Search

Abstract Background Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochondrial membrane potential with optimal mitochondrial performance is essential for sperm motility, capacitation, acrosome reaction, and DNA integrity. Results Defects in the sperm mitochondrial function can severely harm the fertility potential of males. The role of sperm mitochondria in fertilization and its final fate after fertilization is still controversial. Here, we review the current knowledge on human sperm mitochondria characteristics and their physiological and pathological conditions, paying special attention to improvements in assistant reproductive technology and available treatments to ameliorate male infertility. Conclusion Although mitochondrial variants associated with male infertility have potential clinical use, research is limited. Further understanding is needed to determine how these characteristics lead to adverse pregnancy outcomes and affect male fertility potential.

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intraperson before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

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.

Infertility affects millions of couples worldwide. Oxidative stress (OS) causes peroxidation of lipids and damage to spermatozoa, thus, reducing the quality of seminal parameters. In addition, the differences in the levels of antioxidants and reactive oxygen species (ROS) caused by intrinsic and extrinsic variables linked to lifestyle, diet, genetics, and OS also contribute to male infertility. High levels of ROS result in sperm damage of sperm parameters due to lipid peroxidation and oxidation of proteins. Other significant causes of ROS include changes in sex hormone levels, sperm DNA damage, including mutations, and immature spermatozoa. Treating the root causes of OS, by changing one’s lifestyle, as well as antioxidant therapy, may be helpful strategies to fight OS-related infertility. However, the determination of male infertility induced by OS is currently a challenge in the field of reproductive health research. This review intends to describe the role of oxidative stress on male infertility and the current understanding of its management.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Abstract There are conflicting reports on trends of semen parameters from different parts of the globe. However, in recent times there is dearth of information on the trend in Sub-Saharan countries. Therefore, in this study we aimed at determining the trends in semen parameters in Nigeria and South Africa between 2010 and 2019. A retrospective study of semen analyses of 17,292 men attending fertility hospitals in Nigeria and South Africa in 2010, 2015 and 2019. Patients who had undergone vasectomy and those who had a pH less than 5 or greater than 10 were excluded from this study. The following variables were assessed: ejaculate volume, sperm concentration, progressive motility, total progressively motile sperm count (TPMSC), total sperm count, and normal sperm morphology. Between 2010 and 2019, significant trends of decreasing values were observed in normal sperm morphology (− 50%), and the ejaculatory volume (− 7.4%), indicating a progressive deterioration of the values in both countries. In Nigeria, there were significant decreases in progressive motility (− 87%), TPMSC (− 78%), and sperm morphology (− 55%) between 2010 and 2019 (P

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Purpose: Azoospermia is defined as the absence of spermatozoa in the pellet of a centrifuged semen sample. In fact, when a basic semen analysis fails to detect sperm in the ejaculate, there is still the possibility of detecting rare sperm after centrifugation of the sample and examination of the pellet. In this study, we assessed the role of Cytospin centrifugation in combination with the nuclear fast picroindigocarmine (NF-PIC) staining in identifying sperm in azoospermic samples. Materials and Methods: Semen samples of 251 men diagnosed as having azoospermia after standard examination were further analyzed by Cytospin centrifugation in combination with NF-PIC staining. Results: Sperm were detected in 60 men (23.9%), thus changing their diagnosis to cryptozoospermia. Conclusions: By identifying sperm in the semen of men who were thought to have total azoospermia, the Cytospin NF-PIC test can alter the diagnosis and further treatment of these men.

Purpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. Materials and Methods: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software. Results: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature. Conclusions: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele’s impact on men’s health and male fertility.

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the im-mune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relation-ship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this ar-ticle, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for as-sessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are pre-sented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.

