Antioxidant treatment for oligoasthenoteratozoospermia and varicocele: a DBPC trial to evaluate the impact of age and body mass index.

Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group ( P = 0.0186). Total sperm count also significantly increased in the supplemented group ( P = 0.0117), as did sperm motility ( P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration ( P = 0.0352), while a body mass index (BMI) above 25 kg m -2 had a negative effect on sperm concentration ( P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

Researching the molecular mechanisms of Taohong Siwu Decoction in the treatment of varicocele-associated male infertility using network pharmacology and molecular docking: A review.

Taohong Siwu Decoction (THSWD) was widely used for the treatment of varicocele-associated male infertility. However, the pharmacological mechanism of action is not completely clear. Therefore, network pharmacology and molecular docking were performed to explore potential mechanism of THSWD in the treatment of varicocele-associated male infertility. The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Swiss Target Prediction, and GeneCards were used to retrieve candidate compounds, action targets, and disease-related targets. The construction of the protein-protein interaction (PPI) network and the screening of core genes were completed by the STRING and Cytoscape 3.9.1, respectively. The DAVID was used to obtain results of gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The Mcule analysis platform was used to perform molecular docking. There were a total of 53 candidate compounds and 782 relevant targets in THSWD. There were 45 common targets between THSWD, varicocele, and male infertility, and 23 core genes were found in the PPI network. Biological processes involved response to hypoxia, regulation of blood pressure, cellular response to hypoxia, and regulation of the nitric oxide biosynthetic process. Furthermore, the KEGG pathway enrichment analysis showed that the common targets mainly regulated the disease of varicocele-associated male infertility through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, Relaxin signaling pathway, and TNF signaling pathway. Finally, the molecular docking showed that luteolin, quercetin, and kaempferol had good intercalation with major targets. As predicted by network pharmacology, THSWD regulated varicocele-associated male infertility through multiple compounds and targets, and its mechanism was closely related to inflammatory response, reactive oxygen species damage, and function of blood vessels.

[The application of acupuncture in varicocele infertility based on " Visceral Collateral " theory].

The occurrence of varicocele infertility can be attributed to the small and flexural spermatic plexus which constitutes the main structure of spermatic cord.Obstruction of blood circulation, stagnation of qi and blood, ultimately leading to infertility. The spermatic plexus ' physiological and pathological symptoms are consistent with the theory of visceral collateral. Based on the theory of visceral collaterals, the varicocele infertility caused by stagnation of liver collateral and deficiency of kidney collateral. And the acupuncture is used to directly act on the relevant points on the meridians, so as to dredge the meridians, strengthen the healthy and expel the evil, and harmonize the yin and yang of visceral, which is more in line with the therapeutic principle of " unblocking the meridians " for collateral diseases. For varicocele infertility caused by liver meridian stasis, it can regulate the liver meridian Chong Ren, eliminate blood stasis and promote stagnation, and be combined with LR3, LI4, GB34, SP6, CV3. For varicocele infertility caused by kidney deficiency and meridian syndrome, it can tonify the kidney meridian Du Yang, warm and disperse the essence, and mainly focus on GV4, CV4, KI3, BL23 and BL43.

[Exploring the mechanisms of Jujing pill on varicocele-associated male infertility via network pharmacology and molecular docking technology].

