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Varicocele in Infertility: Incidence and Results of Surgical Therapy
Vol. 112, August
THE JOURNAL OF U ROLOGY
Printed in U.S.A .
Copyright © 1974 by The Will iams & Wilkins Co.
~
VARICOCELE IN INFERTILITY: INCIDENCE AND RESULTS OF SURGICAL THERAPY BRUCE H. STEW ART
Correction of varicocele by ligation of t he internal spermatic vein has been standard therapy for more than half a century. 1 However, the causal role of the varicocele in male infertility has been a relatively recent d evelopment . 2 Significant improvement in semen quality in most infert ile patients with varicocele treated surgically has been demonstrated in several large series (table 1). 3- 7 A varicocele develops as a result of incompetency of the valves in the left internal spermatic vein and is probably enhanced by compression of t he left renal vein between the simultaneously pulsating aorta and superior mesenteric artery. Retrograde venous blood flow when the subject is in the erect position affects both testes, since there is extensive cross-venous circulation between the vasal and cremasteric systems. 8 • 9 The precise reason why spermatic vein backflow impairs spermatogenesis is still not clear. Various circulatory, t hermal and endocrine factors have been implicated but as yet have not been proved. 10- 18 HowAccepted for publication January 25, 1974. Read at annual meeting of North Central Section, American Urological Association, Acapulco, Mexico, November 11- 18, 1973. 1 Ivanissevich, 0 .: Left varicocele due to reflux, experience with 4,470 operative cases in 42 years. J. Int. Coll. Surg., 34: 742, 1960. 'Tulloch, W. S.: Consideration of sterility factors in light of subsequent pregnancies; subfertility in the male. Edinburgh Med. J., 59: 29, 1952. 'Tulloch, W. S.: Varicocele in subfertility, results of treatment. Brit . Med. J ., 2: 356, 1955. 'Scott, L. S. and Young, D.: Varicocele: a study of its effects on human spermatogenesis, and of the results produced by spermatic vein ligation. Fertil. Steril., 13 : 325, 1962. 5 Zorgniotti, A. W., MacLeod, J . and Hotchkiss, R. S.: Treatment and results of varicocelectomy in the subfertile male. Presented at annual meeting of The American Fertility Society, Chicago, Illinois, April 1966 . • Charny, C. W. and Baum, S.: Varicocele and infertility. J.A.M.A., 204: 1165, 1968 . 7 Dubin, L. and Amelar, R. D.: Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil. Steril., 21: 606, 1970. 'El-Sadr, A. R. and Mina, E.: Anatomical and surgical aspects in operative management of varicocele. Urol. & Cutan. Rev., 54: 257, 1950. 'Brown, J. S., Dubin, L., Becker, M. and Hotchkiss, R. S.: Venography in the subfertile man with varicocele. J. Urol., 98: 388, 1967. 1 0 Russell, J. K. : Varicocele in groups of fertile and subfertile males. Proc. Soc. Steril. Fertil., 5: 31, 1953. 11 Hanley, H . G. and Harrison, R. G.: Nature and surgical treatment of varicocele. Brit. J. Surg., 50: 64,
1962.
