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Female sexual function relies on a complex interplay of physical, psychosocial, and neurobiological factors. Over the last decades, increasing attention has been paid to the influence of personality traits on general health and many aspects of quality of life, including sexuality.To assess whether dimensions of the personality are related to the domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) in symptomatic postmenopausal women. Mood was also investigated to explore its association with female sexual dysfunction (FSD).Validated questionnaires to assess sexual function [the Female Sexual Functioning Index (FSFI)], mood [the State-Anxiety Inventory (STAI), and Zung Self Rating Depression Scale (SDS)], and personality traits [the Tridimensional Personality Questionnaire (TPQ)] were filled in by 130 early postmenopausal women experiencing hot flushes (≥30/week).61.5 % (n = 80) of the women had an FSFI total score lower than 26.55, the standard cut-off for FSD. A clinical state of anxiety was present in 53.8 % (n = 70), whereas only 12.3 % (n = 16) showed clinically relevant depressive symptoms. According to the FSFI cut-off score, women with sexual disorders had statistically significantly higher levels of anxiety, depression (p 0.001 for both), and harm avoidance (HA) (p = 0.004) than women without such disorders. Significantly higher levels of anxiety were found in women in the lower quartile (LQ) of the distribution of the total FSFI score than in women in both the interquartile range (IQR) and in the upper quartile (UQ) (p 0.05). Moreover, women in the UQ had a lower grade of depression and HA than others (p 0.05). The Sobel test showed that the personality trait HA significantly mediated the relationship between anxiety and FSFI total score (Z = -2.19, p 0.05) and between depression and FSFI total score (Z = -2.35, p 0.05).The present data suggest the personality trait HA is relevant to sexual function and mediates the impact of mood on FSD in symptomatic menopausal women. In clinical practice, the use of validated psychometric tools for mood screening is useful to establish appropriate diagnosis and treatment of sexual disorders in menopausal women. Moreover, the assessment of personality traits could provide additional information that directs clinicians towards an increasingly tailored and multidimensional treatment of FSD.

Objective: To assess whether varicocele affects testicular 25-hydroxylase activity. Methods: Twenty normozoospermic patients with bilateral varicocele (grade III according to the Dubin and Amelar classification) without indications to undergo varicocele repair (normal sperm parameters and testicular volume; no scrotal pain) were consecutively enrolled and followed-up for four years. Serum levels of parathyroid hormone (PTH), calcium, and 25-hydroxy-cholecalciferol [25(OH)D] along with serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), conventional sperm parameters, sperm DNA fragmentation (SDF) rate, and testicular volume (TV) were measured annually for three years. PTH, calcium, and 25(OH)D serum levels over time were compared with those of age- and body mass index (BMI)-matched control group of twenty varicocelectomized patients. Main results: Both intra- and between-group analyses showed that serum PTH levels increased significantly over time in parallel with a significant decline in 25(OH)D levels. Serum calcium levels did not change significantly. At the same time, signs of mild Leydig and Sertoli cell dysfunction were found, such as an increase in gonadotropins and decreased TT and VT. However, conventional sperm parameters and SDF rate did not change significantly. Conclusion: This prospective controlled study provides the first evidence of a negative impact of bilateral grade III varicocele on testicular 25-hydroxylase activity. Accordingly, the patients included in this study showed a significant increase in PTH and a decrease in 25(OH)D levels over time. Patients with varicocele deserve endocrinologic counseling.

BACKGROUND. Few studies have evaluated the relationship between testicular histology and pathogenic variations of genes regulating spermatogenesis.AIM. To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology.PATIENTS AND METHODS. Sixty patients with NOA referred to the Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb, Croatia, for testicular biopsy were consecutively assessed for eligibility. Twelve patients were excluded from the study because they had Klinefelter syndrome (n=1), Yq microdeletions (n=6), testicular trauma (n=2), or in-situ germ cell neoplasia (n=3). Therefore, 48 patients were considered eligible and included in this study. They were divided into three groups: those who had cryptorchidism (n=9), those with varicocele (n=14), and those with idiopathic NOA (n=25). All included patients underwent blood withdrawal for next-generation sequencing analysis and gene sequencing.RESULTS. We found a possible genetic cause in 4 patients with idiopathic NOA (16%) and in 2 with cryptorchidism (22%). No pathogenic or possibly pathogenic mutations were identified in patients with varicocele. Variants of undetermined significance (VUS) were found in 11 patients with idiopathic NOA (44%), 3 with cryptorchidism (33%), and 8 patients with varicocele (57%). VUSs of the USP9Y gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular, the VUS USP9Y c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cell-only syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele. No direct correlation was found between the gene mutation/variant and the testicular histological picture. CONCLUSION. Different mutations of the same gene cause various testicular histological pictures. These results suggest that it is not the gene itself but the type of mutation/variation that determines the testicular histology picture. Based on the data presented above, it remains challenging to design a genetic panel with prognostic value for the outcome of testicular sperm extraction in patients with NOA.

