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Journal of Reproductive Immunology Mar 2022Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated... (Review)
Review
Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated fertility problems in females, data on males-related fertility are scarce, which explains the lack of guidance. The main objective of this systematic review was to evaluate the reproductive health in males with ARRDs. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until September 16, 2021, and tackling the effects of ARRDs and/or ARRDs treatments on male fertility and/or pregnancy outcomes, were included. A total of twenty-five studies met the inclusion criteria. They were published between 1981 and 2018. The studied ARRDs were spondyloarthritis (n = 9), systematic lupus erythematosus (SLE, n = 6), Behcet disease (BD, n = 5), rheumatoid arthritis (RA, n = 5), antiphospholipid syndrome (n = 1), and dermatomyositis (n = 1). The most reported effects of ARRDs on fertility are i) high levels of reproductive hormones, mainly in RA and SLE; ii) impaired semen quality in SLE, spondyloarthritis, and BD; and iii) higher rate of varicocele in BD and spondyloarthritis. Regarding the treatments effects, i) conventional synthetic disease-modifying anti-rheumatic drugs (e.g.; methotrexate and salazopyrine) increase testosterone level, ii) cyclophosphamide impairs fertility, iii) anti-tumor necrosis factor agents are associated with improvement in semen quality, and iv) no increased number of miscarriages or congenital abnormalities in children fathered by BD was reported. To conclude, both ARRDs and their treatments alter fertility in males with ARRDs. In practice, in addition to the conventional semen analysis, screening for infertility seems legitimate in males with ARRDs.
Topics: Autoimmune Diseases; Child; Female; Humans; Lupus Erythematosus, Systemic; Male; Pregnancy; Reproductive Health; Rheumatic Diseases; Semen Analysis; Spondylarthritis
PubMed: 34998078
DOI: 10.1016/j.jri.2021.103472 -
Andrologia Feb 2022The updated meta-analysis was conducted to further verify the effect of varicocele on sperm DNA damage, supplying clinicians and researchers with high-grade evidence.... (Meta-Analysis)
Meta-Analysis Review
The updated meta-analysis was conducted to further verify the effect of varicocele on sperm DNA damage, supplying clinicians and researchers with high-grade evidence. The sperm DNA damage was evaluated by DNA fragmentation index (DFI), associated with the male fertility capability tightly. PubMed, Web of Science and Cochrane Library were searched extensively for eligible studies with the search terms: varicocele, sperm DNA and sperm DNA damage. Finally, a total of 12 studies were included in our meta-analysis with a total of 845 patients diagnosed with varicocele and 2,377 healthy controls. A statistical difference of DFI between varicocele patients and healthy controls was found after pooling the data ((Standardised mean difference) SMD: 1.40, 95%CI: 0.83-1.98, p < .0001), using the random effect model. We conducted subgroup analysis according to study region (Brazil and Other countries), detection methods of DFI (TUNEL, Comet, and SCSA), sample size (<50 and >50) and age (<30 and >30 years), based on substantial heterogeneity among eligible studies. The stability of pooled results was verified by sensitivity analysis. All these statistical analyses were conducted using Stata version 16.0. In conclusion, patients diagnosed with clinical varicocele had higher DFI than healthy controls, which means varicocele could impair sperm DNA, consequently the fertility potential of affected men.
Topics: Adult; DNA Damage; DNA Fragmentation; Humans; Infertility, Male; Male; Spermatozoa; Varicocele
PubMed: 34658054
DOI: 10.1111/and.14275 -
Human Fertility (Cambridge, England) Jul 2023Genetic association studies (GAS) may have the capability to probe the genetic susceptibility alleles in many disorders. This systemic review aimed to assess whether an... (Review)
Review
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 ( = 5) followed by the nitric oxide synthase 3 (NOS3) gene ( = 3) and the phosphoprotein tyrosine phosphatase 1 gene ( = 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 polymorphism of the 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.
PubMed: 34587863
DOI: 10.1080/14647273.2021.1983214 -
International Journal of Reproductive... Aug 2021In recent years, the incidence of male infertility has increased worldwide. It is necessary to study the factors that influence male infertility in each area/region for...
BACKGROUND
In recent years, the incidence of male infertility has increased worldwide. It is necessary to study the factors that influence male infertility in each area/region for better management.
OBJECTIVE
To determine the factors affecting male infertility in the Iranian male population.
MATERIALS AND METHODS
An online search was conducted in electronic databases including PubMed, Google Scholar, SID, and Scopus to identify articles on the factors associated with male infertility, published in English and Persian. The keywords used to perform the search included "factor", "epidemiology", "causes of infertility", and "male infertility". The search was conducted without a time restriction, up to April 2020.
