Graziani A et al., 2026·Journal of clinical medicine·Free full text on PubMed Central
Erectile dysfunction (ED) is increasingly recognized as an early manifestation of systemic vascular disease and might represent a window for cardiovascular risk assessment. Dynamic penile colour Doppler ultrasound (PCDU) provides quantitative arterial and venous parameters that could reflect subclinical vascular impairment. We investigated the association between PCDU parameters and estimated cardiovascular risk in men with ED. In this single-center retrospective observational study, 275 men undergoing PCDU for ED were evaluated. Clinical characteristics, biochemical data, and QRISK3 10-year cardiovascular risk scores were collected. Mean peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were analyzed. Correlation analyses, logistic regression using a QRISK3 ≥ 10% threshold, linear regression models, age-stratified analyses, and receiver operating characteristic (ROC) curve analyses were performed. Patients with impaired PSV (<35 cm/s) were older and exhibited higher QRISK3 scores and a greater prevalence of diabetes mellitus and previous cardiovascular events. Mean PSV was inversely correlated with QRISK3 (r = -0.203, p < 0.01) and was associated with higher cardiovascular risk categories in unadjusted logistic regression (β = -0.016, p = 0.048), but not after adjustment for age and diabetes mellitus. ROC analysis showed modest discrimination of increased cardiovascular risk (AUC = 0.60). The addition of PSV to a model including age and diabetes resulted in minimal improvement in discrimination (AUC 0.966 vs. 0.968). Age-stratified analysis demonstrated a significant association between lower PSV and higher cardiovascular risk only in patients ≤60 years. A progressive increase in QRISK3 was observed according to the number of abnormal Doppler parameters (p = 0.013). PCDU parameters reflect the overall cardiovascular risk burden in men with ED. Although not independent predictors beyond traditional risk factors, penile Doppler abnormalities might identify a vascular phenotype associated with higher estimated cardiovascular risk, particularly in younger individuals. These findings support the role of comprehensive vascular assessment in selected patients with ED.
Barbato M et al., 2026·Frontiers in Reproductive Health·Free full text on PubMed Central
Couple infertility is a common clinical condition that is too often treated with assisted reproductive techniques (ARTs) without a proper evaluation of both male and female factors. To improve the likelihood of natural conception, fertility awareness methods (FAMs) are widely used. We performed a multicenter prospective study enrolling couples with primary idiopathic infertility who were seeking natural conception. Participants were followed for 12 months using FAMs, and their outcomes were compared with those of couples who only used ARTs. The aim of our study was to evaluate the pregnancy rate after 12 months among couples with idiopathic infertility using FAMs compared with those who immediately pursued ARTs. We evaluated 41 couples in the FAM group and 56 couples in the ART group. In the FAM group, we reported a pregnancy rate (PR) of 51.22%. Among women aged <34 years, we reported a PR of 90.9%, while it decreased to 36.7% among women aged 35-39 years. In the ART group, 10 couples achieved pregnancy (PR 17.8%). Within this group, we reported a PR of 30% among women aged <34 years and 17.4% among women aged 35-39 years. After 12 months of unprotected intercourse without spontaneous conception in women younger than 35 years or after 6 months in women aged 35-39 years, couples should undergo a complete multidisciplinary diagnostic evaluation involving both the male and female partners. If a diagnosis of idiopathic infertility is established at the end of this process, couples (especially younger ones) may be advised to wait an additional 12 months while using FAMs, as no advantage has been observed with direct access to ARTs. They could then be referred to ART if a spontaneous pregnancy is not achieved during this period.
Male Endocrine and Genetic Factors · Genetic Causes of Male Infertility
Genetic variability within the follicle-stimulating hormone (FSH)-related genes might contribute to phenotypic heterogeneity in patients with Klinefelter syndrome (KS), yet its clinical impact on sperm retrieval remains unclear.