Background: Few data are currently available on the treatment of patients with HPV infection. In particular, there is no agreement on the use of antioxidants in these patients. Ellagic acid and annona muricata appear to improve HPV clearance in infected women. However, it is presently unknown whether they could enhance the clearance of HPV infection in infertile male patients. Aim: To evaluate the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with documented papillomavirus (HPV) infection, and on the frequency of HPV DNA detection in seminal fluid after treatment. In addition, anti-sperm antibodies and the percentage of spermatozoa with fragmented DNA were evaluated. Materials and methods: This was a retrospective case-control study including patients attending our center for infertility. Fifty selected patients who were positive for high risk (HR)-HPV with available semen analysis results were consecutively enrolled. Patients were classified into two groups, according to the clinician’s decision to either administer ellagic acid 100 mg and annona muricata 100 mg (combined tablet formulation) for a period of three months (Group A; 25 patients), or to re-evaluate HPV DNA after a period of active surveillance only (protected sexual intercourse) (Group B; 25 patients). Results: Group A patients had a mean age of 31.0  ±  11.0 years, while Group B was 33.0  ±  8.0 years old (p  > 0.05). After three months of treatment with ellagic acid and annona muricata, all conventional seminal parameters improved more significantly in Group A than in Group B patients: sperm concentration = 45 mil/mL vs. 20 mil/mL (p < 0.05); sperm progressive motility = 45% vs. 18% (p < 0.05); and normal sperm morphology = 18% vs. 6% (p < 0.05). After the treatment, the frequency of persistence of HPV DNA in the seminal fluid was significantly lower in Group A patients compared to those in Group B (12/25 = 48% vs. 22/25 = 88%; p < 0.05). Finally, after 3 months, Group A showed a significant reduction in anti-sperm antibodies and in the percentage of spermatozoa with fragmented DNA. Conclusion: The results of this study demonstrate, for the first time, the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with HR-HPV infection, and that this therapy is also associated with a significant reduction in the persistence of HPV DNA in the seminal fluid.

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer’s dementia is the most common, while Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. There is a significant amount of evidence on the complex biological connection between cancer and neurodegeneration. Noncoding RNAs (ncRNAs) are defined as transcribed nucleotides that perform a variety of regulatory functions. The mechanisms by which ncRNAs exert their functions are numerous and involve every aspect of cellular life. The same ncRNA can act in multiple ways, leading to different outcomes; in fact, a single ncRNA can participate in the pathogenesis of more than one disease—even if these seem very different, as cancer and neurodegenerative disorders are. The ncRNA activates specific pathways leading to one or the other clinical phenotype, sometimes with obvious mechanisms of inverse comorbidity. We aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role. We also investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorbidity mechanism between some cancers and PD. We believe it is very important to study the inverse comorbidity relationship between cancer and neurodegenerative diseases because it will help us to better assess these two major areas of human disease.

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

The aim of the study is to describe the clinical features of two unrelated patients with resistance to thyroid hormones (RTH), the first, a total thyroidectomized patient, and the second, a pregnant woman. We report the features found in her newborn who also showed RTH. Patient 1 is a 38-year-old man with total thyroidectomy managed for excessive thyroid stimulating hormone (TSH) production, which poorly responded to the replacement therapy. He was found with a THRβ c.1378G>A p.(Glu460Lys) heterozygous mutation, which was also present in other members of his family (son, brother, and father). Interestingly, Patient 1 had hypertension, dyslipidemia, and hepatic steatosis, which have been recently suggested as RTH-related comorbidities. Patient 2 is a 32-year-old pregnant woman with multinodular goiter, and the THRβ heterozygous variant c.959G>C, that, to the best of our knowledge, has been reported in literature only once. Her newborn had tachycardia and increased thyroid hormone levels, and showed the same mutation. After delivery, high parathyroid hormone (PTH) and calcium serum levels were found in Patient 2 and the scintigraphy showed the presence of adenoma of a parathyroid gland. This case-series study provides a practical example of the management of RTH in a thyroidectomized patient, a pregnant woman, and a newborn. A novel RTH pathogenic mutation is described for the second time in literature. Furthermore, the importance of metabolic assessment in patients with RTHβ has been highlighted and the possible correlation between RTH and primary hyperparathyroidism is discussed.

