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Background: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. Objectives: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. Methods: A cohort of 248 HFM (35.3 +/- 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. Results: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was similar to 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. Conclusions: The present findings will help in better understanding male infertility pathophysiology, improving its management.

Background No data are currently available on the implication of amicrobial leukocytospermia in male adolescents. Therefore, the primary aim of this study was to evaluate the prevalence of amicrobial leukocytospermia among non-smoker late adolescents who were exposed to other risky lifestyles for the andrological health. The main andrological clinical features of adolescents with leukocytospermia were also reported. Methods This is a cross-sectional study carried out in 80 boys. Each adolescent underwent a physical examination, and to the assessment of sperm conventional parameters, seminal leukocytes concentration and immature germ cell evaluation. A possible correlation between seminal leukocytes and immature germ cells and testicular volume (TV) was tested. Results The adolescents enrolled in this study had 18.0 ± 0.4 (range 18.1–18.9) years. Unprotected sexual intercourse was referred by 38% of them. Sexual dysfunctions were found in 25% and isolated hypoactive sexual desire in 12.5% of boys. Low TV and penile length in flaccidity were found in 44% and 30% of them, respectively. Only 41% had normozoospermia at the sperm analysis, whereas 19% had isolated oligozoospermia, 15% oligo-asthenozoospermia, and 25% oligo-astheno-teratozoospermia. Leukocytospermia occurred in 25% (20 out of 80) of adolescents. No seminal infection was detected in 19% (15 out of 80) of them. Adolescents with leukocytospermia had lower progressive sperm motility, percentage of normal forms, TV, and a higher percentage of immature germ cells compared to those without leukocytospermia. Semen leukocyte concentration correlated negatively with TV and positively with the percentage of immature germ cells in the ejaculate. Conclusion Leukocytospermia, increased immature germ cell number, and low TV identify a distinct phenotype suggestive of testicular tubulopathy. Primary prevention of male infertility and the counselling for andrological risky lifestyles is mandatory and should be started as early as possible.

Background: The diagnosis of infertility strongly impacts on psychological and sexological couple health. In this regard, some feelings and psychological states were demonstrated in association with reproductive problems. Depression and anxiety are the most common psychopathologies associated with infertility, although also sexuality is strongly involved in infertility conditions. Objectives: The aim of this study is to develop a tool to probe and assess the emotional aspects, sexuality, and social relationships of the couple seeking medical care for infertility. Materials and methods: A self-reported questionnaire that we will refer to as SEIq (Sexuality and Emotions in Infertility questionnaire) was constructed and developed and, consequently, administered to 162 heterosexual couples (324 subjects) seeking help for reproductive problems. Hence, we performed a specific statistical analysis to assess and validate this new psychometric tool. Results. About 60% of men and women (both partners in 43% of couples) declare that infertility has changed their life (Q10). Moreover, the incidence of sexual disorder declared by the subjects is quite rare in men (10%) but more frequent in women (29%) (p < 0.01). Conclusion and discussion: The results of this pilot test show that the diagnosis of infertility impacts on the couple relationship affecting the emotional area, interpersonal relationships, and sexual functions of the couples. Moreover, the SEIq appears a valuable tool to coherently probe and relate sexological, psychological, relational, and emotive aspects in partners and couples facing the infertility diagnosis. The explorative factor analysis of SEIq data allows to understand the women, men, and couples’ behavior in our sample, individuating a reduced set of factors, prone to an easier evaluation. On the whole, the psychometric evaluation through SEIq might be suitable for the couples during Assisted Reproductive Technologies treatments.

Thyroid gland dysfunction represents an epidemiologically relevant disease in the female gender, where treatment with oral contraceptives (OCs) is frequently prescribed. Although OCs are able to impact the thyroid gland function, scanty data have been released on this matter so far. The aim of this article was to review how hormonal OCs, including estrogen- or progesterone-only containing medications, interact with the hepatic production of thyroid-binding globulin (TBG) and, consequently, their effects on serum levels of thyroxine (T4) and triiodothyronine (T3). We also reviewed the effect of Levo-T4 (LT4) administration in women taking OCs and how they influence the thyroid function in both euthyroid women and in those receiving LT4. The estrogenic component of the pills is capable of increasing various liver proteins, such as TBG, sex hormone-binding protein (SHBG) and coagulation factors. On the other hand, the role of progestogens is to modulate estrogen-dependent effects mainly through their anti-androgenic action. In fact, a reduction in the effects of androgens is useful to keep the thromboembolic and cardiovascular risks low, whereas OCs increase it especially in women with subclinical hypothyroidism or in those treated with LT4. Accordingly, subclinical hypothyroidism is known to be associated with a higher mean platelet volume than normal and this increases cardiovascular risk due to platelet hyperactivity caused by incomplete thrombocytopoietic maturation.

