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Reproductive Biology and Endocrinology... Jan 2023Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF.
METHODS
We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals.
RESULTS
We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52).
CONCLUSION
Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF.
TRIAL REGISTRATION
CRD42021282533.
Topics: Humans; Male; Middle Aged; Semen; DNA Fragmentation; Varicocele; Glucose Intolerance; Spermatozoa; Life Style; Testicular Neoplasms; Infertility, Male
PubMed: 36653793
DOI: 10.1186/s12958-023-01054-0 -
European Journal of Medical Research Jan 2023Oligoasthenospermia (OAT) is the most common cause of male infertility, and the annual incidence of the disease continues to increase due to changing lifestyle habits,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oligoasthenospermia (OAT) is the most common cause of male infertility, and the annual incidence of the disease continues to increase due to changing lifestyle habits, increased work pressure and increased environmental pollution. A variety of nonpharmacological therapies have been reported to be effective for treating OAT; however, there is a lack of direct evidence comparing these different nonpharmacological therapies. Therefore, the optimal strategy has yet to be identified.
OBJECTIVES
A network meta-analysis was performed to evaluate the efficacy and safety of nonpharmacological treatments for OAT, thus providing an evidence-based medical reference for the clinical treatment of oligoasthenospermia.
METHODS
The Web of Science, Cochrane Library, Embase, PubMed, Weipu (VIP), Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature (CBM) databases were searched from inception to April 2022 to identify randomized controlled trials (RCTs) that examined nonpharmacological treatments for oligozoospermia. Grey literature was also searched. Studies that met the quality criteria were analysed using Stata 16.0 and Review Manager 5.4 software.
RESULTS
A total of 4629 publications were initially retrieved; ultimately, 38 RCTs were analysed, including 8 nonpharmacological therapies and 3080 patients. Each intervention outperformed the sham intervention and no treatment approaches in terms of improved efficacy. In terms of improved total effective rate and sperm concentration, warming acupuncture may be the most effective treatment (SUCRA = 80.1% and 93.4%, respectively). Electroacupuncture perhaps resulted in the best improvement in sperm motility a% and a + b% (SUCRA = 96.6% and 82.0%, respectively). In terms of the incidence of adverse reactions, the three safest interventions probably were no treatment, warming acupuncture, and sham intervention (SUCRA = 88.0%, 68.8% and 62.9%, respectively). In terms of improving the reproductive hormones FSH, LH, and T, the best interventions perhaps were hyperbaric oxygen, 2 Hz TEAS, and electroacupuncture (SUCRA = 85.1%, 96.8% and 99.4%, respectively).
CONCLUSIONS
Nonpharmacological treatments for oligoasthenospermia have good clinical efficacy. Warm acupuncture and electroacupuncture have better overall efficacy and safety. These treatment approaches can be recommended based on the actual situation. If a patient is complicated with varicoceles, they should be removed before symptomatic treatment. Due to the limitations of the quality of the included studies, the findings need to be further validated.
Topics: Humans; Male; Acupuncture Therapy; Electroacupuncture; Network Meta-Analysis; Treatment Outcome
PubMed: 36600309
DOI: 10.1186/s40001-022-00968-6 -
The World Journal of Men's Health Apr 2023Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains...
PURPOSE
Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls.
MATERIALS AND METHODS
A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies).
RESULTS
A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%).
CONCLUSIONS
This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.
PubMed: 36326166
DOI: 10.5534/wjmh.220142 -
Archivio Italiano Di Urologia,... Sep 2022Varicocele is known to have impacts in infertility cases and sperm quality. This review aimed to evaluate the effects of microsurgical varicocelectomy on sperm DNA... (Meta-Analysis)
Meta-Analysis
Microsurgical varicocelectomy effects on sperm DNA fragmentation and sperm parameters in infertile male patients: A systematic review and meta-analysis of more recent evidence.
BACKGROUND
Varicocele is known to have impacts in infertility cases and sperm quality. This review aimed to evaluate the effects of microsurgical varicocelectomy on sperm DNA fragmentation index (DFI) and sperm parameters.
METHODS
Open full English text articles from January 2017 to October 2021 were searched from online database including PubMed, EMBASE, Scopus, Cochrane Library and Google Scholar.