Purpose: In recent years, a growing number of studies have supported the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligoasthenozoospermia. However, the results are controversial and no consensus exists regarding whether to request a second semen collection in clinical practice. Therefore, this systematic review and meta-analysis aimed to evaluate the influence of a very short abstinence period (within 4 h) on conventional sperm parameters and sperm DNA fragmentation (SDF) rate. Materials and Methods: The literature search was performed using Scopus and PubMed databases. The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. All eligible studies were selected according to the Population, Intervention, Comparison/Comparator, Outcomes, and Study design (PICOS) model. The quality of evidence of the included studies was analyzed through the Cambridge Quality Checklists. The standardized mean difference (SMD) was used to analyze the outcomes. Cochran-Q and I2 statistics were used to evaluate statistical heterogeneity. Results: We assessed for eligibility 1334 abstracts, and 19 studies were finally included. All 19 articles evaluated the effects of a very short abstinence period on sperm parameters and, among these, 5 articles also evaluated the effects on SDF rate. The quantitative analysis showed a significant reduction in semen volume after a very short abstinence period in both normozoospermic men and patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia (OAT) patients. We found a statistically significant increase in sperm concentration and total and progressive motility in the second ejaculation of patients with OAT. In contrast, the SDF rate decreased significantly in the second ejaculate of OAT patients. Conclusions: This is the first systematic review and meta-analysis investigating the impact of a very short abstinence period on sperm parameters and SDF rate. The results suggest that collecting a second consecutive ejaculation after a very short time from the first could represent a simple and useful strategy for obtaining better-quality spermatozoa, especially in patients with abnormal sperm parameters.

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, the prevalence of which ranges from 8 to 13%. It is characterized by metabolic, reproductive, and psychological alterations. PCOS prevalence is related to body mass index (BMI). Women with BMI < 25 kg/m2 have a prevalence of 4.3%, whereas women with BMI > 30 kg/m2 have a prevalence of 14%. Moreover, women with PCOS have a risk of type 2 diabetes mellitus (T2DM) two-fold higher than controls, independently of BMI. Both PCOS and T2DM are also consequences of lower serum sex-hormone-binding globulin (SHBG) levels, which is currently considered a biomarker of metabolic disorders, in particular T2DM. Aim: To evaluate the effect of the very-low-calorie ketogenic diet (VLCKD) on markers suggested to be predictive of metabolic and ovulatory dysfunction. These comprehend SHBG, anti-Mullerian hormone (AMH), and progesterone levels on day 21 of the menstrual cycle in a cohort of obese non-diabetic women with PCOS and regular menses. Methods: Twenty-five patients (mean age 25.4 ± 3.44 years) with obesity and PCOS underwent VLCKD for 12 weeks. Each of them underwent measurements of anthropometric parameters (body weight, height, and waist circumference) and blood testing to evaluate serum levels of SHBG, AMH, and progesterone before and after 12 weeks of VLCKD. Results: At enrollment, all patients had high BMI, WC, and AMH, whereas SHBG and progesterone levels were low. After VLCKD, the patients showed a significant reduction in BMI, WC, and HOMA index. In particular, 76% of patients (19/25) switched from obesity to overweight, and the HOMA index normalized, reaching values lower than 2.5 in 96% (24/25) of patients. In addition, serum AMH levels significantly decreased, and progesterone and SHBG significantly increased after VLCKD. Conclusions: This is the first study documenting the effects of VLCKD on ovarian reserve and luteal function in women with PCOS. VLCKD could be used to improve metabolic and ovulatory dysfunction in women with PCOS. Further studies are needed to understand the reasons for the AMH reduction.

The relationship between varicocele and hypogonadism becomes clearer everyday thanks to the most recent literature, particularly with regards to the impact of varicocele repair on serum testosterone level improvement in hypogonadal patients. We selected English articles published from 1964 to September 2021. The search terms “varicocele” and “hypogonadism” were used as filters. A total of 102 studies have been obtained. For the meta-analysis, the pooled mean differences (MDs) for continuous variables and the ln(OR) were used for data pooling observational studies. A total of 15 articles have been finally included: nine retrospective and six observational. Testosterone levels pre- and after surgery were reported in four studies. There was statistically significant heterogeneity in these studies (chi2 = 267.09, I2 = 72%; p = 0.01). Mean differences of total testosterone was statistically different in men pre- and after-surgery (mean difference = 106.76; p < 0.0001). It is indeed established that altered environments caused by varicocele cause pantesticular insult, but it has not been unequivocally determined whether men with varicocele are at increased risk for the development of clinical hypogonadal symptoms.

