OBJECTIVE: The purpose of this narrative review is to provide a practical understanding of sperm DNA fragmentation (SDF) in the management of male infertility.
METHODS: A search for systematic reviews and meta-analyses (SRMA) on SDF between April 1st, 2018 and April 1st, 2023 was performed using PubMed and articles were selected as per their relevance to the topic. Guidelines from major societies were also reviewed. Three clinical cases are reported and discussed.
RESULTS: The search initially identified 80 articles. We selected 13 SRMAs based on their relevance to the topic. Of the 13 SRMAs, 7 evaluated the effect of SDF on assisted reproductive technology (ART) outcomes and recurrent pregnancy loss, 3 studied the effect of varicocele repair on SDF, and 3 evaluated the role of SDF involving lifestyle and environmental health factors including body mass index and male factor treatment strategies.
CONCLUSIONS: Evidence suggests that increased SDF has a negative impact on natural pregnancy and ART outcomes. SDF testing may be particularly important in the infertility evaluation of men with varicoceles, idiopathic or unexplained infertility, recurrent pregnancy loss, or previous ART failure. Further studies are needed on SDF testing and the implications it can have on male factor infertility and pregnancy outcomes as well as its implementation in the setting of ART.

OBJECTIVE: To assess the association between varicocele and hypogonadism, or erectile dysfunction.
METHODS: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome.
RESULTS: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele.
CONCLUSIONS: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances.

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).

UNASSIGNED: Antegrade sclerotherapy (Tauber\'s) procedure has been extensively used for the minimally-invasive treatment of varicocele; however, the results in the pediatric population are less defined. This systematic review evaluates the efficacy and safety of antegrade sclerotherapy for varicocele in the pediatric population.
UNASSIGNED: The review was conducted following the PRISMA guidelines. Systematic research of available literature in English language from 1980 until May 2022 was conducted through EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials. For each study, information was gathered regarding the study design, the inclusion/exclusion criteria, the indications for treatment, the success rate and the complications. When available, the details about sperm analysis were reported.
UNASSIGNED: The 10 studies were included in the final sample (564 patients). Median age of patients ranged 13.3-15.3 years. The indications for scleroembolization varied in the different studies, while most studies included patients with clinical G2-G3 varicocele and clinical symptoms or testicular asymmetry. The treatment was successful in 88%-98% of the patients, while the complication rate was <5%.
UNASSIGNED: Tauber\'s sclerotherapy is a safe and effective treatment for varicocele also in the pediatric population. Further studies with standardized inclusion criteria are needed to provide higher level of evidence and compare the outcomes of antegrade sclerotherapy with the other available techniques.

BACKGROUND: Varicocelectomy was considered to be beneficial to patients with varicocele-related infertility. However, there are only a few researchers who have explored the relationship between better timing and postoperative semen improvement in patients.
METHODS: We conducted this meta-analysis by enrolling published prospective studies to find out the best waiting time after varicocelectomy to wait for better improvement of semen quality. An extensive search was conducted in PubMed, Web of Science, and Cochrane Library to identify eligible studies. The included studies were then analyzed comprehensively using STATA software and standardized mean differences (SMDs) and their corresponding 95% confidence intervals were calculated.
RESULTS: Our comprehensive analysis showed that after varicocelectomy, follow-up results within 3 months or longer showed a significant improvement in semen parameters compared to the preoperative period. Notably, no further improvement in semen parameters was observed when the follow-up period reached six months or longer (semen volume: WMD: - 0.07 (- 0.29, 0.16); sperm concentration: WMD: - 1.33 (- 2.33, - 4.99); sperm motility: WMD: 2.31 (- 0.55, 5.18); sperm morphology: WMD: 1.29 (- 0.66, 3.24); sperm total motile count: WMD: 3.95 (- 6.28, 14.19)).
CONCLUSIONS: Three months after varicocelectomy may be the optimal time for semen parameters compared to six months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

OBJECTIVE: Despite the significant role of varicocele in the pathogenesis of male infertility, its association with anti-sperm antibodies (ASA) remains controversial. This systematic review and meta-analysis (SRMA) aims to investigate the frequency of ASA positivity in men with varicocele.
METHODS: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs).
RESULTS: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09-17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81-15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39-25.89]; p<0.01).
CONCLUSIONS: This SRMA indicates that ASA positivity is significantly higher among men with varicocele when tested by direct method (MAR) or indirect method (ELISA). This data suggests an immunological pathology in infertile men with varicocele and may have implications for the management of these patients.

OBJECTIVE: 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.
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 (×106), 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.

Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.

OBJECTIVE: 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).
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.

UNASSIGNED: The authors in this paper discuss a rare disease entity that can cause testicular pain and mimic varicocele.
UNASSIGNED: Citing data from a review of the world literature, spermatic cord thrombosis is most often misdiagnosed as an incarcerated inguinal hernia. Patients usually complain of pain and swelling of the testicle, pain in the inguinal region, and sometimes a palpable mass in the inguinal region.
UNASSIGNED: Ultrasonography with colour Doppler usually establishes the correct diagnosis. Currently, there are no official recommendations for the treatment of this disease.There are reports of conservative treatment of spermatic cord thrombosis in the world literature. However, it seems that the gold standard of management remains surgical exploration, which allows us to unequivocally establish the correct diagnosis. In cases of co-morbid thrombosis with spermatic cord varicocelectomy is recommended.
UNASSIGNED: Due to the rarity of this disease, the topic of this article was undertaken. The paper reviews the world literature relating to the diagnosis and treatment of this disease entity. Our own algorithm for the management of spermatic cord thrombosis is proposed.