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Showing papers in "Andrologia in 2021"


Journal ArticleDOI
TL;DR: The impact of obesity on the male reproductive system and fertility, including associated mechanisms, is discussed and weight management strategies, lifestyle changes, prescription medication, and complementary and alternative medicine in the management of obesity‐induced subfertility is discussed.
Abstract: Obesity is considered a global health problem affecting more than a third of the population. Complications of obesity include cardiovascular diseases, type 2 diabetes mellitus, malignancy (including prostatic cancer), neurodegeneration and accelerated ageing. In males, these further include erectile dysfunction, poor semen quality and subclinical prostatitis. Although poorly understood, important mediators of obesity that may influence the male reproductive system include hyperinsulinemia, hyperleptinemia, chronic inflammation and oxidative stress. Obesity is known to disrupt male fertility and the reproduction potential, particularly through alteration in the hypothalamic-pituitary-gonadal axis, disruption of testicular steroidogenesis and metabolic dysregulation, including insulin, cytokines and adipokines. Importantly, obesity and its underlying mediators result in a negative impact on semen parameters, including sperm concentration, motility, viability and normal morphology. Moreover, obesity inhibits chromatin condensation, DNA fragmentation, increases apoptosis and epigenetic changes that can be transferred to the offspring. This review discusses the impact of obesity on the male reproductive system and fertility, including associated mechanisms. Furthermore, weight management strategies, lifestyle changes, prescription medication, and complementary and alternative medicine in the management of obesity-induced subfertility is discussed.

94 citations


Journal ArticleDOI
TL;DR: This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing and recommendations on possible management strategies to overcome infertility related to spermDNA fragmentation, based on the best available evidence.
Abstract: We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.

86 citations


Journal ArticleDOI
TL;DR: In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19, and it seems that decreased sperm morphology was associated with the acute fever.
Abstract: The study investigated whether there is a male reproductive system coronavirus disease-2019 (COVID-19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study between April and May 2020. The participants were assigned in one of the three groups including COVID-19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS-CoV-2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID-19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID-19 and its treatment had no specific deteriorative effect on male sexual health at a short-time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID-19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.

84 citations


Journal ArticleDOI
TL;DR: The dual role of ROS in male reproduction is discussed, highlighting the physiological role as well as their pathological implications on male fertility.
Abstract: Reactive oxygen species (ROS) are free radicals derived from oxygen during normal cellular metabolism. ROS play a crucial role in the physiological processes and signalling pathways associated with male fertility. At physiological concentrations, ROS act as molecular mediators of signal transduction pathways involved in the regulation of the hypothalamic-pituitary-gonadal axis, spermatogenesis and steroidogenesis. They also trigger the morphological changes required for sperm maturation, such as DNA compaction and flagellar modification. Furthermore, ROS modulate crucial processes involved in the attainment of sperm fertilising ability such as capacitation, hyperactivation, acrosome reaction and sperm-oocyte fusion. Conversely, oxidative stress prevails when the concentration of ROS overwhelms the body's antioxidant defence. Various endogenous and exogenous factors enhance the synthesis of ROS resulting in the disruption of structural and functional integrity of spermatozoa through the induction of apoptotic pathway and oxidation of molecules, such as lipids, proteins and DNA. Therefore, maintenance of a balanced redox state is critical for normal male reproductive functions. This article discusses the dual role of ROS in male reproduction, highlighting the physiological role as well as their pathological implications on male fertility.

63 citations


Journal ArticleDOI
TL;DR: This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility and the impact of environmental exposures and lifestyle factors on gene expression to aid clinicians in developing individualised treatment strategies.
Abstract: Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y-chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies.