Papillomavirus (HPV) often occurs in the semen of patients with male accessory gland infection (MAGI). Ultrasound (US) evaluation has been suggested as a promising diagnostic tool for patients with HPV-related MAGI. No data on the spontaneous clearance of HPV-DNA have been reported so far in HPV-related MAGI. The primary aim of the study was to assess the percentage of early HPV-DNA spontaneous clearance in patients with prostatitis. The secondary aim was to evaluate the frequency of spontaneous clearance of HPV-DNA among patients with prostatitis associated with the presence or absence of US abnormalities. Patients with inflammatory MAGI and at least one suspicious criterion for HPV infection underwent semen HPV-DNA detection and prostate US. The presence of HPV-DNA was further investigated after a 6-month-long follow-up. Eighty patients satisfied the inclusion criteria and were recruited in the study. 69% of patients (55/80) showed HPV-DNA persistence in the semen. Among them, 82% (45/55) was positive for US signs of prostatitis, while they occurred only in 12% (3/25) of those patients with no sign of HPV-DNA persistence (p

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

Purpose: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) Methods: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria. Results: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects. Conclusion: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.

The role of urogenital inflammation in causing infertility and sexual dysfunctions has long been a matter of debate in the international scientific literature. The most recent scientific evidences show that male accessory gland infection/inflammation could alter, with various mechanisms, both conventional and biofunctional sperm parameters, and determine worst reproductive outcome. At the same time, the high prevalence of erectile dysfunction and premature ejaculation in patients with male accessory gland infection/inflammation underlines the close link between these diseases and sexual dysfunctions. The aim of this review was to provide the reader the basis for a correct diagnosis of male accessory gland infection/inflammation and a subsequent appropriate therapeutic approach, particularly in patients with infertility and/or sexual dysfunction.

Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes’ lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Some evidences have supported the link between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and inflammation. In this study, we aimed to evaluate the association between prostatic inflammation (PI) and non-alcoholic steatohepatitis (NASH) evaluated by a non-invasive scores in a cohort of patients affected by BPH/LUTS. Between January 2012 and January 2016, we conducted a prospective study in a single academic outpatient clinic on 132 consecutive patients who underwent surgery for lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO). A non-invasive non-alcoholic steatohepatitis score (NASH score) was calculated, and PI was evaluated through the Irani score. Patients with a NASH score > 1.05 had an average larger prostate volume (55 vs. 45 cc, p < 0.05), a greater waist circumference (103 vs. 93.5 cm, p < 0.01), and high values of blood glucose, triglycerides, insulin, and BMI compared to patients without NASH; 36% of patients with an Irani score ≥ 4 had NASH compared to 16.1% of patients who had a NASH score < 1.05 (p < 0.05). We found that non-alcoholic steatohepatitis (NASH ≥ 1.05) was an independent risk factor for Irani score ≥4 (OR: 3.24; p < 0.05) and of prostate volume ≥ 40 cc (OR: 13.99; p < 0.01). LUTS/BPH and NASH can be closely related, underlying common triggers of induction. In particular, inflammation seems to be associated with both conditions and with prostate gland overgrowth. Early identification of this class of patients could play a key role in preventing complications related to disease progression.

Since varicocele is often associated with other venous abnormalities, this study was undertaken to evaluate the frequency of dilation of the periprostatic venous plexus (DPVP) in these patients and the effects of this association on sperm parameters before and after varicocelectomy. Sperm parameters were evaluated using the conventional WHO criteria, and seminal fluid viscosity was further evaluated by quantitative viscometry, in 50 patients (aged 20–38 years) who underwent surgical treatment for grade III bilateral varicocele. Thirty patients with varicocele had also DPVP (DPVP+) (60 %). Sperm concentration and the percentage of spermatozoa with normal morphology did not differ significantly in patients with DPVP− or DPVP+ before or after surgical repair. On the other hand, sperm progressive motility was low in all patients and increased significantly after varicocele repair, but only in DPVP− patients. Before varicocele treatment, a significantly higher number of DPVP+ patients (25/30 = 83.3 %) had seminal fluid hyperviscosity compared to DPVP− patient (2/20 = 10.0 %). Viscosity quantitative measurement was significantly higher in DPVP+ patients both before and after varicocele repair compared to DPVP− patients. These latter showed a statistically significant reduction of sperm viscosity after varicocele surgical repair compared to pretreatment values. Finally, periprostatic venous plexus diameter and seminal fluid viscosity correlated directly in DPVP+ patients. In conclusion, these results showed that a large number of patients with varicocele had a concomitant DPVP. This subset of patients did not take advantage from varicocele surgical repair since only DPVP− varicocele patients showed a significant improvement of sperm progressive motility and seminal fluid viscosity. These findings suggest the evaluation of the periprostatic venous plexus and seminal fluid viscosity before patients with varicocele undergo surgical repair for asthenozoospemia.

