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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

Objective To evaluate the impact of vitamin E supplementation on sperm analysis results in patients post-varicocelectomy. Martials and method This single-center, triple-blind, randomized controlled trial was conducted at Imam Reza Hospital, Mashhad, Iran. Ninety male patients, aged 15–25 years, with infertility and varicocele grade 2 or 3, were randomized into two groups. The intervention group received 400 units of vitamin E daily for 3 months, while the control group received a placebo. Sperm analysis was conducted before and 3 months after the intervention. Statistical analyses were performed using SPSS version 23, with significance set at P  < 0.05. Results A total of 90 patients were enrolled and equally randomized into two groups ( n  = 45 per group). The mean age was 30.68 ± 6.31 years. Post-intervention, the improvement in sperm motility was significantly higher in the vitamin E group compared to the placebo group ( P  = 0.03). Both groups showed significant improvements in sperm motility, count, and morphology from pre- to post-intervention ( P  < 0.001). Conclusion Vitamin E supplementation post-varicocelectomy is associated with improved sperm parameters, suggesting potential benefits in the management of male infertility related to varicocele. However, varicocelectomy alone also results in significant improvements. Trial registration This study is registered at the Iranian Registry of Clinical Trials (IRCT20200911048689N1). Registered on October 10, 2020.

Male infertility represents a significant global problem due to its essential health, social, and economic implications. It is unsurprising that scientific research is very active in this area and that advances in the diagnostic and therapeutic fields are notable. This review presents the main diagnostic advances in male infertility, starting from the changes made in the latest WHO Manual of semen analysis and discussing the more molecular aspects inherent to “omics”. Furthermore, the usefulness of artificial intelligence in male infertility diagnostics and the latest advances in varicocele diagnosis will be discussed. In particular, the diagnostic path of male infertility is increasingly moving towards a personalized approach to the search for the specific biomarkers of infertility and the prediction of treatment response. The treatment of male infertility remains empirical in many regards, but despite that, advances have been made to help formulate evidence-based recommendations. Varicocele, the most common correctable cause of male infertility, has been explored for expanded indications for repair. The following expanded indications were discussed: elevated sperm DNA fragmentation, hypogonadism, orchalgia, and the role of varicocele repair in non-obstructive azoospermia. Moving forward with the available data, we discussed the stepwise approach to surgical sperm retrieval techniques and the current measures that have been investigated for optimizing such patients before testicular sperm extraction. Finally, the key points and expert recommendations regarding the best practice for diagnosing and treating men with infertility were summarized to conclude this review.

PurposeIt is known that sperm preparation techniques in in vitro fertilisation (IVF) are intended to select the best-quality sperm. The aim of this study is to compare sperm the density gradient method and microfluidic chip (Fertile Plus) method in infertile patients by analysing fertilisation rates, pregnancy rates, and sperm morphology and DNA fragmentation rates posed by these two methods.MethodsUsing semen samples obtained from the patients, sperms were prepared with gradient (n = 312) and microfluidic chip methods (n = 116). Fertilisation and pregnancy rates were compared in the first time and in the recurrent IVF trial patients. In addition, the morphology and DNA fragmentation comparison of sperm samples were evaluated by Toluidine blue in situ chemical staining method.ResultsThere was no statistically significant difference between fertilisation and pregnancy rates when compared with study groups in first-time IVF treatment patients. However, in recurrent IVF failure patients, there was a significant difference in fertilisation rates but no statistically significant difference was found in pregnancy rates. The microfluidic chip method significantly decreased sperm DNA fragmentation index according to density gradient method.ConclusionsMicrofluidic chip method may be recommended in patients with recurrent unsuccessful in vitro trials. The sperm DNA fragmentation test prior to the treatment will be helpful in selecting the appropriate sperm-washing method.

The aim of this study was to evaluate the role of platelet count (PLT) and platelet volume indices (PVI) such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) as a clinical biomarker in 64 infertile males with varicocele and 45 controls. In addition, semen parameters, serum total testosterone, FSH and testicular volume were measured before and at 6 months after varicocelectomy. The mean PLT, MPV, PDW and PCT were 231 ± 42 × 103/µl, 9.6 ± 1.8 fl, 16.2 ± 2.5 fl and 0.18% in the patient group respectively. When the patient and control groups were compared, there was a significant increase in mean MPV, PDW and PCT (p < .0001), while platelet count was lower in patients than control group, but with no significant relationship. MPV had a significant negative correlation with total testosterone (p < .03). No significant correlations were found between PVI and testicular volume. After follow‐up of 37.1 ± 1.9 months, a significant negative correlation was found between the preoperative MPV and varicocelectomy outcome in terms of semen values (p < .007). So, the increase in MPV and low total testosterone in men with varicocele may be a feature of high risk of infertility.

