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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 -
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 -
Fertility and Sterility Sep 2021To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Infertile men with clinical varicocele subjected to varicocelectomy.
INTERVENTION(S)
Systematic search using PubMed/Medline, EMBASE, Cochrane's central database, Scielo, and Google Scholar to identify relevant studies published from inception until January 2021. We included studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele.
MAIN OUTCOME MEASURE(S)
The primary outcome was the difference between the SDF rates before and after varicocelectomy. A meta-analysis of weighted data using random-effects models was performed. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CIs). Subgroup analyses were performed on the basis of the SDF assay, varicocelectomy technique, preoperative SDF levels, varicocele grade, follow-up time, and study design.
RESULT(S)
Nineteen studies involving 1,070 patients provided SDF data. Varicocelectomy was associated with reduced postoperative SDF rates (WMD -7.23%; 95% CI: -8.86 to -5.59; I = 91%). The treatment effect size was moderate (Cohen's d = 0.68; 95% CI: 0.77 to 0.60). The pooled results were consistent for studies using sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, sperm chromatin dispersion test, and microsurgical varicocele repair. Subgroup analyses showed that the treatment effect was more pronounced in men with elevated vs. normal preoperative SDF levels, but the impact of varicocele grade remained equivocal. Meta-regression analysis demonstrated that SDF decreased after varicocelectomy as a function of preoperative SDF levels (coefficient: 0.23; 95% CI: 0.07 to 0.39).
CONCLUSION(S)
We concluded that pooled results from studies including infertile men with clinical varicocele indicated that varicocelectomy reduced the SDF rates. The treatment effect was greater in men with elevated (vs. normal) preoperative SDF levels. Further research is required to determine the full clinical implications of SDF reduction for these men.
Topics: Adult; DNA Fragmentation; Fertility; Humans; Infertility, Male; Male; Spermatozoa; Treatment Outcome; Urologic Surgical Procedures, Male; Varicocele
PubMed: 33985792
DOI: 10.1016/j.fertnstert.2021.04.003 -
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 -
The Cochrane Database of Systematic... Apr 2021Varicoceles are associated with male subfertility; however, the mechanisms by which varicoceles affect fertility have yet to be satisfactorily explained. Several... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Varicoceles are associated with male subfertility; however, the mechanisms by which varicoceles affect fertility have yet to be satisfactorily explained. Several treatment options exist, including surgical or radiological treatment, however the safest and most efficient treatment remains unclear. OBJECTIVES: To evaluate the effectiveness and safety of surgical and radiological treatment of varicoceles on live birth rate, adverse events, pregnancy rate, varicocele recurrence, and quality of life amongst couples where the adult male has a varicocele, and the female partner of childbearing age has no fertility problems.
SEARCH METHODS
We searched the following databases on 4 April 2020: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. We also searched the trial registries and reference lists of articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) if they were relevant to the clinical question posed and compared different forms of surgical ligation, different forms of radiological treatments, surgical treatment compared to radiological treatment, or one of these aforementioned treatment forms compared to non-surgical methods, delayed treatment, or no treatment. We extracted data if the studies reported on live birth, adverse events, pregnancy, varicocele recurrence, and quality of life.