RESULTS
The search resulted in a total number of 691 studies. After an assessment of the articles, finally 14 studies were included in this study with a total number of 26,324 infertile males. The factors associated with male infertility included semen abnormalities, varicocele and testis disorder, smoking, exposure to heat, obesity, anabolic steroids, vascular abnormalities, anti-spermatogenesis factors, antidepressants, taking ranitidine and cimetidine, penile discharge and genital ulcers, painful micturition, occupational factors, alcohol, chronic disease, sexual disorder, Surgical and urological diseases, genetic factors and herpes infection. Among these, the semen and varicocele disorders were common in most studies.
CONCLUSION
The present review suggests that the factors affecting male infertility in Iran are similar to those reported from other countries. The results of this study can be used in adopting appropriate strategies for infertility management in Iran.
PubMed: 34568728
DOI: 10.18502/ijrm.v19i8.9615 -
Arab Journal of Urology 2021To investigate the usage and the efficacy of vitamins as primary or adjuvant treatment in infertile men with varicocele.
OBJECTIVE
To investigate the usage and the efficacy of vitamins as primary or adjuvant treatment in infertile men with varicocele.
METHODS
A systematic search in PubMed, the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Cochrane Library with the terms (varicocele) AND (vitamins) was performed. We searched for studies: a) reporting the administration of vitamins (individually or as part of a complex) in men with varicocele and infertility, b) primarily or adjuvant to invasive treatment, and c) reporting the impact on semen parameters and/or pregnancy rates. Exclusion criteria were animal, adolescent and non-English studies, grey literature and trials reporting abstracts only.
RESULTS
Seven studies were identified eligible for qualitative analysis. All studies were randomised except one (case series). Vitamins were administered dominantly as part of antioxidant complex and only two studies used vitamins (C and E, respectively) as sole agent. In two studies, vitamin monotherapy resulted in improvement in semen quality, but the effect on pregnancy rates is unknown. One study reported no efficacy of adjuvant multivitamin treatment after embolisation in terms of both semen quality and pregnancy rates. Finally, four studies reported a positive effect of vitamins on semen parameters after varicocelectomy, but the effect on pregnancy rates is conflicting; one study reported improved pregnancy rates with adjuvant treatment, two studies did not evaluate the pregnancy rates, and in one study the outcome was unclear due to missing data.
CONCLUSIONS
Vitamins have been used mostly as part of an antioxidant panel for the management of infertile men with varicocele. Most studies have found a positive impact on semen parameters in selected men with varicocele and infertility, as primary or adjuvant treatment. However, the clinical benefit of vitamins administration on pregnancy rate is under-evaluated and should be the target of future research.
PubMed: 34552778
DOI: 10.1080/2090598X.2021.1932124 -
Arab Journal of Urology 2021To review the role of elastography in the evaluation and decision-making of adult, infertile men with varicocele.
OBJECTIVE
To review the role of elastography in the evaluation and decision-making of adult, infertile men with varicocele.
METHODS
A systematic search using the terms (Elastography) AND (Varicocele), (Stiffness) AND (Varicocele), (Elastography) AND (Male infertility) was performed in Pubmed/Medline. Studies reporting a) elastographic characteristics in varicocele-bearing comparing to normal testicles, and b) the correlation of elastography with varicocele grading, parameters of spermatogenesis, and outcomes of varicocele treatment were selected. Exclusion criteria were animal, adolescents, abstracts, and non-English language studies.
RESULTS
In total, 453 articles were identified; 11 eligible studies were selected. Several modalities were used (shear wave elastography, strain elastography, quasistatic ultrasound elastography, acoustic radiation force impulse). Varicocele-bearing testicles have significantly different stiffness and elasticity in comparison to normal and non-varicocele testicles. Although not in full agreement, elastography readings are correlated with semen parameters. Conflicting results were reported regarding grading as most of the studies failed to demonstrate a significant correlation. Shear wave elastography showed a significant correlation with the improvement in semen parameters after varicocelectomy, but the association with pregnancy rates is unknown. Finally, no studies were identified comparing elastography with other modalities.
CONCLUSIONS
Elastography can detect changes in the architecture of varicocele-bearing testicles. Although the role of the modality in grading is uncertain, elastography showed a meaningful correlation with spermatogenesis parameters. Importantly, elastography readings could predict the improvement in semen parameters after varicocelectomy which is useful in terms of decision-making in infertile men with varicocele.
ABBREVIATIONS
ARFI: acoustic radiation force impulse; CDUS: colour Doppler ultrasonography; DWI: diffusion-weighted imaging; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SWE: shear wave elastography; VC: varicocele.
