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.

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Oxidative stress and male infertility—a clinical perspective

This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

Selenium in human health and disease.

The purpose of this evidence summary is to provide the best available information on the effect of anti-oxidants on mortality in patients with various diseases.

/pdf/antioxidant-supplements-for-prevention-of-mortality-in-4y5qa95qy1.pdf

Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Spermatogenesis is an extremely active replicative process capable of generating approxi mately 1,000 sperm a second. The high rates of cell division inherent in this process imply correspondingly high rates of mitochondrial oxygen consumption by the germinal epithelium. However, the poor vascularization of the testes means that oxygen tensions in this tissue are low1 and that competition for this vital element within the testes is extremely intense. Since both spermatogenesis2 and Leydig cell steroidogenesis3,4 are vulnerable to oxidative stress, the low oxygen tension that characterizes this tissue may be an important component of the mechanisms by which the testes protects itself from free radical-mediated damage. In addition, the testes contain an elaborate array of antioxidant enzymes and free radical scavengers to ensure that the twin spermatogenic and steroidogenic functions of this organ are not impacted by oxidative stress. These antioxidant defence systems are of major importance because peroxidative damage is currently regarded as the single most important cause of impaired testicular function underpinning the pathological consequences of a wide range of conditions from testicular torsion to diabetes and xenobiotic exposure. This chapter sets out the specific nature of these antioxidant defence systems and also reviews the factors that have been found to impair their activity, precipitating a state of oxidative stress in the testes and impairing the latter’s ability to produce viable spermatozoa capable of initiating and supporting embryonic development.

/pdf/antioxidant-systems-and-oxidative-stress-in-the-testes-54n1pge1q7.pdf

Antioxidant systems and oxidative stress in the testes.

Background
Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm and 1 man in 20 will be affected by subfertility. Antioxidants are widely available and inexpensive when compared to other fertility treatments and many men are already using these to improve their fertility. It is thought that oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress. Pentoxifylline, a drug that acts like an antioxidant, was also included in this review.  

Objectives
This Cochrane review aimed to evaluate the effectiveness and safety of oral supplementation with antioxidants for subfertile male partners in couples seeking fertility assistance.

Search methods
We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO and AMED databases (from inception until January 2014); trial registers; sources of unpublished literature and reference lists. An updated search was run in August 2014 when potentially eligible studies were placed in 'Studies awaiting assessment'.

Selection criteria
We included randomised controlled trials (RCTs) comparing any type or dose of antioxidant supplement (single or combined) taken by the subfertile male partner of a couple seeking fertility assistance with a placebo, no treatment or another antioxidant.

Data collection and analysis
Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates, adverse events, sperm DNA fragmentation, sperm motility and concentration. Data were combined, where appropriate, to calculate pooled odds ratios (ORs) or mean differences (MD) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I2 statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods.  

Main results
This updated review included 48 RCTs that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy, one enrolled men with a varicocoele, and one recruited men with chronic prostatitis. Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial avenues or university grants. Thirty-three trials did not report any funding sources.

A limitation of this review was that in a sense we had included two different groups of trials, those that reported on the use of antioxidants and the effect on live birth and clinical pregnancy, and a second group that reported on sperm parameters as their primary outcome and had no intention of reporting the primary outcomes of this review. We included 25 trials reporting on sperm parameters and only three of these reported on live birth or clinical pregnancy. Other limitations included poor reporting of study methods, imprecision, the small number of trials providing usable data, the small sample size of many of the included studies and the lack of adverse events reporting. The evidence was graded as 'very low' to 'low'. The data were current to 31 January 2014.

Live birth: antioxidants may have increased live birth rates (OR 4.21, 95% CI 2.08 to 8.51, P< 0.0001, 4 RCTs, 277 men, I2 = 0%, low quality evidence). This suggests that if the chance of a live birth following placebo or no treatment is assumed to be 5%, the chance following the use of antioxidants is estimated to be between 10% and 31%. However, this result was based on only 44 live births from a total of 277 couples in four small studies.

Clinical pregnancy rate: antioxidants may have increased clinical pregnancy rates (OR 3.43, 95% CI 1.92 to 6.11, P < 0.0001, 7 RCTs, 522 men, I2 = 0%, low quality evidence). This suggests that if the chance of clinical pregnancy following placebo or no treatment is assumed to be 6%, the chance following the use of antioxidants is estimated at between 11% and 28%. However, there were only seven small studies in this analysis and the quality of the evidence was rated as low.

Miscarriage: only three trials reported on this outcome and the event rate was very low. There was insufficient evidence to show whether there was a difference in miscarriage rates between the antioxidant and placebo or no treatment groups (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I2 = 0%, very low quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, use of an antioxidant would result in the risk of a miscarriage lying between 1% and 13%.

Gastrointestinal upsets: there was insufficient evidence to show whether there was a difference in gastrointestinal upsets when antioxidants were compared to placebo or no treatment as the event rate was very low (OR 1.60, 95% CI 0.47 to 5.50, P = 0.46, 6 RCTs, 429 men, I2 = 0%).