To address the severity of erectile dysfunction (ED) in consecutive sexually active men seeking a prostate health screening through a multivariable risk stratification including comorbidities and lower urinary tract symptoms (LUTS). Four hundred and twenty five consecutive subjects with stable sexual relationship with normal testosterone levels were enrolled. The International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) questionnaires were collected and health-significant comorbidities were scored with the Charlson comorbidity index (CCI). All the independent predictors of ED were combined to form four different risk categories of ED: low (age⩽65 years and IPSS8 and CCI=0), intermediate (one of the following: age65 years, IPSS⩾8 or CCI⩾1), high (two of the following: age65 years, IPSS⩾8 or CCI⩾1) and very high (age65 years, IPSS⩾8 and CCI⩾1). The prevalence of ED increased with increase of CCI (χ(2) likelihood ratio: 40.85, P=0.001). The median of the IIEF-5 significantly reduced with the increase of the CCI (P0.001) and with the worsening of our risk group stratification (P0.001). At univariate logistic regression analysis very high risk was significantly associated with of ED (odds ratio: 26.85, P0.001). Very high-risk group predicted ED with 88% and 56% of specificity and sensitivity, respectively. Combining these risk factors through our risk stratification may be usefulness in revealing an underling ED.

Summary Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.

We recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans. In animals, IGF1/IGF1R has been found to be involved in testicular development during embryogenesis, in Sertoli cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation. Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular volume. The molecular pathways responsible for testicular differentiation and IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF system may be involved in FSH signaling also in humans. We suggest a possible molecular pathway occurring in human SCs, which involves both IGF1 and FSH through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH-induced effects may open new ways for a targeted therapy in idiopathic non-FSH-responder oligoasthenoteratozoospermia.

The occurrence of a genetic background in the etiology of polycystic ovarian syndrome (PCOS) represents the rational basis to postulate the existence of a male PCOS equivalent. Hormonal and metabolic abnormalities have been described in male relatives of women with PCOS. These males also have a higher prevalence of early onset (

The functional role of the FSHR promoter −29G/A polymorphism (rs1394205) in men is not clear. Some studies failed to find a relationship between the FSHR −29G/A and follicle-stimulating hormone (FSH) levels and did not associate the SNP with male infertility. Only one study showed that the FSHR −29 SNP modulates serum FSH levels in Baltic young male cohort. Because the SNP −29G/A has to be shown to have a strong effect on in vitro transcription activity of the FSHR promoter and the activation of FSHR is necessary for a normal FSH function, this study was undertaken to assess whether the FSHR -29G/A SNP modulates the gonadal endocrine function in men. A total of 200 men with alteration of conventional sperm parameters or normozoospermia (according to the parameters WHO 2010), were genotyped by TaqMan Assay. Hormone levels were measured by immunoassay, and sperm analysis was performed according to the World Health Organization criteria. A significant gradient of increasing FSH levels across the FSHR −29G/A genotypes was observed (p

The FSHB gene -211G/T polymorphism has been reported to modulate gene expression and to cause inter-individual differences in FSH serum levels in men. This study was undertaken to assess the functional relevance of this polymorphism on gonadotropin and total testosterone serum levels and sperm parameters in men from Eastern Sicily (Italy). To accomplish this, 200 men with abnormal conventional sperm parameters or normozoospermia (according to the parameters of WHO 2010) were genotyped by TaqMan Assay. The frequency of FSHB -211 T allele was significantly higher (p

Summary Recently, it has been reported that treatment with testosterone (T) could have favourable effects on prostate inflammation; however, the data appear inconsistent. The main evidences concern experimental studies, and there is lower information obtainable from clinical studies. This study was conducted on patients with diagnosis of male accessory gland infection (MAGI) and a concomitant hormonal condition of acquired hypergonadotropic hypogonadism and has evaluated the effects on sperm parameters of the administration of a transdermal formulation of T gel for 3 months. The treated patients showed a significantly increased percentage of spermatozoa with normal form and progressive motility (p