DATA COLLECTION AND ANALYSIS
Screening of abstracts and full-text publications, alongside data extraction and 'Risk of bias' assessment, were done dually using the Covidence software. When we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses; otherwise, we reported results narratively. We used the I statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We dually rated the risk of bias of studies using the Cochrane 'Risk of bias' tool, and the certainty of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified 1897 citations after de-duplicating the search results. We excluded 1773 during title and abstract screening. From the 113 new full texts assessed in addition to the 10 studies (11 references) included in the previous version of this review, we included 38 new studies, resulting in a total of 48 studies (59 references) in the review providing data for 5384 participants. Two studies (three references) are ongoing studies and two studies are awaiting classification. Treatment versus non-surgical, non-radiological, delayed, or no treatment Two studies comparing surgical or radiological treatment versus no treatment reported on live birth with differing directions of effect. As a result, we are uncertain whether surgical or radiological treatment improves live birth rates when compared to no treatment (risk ratio (RR) 2.27, 95% confidence interval (CI) 0.19 to 26.93; 2 RCTs, N = 204; I = 74%, very low-certainty evidence). Treatment may improve pregnancy rates compared to delayed or no treatment (RR 1.55, 95% CI 1.06 to 2.26; 13 RCTs, N = 1193; I = 65%, low-certainty evidence). This suggests that couples with no or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 22% and 48%. We identified no evidence on adverse events, varicocele recurrence, or quality of life for this comparison. Surgical versus radiological treatment We are uncertain about the effect of surgical versus radiological treatment on live birth and on the following adverse events: hydrocele formation, pain, epididymitis, haematoma, and suture granuloma. We are uncertain about the effect of surgical versus radiological treatment on pregnancy rate (RR 1.13, 95% CI 0.75 to 1.70; 5 RCTs, N = 456, low-certainty evidence) and varicocele recurrence (RR 1.31, 95% CI 0.82 to 2.08; 3 RCTs, N = 380, low-certainty evidence). We identified no evidence on quality of life for this comparison. Surgery versus other surgical treatment We identified 19 studies comparing microscopic subinguinal surgical treatment to any other surgical treatment. Microscopic subinguinal surgical treatment probably improves pregnancy rates slightly compared to other surgical treatments (RR 1.18, 95% CI 1.02 to 1.36; 12 RCTs, N = 1473, moderate-certainty evidence). This suggests that couples with microscopic subinguinal surgical treatment have a 10% to 14% chance of pregnancy after treatment, whilst the pregnancy rate in couples after other surgical treatments is 10%. This procedure also probably reduces the risk of varicocele recurrence (RR 0.48, 95% CI 0.29, 0.79; 14 RCTs, N = 1565, moderate-certainty evidence). This suggests that 0.4% to 1.1% of men undergoing microscopic subinguinal surgical treatment experience recurrent varicocele, whilst 1.4% of men undergoing other surgical treatments do. Results for the following adverse events were inconclusive: hydrocele formation, haematoma, abdominal distension, testicular atrophy, wound infection, scrotal pain, and oedema. We identified no evidence on live birth or quality of life for this comparison. Nine studies compared open inguinal surgical treatment to retroperitoneal surgical treatment. Due to small sample sizes and methodological limitations, we identified neither treatment type as superior or inferior to the other regarding adverse events, pregnancy rates, or varicocele recurrence. We identified no evidence on live birth or quality of life for this comparison. Radiological versus other radiological treatment One study compared two types of radiological treatment (sclerotherapy versus embolisation) and reported 13% varicocele recurrence in both groups. Due to the broad confidence interval, no valid conclusion could be drawn (RR 1.00, 95% CI 0.16 to 6.20; 1 RCT, N = 30, very low-certainty evidence). We identified no evidence on live birth, adverse events, pregnancy, or quality of life for this comparison.
AUTHORS' CONCLUSIONS
Based on the limited evidence, it remains uncertain whether any treatment (surgical or radiological) compared to no treatment in subfertile men may be of benefit on live birth rates; however, treatment may improve the chances for pregnancy. The evidence was also insufficient to determine whether surgical treatment was superior to radiological treatment. However, microscopic subinguinal surgical treatment probably improves pregnancy rates and reduces the risk of varicocele recurrence compared to other surgical treatments. High-quality, head-to-head comparative RCTs focusing on live birth rate and also assessing adverse events and quality of life are warranted.
Topics: Bias; Confidence Intervals; Embolization, Therapeutic; Female; Humans; Infertility, Male; Live Birth; Male; Outcome Assessment, Health Care; Postoperative Complications; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Recurrence; Sclerotherapy; Sperm Count; Testicular Hydrocele; Varicocele
PubMed: 33890288
DOI: 10.1002/14651858.CD000479.pub6 -
The World Journal of Men's Health Feb 2024Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s)...