OBJECTIVE: To investigate the potential mechanism of treating varicocele-associated male infertility with Jujing pill using network pharmacology and molecular docking technology. METHODS: The TCMSP and BATMAN databases were used to search for the Chinese medicine components of the Jujing pill and obtain the corresponding targets. The databases GeneCards, DISGENET, OMIM, and HPO were searched for 'varicocele' and 'male infertility' to identify the potential targets of varicocele-associated male infertility. Wayne diagrams were drawn using the jvenn tool to determine the intersection targets of the Chinese medicine targets and disease targets. The intersecting targets were further analyzed to identify the components and Chinese medicine corresponding to them. A Chinese medicine-active ingredient-target network map was constructed in Cytoscape 3.8.2. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING platform. The intersecting targets were imported into the DAVID database for GO enrichment analysis and KEGG-based pathway enrichment analysis. The KEGG database was used to select the most relevant pathway to the topic, and a KEGG pathway map was constructed using the mapper tool. The top 15 pathways with FDR values and their related targets and components were used to draw a core ingredient-target-pathway map. Finally, molecular docking was performed to verify the protein receptors and small molecule ligands of the core genes, and the results were visualized using AutoDock and PyMol software. RESULTS: A total of 207 ingredients and 1103 predicted targets of Jujing pill were screened. Additionally, 285 targets of varicocele were also identified. By using a Venn diagram, 86 common targets were obtained. The analysis of Gene Ontology (GO) results revealed significant enrichment in various biological processes (BP) such as positive regulation of gene expression, positive regulation of transcription, positive and negative regulation of apoptotic processes, response to hypoxia, response to estradiol, and positive regulation of nitric oxide biosynthesis processes. Furthermore, significant enrichment in cellular components (CC) was observed in macromolecules, cytoplasm, nucleus, and phosphatidylinositol 3-kinase complex. In terms of molecular function (MF), enrichment was found in enzyme binding, identical protein binding, transcriptional co-activator binding, and others. KEGG analysis demonstrated enrichment in pathways related to cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, FoxO signaling pathway, and more. Molecular docking results indicated that the core ingredients exhibited a strong binding capacity with the key targets. Conclusion： The effective active ingredients of Jujing pill exert their therapeutic effects on varicocele-associated male infertility through multiple targets and pathways. These findings provide a theoretical basis for future cell and animal experiments to verify the mechanism of action of Jujing pill in treating varicocele-associated male infertility.

Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial.

BACKGROUND: Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. METHODS: In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People's Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. DISCUSSION: Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021.

Varicocele, Functional Foods and Nutraceuticals: From Mechanisms of Action in Animal Models to Therapeutic Application.

Varicocele is one of the main causes of infertility in men, thus representing an important clinical problem worldwide. Inflammation contributes mainly to its pathogenesis, even if the exact pathophysiological mechanisms that correlate varicocele and infertility are still unknown. In addition, oxidative stress, apoptosis, hypoxia, and scrotal hyperthermia seem to play important roles. So far, the treatment of varicocele and the care of the fertility-associated problems still represent an area of interest for researchers, although many advances have occurred over the past few years. Recent experimental animal studies, as well as the current epidemiological evidence in humans, demonstrated that many functional foods of natural origin and nutraceuticals that are particularly abundant in the Mediterranean diet showed anti-inflammatory effects in varicocele. The aim of the present narrative review is to mainly evaluate recent experimental animal studies regarding the molecular mechanisms of varicocele and the state of the art about possible therapeutic approaches. As the current literature demonstrates convincing associations between diet, food components and fertility, the rational intake of nutraceuticals, which are particularly abundant in foods typical of plant-based eating patterns, may be a reliable therapeutic supportive care against varicocele and, consequently, could be very useful in the cure of fertility-associated problems in patients.

Safety and efficacy of acupuncture for varicocele-induced male infertility: a systematic review protocol.

INTRODUCTION: Varicocele (VC) is a common clinical disease in andrology. Among a number of ways for VC treatment, surgery is the most common one, but the measurable benefit of surgical repair was slight. A growing exploration of complementary therapies has been conducted in clinical research on acupuncture for VC, but there is no relevant systematic review and meta-analysis to assess the efficacy and safety of acupuncture for VC. METHODS AND ANALYSIS: All relevant publications published from database inception through August 2022 will be searched in three English-language databases (Embase, CENTRAL, MEDLINE) and four Chinese-language databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese Biomedical Literature Database and Wanfang Data). Randomised controlled trials in English and Chinese concerned with acupuncture for patients with VC will be included. The input clinical data will be processed by the Review Manager software (RevMan). The literature will be appraised with the Cochrane Collaboration risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation system (GRADE system) will be used to evaluate the quality of evidence. ETHICS AND DISSEMINATION: This study is a secondary study based on clinical studies so it does not relate to any individual patient information or infringe the rights of participants. Hence no ethical approval is required. The results will be reported in peer-reviewed journals or disseminated at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42022316005.

Varicocoele-associated male infertility: Cellular and molecular perspectives of pathophysiology.

