AIMTo assess the relation of reactive oxygen species (ROS) and antioxidants in the internal spermatic vein blood compared to the peripheral venous blood.

METHODSSixty-eight infertile oligoasthenozoospemic patients associated with varicocele were investigated. During inguinal varicocelectomy, blood samples of internal spermatic as well as median cubital veins were withdrawn. Three ROS factors (malondialdehyde [MDA], hydrogen peroxide H(2)O(2), nitric oxide [NO]) and four antioxidants (superoxide dismutase [SOD], catalase [Cat], glutathione peroxidase [GPx] and vitamin C) were estimated in these blood samples.

RESULTSMean levels of tested ROS factors were significantly higher in the internal spermatic venous blood compared to those in the peripheral one (mean+/-SD) (MDA 18.7+/-1.4 nmol/mL vs. 15.4+/-1.4 nmol/mL, H(2)O(2) 43.6+/-8.0 micromol/mL vs. 30.8+/-8.1 micromol/mL, NO 2.3+/-0.5 nmol/L vs. 1.6+/-0.4 nmol/L, P<0.01). Mean levels of tested antioxidants were significantly lower in the internal spermatic venous blood compared to those in the peripheral one (superoxide dismutase 1 690.7+/-130.0 U/mL vs. 1 818.5+/-143.0 U/mL, catalase 38.9+/-6.1 mol/L vs. 47.9+/-10.2 mol/L, GPx 20.4+/-8.1 U/mL vs. 23.0+/-8.4 U/mL, vitamin C 0.3+/-0.1 vs. 0.4+/-0.1 mg/dL, P<0.05).

CONCLUSIONInternal spermatic venous blood of infertile male cases associated with varicocele demonstrated elevated levels of ROS and decreased levels of antioxidants compared to peripheral venous circulation.

Adult ; Antioxidants ; metabolism ; Ascorbic Acid ; blood ; Catalase ; blood ; Glutathione Peroxidase ; blood ; Humans ; Hydrogen Peroxide ; metabolism ; Infertility, Male ; enzymology ; metabolism ; Male ; Malondialdehyde ; metabolism ; Middle Aged ; Nitric Oxide ; blood ; Prospective Studies ; Reactive Oxygen Species ; Spermatic Cord ; blood supply ; Superoxide Dismutase ; blood ; Varicocele ; enzymology ; metabolism ; Veins ; enzymology ; metabolism

AIMTo assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.

METHODSOne hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor (zinc protoporphyrin, ZnPP); and group 4 received sildenafil and nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME). Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated.

RESULTSIn cavernous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO-1 cavernous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels (r = 0.646, r = 0.612 respectively; P < 0.001).

CONCLUSIONThe actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

Administration, Oral ; Animals ; Cyclic GMP ; metabolism ; Drug Interactions ; Drug Therapy, Combination ; Enzyme Inhibitors ; pharmacology ; Heme Oxygenase-1 ; antagonists & inhibitors ; metabolism ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; metabolism ; Penis ; drug effects ; enzymology ; Piperazines ; pharmacology ; Protoporphyrins ; pharmacology ; Purines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfones ; pharmacology ; Vasodilator Agents ; pharmacology

AIMTo assess seminal plasma anti-Müllerian hormone (AMH) level relationships in fertile and infertile males.

METHODSEighty-four male cases were studied and divided into four groups: fertile normozoospermia (n = 16), oligoasthenoteratozoospermia (n = 15), obstructive azoospermia (OA) (n = 13) and non-obstructive azoospermia (NOA) (n = 40). Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction (TESE) in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE (n = 19) and successful TESE (n = 21). Seminal plasma AMH was estimated by enzyme linked immunosorbent assay (ELISA) and serum follicular stimulating hormone (FSH) was estimated in NOA cases only by radioimmunoassay (RIA).

RESULTSMean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance (41.5 +/- 10.9 pmol/L vs. 30.5 +/- 10.3 pmol/L, P < 0.05). Seminal AMH was not detected in any OA patients. Seminal AMH was correlated positively with testicular volume (r = 0.329, P = 0.005), sperm count (r = 0.483, P = 0.007), sperm motility percent (r = 0.419, P = 0.021) and negatively with sperm abnormal forms percent (r = -0.413, P = 0.023). Nonsignificant correlation was evident with age (r = -0.155, P = 0.414) and plasma FSH (r = -0.014, P = 0.943). In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE (57.5%) and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE (58.2%).

CONCLUSIONSeminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.

