The impact of male overweight on semen quality and outcome of assisted reproduction

The impact of obesity on male reproductive health remains a contested topic as evidence is inconclusive and inconsistent. Even more debatable is the effect of male obesity in assisted reproduction. In the manuscript, “the impact of male overweight on semen quality and outcome of assisted reproduction” published in Asian Journal of Andrology, Thomsen et al. investigated the effect of male obesity on fertilization outcomes in intrauterine insemination, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) programs further contributes to the increasing body of evidence in this field.Web of Scienc

The effect of insulin, leptin and inflammatory cytokines on reproductive health and hypogonadism in males diagnosed with the metabolic syndrome

Philosophiae Doctor - PhDThe metabolic syndrome (MetS) is a collection of various metabolic, hormonal and immunological risk factors that cluster together, closely related to poorly understood phenomena such a hyperinsulinaemia (insulin resistance), hyperleptinaemia (leptin resistance), a low grade, systemic and chronic inflammation and, in males, hypogonadism. Infertility is increasing globally, and male factor infertility accounts for a large percentage of couples who are not able to conceive. The relationship between components of MetS and male reproductive health is not clear, and requires further investigation, as does the impact of MetS on male reproductive health in a case controlled study. The impact of hyperinsulinaemia, hyperleptinaemia and inflammatory cytokines on the male reproductive tract also requires investigation. Furthermore, it is hypothesised that these phenomena negatively impact steroidogenesis cascades. In order to investigate this, a case controlled study and TM3 Leydig cell culture experiments were designed.Participants were recruited from public advertisements, and screened for strict exclusion criteria, including acute or chronic inflammation, hormonal treatments, vasectomy and leukocytospermia (> 106/ml). Following clinical diagnostics, 78 males were either placed into a control group (CG) or the MetS group, with numerous parameters compared between them. Serum was assayed for routine risk markers including HDL cholesterol, triglycerides, glucose and C-reactive protein (CRP). Saliva was assayed for free testosterone and progesterone. Semen samples underwent semen analysis for ejaculation volume, sperm concentration and motility, vitality, morphology and leukocyte concentration, in addition to mitochondrial membrane potential (MMP) and DNA fragmentation (DF). Both serum and seminal fluid were further assayed for insulin, leptin, tumour necrosis factor-alpha (TNF ) and interleukins 1-beta (IL1 ), 6 (IL6) and 8 (IL8). Glucose was also assayed in seminal fluid. Separately, hCG stimulated TM3 Leydig cells were exposed to varying concentrations of insulin (0.01, 0.1, 1 & 10 pg/ml), TNF , IL1 , IL6 and IL8 (0.1, 1, 10 & 100 pg/ml) for 48 hours at optimal cell culture conditions. TM3 cell viability, protein concentration and testosterone and progesterone concentrations were assessed.XXII Results indicated that males in the MetS group (n=34) had significantly increased body mass index, waist circumference, blood pressure, triglycerides, glucose, and Creactive protein (CRP) with decreased HDL cholesterol, as compared to the CG. Furthermore, ejaculation volume, sperm concentration, total sperm count, progressive and total motility were significantly decreased in the MetS group, and sperm with abnormal MMP and DF were increased in this group. No difference was found for morphology. Serum and seminal insulin, leptin, TNF , IL1 , IL6 and IL8 were all significantly increased in the MetS group. Both testosterone and progesterone were also significantly decreased in the MetS group. Insulin increased testosterone and decreased progesterone in the TM3 cells. TNF , IL1 and IL6 all decreased testosterone and progesterone concentrations and TM3 cell viability. IL8 increased TM3 cell viability and decreased progesterone, will no effect on testosterone. These results suggest MetS is associated with decreased fertility potential in males. Furthermore, a significant increase in seminal insulin, leptin, TNF , IL1 , IL6 and IL8 suggests local reproductive tract inflammation in the absence of leukocytospermia. Strong correlations between serum and seminal insulin, leptin, TNF , IL1 , IL6 and IL8, as well as serum CRP, imply that these systemic phenomenons are related to the reproductive tract changes observed. Therefore, the underlying pathophysiology of MetS negatively affects male reproduction, in addition to general health and wellbeing. A decrease in progesterone and testosterone suggests a collapse in steroidogenesis cascades. Additionally, inflammation, increased leptin and insulin resistance likely contribute to this collapse in steroidogenesis based on TM3 cell culture experiments. These results provide novel avenues for further investigations

A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility

Globally, infertility impacts 15% of couples trying to conceive. The incidence of male infertility has been increasing over the past several decades, ranging from 20% to 70% worldwide [1,2]. The male partner is found to be solely responsible in 20%–30% of cases, and contributes to couple infertility in approximately 50% of cases [3]. The etiologies and risk factors for male infertility are diverse. In addition to genetic causes, common acquired causes include varicocele, reproductive tract infections/inflammation, endocrine abnormalities, cryptorchidism, medications, malignancy, radiation and chemical or chemotherapy exposure, environmental and lifestyle factors, and underlying medical comorbidities [4]

The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease

Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male repro- ductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is com- monly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, ad-herence to the optimal body mass index, and dietary antioxidant supplementation and/or phyto-medicines.O

Utility of Antioxidants in the Treatment of Male Infertility: Clinical Guidelines Based on a Systematic Review and Analysis of Evidence

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 addi- tional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for anti- oxidant 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

Do lifestyle practices impede male fertility?