PubMed: 34552777
DOI: 10.1080/2090598X.2021.1964256 -
Arab Journal of Urology 2021: To review the available literature and identify factors associated with successful outcomes after varicocele repair (VR) in the setting of non-obstructive azoospermia... (Review)
Review
: To review the available literature and identify factors associated with successful outcomes after varicocele repair (VR) in the setting of non-obstructive azoospermia (NOA). : The PubMed and EMBASE databases were searched for relevant articles. Primary outcomes were return of spontaneous spermatogenesis, sperm retrieval rates (SRRs), and unassisted and assisted pregnancy rates. Histopathological subtypes, when available, were used for subgroup analysis. : A total of 16 articles were finally included. The average sample size was 43 and average duration of follow-up was 10.5 months. The average rate of primary spermatogenesis after VR was 27.3%. The average SRR, across five studies in men with NOA undergoing microscopic testicular sperm extraction status after varicocelectomy, was 48.9% vs 32.1% for the untreated cohort groups, and the average spontaneous pregnancy rate was 5.24%. Histopathology subtype was a significant contributing factor when analysed. : Varicocele repair should be considered in men with NOA, as it may allow some patients to avoid assisted reproductive technologies and improves success rates when utilised.
PubMed: 34552773
DOI: 10.1080/2090598X.2021.1956838 -
Antioxidants (Basel, Switzerland) Jul 2021In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. We performed a systematic review and meta-analysis... (Review)
Review
In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. We performed a systematic review and meta-analysis to explore their role in patients with operated or non-operated varicocele. We searched major databases and sources of grey literature until May 2021 (PROSPERO: CRD42021248195). We included 14 studies (980 individuals) in the systematic review. Of the 14 studies, 2 explored the effect of antioxidant supplementation in patients with non-operated varicocele, 1 compared antioxidants versus surgical repair of varicocele, while 11 explored antioxidants after surgical repair of varicocele and were also included in the meta-analysis. Regarding pregnancy rates, no significant differences were demonstrated after treatment with antioxidants versus no treatment at three (OR: 2.28, 95% CI: 0.7-7.48) and six months (OR: 1.88, 95% CI: 0.62-5.72). Accordingly, contradictory findings were reported in sperm concentration, morphology, and motility, as well as DNA fragmentation. Our findings indicate that antioxidant supplementation does not improve pregnancy rates and semen parameters in patients with varicocele-associated infertility, in the absence of previous screening for oxidative stress. Based on the previous notion, most included studies also raised methodological concerns. Therefore, definitive conclusions about the efficacy of antioxidant supplementation in this setting cannot be drawn and further research on the field is mandatory.
PubMed: 34356300
DOI: 10.3390/antiox10071067 -
Reproductive Sciences (Thousand Oaks,... Oct 2022Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha... (Review)
Review
Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha (HIF1-α) is associated with the incidence of hypoxia. In this study, we investigated the expression of HIF1-α in varicocele disease through a comprehensive systematic review. We searched PubMed, Scopus, Web of Science, and Embase databases to identify the related studies published up to February 2021. Human studies have demonstrated an increase in the HIF-1α protein expression in the internal spermatic vein (ISV) of the varicocele testicle. HIF-1α mRNA expression in the seminal plasma was significantly higher in infertile varicocele patient compared with fertile ones. Similarly, most animal studies demonstrated a significant increase in HIF-1α gene and protein expression in varicocele testicular tissue compared with control groups. The studies illustrated that hypoxia followed by increased expression of hypoxia-inducible factor 1-alpha (HIF1-α) mRNA and protein occurs in varicocele disease. Expression of HIF-1α regulates the expression of many genes, including VEGF, p53, GLUT, Bax, and Caspase-3, that could be involved in many of the varicocele pathophysiological effects such as DNA fragmentation and apoptosis of sperm cells. Further studies with a large number of patients are necessary and can provide more definitive evidence.
Topics: Animals; Caspase 3; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Male; RNA, Messenger; Semen; Tumor Suppressor Protein p53; Varicocele; Vascular Endothelial Growth Factor A; bcl-2-Associated X Protein
PubMed: 34313997
DOI: 10.1007/s43032-021-00696-y -
Jornal Vascular Brasileiro Apr 2021This systematic review was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, including... (Review)
Review
This systematic review was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, including clinical studies in which one of the outcomes was semen parameter improvement after varicocele embolization using coils only. The objective of the review was to assess the evidence on the role of embolization using coils alone for semen parameter improvement in men with varicocele, since embolization using coils is the most cost-effective method of varicocele repair. Study quality was assessed using the methodological index for non-randomized studies (MINORS). Out of six retrospective and two prospective observational or comparative clinical studies involving 701 patients, semen concentration improved significantly in all five studies that assessed this parameter. Mean semen motility improved significantly in seven studies. The impact of embolization on semen density could not be analyzed.
PubMed: 34093687
DOI: 10.1590/1677-5449.200137