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 ~ 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 Infertility affects 7%‐12% of men, and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract color‐Doppler ultrasound (MGT‐CDUS) has progressively expanded. However, MGT‐CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study (“EAA ultrasound study”) to assess MGT‐CDUS characteristics of healthy, fertile men to obtain normative parameters. Objectives To report (a) the development and methodology of the “EAA ultrasound study,” (b) the clinical characteristics of the cohort of healthy, fertile men, and (c) the correlations of both fertility history and seminal features with clinical parameters. Methods A cohort of 248 healthy, fertile men (35.3 ± 5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, and seminal evaluation and MGT‐CDUS before and after ejaculation. Results The clinical, seminal, and biochemical characteristics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50th and 5th centiles for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy (TTP) was 3.0[1.0‐6.0] months. TTP was negatively correlated with sperm vitality (Adj.r =−.310, P = .011), but not with other seminal, clinical, or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r = .244, P < .05 and Adj.r = .232, P = .002). Sperm concentration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4 ± 4.0 mL, and the lower reference values for right and left testes were 15.0 and 14.0 mL. Mean TV was negatively associated with gonadotropin levels and pulse pressure. Varicocoele was found in 33% of men. Conclusions The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT‐CDUS normative parameters.

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Background Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy‐fertile men (HFM) to establish normative parameters. Objectives To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters. Methods 188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures. Results TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior‐posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed. Conclusions The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings.

Even though inflammatory conditions are known to exert adverse effects on bone metabolism, there are no published data regarding SARS-CoV-2 infection and subsequent fracture risk. We present a brief review of the molecular mechanisms linking inflammatory diseases to increased fracture risk/osteoporosis and of the therapeutic strategies that can prevent bone resorption in patients with inflammatory disease, focusing on the RANK-RANKL system. We also make some considerations on gender differences in infection response and on their implications for survival and for the consequences of COVID-19. Several inflammatory cytokines, especially IL-1, IL-6, and TNF-α, stimulate osteoclast activity, favoring bone resorption through the RANK-RANKL system. Data from the previous SARS-CoV outbreak suggest that the present disease also has the potential to act directly on bone resorption units, although confirmation is clearly needed. Even though the available data are limited, the RANK-RANKL system may provide the best therapeutic target to prevent bone resorption after COVID-19 disease. Vitamin D supplementation in case of deficiency could definitely be beneficial for bone metabolism, as well as for the immune system. Supplementation of vitamin D in case of deficiency could be further advantageous. In COVID-19 patients, it would be useful to measure the bone metabolism markers and vitamin D. Targeting the RANK-RANKL system should be a priority, and denosumab could represent a safe and effective choice. In the near future, every effort should be made to investigate the fracture risk after SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus infectious disease (COVID-19) and has rapidly spread worldwide, causing serious problems to the healthcare systems of many countries and hundreds of thousand deaths. In this review we discuss data from the literature to understand whether the various districts of the male reproductive system may represent another vulnerable target for SARS-CoV-2. Studies were searched from electronic databases such as Google Scholar, PubMed, Scopus, and COVID-19 specific databases such as LitCovid, until July 31, 2021. It appears that SARS-CoV-2 virus infection not only causes damage to the respiratory system, but could have a serious impact on the reproductive system of male patients modulating many physiological processes. Like some other infections, SARS-CoV-2 also leads to a worsening of semen quality and an increase in oxidative stress (OS) levels. However, due to the limited number of studies, it is unclear whether this deterioration in semen parameters is temporary or lasts over time. It is certainly important that patients' reproductive function is monitored after coronavirus infection to avoid problems in reproductive health in the future.

Objective: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on COVID-19-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact. Study design and methods: 117 patients (81 males, 64±13 years) hospitalized for COVID-19 between 1st March and 30th April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurements, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death. Results: At admission, 26.5% patients had hyponatremia, 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders (“mixed dysnatremia”). Lower sodium levels at admission were correlated with higher CRP (p=0.039) and serum lactate levels (p= 0.019), but not IL-6. Hypernatremia and a wider sodium variability were associated to maximum required ventilation, need of ICU assistance and duration of the hospitalization. Mean estimated time to ICU admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (Log-Rank test p=0.032). Conclusions: Sodium alterations frequently affect hospitalized COVID-19 patients. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients’ prognosis.

Background:The management of male idiopathic infertility is heterogeneous.Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters.Aim: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment. Methods:A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner. Results:A total of 718 infertile couples were enrolled, and 241 patients were reevaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001).Discussion: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events. K E Y W O R D Sfollicle-stimulating hormone, FSH, male idiopathic infertility, open registry