Background: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. Methods: A literature search was performed using the Pubmed, Scopus, Web of Science, and Cochrane databases. A meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for randomized controlled trials (RCTs). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study type) model. The following pregnancy outcomes after ART were considered: fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). This study was registered on PROSPERO (CRD42023396429). Results: We evaluated 414 records for eligibility, and 7 studies were ultimately included. Our analysis showed that a very short abstinence period significantly increased the IR, CPR, and LBR after ART. No significant differences were found for the FR and MR. Conclusions: A second ejaculation collected very shortly after the first one could represent a simple strategy to improve the results of ART, especially in couples including patients with abnormal sperm parameters.

Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of childbearing age (18–35 years) with metabolic hypogonadism were enrolled and divided into three groups, according to their desire to have children. Group A was made up of men actively seeking fatherhood, Group B, of men who did not seek fatherhood, and Group C, of men who had already fathered a child. Group A patients were treated with gonadotropins (urofollitropin at 150 IU, three times a week, and human chorionic gonadotropin at 2000 IU, twice a week), Group B patients with liraglutide (3 mg daily), and Group C patients with transdermal testosterone (60 mg per day). All patients were treated for 4 months. Results: Patients treated with liraglutide (Group B) showed significant improvement in conventional sperm parameters, compared to baseline and Group A patients, and in the quality of erectile function compared to baseline and patients of Groups A and C. In addition, they had significantly higher levels of total testosterone and sex hormone-binding globulin serum levels after 4 months of treatment with liraglutide than those achieved by patients in the other two groups at the end of the respective treatments. Finally, Group B patients also showed significantly higher serum gonadotropin levels than the other groups. Conclusions: The results of this study showed, for the first time, the efficacy of liraglutide, a GLP1 analog, for the pharmacological treatment of male patients with metabolic hypogonadism. Liraglutide has also shown advantages over traditional treatments on both reproductive and sexual function and appears to offer greater benefits in terms of metabolic protection. These findings suggest that liraglutide is a useful drug for the treatment of obese males with metabolic hypogonadism.

The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along with preimplantation genetic testing, although developed to improve the live birth rate (LBR) and reduce the risk of multiple pregnancies, are drawing attention to the possible increase in obstetric and perinatal risks, and adverse epigenetic consequences in offspring. Furthermore, ethical–legal concerns are growing regarding the increase in cryopreservation and storage of frozen embryos. In an attempt to reduce the risk associated with prolonged embryo culture and avoid embryo storage, we have chosen to inseminate a limited number of oocytes not exceeding the number of embryos to be transferred, after two days or less of culture. We retrospectively analyzed 245 ICSI cycles performed in 184 infertile couples with a female partner aged ≥40 from January 2016 to July 2021. The results showed a fertilization rate of 95.7%, a miscarriage rate of 48.9%, and a LBR of 10% with twin pregnancies of 16.7%. The cumulative LBR in our group of couples was 13%. No embryos were frozen. In conclusion, these results suggest that oocyte selection and embryo transfer at the cleaving stage constitute a practice that has a LBR comparable to that of the more commonly used protocols in older women who have reduced ovarian reserve.

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.

In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.

Infertility is a worldwide problem that affects 9-15% of couples of reproductive age. In about half of the cases, it recognizes, alone or in combination, a male cause. In addition to a reproductive problem, male infertility can result from a systemic disease. Consequently, semen analysis, a fundamental test in the diagnosis of male infertility, represents a useful indicator not only of a man's reproductive capacity but also of his health and lifestyle. Given the key role of semen analysis, only accredited laboratories should perform it and experienced clinicians should be called into play in its interpretation. In this article, we have extensively examined how the macroscopic and microscopic parameters of semen analysis, alone or associated with each other, allow clinicians to orient towards specific diagnoses that can be confirmed by further ad hoc tests. On this basis, we also proposed a diagnostic flowchart focused on the results of the semen analysis.

