Varicocele-induced infertility: Newer insights into its pathophysiology

Department of Urology, Division of Male Reproductive Medicine and Surgery, Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.
Indian Journal of Urology 01/2011; 27(1):58-64. DOI: 10.4103/0970-1591.78428
Source: PubMed


The association between varicoceles and male infertility has been known since the 1950s; however, the pathophysiology of the process remains uncertain. The primary proposed hypotheses involve hyperthermia, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, and reactive oxygen species. It is difficult to identify a single or dominant factor, and it is likely that many of these factors contribute to the infertile phenotype seen in clinical practice. Moreover, patient lifestyle and genetic factors likely affect patient susceptibilities to the varicocele insult. While the current studies have weaknesses, they provide building blocks for futures studies into the pathophysiology of the varicocele.

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    • "4–6, 7–9 and others – the differences between the table groups are significant according to Chi-squared test with p < 0.05. antagonists and factors that impact the proliferation–apoptosis balance (Marmar, 2001; Benoff et al., 2009; Chang et al., 2010; Eisenberg & Lipshultz, 2011; Esteves, 2012; Guo et al., 2012; Gashti et al., 2013 and others). "
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    ABSTRACT: The role of antisperm antibodies (ASA) in the aetiopathogenesis of varicocoele-related male infertility remains unclear. The objective of this study was to determine whether varicocoele is associated with antisperm immune response and whether this factor provides additional affect on male fertility. We performed a multicentral, prospective study that included the clinical examination of 1639 male subjects from infertile couples and 90 fertile men, the evaluation of the absolute and relative risks of immune infertility associated with varicocoele and the impact of the autoimmune response on the semen quality. The methods used were as follows: standard examination of seminal fluid according to WHO criteria; ASA detection in seminal fluid using mixed antiglobulin reaction (MAR) and direct flow cytometry; measurement of spontaneous and ionophore-induced acrosome reactions; oxidative stress evaluation with luminal-dependent chemiluminescence method and evaluation of DNA fragmentation by sperm chromatin dispersion. The prevalence of varicocoele-related immune infertility is about 15% and does not depend on the grade of vein dilatation both in primary and secondary fertility disorders. Varicocoele is not an immediate cause of autoimmune reactions against spermatozoa, but is a cofactor increasing ASA risk; the OR of immune infertility after a testicular trauma in varicocoele patients increases twofold. In varicocoele patients, the autoimmune antisperm reaction is accompanied by a more significant decrease in the semen quality (concentration and number of progressively motile and morphologically normal spermatozoa in the ejaculate), acrosome reaction disorders (presence of pre-term spontaneous and lack of induced reactions) and an increase in the proportion of spermatozoa with DNA fragmentation. These disorders correlate with the level of sperm oxidative stress; reactive oxygen species (ROS) production in ASA-positive varicocoele patients is 2.8 and 3.5 times higher than in ASA-negative varicocoele patients and fertile men respectively. We did not find correlation between the grade of spermatic cord vein dilatation and ROS production.
    Preview · Article · Nov 2013 · Andrology
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    • "Varicoceles can present bilaterally, but the left testis is usually more affected at the age of puberty. These anatomical and age predilections might be attributed to the difference in the drainage of the testicular veins between right and left testis and the increase in the blood flow in testicular veins, respectively (Dobanovacki, 2010; Eisenberg and Lipshultz, 2011). Varicoceles are often classified as clinical or subclinical types. "
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    ABSTRACT: Varicocele is a dilatation of the pampiniform venous plexus and internal spermatic veins. It affects about 15-20% of male population and can cause infertility. To describe the most significant ultrastructural changes of the smooth muscle cells in grade 3 varicocele veins. The authors analyzed 2- to 3-cm tracts of pampiniform venous plexus from 20 patients who underwent varicocelectomy for left varicocele. Light microscopic examination was performed with Van Gieson's stain. Ultrastructural examination was done using scanning and transmission electron microscopy. Light microscopic examination revealed irregularity and separation of medial smooth muscle cells by abundant collagen fibers in varicocele veins. On scanning electron microscopy, the medial layer of varicocele veins showed hypertrophy, irregularity, and separation of the outer longitudinal smooth muscle cells and deposition of numerous fatty globules in between muscle fibers. Transmission electron microscopy showed marked indentation and chromatin condensation of the nucleus, presence of clear vacuoles and myelin figures in the cytoplasm and plasmalemmal projections and formation of ghost bodies. Furthermore, smooth muscle cells were found to have pseudopodia-like projections around adjacent elastic and collagen fibers. The degenerative changes observed in smooth muscle cells and presence of abundant collagen fibers in the medial layer may contribute to the development of the varicocele of pampiniform venous plexus. Further molecular studies are required to shed more light for the underlying mechanism.
    Full-text · Article · Aug 2012 · Ultrastructural Pathology
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    ABSTRACT: Of all men consulted for infertility, around 30% appear to have a varicocele, therefore, this male dysfunction has been considered as a potential cause of infertility in many patients. Emerging studies point out spermatozoa progressive motility as the most important predictor of fertility provided that the analysis was carried out with infertility duration, thus leaving unsolved problem to evaluate the spontaneous testicular damage during the very early phase in varicoceles. Given the deterioration of testicular function caused by varicoceles is progressive, the early and efficient evaluation of testicular damage would be of great importance for the future medical intervention in this population. The resultant mechanism by which varicoceles affect testicular function remains unclear, but the increase in testicular temperature is most commonly accepted aetiology. In this context, we hypothesize that metastasis-associated protein 1 (MTA1), an intrinsic DNA damage response component, possessing transient protective effect in primary spermatocytes against heat stress, bears the potential to be a diagnostic biomarker for the assessment of early testicular damage in varicoceles. The facet that the decrease of MTA1 expression appears much earlier than the beginning of apoptotic wave after heat stress warrants its theoretical rationality and technical accessibility for biochemical application. Basically, MTA1 participates in the maintenance of early apoptotic balance induced by hyperthermal stimulation by elevating the deacetylation level of p53, a master regulator responsible for the initial phase of germ cell apoptosis induced by hyperthermia. These knowledges collectively promote our belief that information from future experiments designed to further study MTA1 during spermatogenesis will provide a scientific basis for the development of a novel biomarker for early diagnosis of testicular detriment in varicoceles, which should lead to improved outcomes in this progressive pathology.
    No preview · Article · Feb 2012 · Medical Hypotheses
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