To investigate the association between FSHB c.211 G > T and FSHR polymorphisms (c.2039 A > G and c.29 G > A) and hormonal parameters, as well as their potential role in predicting sperm retrieval rate (SRR) in patients with KS undergoing testicular sperm extraction (TESE).
A retrospective cohort of patients with KS was analyzed. Only subjects not receiving testosterone replacement therapy were included (n = 417). Hormonal, anthropometric, and clinical variables were compared across genotypes using nonparametric tests. Additive genetic models were applied to evaluate allele-dose effects. Multivariable logistic regression was performed to identify independent predictors of SRR. Predictive performance of clinical and combined clinical-genetic models was assessed using ROC curve analysis.
FSHB and FSHR genes polymorphisms were associated with variations in serum FSH concentrations, confirming a modulatory role of the FSH-related genes. In additive modeling, the FSHR c.29 G > A polymorphism emerged as an independent predictor of SRR (adjusted OR: 0.29; 95% CI, 0.09-0.97), whereas FSHB c.211 G > T showed a nonsignificant trend. The inclusion of genetic variants modestly improved predictive accuracy compared with clinical variables alone, as demonstrated by ROC analysis.
Genetic variants within the genes involved in FSH action might contribute incremental information for the prediction of sperm retrieval in patients with KS. While the overall predictive gain remains moderate, additive genetic modeling highlights a potential allele-dose effect of FSHR c.29 G > A on reproductive outcome, supporting a role for integrated clinical-genetic assessment in this population, although external validation remains required.
Klinefelter syndrome (KS) is characterized by marked phenotypic heterogeneity that might be influenced by genetic modifiers, including androgen receptor (AR) repeat length (CAGn and GGCn). The clinical relevance of these repeat lengths in patients with KS before testosterone replacement therapy (TRT) remains unclear.
To investigate the association between AR repeat length and anthropometric, hormonal, metabolic, and reproductive parameters in a well-characterized cohort of untreated adult patients with KS.
In this cross-sectional single-center study, 214 men with classical 47, XXY karyotype were evaluated prior to TRT. Clinical, biochemical, and reproductive parameters were analyzed according to AR CAGn and GGCn repeat length. Nonparametric tests, multivariable linear and logistic regression models, and interaction terms between CAGn and GGCn were tested. Standardized beta coefficients were used to compare the relative contribution of AR repeat length with major clinical determinants.
In unadjusted analyses, CAG repeat length was associated with estradiol concentrations, whereas GGC repeat length showed associations with hematocrit, platelet count, and total cholesterol. However, most associations were characterized by small effect sizes and did not persist after multivariable adjustment for possible confounders (age, BMI, and total testosterone levels). Moreover, AR repeat length was not associated with sperm retrieval rate. Standardized beta analyses demonstrated that testosterone levels, BMI, and age accounted for the largest proportion of phenotypic variability, whereas CAGn and GGCn repeat length had minimal roles.
In untreated patients with KS, AR repeat length (CAGn and GGCn) appears to have a limited clinical impact compared with classical endocrine and metabolic determinants. These findings suggest that phenotypic variability in KS might be primarily driven by chromosomal aneuploidy and primary testicular dysfunction rather than AR repeat length.