We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as not enough trials compared the same interventions.

Authors' conclusions
There is low quality evidence from only four small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low quality evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage but this is uncertain as the evidence is of very low quality. Data were lacking on other adverse effects. Further large well-designed randomised placebo-controlled trials are needed to clarify these results.

Antioxidants for male subfertility

Numerous studies have reported beneficial effects of antioxidant drugs on semen quality, but there is no well-defined therapeutical protocol in male infertility. This study aimed to test the effect...

https://www.tandfonline.com/doi/pdf/10.1080/01485010390129269

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.

During the month of Ramadan, over one billion Muslims observe a water and food fast from sunrise to sunset. The practice of this religious duty causes marked changes in eating and sleeping habits. With the increasing incidence of cardiovascular (CV) risk factors, the number of patients with CV pathologies who wish to fast is increasing worldwide, and in Tunisia, which is ranked as a high CV risk country. If fasting has been shown to be beneficial for the improvement of some metabolic parameters, its practice in patients with CV pathology remains debated. The Tunisian Society of Cardiology and Cardiovascular Surgery (STCCCV) in consultation with the National Instance of Evaluation and Accreditation in Health (INEAS) has established this document in the form of a consensus after having analysed the literature with the aim of addressing these questions: -What is the impact of fasting in patients with CV pathologies? -How to stratify the risk of fasting according to CV pathology and comorbidities? -How to plan fasting in patients with CV diseases? -What are the hygienic and dietary measures to be recommended during fasting in patients with CV pathologies? -How to manage medication during the month of Ramadan in patients with CV diseases?

Management of patients with cardiovascular diseases during Ramadan.

La tuberculose représente un problème majeur de santé publique. Bien que l’efficacité des antituberculeux soit indéniable, leurs effets secondaires notamment hépatiques peuvent être sérieux. Le polymorphisme génétique concernant l’acétylation de l’isoniazide (INH) est responsable d’une répartition bimodale de la population en acétyleurs lents et rapides pouvant avoir des conséquences cliniques, notamment concernant ses effets indésirables. But : étudier le profil d’acétylation des patients traités pour tuberculose et évaluer l’intérêt du test d’acétylation dans leur suivi. Il s’agit d’une étude rétrospective descriptive menée dans notre service de pharmacovigilance sur une période de 21 ans allant de janvier 2000 à décembre 2020. Nous avons inclus les patients qui ont consulté pour effet indésirable à l’isoniazide et qui ont bénéficié d’un test d’acétylation au début du traitement antituberculeux. L’imputabilité médicamenteuse a été établie selon la méthode française de Bégaud et al. La saisie et l’analyse des données ont été réalisées en utilisant le logiciel Statistical Package for the Social Sciences (SPSS) dans sa 22e version. Nous avons colligé 31 dossiers de patients ayant présenté des effets indésirables à l’isoniazide. Notre population était à prédominance féminine (58,1 %). L’âge moyen était de 44,48 ± 16,62 ans. L’indication thérapeutique était une tuberculose maladie dans 100 % des cas. La localisation de la tuberculose était extrapulmonaire dans 74,2 % des cas, pulmonaire chez 19,4 % des patients et disséminée dans 6,5 % des cas. La forme thérapeutique prescrite était dissociée dans 87,1 % des cas et combinée dans 12,9 % des cas. L’indice d’acétylation moyen était de 0,86 ± 0,41. Nous avons constaté que le phénotype « acétyleur lent » était plus fréquent au sein de notre population d’étude (72,4 %). La concentration plasmatique moyenne de l’isoniazide était de 2,7 μg/mL [0,47–6,85]. Elle était supérieure à 2 μg/mL dans 56,7 % des cas. L’effet indésirable le plus constaté était une hépatotoxicité dans 74,2 % des cas. L’atteinte hépatique était cytolytique dans 52,2 % des cas, cholestatique dans des 13,8 % des cas et mixte dans 13 % des cas. La dose recommandée était inférieure à la dose prescrite chez 8 patients. La conclusion de l’enquête de pharmacovigilance était essentiellement une réintroduction de l’isoniazide après normalisation du bilan hépatique, en fonction de son indice d’acétylation dans 25,8 % des cas. Nos résultats incitent à effectuer le monitoring de l’isoniazide en pratique clinique et d’ajuster ses doses en se basant sur le statut d’acétylation afin d’éviter la survenue d’effets indésirables surtout hépatiques. 

