Varicocele and male infertility: Part I (2001)

To whom correspondence should be addressed at: NS-LIJ Research Institute, 350 Community Drive, Room 125, Manhasset, NewYork 11030 USA. E-mail: sbenoff@nshs.eduThe term ‘varicocele’, which was coined by Curling in 1843(Noske and Weidner, 1999), refers to an abnormal dilation of thetesticular veins within the pampiniform plexus. Varicocele occurmore frequently on the left side (Riba, 1947), most probably dueto asymmetry of the internal spermatic veins resulting inalterations in biochemical properties (e.g. increased extensibilityin comparison with the right spermatic vein) (Lund et al., 1998).Varicocele was recognized and treated as early as the 1st centuryAD and, over the centuries, the condition was an importantexclusion criterion for military service (Noske and Weidner,1999). However, it was not until 1952 that the possibleassociation between the presence of a varicocele and humanmale subfertility was formally recognized. Such recognition wasderived from a single case report, of a man diagnosed withmaturation arrest by testis biopsy, in which bilateral varicoce-lectomy resulted in improved sperm count and pregnancy bycoitus (Tulloch, 1952). A ﬂurry of reports followed, suggestingthat the incidence of varicocele was increased in subfertile men(Russell, 1954; Scott, 1958) and that improvement in semenparameters occurred after surgical intervention (Davidson, 1954;Tulloch, 1955; Young, 1956; Scott, 1961; Charny, 1962;MacLeod, 1965; Dubin and Hotchkiss, 1969).In current medical practice, impairment of semen parameterssuggests that a varicocele may be present. In particular, a decreasein sperm number, motility and morphologically normal sperma-tozoa with an increase in head abnormalities is most often found(MacLeod, 1965; Brown, 1976; Belker, 1981; Naftulin et al.,1991). This ﬁnding alone should provide sufﬁcient impetus forfurther evaluation of the male. Of particular clinical importance isthat a signiﬁcant number of men presenting with subfertility havemedical issues that would not have been diagnosed if an impairedsemen analysis had not led to further evaluation (Honig et al.,1994; Jarow, 1994). Several investigators have also presentedcompelling data suggesting that a varicocele causes a progressivedecline in fertility with upwards of 80% of men presenting withsecondary subfertility having a varicocele (Gorelick andGoldstein, 1993; Witt and Lipshultz, 1993). This decline isthought to be due to progressive testicular damage, as testicularmass and sperm counts in patients with varicocele decline withage (Lipshultz and Corriere, 1977). The occurrence of testiculardamage with varicocele has alternatively been attributed to: (i)increased scrotal (intratesticular) temperature; (ii) venous stasis;(iii) reduced oxygen tension, and/or (iv) toxic metabolites fromthe adrenals or kidney (Brown et al., 1967). To date, heat stressremains the favoured mechanism (Comhaire, 1991; Mieusset andBujan, 1995; Wright et al., 1997).Despite such ﬁndings, it is apparent that >85% of men withvaricocele are fertile (Sylora and Pryor, 1994). The same semenabnormalities are observed in fertile and infertile men withvaricocele (Nagao et al., 1986). Although varicocele repair canreduce testicular temperature (Agger, 1971; Yamaguchi et al.,1989; Wright et al., 1997), only about one half of the studies onthe effects of varicocele repair report a signiﬁcant improvement inpregnancy rates after treatment, when compared with a control(no treatment) group. In the absence of molecular markers, whichdiscriminate between fertile and infertile men with varicocele,whether or not patient selection contributes to these disparateﬁndings is an open question. As will be seen from the contents ofthis mini symposium, varicocele remains a controversial topic,which is often the subject of heated debates between andrologistsand urologists, both about appropriate clinical management andabout the mechanisms producing infertility with varicocele. Thismini symposium was organized to address these issues.This mini symposium is divided into two parts: both temporallyand with regard to content. The ﬁrst part, in this issue of HumanReproduction Update (Cozzolino and Lipschultz, 2001; Jarrow,2001; Kamischke and Nieschlag, 2001; Silber, 2001; Turner,2001) covers two main questions: ﬁrstly, does varicocele producean infertile state? and, secondly, does varicocele repair increasepregnancy rates? The second part of this mini symposium (to bepublished in a later issue of Human Reproduction Update)isdirected at the identiﬁcation of varicocele-associated defects insperm function and the underlying pathophysiology of theinfertile state, including the role of ancillary factors.