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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 -
Therapeutic Advances in Urology 2023The ideal surgical approach for the management of varicocele in children and adolescents remains controversial. Several techniques are available including artery- or...
BACKGROUND
The ideal surgical approach for the management of varicocele in children and adolescents remains controversial. Several techniques are available including artery- or lymphatic-sparing with optical magnification ( open inguinal or sub-inguinal approach), laparoscopic, antegrade and retrograde embolization/sclerotherapy.
OBJECTIVES
We aimed to appraise the clinical outcomes of these techniques in children and adolescents.
DATA SOURCES AND METHODS
A systematic review was conducted (1997-2023). Meta-analysis or proportional meta-analysis for non-comparative studies (Freeman-Tukey transformation) using the random effects model was conducted. Results are expressed as overall proportion % and 95% confidence interval (CI).
RESULTS
We identified 1910 studies; 632 duplicates were removed, 1278 were screened, 203 were reviewed and 56 were included, with 12 reporting on 2 different techniques (total of 68 data sets). Optical magnification inguinal approach (498 cases): recurrence 2.5% (0.6-5.6), hydrocele 1.6% (0.47-3.4), testicular atrophy 1% (0.3-2.0), complications 1.1% (0.2-2.6); optical magnification sub-inguinal approach (592 cases): recurrence 2.1% (0.7-4.4), hydrocele 1.26% (0.5-2.3), testicular atrophy 0.5% (0.1-1.3), complications 4% (1.0-8.8). Laparoscopic with mass-ligation/division (1943 cases): recurrence 2.9% (1.5-4.6), hydrocele 11.4% (8.3-14.9); complications 1.5% (0.6-2.9); laparoscopic with lymphatic-sparing (974 cases): recurrence 2.4% (1.5-3.5), hydrocele 1.2% (0.45-3.36), complications 1.2% (0.05-3.9); laparoscopic with artery-sparing (228 cases): recurrence 6.6% (2.3-12.9), hydrocele 6.5% (2.6-12.0). Antegrade embolization/sclerotherapy (403 cases): recurrence 7.6% (5.2-10.4), hydrocele 0.8% (0.17-1.9), technical failure 0.6% (0.1-1.6), complications 4.0% (2.3-6.1); retrograde embolization/sclerotherapy (509 cases): recurrence 6.9% (4.6-9.5), hydrocele 0.8% (0.05-2.5), technical failure 10.2% (4.6-17.6), and complications 4.8% (1.0-11.2).
CONCLUSION
The recurrence rate varies between 2.1% and 7.6% and is higher with the embolization/sclerotherapy techniques. Post-operative hydrocele rate varies between 0.8% and 11.4% and is higher with the laparoscopic mass-ligation/division technique. Testicular atrophy has not been reported with the laparoscopic and embolization/sclerotherapy techniques. The retrograde embolization technique is associated with 10% technical failure (inability to complete the procedure). The laparoscopic lymphatic-sparing technique is characterized by the lowest recurrence rate, incidence of hydrocele and other complications, and no reports of testicular atrophy.
PubMed: 37868369
DOI: 10.1177/17562872231206239 -
American Journal of Men's Health 2023Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the... (Meta-Analysis)
Meta-Analysis Review
Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the effects of varicocele surgical repair on serum hormones and inhibin B levels in patients with varicocele. A literature search was performed in August 2022, and no language or geographic region restrictions were applied. The search included the following databases: PubMed, Embase, and Medline. A literature review was performed to identify all published clinical trials assessing serum hormone and inhibin B levels before and after varicocele surgical repair. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Eight articles were selected from 162 articles, including 452 patients. The combined analysis showed that after surgical treatment, mean serum testosterone, inhibin B, and sperm concentration levels increased compared with preoperative levels ( .05). After surgical treatment, mean serum follicle-stimulating hormon (FSH), and Luteinizing hormone (LH) levels decreased compared with preoperative levels ( .05). This meta-analysis demonstrates that varicocele surgical repair can improve testicular function, increase serum testosterone, and inhibin B levels and decrease serum FSH and LH levels in patients with varicocele. This might be related to the improvement of infertility. A large-scale multicenter randomized controlled study is needed for further confirmation.