62 citations


Journal ArticleDOI
TL;DR: It is recommended that relevant lifestyle practices are investigated in clinical history of male infertility cases, particularly in unexplained or idiopathic male infertility, and Appropriate modification of detrimental lifestyle practices is further suggested and recommended in the management ofmale infertility.
Abstract: Alongside an increasing prevalence of couple and male infertility, evidence suggests there is a global declining trend in male fertility parameters over the past few decades. This may, at least in part, be explained through detrimental lifestyle practices and exposures. These include alcohol and tobacco consumption, use of recreational drugs (e.g., cannabis, opioids and anabolic steroids), poor nutritional habits, obesity and metabolic syndrome, genital heat stress (e.g., radiation exposure through cell phones and laptops, prolonged periods of sitting, tight-fitting underwear and recurrent hot baths or saunas), exposure to endocrine-disrupting chemicals (e.g., pesticide residue, bisphenol A, phthalates and dioxins) and psychological stress. This review discusses these lifestyle practices and the current evidence associated with male infertility. Furthermore, known mechanisms of action are also discussed for each of these. Common mechanisms associated with a reduction in spermatogenesis and/or steroidogenesis due to unfavourable lifestyle practices include inflammation and oxidative stress locally or systemically. It is recommended that relevant lifestyle practices are investigated in clinical history of male infertility cases, particularly in unexplained or idiopathic male infertility. Appropriate modification of detrimental lifestyle practices is further suggested and recommended in the management of male infertility.

61 citations


Journal ArticleDOI
TL;DR: Way in which oxidative stress has the potential to impact fertility in a negative way is seen, as well as subtle variations in the ways reactive oxygen species can operate.
Abstract: The effects of reactive oxygen species on male fertility are governed by the oxidative paradox, defined by a delicate balance between oxidative stress and antioxidant capacity. When regulated appropriately, reactive oxygen species ensure effective function; however, when uninhibited, they represent key players in male factor infertility. Mechanisms responsible for this include oxidative destruction of sperm lipid membranes, damage to gamete DNA both by gene mutation and by direct breakdown of the DNA backbone, mitochondrial dysfunction and apoptotic cell death. Utilizing various male pathologies as case studies, we see ways in which oxidative stress has the potential to impact fertility in a negative way. Varicocele, erectile dysfunction, testicular cancer and even idiopathic male infertility highlight common mechanistic pathways, as well as subtle variations in the ways reactive oxygen species can operate. Oxidative biomarkers have emerged to better study male infertility, predict reproductive success and modify assisted reproductive technologies to minimize oxidative stress.

54 citations


Journal ArticleDOI
TL;DR: In this article, the authors identified trends in internet search queries on public concerns regarding COVID-19 vaccine side effects on fertility that might impact vaccine uptake and used Google Trends to investigate queries in Google's Search Engine relating to the coronavirus vaccine and fertility between 10/24/2020 and 1/27/2021.
Abstract: The Emergency Use Authorization (EUA) of the COVID-19 vaccine on December 11, 2020 has been met with hesitancy for uptake with some citing potential impacts on future fertility. We hypothesised that irrespective of sex, fertility-related queries would markedly increase during the 48 days following EUA of the coronavirus vaccine. We sought to objectively identify trends in internet search queries on public concerns regarding COVID-19 vaccine side effects on fertility that might impact vaccine uptake. We used Google Trends to investigate queries in Google's Search Engine relating to the coronavirus vaccine and fertility between 10/24/2020 and 1/27/2021. The five most queried terms were identified as: 'COVID Vaccine Fertility', 'COVID Vaccine and Infertility', 'COVID Vaccine Infertility', 'COVID Vaccine Fertility CDC', and 'COVID 19 Vaccine Infertility' with an increase of 710.47%, 207.56%, 264.35%, 2,943.7%, and 529.26%, respectively, all p < .001. This study indicates that there was an increase in online COVID-19 vaccine-related queries regarding fertility side effects coinciding with the Emergency Use Authorization (EUA) on December 11, 2020. Our results objectively evidence the increased concern regarding the vaccine and likely demonstrate a major cause for hesitancy in vaccine uptake. Future studies and counselling with patients should be undertaken to help mitigate these concerns.

53 citations


Journal ArticleDOI
TL;DR: Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.
Abstract: Mitochondria have multiple functions, including synthesis of adenine triphosphate, production of reactive oxygen species, calcium signalling, thermogenesis and apoptosis. Mitochondria have a significant contribution in regulating the various physiological aspects of reproductive function, from spermatogenesis up to fertilisation. Mitochondrial functionality and intact mitochondrial membrane potential are a pre-requisite for sperm motility, hyperactivation, capacitation, acrosin activity, acrosome reaction and DNA integrity. Optimal mitochondrial activity is therefore crucial for human sperm function and semen quality. However, the precise role of mitochondria in spermatozoa remains to be fully explored. Defects in sperm mitochondrial function severely impair the maintenance of energy production required for sperm motility and may be an underlying cause of asthenozoospermia. Sperm mtDNA is susceptible to oxidative damage and mutations that could compromise sperm function leading to infertility. Males with abnormal semen parameters have increased mtDNA copy number and reduced mtDNA integrity. This review discusses the role of mitochondria in sperm function, along with the causes and impact of its dysfunction on male fertility. Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.