Grande G et al., 2025·Andrology·Free full text on PubMed Central
In infertile couples whose male partner has alterations in semen parameters frequently, a comprehensive andrological approach is lacking and approximately 30-50% are classified as idiopathic infertility. These couples are often directly addressed to assisted reproduction techniques (ARTs). However, several clinical conditions may benefit from medical treatment. By acting on etiology and/or risk factors, this aims at improving seminal parameters and restoring natural fertility. To verify the impact of a comprehensive andrological assessment on the management of infertility (in particular, in couples with isolated male factor infertility) using as the primary outcome the natural pregnancy rate. A multicenter retrospective study was conducted between 2015 and 2022 in 1014 couples with primary infertility seeking natural conception (including 266 couples with previous ART failure). Each couple underwent a multidisciplinary evaluation. This involved: a gynecologist and an andrologist both with expertise in infertility, a psychologist when requested, and a fertility awareness practitioner according to a unique diagnostic and therapeutic multidisciplinary protocol. An isolated male factor was found in 23% of couples. In 45%, it was associated with female factors also. The comprehensive diagnostic approach reduced the proportion of idiopathic infertility to 8% of the couples. Targeted treatment, based on diagnostic categories, was associated with spontaneous pregnancy in 40.9% of the couples. In the 233 cases without female factors, normal semen parameters were observed only in 13% of patients. Male genital tract inflammation was observed in 48.8% of the patients, genital tract infection in 43.1%, and hypospermatogenesis in 16.7%. Patients with infections were treated with antibiotics and probiotics. If further inflammation was documented, this was followed by low-dose corticosteroids and antioxidants. Follicle stimulating hormone (FSH) treatment was used in patients with hypospermatogenesis, and varicocele repair surgery was performed in four patients. Our data underline the efficacy of a comprehensive approach to the diagnostic process of male factor infertility, both in reducing the percentage of idiopathic infertility and in restoring natural fertility based on a targeted treatment.
Graziani A et al., 2025·Cancers·Free full text on PubMed Central
Background/Objectives: Semen cryopreservation has been widely used in recent decades, mainly in patients with male factor infertility (MFI) and patients with cancer (to preserve their fertility potential before undergoing gonadotoxic treatments, such as chemotherapy or radiotherapy). we evaluated the temporal trend and the existence of factors determining the usage of cryopreserved semen (in order, for instance, to conceive using assisted reproduction techniques (ARTs)). We evaluated 7044 patients who cryopreserved since 1991, evaluating clinical information such as the diagnosis, age, the method with which the collection took place and the number of pick-ups for use in ART. The mean age of the patients was 33.12 ± 8.41 years. The most common cancers were testicular (1758/3262) and hematological cancers (942/3262). Patients who underwent cryopreservation for MFI picked up their samples much more than neoplastic patients (42.15% vs. 8.55%). Patients 35-40 years old picked up their samples more frequently when compared with other age groups. Moreover, we found several data regarding the sub-types of cancers and the methods of semen collection. According to our results, the indication for semen cryopreservation, age and the method of collection might represent a simple way to predict the future use of semen for ART.
Milardi D et al., 2025·Proteomes·Free full text on PubMed Central
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.
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.
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.
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.
Recurrent pregnancy loss (RPL), defined as two or more failed clinical pregnancies, affects 1%-3% of couples trying to conceive. Nowadays up to 50% of cases remain idiopathic. In this context, paternal factors evaluation is still very limited. The aim is to address the topic of the male factor in RPL with a broad approach, analyzing collectively data on sperm DNA fragmentation (SDF) and semen parameters. We systematically searched in Pubmed/MEDLINE and Google Scholar from inception to February 2023. A protocol has been registered on PROSPERO (ID number CRD42022278616). PRISMA guidelines were followed.
Pooled results from 20 studies revealed a higher DNA fragmentation rate in the RPL group compared to controls (mean difference [MD] 9.21, 95% CI 5.58-12.85, p < 0.00001, I2 98%). Age, body mass index (BMI), smoking, and alcohol intake were not associated with DNA fragmentation. Subgroup analysis by different SDF assays (TUNEL and COMET at a neutral pH vs. indirect assessment with other assays) and ethnicity did not highlight different results (p = 0.25 and 0.44).
Results pooled from 25 studies showed a significant difference comparing RPL and control groups regarding ejaculation volume (MD -0.24, 95% CI -0.43; -0.06, p 0.01, I2 66%), total sperm number (MD -10.03, 95% CI -14.65; -5.41, p < 0.0001, I2 76%), total sperm motility (MD -11.20, 95% CI -16.15; -6.25, p < 0.0001, I2 96%), progressive sperm motility (MD -7.34, 95% CI -10.87; -3.80, p < 0.0001, I2 97%), and normal sperm morphology (MD -5.99, 95% CI -9.08; -2.90, p 0.0001, I2 98%). A sub-analysis revealed that Asian and Africans, but not white-European RPL men had lower progressive sperm motility compared to controls.