Introduction: Androgen insensitivity syndrome (AIS), an X-linked recessive disorder of sex development (DSD), is caused by variants of the androgen receptor (AR) gene, mapping in the long arm of the X chromosome, which cause a complete loss of function of the receptor. Case presentation: We report a patient diagnosed with complete AIS (CAIS) at birth due to swelling in the bilateral inguinal region. Transabdominal ultrasound revealed the absence of the uterus and ovaries and the presence of bilateral testes in the inguinal region. The karyotype was 46,XY. She underwent bilateral orchiectomy at 9 months and was given estrogen substitutive therapy at the age of 11 years. Genetic analysis of the AR gene variants was requested when, at the age of 20, the patient came to our observation. Methods: The genetic testing was performed by next-generation sequence (NGS) analysis. Results: The genetic analysis showed the presence of the c.2242T>A, p.(Phe748Ile) variant in the AR gene. To the best of our knowledge, this variant has not been published so far. Furthermore, the patient has a heterozygous c.317A>G, p.(Gln106Arg) variation of the gonadotropin-releasing hormone receptor (GNRHR) gene, a heterozygous c.2273G>A, p.Arg758His variation of the chromodomain helicase DNA binding protein 7 (CHD7) gene, and compound heterozygous c.875A>G, p.Tyr292Cys, and c.8023A>G, p.Ile2675Val variations of the Dynein Axonemal Heavy Chain 11 (DNAH11) gene. Conclusions: The case herein reported underlines the importance of an accurate genetic analysis that has to include karyotype and AR gene variant analysis. This is useful to confirm a clinical diagnosis and establish the proper management of patients with CAIS. Numerous variants of the AR gene have not yet been identified. Moreover, several pitfalls are still present in the management of these patients. More studies are needed to answer unresolved questions, and common protocols are required for the clinical follow-up of patients with CAIS.

Air pollution has been suggested to affect semen quality, but the evidence is still contradictory. To assess whether any differences occur in conventional sperm parameters of men life-long resident in low, middle-low, middle, and high industrial density zones in the province of Messina. We retrospectively analyzed the conventional sperm parameters of patients to whom the sperm analysis was requested during their female partner counseling for infertility in an assisted reproductive technique (ART) center. A total of 184 men were enrolled. Total sperm count was higher in patients living in low and middle-low industrial density areas compared with that of men living in middle and high ones (123.5 ± 146.8 vs. 80.7 ± 92.7 mil/ejaculate, p

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

Background: Selective estrogen receptor modulators (SERMs) represent a poorly investigated class of drugs for the treatment of male infertility. The aim of this study was to assess the effects of SERMs on conventional sperm parameters, serum gonadotropin and testosterone levels, and pregnancy rate in patients with idiopathic infertility. Methods: The authors performed a comprehensive systematic review with meta-analysis of all available controlled and not-controlled studies of the literature reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate following SERM administration in normogonadotropic patients with idiopathic oligozoospermia. Results: From the 418 papers retrieved, 16 controlled and not-controlled trials were lastly included. SERM administration increased significantly sperm concentration, total sperm count, and serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels compared with baseline values. In contrast, SERMs did not have any significant effect on sperm concentration and progressive and total motility, but improved total sperm count, sperm morphology, and increased the pregnancy rate compared to the control group, which included studies done with placebo or other treatments. Conclusions: The results of this meta-analysis suggest that SERMs may be effective in the treatment of infertile patients with idiopathic infertility. However, the paucity of data does not allow to draw a definitive conclusion.

Background Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32-65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45-50% of cases. Objectives The aim was to provide clinical practice guidelines for the evaluation and management of GM. Materials and methods A literature search of articles in English for the term 'gynecomastia' was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Results A set of five statements and fifteen clinical recommendations was formulated. Conclusions The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha-fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non-aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long-lasting GM. Summary of statements (s) and recommendations (r) S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. S3. GM of puberty is a common condition, affecting approximately 50% of mid-pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45-50% of the cases. S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into 'strong', denoted by the number 1 and associated with the terminology 'we recommend', and 'weak' denoted by the number 2 and associated with the phrase 'we suggest'. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low-quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non-specialist (2 ⊕○○○). R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). R5. We recommend that the physical examination should detect signs of under-virilization or systemic disease (1 ⊕⊕⊕⊕). R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo-gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). R9. We suggest that a set of evaluations may include T, E2 , SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). R15. We suggest surgical treatment only for patients with long-lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○).

The aim of this article is to propose an algorithm that aids the clinician to choose the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme.We subdivided patients in four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); patient with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: treated with FSH alone for at least 3 months; group B: treated with hCG alone twice a week for 3 months and addition of FSH for poor responders (unmodified sperm parameters); group C: treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in term of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate.40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate.To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician to choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups).