46 citations


Journal ArticleDOI
TL;DR: The escalating prevalence of male infertility and decreasing trend in sperm quality have been correlated with rapid industrialisation and the associated discharge of an excess of synthetic substances into the environment and the possible mechanisms of action are discussed.
Abstract: The escalating prevalence of male infertility and decreasing trend in sperm quality have been correlated with rapid industrialisation and the associated discharge of an excess of synthetic substances into the environment. Humans are inevitably exposed to these ubiquitously distributed environmental contaminants, which possess the ability to intervene with the growth and function of male reproductive organs. Several epidemiological reports have correlated the blood and seminal levels of environmental contaminants with poor sperm quality. Numerous in vivo and in vitro studies have been conducted to investigate the effect of various environmental contaminants on spermatogenesis, steroidogenesis, Sertoli cells, blood-testis barrier, epididymis and sperm functions. The reported reprotoxic effects include alterations in the spermatogenic cycle, increased germ cell apoptosis, inhibition of steroidogenesis, decreased Leydig cell viability, impairment of Sertoli cell structure and function, altered expression of steroid receptors, increased permeability of blood-testis barrier, induction of peroxidative and epigenetic alterations in spermatozoa resulting in poor sperm quality and function. In light of recent scientific reports, this review discusses the effects of environmental contaminants on the male reproductive function and the possible mechanisms of action.

45 citations


Journal ArticleDOI
TL;DR: The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of Sars‐Co V‐2 infection.
Abstract: The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin-converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS-CoV-2 are not fully elucidated. The major focus of the present studies is on the short-term complications of the coronavirus and gains importance on studying the long-term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS-CoV-2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID-19, possible formation of anti-sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS-CoV-2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID-19 along with other options such as sex-related hormones and semen analysis. Invasion of SARS-CoV-2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.

Journal ArticleDOI
TL;DR: The mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction and the clinical applicability of sperm DNA fragmentation testing are discussed.
Abstract: Male factor is responsible for up to 50% of infertility cases in the world Semen analysis is considered the cornerstone of laboratory evaluation of male infertility, but it has its own drawbacks and fails to predict the male fertility potential with high sensitivity and specificity Different etiologies have been linked with male infertility, of which sperm DNA damage has gained significant attention with extensive research on sperm function tests The associations between sperm DNA damage and a variety of disorders such as varicocele, obesity, cancer, radiation and lifestyle factors are explored in this review Furthermore, we discuss the mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction Finally, we review the clinical applicability of sperm DNA fragmentation testing in the management of male infertility

Journal ArticleDOI
TL;DR: It is proposed that high concentrations of seminal leukocyte and infectious agents may affect sperm function resulting in clumping of motile spermatozoa, decreasing acrosomal functionality and also causing alterations in sperm morphology.
Abstract: Declining birth rates are one of the problems facing society today. Male counterparts are responsible for about half of the infertility cases, and genitourinary tract infections may play a contributing role in approximately 15% of male infertility cases. Leukocytospermia is an established indicator of infection in the male urogenital tract, although other microorganisms such as bacteria and virus may also be contributors to the etiology of male infertility. The pathophysiology of these infectious agents may be initiated by a local inflammatory reaction resulting in an increase in reactive oxygen species (ROS). This results in testicular injury, thereby affecting sperm morphology, sperm motility, sperm viability and elevation of the seminal leukocyte as a result of the genital tract infection. The infectious and inflammatory changes can result in male infertility. It is proposed that high concentrations of seminal leukocyte and infectious agents may affect sperm function resulting in clumping of motile spermatozoa, decreasing acrosomal functionality and also causing alterations in sperm morphology. However, the literature has poorly clarified the role of infection in male infertility, provoking further debate and research on this topic.