Prostatitis is a very common urogenital disease of the male with prevalence ranging from 2.2 to 9.7% worldwide. Interestingly, some recent evidences have showed a significant association between chronic prostatitis (CP) and male infertility including a detrimental effect on sperm parameters, reduction of zinc concentration on semen sperm and production of anti-semen antibodies (ASAs). The aim of the current meta-analysis was to evaluate the association between CP and alteration of semen parameters. This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and we included in the final analysis 27 studies, with a total of 3241 participants, including 381 (11.75%) with chronic bacterial prostatitis (CBP), 1670 (51.53%) with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and 1190 (36.72%) controls. CBP was associated with reduction of sperm concentration, sperm vitality, sperm total and progressive motility, while CP/CPPS was related to the reduction of semen volume, sperm concentration, sperm progressive motility and sperm normal morphology. We found that CP was significantly associated with reduced zinc concentration on seminal plasma (SMD: −20.73; p = 0.005). Finally, CP statistically increased the risk of developing ASA on seminal plasma (OR 3.26; p

The aim of this study was to evaluate the impact of risk factors of erectile dysfunction (ED) after transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms caused by bladder outlet obstruction secondary to benign prostatic hyperplasia. The study was conducted prospectively on 178 consecutive patients (normal IIEF-5 before surgery, ≥ 22) who underwent TURP. Patients were assessed before surgery and at 12 months. At 12 months, the IIEF-5 score significantly decreased from24 to 18 (p

Summary This review explores the role of carnitine in male infertility. The structure of this review is organized into short paragraphs that address the following aspects: antiapoptotic effect of l-carnitine on germ cells, effects of l-carnitine on conventional sperm parameters, in vitro effects of l-carnitine on sperm function, and the role of l-carnitine on erectile function.

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disease among aging men. Androgens play a key role in the development and growth of the male genital tract favoring differentiation and proliferation of stromal and epithelial cells of the prostate gland. It is known that growth factors play a crucial role in the cross-talk between stromal cells and epithelial cells. These factors, mainly secreted by stromal cells, act in an autocrine/paracrine manner to maintain prostate cellular homeostasis. A number of experimental studies support the interdependence between growth factors (IGF, FGF, TGF) and the steroid hormone milieu of the prostate. Alterations of these interactions may alter the balance between proliferation and cell death leading to the development of BPH. The onset of BPH is closely related to an inflammatory microenvironment. Chronic inflammation, which generally follows the acute inflammation because of infectious agents, is favored by hormonal or metabolic abnormalities. However, a close correlation between these mechanisms and metabolic or sexual hormones (androgen/estrogen ratio) alteration has been shown suggesting a key role of hypogonadism in the development of prostate inflammation. This review clear shows that the BPH pathogenesis and the subsequent onset of the lower urinary tract symptoms (LUTS) depends from different etio-pathogenetic factors whose mechanism of action remains to be evaluated.

The study was aimed at evaluating a new diagnostic interview, arbitrarily named Structured Interview about male accessory gland infections (SI-MAGI), administered to three different groups of patients with MAGI according to ultrasound evaluation [prostatitis (P) or prostato-vesciculitis (PV) or prostato-vesciculo-epididymitis (PVE)]. We evaluated 110 consecutively selected infertile patients, with diagnosis of MAGI and underwent to transrectal and scrotal ultrasound (US) examination. After ultrasound evaluation, they were divided into three well-characterised, aged-matched groups: prostatitis (P; n = 45), prostato-vesciculitis (PV; n = 30) and prostato-vesciculo-epididymitis (PVE; n = 35). Then, all patients were submitted to active clinical history oriented by SI-MAGI questionnaire elucidated by the operator. The SI-MAGI was structured in four domains (urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction and quality-of-life impact) for a total of 30 questions with four possible answers. Infertile patients of PVE and PV groups showed scores significantly higher than P group in all domains (anovaP < 0.005). PVE showed scores significantly higher than PV group in domain 2 and 3. Our study demonstrates the MAGI's symptoms worsen with major extension of inflammation and ultrasound can evaluate the true extent of MAGI and symptoms can help to suggest the severity of MAGI.