Background In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula — Wuzi Yanzong pill — showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. Methods This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. Discussion To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.

Sperm concentration, motility, and morphology were assessed in 765 men in infertile couples and 696 men in fertile couples to identify values that would distinguish fertile from subfertile men. Subfertile ranges were a sperm concentration of less than 13.5 million per milliliter, less than 32 percent motility, and less than 9 percent sperm with normal morphologic features. Fertile ranges were a concentration greater than 48.0 million per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. However, there was extensive overlap between fertile and infertile men with regard to all measures. Semen analysis is routinely used to evaluate the male partner in infertile couples 1 , 2 and to assess the reproductive toxicity of environmental or therapeutic agents. 3 Although widely used thresholds for normal semen measurements have been published by the World Health Organization (WHO), 4 – 7 the available norms for sperm concentration, motility, and morphology fail to meet rigorous clinical, technical, and statistical standards. In recognition of these limitations, the nomenclature in the most recent WHO manual 7 for semen evaluation was changed from “normal” to “reference” values. Two recent prospective studies of semen quality and fertility concluded that the current WHO reference values . . .

Background While reproductive technologies are increasingly used worldwide, epidemiologic, clinical and genetic data regarding infertile men with combined genital tract and renal abnormalities remain scarce, preventing adequate genetic counseling. Methods In a cohort-based study, we assessed the prevalence (1995–2014) and the clinical characteristics of renal disorders in infertile males with genital tract malformation. In a subset of 34 patients, we performed a detailed phenotype analysis of renal and genital tract disorders. Results Among the 180 patients with congenital uni- or bilateral absence of vas deferens (CU/BAVD), 45 (25 %) had a renal malformation. We also identified 14 infertile men with combined seminal vesicle (SV) and renal malformation but no CU/BAVD. Among the 34 patients with detailed clinical description, renal disease was unknown before the assessment of the infertility in 27 (79.4 %), and 7 (20.6 %) had chronic renal failure. Four main renal phenotypes were observed: solitary kidney (47 %); autosomal-dominant polycystic kidney disease (ADPKD, 0.6 %); uni- or bilateral hypoplastic kidneys (20.6 %); and a complex renal phenotype associated with a mutation of the HNF1B gene (5.8 %). Absence of SV and azoospermia were significantly associated with the presence of a solitary kidney, while dilatation of SV and necroasthenozoospermia were suggestive of ADPKD. Conclusion A dominantly inherited renal disease (ADPKD or HNF1B -related nephropathy) is frequent in males with infertility and combined renal and genital tract abnormalities (26 %). A systematic renal screening should be proposed in infertile males with CU/BAVD or SV disorders.

Purpose Despite controversy regarding its clinical value, male fertility investigation mainly relies on semen analysis. Even though reference guidelines are available, manual sperm analysis still suffers from analytical variability, thus questioning the interest of automated sperm analysis systems. The aim of this study is to compared automated computerized semen analysis systems (SQA-V GOLD and CASA CEROS) to the conventional manual method in terms of accuracy and precision. Methods We included 250 men in this double-blind prospective study. The SQA-V GOLD (Medical Electronic Systems) and CEROS, CASA system (Hamilton Thorne) were compared to the standard manual assessment based on the WHO 5th Edition. The main outcome measures were sperm concentration, total sperm number, total motility, progressive motility, non-progressive motility, morphology, motile sperm concentration (MSC) and progressively motile sperm concentration (PMSC) with the three methods. Results Statistical analysis of the test results from the automated systems and the manual method demonstrated no significant differences for most of the semen parameters. The Spearman coefficients of rank correlation (rho) for CASA and the SQA-V GOLD automated systems vs. the manual method were: Sperm concentration (0.95 and 0.95), total sperm number (0.95 and 0.95), MSC (0.94 and 0.96) and PMSC (0.94 and 0.93) correspondingly. Concerning sperm morphology, both automated systems demonstrated high specificity (Sp) and negative predictive values (NPV), despite significantly different medians (CASA: 83.7 % for Sp and 95.2 % for NPV, SQA-V: 97.9 % for Sp and 92.5 %). The highest precision (lowest 95 % confidence interval for duplicate tests) for all semen variables was found in the SQA-V GOLD. Conclusions The advantages of using automated semen analysers are: Standardization, speed (lower turnaround time), precision, reduced potential for human error, automated data recording and less need for highly skilled professionals to run the systems. The disadvantages of using automated systems are: notably the problem with testing some atypical samples and the inability to perform an assessment of morphology abnormalities. Based on the results of this study, the SQA-V Gold demonstrated better agreement vs. the manual method. In conclusion, automated semen analyzers can be used for routine semen analysis providing rapid clinically acceptable results with higher precision, and positively impacting laboratory standardization.

Abstract Context Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date. Evidence Acquisition The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail. Evidence Synthesis/Results Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking. Conclusions Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.