Semen analysis is the first, and frequently, the only step in the evaluation of male fertility. Although the laboratory procedures are conducted according to the World Health Organization (WHO) guidelines, semen analysis and especially sperm mor-phology assessment is very difficult to standardize and obtain reproducible results. This is mainly due to the highly subjective nature of their evaluation. ICSI is the choice of treatment when sperm morphology is severely abnormal (teratozoospermic). Hence, the standardization of laboratory protocols for sperm morphology evaluation represents a fundamental step to ensure reliable, accurate and consistent laboratory results that avoid misdiagnoses and inadequate treatment of the infertile patient. This article aims to promote standardized laboratory procedures for an accurate evaluation of sperm morphology, including the establishment of quality control and quality assurance policies. Additionally, the clinical importance of sperm morphol-ogy results in assisted reproductive outcomes is discussed, along with the clinical management of teratozoospermic patients.

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

Background: Extractions of Lessertia frutescens (Lf) are shown to have immune modulation, anti-inflammatory and antioxidant properties. However, Lf is also cytotoxic, antiproliferative, and pro-apoptotic in vitro. Furthermore, Lf extractions may influence steroidogenesis. Nevertheless, the impact on Leydig cell function has not previously been investigated. As tumor necrosis factor-alpha (TNF-α) is known to cause Leydig cell dysfunction under inflammatory conditions, it is further proposed that Lf extracts may protect against the negative impact of TNF-α on Leydig cells. The aim of the study was to investigate the effect of an aqueous Lessertia frutescens extract (LFE) on Leydig cells exposed to TNF-αin vitro. Methods: Human chorionic gonadotrophin-stimulated TM3 Leydig cells were exposed for 24 h to (a) TNF-α (0.1, 1, 10, 100 ng/mL), (b) LFE (0.01, 0.1, 1, 10, 100 ng/mL), and (c) co-exposure to 10 ng/mL TNF-α and LFE (0.01, 0.1, 1, 10, 100 ng/mL). We analyzed cell viability, cytotoxicity, caspase 3/7 activation, testosterone concentration, and intracellular superoxide. Results: TNF-α exposure decreased cell viability, increased cytotoxicity, and caspase 3/7, with no significant effect on intracellular superoxide in TM3 Leydig cells. When LFE concentrations of 0.01–10 ng/mL were tested, we observed improved vitality and reduced levels of caspase 3/7. At 100 ng/mL, LFE decreased viability and increased cytotoxicity and caspase 3/7. However, LFE did not affect intracellular superoxide. Furthermore, LFE protected against 10 ng/mL TNF-α-induced cytotoxicity and apoptosis, except at the highest concentration. LFE alone and in co-culture with 10 ng/mL TNF-α increased testosterone at high concentrations. Conclusions: In our TM3 Leydig cell model, LFE protected against TNF-α-induced cytotoxicity and early apoptosis, except at the highest experimental concentrations, where it was cytotoxic. These effects were not mediated through a change in intracellular superoxide. Although further investigations are warranted, aqueous LFE may protect against TNF-α-induced Leydig cell dysfunction.

Semen analysis is a basic test for evaluating male fertility potential, as it plays an essential role in driving the future management and treatment of infertility in couples. Manual semen analysis includes the evaluation of both macroscopic and microscopic parameters, whereas automated semen analysis is conducted through a computer-aided sperm analysis system and can include additional parameters that are not evaluated by manual analysis. Both quality control (QC) and quality assurance (QA) are important to ensure reproducible results for semen analysis, and represent fundamental checks and balances of all stages (pre-analytical, analytical, and post-analytical) of semen analysis. To ensure accuracy and precision, the laboratory technicians’ performance should be evaluated biannually. This narrative review aims to describe standardized laboratory procedures for an accurate assessment of semen parameters that incorporate both QC and QA practices.

IntroductionMetabolic Age (MetAge) and body composition analysis may reflect an individual’s metabolic status, which is believed to influence male sexual and gonadal functions. Although erectile dysfunction (ED) and hypogonadism are increasingly prevalent with age, they are also detected among younger men. This study aims to assess the impact of MetAge and body composition on male sexual and gonadal status overall, and particularly in men younger than 40 years of age.MethodsThis was a cross-sectional study of 90 male healthcare workers, between the ages of 18-55, randomly selected based on their corporation numbers. In addition to Bioelectric Impedance Analysis, subjects were requested to fill the International Index of Erectile Function questionnaire (IIEF-5) and to provide an early morning serum testosterone (T) sample. ResultsThe mean participants’ age was 39.4 ± 9.4 years, MetAge was 45.54 ± 10.35 years, serum T level was 13.68 ± 4.49 nmol/L and BMI was 28.8 ± 4.7 kg/m2. Significant negative correlations were obtained between serum T, MetAge, body weight and fat composition. Significant negative correlations between the IIEF-5 score, MetAge, and fat composition, were only reported in subjects