Introduction: Male accessory gland infection (MAGI) exerts a negative influence on male fertility which depends upon its extension. Indeed, we have shown that patients with MAGI involving prostate, seminal vesicles and epididymis have worse sperm parameters compared with patients with prostatitis alone or prostate-vesiculitis. Similarly, MAGI extending bilaterally is associated with a worse sperm output. The aims of this study were to evaluate the prevalence of two different additional ultrasound (US) findings (hypertrophic-congestive and a fibro-sclerotic US form) and to evaluate their semen quality. Materials and methods: One hundred infertile patients with MAGI, diagnosed according to the World Health Organization (WHO) 1993 criteria, were evaluated by scrotal and transrectal ultrasound scans. The control group consisted of 100 healthy, age-matched men. Results: The ultrasound examination confirms two separate US variants of MAGI: a hypertrophic-congestive (prevalence of 56%) and a fibro-sclerotic form (prevalence of 29%). Patients with hypertrophic-congestive MAGI showed higher sperm concentration, motility and normal forms, but also higher sperm leukocytes concentration and seminal reactive oxygen species compared to patients with fibro-sclerotic MAGI. However, all these parameters were significantly worse than those observed in the control group. Discussion: Infertile patients with hypertrophic-congestive MAGI have a better sperm quality compared with patients with fibrosclerotic MAGI; however, they showed higher oxidative stress in semen.

Recently, we reported an increased prevalence of chronic bacterial prostatitis (CBP) in patients with prostatitis syndromes (PS) and irritable bowel syndrome (IBS) compared with patients with PS alone. The aim of this study was to evaluate the frequency of male accessory gland infections (MAGI) in patients with CBP plus IBS and to compare the sperm parameters of patients with or without MAGI. Fifty consecutive patients with the following criteria were enrolled: (i) infertility; (ii) diagnosis of CBP; and (iii) diagnosis of IBS according to the Rome III criteria. The following two aged-matched control groups were also studied: infertile patients with CBP alone (n = 56) and fertile men (n = 30) who fathered a child within the previous 3 months. Patients and controls underwent to an accurate anamnesis, administration of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and the Rome III questionnaires for prostatitis and IBS, respectively, physical examination, and semen analysis. A significantly higher frequency of MAGI was found in patients with CBP plus IBS (82.0%) compared with the patients with CBP alone (53.6%) or the fertile men (0%). The presence of MAGI in the patients with CBP plus IBS was associated with a significantly lower sperm concentration, total number, and forward motility, and with a higher seminal leucocyte concentration compared with the patients with CBP alone and MAGI. Sperm normal morphology was similar in the groups of patients. All sperm parameters did not differ significantly in both the groups of patients without MAGI. The patients with CBP plus IBS had a significantly higher frequency of MAGI compared with the patients with CBP alone. This was associated with worse sperm parameters and, hence, poorer reproductive prognosis. We suggest to search for the presence of IBS in the patients with PS and in particular when CBP and/or worse sperm parameters are present.

Summary MAGI is the inflammation of the accessory male glands that notoriously exerts a negative influence on male fertility. The diagnosis is integrated by clinical, laboratory and ultrasound evaluation. In particular, the ultrasound criteria were published in 1999. The aim of this study was to analyse the sensitivity and specificity of additional diagnostic ultrasound criteria as well as of conventional criteria in a selected category of infertile patients with MAGI. To accomplish this, 100 patients with MAGI were evaluated by scrotal and transrectal ultrasound by three different operators. The control group consisted of 100 age-matched healthy men. Statistical analysis was performed to evaluate sensitivity, specificity, positive and negative predictive values, and ROC curve analysis. The results showed that additional ultrasound criteria had a diagnostic accuracy similar to traditional criteria. The threshold value of two criteria for each diagnostic category (traditional and additional criteria) obtained high values of sensitivity and specificity. In conclusion, this study confirms the validity of the ultrasound criteria of MAGI previously published; in addition, it suggests the clinical utility of other indicators in clinical practice with good diagnostic accuracy and finally it establishes a clear threshold ultrasonographic value for the diagnosis of MAGI.