RESULTS
Systematic search resulted in 277 potential papers. After throughout paper analysis, 5 studies were included in this review. From all five analyzed studies, microsurgical varicocelectomy was statistically proven to reduce DNA fragmentation index by 5.46% (mean difference -5.46; 95% CI: -4.79, -6.13; p < 0.00001). Moreover, the procedure also significantly improved other sperm parameters (sperm concentration +8.23%, sperm motility +7.17%, sperm progressive motility +2.77%, sperm morphology +0.64%).
CONCLUSION
Microsurgical varicocelectomy significantly improves spermatogenesis as reflected by biomarkers of infertile men including semen parameters and sperm DNA fragmentation (SDF).
Topics: Biomarkers; DNA Fragmentation; Humans; Infertility, Male; Male; Microsurgery; Semen; Sperm Count; Sperm Motility; Spermatozoa; Varicocele
PubMed: 36165486
DOI: 10.4081/aiua.2022.3.360 -
The World Journal of Men's Health Jan 2023Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and...
PURPOSE
Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.
MATERIALS AND METHODS
Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.
RESULTS
We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.
CONCLUSIONS
The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.
PubMed: 36102104
DOI: 10.5534/wjmh.220067 -
Basic and Clinical Andrology May 2022Infertility related to varicocele, infections, metabolic dysfunctions, oxidative stress and environmental toxicants is also associated with inflammatory processes that... (Review)
Review
BACKGROUND
Infertility related to varicocele, infections, metabolic dysfunctions, oxidative stress and environmental toxicants is also associated with inflammatory processes that ultimately lead to the activation of the inflammasome pathway (IP). IP is classically activated by DAMPs, MAMPs or LAMPs, which stand for Damage-, Microbe- or Lifestyle-Associated Molecular Patterns, respectively. The most important player in IP activation is the NLRP3 (NOD[Nuclear oligomerization domain]-, LRR[Leucine rich repeat]- and pyrin domain-containing protein 3) which functions as an intracellular sensor of D/M/L-AMPs resulting in activation of caspase-1, promotion of apoptosis, pyroptosis and generation of inflammatory cytokines. This review addresses the question of whether IP activation might be associated with male infertility situations.
RESULTS & CONCLUSIONS
We conducted a systematic review of articles published in the Google Scholar, and PubMed databases through October 2021. It turns out that inflammasome activation and its consequences including cytokine storms, apoptosis and pyroptosis could be associated with the reduced sperm count as well as the structural and functional sperm defects recorded in several situations associated with male infertility suggesting that anti-inflammatory therapeutic strategies could be possibly considered to restore male fertility in future research.
PubMed: 35637440
DOI: 10.1186/s12610-022-00157-9 -
Asian Journal of Andrology 2023In this review, we tried to systematize all the evidence (from PubMed [MEDLINE], Scopus, Cochrane Library, EBSCO, Embase, and Google Scholar) from 1993 to 2021 on the... (Review)
Review
In this review, we tried to systematize all the evidence (from PubMed [MEDLINE], Scopus, Cochrane Library, EBSCO, Embase, and Google Scholar) from 1993 to 2021 on the predictors of microsurgical varicocelectomy efficacy in male infertility treatment. Regarding the outcomes of varicocele repair, we considered semen improvement and pregnancy and analyzed them separately. Based on the 2011 Oxford CEBM Levels of Evidence, we assigned a score to each trial that studied the role of the predictor. We systematized the studied predictors based on the total points, which were, in turn, calculated based on the number and quality of studies that confirmed or rejected the studied predictor as significant, into three levels of significance: predictors of high, moderate, and low clinical significance. Preoperative total motile sperm count (TMSC) coupled with sperm concentration can be a significant predictor of semen improvement and pregnancy after varicocelectomy. In addition, for semen improvement alone, scrotal Doppler ultrasound (DUS) parameters, sperm DNA fragmentation index (DFI), and bilateral varicocelectomy are reliable predictors of microsurgical varicocelectomy efficacy.
Topics: Female; Humans; Male; Pregnancy; Infertility, Male; Microsurgery; Semen; Sperm Count; Sperm Motility; Varicocele
PubMed: 35381691
DOI: 10.4103/aja2021125 -
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