Purpose: The objective of this scientometric analysis was to recognize the top 100 cited articles on ‘Male infertility and Antioxidants’ and analyze its publication characteristics. Materials and Methods: The Scopus database was used to retrieve related articles and the top 100 identified based on citation rate. Results: The articles were published in 56 journals between 1995 and 2019 with a median (interquartile range) citation score of 17 (5–62). Among the top 100 articles, 69 were clinical studies, which included controlled and blinded (33.33%), prospective (27.54%), randomized-controlled trials (26.09%), uncontrolled (11.59%), and retrospective (1.45%) studies. In addition to conventional semen parameters, advanced sperm function tests such as oxidative stress (51%) and sperm DNA damage (23%) were reported. Pregnancy rate (33%) was found to be the most reported reproductive outcome. Antioxidant therapy was mostly investigated in male cohorts with sperm abnormalities such as asthenozoospermia (28%) and clinical conditions such as idiopathic male infertility (20%), varicocele/varicocelectomy (17%) and general male infertility (16%). Conclusions: The most influential publications on antioxidants and male infertility were identified for the first time in the literature. This will serve as a reliable source of information for researchers and clinicians alike.

Purpose: In response to the COVID-19 pandemic, the American Center for Reproductive Medicine (ACRM) transitioned its annual training in assisted reproductive technology (ART) from a hands-on, laboratory-based training course to a fully online training endorsed by the American College of Embryology. Here we describe our experience and assess the quality of an online training format based on participant outcomes for the first three modules of a planned series of online ART training. Materials and Methods: These modules included manual semen analysis, sperm morphology and ancillary semen tests (testing for leukocytospermia, sperm vitality, and anti-sperm antibody screening). The virtual format consisted of lecture presentations featuring laboratory protocols with corresponding video demonstrations of routine techniques and best practices. Practical scenarios, troubleshooting, and clinical interpretation of laboratory results were also discussed. At the end of each module, an optional multiple choice question test was held as a prerequisite to obtain certification on the topics presented. Course quality was assessed using participant responses collected via online surveys. Results: The digital delivery methods used were found to have largely or completely met the participants’ expectations for all questions (>85%). The majority (>87%) of the participants either strongly agreed or agreed that the course content was well-structured with appropriate depth, and that their overall expectations of the course had been met. Conclusions: This training format appears to be a realistic teaching option to freely share highly specialized expertise and technical knowledge with participants from anywhere in the world with varying levels of competency or experience.

Background: Idiopathic causes of infertility is associated with oxidative stress. Antioxidants are known to scavenge the excessive production of reactive oxygen species (ROS). Green tea (Camellia sinensis) contains polyphenols that enhance its antioxidant potential. Aim: This study focused on the impact of aqueous green tea extract on normozoospermic human spermatozoa. Setting: Department of Medical Biosciences, University of the Western Cape (UWC), South Africa. Methods: Semen samples obtained using masturbation method following three to five days of sexual abstinence from consenting men (n = 59) at the University of the Western Cape (UWC) were liquefied and analysed. Normozoospermic samples were selected according to the World Health Organization (WHO) 5th guideline. Thereafter, semen samples (7.5 × 106 /mL) were washed in human tubular fluid (HTF; 10 min at 300 ×g) and exposed to aqueous extracts of green tea (0 μg/mL, 0.4 μg/mL, 4 μg/mL, 40 μg/mL, 405 μg/mL) for 1 h with various sperm parameters analyzed. Human tubular fluid supplemented with bovine serum albumin (HTF-BSA; 10%) served as control. Results: Sperm motility, reactive oxygen species production, across some reaction and deoxyribonucleic acid (DNA) fragmentation decreased significantly, particularly at the highest concentration (405 μg/mL; p 0.001). A substantial increase in the percentage of viable spermatozoa and those with intact mitochondrial membrane potential (MMP) were observed (p 0.001). Conclusion: Aqueous extract of green tea prolonged sperm viability and MMP while reducing sperm intracellular ROS production, capacitation and across some reaction and DNA fragmentation, and may be attributed to its antioxidant potential. However, a high concentration of the extract appears to be detrimental to the functioning of human spermatozoa.