Summary The aim of this study was to evaluate the level of malondialdehyde (MDA) (one of the final products of lipid peroxidation and well-known marker of oxidative stress) in semen of infertile men with type 2 diabetes and to investigate its relationship with their glycaemic control. Forty infertile men with type 2 diabetes were evaluated. The mean ages were 36.5 ± 8.0. Men with diabetes were divided into two groups. Group A (n = 20) with glycated haemoglobin >10% and group B (n = 20) with glycated haemoglobin

The aim of this study was to evaluate whether the viscosity of semen in patients with male accessory gland infection is related to the extension of the inflammatory process to the various glands. To achieve this, viscosity was assessed by quantitative viscosimeter and the results were expressed in centipoise (cps). The study was conducted on 30 infertile patients with clinical evidence of male accessory gland infection and a mean age of 29.0 ± 4.0 years. Their semen viscosity was evaluated through quantitative viscometer. All patients showed an increase of viscosity evaluated according to WHO criteria, while this parameter was normal in all controls. Semen viscosity of patients with male accessory gland infection (28.6 ± 2.2 cps) was significantly (P < 0.05) higher than that in the controls (10.7 ± 0.6 cps). Significantly increasing values were observed in patients with involvement of multiple gland inflammation (prostatitis

Summary The aim of this study was to administer to two groups of patients with male accessory gland infection (MAGI), respectively, with positive or negative alterations in ultrasonography, a new diagnostic interview, arbitrarily named structured interview about MAGI (SI-MAGI), to evaluate differences between these groups, especially about the prevalence of sexual dysfunction. After ultrasound examinations, patients with MAGI were divided into two age-matched groups: positive and negative for ultrasound signs (US+ and US−). The SI-MAGI was structured into four domains (urinary tract symptoms, ejaculatory pain or discomfort, sexual dysfunction and quality-of-life impact) for a total of 30 questions with four possible answers. Infertile patients of MAGI US+ group showed scores significantly higher than MAGI US− and healthy control group in all domains (anovaP

Summary The aim of this retrospective study was to determine the prevalence of testicular microlithiasis (TM) in central-eastern Sicilian men and to evaluate the association between TM and testicular tumour or infertility. A total of 1056 Sicilian patients underwent scrotal US between 2005 and 2010. TM was found in 106 men with an overall prevalence of 10%; roughly about four times the median prevalence reported in the previous studies (0.6–18.1%). Forty men (3.8%) had a classic TM, whereas 66 (6.2%) had a limited TM. The prevalence of testicular tumour in this cohort was 2.4% (25/1056). At the moment when the testicular tumour was diagnosed, 15 patients (60%) had TM. There was a significant difference (P

Summary Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males (Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate-vesiculitis and prostate-vesiculo-epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non-conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub-obstruction of the seminal tract.

Although it is well known that phosphodiesterase V inhibitors, used to treat patients with ED, can improve the endothelial dysfunction in organic vascular forms, few studies have explored the duration of their effect on the endothelium after discontinuation. Therefore, the purpose of this study was to evaluate the serum concentrations of apoptotic endothelial microparticles (EMPa), selected as a marker of endothelial damage, in patients with arterial ED at baseline, during tadalafil administration and 3 and 6 months after its discontinuation. In all, 50 patients with arterial ED were evaluated at baseline and 1 week after administration of tadalafil 5 mg once daily for 90 days. Clinical (International Index of Erectile Function-5 score), instrumental (dynamic penile echo color Doppler) and flow-cytometric (serum EMPa concentrations) analyses were performed before (T0) and 1 week (T1), 3 months (T2) and 6 months (T3) after tadalafil discontinuation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined as EMPa. At T0, patients with arterial ED had serum EMPa concentration significantly higher than 20 healthy men (controls). At T1, patients with arterial ED showed a serum EMPa concentration significantly lower than T0. The significant difference was maintained, though reduced, at T2 and completely lost at T3. In conclusion, the administration of tadalafil decreased serum EMPa concentration in patients with arterial ED. This positive effect on the endothelial dysfunction disappeared 6 months after tadalafil discontinuation.