Intérêt du test d’acétylation de l’isoniazide dans la gestion des effets indésirables chez les patients ayant une tuberculose

Depuis la pandémie mondiale du COVID-19 et l’avancement de la vaccination contre ce virus, des cas de péricardites chez les sujets jeunes ont été décrits surtout après vaccin à ARN messager mais l’association d’une pleurésie et d’une péricardite a été décrite seulement dans un seul cas dans la littérature. À notre connaissance, l’association d’une péricardite, pleurésie et d’un épanchement abdominal (polysérite) après vaccin COVID 19 à ARN messager n’a pas été décrite dans la littérature. Nous rapportons le premier cas de polysérite survenue après le vaccin COVID 19 Pfizer-BioNTech notifié au service régional de pharmacovigilance de Sfax. Il s’agit d’un patient âgé de 39 ans, sportif, sans ATCD particuliers, ayant reçu deux doses de vaccin anti-COVID-19 à ARN messager (Pfizer-BioNTech). La symptomatologie a débuté, 13 jours après la 2e dose de ce vaccin, marquée par l’apparition d’une douleur abdominale et épigastrique avec des frissons, des douleurs thoraciques et une dyspnée. Le patient a effectué un effort physique important dans les jours suivants la vaccination. Le patient a été hospitalisé. L’écho cardiaque a montré un décollement péricardique minime. La TDM abdominopelvien et thoracique a montré un épanchement pleural droit de moyenne abondance avec un collapsus en regard, une lame d’épanchement péricardique et du cul de sac du Douglas. La PCR COVID-19 était négative. Le bilan biologique a objectivé un syndrome inflammatoire : CRP 56, GB : 9180, dimères 2800, troponine : neg. Un angiosacnner a éliminé une embolie pulmonaire. L’analyse biochimique, bactériologique et l’examen cytologique du liquide pleural ont montré un liquide exsudatif avec absence de cellules atypiques et absence de mycobactéries tuberculosis. Le bilan immunologique et les marqueurs tumoraux étaient négatifs. L’évolution a été favorable après repos, antalgiques, et corticothérapie au bout de 2 mois. Nous rapportons le premier cas de polysérite survenue après vaccin anti-COVID-19 (Pfizer-BioNTech). Bien que cet évènement était un élément inquiétant pour ce patient, mais il reste une complication exceptionnelle et réversible. 

Polysérite après vaccin COVID-19 à ARN messager

La quadrithérapie bismuthée (QB) est une association d’inhibiteurs de la pompe à protons (IPP) et d’antibiotiques à type de métronidazole, cyclines et sels de bismuth. Il s’agit d’une alternative thérapeutique de l’infection à Helicobacter pylori (H. pylori) en première et aussi en deuxième ligne. Analyser la réponse à la quadrithérapie bismuthée et la comparer aux autres schémas thérapeutiques dans le traitement de deuxième ligne de l’infection à H. pylori. Étude prospective menée entre avril 2016 et janvier 2021, dans un service de gastroentérologie, incluant des patients ayant une gastrite active à H. pylori n’ayant pas répondu à un schéma thérapeutique de première ligne. L’échec d’éradication était documenté par une série de biopsies. Ont été exclus de l’étude tous les patients qui avaient refusé un contrôle systématique de l’éradication de H. pylori. Les traitements de deuxième ligne étaient la QB (IPP, cycline, métronidazole et sels de bismuth [Pylera*]), la quadrithérapie concomitante (QC) (IPP, amoxicilline, clarithromycine et métronidazole) et la trithérapie AL (IPP, amoxicilline et levofloxacine). La saisie et l’analyse des données ont été réalisées au moyen du logiciel SPSS version 23.0 avec un seuil de signification statistique fixé à 5 %. Au total, 104 patients ayant une gastrite active à H. pylori, traitée par un traitement de première ligne avec échec d’éradication, étaient inclus. L’âge moyen de nos patients était de 48,8 ± 14,8 ans avec un sexe-ratio (H/F) de 1,12. Une intoxication tabagique était notée chez 15 patients. La lésion initiale à l’endoscopie, la plus fréquente, était la gastropathie congestive (56,7 %). À l’histologie, 60,6 % avaient une atrophie et 18,3 % aveint une métaplasie intestinale gastrique. Les schémas utilisés en première ligne étaient les trithérapies (amoxicilline et clarithromycine ou métronidazole) ou la QC. Les schémas thérapeutiques des deuxièmes lignes administrés étaient la QB chez 53 patients, la QC chez 35 patients et la trithérapie AL chez 16 patients. Le taux d’efficacité de la QB était de 92,4 %, alors que celui de la QC de 60 % et de l’AL de 56,2 %. L’efficacité thérapeutique de la QB était supérieure à la QC (p = 0,001) et à l’AL (p = 0,002) dans l’éradication de H. pylori en deuxième ligne. En l’absence d’un traitement guidée par la résistance aux antibiotiques, la quadrithérapie bismuthée est supérieure à la quadrithérapie concomitante et à la trithérapie comportant la lévofloxacine en traitement de deuxième ligne de l’infection à H. pylori. 

K. Zghal

Papers

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.

Management of patients with cardiovascular diseases during Ramadan.

Intérêt du test d’acétylation de l’isoniazide dans la gestion des effets indésirables chez les patients ayant une tuberculose

Polysérite après vaccin COVID-19 à ARN messager

Le bismuth dans le traitement de la gastrite à Helicobacter pylori en deuxième ligne