BACKGROUND: Varicocoele is a common risk factor associated with reduced male fertility potential. The current understanding of varicocoele pathophysiology does not completely explain the clinical manifestation of infertility. The present treatment options such as antioxidant supplementation and varicocoelectomy only help ≈35% of men to achieve spontaneous pregnancy. OBJECTIVE: This review aims to summarize the available knowledge on cellular and molecular alterations implicated to varicocoele-associated male infertility and also highlights the new knowledge generated by "omics" technologies. MATERIALS AND METHODS: PubMed, MEDLINE, Cochrane and Google Scholar databases are searched using different combinations of keywords (varicocoele, infertile/fertile men with varicocoele, cellular changes, molecular mechanisms, proteome, epigenome, transcriptome and metabolome). A total of 229 relevant human and animal studies published till 2021 were included in this review. RESULTS: Current understanding advocates oxidative stress (OS) as a major contributory factor to varicocoele-associated male infertility. Excessive OS causes alteration in testicular microenvironment and sperm DNA fragmentation, which further contributes to infertility. Molecular and omics studies have identified several promising biomarkers such as AAMP, SPINT1, MKI67 (genetic markers), sperm quality and function related protein markers, global sperm DNA methylation level (epigenetic marker), Hspa2, Protamine, Gadd7, Dynlt1 and Beclin1 (mRNA markers), PRDX2, HSPA, APOA2, YKL40 (seminal protein markers), total choline and PHGDH (metabolic markers). DISCUSSION: Mature spermatozoa harbours a plethora of molecular information in form of proteome, epigenome and transcriptome, which could provide very important clues regarding pathophysiology of varicocoele-associated infertility. Recent molecular and omics studies in infertile men with varicocoele have identified several promising biomarkers. Upon further validation with larger and well-defined studies, some of these biomarkers could aid in varicocoele management. CONCLUSION: The present evidences suggest that inclusion of OS and sperm DNA fragmentation tests could be useful to the diagnostic workup for men with varicocoele. Furthermore, including precise molecular markers may assist in diagnostics and prognostics of varicocoele-associated male infertility.

Improvement in sperm quality by oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: Systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether oral antioxidant supplementation improves sperm quality in men with infertility and varicocele (VCL) who have not undergone surgical repair. In men with infertility and VCL who had not undergone surgical repair oral antioxidant supplementation significantly increased sperm concentration (WMD +5.86 × 106 /ml 95% CI: +1.47 to +10.24, p < 0.01; random effects model, six studies, 213 patients), total motility (WMD + 3.76%, 95% CI: +0.18 to +7.34, p = 0.04; random effects model, three studies, 93 patients), progressive motility (WMD + 6.38%, 95% CI: +3.04 to +9.71, p < 0.01; random effects model, three studies, 84 patients) and seminal volume (WMD +0.55 ml, 95%CI: +0.06 to +1.04, p = 0.03; random effects model, four studies, 120 patients). On the other hand, no significance difference was observed in sperm morphology (WMD +3.89%, 95% CI: -0.14 to +7.92, p = 0.06; random effects model, five studies, 187 patients). In conclusion, limited evidence suggests that the use of oral antioxidants in men with infertility and VCL, who have not undergone surgical repair improves their seminal volume, sperm concentration, total and progressive motility.

[Danhong Tongjing Prescription versus microsurgery in the treatment of varicocele-induced infertility: A retrospective multivariate analysis of 218 cases].