Down syndrome (DS) is defined by the presence of a third copy of chromosome 21. Several comorbidities can be found in these patients, such as intellectual disability (ID), muscle weakness, hypotonia, congenital heart disease, and autoimmune diseases. The molecular mechanisms playing a role in the development of such comorbidities are still unclear. The regulation and expression of genes that map to chromosome 21 are dynamic and complex, so it is important to perform global gene expression studies with high statistical power to fully characterize the transcriptome in DS patients. This study was undertaken to evaluate mRNAs and lncRNA expression in patients with DS versus a matched cohort of healthy subjects. RNA sequencing was used to perform this transcriptome study. Differential expression analysis revealed 967 transcripts with padj ≤ 0.05. Among them, 447 transcripts were differentially expressed in patients with DS compared to controls. Particularly, 203 transcripts were down expressed (151 protein-coding mRNAs, 45 lncRNAs, 1 microRNA, 1 mitochondrial tRNA, 1 ribozyme, and 1 small nuclear RNA) and 244 were over expressed (210 protein-coding mRNAs and 34 lncRNAs). Interestingly, deregulated lncRNAs are involved in pathways that play a role in developmental disorders, neurological diseases, DNA replication and repair mechanisms, and cancer development in DS patients. In conclusion, these results suggest a role of lncRNAs in the phenotype of DS patients.

Background: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. Aim: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. Patients and Methods: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. Results: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. Conclusion: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified.

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs.

Introduction The prevalence of testicular tumor is constantly increasing, with an estimated incidence rate of about 3-10 new cases per 100,000 males/per year. Radical orchiectomy or testis sparing surgery (TSS) are recognized therapeutic approaches in these cases. However, the risk for hypogonadism and infertility is higher with the former compared with the latter. The aim of this systematic review is to evaluate the oncological outcome and testicular function (endocrine and reproductive aspects) in patients who had undergone TSS for small testicular lesions. Evidence acquisition To accomplish this, 684 items were retrieved and screened; 24 retrospective and 2 prospective studies were selected and finally included in this systematic review. Evidence synthesis Overall the TSS attempts were 1096 but TSS was definitively performed in 603 cases (55%). Frozen section examination was performed in 996 TSS attempts (22 out of the 26 studies selected) and showed a benign histology in 37-100% of cases, a malignant histology in 0-63%, and an inconclusive result in 0-16%, respectively. Five studies reported that a total of 22 patients were able to father after conservative surgery. None of these studies reported cases of hypotestosteronemia after surgery and a low prevalence (1.66%) of complications was associated with this type of surgery. Conclusions In conclusion, TSS showed to be safe and practicable if used according to the specific guidelines. It can be safely performed to treat recurrence eventually associated to local adjuvant radiotherapy when an intra-tubular neoplasia is present. Urologists can therefore consider TSS as an important means against testicular tumor in selected and well-informed patients.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19. Methods: Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: “Vitamin D”, “25 hydroxy Vitamin D”, “25 hydroxycholecalciferol”, “cholecalciferol”, “COVID 19″, “SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25‑hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D

Endocrine diseases have a considerable impact on public health from an epidemiological point of view and because they may cause long-term disability, alteration of the quality-of-life of the affected patients, and are the fifth leading cause of death. In this extensive review of the literature, we have evaluated the prevalence of the different disorders of endocrine interest in the world and Italy, highlighting their epidemiological, clinical, and economic impact.

Polycystic ovary syndrome (PCOS) is a very common endocrine and metabolic disorder with the involvement of both genetic and environmental factors. Although much has been clarified on its pathogenesis, diagnosis, clinical manifestations, and therapy, there are still areas of uncertainty. To address fundamental concepts, novel aspects and hypotheses, and future perspectives, including the possible additional benefits of treatment with nutraceuticals, an expert consensus panel formed by endocrinologists and gynecologists was established. After an independent review of the literature, the panel convened electronically on February 3, 2020, and six resolutions were created, debated, and agreed upon discussion, and finally approved in their final form in a consensus livestream meeting held on April 15. The summary of the resolutions are: (1) PCOS is a well-established medical condition that negatively affects reproduction, general health, sexual health, and quality of life; (2) the symptoms and signs of PCOS appear early in life especially in female newborns from PCOS carriers; (3) women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes mellitus; (4) a male PCOS equivalent exists, and it may impact on metabolic health and probably on reproduction; (5) the evidence supports that medical therapy for PCOS is effective, rational, and evidence-based; (6) the evidence supports a major research initiative to explore possible benefits of nutraceutical therapy for PCOS. The proposed resolutions may be regarded as points of agreement based on the current scientific evidence available.

