Does alcohol have any effect on male reproductive Function？ A review of literature

Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.

Chronic bacterial prostatitis and irritable bowel syndrome： effectiveness of treatment with rifaximin followed by the probiotic VSL#3

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis （PV） or prostate-vesiculo-epididymitis （PVE）. A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis （CBP） and irritable bowel syndrome （IBS） were randomly prescribed rifaximin （200 mg, 2 tablets bid, for 7 days monthly for 12 months） and probiotic containing multiple strains VSL#3 （450 × 10^9 CFU per day） or no treatment. Ninety-five of them （89.6%） complied with the therapeutic plan and were included in this study. Group A = ＂6Tx/6-＂： treatment for the initial 6 and no treatment for the following 6 months （n = 26）; Group B = ＂12Tx＂： 12 months of treatment （n = 22）; Group C = ＂6-/6Tx＂： no treatment for the initial 6 months and treatment in the last 6 months （n = 23）; Group D = ＂12-＂： no treatment （n = 24）. The patients of Groups A = ＂6Tx/6-＂ and B = ＂12Tx＂ had the highest frequency of chronic prostatitis （88.5% and 86.4%, respectively）. In contrast, group ＂12-＂： patients had the lowest frequency of prostatitis （33.4%）. The progression of prostatitis into PV in groups ＂6Tx/6-＂ （15.5%） and ＂6-/6Tx＂ （13.6%） was lower than that found in the patients of group ＂12-＂ （45.8%）. Finally, no patient of groups ＂6Tx/6-＂ and ＂6-/6Tx＂ had PVE, whereas it was diagnosed in 20.8% of group ＂12-＂ patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

Persistence of ultrasound alterations after antibiotic treatment with levofloxacin in patients with male accessory gland infection

No studies have evaluated the ultrasound features of the male sex accessory glands in infertile patients with bacterial male accessory gland infection （MAGI） according to the microbiological outcomes of bacterial cultures （absent, partial or complete） following antibiotic therapy administration. Therefore, the aim of this study was to evaluate the ultrasound characteristics of the prostate, seminal vesicles, and epididymal tracts after treatment with levofloxacin （a common quinolone antibiotic）, in patients with infections caused by Escherichia coil （a Gram-negative bacterium） according to the Naber＇s classification, which includes the following categories： eradication, eradication with superinfection, persistence and persistence with superinfection. The study was conducted in 100 patients aged 25±8 years （range： 20-40 years） with bacterial MAGI and bacterial cultures positive only for E. coil（colony forming units ≥ 106 per ml）. Retrospective analysis was conducted only on patients treated with oral levofloxacin （500 mg） administered once daily for 28 days who were recruited over the last 5 years. Following antibiotic treatment, patients with microbiological persistence or persistence with superinfection had a significantly higher percentage of ultrasound abnormalities suggestive of prostato-vesiculitis （PV） （30.2% and 36.0%, respectively） or prostato-vesiculo-epididymitis （PVE） （60.2% and 70.0%, respectively） compared with patients with microbiological eradication （PV= 10.2% and PVE=8.2%, respectively） or eradication with superinfection （PV= 18.8% and PVE=21.2%, respectively）. In conclusion, patients with microbiological persistence or persistence plus superinfection showed the highest prevalence of complicated forms of MAGI （PV and PVE）, compared with patients with microbiological eradication or eradication with superinfection.

Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome model.Population:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for eligibility.Twenty-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,respectively.Based on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was observed.The risk for DVT remains uncertain,due to the paucity of RCT-based data.TRT in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular events.Further studies specifically assessing the risk of DVT in men on TRT are needed.

Predictive parameters of the efficacy of varicocele repair: a review

Varicocele has a prevalence of 15%in the population and represents a primary cause of infertility in 40%of cases and a secondary cause in approximately 80%of cases.It is considered the major correctable cause of male infertility.Despite its high prevalence in the infertile population,a large number of patients with varicocele do not experience reproductive difficulties.For this reason,it is still highly debated which parameters could be used to predict which patients with varicocele will be most likely to benefit from its repair.The main international and European guidelines state that treatment should only be considered in infertile patients with abnormal sperm quality.However,these guidelines do not help physicians to identify which of these patients may benefit from the treatment.Therefore,this narrative review collects the evidence in the literature on the usefulness of some factors as predictors of improvement,highlighting how some of them may be effective in an initial selection of patients to be treated,while others are promising but further studies are needed.Finally,a brief consideration on the possible role of artificial intelligence is proposed.