OBJECTIVE: To compared the traditional Chinese medicine Danhong Tongjing Prescription (DTP) and microsurgery in the treatment of varicocele (VC)-induced infertility and investigate the factors influencing the recovery of semen parameters of the patients. METHODS: We retrospectively analyzed the clinical data on 218 cases of VC-induced infertility with qi-deficiency and blood-stasis treated with DTP (n = 86) or by microsurgery (n = 132) in our hospital from January 2017 to July 2019, and compared the semen parameters between the two groups of patients after treatment. With age, course of disease, degree of VC, change of the testis volume, estrogen/testosterone (E/T) ratio and levels of FSH and LH as independent variables, and increased semen parameters after treatment as dependent variables, we constructed a multivariate linear regression model and identified statistically significant independent variables. RESULTS: After treatment, sperm concentration and the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) were obviously improved in both the DTP and microsurgery groups, with statistically significant difference between the two groups in sperm concentration and MNS, but not in PMS. Linear regression analysis showed that the severity of VC was an influencing factor for the recovery of sperm concentration after treatment in the DTP group (r = －11.599, Ra2 = 0.044 9) and the course of VC infertility was a factor affecting the recovery of sperm count in the microsurgery group (r = －1.837, Ra2 = 0.035 7). CONCLUSION: DTP is comparable to microsurgery in improving sperm motility while microsurgery is more effective in increasing the percentage of MNS in the treatment of VC-induced infertility. Early surgery is recommended for the treatment of infertility induced by severe bilateral VC, and DTP can be selected for infertility caused by mild or moderate bilateral VC if the patient is unwilling to accept surgery or microsurgery is inaccessible in the hospital.

Assessment of seminal calcium and magnesium levels in infertile men with varicocele before and after varicocelectomy.

BACKGROUND: Trace elements perform a vital role in all stages of human physiology, as well as reproduction. OBJECTIVE: This study aimed to assess seminal calcium (Ca) and magnesium (Mg) in infertile men associated with varicocele (Vx). MATERIALS AND METHODS: Overall, 50 men were divided into two groups: fertile men (n = 20) and infertile men who were scheduled for Vx surgical repair (n = 30). Exclusion criteria were as follows: azoospermia, smoking, leukocytospermia, and consumption of Ca and/or Mg supplements. All cases were subjected to history taking and clinical examination. Semen analysis and assessment of seminal Ca and Mg by the colorimetric method were carried out for all cases at the base point and 3 months postvaricocelectomy. RESULTS: Generally, the mean seminal Ca and Mg levels demonstrated significant decreases in infertile men with Vx compared with the healthy fertile men linked to higher Vx grade as well as Vx bilaterality. These seminal decreases demonstrated significant increases after Vx surgical repair. Collectively, seminal Ca and Mg levels showed a significant positive correlation (r = 0.665, p= 0.001). Besides, seminal Ca, Mg levels, and Ca/Mg ratio showed significant positive correlation with sperm concentration (r = 0.479, p = 0.001; r = 0.541, p = 0.001; r = 0.282, p = 0.001, respectively), sperm motility percentage (r = 0.493, p = 0.001; r = 0.477, p = 0.001; r = 0.353, P = 0.001, respectively), and sperm normal forms percentage (r = 0.578, p = 0.001; r = 0.520, p = 0.001; r = 0.430, p = 0.001, respectively). DISCUSSION AND CONCLUSION: Seminal Ca and Mg levels and Ca/Mg ratio are significantly decreased in infertile men associated with Vx compared with fertile men with significant increases after varicocelectomy.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

[Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele].

OBJECTIVE: To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC). METHODS: Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters. RESULTS: Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (ï¼»21.62 ± 9.25ï¼½ vs ï¼»28.88 ± 12.92ï¼½ ×106/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (ï¼»98.33 ± 0.15ï¼½% vs ï¼»96.27 ± 0.18ï¼½%, P < 0.05) and DNA fragmentation index (ï¼»19.72 ± 3.17ï¼½% vs ï¼»10.96 ± 3.82ï¼½%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types. CONCLUSIONS: Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

[Varicocelectomy combined with Qilin Pills for the treatment of varicocele-associated male infertility: A multi-center retrospective study].