Purpose: The use of antioxidants is common practice in the management of infertile patients. However, there are no estab-lished guidelines by professional societies on antioxidant use for male infertility. Materials and Materials and Methods:Methods: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. Results:Results: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3?? months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician?셲 age, geographic origin, experience or training in male infertility. Conclusions:Conclusions: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide under-standing of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Conventional semen analysis (SA) is an essential component of the male infertility workup, but requires laboratories to rigorously train and monitor technicians as well as regularly perform quality assurance assessments. Without such measures there is room for error and, consequently, unreliable results. Furthermore, clinicians often rely heavily on SA results when making diagnostic and treatment decisions, however conventional SA is only a surrogate marker of male fecundity and does not guarantee fertility. Considering these challenges, the last several decades have seen the development of many advances in SA methodology, including tests for sperm DNA fragmentation, acrosome reaction, and capacitation. While these new diagnostic tests have improved the scope of information available to clinicians, they are expensive, time-consuming, and require specialized training. The latest advance in laboratory diagnostics is the measurement of seminal oxidation-reduction potential (ORP). The measurement of ORP in an easy, reproducible manner using a new tool called the Male Infertility Oxidative Stress System (MiOXSYS) has demonstrated ORP’s potential as a feasible adjunct test to conventional SA. Additionally, the measurement of ORP by this device has been shown to be predictive of both poor semen quality and male infertility. Assessing ORP is a novel approach to both validating manual SA results and identifying patients who may benefit from treatment of male oxidative stress infertility.

It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.

Purpose: Male infertility is emerging as a major, escalating global health problem that imposes the need to investigate research trends in male infertility. The purpose of this study is to analyze male infertility research trends in the past 20 years using the bibliometric database from Scopus. Materials and Methods: In order to perform an in-depth bibliometric analysis, we propose a ‘Funnel Model’, which includes several layers representing different sub-areas of male infertility research. Adopting this Funnel Model, using Scopus, we retrieved relevant bibliometric data (articles per year, authors, affiliations, journals, and countries) for various areas of male infertility research and performed descriptive statistics. Results: The bibliometric analysis showed an exponential increase in male infertility research in the last 20 years. USA dominated in research output, with Agarwal, A. as the most prolific researcher. Testicular cancer, obesity and metabolic syndrome, and azoospermia were found to dominate male infertility research, whereas erectile dysfunction and unexplained male infertility had lesser attention. Interestingly, prognostic/diagnostic and mechanistic studies have significantly increased in parallel over the last 20 years. Furthermore, our bibliometric analysis revealed fewer publications in proteomics, transcriptomics and metabolomics when compared to genomics. Also, an increasing trend in publication was seen in assisted reproductive technology (ART) research. Conclusions: An integrated and steep escalation in the field of omics and ART research appears to be a prerequisite for further development of future diagnostic and therapeutic strategies for male infertility.

Background: The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines. Methods: A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores. Results: Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action. Conclusions: There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extracts based on identification of active constituents, as well as dosage and long-term safety studies are warrented.

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.

Purpose: Since its discovery in December 2019, the novel coronavirus SARS-CoV-2 has spread globally, causing the current COVID-19 (coronavirus disease-19) pandemic. As there is an increase of infections in the male population, concerns have emerged about the potential impact of COVID-19 on male reproductive organs and male fertility. Therefore, this study systematically investigates the current evidence of SARS-CoV-2 impact on male reproduction and pregnancy outcomes, discussing them in light of the evidence published on other coronaviruses. Materials and Methods: Literature search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 24 original articles were included for the analysis, investigating the effects of the infection on semen parameters, male reproductive hormones, and pregnancy outcomes. Further, a Strengths-Weaknesses- Opportunities-Threats (SWOT) analysis was conducted based on the available evidence linking the virus with male reproduction and conception. Results: Although there is limited data, viral mRNA has been identified in semen of infected men, with some evidence of altered seminal parameters. Low testosterone and dihydrotestosterone with raised luteinizing hormone has been reported as well as preterm delivery in pregnant women; however, data regarding vertical transmission remains contradictory and inconclusive. Conclusions: The recent literature provides evidence that male gonads may be potentially vulnerable to SARS-CoV-2 infection, recommending caution to pregnant women and couples planning natural pregnancy or assisted reproduction.

