The Varicocele as Related to Fertility

The Varicocele as Related to Fertility JORDAN S. BROWN, M.D., LAWRENCE DUBIN, M.D., and ROBERT S. HOTCHKISS, M.D. VARICOCELECTOMY in the subfertile male, where indication for this procedure exists, has frequently resulted in impressive improvement in semen quality. During the past few years, we have performed this procedure in approximately 150 subfertile males. Our results confirm the improvement reported by the British investigators 3, 10, 12 and by Charny in the United States. MacLeod, in 1965, and more recently Zorgniotti and MacLeod reported a 40% conception rate following varicocelectomy in 117 patientsa series in which we participated. Arterial CIRCULATORY ANATOMY OF THE TESTIS The internal spermatic or testicular artery arises from the aorta, below the renal arteries, parallels the internal spermatic vein, and descends via the spermatic cord into the scrotum, supplying the head of the epididymis and testis. The deferential or vasal artery arises from the superior vesical artery, a branch of the hypogastric artery, and accompanies the vas deferens with its companion vein into the scrotum. It supplies the lower pole of the epididymis and testis. The cremasteric or external spermatic artery is derived from the deep epigastric artery, which is a branch of the external iliac artery. It joins the cord at the level of the external inguinal ring and supplies the tail of the epididymis and the lower pole of the testis. This artery is inconstant and, according to Harrison, exists in a functional fashion in only two-thirds of men. These arteries communicate with each other just below the external From the Department of Urology, New York University School of Medicine, New York, N. Y. Supported by Grant HD 01301-01 SI from the U. S. Public Health Service. Presented at the 22nd Annual Meeting of the American Fertility Society, Chicago. Ill., Apr. 29-May 1, J966. 46

VOL. 18, No.1, 1967 V ARICOCELE AND FERTILITY 47 inguinal ring (Fig. 1). The arteries distal to this point are end arteries. Any injury to an artery inferior to the anastomoses may result in partial infarction of the testis. Unlike the venous circulation, these arteries do not anastomose with vessels outside their group. Venous The anterior group or internal spermatic vein on the right drains the testis and enters the vena cava obliquely, caudad to the renal vein, while on the left it inserts at a right angle into the renal vein (Fig. 2). As pointed Vasal veshls Spermatic vessels Vas deferens Vasal anastomoses with spermatic Fig. 1 (above). Distal arterial blood supply of testes, showing arterial anastomoses. Fig. 2 (at side). Venous anatomy of testis.

48 BROWN ET AL. FERTILITY & STERILITY out by Rivington, this vein has a variable number of valves, the largest usually appearing in the distal vein, adjacent to or inside the renal vein. The middle group or the vasal vein accompanies the vas and empties into the superior vesical vein. The posterior group, cremasteric, or external spermatic vein leaves the cord, generally at the external inguinal ring. It communicates with the superficial and deep pudendal systems before terminating in the deep epigastric vein. The venous channels, unlike the arterial, anastomose extensively with each other and with veins outside their immediate area. In 1950, EI-Sadr and Mina demonstrated in cadavers marked collateral venous circulation, including the presence of contralateral communications. VENOGRAPHY IN THE SUBFERTILE MALE In the hope of better understanding the venous anatomy, the etiology of varicocele, and the manner in which varicocele adversely affects spermatogenesis, internal spermatic venography has been performed in 32 patients. Three studies have been done in subfertile male patients without varicocele, 25 in patients with the usual left varicocele, and 4 in men with bilateral varicoceles. The method employed, an original one (Fig. 3), is as follows. During varicocelectomy, the internal spermatic vein was exposed above the internal inguinal ring, and a No. 16 angiocath was introduced 3-4 cm., initially in the direction of the renal vein and subsequently toward the testis. With the patient's head elevated at a 45 angle, radiopaque material was introduced under low pressure at a rate of 4-6 cc./min. X-ray films were obtained during both injections. Figures 4-13 illustrate representative findings on the venograms. Venogram in the Subfertile Male Without Varicocele The left renal vein was normal (Fig. 4), and the right-angle termination of the internal spermatic vein into the renal vein was clearly demonstrated. There was no retrograde passage of radiopaque media down the internal spermatic vein (Fig. 4). Valve-like irregularities appeared along the internal spermatic vein (Fig. 5). When the radiopaque media was introduced in the direction of the left testis, the venous anatomy of the testis was clearly depicted (Fig. 6), and cross-collateral venous circulation was in part demonstrated (Fig. 6).