Journal ArticleDOI
TL;DR: There is substantial evidence in the literature to show that infertile patients have lower seminal TAC in comparison with fertile men, and there is a positive correlation between TAC and seminal parameters, such as sperm concentration, motility and morphology.
Abstract: Oxidative stress is pre-empted by an adequate level of antioxidants, which scavenge oxidants when they are produced in excess by different sources, including leukocytes and immature spermatozoa. Enzymatic antioxidants, such as superoxide dismutase, catalase and glutathione peroxidase, and several non-enzymatic antioxidants (proteins, vitamins and minerals), working as oxidant scavengers and cofactors of enzymatic antioxidants have been identified in seminal plasma. The total antioxidant capacity (TAC) is a diagnostic test that can be utilised in the male infertility workup. TAC measures the amount of total antioxidants in seminal plasma. Therefore, it provides an assessment of the reductive potential in seminal plasma. Several studies have investigated the diagnostic application of TAC in various andrology conditions. There is substantial evidence in the literature to show that infertile patients have lower seminal TAC in comparison with fertile men. Moreover, there is a positive correlation between TAC and seminal parameters, such as sperm concentration, motility and morphology. Evaluation of TAC together with reactive oxygen species (ROS) and sperm DNA fragmentation index (DFI) may be beneficial in the diagnosis of male infertility.

Journal ArticleDOI
TL;DR: Testosterone levels seem to decrease during acute COVID‐19 infection, especially in the patient group with viral pneumonia, and when FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values.
Abstract: To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID-19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID-19 and those who were not. Any differences between those who had COVID-19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID-19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID-19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID-19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID-19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID-19 infection, especially in the patient group with viral pneumonia.

Journal ArticleDOI
TL;DR: Though several computer‐assisted sperm analysis (CASA) systems have been developed, conventional methods for semen analysis are still widely accepted in clinical practice and their diagnostic value in clinical andrology is summarized.
Abstract: Infertility is a major health issue affecting over 48.5 million couples around the world, with the male factor accounting for about 50% of the cases. The conventional semen analysis recommended by the World Health Organization (WHO) is the cornerstone in the evaluation of male fertility status. It includes macroscopic and microscopic evaluation of the ejaculate, which reflects the production of spermatozoa in the testes, the patency of the duct system and the glandular secretory activity. Evaluation of seminal fructose, sperm vitality and leucocytes (Endtz test) are useful adjuncts to semen analysis that provide information on specific clinical conditions. Though several computer-assisted sperm analysis (CASA) systems have been developed, conventional methods for semen analysis are still widely accepted in clinical practice. This review summarises the conventional techniques used in routine semen analysis and their diagnostic value in clinical andrology.

Journal ArticleDOI
TL;DR: Microsurgical varicocelectomy remains the gold standard treatment option for infertile men with a clinically palpable varicocele and abnormal semen parameters and newer evidence suggests a potential role for antioxidant supplementation and a meaningful role for patients destined for ART to improve pregnancy outcomes.
Abstract: Varicocele is the most common correctable cause for male infertility, but not all men with varicocele are affected equally by this condition. The pathophysiology of varicocele-induced fertility remains ill-defined. While evidence suggests that oxidative stress remains a central factor, other mechanisms likely include scrotal hyperthermia, reflux of metabolites, hypoxia and cadmium accumulation. Microsurgical varicocelectomy remains the gold standard treatment option for infertile men with a clinically palpable varicocele and abnormal semen parameters. Newer evidence suggests a potential role for antioxidant supplementation and a meaningful role of varicocelectomy for patients destined for ART to improve pregnancy outcomes.

