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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.

Transgender and gender diverse (TGD) individuals face significant healthcare barriers, resulting in inequities and unmet needs. Mobile health (mHealth) applications offer promising solutions by providing accessible, cost-effective, personalized, and gender-affirming care. This systematic review, conducted using PRISMA 2020 guidelines and the PICO framework, screened 5005 records from 4 databases and included 11 articles. The review aimed to identify key features of mHealth apps developed for TGD individuals, focusing on theoretical frameworks, design strategies, and their approaches to addressing healthcare barriers. Key challenges in developing mHealth apps include implementing systemic changes in healthcare settings to combat stigma and discrimination, grounding app development in TGD-specific theoretical frameworks, adequately addressing stressors and protective factors, and overcoming methodological limitations that hinder the evaluation of health outcomes. Overcoming these challenges requires rigorous research methodologies, inclusive designs, reliance on evidence-based TGD frameworks, and stronger collaboration among researchers, healthcare providers, and TGD communities.

The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis. We obtained semen samples from 16 normozoospermic subjects attending an infertility survey programme, testis biopsies from 6 patients with testicular germ cell cancer and testis fine needle aspirates from 6 patients with obstructive azoospermia undergoing assisted reproductive technologies. Expression of TRPV1 mRNA was assessed by RT-PCR. Protein expression of TRPV1 was determined by western blot, flow cytometry and immunofluorescence. Sperm motility was assessed by Sperm Class Analyser. Acrosome reaction, apoptosis and intracellular-Ca2+ content were assessed by flow cytometry. We found that TRPV1 mRNA and protein were highly expressed in the testis, in both Sertoli cells and germ-line cells. Moreover, compared to no-gradient controls at 31°C or 37°C (Ctrl 31°C and Ctrl 37°C respectively), sperm migration towards a temperature gradient of 31-37°C (T gradient) in non-capacitated conditions selected a higher number of cells (14,9 ± 4,2×106 cells T gradient vs 5,1± 0,3×106 cells Ctrl 31°C and 5,71±0,74×106 cells Ctrl 37°C; P = 0,039). Capacitation amplified the migrating capability towards the T gradient. Sperms migrated towards the T gradient showed enriched levels of both TRPV1 protein and mRNA. In addition, sperm cells were able to migrate toward a gradient of capsaicin, a specific agonist of TRPV1, whilst capsazepine, a specific agonist of TRPV1, blocked this effect. Finally, capsazepine severely blunted migration towards T gradient without abolishing. These results suggest that TRPV1 may represent a facilitating mediator of sperm thermotaxis.

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”.

Background This study adopts a qualitative methodological framework to investigate the overall experiences of institutional gender affirmation pathway (GAP) with a focus on the narratives of mandatory psychological assessment in Trans and Nonbinary (TNB) people in Italy, who face daily discrimination, social prejudice, episodes of violence, and victimization. In the Italian context, psychological assessment is a prerequisite to receive a diagnosis of gender dysphoria, which is essential to access hormone therapy, surgical interventions, and legal change of name and gender marker. Methods The study employed a qualitative methodological design, since it allows a deep and flexible exploration of participants’ experiences and perspectives. Specifically, the data collection technique consisted of semi-structured interviews with N  = 21 participants. The corpus of data was analyzed consistently with thematic analysis and reflexive thematic analytic approach, for identifying, analysing and reporting patterns in data, allowing the corpus of data to be examined in terms of their principal themes, using both theory-driven (top-down) and bottom-up analytical strategies. Results Through the reflexive thematic approach, we generated two themes, further divided into sub-themes. The first theme is “Being trans + in our society” and it is composed by the following sub-themes: “personal experiences of identity affirmation”; “minority stress and transphobia”; “supportive familiar and working contexts”, “institutional gender affirmation process”; “resilience and self-determination”. The second theme, “Experiences of mandatory psychological assessment” is divided in: “disrespectful experiences”; “affirming and supportive interactions”; “to take better care”. The results highlight how TNB individuals often experience significant stress related to their minority status and face discrimination in healthcare settings. Furthermore, there is a lack of individualization in the approach by healthcare providers and a shortage of knowledge about gender sensible topics among them. This study therefore highlights an insufficient provision of effective psychological support and the need to adopt more inclusive approaches, dismantling the pathologizing dimension of the diagnostic process for TNB people. Conclusions It is therefore crucial to promote awareness programs on gender identity issues to foster a more welcoming and informed environment in healthcare settings. Trial registration The study has been approved by the Ethics Committee of the University of Padua with unique number D120DC6FDC5DF2694CF281D76B2CDB41 and protocol number 5003.

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.