" VOL. 18, No.1, 1967 VARICOCELE AND FERTILITY 49 Venogram in the Subfertile Male with Left Varicocele In the presence of varicocele, valvular impressions were not seen in the internal spermatic vein (Fig. 7), and there was retrograde How of blood down the internal spermatic vein. The venous circulation of the left testis was abnormally dilated, a state consistent with varicocele (Fig. 8). Crossvenous collateral circulation was again visualized (Fig. 8). Fig. 3. Method employed in internal spermatic venography, showing introduction of radiopaque media into patient's internal spermatic vein. Venogram in the Subfertile Male with Bilateral Varicoceles With bilateral varicocele, the right internal spermatic vein entered the right renal vein in an anomalous fashion (Fig. 9), rather than terminating in the vena cava. This observation was further substantiated by an X-ray of the inferior vena cava. Again, there was extensive cross-collateral venous circulation, but in addition, the left internal spermatic vein could be visualized at the time of injection of the right varicocele (Fig. 10). The left renal vein was dilated and filled abundantly in a retrograde fashion (Fig. 11 and 12). The radiopaque material which outlined the left renal vein sharply terminated proximal to the juncture of the renal vein with the inferior vena cava (Fig. 11 and 12). Retrograde passage of radiopaque material down the internal spermatic vein was again noted,

Fig. 4 (left). Left internal spennatic venography in subfertile male without varicocele, showing radiopaque media introduced in direction of left renal vein. Fig. 5 (center). Enlargement of Fig. 4 showing valve-like impressions in internal spermatic veins. Fig. 6 (right). Left internal spennatic venography in same patient as in Fig. 4, with radiopaque media introduced in direction of left testis, showing cross-venous collateral circulation.

VOL. 18, No.1, 1967 VARICOCELE AND FERTILITY 51 (Fig. 11). The entire venous system of the left testis, including the left vasal vein, appeared tortuous and dilated, and there was cross-venous anastomosis (Fig. 13). Etiology VARICOCELE Varicocele is a pathologic alteration in the venous circulation of the testis. Our venographic studies support the belief that the entire venous circulation is involved. It has been estimated that 98% of varicoceles occur on the left, while the remainder exist on the right alone or as a bilateral condition. Fig. 7 (left). Left internal spermatic venography in subfertile male with left varicoeele. Radiopaque media injected in direction of left renal vein, indicating absence of valvelike impressions but retrogression of blood How. Fig. 8 (right). Left internal spermatic venography in same patient as in Fig. 7. Injection now in direction of left testis, showing dilation of veins and cross-venous collateral circulation.

52 BROWN ET AL. FERTILITY & STERILITY There is, in general, agreement that varicocele is the result of the retrograde passage of blood from the renal vein down the internal spermatic vein, as demonstrated often in our radiologic studies. To accommodate this increased retrograde flow of blood, the veins of the testis become dilated or varicose. Incompetency of the cremasteric and vasal vein is suspected as being a potential cause or contributing factor in the etiology of varicoceles. However, this has not been noted to exist in our series or reported by others as yet. Ahlberg et az., in 1965, during trans femoral aortography, demonstrated a 12% incidence of retrograde flow into the gonadal vein in 105 patients studied. This was more frequently seen in females than in males. Further observations made by this same group in Fig. 9 (left). Right internal spermatic venography in subfertile male with bilateral varicocele, with radiopaque media introduced in direction of right renal vein. Fig. 10 (right). Right internal spermatic venography in same patient as in Fig. 9. Radiopaque media injected in direction of right testis, showing extensive cross-venous collateral circulation and presence of media in left internal spermatic vein.

VOL. 18, No.1, 1967 V ARICOCELE AND FERTILITY 53 Fig. 11 (top left). Left internal spermatic venography in same patient as in Fig. 9. Radiopaque media introduced in direction of left renal vein. Fig. 12 (top right) Left internal spermatic venography in patient with left varicocele. Radiopaque media introduced in direction of left renal vein, clearly demonstrating filling of renal vein. Fig. 13 (bottom right). Left internal spermatic venography in same patient depicted in Fig. 9. Radiopaque media introduced in direction of left testis, showing tortuosity and dilatation of veins.