Topics: Humans; Male; Follicle Stimulating Hormone; Luteinizing Hormone; Varicocele; Testosterone; Semen; Multicenter Studies as Topic
PubMed: 37694823
DOI: 10.1177/15579883231199400 -
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 -
Urology Annals 2024Varicocele is the dilatation of the scrotal veins and may affect sperm count and infertility. It is caused by congenital vein insufficiency or absence of venous valve.... (Review)
Review
Varicocele is the dilatation of the scrotal veins and may affect sperm count and infertility. It is caused by congenital vein insufficiency or absence of venous valve. The main treatment is by surgery, and currently, there are two minimally invasive choices: laparoscopic and microsurgical varicocelectomy. This systematic review aimed to record randomized clinical trials from various sources using all qualified studies up to June 2022. The assessed outcomes were operation time, hydrocele, hospital stay, change in semen parameter, recurrence rate, and pregnancy rate. The essential data extracted were Jadad score, publication year, age, and sample size. This systematic review consisted of 509 and 512 patients in the laparoscopic and microsurgery group, respectively, taken from 12 out of 281 studies. The result of this systematic review was significant difference in operation time between patients from two groups (weighted mean difference [WMD] -21.40, 95% confidence interval [CI]: -28.90--13.89); length of hospitalization (WMD: 0.38, 95% CI: 0.02-0.74); laparoscopic could significantly increase the risk of hydrocele by 3.30-fold (risk ratio [RR]: 3.30, 95% CI: 1.07-10.12); laparoscopic could significantly increase the recurrence rate by 6.98-fold (RR: 6.98, 95% CI: 3.46-14.08); no significant difference in spontaneous pregnancy between patients in both groups (RR: 0.81, 95% CI: 0.57-1.16); and laparoscopic surgery decreased the occurrence of sperm parameter changes by 40% (RR = 0.40, 95% CI: 0.25-0.62).
PubMed: 38818427
DOI: 10.4103/ua.ua_3_23 -
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 -
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 -
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 -
The World Journal of Men's Health Apr 2024Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could...
Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.
PURPOSE
Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA).
MATERIALS AND METHODS
A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD).
RESULTS
Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%).
CONCLUSIONS
Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.
PubMed: 38164034
DOI: 10.5534/wjmh.230235 -
Asian Journal of Andrology Jun 2024Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce...
Varicocele repair in improving spermatozoa, follicle-stimulating hormone, and luteinizing hormone parameters in infertile males with azoospermia: a systematic review and meta-analysis.
Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce high-quality semen following varicocele treatment. Advising varicocelectomy prior to sperm retrieval in a reproductive program is still debated. This study reviewed the impact of varicocele repair on male infertility using several factors. A literature search was conducted using Scopus, PubMed, Embase, the Wiley Online Library, and Cochrane databases. Sperm concentration, sperm progression, overall sperm motility, sperm morphology, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were also compared. Outcomes were compared between those who received treatment for varicocele and those who did not. The data from the pooled analysis were presented as standardized mean difference (SMD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Additionally, we conducted analyses for publication bias, sensitivity, and subgroup analysis as appropriate. Nine studies were included after screening relevant literature. Statistical analysis revealed a significant improvement in sperm concentration (SMD: 1.81, 95% CI: 0.84-2.77, P < 0.001), progressive sperm motility (SMD: 4.28, 95% CI: 2.34-6.22, P < 0.001), and sperm morphology (SMD: 3.59, 95% CI: 2.27-4.92, P < 0.001). Total sperm motility showed no significant difference following varicocele repair (SMD: 0.81, 95% CI: -0.61-2.22, P = 0.26). No significant differences were seen in serum FSH (SMD: 0.01, 95% CI: -0.16-0.19, P = 0.87) and LH (SMD: 0.19, 95% CI: -0.01-0.40, P = 0.07) levels as well. This study supports varicocele repair in infertile men with clinical varicocele, as reflected by the improvement in sperm parameters after varicocelectomy compared with no treatment. There were no significant improvements in serum FSH and LH levels.
PubMed: 38877692
DOI: 10.4103/aja202426