In conclusion, current review and meta-analysis findings suggested that SDF and some specific semen parameters were associated with RPL in a multi-ethnic evaluation. This effort opens future direction on a growing awareness of, first, how the male factor plays a key role and, second, how appropriate would be to establish a direct dialogue between the gynecologist and the urologist.
We performed a systematic review and meta-analysis on the male component of RPL. We found that sperm DNA fragmentation and some specific sperm parameters are significantly associated with RPL.
Grande G et al., 2024·Life (Basel, Switzerland)·Free full text on PubMed Central
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.
Male Endocrine and Genetic Factors · Genetic Causes of Male Infertility
Graziani A et al., 2024·Genes·Free full text on PubMed Central
Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.
Grande G et al., 2024·Cells·Free full text on PubMed Central
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".
Grande G et al., 2023·Life (Basel, Switzerland)·Free full text on PubMed Central
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.
Graziani A et al., 2023·Life (Basel, Switzerland)·Free full text on PubMed Central
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.
Infertility Distress · Anxiety and Depression in Infertility
Inversetti A et al., 2023·Life (Basel, Switzerland)·Free full text on PubMed Central
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.
Supplements and Botanicals · Herbal and Botanical Products
Petre GC et al., 2023·Nutrients·Free full text on PubMed Central
The use of nutraceutical products to enhance male sexual performance has a long history, especially with regard to the treatment of erectile dysfunction (ED). Alternative treatments for ED are becoming increasingly popular, with growing interest from consumers, as well as increased revenue for manufacturers. Dietary supplements (DSs), which are a mixture of active ingredients, are mainly sold online. In randomized controlled trials, the molecules contained in DSs have demonstrated varying degrees of effectiveness, or even have no evidence to support their use. However, none of the studies carried out provided sufficient evidence to consider these products a first-line therapy. Therefore, the combination of the various active ingredients, especially in relation to the daily dose, leaves doubts about the real effectiveness. In order to evaluate the potential efficacy of DS formulations, we analyzed the products marketed in Italy using a scoring approach. A systematic review of the literature was performed to evaluate the effect of DS and to detect the active ingredients able to improve erectile function-called effective ingredients (EIs)-and their minimal effective daily dose (mED). A metanalysis identified some nutraceuticals, such as Panax ginseng, Tribulus terrestris and L-arginine, that are able to improve male sexual function. Based on the scoring system, 2 (8%) supplements matched with the cluster of higher expected efficacy, 3 (12%) with the lower efficacy cluster and 20 (80%) matched with the criterion of no expected efficacy. DSs marketed in Italy are usually blends of many substances that are frequently employed at a negligible dose or without any evidence.
Petre GC et al., 2023·Nutrients·Free full text on PubMed Central
Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40-50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059-0.133; p < 0.00)]. Therefore, adhering to the MD with at least a MEDAS score of 6.26 increases the probability of normozoospermia. Moreover, subjects who had a MEDAS value lower than 6.25 had an Odds Ratio of 6.28 (CI = 3.967-9.945) for having at least one altered sperm parameter compared to those who were more adherent to the MD. In conclusion, our findings show that a higher adherence to the MD is associated with better semen parameters, in particular in relation to sperm count, sperm concentration, typical sperm morphology, and sperm progressive motility.
Grande G et al., 2023·Endocrine connections·Free full text on PubMed Central
Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6-15% of osteoporosis and of 25-48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.
Anti-Infective and Anti-Inflammatory Agents · Antibiotics in Reproductive Care
Grande G et al., 2022·American journal of men's health·Free full text on PubMed Central
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.
Fernandez-Hermida Y et al., 2022·Life (Basel, Switzerland)·Free full text on PubMed Central
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.