Phosholipase A2 (PLA2 ) activity in the seminal plasma and in sperm heads is closely related to sperm motility and male fertility. Therefore, the purpose of this study was to investigate the possible involvement of different isoforms of phospholipase in asthenozoospermia. To accomplish this, cPLA2 , phospho-cPLA2 , iPLA2 , and sPLA2 were evaluated by immunofluorescence and immunoblot analyses in spermatozoa obtained from 22 normozoospermic men and 28 asthenozoospermic patients. We found significant differences in cPLA2 and its phosphorylated/activated form, iPLA2 , and sPLA2 content and distribution in normal and asthenozoospermic patients. cPLA2 was localized in heads, midpieces, and tails of all spermatozoa as constitutive enzyme, less expressed in the tail of spermatozoa with low progressive motility. While active phospho-cPLA2 distribution was homogeneous throughout the cell body of control-donor spermatozoa, lower levels were detected in the tails of asthenozoospermic patients, as opposed to its strong presence in heads. Low immunofluorescence signal for iPLA2 was found in astenozoospermic patients, whereas sPLA2 was significantly lower in the heads of asthenozoospermic patients. Spermatozoa with low progressive motility showed differences both in terms of total specific activity and of intracellular distribution. cPLA2 , iPLA2 , and sPLA2 specific activities correlated positively and in a significantly manner with sperm progressive motility both in normozoospermic men and asthenozoospermic patients. In conclusion, PLA2 s are expressed in different areas of human spermatozoa. Spermatozoa with low motility showed differences in total specific activity and enzyme distributions. We speculated that PLA2 expression and/or different distribution could be potential biomarkers of asthenozoospermia, one of the major causes of male factor infertility.

This study was undertaken to evaluate conventional and some of the main bio-functional spermatozoa parameters, serum gonadal hormones and didymo-epididymal ultrasound features in patients with type 1 diabetes mellitus (DM1). DM1 affects an increasing number of men of reproductive age. Diabetes may affect male reproduction by acting on the hypothalamic-pituitary-testicular axis, causing sexual dysfunction or disrupting male accessory gland function. However, data on spermatozoa parameters and other aspects of the reproductive function in these patients are scanty. Thirty-two patients with DM1 [27.0 (25.0-30.0 years)] and 20 age-matched fertile healthy men [28.0 (27.25-30.75 years)] were enrolled. Patients with diabetic neuropathy, other endocrine disorders or conditions known to alter spermatozoa parameters were excluded. Each subject underwent semen analysis, blood withdrawal for fasting and post-prandial glycaemia, hormonal analysis and didymo-epididymal ultrasound evaluation before and after ejaculation. Patients with DM1 had a lower percentage of spermatozoa with progressive motility [10.0 (7.0-12.75) vs. 45.0 (42.0-47.75) %; p < 0.01] and a higher percentage of spermatozoa with abnormal mitochondrial function than controls [47.0 (43.0-55.0) vs. 2.0 (1.0-5.0) %; p < 0.01]. Patients also had greater post-ejaculatory diameters of cephalic [11.5 (10.2-13.6) vs. 6.0 (4.0-7.0) mm; p < 0.01] and caudal epididymis [5.5 (4.00-7.55) vs. 3.0 (2.0-4.0) mm; p < 0.01] compared to controls, suggesting a lack of the physiological post-ejaculation epididymal shrinkage. Correlation analysis suggested that progressive motility was associated with fasting glucose (r = -0.68; p < 0.01). The other parameters did not show any significant difference. Patients with DM1 had a lower percentage of spermatozoa with progressive motility, impaired mitochondrial function and epididymal post-ejaculatory dysfunction. These findings may explain why patients with DM1 experience fertility disturbance. Larger multi-centric studies are necessary to confirm these results.

The present article describes the recent clinical experience and the main clinical and experimental evidences on this topic. In the first part, we present retrospective data collected over the last year on the semen quality and hormonal characteristics of the alcohol consumers evaluated in our centre. In the second part, we describe the mechanisms by which chronic alcohol intoxication impairs the testicular function (evidences for an ethanol-mediated effect at pre-testicular/testicular and post-testicular level). In the third part, we present data on ethanol taken a male risk factor of infertility, being present as one among other recreational drugs (also called lifestyle). Finally, is discussed the role of individual susceptibility factors and other variables.

The aim of this study was to evaluate the concentrations of CD45pos leukocytes in the semen samples of infertile patients with low testicular volume (TV) compared to subjects with normal TV. The testis was considered normal in size when it had a volume between 15 and 25 cm3, low–normal with a volume between 10 and 12 cm3 and hypotrophic when the volume was 3. The patients with low testicular volume (3) showed significantly higher concentrations of CD45pos leukocytes compared to other groups ( P 3) have significantly increased CD45pos leukocyte concentrations associated with increased percentages of immature germ elements, spermatozoa with signs of early apoptosis and spermatozoa with abnormal morphology.