The practice of male infertility has dramatically evolved over the past few decades. This has been achieved after the realization of the important contribution the male counterpart holds in the couple’s infertility. It is also supported by a number of breakthroughs in the diagnosis and treatment of this medical condition. Several tests to investigate sperm quality and function were introduced along with refinements and/or institution of novel surgical techniques that can correct several causes of infertility. This manuscript is aimed at highlighting the current state of male infertility practice in a robust, schematic method addressing a broader audience involved in the treatment of male infertility.

IndiaPurpose: To evaluate the in vitro impact of ritalinic acid (RA), a major metabolite of methylphenidate (drug to treat attention-deficit hyperactivity disorder), on sperm motility, vitality and oxidative stress.Materials and Methods: Semen samples (n=13) were collected from healthy donors and a semen analysis was performed according to World Health Organization. Density gradient centrifugation was performed to isolate motile sperm. Samples were incubated with different concentrations (0, 1, 10, 100, and 1,000 ng/mL) of RA. The non-exposed group (0 ng/mL) was defined as the control group. Samples were analyzed for motility at different time points (0, 60, 150, 240, and 300 minutes) and for vitality and oxidation reduction potential (ORP) (at 0, 240, and 300 minutes). Sperm motility was assessed manually and motion kinetic parameters were recorded by computer aided semen analysis. Results: RA at any tested concentration significantly increased sperm motility compared to the control in a time-dependent manner with a maximum increase after 240 minutes. Motion kinetic parameters were not comparable. For sperm vitality, supplementation with RA significantly maintained survival at higher levels, while non-treated sperm gradually died. These higher levels of vitality were maintained with rising RA concentrations of up to 1,000 ng/mL. A non-significant trend of increased ORP was observed in all study groups.Conclusions: RA increases sperm motility and maintains vitality at any concentration tested. Therefore, RA might be utilized to improve sperm quality in asthenozoospermic specimens. However, further investigation is ongoing to evaluate the effect of RA on other sperm parameters.

Microtubules are the prime component of the cytoskeleton along with microfilaments. Being vital for organelle transport and cellular divisions during spermatogenesis and sperm motility process, microtubules ascertain functional capacity of sperm. Also, microtubule based structures such as axoneme and manchette are crucial for sperm head and tail formation. This review (a) presents a concise, yet detailed structural overview of the microtubules, (b) analyses the role of microtubule structures in various male reproductive functions, and (c) presents the association of microtubular dysfunctions with male infertility. Considering the immense importance of microtubule structures in the formation and maintenance of physiological functions of sperm cells, this review serves as a scientific trigger in stimulating further male infertility research in this direction.

Abstract Background This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999–2018) using a scientometric approach. Methods A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology. Results A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933). Conclusions Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes.

Varicocele, a condition associated with increased oxidative stress, negatively affects sperm DNA integrity and reduces pregnancy rates. However, the molecular mechanisms related to DNA integrity, damage, and repair in varicocele patients remain unclear. This study aimed to determine the role of DNA repair molecular mechanisms in varicocele-related infertility by combining an in silico proteomics approach with wet-laboratory techniques. Proteomics results previously generated from varicocele patients (n=50) and fertile controls (n=10) attending our Andrology Center were reanalyzed using bioinformatics tools, including the WEB-based Gene SeT AnaLysis Toolkit, Open Target Platform, and Ingenuity Pathway Analysis (IPA), to identify differentially expressed proteins (DEPs) involved in DNA repair. Subsequently, selected DEPs in spermatozoa were validated using western blotting in varicocele (n = 13) and fertile control (n = 5) samples. We identified 99 DEPs mainly involved in male reproductive system disease (n=66) and male infertility (n=47). IPA analysis identified five proteins [fatty acid synthase (FASN), myeloperoxidase (MPO), mitochondrial aconitate hydratase (ACO2), nucleoporin 93 (NUP93), and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14)] associated with DNA repair deficiency, which showed altered expression in varicocele (P

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

We would like to thank F. Pallotti and his colleagues for their positive comments [...]

