Though a varicocele is more common on the left, bilateralism seems to be on the rise with recent data suggesting over 30–80 % of varicocele being bilateral (Gat and Bachar 2004). When an isolated right-sided varicocele is identified, it warrants further investigation to rule out a retroperitoneal anomaly, although it could also be a normal anatomical variant. Why are varicoceles more common on the left side? The left internal spermatic vein follows a perpendicular course that is approximately 8–10 cm longer than the right before it enters the left renal vein. This results in increased hydrostatic pressure in the left internal spermatic vein. Also, the left internal spermatic vein because of its perpendicular insertion allows the direct transmission of renal vein pressure to the left internal spermatic vein. The right spermatic vein enters the inferior vena cava at an angle, thus preventing direct pressure transmissions from occurring (Siegel et al. 2006). Furthermore, the left internal spermatic vein lacks functional valves that can lead to regression of blood. There could be a partial obstruction of the left internal spermatic vein because of the compression of the left renal vein between the aorta and upper mesenteric artery (nutcracker syndrome) (Naugton et al. 2001).

The etiology of varicocele is multifactorial; similarly the pathophysiology too involves multiple mechanisms. Increased scrotal temperature, high intratesticular pressures, reflux of toxic metabolites, hypoxia and reactive oxygen species, and effect on hormones have all been suggested as possible mechanisms (Fuzisawa et al. 1989; Comhaire 1991). The increased temperature of the scrotum results from reflux of warm blood from the abdominal cavity. This may be a result of the damage or absence of valves in both the internal spermatic vein and cremasteric or external spermatic veins (Goldstein and Eid 1989). The venous tone of the spermatic plexus increases resulting in high hydrostatic pressures.

One study demonstrated that the pressures were actually 19.7 mmHg higher than when compared to the control groups (Shafik and Bedeir 1980). This increased venous pressure can compromise arterial pressure which is required to maintain homeostasis of intratesticular pressure. In the lab looking at fragments from the spermatic vein has revealed alterations in the longitudinal muscle layers, in addition to a decrease in the number of nerve elements and vasa vasorum present in the vessel wall. However, we do not know whether the decrease in the vasa vasorum is a change that suggests causation due to the varicocele or whether this is simply a reactive change of no clinical significance. Nevertheless, these findings suggest a defective contractile mechanism of blood transport through the venous plexus (Tilki et al. 2007). Dysfunction may result by means of chronic vasoconstriction of the spermatic epithelium caused by an increased concentration of toxic metabolites from the adrenal gland (Naugton et al. 2001). Oxidative stress which results from excessive reactive oxygen species (ROS) is increasingly being recognized as a major factor in infertility Said et al. 2005, 1; Agarwal et al. 1994; De Lamirande and Gagnon 1992).

The human body possesses a minimum quantity of ROS for regulating normal sperm function; however, in about 25–40 % of infertile men, the semen contains an excessive amount Marmar 2001; Padron et al. 1997). ROS are needed for regulating normal sperm functions such as sperm capacitation, the acrosome reaction, and sperm–oocyte fusion (De Lamirande and Gagnon 1992; Marmar 2001; Padron et al. 1997).

Elevated ROS and diminished antioxidant capacity have been associated with varicocele (Hendin et al. 1999). However, since both fertile and infertile men show similar findings, it is unclear whether ROS is a cause or consequence. Oxidative stress has also been associated with increased DNA fragmentation in patients with varicocele (Smith et al. 2006). Altered production of steroids in the testis is also a proposed mechanism of varicocele affecting fertility. Some early reports suggested decreased testosterone levels in men with varicocele, whereas others suggested that this was not the cause (Hudson et al. 1983; Swerdloff and Walsh 1975).

The jury has still not given a verdict on the effect that varicocele has on semen parameters and its subsequent effect on male infertility. Semen parameters can either be normal, or there can be different findings like oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of findings. Some studies suggest a gradual deterioration of seminal parameters in the presence of varicocele, ultimately leading to azoospermia (Papadimas and Mantalenakis 1983). Other studies reveal that semen parameters may not be affected at all as there is no significant difference between infertile men and men in the general population with or without varicocele (Redmon et al. 2002). Interestingly, a large-scale study by the WHO showed significantly lower sperm concentration in infertile men with varicocele compared to men with idiopathic infertility, but did not give any evidence regarding the impact of varicocele on sperm motility and morphology (WHO 1992). Strictly speaking a cause–effect relationship between the presence of varicocele and its impact on semen parameters remains unproven. Another plausibility explanation is that varicocele may be an incidental finding in men with idiopathic infertility and men with isolated seminal plasma abnormalities.

Varicocele and its effect on semen parameters have been a subject of intense debate. Varicocele can affect sperm concentration, count, and motility. Some studies suggest that varicocele may affect spermatogenesis, regardless of fertility status. Sperm counts in both fertile and infertile men with varicocele were lower compared to controls, but the fertile group showed higher sperm counts (Nagao et al. 1986). The lower concentration and motility reported according to researchers could be attributed to germ cell apoptosis, to increased concentration of reactive oxygen species, or to the presence of antisperm antibodies (Yeniyol et al. 2003). According to MacLeod and colleagues, varicocele induces what is known as a stress pattern on sperm morphology in over 90 % of his infertile patients (MacLeod 1965). Others opined that the stress pattern may not be pathognomonic of a varicocele (Saypol 1981). It is currently difficult to come to any conclusion regarding the effect of varicocele on semen parameters.