The frequency of human papillomavirus (HPV) infection in the semen of patients with male accessory gland infection (MAGI) was evaluated. One hundred infertile patients with MAGI were classified into group A: patients with an inflammatory MAGI (n = 48) and group B: patients with a microbial form (n = 52). Healthy age-matched fertile men (34.0 ± 4.0 years) made up the control group (n = 20). Amplification of HPV DNA was carried out by HPV-HS Bio nested polymerase chain reaction for the detection of HPV DNA sequences within the L1 ORF. Ten patients in group A (20.8%) and 15 patients in group B (28.8%) had a HPV infection; two controls (10.0%) had HPV infection. Patients with MAGI had a significantly higher frequency of HPV infection compared with controls; patients with a microbial MAGI had significantly higher frequency of HPV infection compared with patients with an inflammatory form (both P < 0.05). Patients with MAGI and HPV had a slight, but significantly lower sperm progressive motility and normal morphology compared with patients with MAGI HPV-negative (P < 0.05). Elevated frequency of HPV infection occurred in patients with MAGI, suggesting that HPV should be investigated in the diagnostic work-up of these patients.

Aim of the present study was to evaluate the different ultrasound characterization of fertile symptomatic patients with MAGI (male accessory gland infection) according to different serum concentrations of total T (TT). We analyzed the ultrasound and hormonal data of 200 patients aged between 24.0 and 67.0 years. Patients were divided into six groups according to the sextile distribution of TT. Patients with serum concentrations of TT < 3.6 ng mL−1had a higher mean duration of symptoms compared to the other examined groups. Patients with serum concentrations of TT > 6.6 ng mL−1showed a frequency of ultrasound criteria suggestive for bilateral form of prostatitis and prostate-vesiculo-epididymitis and significantly lower compared to the other examined groups. At multivariate logistic regression analysis adjusted for age and BMI, TT was an independent predictive factor of prostatovesiculitis (OR = 0.818 [95% CI: 0.675–0.992];P<0.01) and prostate-vesiculo-epididymitis (OR = 0.714 [95% CI: 0.578–0.880];P<0.01), which represent the main forms of complicated MAGI. The results of this study suggest that male hypogonadism could be associated with a different ultrasound characterization of these patients.

Summary Arterial erectile dysfunction (ED) is commonly associated with classic cardiovascular and metabolic risk factors, such as smoking, hypertension, diabetes mellitus, dyslipidaemia and obesity. However, some patients with arterial ED do not present any cardiovascular risk factor. As mean platelet volume (MPV) has been shown to be directly related to the cardiovascular risk and the percentage of platelets expressing the vitronectin receptor (αVβ3), involved in the early stages of platelet adhesion, is higher in patients with ED, the present study was undertaken to evaluate MPV and αVβ3 in 15 patients with arterial ED not associated with any cardiovascular risk factor. Their MPV and αVβ3 values were compared with those of men with normal penile haemodynamic. Patients with arterial ED had a mean value of MPV (11.25 vs. 9.88 fL; p

Summary We have previously reported that infertile patients with diabetes mellitus (DM) have a particular ultrasound features of the seminal vesicles (SV) characterized by higher fundus-to-body ratio and lower pre- and post-ejaculatory difference in body antero-posterior diameter (APD). Based on these premises the aim of the present study was to investigate possible ultrasound SV changes in infertile patients with DM and diabetic neuropathy (DN), after prolonged administration of tadalafil (TAD) (a specific phosphodiesterase-5 inhibitor). To accomplish this, 20 infertile patients with symptomatic DN and erectile dysfunction were selected and arbitrarily divided into two groups which were assigned to: daily administration of 5 mg TAD for 3 months (Group A) (n = 10) and administration of placebo (Group B) (n = 10). All patients underwent to scrotal and prostate-vesicular transrectal ultrasound evaluation and semen analysis (Laboratory Manual for the Examination and Processing of Human Semen, WHO, 2010) before and after treatment. The following SV US parameters were recorded: (i) body APD; (ii) fundus APD; (iii) parietal thickness of the right and left SVs; and (iv) number of polycyclic areas within both SVs. We then calculated the following parameters: (i) fundus/body (F/B) ratio; (ii) difference of the parietal thickness between the right and the left SV and (iii) pre- and post-ejaculatory APD difference. In addition, we also evaluated the SV ejection fraction. Group A patients showed a significant reduction in F/B ratio and higher pre- and post-ejaculatory body SV APD difference compared with baseline or Group B after 3 months. These patients showed also a significant increase in SV ejection fraction and a significant improvement of the total sperm count, progressive motility, seminal levels of fructose, leucocytes and ejaculate volume. In conclusion, these results suggest that infertile DM patients with DN and erectile dysfunction had an improvement of ultrasound features suggestive of diabetic neuropathy after daily treatment with low doses of TAD.