Journal ArticleDOI
TL;DR: In this article, the impact of SARS-CoV-2 infection on semen parameters in a cohort of men who had recently recovered from COVID-19 was investigated, and the results showed that sperm motility and total motile sperm count were the semen parameters which showed a significant reduction in cases with a history of mild CoV-19 infection.
Abstract: In this prospective study, we investigated the impact of SARS-CoV-2 infection on semen parameters in a cohort of men who had recently recovered from COVID-19. A total of 24 men who had recently recovered from mild COVID-19 were included in the study. Their semen parameters were normal before COVID-19 according to the World Health Organization 2010 reference values. Semen samples were collected from these participants in the recovery phases of COVID-19. To determine the effect of SARS-CoV-2 infection on semen parameters, the patients' pre-COVID-19 and post-COVID-19 semen analyses were compared. The mean age of the participants was 34.7 ± 6.4 years. The median interval between the positive nasopharyngeal swab test and obtaining semen samples was 111.5 (158) days. There was no significant difference in semen parameters before and after COVID-19 in terms of semen volume (p = .56), sperm concentration (p = .06), and progressive motility (p = .14). Total motility (p = .01) and total motile sperm count (p = .02) decreased significantly after SARS-CoV-2 infection compared to the pre-infection values. This study demonstrated that sperm motility and total motile sperm count were the semen parameters which showed a significant reduction in cases with a history of mild COVID-19.

Journal ArticleDOI
TL;DR: In this article, a cross-sectional study in 18 to 55-year-old men hospitalised for confirmed COVID-19 infection was conducted, where a senior radiologist executed the ultrasound with multi-frequency linear probe in all participants, regardless of any scrotal complaints.
Abstract: The testis is a potential target organ for SARS-CoV-2 infection. Our study intended to investigate any testicular involvement in mild-to-moderate COVID-19 men. We conduct a cross-sectional study in 18 to 55-year-old men hospitalised for confirmed COVID-19. A senior radiologist executed the ultrasound with multi-frequency linear probe in all participants, regardless of any scrotal complaints. Exclusion criteria involved any situation that could impair testicular function. Statistical analysis compared independent groups, classified by any pathological change. Categorical and numerical outcome hypotheses were tested by Fisher's Exact and Mann-Whitney tests, using the Excel for Mac, version 16.29 (p 1.2 cm (p = .002). Two distinct epididymitis' patterns were reported: (a) disseminated micro-abscesses (n = 6) and (b) inhomogeneous echogenicity with reactional hydrocele (n = 5). Both patterns revealed increased epididymal head, augmented Doppler flow and scrotal skin thickening. The use of colour Doppler ultrasound in mild-to-moderate COVID-19 men, even in the absence of testicular complaints, might be useful to diagnose epididymitis that could elicit fertility complications.

Journal ArticleDOI
TL;DR: The protocol, quality control and measurement of sperm DNA fragmentation using a benchtop flow cytometer using the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐nick end labelling TUNEL assay using flow cytometry is described.
Abstract: Sperm DNA integrity is important for normal functions such as fertilization, implantation, pregnancy and fetal development. Sperm DNA fragmentation (SDF) is more common in infertile men and may be responsible for poor reproductive function. Although there are a number of tests available to measure SDF, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling TUNEL) assay using flow cytometry is becoming more popular to measure the sperm DNA fragmentation. It is a direct test that measures both single- and double- DNA strand breaks. In this review, we describe the protocol, quality control and measurement of sperm DNA fragmentation using a benchtop flow cytometer. We also briefly discuss the factors that can affect the results, challenges and clinical implications of TUNEL in assessing male infertility.

Journal ArticleDOI
TL;DR: Attention is drawn to recognise a disturbed epididymal environment as a potential cause of male infertility because the data are limited regarding critical markers of sperm maturation and studies that can identify such markers for diagnosis and managing epididcyal dysfunction are scarce.
Abstract: The diagnosis and treatment of male infertility, excluding assisted conception, are limited because of, but not limited to, poor understanding of sperm post-testicular development and storage. Many may think that sperm dysfunction is only self-contained in the sperm cell itself as a result of defective spermatogenesis. However, it can also be a consequence of inadequate epididymal maturation following disorders of the epididymis. Improper epididymal functions can disturb semen parameters and sperm DNA integrity, result in high leucocyte concentrations and high numbers of immature germ cells and debris or even cause idiopathic infertility. To date, the data are limited regarding critical markers of sperm maturation and studies that can identify such markers for diagnosis and managing epididymal dysfunction are scarce. Therefore, this article aims to draw attention to recognise a disturbed epididymal environment as a potential cause of male infertility.

Journal ArticleDOI
TL;DR: Genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues and the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms.
Abstract: COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors' expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.