Adult ; Anti-Mullerian Hormone ; Asthenozoospermia ; therapy ; Azoospermia ; therapy ; Follicle Stimulating Hormone ; analysis ; Glycoproteins ; analysis ; Humans ; Infertility, Male ; therapy ; Male ; Predictive Value of Tests ; Semen ; chemistry ; physiology ; Sperm Count ; Sperm Motility ; Spermatozoa ; physiology ; Testicular Hormones ; analysis ; Tissue and Organ Harvesting ; methods

AIMTo assess laminin levels in the seminal plasma of infertile and fertile men, and to analyze the correlation of laminin levels with sperm count, age, sperm motility and semen volume.

METHODSOne hundred and twenty-five recruited men were equally divided into five groups according to their sperm concentration and clinical examination: fertile normozoospermia, oligoasthenozoospermia, non-obstructive azoospermia (NOA), obstructive azoospermia (OA) and congenital bilateral absent vas deferens (CBAVD). The patients' medical history was investigated and patients underwent clinical examination, conventional semen analysis and estimation of seminal plasma laminin by radioimmunoassay.

RESULTSSeminal plasma laminin levels of successive groups were: 2.82 +/- 0.62, 2.49 +/- 0.44, 1.77 +/- 0.56, 1.72 +/- 0.76, 1.35 +/- 0.63 U/mL, respectively. The fertile normozoospermic group showed the highest concentration compared to all infertile groups with significant differences compared to azoospermic groups (P<0.05). Testicular contribution was estimated to be approximately one-third of the seminal laminin. Seminal plasma laminin demonstrated significant correlation with sperm concentration (r = 0.460, P < 0.001) and nonsignificant correlation with age (r = 0.021, P = 0.940), sperm motility percentage (r = 0.142, P = 0.615) and semen volume (r = 0.035, P = 0.087).

CONCLUSIONSeminal plasma laminin is derived mostly from prostatic and testicular portions and minimally from the seminal vesicle and vas deferens. Estimating seminal laminin alone is not conclusive in diagnosing different cases of male infertility.

Adult ; Azoospermia ; physiopathology ; Fertility ; physiology ; Humans ; Infertility, Male ; physiopathology ; Laminin ; metabolism ; Male ; Oligospermia ; physiopathology ; Semen ; physiology ; Sperm Count ; Sperm Motility

AIMTo access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups.

METHODSBeta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay (ELISA) method in 80 infertile men equally divided into four groups: non-obstructive azoospermia (NOA), obstructive azoospermia (OA), congenital bilateral absent vas deferens (CBVAD) and asthenozoospermia. The results were compared to those of 20 normozoospermic proven fertile men.

RESULTSThere was a decrease in the mean levels of beta-endorphin in the seminal plasma of all successive infertile groups (mean +/- SD: NOA 51.30 +/- 27.37, OA 51.88 +/- 9.47, CBAVD 20.36 +/- 13.39, asthenozoospermia 49.26 +/- 12.49 pg/mL, respectively) compared to the normozoospermic fertile control (87.23 +/- 29.55 pg/mL). This relation was not present in mean serum level of beta-endorphin between four infertile groups (51.09 +/- 14.71, 49.76 +/- 12.4, 33.96 +/- 7.2, 69.1 +/- 16.57 pg/mL, respectively) and the fertile control group (49.26 +/- 31.32 pg/mL). The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin. Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%. Seminal beta-endorphin showed significant correlation with the sperm concentration (r = 0.699, P = 0.0188) and nonsignificant correlation with its serum level (r = 0.375, P = 0.185) or with the sperm motility percentage (r = 0.470, P = 0.899).

CONCLUSIONThe estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there are many other opiates acting at the hypothalamic pituitary gonadal axis.

Asthenozoospermia ; blood ; metabolism ; Azoospermia ; blood ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Infertility, Male ; blood ; metabolism ; Male ; Prospective Studies ; Semen ; chemistry ; Vas Deferens ; abnormalities ; beta-Endorphin ; blood ; metabolism

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/ andrology, and further development of andrology as an independent specialty.

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.

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD −1.125, 95% confidence interval [CI] −1.410, −0.840; p<0.0001) with high inter-study heterogeneity (I2=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD −1.014, 95% CI −1.263, −0.765; p<0.0001, and SMD −1.495, 95% CI −2.116, −0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD −2.197, 95% CI −3.187, −1.207; p<0.0001), sperm chromatin structure assay (SMD −0.857, 95% CI −1.156, −0.559; p<0.0001) or TUNEL (SMD −1.599, 95% CI −2.478, −0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD −2.450, 95% CI −3.903 to −0.997, p=0.001) with high inter-study heterogeneity (I2=93.7%). Conclusions Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Purpose: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. Materials and Methods: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. Results: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT’s future use, despite pending guidelines support. Conclusions This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.