Acquired premature ejaculation and male accessory gland infection： relevance of ultrasound examination

We have previously demonstrated a high frequency of premature ejaculation （PE） among patients with male accessory gland infection （MAGI）. The aim of this study was to evaluate the ultrasound （US） features of patients with MAGI and acquired premature ejaculation （APE） associated （MAGI-APEpos）. US evaluation of 50 MAGI-APEpos patients compared to 50 patients with MAGI without PE （MAGI-PEneg） which represent the control group. The diagnosis of APE was made through the evaluation of Intravaginal ejaculation latency time （IELT） and confirmed with the questionnaire PEDT （Premature Ejaculation Diagnostic Tool）. The main outcome measure was represented by the frequency of US criteria suggestive of P （prostatitis）, V （vesiculitis）, and E （epididymitis） in MAGI-APEpos and MAGI-PEneg patients. MAGI-APEpos patients showed a total number of US criteria significantly higher compared to MAGI-PEneg patients. MAGI-APEpos showed a higher frequency of US criteria of V and E （complicated forms of MAGI）. Finally, in MAGI-APEpos group, it was found a positive relationship between the anteroposterior diameter （APD） of the caudal tract of the epididymis and the APD of the seminal vesicles, as well as between both diameters and the PEDT score. MAGI-APEpos patients have a peculiar US characterization compared to MAGI-PEneg patients. According to these results, US evaluation of the epididymal and of the prostato vesicular tract should be considered in the practical clinical approach of patients with MAGI and APE. In particular, it could be a SUDDort for a possible Dathoahysiological interpretation of this clinical problem in these patients.

Next-generation sequencing:toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure

A large proportion of patients with idiopathic spermatogenic failure(SPGF;oligozoospermia or nonobstructive azoospermia[NOA])do not receive a diagnosis despite an extensive diagnostic workup.Recent evidence has shown that the etiology remains undefined in up to 75%of these patients.A number of genes involved in germ-cell proliferation,spermatocyte meiotic divisions,and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA.However,this evidence mainly comes from case reports.Therefore,this study was undertaken to identify the molecular causes of SPGF.To accomplish this,15 genes(USP9Y,NR5A1,KLHL10,ZMYND15,PLK4,TEX15,TEX11,MEIOB,SOHLH1,HSF2,SYCP3,TAF4B,NANOS1,SYCE1,and RHOXF2)involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA,accurately selected after a thorough diagnostic workup.After next-generation sequencing(NGS)analysis,we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25(12.0%)patients.Seventeen other different variants were identified,and among them,13 have never been reported before.Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies.The genes most frequently mutated were MEIOB,followed by USP9Y,KLHL10,NR5A1,and SOHLH1.No alterations were found in the SYCP3,TAF4B,NANOS1,SYCE1,or RH0XF2 genes.In conclusion,NGS technology,by screening a specific custom-made panel of genes,could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA.

FSH dosage effect on conventional sperm parameters:a meta-analysis of randomized controlled studies

Follicle-stimulating hormone(FSH)represents a therapeutic option in normogonadotropic patients with idiopathic oligozoospermia.The aim of this review was to evaluate the possible dose-and drug-dependent efficacy of FSH treatment on conventional sperm parameters.We performed a comprehensive systematic review via a meta-analysis of all available randomized controlled trials,in which FSH administration was compared with placebo or no treatment when administered to normogonadotropic patients with idiopathic oligozoospermia.Of the 971 articles that were retrieved,5 were fin ally included,in eluding a total of 372 patie nts and 294 controls.Overall,FSH treatment was effective in ameliorating the sperm concentration,total count,progressive motility,but not normal forms.On the basis of the weekly dosage,the studies were classified into those using low(175-262.5 IU per week),intermediate(350-525 IU per week),and high(700-1050 IU per week)doses.At low doses,FSH improved only sperm motility.At intermediate doses,FSH ameliorated sperm concentration and morphology.Total sperm count and progressive motility showed a trend toward the increase.At high doses,FSH increased sperm concentration,total sperm count,and progressive motility.Sperm morphology showed a trend toward the increase.Finally,both highly purified FSH(hpFSH)and recombinant human FSH(rhFSH)improved sperm concentration,total sperm count,progressive motility,but not morphology.No different efficacy was observed between these two preparations.This meta-analysis provides evidence in favor of high FSH doses.The FSH efficacy was not related to the preparation type(recombinant vs highly purified).Further studies are needed to evaluate the effectiveness of Iong-standing treatment regimes.

SOX13 gene downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome

Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.