Journal ArticleDOI
TL;DR: Different methods used to evaluate sperm chromatin integrity and condensation are discussed and compared, and their inclusion in the routine evaluation of the male infertility is compared.
Abstract: Male infertility has a complex etiology, and many times, the cause is unknown. While routine semen analysis provides an overview of basic semen parameters, such as sperm concentration, motility, viability and morphology, a significant overlap of these parameters has been reported in fertile and infertile men. Moreover, conventional semen parameters do not reveal the cellular or molecular mechanisms of sperm dysfunctions leading to infertility. Therefore, sperm functional parameters, including sperm chromatin integrity, are evaluated to provide information on subtle sperm defects that are not routinely identified. Incomplete or defective sperm chromatin condensation increases the susceptibility of the sperm DNA to oxidative damage or other factors. To evaluate sperm chromatin integrity, different methods with varying degrees of diagnostic and prognostic capabilities are available. Among these assays, SCSA, TUNEL and SCD assays are most commonly used. While these assays rather evaluate the DNA directly for damages, the aniline blue and chromomycin A3 stains test for the quality of chromatin condensation. Thus, this review discusses and compares different methods used to evaluate sperm chromatin integrity and condensation, and their inclusion in the routine evaluation of the male infertility.

Journal ArticleDOI
TL;DR: Sperm DNA integrity of clinical varicocele patients was significantly improved following varicocelectomy, and it is necessary to include elevated sperm DNA fragmentation index as a molecular indicator for varicoCElectomy among clinicalvaricocele cases.
Abstract: Varicocele is common among male adolescents and adults. Varicocelectomy is the major means of varicocele repair. There is evidence that varicocelectomy could decrease sperm DNA fragmentation. However, studies evaluating the efficacy of varicocelectomy for sperm DNA integrity usually have a small sample size, and there is no up-to-date meta-analysis in this area. The present meta-analysis is to evaluate the efficacy of varicocelectomy for sperm DNA integrity. A literature search was conducted to identify all relevant studies from Medline database (PubMed), Cochrane Library, and OVID Embase from the inception dates to 08 June 2020. A total of 11 prospective studies including 394 cases were included in this meta-analysis. All analysis was performed using Stata version 16.0. In the random-effect model for 11 studies, DNA fragmentation index (%) of clinical varicocele patients decreased by 5.79 (95% CI, -7.39 to -4.19) after varicocelectomy. While after excluding one study with high heterogeneity, from the results of fixed-effect model, DNA fragmentation index decreased by 6.14 (95% CI, -6.90 to -5.37) on average. Sperm DNA integrity of clinical varicocele patients was significantly improved following varicocelectomy. Therefore, it is necessary to include elevated sperm DNA fragmentation index as a molecular indicator for varicocelectomy among clinical varicocele cases.

Journal ArticleDOI
TL;DR: In this review, different sperm selection strategies for retrieving spermatozoa with the highest fertilising potential and their impact on ART outcomes are discussed.
Abstract: The application of assisted reproductive technologies (ART) has revolutionised the treatment of human infertility, giving hope to the patients previously considered incapable of establishing pregnancy While semen analysis is performed to access whether a sample has an adequate number of viable, motile and morphologically normal sperm cells able to achieve fertilisation, sperm selection techniques for ART aim to isolate the most competent spermatozoon which is characterised by the highest fertilising potential Based on the semen analysis results, the correct sperm selection technique must be chosen and applied In this review, different sperm selection strategies for retrieving spermatozoa with the highest fertilising potential and their impact on ART outcomes are discussed In addition, advantages and disadvantages of each method and the best suited techniques for each clinical scenario are described

Journal ArticleDOI
TL;DR: In this article, the impact of the COVID-19 outbreak on the sexual function of healthcare professionals has been investigated using the IES-R and the Index of Erectile Function (IIEF-5).
Abstract: Studies have shown that healthcare professionals struggling with epidemics develop symptoms of post-traumatic stress disorder. The aim of this study is to show how often and severely erectile dysfunction, one of the components of post-traumatic stress disorder, is seen among healthcare professionals during COVID-19 outbreak. The Impact of Event Scale-Revised (IES-R) and the Index of Erectile Function-5 (IIEF-5) were applied to 159 male healthcare professionals working in COVID-19 units and a control group of 200 people. Healthcare professional group was divided into subgroups according to occupation (physician, nurse), age-group (18-25, 26-30, >30), marital status and unit of work (Suspected Patient Area, Diagnosed Patient Area). Both stress disorder and erectile dysfunction were seen at higher rates in healthcare professionals group (p < .001). The median IIEF-5 scores of nurses, married subjects and those working in the Diagnosed Patient Area, were found to be higher (p < .001, p = .014, p = .011 respectively). During the COVID-19 outbreak, healthcare professionals are exposed to psychological trauma and their sexual function may be negatively affected. The measures to be taken are important to estimate which groups are more affected.