Thyroid and Metabolic Function · Insulin and Metabolism
Zolla L et al., 2022·International journal of molecular sciences·Free full text on PubMed Central
Hypogonadic subjects with insulin resistance (IR) showed different metabonomic profiles compared to normo-insulinemic subjects (IS). Testosterone replacement therapy (TRT) may have a different impact on the metabolisms of those with the presence or absence of insulin resistance. We evaluated the changes in the metabolism of IR hypogonadic patients before and after 60 days of TRT. The metabonomic plasma profiles from 20 IR hypogonadal patients were recorded using ultra-high-performance liquid chromatography (UHPLC) and high-resolution mass spectrometry (HRMS). Plasma metabolites, before and after 60 days of TRT, were compared. In hypogonadic patients, carnosine, which is important for improving performance during exercise, increased. Conversely, proline and lysine-amino acids involved in the synthesis of collagen-reduced. Triglycerides decreased and fatty acids (FFAs) increased in the blood as a consequence of reduced FFA β-oxidation. Glycolysis slightly improved, while the Krebs cycle was not activated. Gluconeogenesis (which is the main energy source for hypogonadal IR before TRT) stopped after treatment. As a consequence, lactate and acetyl CoA increased significantly. Both lactate and acetyl CoA were metabolized into ketone bodies which increased greatly, also due to leucine/isoleucine degradation. Ketone bodies were derived predominantly from acetyl CoA because the reaction of acetyl CoA into ketone bodies is catalyzed by mtHMGCoA synthase. This enzyme is inhibited by insulin, which is absent in IR patients but overexpressed following testosterone administration. Ketosis is an alternative route for energy supply and provides the same metabolic effects as insulin but at the metabolic or primitive control level, which bypasses the complex signaling pathway of insulin. After treatment, the hypogonadic patients showed clinical symptoms related to ketonuria. They presented similarly to those following a ketogenic diet, the so-called 'keto flu'. This must be taken into account before the administration of TRT to hypogonadic patients.
Garolla A et al., 2021·Andrology·Free full text on PubMed Central
Scrotal color Doppler ultrasonography and transrectal ultrasonography provide crucial information about the clinical status of testes and male accessory glands.
To analyze the impact of ultrasound in the evaluation of infertile males.
A total of 1120 records from infertile men were retrospectively evaluated (from January 2016 up to June 2020). Data on physical examination, semen analysis, sperm culture, scrotal color Doppler ultrasonography and transrectal ultrasonography, as well as sex hormones were analyzed. Among them, 238 reports from oligozoospermic/azoospermic infertile patients (P) fulfilling the inclusion criteria were considered for data analysis. Patients were subdivided into two groups according to follicle-stimulating hormone (FSH) values (Pa with FSH < 8 U/L and Pb with FSH ≥ 8 U/L). Sixty-three fertile volunteers (mean ± SD years) were enrolled as controls (C).
A higher prevalence of ultrasound abnormalities was recorded in P compared to C. Pb group had significantly lower bitesticular volume compared to Pa and C. Pa had a higher prevalence of transrectal ultrasonography abnormalities than Pb (69.9% vs. 38.4%), whereas Pb had a higher prevalence of abnormalities at scrotal color Doppler ultrasonography (60.0% vs. 28.3%, both p < 0.01). Bitesticular volume was inversely proportional to the number of altered seminal parameters and able to predict gonadotropin levels. A bitesticular volume <17 cc was associated with a higher risk of azoospermia (odds ratio = 1.799). Intratesticular vascularization was inversely correlated with gonadotropin levels and directly correlated with sperm count. A higher prevalence of prostate and seminal vesicle alterations was detected in patients and in Pa group, when compared with Pb group.
Ultrasound abnormalities are correlated with seminal parameters and may guide the clinician in the diagnostic workflow of male infertility, suggesting spermatogenesis impairment or genital tract obstructions.