93 t of N loss and 20.05 t of P loss can be reduced in plain areas, 122.88 t of N loss and 46.29 t of P loss can be reduced in mountainous and hilly areas, and 5.65 t of t N loss and 3.54 t of P loss can be reduced in plateau areas. It can be concluded that there were rich crop straw nutrient resources in Sichuan Province with obvious spatial variability, solid consideration should be put on to the proper use of crop straw nutrient resources, with the aim of chemical fertilizer reduction, nutrient loss reduction and sustainable development.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction.

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

Therapeutic Effects of Xianlu Oral Solution on Rats with Oligoasthenozoospermia through Alleviating Apoptosis and Oxidative Stress.

Idiopathic oligoasthenozoospermia (iOAZS) is one of the major causes of male infertility, and the ideal therapies for iOAZS have not been established yet. Traditional Chinese medicine (TCM), including Xianlu oral solution (XL), has been widely used as an adjunct treatment for male infertility in the clinic. However, the underlying mechanisms of XL treatment on iOAZS are still not known. Here, we found that XL treatment has therapeutic effects on ornidazole (ORN)-induced OAZS model rats through the amelioration of testis tissues spermatogenesis and the improvement of sperm concentration and motility. Moreover, XL treatment ameliorated the serum hormone levels, mitochondrial membrane potential, apoptosis status, and oxidative stress status in the testis tissues of iOAZS model rats. These findings identify a potential mechanism underlying the therapeutic effects of Xianlu oral solution on iOAZS, and Xianlu oral solution may be used as a traditional Chinese medicine (TCM) therapy for male infertility caused by iOAZS in clinical practice.

Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer.

Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum-based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V-PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co-incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1-containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients.

Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus.

AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman's correlation analysis was used to evaluate the correlation between those microRNAs and the risk factors of GDM, and receiver operating characteristic curve analysis was used to evaluate diagnostic sensitivity and specificity. RESULTS: Compared with non-GDM women, the relative and absolute expression of plasma microRNA-16-5p, -17-5p, -20a-5p from GDM women were significantly upregulated, when those women were diagnosed as GDM. During pregnancy, the expression of those microRNAs from GDM women also were significantly upregulated. The expression of those microRNAs was also positively correlated with IR, a risk factor of GDM. Plasma microRNA-16-5p, -17-5p, -20a-5p reflected an obvious separation between GDM women and non-GDM women, with areas under the curve of 0.92 (95%CI: 0.871-0.984), 0.88 (95%CI: 0.798-0.962), and 0.74 (95%CI: 0.618-0.870), respectively, cut-offs >2554, 1820, 3886 copies/µL, respectively; sensitivity 41.6%, 21.4% and 17.8%, respectively; and specificity 95.8%, 95.4% and 95.4%, respectively. CONCLUSION: Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.