BACKGROUND The recently published guidelines of the European Academy of Andrology (EAA) recommended not to prescribe testosterone replacement therapy (TRT) in male patients with hypotestosteronemia and severe heart failure (HF) [New York Hearth Association (NYHA) class III and IV] since the risk in these patients has not been formally documented. Therefore, the aim of this study was to systematically evaluate the risk of TRT on the cardiac function and angina, in male patients with hypotestosteronemia and HF or coronary heart disease. METHODS Randomized controlled trials (RCTs) on male patients with hypotestosteronemia and chronic HF (ejection fraction

Background The ultrasound (US) evaluation of the male sex accessory gland inflammation (MAGI) helps the clinicians to understand the severity of this condition, allowing them to distinguish the uncomplicated form (prostatitis) from the complicated ones (prostate-vesiculitis and prostate-vesiculitis-epididymitis), as well as the unilateral from the bilateral forms, the fibrosclerotic and the hypertrophic-congestive form. Objective This retrospective study aimed to evaluate the US features of MAGI patients with active symptoms compared to patients without sexual, voiding, and ejaculatory dysfunction. Materials/methods To achieve this aim, an analysis of the prevalence of MAGI US criteria was carried out on a very large series of over 500 patients diagnosed with MAGI classified according to the different symptom profile evaluated through a dedicated questionnaire (previously conceived and published by our group) arbitrarily named "structured interview about MAGI" (SI-MAGI) for sexual, voiding, and ejaculatory disorders reported by these patients. Results The results of this study revealed that US criteria most frequently detected in patients with severe urinary symptoms were the presence of areas of high echogenicity (almost exclusively in the periurethral prostatic zone) together with the presence of single or multiple areas of acinar ectasia of the prostate. The presence of seminal vesicles with polycyclic areas within the glandular lumen separated by hyperechoic septa represented US criterion most frequently detected in patients with severe spontaneous or post-ejaculate pain. Finally, US criterion most frequently detected in patients with severe sexual dysfunction was the dilation of the periprostatic venous plexus, suggesting the hypothesis of a possible alternative therapeutic approach. Conclusion The data of the present study suggest that symptoms may associate with US signs in patients with MAGI. Also, specific US signs may associate with specific symptoms. Further studies are needed to understand whether patients with specific US signs may in turn benefit from a personalized therapeutic choice.

Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson’s disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence of Lewy bodies (LBs) and genetic factors are involved in its pathogenesis. Several studies have indicated that the expression of target genes in patients with PD is inversely related to cancer development; this phenomenon has been named “inverse comorbidity”. The present study was undertaken to evaluate whether a genetic dysregulation occurs in opposite directions in patients with PD or PCa. In the present study, next-generation sequencing (NGS) transcriptome analysis was used to assess whether a genetic dysregulation in opposite directions occurs in patients with PD or PCa. The genes SLC30A1, ADO, SRGAP2C, and TBC1D12 resulted up-regulated in patients with PD compared to healthy donors as controls and down-regulated in patients with PCa compared with the same control group. These results support the hypothesis of the presence of inverse comorbidity between PD and PCa.

Objective: To evaluate the changes of conventional sperm parameters in men who referred to an andrology reference center in Catania (Eastern Sicily, Italy) in the decade 2011–2020. Methods: For this purpose, we selected–retrospectively and randomly–the reports of 1409 semen analyses performed according to the 2010 WHO criteria. Data on sperm concentration, total sperm count, progressive sperm motility, and percentage of normal forms were analyzed using linear regression of the raw and logarithmic-transformed data. The sperm parameters were subsequently pooled in two five-year periods (2011–2015 and 2016–2020) and compared with each other. Finally, the influence of the city of residence was assessed on five-year pooled data. Main results: A slight but non-significant decline of total sperm count (−2.26 million/year, p = 0.065) and the percentage of spermatozoa with normal morphology (−0.08%/year, p = 0.057) was observed. In contrast, a significant increase of progressive sperm motility (+0.28%/year, p = 0.008) over time was found. The total sperm count of the quinquennium 2016–2020 was significantly lower. and an upward trend of progressive sperm motility was found. compared to the years 2011–2015. No changes in sperm concentration and morphology occurred in the years 2011–2015 vs. 2016–2020. Sperm conventional parameters did not differ when the five-year pooled data were analyzed according to the town of residence. Conclusions: Divergent trends of total sperm count and progressive sperm motility over time were found in patients from Eastern Sicily. This may point out the need of assessing whether a time-dependent change of biofunctional sperm parameters occurs to really understand the trend of sperm quality over time.