Abstract During recent years, an increasing percentage of male infertility has to be attributed to an array of environmental, health and lifestyle factors. Male infertility is likely to be affected by the intense exposure to heat and extreme exposure to pesticides, radiations, radioactivity and other hazardous substances. We are surrounded by several types of ionizing and non-ionizing radiations and both have recognized causative effects on spermatogenesis. Since it is impossible to cover all types of radiation sources and their biological effects under a single title, this review is focusing on radiation deriving from cell phones, laptops, Wi-Fi and microwave ovens, as these are the most common sources of non-ionizing radiations, which may contribute to the cause of infertility by exploring the effect of exposure to radiofrequency radiations on the male fertility pattern. From currently available studies it is clear that radiofrequency electromagnetic fields (RF-EMF) have deleterious effects on sperm parameters (like sperm count, morphology, motility), affects the role of kinases in cellular metabolism and the endocrine system, and produces genotoxicity, genomic instability and oxidative stress. This is followed with protective measures for these radiations and future recommendations. The study concludes that the RF-EMF may induce oxidative stress with an increased level of reactive oxygen species, which may lead to infertility. This has been concluded based on available evidences from in vitro and in vivo studies suggesting that RF-EMF exposure negatively affects sperm quality.

Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.

Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, organelles, and DNA, alteration of enzymatic function, and apoptosis. ROS can be produced intracellularly, from immature sperm, oocytes, and embryos. Additionally, several external factors may induce high ROS production in the ART setup, including atmospheric oxygen, CO2 incubators, consumables, visible light, temperature, humidity, volatile organic compounds, and culture media additives. Pathological amounts of ROS can also be generated during the cryopreservation-thawing process of gametes or embryos. Generally, these factors can act at any stage during ART, from gamete preparation to embryo development, till the blastocyst stage. In this review, we discuss the in vitro conditions and environmental factors responsible for the induction of OS in an ART setting. In addition, we describe the effects of OS on gametes and embryos. Furthermore, we highlight strategies to ameliorate the impact of OS during the whole human embryo culture period, from gametes to blastocyst stage.

Abstract Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility.

Abstract Background Cytokines and hormones, including insulin, are known to modulate the hypothalamic-pituitary-testes axis and steroidogenesis, both centrally and peripherally. In the context of chronic inflammation and hyperinsulinaemia mediating male hypogonadism associated with obesity, metabolic syndrome and type 2 diabetes mellitus, these mechanisms are poorly understood and the impact of cytokines and insulin on Leydig cell steroidogenesis has not been fully elicited. This study aimed to further investigate the in vitro impact of TNFα, IL1ß, IL6, IL8 and insulin on Leydig cell function and steroidogenesis. Methods hCG-stimulated TM3 Leydig cells were exposed to various concentrations of TNFα, IL1ß, IL6, IL8 (100 ng/ml, 10 ng/ml, 1 ng/ml and 0.1 ng/ml) and insulin (10 ng/ml, 1 ng/ml, 0.1 ng/ml and 0.01 ng/ml) in optimal cell culture conditions over 48 h. Cell viability (XTT) and testosterone and progesterone concentrations (ELISA) were assessed using standardised laboratory techniques. Results TNFα significantly decreased cell viability and progesterone and testosterone concentrations in a dose-dependent relationship. IL1ß and IL6 had a subtle but significant negative effect on cell viability and testosterone concentrations, with a marked significant decrease in progesterone concentration at all concentrations investigated. IL8 showed an increase in cell viability, with no significant effect on testosterone concentrations alongside a significant decrease in progesterone concentrations. Insulin significantly increased cell viability and testosterone concentrations in a dose dependent relationship, but interestingly significantly decreased progesterone concentrations. Conclusions The inflammatory cytokines TNFα, IL1β and IL6 cause a dose dependent decline in steroidogenesis in TM3 Leydig cells. These results suggest that chronic inflammation may downregulate steroidogenesis in males via direct modulation of Leydig cell function. However, IL8 may stimulate TM3 Leydig cell growth. Insulin is associated with a dose-dependent increase in testosterone synthesis, with a significant decline in progesterone synthesis. With the phenomenon of insulin resistance, the literature is unclear on the potential role of hyperinsulinaemia in steroidogenesis. Further studies are warranted in order to fully elicit the molecular mechanisms and interactions of these molecules on male steroidogenesis.