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

Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort

Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated.Web of Scienc

The Use of Probiotics in the Primary Prevention of Atopic Dermatitis: A Systemic Review of the Literature in Light of the Hygiene Hypothesis

Atopic dermatitis (eczema) is a type 1 hypersensitivity reaction that is common in infants and young children, with incidence increasing in the Industrialised world. Based on epidemiological evidence, the hygiene hypothesis proposes that reduced exposure to infective organisms is associated with immune dysfunction (Seroni et al., 2010). Caesarean sections, lack of breast feeding, lack of exposure to micro-organisms and parasites in early life, widespread use of antibiotics and a more hygienic or clean environment is closely associated with the development of atopic dermatitis. This is explained by type 2 helper T-lymphocyte (Th2) cell dominance and a reduction in T-regulatory (Treg) cell function due to lack of stimulation via infectious organisms (Boon et al., 2006; Seroni et al., 2010) (Fig. 1). Furthermore, altered gut microbiota and dysbiosis due to similar risk factors has been implicated in the development of atopic dermatitis (Kranich et al, 2011). There has been recent interest in the use of probiotics in the prevention of atopic dermatitis. The terms atopic dermatitis and atopy are incorrectly used interchangeable in much of the literature, and this study will follow this protocol

The impact of Covid-19 vaccines on male semen parameters: A retrospective cohort study

The emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic necessitated the development of adequate vaccines. Despite vaccines being demonstrated to be safe and effective for preventing severe disease and death, vaccine hesitancy remains. Reasons include concerns over adverse effects on male fertility, which have not been widely investigated. Therefore, this study is aimed at determining the impact of COVID-19 vaccination on semen parameters in a retrospective cohort study of South African males undergoing fertility assessment. The patients for this study were adult men who have previously undergone routine semen analysis for fertility assessment at Androcryos Andrology Laboratory (Johannesburg, South Africa) between March 2021 and March 2022. They also received vaccination within 3 months following a semen analysis and underwent a second semen analysis any time post-COVID-19 vaccination. From 277 records analysed, 46 patients met the inclusion criteria, receiving the Pfizer-BioNTech (BNT162b1) (63%), Johnson and Johnson (JNJ-78436735/Ad26.COV2S) (34.8%), and the AstraZeneca (AZD1222) (2.2%) vaccines. Sperm concentration significantly increased postvaccination (P = 0:0001), with no significant changes in semen pH, volume, total sperm count, progressive motility, normal sperm morphology, or chromatin condensation. Results were not influenced by age, type of vaccine received, and the number of days following vaccination, as depicted by multiple regression analysis. In conclusion, there is no evidence of a negative impact of COVID-19 vaccination on male semen parameters, which is consistent with the emerging literature on COVID-19 vaccination and male fertility. COVID-19 vaccinations should not be dismissed based on fear of adverse effects on male fertility parameters

The impact of COVID-19 on the male reproductive tract and fertility: A systematic review

Objective: The COVID-19 pandemic, caused by the acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), remains an ongoing public health challenge. Although males are affected slightly more than females, the impact of SARS-COV-2 on male reproductive system remains unclear. This systematic review aims to provide a concise update on the effects of COVID-19 on male reproductive health, including the presence of viral RNA in semen, and the impact on semen quality, testicular histology, testicular pain and male reproductive hormones. The global health is fronting an immediate as well as impending threat from the novel coronavirus (SARS- CoV-2) causing coronavirus disease (COVID-19), that inflicts more males than females. Evidence suggest that male reproductive system is susceptible to this viral infection. However, there are still several pertinent queries that remain to be fully explained regarding the mechanism in testicular SARS-CoV-2 dynamics and the exact mode of its actions. Thus, the present systematic review aims to provide a concise update on the effects of coronavirus disease 2019 (COVID-19) on male reproduction. Methods: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines searching the PubMed database. Eligibility for inclusion were original human studies evaluating the impact of COVID-19 on male repro- ductive health. Specific outcomes required for inclusion were at least one of the following: i) seminal detection of mRNA virus, or evaluation of ii) semen analysis, iii) testicular histology or ultrasonography, iv) testicular clinical symptoms and/or v) male reproductive hormones in COVID-19-positive patients. Results: Of 553 retrieved articles, 25 met the inclusion criteria. This included studies primarily investigating the presence of viral RNA in semen (n = 12), semen quality (n = 2), testicular histology (n = 5), testicular pain (n = 2) and male reproductive hormones (n= 4). Results show little evidence for the presence of viral RNA in semen, although COVID-19 seems to affect seminal parameters, induce orchitis, and cause hypogonadism. Mortality cases suggest severe histological disruption of testicular architecture, probably due to a systemic and local reproductive tract inflammatory response and oxidative stress-induced damage. Conclusions: Clinical evaluation of the male reproductive tract, seminal parameters and reproductive hormones is recommended in patients with current or a history of COVID-19,y treatment. Any long-term negative impact on male reproduction remains unexplored and an important future consideration