Introduction: Seminal fluid viscosity is a key parameter to achieve fertilization. Viscosity is more frequently increased in patients with infertility. However, the mechanism by which hyperviscosity causes infertility is still poorly understood. As an increased blood viscosity is associated with diseases caused by oxidative stress, it can be supposed that there is a relationship between seminal fluid viscosity and oxidative stress in male infertility. Therefore, this systematic review aims to investigate the relationship between hyperviscous seminal fluid and oxidative stress. Materials and methods: We performed a systematic search on the following databases Pubmed, MEDLINE, Cochrane, and Scopus from the earliest available date to 10 January 2021, using Medical Subjects Headings (MeSH) indexes and keywords searches. The study included all the articles that evaluated the relationship between increased seminal fluid viscosity and oxidative stress. Article reviews even though dealing with seminal fluid hyperviscosity were excluded. Results: 5 articles were included in this systematic review. The results demonstrated an important impairment of antioxidant systems and increased oxidative stress in patients with high seminal fluid viscosity. Conclusions: These findings suggest that a careful assessment of oxidative stress in patients with hyperviscosity may be very useful in clinical practice. Infertile patients with seminal fluid hyperviscosity could benefit from the treatment with antioxidants to protect sperm cells from oxidative damage and to improve their functional properties.

Background: Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. Aim: To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED. Methods: Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 μg. Results: In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = −0.9, p < 0.01), 10 (r = −0.9, p < 0.01), 15 (r = −0.9, p < 0.01), and 20 (r = −0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a “late-responder” profile. Conclusion: If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED, since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.

Previous data have shown that patients with metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) could be refractory to the medical treatment. In this context, the evidence suggests a role for statin use in LUTS/BPE patients. The present systematic review aimed to evaluate the impact of statins on the treatment of men with LUTS/BPE. This review has been registered on PROSPERO (CRD42019120729). A systematic review of English-language literature was performed up to January 2020 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement) criteria. Retrieved studies had to include adults with LUTS connected to BPE treated with statins drugs for metabolic syndrome. After removing duplicates, a total of 381 studies were identified by the literature search and independently screened. Of these articles, 10 fit the inclusion criteria and were further assessed for eligibility. Data from our systematic review suggest that a long-term therapy with statins, at least 6 months, is required to achieve significant impacts on prostate tissue and LUTS. Moreover, besides statins’ direct activity, the risk reduction of LUTS might be connected to the improvement of hypercholesterolemia and MetS. The role of statins for the treatment of LUTS/BPE may be beneficial; however, evidence from robust studies is not enough, and more clinical trial are required.

Pediatric varicocele, having a prevalence between 1 and 15% according to age, is more frequent as puberty begins. By interfering with Sertoli cell proliferation and hormone secretion, testicular growth, and spermatogenesis, it can damage testicular function. Proper management has a pivotal role for future fertility preservation. In this chapter, diagnosis, management, and treatment of childhood and adolescent varicocele will be discussed from an endocrinological perspective, overviewing the current evidence and the established guidelines by the European Society for Pediatric Urology, the European Association of Urology, the American Urological Association, and the American Society for Reproductive Medicine.

Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered methylation of sperm-imprinted genes associates with sperm DNA fragmentation (SDF), pregnancy loss rate and assisted reproductive technique (ART) outcome. To accomplish this, Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases were used for search strategy from each database inception until December 2020. Specific keywords were used. Studies satisfying the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model were retrieved. Ten studies could be included in the qualitative analysis. A significant association was reported between increased SDF rate and aberrant methylation of H19/IGF2 and KCNQ1 genes by two studies. A significantly lower H19 methylation was found in patients with idiopathic recurrent pregnancy loss (RPL) and in infertile patients compared to fertile men. Methylation of GLT2, PEG1/MEST, and ZAC/PLACL1 were similar in patients with RPL and controls. The ART outcome was similar in patients with aberrant and normal methylation of H19, SNRPN, KCNQ1OT1, PEG1/MEST, LIT1, PEG3, NESPAS, and GLT2. By contrast, a study showed an association between altered GLT2 methylation and more inferior ART results. If further confirmed by well-sized studies, these data might be helpful to identify possible epigenetic predictors of ART outcome. Particularly, aberrant methylation of H19/IGF2 and KCNQ1 genes might represent interesting targets that deserve further investigation.

The current issue of the Croatian Medical Journal features two interesting articles on reproductive health. Sengun et al (1) present their findings of novel mutations in the gene coding for FK506 binding protein-like (FKBPL) associated with male infertility, while Bilić et al (2) discuss the benefits of ovarian tissue cryopreservation. In spite of tremendous advances in the field, various aspects of reproductive health, particularly infertility, still necessitate further study and development of novel diagnostic and therapeutic approaches.