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.

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.

Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele / 中华男科学杂志

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 (［21.62 ± 9.25］ vs ［28.88 ± 12.92］ ×10⁶/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (［98.33 ± 0.15］% vs ［96.27 ± 0.18］%, P < 0.05) and DNA fragmentation index (［19.72 ± 3.17］% vs ［10.96 ± 3.82］%, 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.

A correlation between selenium and carnitine levels with hypo-osmotic swelling test for sperm membrane in low-grade varicocele patients.

OBJECTIVE: The hypo-osmotic swelling (HOS) test predicts membrane integrity by determining the ability of the sperm membrane to maintain equilibrium between the sperm cell and its environment. The aim of our study was to determine the correlation between selenium and carnitine levels in the seminal fluid with HOS test for sperm membrane in low-grade varicocele patients. PATIENTS AND METHODS: Study numbered 64 examinees who suffered from low-grade varicocele and were divided into two groups, according to fertility potential and HOS test outcome. The study also included a control group of 64 healthy subjects, with no varicocele. RESULTS: From the Shapiro-Wilk's test, it is clear that carnitine distribution differs significantly from normal (0.938, p = 0.03). In distribution of selenium, Kolmogorov-Smirnov test clearly shows statistically significant deviation from the normal curve (z = 0.225, p < 0.000), likewise Shapiro-Wilk's statistic (0.787, p < 0.000). According to the results, the second group had significantly higher levels of carnitine and selenium than the first group of examinees (p < 0.05); therefore, when we compared epididymal markers with HOS tests outcomes, we found significant differences between the two groups. There were no significant differences between second group and healthy subjects (p > 0.05). CONCLUSIONS: HOS test outcome in varicocele patients is directly proportional to the carnitine and selenium levels, which could play a major role in both determining fertility parameters and in the treatment of its impairment. This result is important for sub-clinical varicocele in infertile patients with normal semen analysis, since there is no evidence of benefit from any treatment so far.

The impact of vitamin E supplementation on semen parameters and pregnancy rates after varicocelectomy: a randomised controlled study.

In this study, we aimed to investigate the impact of vitamin E supplementation on semen parameters and pregnancy after varicocelectomy. Forty-five infertile male patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 22 receiving vitamin E for 12 months, and 23 as the control group without receiving any supplementation. The pre-operative parameters of semen analyses and pregnancy rates of both groups were compared with those of post-operative parameters. There were no statistically significant differences between the groups in terms of sperm count and motile sperm percentage, in pre-operative, post-operative 3rd month, post-operative 6th month and post-operative 12th month periods. Repeated-measures anova was performed, and sperm count, percentage of change in sperm count, motile sperm count and percentage of change in motile sperm count of the groups were compared. The administration of vitamin E increased all of these parameters; however, they were not found to be statistically significant. In conclusion, vitamin E supplementation might improve the sperm parameters after varicocelectomy; however, further studies including larger number of samples are needed to make a proper decision on vitamin E supplementation after varicocelectomy.

Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: a case control study.

Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele.

Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

[Treatment of varicocele infertility men patients of different Chinese medical syndrome types by integrative medicine treatment selection: a primary research].

OBJECTIVE: To explore the optimal treatment selection for treating varicocele (VC) male infertility patients accompanied with oligozoospermia or azoospermia of different Chinese medical syndrome types by comparing the efficacies of integrative medicine. METHODS: One hundred and twenty male infertility patients with VC accompanied with oligozoospermia or azoospermia were assigned to Chinese medical treatment group (A) and the surgical group (B), each consisting of three Chinese medical syndrome types, i.e., damp-heat stagnation syndrome (DHSS), Shen-deficiency blood stasis syndrome (SDBSS), and blood stasis stagnation syndrome (BSSS), 20 in each group. Corresponding Chinese medical treatment was administered to those in Group A, C, and E, while microscopic ligation of internal vena spermatic was administered to those in Group B, D, and F. The routine analysis of semen, biochemical analysis of seminal plasma, and serum sex hormones (prolactin, testosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) were performed before treatment and by the end of the 24th week after treatment. RESULTS: Totally 18 patients' spouses were pregnant. Of them, 1 in Group A of DHSS (abbreviated as Group A), 3 in Group B of DHSS (abbreviated as Group B), 4 in Group A of SDB-SS (abbreviated as Group C), 5 in Group A of SDBSS (abbreviated as Group D), 1 in Group A of BSSS (abbreviated as Group E), and 4 in Group B of BSSS (abbreviated as Group F). After 24-week treatment, the sperm concentration, class a sperm percentage, class a + b sperm percentage, the motility rate, the seminal plasma of fructose density, and the seminal plasma neutral alpha-glucosidase were more significantly improved in Group B, C, D and F, when compared with the same group before treatment (P <0. 01, P <0. 05). There was no statistical difference in the aforesaid indices between before and after treatment in Group A and Group E (P >0.05). As for the improvement percentage of seminal routine indices, the difference of the seminal plasma of fructose density, and the difference of seminal plasma neutral alpha-glucosidase between before and after treatment in the same Chinese medical syndrome types, better effects were obtained in Group B than in Group A (P <0.01), and better effects were obtained in Group F than in Group E (P <0.01). There was no statistical difference between Group C and D (P >0.05). There was no statistical difference in the 5 items of sex hormones in each group between before and after treatment (P >0.05). CONCLUSIONS: Surgical treatment could effectively improve the semen quality for male infertility VC patients accompanied with oligozoospermia or azoospermia. Of them, Chinese medical treatment could be recommended to those of SDBSS who would not receive surgical treatment.

