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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 -
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 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 -
Reproductive Biology and Endocrinology... Jan 2021Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and meta-analysis to investigate the possible effects of age, height, weight, and body mass index (BMI) on the presence and severity of varicoceles.
METHODS
Databases including EMBASE, MEDLINE, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, and Google Scholar were systematically searched to identify relevant articles published up to March 2020. Two researchers independently identified eligible articles and extracted data. Cochran's Q statistic and I statistics were used to assess heterogeneity. Meta-analysis was performed using StataSE 12.0 software (StataCorp LP, USA). Random-effects models were used to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Publication bias was assessed using Begg's funnel plot and Egger's regression test.
RESULTS
The search strategy produced 272 articles, of which 18 articles were eligible according to the inclusion/exclusion criteria. A total of 56,325 patients with varicocele and 1,334,694 patients without varicocele were included in the meta-analysis to evaluate the effect of somatometric parameters on the presence and severity of varicocele. The overall results demonstrated that the presence of varicoceles was significantly associated with height (WMD = 1.41, 95% CI = 1.07 to 1.74, P < 0.001) and inversely correlated with BMI (WMD = - 1.35, 95% CI = -1.67 to - 1.03, P < 0.001) but not with age (WMD = -0.93, 95% CI = -2.19 to 0.33, P = 0.149) or weight (WMD = 0.24, 95% CI = -2.24 to 2.72, P = 0.850). The severity of varicocele was inversely correlated with increased BMI but not with age.
CONCLUSION
The presence of varicoceles was significantly associated with height and inversely correlated with BMI.
Topics: Age Factors; Body Mass Index; Body Weight; Body Weights and Measures; China; Humans; Male; Prevalence; Risk Factors; Severity of Illness Index; Somatotypes; Varicocele
PubMed: 33472653
DOI: 10.1186/s12958-021-00695-3 -
Andrologia Mar 2021The updated systematic review and meta-analysis was conducted to assess the platelet indices between patients with varicocele and healthy subject. The main purpose of... (Meta-Analysis)
Meta-Analysis Review
The updated systematic review and meta-analysis was conducted to assess the platelet indices between patients with varicocele and healthy subject. The main purpose of our study was to explore the relationship between platelet and the pathogenesis of varicocele. Databases including Cochrane Library, PubMed, and MEDLINE were retrieved to identify studies. Two independent investigators extracted the related information of the included original passages. In order to estimate the difference of varicocele patients and healthy subjects, we applied the standardised mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs). 1,156 patients and 797 healthy subjects of nine studies met the pre-set inclusion criteria. The estimated SMD in MPV between varicocele patients and healthy subjects was 0.61 (95% CI: 0.29-0.93, p < 0.001). The estimated SMD in MPV between preoperative varicocele patients and post-operative varicocele patients was 0.22 (95% CI: 0.03-0.41, p = 0.02). The estimated SMD in PLT between varicocele patients and healthy subjects was -0.19 (95% CI: -0.28, -0.08, p = 0.001). The available data suggest that a higher MPV level in varicocele patients, and the varicocele operation can normalise the preoperatively elevated mean platelet volume levels. Further researches are needed to investigate the potential role of platelet with varicocele.
Topics: Blood Platelets; Humans; Male; Mean Platelet Volume; Platelet Count; Postoperative Period; Varicocele
PubMed: 33369777
DOI: 10.1111/and.13939 -
Frontiers in Surgery 2020To investigate the effect of primary varicocele and related surgery in male infertility through meta-analysis. A systematic search of the literature was conducted...
To investigate the effect of primary varicocele and related surgery in male infertility through meta-analysis. A systematic search of the literature was conducted using the Medline, Embase, Cochrane, and CNKI databases. The search was up to September 2019. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using RevMan 5.2. A random-effects model was used to calculate the overall combined risk estimates. After screening 687 articles, 4 randomized controlled trials with 349 patients were included. One hundred seventy two patients were addressed in embolization/ligation, with 177 patient's observation treatment. The number of spontaneous pregnancies in the two groups was 41 and 40, respectively. There was no significant difference in pregnancy rate between the operation group and the control group. RR = 1.05 [0.72, 1.54]. There is not enough evidence to explain the surgical treatment of varicocele can improve the natural fertility of the infertile couples, and there is still a need for most of prospective randomized controlled trials to verify the efficacy of varicocele surgery for treating of male infertility. We do not deny the importance of this operation, we just want to call on everyone to strictly grasp the indications of the operation, avoid ineffective medical expenses, and avoid unnecessary pain to patients.
PubMed: 33330606
DOI: 10.3389/fsurg.2020.586153 -
Fertility Research and Practice Dec 2020Infertility is a practical concern of Africans due to social disgrace and exclusion. This meta-analysis aims to analyze the proportion of primary and secondary...
BACKGROUND
Infertility is a practical concern of Africans due to social disgrace and exclusion. This meta-analysis aims to analyze the proportion of primary and secondary infertility and identify the etiologic factors based on the studies conducted in Africa.
METHODS
An internet-based search was conducted on the following databases; PubMed/Medline, EMBASE, Cochrane library, and google scholar. Both population and institution-based studies conducted among African couples, males, and females were included. Data extraction and critical appraisal of the articles were done by two independent investigators. Meta-analysis using a random effect model was conducted by Stata version 14. Forest plot, heterogeneity test, and funnel plot for publication bias were performed.
