CAPN2 correlates with insulin resistance states in PCOS as evidenced by multi-dataset analysis.

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies. METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD. RESULTS: Thirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS. CONCLUSIONS: This study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.

Association of SGLT2is with cardiovascular and reproductive diseases: a meta-analysis based on 14 large-scale randomized trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can improve long-term cardio-renal outcomes in patients with diabetes, heart failure (HF), or renal failure. We aimed to investigate the association of SGLT2is with the risks of various cardiovascular and reproductive diseases. METHODS: Large-scale randomized trials enrolling more than 1000 participants and assessing SGLT2is were included. Outcomes of interest were the various serious adverse events related to cardiovascular or reproductive diseases. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 14 large trials and evaluated 169 types of cardiovascular and reproductive diseases. SGLT2is were significantly associated with the lower risks of 13 types of cardiovascular diseases, e.g., cardiac failure chronic (RR 0.70, 95% CI 0.57-0.87), cardiac failure congestive (RR 0.74, 95% CI 0.66-0.83), acute cardiac failure (RR 0.72, 95% CI 0.60-0.86), coronary artery disease (RR 0.75, 95% CI 0.58-0.97), ischemic cardiomyopathy (RR 0.72, 95% CI 0.52-0.99), atrial fibrillation (RR 0.88, 95% CI 0.78-0.99), bradycardia (RR 0.72, 95% CI 0.53-0.99), and hypertension (RR 0.70, 95% CI 0.54-0.91). SGLT2is were not significantly associated with 18 types of reproductive diseases, e.g., adenomyosis, endometrial hyperplasia, and metrorrhagia. Although SGLT2is were observed to have a significant association with a higher risk of uterine prolapse, the 95% CI of RR for this outcome was relatively wide. CONCLUSION: This meta-analysis confirms the benefits of SGLT2is against chronic congestive HF again; reveals the possible benefits of SGLT2is against acute HF, myocardial infarction, arrhythmias, and hypertension; and identifies that SGLT2is are safe in general for the reproductive system.

Effects of the body mass index of males on hormone levels, sperm and embryo parameters, and clinical outcomes in non-obstructive azoospermia: a systematic review and meta-analysis.

Background: Research has shown that the body mass index (BMI) is not correlated with sperm retrieval outcomes, while serum testosterone and gonadotropins are related to the BMI in non-obstructive azoospermia (NOA). Previously, no comprehensive assessment had been conducted on the effect of the BMI of males in NOA. This study sought to comprehensively evaluate the effects of the BMI of males on hormone levels, sperm and embryo parameters, and clinical outcomes in NOA. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to retrieved relevant articles published up to May 27, 2022. Articles which examined patients with NOA (population), included patients with a BMI ≥25 kg/m2 (intervention) versus patients with a BMI <25 kg/m2 (comparator), assessed reproductive hormones, sperm and embryo parameters, and clinical outcomes (outcome), and were cohort studies (study design) were included. The quality of the included studies was assessed by the Newcastle-Ottawa Scale (NOS). A sensitivity analysis was conducted for all the outcomes. Results: A total of 12 studies comprising 2,994 NOA patients were included. Patients with a BMI ≥25 kg/m2 had lower follicle-stimulating hormone (FSH) [pooled weighted mean difference (WMD): -0.67, 95% confidence interval (CI): -0.94 to -0.41, P<0.001] and total testosterone (TT) (pooled WMD: -1.35, 95% CI: -2.10 to -0.60, P<0.001) levels than those with a normal weight (BMI <25 kg/m2). The testicular volume of the BMI ≥25 kg/m2 group was larger than that of the normal weight group (pooled WMD: 0.26, 95% CI: 0.09 to 0.44, P=0.003). The average BMI of the group with successful sperm extraction was lower than that of the group with failed sperm extraction (pooled WMD: -0.97, 95% CI: -1.89 to -0.04, P=0.041). The live-birth rate of the BMI ≥25 kg/m2 group was lower than that of the normal weight group [pooled relative risk (RR) =0.88, 95% CI: 0.78 to 0.99, P=0.031]. Conclusions: The BMI of the males was an important factor affecting the FSH and TT levels, testicular volume, sperm retrieval success, and live-birth rate in NOA. Weight management may benefit NOA patients.

Progesterone elevation on the day of hCG trigger has detrimental effect on live birth rate in low and intermediate ovarian responders, but not in high responders.

Progesterone elevation (PE) on the day of hCG trigger is associated with decreased pregnancy outcome in fresh cycles. Evidence for this comes from overall patient estimates that mostly ignore different ovarian responses. To compare the impacts of PE on the day of hCG trigger on live birth rates (LBs) in low, intermediate and high ovarian responders and to explore the cut-off value for PE in different populations according to the ovarian response, we retrospectively analyzed a total of 2,351 patients receiving fresh assisted reproduction technology (ART) transfer cycles with GnRH agonist using a long or short protocol. Trend and multivariate logistic regression analyses were performed to identify the cutoff values of PE and to evaluate the effects of PE on LB rates (LBRs) in different ovarian responders. The study found that PE has a detrimental effect on LBRs in low to intermediate ovarian responders rather than in high responders. The cut-off values for PE were 1.0 ng/mL and 2.0 ng/mL for low and intermediate ovarian responders, respectively. The different associations between PE and LBRs according to ovarian response could more accurately predict the prognosis of the IVF cycle and could be used to optimize the treatment of patients undergoing In Vitro Fertilization (IVF)/ Intracytoplasmic Sperm Injection (ICSI).