Semen analysis is the cornerstone of male fertility evaluation with WHO guidelines providing the basis for procedural standardization and reference values worldwide. The first WHO manual was published in 1980, and five editions have been subsequently released over the last four decades. The 6th Edition was published in July 2021. In this review, we identify the key changes of this 6th Edition. Additionally, we evaluate the utility of this 6th Edition in clinical practice using SWOT (strengths, weaknesses, opportunities, and threats) analysis. This new Edition has made the analysis of basic semen parameters more robust, taking into account the criticisms and grey areas of the previous editions. The tests assessing sperm DNA fragmentation and seminal oxidative stress are well-described. The main novelty is that this latest edition abandons the notion of reference thresholds, suggesting instead to replace them with “decision limits”. While this seems attractive, no decision limits are proposed for either basic semen parameters, or for extended or advanced parameters. This critical review of the 6th Edition of the WHO laboratory manual combined with a SWOT analysis summarizes the changes and novelties present in this new Edition and provides an in-depth analysis that could help its global use in the coming years.

The male factor contributes approximately 50% to infertility-related cases in couples with an estimated 12%–35% of these cases attributable to male genital tract infections. Depending on the nature of the infection, testicular sperm production, sperm transport, and sperm function can be compromised. Yet, infections are potentially treatable causes of infertility. Male genital tract infections are increasingly difficult to detect. Moreover, they often remain asymptomatic (“silent”) with the result that they are then passed on to the relevant sexual partner leading to fertilization and pregnancy failure as well as illness of the offspring. With the worldwide increasing problem of antibiotic resistance of pathogens, proper diagnosis and therapy of the patient is important. This testing, however, should include not only aerobic microbes but also anaerobic as these can be found in almost all ejaculates with about 71% being potentially pathogenic. Therefore, in cases of any indication of a male genital tract infection, a semen culture should be carried out, particularly in patients with questionable semen quality. Globally, an estimate of 340 million new infections with sexually transmitted pathogens is recorded annually. Among these, the most prevalent pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, and Mycoplasma hominis. Escherichia coli are considered the most common nonsexually transmitted urogenital tract microbes. These pathogens cause epididymitis, epididymo-orchitis, or prostatitis and contribute to increased seminal leukocyte concentrations.

Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist′s profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact.

Antioxidants are used in the empirical treatment of infertile men. The aim of this study was to evaluate the effects of antioxidant therapy on conventional semen parameters and advanced sperm function tests in men seeking fertility treatment. A total of 148 infertile men of unknown etiology were divided into idiopathic (n = 119) and unexplained male infertility (UMI; n = 29). All participants were treated with the antioxidant supplement ‘FH PRO for Men’ for a period of three months. Compared with pretreatment results, there was a significant improvement in conventional semen parameters including sperm concentration, total and progressive motility and normal morphology, and seminal oxidation reduction potential (ORP), and sperm DNA fragmentation (SDF) in idiopathic infertile men. The changes were more prominent in idiopathic infertile men positive for ORP and SDF. UMI patients showed an improvement in progressive motility, ORP, and SDF after antioxidant treatment. Statistical analysis revealed that the efficacy of FH PRO for Men was significant in idiopathic male infertility compared with UMI. Treatment of idiopathic male infertility patients with the FH PRO for Men antioxidant regimen for three months resulted in a significant improvement in conventional semen parameters and sperm function. Therefore, FH PRO for Men offers promise for the medical treatment of idiopathic male infertility.