RESULTS
The pooled proportion of primary and secondary infertility in Africa was 49.91% (I = 98.7, chi-square = 1509.01, degree of freedom = 19 and p < 0.001) and 49.79% (I = 98.7, chi-square = 1472.69, degree of freedom = 19 and p < 0.001) respectively. The pooled prevalence of the causes of infertility indicated that 54.01% and 22.26% of the infertility cases were respectively due to female and male-related problems. In 21.36% of infertility cases, both sexes were affected, while 10.4% of the causes of infertility were unexplained. The pooled prevalence of mostly reported causes of male infertility was 31% (oligospermia), 19.39% (asthenozoospermia), and 19.2% (varicocele). The most commonly identified causes of female infertility were pelvic inflammatory disease, tubal factors, and abortion with a pooled prevalence of 39.38%, 39.17%, and 36.41% respectively.
CONCLUSIONS
In Africa, the proportion of primary and secondary infertility is approximately equal. Infertility is mostly due to female-related causes like; pelvic inflammatory diseases, uterine tube related problems, and abortion. Oligospermia, asthenozoospermia, and varicocele were the commonest causes of male-related infertility. It is suggested that interpretation and utilization of these findings should consider the presence of substantial heterogeneity between the included studies.
PubMed: 33292584
DOI: 10.1186/s40738-020-00090-3 -
Heliyon Nov 2020Varicocele is one of the most common treatable causes of male infertility. However, the decision to perform varicocelectomy before starting a fertility program remains... (Review)
Review
INTRODUCTION
Varicocele is one of the most common treatable causes of male infertility. However, the decision to perform varicocelectomy before starting a fertility program remains controversial. This study aimed to thoroughly review and analyze the benefit of varicocele repair and its impact on the success rate of a fertility program.
MATERIALS AND METHODS
A systematic literature search was performed using MEDLINE, Cochrane Library, and Wiley Library. The primary outcome was the pregnancy rate, and the secondary outcomes were live birth rate and surgical sperm retrieval success rate. Outcomes were compared between men who underwent treatment for a varicocele and those that did not. The pooled analysis data are presented as odds ratios with 95% confidence intervals.
RESULTS
A total of 31 articles were included in the meta-analysis. The pregnancy rate was significantly higher in the treated group (odds ratio = 1.82; 95% confidence interval: 1.37-2.41; P < 0.0001) along with the live birth rate (odds ratio = 2.80; 95% confidence interval: 1.67-4.72; P = 0.0001). The further subgroup analysis revealed a higher pregnancy rate in treated men with azoospermia, subnormal semen parameters, and normozoospermia (P = 0.04, P = 0.0005, and P = 0.002, respectively), while the live birth rate was only significantly higher in the treated men with subnormal semen parameters and normozoospermia (P = 0.001 and P < 0.0001). Treated varicocele also led to a higher sperm retrieval rate in azoospermic patients (odds ratio = 1.69; 95% confidence interval: 1.16-2.45; P = 0.006).
CONCLUSIONS
Varicocele repair increased the pregnancy and live birth rates regardless the semen analysis result, along with the sperm retrieval success rate in azoospermic men. Thus, varicocele repair may be beneficial prior to joining a fertility program.
PubMed: 33204888
DOI: 10.1016/j.heliyon.2020.e05439 -
Archivio Italiano Di Urologia,... Oct 2020Varicocele has been found to impair the function of the epididymis resulting in subfertility whereas the varicocelectomy can resolve the phenomenon. L-carnitine is...
BACKGROUND
Varicocele has been found to impair the function of the epididymis resulting in subfertility whereas the varicocelectomy can resolve the phenomenon. L-carnitine is regarded as a biomarker for the function of the epididymis and has been found in reduced concentrations in infertile patients of various causes, including infertile men with varicocele. It seems that Lcarnitine and varicocele share clinical significance and the area of research looks promising.
OBJECTIVE
To identify the role of L-carnitine in the treatment of varicocele.
MATERIALS AND METHODS
A systematic search was performed in Pubmed/Medline with the terms (L-carnitine) and (varicocele) and (L-carnitine) and (varicocelectomy). Inclusion criteria were studies reported outcomes of L-carnitine administration alone or in duet, as primary or adjuvant treatment to varicocele. Exclusion criteria were non-English language and animal studies. Studies using L-carnitine as part of a panel of therapeutic agents were avoided.
RESULTS
Only four suitable studies were identified for discussion. In one randomized study, the combination of L-carnitine and cinnoxicam improved semen parameters in patients with non-high-grade varicocele compared to L-carnitine alone and had a favourable effect on pregnancy rates but the effect of grade is unknown. In another study, as an adjuvant treatment to varicocelectomy, L-carnitine showed no clear benefit. Finally, in comparison to surgery, the results are inconclusive; two studies showed some benefit might be expected in low-grade or subclinical varicocele, but surgery appears superior.
CONCLUSIONS
The evidence regarding the role of L-carnitine as a primary or adjuvant treatment of varicocele is sparse. The pathophysiological significance of L-carnitine implicates a potential role of the molecule in the management of varicocele, but the evidence so far is controversial for any recommendations. L-carnitine might be taken into consideration in selected cases; however, further search is needed in order the optimal role of L-carnitine in infertile patients with varicocele to be clarified.
Topics: Carnitine; Chemotherapy, Adjuvant; Humans; Infertility, Male; Male; Treatment Outcome; Urologic Surgical Procedures, Male; Varicocele
PubMed: 33016059
DOI: 10.4081/aiua.2020.3.263 -
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