OBJECTIVE: To investigate the effect of varicocelectomy (VCE) combined with medication of Qilin Pills (QLP) in the treatment of varicocele (VC)-associated male infertility. METHODS: We retrospectively analyzed the clinical data on 180 cases of VC-associated male infertility treated in our hospitals between October 2017 and March 2019, 67 by VCE ( the control group) and 113 by VCE in combination with 6-month medication of QLP after operation (the VCE+QLP group). We obtained the semen parameters from the patients before and at 1, 2, 3 and 6 months after surgery, measured their sperm DNA fragmentation index (DFI) before and at 6 months after operation, and recorded the rate of pregnancy at months postoperatively. RESULTS: There were no severe complications in any of the cases after surgery or during the whole course of medication. Compared with the baseline, the patients in control group showed significant increases at 6 months postoperatively in sperm concentration (ï¼»17.1 ± 12.4ï¼½ vs ï¼»29.5 ± 14.4ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»33.6±13.5ï¼½% vs ï¼»54.5±12.0ï¼½% , P <) and the percentage of progressively motile sperm (PMS) (ï¼»22.8 ± 10.9ï¼½% vs ï¼»43.7 ± 11.7ï¼½%, P <) but a remarkable decrease in sperm DFI (16.5 ± 7.6ï¼½% vs ï¼»13.3 ± 4.4ï¼½% , P <), and so did those in the VCE+QLP group in sperm concentration (ï¼»16.8 ± 10.7ï¼½ vs ï¼»38.9 ± 24.1)×106/ml, P < 0.01), sperm motility (ï¼»32.8 ± 14.0ï¼½% vs ï¼»50.1 ± 15.0)%, P <), PMS (ï¼»21.8 ± 11.3ï¼½% vs ï¼»39.6 ± 13.3ï¼½% , P <) and sperm DFI (ï¼»17.8 ± 9.0ï¼½% vs ï¼»11.8 ± 4.8ï¼½%, P <). There were even more statistically significant differences between the control and VCE+QLP groups at 6 months in the above semen parameters (P < 0.01) and in the rate of natural pregnancy (32.8% ï¼»22/67ï¼½ vs 48.7% ï¼»55/113ï¼½, P < 0.05). CONCLUSIONS: Varicocelectomy combined with medication of Qilin Pills can effectively improve semen quality and increase the rate of natural pregnancy in the treatment of VC-associated male infertility.

[Yishen Tongluo Recipe combined with minimally invasive surgery for the treatment of varicocele-associated asthenospermia].

OBJECTIVE: To observe the clinical effect of Yishen Tongluo Recipe (YTR) combined with minimally invasive surgery (MIS) in the treatment of varicocele-associated asthenospermia (of the kidney-deficiency and collateral-obstruction type). METHODS: We randomly divided 116 patients with varicocele-associated asthenospermia and up to the inclusion criteria into three groups and treated them by YTR combined with MIS (low spermatic vein ligation at the external inguinal ring orifice under the microscope) (the YTR+MIS group, n = 39), YTR alone (the YTR group, n = 38), or MIS alone (the MIS group, n = 39). At 12 weeks after treatment, we compared the total effectiveness rate, the percentage of progressively motile sperm (PMS), sperm straight line velocity (VSL), sperm DNA fragmentation index (DFI) and symptoms among the three groups of patients. RESULTS: After treatment, the total effectiveness rate was significantly higher in the YTR+MIS than in the YTR and the MIS group (89.74% vs 63.16% and 64.10%, P < 0.05), and so were the percentage of PMS (31.67 ± 3.93 vs 24.48 ± 3.15 and 25.57 ± 3.37, P < 0.05) and VSL (ï¼»30.19 ± 5.32ï¼½ vs ï¼»27.19 ± 5.48ï¼½ and ï¼»27.55 ± 5.24ï¼½ µm/s, P < 0.05), but the DFI was remarkably lower in the former than in the latter two groups (11.25 ± 8.27 vs 15.87 ± 5.45 and 15.26 ± 4.36, P < 0.05). The symptoms were improved more significantly in the YTR+MIS than in the YTR and MIS groups (P < 0.05). CONCLUSIONS: Yishen Tongluo Recipe combined with minimally invasive surgery, as an effective and safe strategy, can significantly improve sperm quality and sperm DNA integrity in patients with varicocele-associated asthenospermia.

Alpha-lipoic acid improves sperm motility in infertile men after varicocelectomy: a triple-blind randomized controlled trial.

