Context: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.Evidence Acquisition: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.Evidence Synthesis/Results: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking.Conclusions: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.

Background: A number of different types of endocrine‐disrupting chemicals (EDCs) including bisphenol A, phthalates, pesticides, and other environmental chemicals have been shown to adversely impact upon male reproductive health. Understanding the potential effects of EDCs on male reproductive health may enable the development of novel treatments and early prevention of the effects of EDCs on male infertility and their potential long‐term sequelae. This review critically evaluates the research performed in this area and explores potential harmful effects of EDCs in animals and humans, including the possibility of trans‐generational transmission.Methods: A literature review was conducted using electronic databases using the following terms: ‘endocrine disrupt*’ OR ‘endocrine disruptors’ OR ‘endocrine disruptor chemicals’ OR ‘EDC’ AND ‘sperm*’ OR ‘spermatozoa’ OR ‘spermatozoon’ OR ‘male reproductive health’ OR’ male fertility’.Main findings: Several studies have shown that EDCs have a variety of pathophysiological effects. These include failure of spermatogenesis, embryonic development, the association with testicular cancer, and long‐term metabolic effects.Conclusions: Several studies observe correlations between chemical doses and at least one sperm parameter; however, such correlations are sometimes inconsistent between different studies. Mechanisms through which EDCs exert their pathophysiological effects have not yet been fully elucidated in human studies.

The role of kisspeptin in stimulating hypothalamic GnRH is undisputed. However, the role of kisspeptin signaling in testicular function is less clear. The testes are essential for male reproduction through their functions of spermatogenesis and steroidogenesis. Our review focused on the current literature investigating the distribution, regulation and effects of kisspeptin and its receptor (KISS1/KISS1R) within the testes of species studied to date. There is substantial evidence of localised KISS1/KISS1R expression and peptide distribution in the testes. However, variability is observed in the testicular cell types expressing KISS1/KISS1R. Evidence is presented for modulation of steroidogenesis and sperm function by kisspeptin signaling. However, the physiological importance of such effects, and whether these are paracrine or endocrine manifestations, remain unclear.

Objectives: To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women.Background: Complaints of impaired cognition and mood are common in the peri‐menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon.Design: A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included.Patients: Perimenopausal and menopausal women.Results: Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a ‘critical window’ for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri‐menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear.Conclusions: Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence‐based conclusions can be drawn.

Background Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS. Methods A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (<= 10RLU/SEC/10(6)sperm; n = 29) and High ROS (>10 RLU/SEC/10(6)sperm; n = 15) levels measured using an established colorimetric-luminol method. Results In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5 + 7.2, baseline; 32.6 + 9.5, post-treatment,P = .0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8 + 5.0, baseline: 39.4 + 6.2, post-treatment,P = .004; mean progressive sperm motility in % 23.1 + 4.6, baseline: 30.0 + 5.5, post-treatment,P = .014 vs. baseline). Conclusions We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians.

Background: There are no current pharmacological therapies to improve sperm quality in men with sub‐fertility. Reducing the exposure to lifestyle risk factor (LSF) is currently the only intervention for improving sperm quality in men with sub‐fertility. No previous study has investigated what proportion of men with sub‐fertility are exposed to adverse lifestyle factors. Furthermore, it is not known to what extent men with sub‐fertility are aware of lifestyle factors potentially adversely impacting their fertility.Methods: A cross‐sectional anonymous questionnaire‐based study on self‐reported exposure and awareness of LSF was conducted in 1149 male partners of couples investigated for sub‐fertility in a tertiary andrology centre in London, UK.Results: Seventy per cent of men investigated for sub‐fertility had ≥1 LSF, and twenty‐nine per cent had ≥2 LSF. Excessive alcohol consumption was the most common LSF (40% respondents). Seventeen per cent of respondents used recreational drugs (RD) regularly, but only 32% of RD users believed RD impair male fertility. Twenty‐five per cent of respondents were smokers, which is higher than the UK average (20%). Twenty‐seven per cent of respondents had a waist circumference (WC) >36 inches (91 cm), and 4% had WC >40 inches (102 cm). Seventy‐nine per cent of respondents wanted further lifestyle education to improve their fertility.Conclusions: Our data suggest that men with sub‐fertility are as follows: (a) exposed to one or more LSF; (b) have incomplete education about how LSF may cause male sub‐fertility; (c) want more education about reducing LSF. Further studies are needed to investigate the potential of enhanced education of men about LSF to treat couples with sub‐fertility.