PURPOSE
Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele.
MATERIALS AND METHODS
A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×10), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist.
RESULTS
Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high.
CONCLUSIONS
This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.
PubMed: 38449451
DOI: 10.5534/wjmh.230260 -
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 -
Urology Journal Oct 2019This study reviewed the efficacy and safety of the microsurgical subinguinal varicocelectomy (MSV) with and without testicular delivery (TD) for varicocele patients. (Meta-Analysis)
Meta-Analysis
PURPOSE
This study reviewed the efficacy and safety of the microsurgical subinguinal varicocelectomy (MSV) with and without testicular delivery (TD) for varicocele patients.
MATERIALS AND METHODS
A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, Cochrane databases, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Google Scholar databases to identify relevant studies that reported MSV with and without TD for varicocele patients published in English or Chinese up to October 2018. The Newcastle-Ottawa Scale (NOS) and the Jadad scores were used to evaluate the methodological quality of all the included studies. We also used the Cochrane Collaboration's tool for assessing risk of bias for each study. The Review Manager Software version 5.3 was used to conduct data analysis.
RESULTS
Four RCTs and three retrospective studies consisting of 993 patients were included. Meta-analysis results indicated that both of the two treatments were effective and safe. MSV with TD had a lower recurrence rate (OR = 0.20, 95% CI: 0.06 - 0.65, P = .007, I2 = 0%) and postoperative serum testosterone level (MD = -39.07, 95% CI: -51.95 - -26.18, P = .00001, I2 = 0%) compared with MSV without TD but was associated with higher postopera-tive complications rate (OR=7.35, 95% CI: 2.92-18.53, P < .0001, I2 = 0%). We found no significant differences in operation time (MD = 12.46, 95% CI:0.11-24.81,P= .05, I2 = 87%), sperm concentration (MD = 3.73, 95% CI: -2.88 - 10.35, P = .27, I2 = 81%), sperm motility (MD = 10.96, 95% CI: -11.93 - 33.86, P = .35, I2 = 99%), and pregnancy rate(OR = 0.65, 95% CI: 0.37- 1.16, P = .15, I2 = 0%).
CONCLUSION
This meta-analysis compared efficacy and safety of MSV with and without TD for varicocele pa-tients. MSV with TD was associated with a higher postoperative complication rate but lower recurrence rate and postoperative serum testosterone level than MSV without TD. In terms of preoperative serum testosterone level, operation time, sperm concentration, sperm motility, and pregnancy rate, we found no significant differences.
Topics: Humans; Inguinal Canal; Male; Microsurgery; Treatment Outcome; Urologic Surgical Procedures, Male; Varicocele
PubMed: 31473994
DOI: 10.22037/uj.v0i0.5095 -
The World Journal of Men's Health Apr 2021It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the... (Review)
Review
It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.
PubMed: 33474843
DOI: 10.5534/wjmh.200196 -
Journal of Ultrasound Dec 2020Although often asymptomatic and detected incidentally, varicocele is a relatively common problem in patients who seek medical attention for infertility problems....
Although often asymptomatic and detected incidentally, varicocele is a relatively common problem in patients who seek medical attention for infertility problems. Ultrasound (US) is the imaging modality of choice for evaluation, but there is no consensus on the diagnostic criteria, classification, and examination technique. In view of this uncertainty, the Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology (ESUR-SPIWG) undertook a systematic review of the available literature on this topic, to use as the basis for evidence-based guidelines and recommendations. This paper provides the results of the systematic review on which guidelines were constructed.
Topics: Humans; Infertility, Male; Male; Penis; Practice Guidelines as Topic; Scrotum; Spermatogenesis; Ultrasonography; Varicocele
PubMed: 32720266
DOI: 10.1007/s40477-020-00509-z