54 BROWN ET AL. FERTILITY & STERILITY cadavers disclosed that congenital absence of valves was more commonly noted in males and, conversely, incompetency of existing valves occurred more frequently in females. Retrograde flow down the female gonadal vein does exist. Whether a varicocele-like state of the broad ligament resuits and, if so, whether this could be detrimental to female fertility is not known. The etiology of retrograde flow is not always apparent. Mechanisms that are thought to contribute to this phenomenon are congenital absence of valves in the gonadal vein, and incompetency of existing valves. Possible factors leading to incompetency are as follows: (1) The long course of the internal spermatic vein and the frequently assumed erect posture of man tend to act as a deterrent to valvular competency. (2) The right angle termination of the internal spermatic vein poorly equips this vein to resist valvular incompetency. (3) The presence of adrenalin-iaden blood bathing the orifice of the gonadal vein possibly adversely affects competency. ( 4) The left renal vein is compressed between the superior mesenteric artery anteriorly and the aorta posteriorly, very much like a nut within a nutcracker. This phenomenon was frequently observed, and consequently supported, in our venographic studies. The pinching effect by these arteries on the renal vein could cause an increased renal vein pressure, which in time could be transmitted to the internal spermatic vein, mechanically rendering their valves incompetent. Effect on Fertility The mechanism by which varicocele impairs spermatogenesis is not clear. Whether varicocele in itself is responsible or whether it is merely one manifestation of a more complex pathologic state is not, as yet, known. The fact that some men with varicoceles are fertile should not minimize the potentially detrimental role of this abnormality. It would be reasonable to claim that varicocele is uniformly detrimental. One might postulate that a fertile male with a varicocele would have better semen without this condition. Furthermore, in the past, there has been reluctance to accept the varicocele as a factor in male infertility because of the erroneous concept that this was a unilateral circulatory disturbance. The work of EI-Sadr and Mina in cadavers and our venographic studies in human male patients establishes the bilaterality of this vascular abnormality. Mechanisms by which varicocele could adversely affect spermatogenesis are as follows. 1. Varicocele may interfere with the necessary thermoregulatory mechanism, as proposed by Hanley. He reported a decrease in testicular tem-

VOL. 18, No.1, 1967 V ARICOCELE AND FERTILITY 55 perature following varicocelectomy in most of his patients. Subsequent studies9 11 elsewhere could not support any thermal changes. 2. Venous stasis may result in secondary changes in the testicular anatomy, which may be analogous to stasis changes seen in the lower extremities with varicose veins. 3. Venous stasis may result in decreased oxygen tension, which in turn may interfere with tissue metabolism. 4. In the retrogressing venous blood, toxic-metabolic or endocrine substances from either the adrenal gland or kidney may be present in sufficiently high concentrations to render them spermatocidal. This possibility is presently favored by us as being the most likely cause for the bilateral testicular damage seen in the subfertile male Witll varicocele. SUMMARY The venous anatomy of the testis has been presented. Internal spermatic venography has demonstrated (1) the absence of valves in the left internal spermatic vein in the presence of varicocele, (2) the right-angle termination of the left internal spermatic vein with the renal vein, and (3) the retrograde passage of blood down the internal spermatic vein. In addition, varicocele has been demonstrated to be comprised of dilated veins of the entire venous circulation of the testes. Crosscollateral venous communications were found in living human males with and without varicoceles. The etiology of varicocele is reviewed. Possible mechanisms by which it impairs spermatogenesis are interference with the thermoregulatory mechanism, venous stasis causing testicular anatomic changes or decreased oxygen tension, and/or spermatocidal concentrations of metabolic or endocrine products in the retrogressing venous blood. New York University School of Medicine 566 First Ave. New York, N. Y. 10016 REFERENCES 1. AHLBERG, N. E., BARTLEY, 0., and CHIDEKEL, N. Retrograde contrast filling of the left gonadal vein. Acta Radiol (Stockh) 3:385, 1965. 2. CHARNY, C. W. Effect of varicocele on fertility. Fertil Steril13:47, 1962. 3. DAVIDSON, H. A. Testicular temperature and varicocele. Practitioner 173:703, 1954. 4. EL-SADR, A. R., and MINA, E. Anatomical and surgical aspects in the operative management of varicocele. Urol Cutan Rev 54:257, 1950. 5. HANLEY, H. C. "Surgical Correction of Errors of Temperature Regulation." In Proceedings, 2nd World Congress on Fertility and Sterility, 1956.

56 BROWN ET AL. FERTILITY & STERILITY 6. 7. 8. 9. 10. II. 12. 13. HARRISON, R. G. Functional importance of vascularization of the testis and epididymis for maintenance of normal spermatogenesis. Fertil Steril 3:366, 1952. MAcLEOD, J. Seminal cytology in the presence of varicocele. Fertil Steril16:735, 1965. fuvington, W. Values in renal veins. J Anat Physiol7:163, 1873. RIVO, E., and ROCK, J. Thermogenic effect on spermatogenesis. Presented at the 21st Annual Meeting of The American Society for the Study of Sterility, San Francisco, Calif., Apr. 1965. SCOTT, L. S., and YOUNG, D. Varicocele. Fertil Steril13:325, 1962. TESSLER, A. N., and KRAHN, H. P. Varicocele and testicular temperature. Fertil Steril 17:201, 1966. TULLOCH, W. S. Consideration of sterility. Subfertility in the male. Edinburgh Med J 59:29, 1952. ZORGNIOTTI, A. W., and MACLEOD, J. Treatment and results of varicocelectomy in the subfertile male. Presented at the American Fertility Society, Chicago, Ill., April 1966.