Journal ArticleDOI
TL;DR: In this article, the authors evaluated the quality of information on YouTube regarding penile prosthesis and found that the quality according to PEMAT and DISCERN score is mostly poor.
Abstract: The purpose of this study is to evaluate the quality of information on YouTube regarding penile prosthesis. We searched the term 'penile prosthesis' on YouTube recording the first 100 video links. Each video was analysed by three evaluators through the validate Patient Education Materials Assessment Tool (PEMAT), the DISCERN quality criteria for consumer health information and a misinformation assessment tool specifically created for this subject. All the videos were viewed 10'011'232 times. Median duration time was 5'13″ (IQR = 7'25″-1'58″). Sixty-eight per cent were nonsurgical videos and 32% of them contained surgical procedures. Most of the videos were uploaded by Private Companies (51%). Videos were primarily directed at patients (73 of 100 videos). The mean PEMAT understandability score was 57.8% ± 19.2%, the actionability score was 0% (IQR = 33%-0%). The median DISCERN score was 26 (IQR = 30-21). None of the videos provided a complete patients' information and the overall mean misinformation score was 3.21 ± 2.24. Based on our data, video's quality according to PEMAT and DISCERN score is mostly poor. Furthermore popularity does not correlate with the quality of the videos, and most of them fail to provide adequate patient's information.

Journal ArticleDOI
TL;DR: The focus of this article is to present recent evidence assessing the viability of antioxidant therapy in the treatment of male infertility.
Abstract: Oxidative stress is caused by an imbalance between ROS and antioxidants, which plays a significant role in the pathophysiology of many human diseases. There is extensive evidence highlighting the role of oxidative stress in male infertility due to elevated levels of sperm DNA fragmentation and abnormal semen parameters. The use of antioxidants is a potential therapeutic option to reduce ROS and improve semen quality. The appeal is that antioxidants can be easily obtained over the counter and are considered all-natural and therefore healthy. The hypothesis has been that by decreasing oxidative stress, antioxidants may be used for the treatment of male infertility. While initial studies of antioxidant supplementation suggested a beneficial role in the management of male subfertility, additional research has questioned the benefit of these therapies. The focus of this article is to present recent evidence assessing the viability of antioxidant therapy in the treatment of male infertility.

Journal ArticleDOI
TL;DR: In this article, an up-to-date review and discussion to collectively reveal the effect of SARS-CoV-2 infection on human semen quality is provided, which reveals that, at both symptomatic and recovery stages of infection, no investigational evidence of shedding in human semen.
Abstract: Revealing the effect of SARS-CoV-2 infection on semen quality is a dynamic priority for many healthcare providers in the field as well as subfertile patients. Therefore, the collective summary in this research approach is still highly needed, especially with the continuous increase in original publications. Here, we provide an up-to-date review and discussion to collectively reveal the effect of SARS-CoV-2 infection on human semen quality. To do this, we reviewed all articles and abstracts published in Scopus and PubMed using the keywords 'SARS-CoV-2' and 'COVID' versus 'sperm' and 'semen'. In summary, it can be revealed that, at both symptomatic and recovery stages of infection, no investigational evidence of SARS-CoV-2 shedding in human semen. Also, the mainstream of the up-to-date published work reveals a negative impact of SARS-CoV-2 infection on semen quality parameters, particularly sperm count and motility. However, long-term post-recovery comparative studies seem very important in this particular setting.

Journal ArticleDOI
TL;DR: It is found that normal sperm parameters per se do not reliably account for fertility in the real‐life setting and the longer the infertility period, the greater the number of sperm parameters abnormalities.
Abstract: A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.