RESEARCH QUESTION: Does supplementation with alpha-lipoic acid (ALA) enhance sperm parameters and/or the status of sperm lipid peroxidation and DNA fragmentation in men who have undergone microsurgical repair of a varicocele? DESIGN: Individuals with a varicocele who had undergone varicocelectomy were divided into two groups receiving either 600 mg of ALA or an identical placebo for 80 days. Semen samples obtained from the participants before surgery and after completion of the course of medication were analysed and compared. Participants, clinicians and data analysts were blinded to the randomization sequence. RESULTS: In the ALA group, total motility (P = 0.01) and progressive motility (P = 0.002) of the spermatozoa were significantly higher compared with the placebo group after surgery. Sperm lipid peroxidation and DNA damage (assessed by sperm chromatin structure assay) showed significant decreases in both the ALA and placebo groups (P ≤ 0.02) after treatment. CONCLUSIONS: An 80-day course of ALA medication after surgical repair improves total motility and progressive motility of the spermatozoa in individuals with a varicocele.

L-carnitine as primary or adjuvant treatment in infertile patients with varicocele. A systematic review.

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.

Body mass index and age correlate with antioxidant supplementation effects on sperm quality: Post hoc analyses from a double-blind placebo-controlled trial.

Spermatozoa are vulnerable to lack of energy and oxidative stress as a result of elevated levels of reactive oxygen species. Therefore, it is essential that appropriate nutrients are available during maturation. This randomised, double-blind, placebo-controlled trial investigated the effect of 6-month supplementation with carnitines and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. Semen analyses were done at the beginning and end of the treatment. In addition to main analyses, post hoc analyses for age and body mass index (BMI) were carried out. Results were interpreted by dividing the population into two age and BMI classes. In 94 patients who completed the study, all sperm parameters increased in supplemented patients compared to the placebo group. A significant (p = .0272) difference in supplementation efficacy was observed for total motility on patients with varicocele and BMI < 25. In the same group, also the progressive motility was significantly superior (p = .0159). For Responder analysis, total motility results were confirmed in both the cited group (p = .0066) and in the varicocele group with BMI < 25 and age < 35 (p = .0078). This study suggests that supplementation is more effective in subjects with varicocele younger than 35 years with BMI < 25.

Correlation of oxidation-reduction potential with hormones, semen parameters and testicular volume.

Seminal oxidative stress (OS) is a major cause of male factor infertility and can be measured as oxidation-reduction potential (ORP). Studies showed significant negative relationships of ORP with sperm count, motility or DNA integrity. Since these parameters are also positively or negatively associated with reproductive hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), testosterone, testicular volume and the occurrence of varicocele, it is important to understand the mechanistic relationship between ORP and hormonal and/or testicular parameters. Therefore, we studied the relationship between ORP levels, standard hormone profiles and testicular volume in infertile men with and without varicocele. Results show a highly significant negative relationship of ORP with testicular volume and significantly positive correlations with FSH and LH. Yet, when adding varicocele as covariate, the relationship with FSH/LH became nonsignificant. Contrary, the presence of varicocele had only a contributing influence on the association of ORP with the testis volume. No association was found with estradiol. We propose that since OS causes degeneration of Sertoli cell with testicular shrinkage, such negative effect would result in a negative feedback on the hypothalamus with less inhibin secretion. This may result in increased secretion of LH and FSH. Thus, systemic and/or local OS may be responsible for smaller testis volumes.

Evaluation of sperm DNA fragmentation index, Zinc concentration and seminal parameters from infertile men with varicocele.

The aim of this study was to investigate the effect of varicocele on DNA fragmentation index (DFI), zinc concentration and seminal parameters in infertile patients. In this prospective study, 179 men with at least 1-year history of infertility and varicocele were examined for semen quality at Hanoi Medical University Hospital (HMUH), Hanoi, Vietnam. In addition, an inverse correlation between zinc concentration and the degree of sperm DNA fragmentation in patients with clinical varicocele was found. The difference in mean values of sperm DNA fragmentation index in patients with various grades of varicoceles can be neglected, whereas most patients with varicocele of grades II and III had DFI >30%. Varicocele is associated with high levels of DNA damage in spermatozoa and reduced zinc levels that correlate with different grades of disease. Therefore, DNA fragmentation index and zinc concentration can be used as essential additional diagnostic test for patients with clinical varicocele. A study should be conducted to evaluate the benefits of zinc supplementation to improve seminal parameters in patients with varicocele.