Although precision medicine took its first steps from genomic medicine, it has gone far beyond genomics, considering the full complexity of cellular physiology. Therefore, the present time can be considered as the “post-genomic era”. In detail, proteomics captures the overall protein profile of an analyzed sample, whilst metabolomics has the purpose of studying the molecular aspects of a known medical condition through the measurement of metabolites with low molecular weight in biological specimens. In this review, the role of post-genomic platforms, namely proteomics and metabolomics, is evaluated with a specific interest in their application for the identification of novel biomarkers in male hypogonadism and in the identification of new perspectives of knowledge on the pathophysiological function of testosterone. Post-genomic platforms, including MS-based proteomics and metabolomics based on ultra-high-performance liquid chromatography-HRMS, have been applied to find solutions to clinical questions related to the diagnosis and treatment of male hypogonadism. In detail, seminal proteomics helped us in identifying novel non-invasive markers of androgen activity to be translated into clinical practice, sperm proteomics revealed the role of testosterone in spermatogenesis, while serum metabolomics helped identify the different metabolic pathways associated with testosterone deficiency and replacement treatment, both in patients with insulin sensitivity and patients with insulin resistance.

We analyzed the efficacy of penile low-intensity extracorporeal shockwave treatment for erectile dysfunction (ED) combined with cavernous artery disease (CAD). ED was evaluated by the International Index of Erectile Function, subdividing patients into mild and moderate/severe forms. CAD was assessed using penile color Doppler ultrasonography. Patients (n = 111) with a positive outcome after treatment, based upon the minimal clinically important difference of the International Index of ED, were followed up for 3 months and 6 months. We found a significant mean increase in the index of erectile function, with an overall improvement in hemodynamic parameters of the cavernous artery. In particular, 93.9% of the patients with mild ED without CAD responded to treatment and 72.7% resumed normal erectile function. Only 31.2% of the patients with moderate/severe ED and CAD responded to treatment, and none resumed normal erectile function. All patients with mild ED and no CAD maintained the effects of therapy after 3 months, while no patients with moderate/severe ED and CAD maintained the benefits of treatment after 3 months. Thus, patients with mild ED and no CAD have better and longer lasting responses to such treatment, with a higher probability of resuming normal erectile function than patients with moderate/severe ED and CAD.

Background and Aims Increasing attention is being paid to the role of human papillomavirus (HPV) in men and specifically reproduction. Growing evidence suggests an association between HPV infection with many adverse effects including the impairment of semen parameters, the increase of blastocyst apoptosis, the reduction of endometrial implantation of trophoblastic cells, as well as the increase rate of miscarriages and spontaneous preterm birth. Methods We systematically searched PubMed/MEDLINE, Scopus, Embase, Web of Science, CINHAL, PsycINFO, and ERIC from inception to 2nd of July 2024, for studies that investigated the association between HPV infection with sperm parameters and fertility outcomes. The meta‐analysis was conducted on mean data and standard deviations. Results We included 25 studies with a total of 6942 patients. Sperm morphology was lower in HPV positive groups versus HPV negative control groups (SMD = ‐0.52 95% CI −0.84; −0.21; p = 0.001). Sperm motility was also significantly lower in HPV positive groups when compared to HPV negative controls (SMD = −0.82 95% CI −1.07; −0.57; p = <0.001). Sperm volume, concentration, and pH were not significantly different between the two groups. The other 15 studies included in the systematic review for which it was not possible to conduct a meta‐analysis showed strong associations between HPV infection and impairment of sperm parameters, reduced couple fertility and increased risk of pregnancy loss. Conclusions The current evidence highlights the link between HPV infection and sperm parameters, male fertility and reproductive outcomes, which has the potential to lead to a decreased couple fertility, increased risk of pregnancy loss, re‐infection and increased treatment costs.

No valid method is currently available to analyze the entire genome of sperm, including aneuploidies and structural chromosomal alterations. Here we describe the optimization and application of array-Comparative Genomic Hybridization (aCGH) on single human sperm. The aCGH procedure involves screening of the entire chromosome complement by DNA microarray allowing having a molecular karyotype, and it is currently used in research and in diagnostic clinical practice (prenatal diagnosis, pre-implantation genetic diagnosis), but it has never been applied on sperm. DNA from single human sperm isolated by micromanipulator was extracted, decondensed and amplified by whole-genome amplification (WGA) and then labeled, hybridized to BAC array, and scanned by microarray scanner. Application of this protocol to 129 single sperm from normozoospermic donors identified 7.8% of sperm with different genetic anomalies, including aneuploidies and gains and losses in different chromosomes (unbalanced sperm). On the contrary, of 130 single sperm from men affected by Hodgkin lymphoma at the end of three months of chemotherapy cycles 23.8% were unbalanced. Validation of the method also included analysis of 43 sperm from a man with a balanced translocation [46,XY,t(2;12)(p11.2;q24.31)], which showed gains and losses corresponding to the regions involved in the translocation in 18.6% of sperm and alterations in other chromosomes in 16.3% of sperm. Future application of this method might give important information on the biology and pathophysiology of spermatogenesis and sperm chromosome aberrations in normal subjects and in patients at higher risk of producing unbalanced sperm, such as infertile men, carriers of karyotype anomalies, men with advanced age, subjects treated with chemotherapy, and partners of couples with repeated miscarriage and repeated failure during assisted reproduction techniques.