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One of the biggest problems facing modern medicine is infertility [...]

Background and aim Remimazolam has proved to be a very promising sedative drug in randomized clinical trials for usage in a wide spectrum of patients, including critically ill ones. The purpose of our study was to verify efficacy and safety of remimazolam for procedural sedation during diagnostic and first level operative endoscopy in a real-world setting. Methods This single centre prospective study evaluated sedation regimen with remimazolam for EGDS and fentanyl and remimazolam for colonoscopy in consecutive ASA 1–3 patients. Results Seventy-one patients underwent 73 procedures (25 EGDS, 48 colonoscopies) with a total amount of 13.2 ± 8.7 mg and 10.2 ± 6.2 mg of remimazolam administered respectively. In 6 EGDS, rescue sedation with propofol was needed. Transient hypotension was frequent (37%) and no cases of hypoxia occurred. One case of suspected allergy (erythema of the trunk) without anaphylaxis was reported. Conclusions Procedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70–75% of cases.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as urologic pain or discomfort in the pelvic region, associated with urinary symptoms and/or sexual dysfunction, lasting for at least 3 of the previous 6 months. The rate of symptoms related to prostatitis has a mean prevalence of 8–8.2%. CP/CPPS is most frequent in men younger than 50 years, among whom it is the most common urologic diagnosis. In the last decades, many studies have been published on CP/CPPS and its association with male infertility. The pathophysiologic relation between CP/CPPS and male infertility involves several aspects, which are not well studied yet. A reduction in semen parameters has been demonstrated in patients with CP/CPPS, and several mechanisms have been proposed to represent putative pathophysiological links between CP/CPPS and infertility, including male accessory gland inflammation, metabolic syndrome, inflammatory bowel disease, HPV co-infection and autoimmunity. In light of this evidence, a multidisciplinary approach is advocated for patients with known CP/CPPS, and particular attention is needed for male patients of infertile couples in order to evaluate male accessory glands correctly. In addition, it is advisable that future studies dealing with the treatment of CP/CPPS take into consideration all the different pathophysiological aspects implicated.

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10–18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as “non-responders”. For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review’s objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the “couple genital microbiota”.

The aim of the present study is to perform a systematic review and meta-analysis on depression, stress and anxiety in women who experienced recurrent pregnancy loss (RPL) compared to controls and to men who experienced RPL. The pooled results showed a higher level of moderate/severe depression among women who experienced RPL compared to controls (5359 women, random effects model, odds ratio (OR) 3.77, 95% Confidence Interval (CI) 2.71–5.23, p < 0.00001, I2 0%). Anxiety and stress levels were also higher among women experiencing RPL compared to controls. The pooled results showed a higher level of moderate/severe depression in women who experienced RPL compared to men who underwent the same experience (113/577 (19.5%) women versus 33/446 (7%) men versus random effects model, OR 4.63; 95% CI 2.95–7.25, p < 0.00001 I2 0%). Similarly, higher levels of stress and anxiety in women experiencing RPL compared to men experiencing RPL were described. Women who experienced RPL showed higher rates of moderate–severe depression, stress and anxiety compared to both controls and men who experienced RPL. Healthcare professionals should implement screening for anxiety and depression and social support for both partners and support them in dealing with RPL according to sex-specific responses to this stressful event.

Male tract infections (MTIs) are a common clinical condition, often presenting without any signs nor symptoms of disease. As advised by the European Urology Guidelines dealing with this topic, patients are typically treated with antibiotics alone. Nevertheless, in between 40% and 50% of cases, antibiotic therapy is not effective in eradicating the semen infection. Therefore, persistent semen infection is frequently found upon semen culture evaluation following antibiotic therapy. In this study, we aimed to analyze the fecal microbiota of male infertile patients with persistent MTI in order to verify the prevalence of gut dysbiosis in these patients. We therefore enrolled 20 infertile patients with persistent MTIs after a proper cycle of antibiotic treatment. All patients performed the study for gut microbiota analysis after about 30 days after the last dose of antibiotic treatment. Gut microbiota analysis revealed that 50% of patients with persistent MTI presented a reduction in microbial biodiversity. Indeed, a situation of gut dysbiosis was reported in 75% of patients. In details, the Firmicutes–Bacteroidetes ratio was reduced in 70% of such patients, including 40% of patients where a severe reduction was observed due to an elevated abundance of Bacteroidetes (putrefactive dysbiosis). The most frequent enterotype was Prevotella-dominant (43%). We demonstrated for the first time that patients with recurrent MTIs have enterotypes associated with increased gut permeability and systemic inflammation. Further studies are required to analyze the molecular machinery by which gut dysbiosis exerts its role in patients with MTIs, in particular persistent MTIs, and how supplementation with probiotics might impact in terms of restoring eubiosis, in terms of eradicating the infection, and reducing prostate inflammation and eventually in terms of improving semen evaluation in male infertile patients.

Male accessory gland infection (MAGI) represents a frequent disease, commonly treated with antibiotics alone. However, in approximately 40% to 50% of patients, persistent infection is detected. Intestinal dysbiosis is involved in the pathogenesis of prostatitis. We aimed to evaluate the efficacy of antibiotic treatment in association with a specific probiotic supplementation. A total of 104 infertile patients, with microbiological analysis on semen and/or prostatic secretions positive for Gram-negative bacteria, have been enrolled. All patients received antibiotic treatment with fluoroquinolones. In total, 84 patients received a commercial association of Enterococcus faecium and Saccharomyces boulardii during antibiotic treatment, followed by treatment with Lactobacilli. After the treatment, a complete microbiological analysis was repeated. Polymicrobial infections have been observed in 11% of patients, while infections due to a single germ were reported in 89% of the patients. After the treatment was performed, a complete eradication with negative semen culture and microbiological analysis on prostatic secretion was observed in 64 of 84 patients (76.2%), while only 10 of 20 patients receiving antibiotics alone (50%; p < .05) reported negative microbiological analysis. Persistent infections have been observed only in patients with infections due to Enterococcus faecalis and Escherichia coli. This study represents the first approach demonstrating the efficacy of a specific probiotic treatment in reducing the rate of persistent infections in patients with MAGI.

There is an increasing number of couples interested in identifying the fertile window for the purpose of conceiving. From what has been published so far, it can be concluded that there are no reliable methods to predict ovulation, and, therefore, to predict the fertile window. Proteins of the cervical mucus (CM) could behave as biomarkers to allow the early and precise identification of ovulation. CM samples were collected from the lumen of the cervical canal from women of reproductive age, on three different days of the same menstrual cycle. Samples were first analyzed and classified by light microscopy. High-resolution mass spectrometry and bioinformatic analysis were performed afterwards to determine the in vivo changes of CM protein composition. CM underwent cyclical changes in its biophysical composition, which were evidenced by changes in the crystallographic patterns observed under the light microscope. The proteomic analysis revealed changes in the protein composition of CM along the cycle. Twenty-five out of the forty-eight total proteins identified could become potential biomarkers of ovulation. The coordinated changes in the composition of the CM around the time of ovulation could be happening to specifically grant access to a foreign body, such as the sperm might be.

Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies.