Genetic variants in varicocele-related male infertility: a systematic review and future directions.

Genetic association studies (GAS) may have the capability to probe the genetic susceptibility alleles in many disorders. This systemic review aimed to assess whether an association exists between gene(s)/allelic variant(s), and varicocele-related male infertility (VRMI). This review included 19 GAS that investigated 26 genes in 1,826 men with varicocele compared to 2,070 healthy men, and 263 infertile men without varicocele. These studies focussed on candidate genes and relevant variants, with glutathione S-transferase gene being the most frequently studied (n = 5) followed by the nitric oxide synthase 3 (NOS3) gene (n = 3) and the phosphoprotein tyrosine phosphatase 1 gene (n = 2). In one study the genes for NAD(P)H quinone oxidoreductase 1, sperm protamine, human 8-oxoguanine DNA glycosylase 1, methylenetetrahydrofolate reductase, polymerase gamma, heat shock protein 90, mitochondrial DNA, superoxide dismutase 2, transition nuclear protein 1, and transition nuclear protein 2, were assessed. There is no clear indication that any of these polymorphisms are sturdily associated with VRMI. However, three studies established that the polymorphic genotype (GT + TT) for rs1799983 polymorphism of the NOS3 gene is more frequent in varicocele patients. Further endeavours such as standardising reporting, exploring complementary designs, and the use of GWAS technology are justified to help replicate these early findings.

Pseudofolliculitis barbae treatment: Efficacy of topical eflornithine, long-pulsed Nd-YAG laser versus their combination.

BACKGROUND: Pseudofolliculitis barbae (PFB) is a chronic inflammatory disorder occurring mostly in regions of thick hair growth after shaving. PFB is characterized clinically by multiple painful, pruritic erythematous papules and, less commonly, pustules, nodules, or abscesses. AIM: To evaluate the efficacy of topical eflornithine cream only, long-pulsed Nd-YAG laser, versus their combination for PFB management. PATIENTS AND METHODS: Overall, 40 male patients with PFB were allocated into 3 treatment groups; Group 1 (n = 12): Treated by topical eflornithine cream twice daily for 16 weeks, Group II (n = 13): Treated by long-pulsed Nd-YAG laser for 4 sessions 4-week interval, Group III (n = 15): Treated by this combination for 16 weeks. The patients were evaluated after 16 weeks and for a further 12 weeks through serial photographs, Folliscopic evaluation, and a quartile grading system for improvement. RESULTS: After 16 weeks of treatments, the mean improvement percentages of the inflammatory papules, as well as hair density in the long-pulsed Nd-YAG laser +eflornithine cream, treated group were significantly higher compared with either eflornithine cream treated group or laser-only treated group. The same relationship was demonstrated after 12 weeks of follow-up but with lower improvements compared with 16 weeks of treatment outcome. CONCLUSIONS: Topical eflornithine cream exerts an additive effect on long-pulsed Nd-YAG laser in enhancing the rate and degree of hair reduction and inflammatory papules in PFB cases with a further follow-up improvement. This combined approach should be long-established in larger sample sizes and long-term studies.

Gene Variants in Premature Ejaculation: Systematic Review and Future Directions.

INTRODUCTION: A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature ejaculation (PE); however, the results remain inconclusive. OBJECTIVES: This systematic review aimed: (i) to determine whether an association exists between gene(s) or allelic variant(s) and PE; (ii) to assess whether the associations are consistent across studies in magnitude and direction, and (iii) to identify any limitation, gap, or shortcoming in the included studies. METHODS: The literature search was conducted in PubMed, MEDLINE, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases. RESULTS: Different gene variants associated with PE were assessed. 25 genetic association studies met the inclusion criteria that investigated 11 genes, 2,624 men with PE compared with 9,346 men as controls, twins, and siblings. 19 studies demonstrated a significant association with PE, whereas 4 studies denied such a relationship. SLC6A4 gene polymorphism was investigated in 11 studies (7 studies demonstrated a significant relationship with PE, and 4 studies denied such a relationship). Dopamine transporter gene (DAT1) polymorphism was investigated in 4 studies exhibiting a significant relationship. Androgen receptor gene polymorphisms were investigated in 2 studies, 1 with a significant relationship and the other with a non-significant relationship. Oxytocin gene polymorphisms and tryptophan hydroxylase 2 gene polymorphisms were investigated in 2 studies with a significant relationship. CONCLUSION: While this review has highlighted several genes that may be potentially associated with PE such as SLC6A4, limitations such as variance in study methods, lack of robust findings, small sample sizes, lack of reproducibility, quality of reporting, and quality of assessment remain a major concern. Further efforts such as standardizing reporting, exploring complementary designs, and the use of genome-wide association studies technology are warranted to test the reproducibility of these early findings. Mostafa T, Abdel-Hamid IA, Taymour M, et al. Gene Variants in Premature Ejaculation: Systematic Review and Future Directions. Sex Med Rev 2020;8:586-602.

Gene Polymorphisms Affecting Erectile Dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is usually developed from psychological, neurological, hormonal, and vascular pathologies or a combination of these factors. However, the possible genetic polymorphisms that might underlie this disorder were not thoroughly investigated. OBJECTIVES: This review article aimed to assess the possible involvement of gene polymorphisms in men with ED. METHODS: A systematic review was conducted until January 2020 based on a search of all relevant articles in many electronic sites such as PubMed, Medline Medical Subject Headings, Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, and Egyptian Knowledge Bank databases with no language restriction. Keywords used to assess the outcome and estimates for relevant associations were sexual health, genes, erectile dysfunction, polymorphisms, and cavernous tissues. RESULTS: Many genetic studies were carried out to inspect the contribution of different encoded genotypes and ED. Overall, 50 studies were reviewed and were classified as per the type of gene polymorphisms. These studies have investigated 10,174 men with ED compared with 6,891 healthy men as controls. 35 studies were case-controlled, 13 cross-sectional cohort studies, one retrospective study, and one genome-wide association study. So far, the most relevant gene polymorphisms linked with men with ED included endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), androgen receptor (AR) CAG repeat, G-protein ß3 (GNB3) subunit, methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), TGFB1, proprotein convertase subtilisin/kexin type 9 (PCSK9), ARG1, DRD2, DRD4, DDAH, and HNF4A genes. Both PROGINS and IGFBP-3 polymorphisms were investigated in only one study each but with irrelevant significance. CONCLUSIONS: Although several genetic studies exposed the association between different genotypes and men with ED with varied outcomes, such a relationship should not be overlooked. Therefore, more studies should be encouraged to elucidate the exact role, if any, for such association. Mostafa T, Taymour M. Gene Polymorphisms Affecting Erectile Dysfunction. Sex Med 2020;8:561-572.

TNF-α -308 polymorphisms and male infertility risk: A meta-analysis and systematic review.

This study aimed to conduct a systematic review and meta-analysis of prospective studies discussing TNF-α -308 polymorphism and male infertility. This study was conformed to Preferred Reported Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase and Scopus databases were searched to identify relevant studies by two independent reviewers. Hazard ratios were pooled using fixed-effect or random-effects models when appropriate. Q-test was performed to evaluate study heterogeneity and publication bias appraised using funnel plots. The search yielded five studies (three of Caucasians ethnicity and 2 of Asian ethnicity) comprising 2939 men (2262 infertile men and 677 fertile controls). Most of the studied cases were carried out on TNF-α promoter region at positions -308 G/A (four studies) where -308 C/T was dealt with in one study. Overall, significant associations between TNF-α -308 gene polymorphisms and idiopathic male infertility risk were observed (fixed effect: OR = 0.472, 95% CI: 0.378-0.589; P = 0.001; random effect: OR = 0.407, 95% CI: 0.211-0.785; P = 0.007) with robust findings according to sensitivity analyses. Funnel plot inspections did not give evidences of publication bias. A stratified analysis performed for ethnic groups revealed significant association in both Caucasian and Asian populations. It is concluded that there are evidences of associations between TNF-α -308 gene polymorphisms and male infertility risk.

Seminal clusterin gene expression associated with seminal variables in fertile and infertile men.

PURPOSE: CLU is a disulfide linked, heterodimeric protein associated with the clearance of cellular debris and apoptosis. We assessed the association of seminal CLU gene expression with seminal variables in fertile and infertile men. MATERIALS AND METHODS: A total of 124 men were divided into healthy, fertile men with normozoospermia, and men with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia. History was obtained, and clinical examination and semen analysis were done. In semen we assessed sperm acrosin activity, sperm DNA fragmentation and seminal CLU gene expression. RESULTS: CLU RNA and CLU protein gene expression were significantly increased in semen samples of infertile men with oligoasthenoteratozoospermia > asthenoteratozoospermia > asthenozoospermia compared with healthy, fertile controls. CLU gene expression significantly correlated negatively with sperm count, motility, acrosin activity index, linearity index and linear velocity, and significantly correlated positively with the percent of sperm abnormal forms and DNA fragmentation. CONCLUSION: CLU gene expression was significantly increased in the semen samples of infertile men. It correlated negatively with sperm count, motility, acrosin activity, linearity index and linear velocity, and positively with the percent of sperm abnormal forms and DNA fragmentation.