The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/tmi.13383

The COVID-19 epidemic.

Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.

/pdf/oxidative-stress-and-male-infertility-a-clinical-perspective-2nu3kdi0jn.pdf

Oxidative stress and male infertility—a clinical perspective

Diabetic autonomic neuropathy

https://uroweb.org/wp-content/uploads/Jungwirth-A-et-al-Eur-Urol-2012-622342-EAU-Guidelines-on-Male-Infertility-the-2012-update.pdf

European Association of Urology Guidelines on Male Infertility: The 2012 Update

BACKGROUND Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. OBJECTIVE AND RATIONALE To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. SEARCH METHODS PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. OUTCOMES SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). WIDER IMPLICATIONS This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

Summary
This review explores the role of carnitine in male infertility. The structure of this review is organized into short paragraphs that address the following aspects: antiapoptotic effect of l-carnitine on germ cells, effects of l-carnitine on conventional sperm parameters, in vitro effects of l-carnitine on sperm function, and the role of l-carnitine on erectile function.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12191

The role of carnitine in male infertility

Aim In the management of the chronic complications caused by diabetes mellitus, an important role is played to andrological problematics, which require a specialistic evaluation combined in order to concretely contribute to the improvement of quality of life of such patients. The erectile disfunction in the diabetic patient notoriously correlates with the main cardiometabolics risk factors, and recently it has been pointed out how after chronic use of inhibitors of the phospodiesterase-enzyme-5 (PDE5-I) it is possible to improve the vascular response profile, evaluated through ecolor doppler (ECD) penile dynamic. The incidence of the vascular extra-genital pathology in the patients with ED of organic arterial type has also been observed, underlining in particular the correlation with a low value of the systolic peak at penile level. Little attention has been paid to other andrologic pathologies that preliminary clinic evidences or less followed research points have individuated as real emerging problems; among them there are: 1) the hypogonadism in adult age (late onset hypogonadism); 2) the lower urinary tract symptoms (LUTS) correlated to the condition of prostatic hypertrophy; 3) the infections of the male genito-urinary tract with different characterization for imaging respect to the not diabetic population; 4) different sexual disorders; 5) implications over the male reproductive sphere. Methods Retrospective analysis of the clinic, laboratory (spermatic, microbiologic and hormonal), ultrasonography integrated data, led on a diabetic population examined during the last 3 years; finalized at the estimation of the distribution of the andrological pathology characterizing such population, with the comparison of the data on the basis of years of duration disease, grade of glicometabolic compensation and levels of total testosterone. Results ED was present in 16.36% of the examined population; 50% showed vascular arterial form; hypogonadism was present in 10% of the population. A very high prevalence of subfertility was observed 51.82%. The ultrasonographic characterization of the didimo-epididimary and prostatic-vesicular regions showed reduced testicular volume the 16.36% of cases, increase of the prostatic glandular volume in 45.45% of cases, altered thickness of the seminal vesicles in the 24.45% of cases. The microbiologic characterization evidences the contemporary positivity of the 3 prechosen indicators (spermiocolture, urinocolture, leukocytospermia) in 34.55% of patients. Conclusions The study has contributed to enrich the data relative to the heterogeneity of the clinic-andrological presentation of the diabetic patient.

Andrological characterization of the patient with diabetes mellitus.

Background and Objectives: Inositol is a component of the vitamin B com - plex. Myo-inositol (MYO) is the most biologically important form in nature. It is involved in several systemic processes and in mechanisms of sig - nal transduction in the plasma membrane as precursor of second messengers. On the male reproductive function, MYO appears to regulate seminal plasma osmolarity and volume; the ex - pression of proteins essential for embryogenetic development and sperm chemiotaxis; and sperm motility, capacitation, and acrosome reaction. Recently, a seminal antioxidant action has also been suggested. Aim of the Study: To evaluate the effects of MYO on sperm mitochondrial function and apop - tosis. Materials and Methods: Spermatozoa isolat - ed from 5 normozoospermic men and from 7 pa - tients with oligo-astheno-teratozoospermia (OAT) were incubated in-vitro with 2 mg/ml of MYO or placebo (control) for 2 hours. After this incubation period, the following sperm parame - ters were evaluated by flow cytometry: mito - chondrial membrane potential (MMP) by JC-1 staining; phosphatidylserine (PS) externalization by annexin V and propidium iodide double stain - ing; and chromatin compactness following pro - pidium iodide staining. Results: MYO did not affect the mitochondrial function of spermatozoa isolated from normo - zoospermic men, whereas it increased signifi - cantly the number of spermatozoa with high MMP and decreased significantly the number of those with low MMP in OAT patients. No effect of MYO was observed on PS externalization and chromatin compactness in both normozoosper - mic men and OAT patients. Conclusion: The data suggest that MYO is able to ameliorate mitochondrial function in OAT patients. We conclude that this compound may be useful for the treatment of male infertility.

/pdf/effects-of-myoinositol-on-sperm-mitochondrial-function-in-54cnqmgv5e.pdf

Effects of myoinositol on sperm mitochondrial function in-vitro.

Summary
Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12025

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study.

The present article describes the recent clinical experience and the main clinical and experimental evidences on this topic. In the first part, we present retrospective data collected over the last year on the semen quality and hormonal characteristics of the alcohol consumers evaluated in our centre. In the second part, we describe the mechanisms by which chronic alcohol intoxication impairs the testicular function (evidences for an ethanol-mediated effect at pre-testicular/testicular and post-testicular level). In the third part, we present data on ethanol taken a male risk factor of infertility, being present as one among other recreational drugs (also called lifestyle). Finally, is discussed the role of individual susceptibility factors and other variables.

S. La Vignera

Papers

The role of carnitine in male infertility

Andrological characterization of the patient with diabetes mellitus.

Effects of myoinositol on sperm mitochondrial function in-vitro.

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study.

Chronic consumption of alcohol and sperm parameters: our experience and the main evidences.