Varicocele retrograde embolization with boiling contrast medium and gelatin sponges in adolescent subjects: a clinically effective therapeutic alternative.

PURPOSE: Varicoceles occur in approximately 15% of adolescent male subjects and may impair future fertility. The present study describes a varicocele treatment technique involving percutaneous retrograde embolization with boiling hot contrast medium and gelatin sponge pledgets. MATERIALS AND METHODS: A retrospective review of medical records and imaging of all patients who underwent percutaneous retrograde varicocele embolization from 2005 to 2010 was performed. Pre- and postembolization symptoms, physical findings, and ultrasound findings were documented. Fifteen patients (16 embolizations) were identified, with an average age of 15.9 years (range, 12-18 y). Nine were referred because of persistent varicocele after surgical ligation. Three had grade 2 and nine had grade 3 varicoceles. Two had grade 1 varicoceles; one was painful and one was associated with poor semen quality. One varicocele was not clinically evident, but was associated with persistently decreased testicular size. Nine patients had pain or discomfort, and six had no discomfort. Clinical resolution was defined by a combination of symptom resolution and a lack of physical examination findings of varicocele or findings of treated varicocele. RESULTS: Fifteen of the 16 embolizations (94%) were technically successful. Clinical resolution was documented in 14 of 15 patients (95%); one patient experienced a recurrence at 30 months, which was successfully reembolized. One patient experienced temporary paresthesia of the left thigh. There were no major postprocedural complications. Mean follow-up duration was 11 months. CONCLUSIONS: Retrograde embolization of varicoceles in adolescent subjects with the use of boiling hot contrast medium and gelatin sponges is a promising technique that appears effective.

[Comparative assessment of extraperitoneoscopic and laparoscopic methods of varicocele treatment].

The article presents a comparative analysis of the results of extraperitoneoscopic and laparoscopic methods of internal seminal vein ligation in 90 varicocele patients (40 and 50 patients, respectively); describes insufficiently known method--extraperitoneoscopic operations. The working space in the prevesical space is created by direct introduction of trocars with optics into the prevesical space without any additional tools. The operations took the same time. Laparoscopic operations required more postoperative analgetic drugs than extraperitoneoscopic ones. By pain intensity and physical activity scales, varicocele patients' quality of life was higher after extraperitoneoscopic operations than after laparoscopic and open operations. Thus, extraperitoneal ligation of the seminal veins by direct introduction of endoscope into the preperitoneal space with CO2 insufflation without prior creation of working space is simple for use, low invasive, has low risk of visceral injury and can be applied as an alternative to laparoscopy.

May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele?

We performed a randomized, prospective, controlled, intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia (5-20 million/ml) 6 months after retrograde embolization. Forty-two subjects were enrolled and randomized in the study. Treated group (20 subjects) was assigned to receive antioxidant therapy (NAC 600 mg and vitamins-minerals). Untreated group (22 subjects) received no adjunctive medical therapy and was used as controls. Our data were analyzed with an intention to treat strategy. A statistically significant increase in sperm count after antioxidant therapy was recorded (P=0.009). After this therapy, no statistical differences in percentage of WHO class A motile sperm (P=0.752) and typical forms (P=0.926) were found. The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold (OR=20.1; CI 95%=1.05-43.2; P=0.014) higher than a man who was untreated. No significant impact on spontaneous pregnancies was found after antioxidant therapy. Despite this preliminary data, we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males. However, this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months.

Modified high varicocelectomy: outpatient microsurgical procedure.

Fifty patients underwent modified high varicocelectomy as outpatients. Twelve of the 22 unilateral varicocelectomies were performed under local anesthesia. All patients tolerated the procedures well, and none required admission to the hospital. The modified high approach, which exposes the area above the internal inguinal ring and of the posterior spermatic cord, is straightforward and insures that both internal spermatic and cremasteric veins can be ligated. Use of the operating microscope prevents the inadvertent ligation of the testicular artery and lymphatics.