"Tessler, A. N. and Krahn, H. P.: Varicocele and testicular temperature. Fertil. Steril., 17: 201, 1966. 13 Brown, J. S., Dubin, L. and Hotchkiss, R. S.: Varicocele as related to fert ility. Fertil. Steril. , 18: 46, 1967. 14
Amelar, R. D. and Dubin, L.: Male infertility: 222
ever, we do know t h at the size of the varicocele bears no relation to the effi cacy of surgical therapy and that ligation of the left internal spermatic vein alone is usually sufficient to correct the condition. 7 Although some patients with virtual azoospermia achieve fat herhood followin g an operation, best results have been obtained in atients who have mo erate oligospermia, a decrease in sperm motility and the stress pattern on seminal cytology . This pattern was first described by MacLeod and consists of an increase in the percentage of tapering, amorphous and immature forms as seen on Papanicolaou stain. 19 D u bin and Hotchkiss have since reported results of testis biopsy in patients with varicocele and found bilateral germinal hypoplasia with premature sloughing of immature cells into the lumina of the seminiferous tubules . 20 These immature cells, combined with spermatids and tapering forms, are similar to the abnormal cells found in the ejaculate. Encouraging results in patients with surgically treated varicoceles provided the stimulus that led to the present study. An attempt has been made to determine the incidence of a surgically correctable varicocele in the general infertile m a le population, to establish the percentage of properly selected patients t hat can achieve fatherhood after ligation of the internal spermatic vein and to establish the expected fertility rate in untreated patients with varicocele. MATERIAL AND METHODS
A total of 195 patients were evaluated for male infertility between 1965 and 1970. These patients were u nselected and constituted a relatively small fraction of a general urology practice . A varicocele was found in 48 patients and 20 were treated subsequently by ligation of the internal spermatic vein. Of the operated cases, 18 had only a left varicocele and were treated by ligation of the left internal current diagnosis and treatment. Urology, l: 1, 1973. 1 5 Donohue, R. E. and Brown, J. S.: Blood gases and pH determinations in t he internal spermatic veins of subfertile men with varicocele. Fertil. Steril. , 20: 365, 1969. 16
Agger, P.: Plasma cortisol in t he left spermatic vein
in patients with varicocele. Fertil . Steril. , 22: 270, 1971. 17 Comhaire, F. and Vermeulen, A.: Varicocele sterility: cortisol and catecholamines. Fertil. Steril., 25: 88,
1974. 18 Zorgniotti, A. W. and MacLeod, J.: St udies in temperature, human semen quality, and varicocele. Fertil. Steril. , 24: 854, 1973. 19 MacLeod, J. : Seminal cytology in the presence of varicocele. Fertil. Steril., 16: 735, 1965. 20 Dubin, L. and Hotchkiss, R. S. : Testis biopsy in subfertile men with varicocele. Fertil. Steril., 20: 50,
1969.
I
223
VARICO CELE IN INFERTILITY
.\ :1
TABLE
1. Results following internal spermatic vein
TABLE
ligation in subfertile men with varicocele
n
Reference
Semen Improved Pregnancy (%) ( %)
Tulloch' Scott and Young ' Zorgniotti and assoc iates' Charny and Baum' Dubin and Amelar'
~ ., '
No. Pts. 30 166 117 104 111
67 70 70 62 81
30 27 40 24 48
l
2. Varicocele in 48 patients No. P ts.
No operation Ligation of internal spermatic vein: Postoperative pregnancies, 11 Postoperative improvement in semen qual ity , 6 No change in semen quality postoperatively, 3
28 20
spermatic vein , 1 had a right varicocele and was treated by ligation of the right internal spermatic vein and 1 had bilateral varicoceles and was treated by bilateral spermatic vein ligation. The remainder received no treatment and served as a control series . All patients were considered subfertile on the basis of multiple semen analyses. A decrease in sperm count to less than 40 ,000,000 per cc, a decrease in motility to less than 60 per cent 3 plus activity at 2 hours and an increase in immature and tapering forms on seminal cytology exceeding 5 and 10 per cent, respectively, were considered factors in declaring a particular specimen subfer tile. Most patients were deficient in all 3 cate gories , although some had only a decrease in motility or an increase in the percentage of abnormal forms on cytologic exa mination . General physical examination, routine laboratory studies and a complete endocrine profile were within normal limits in all patients . The wives of these patients had all been examined by competent gynecologists and we re considered fertile . Followup semen analyses were obtained at 3month intervals in all operated cases. Most pa tients in the non-operative series were not treated or followed medically but were contacted by mail to determine their clinical status and whether their wives had become pregnant .
surgically treated varicocele indeed achieve the htgnest percentage of fatherhood of an y groug of 011gosperm1c patients. For these reasons the 12resence 6f av aricocele should be di ligently sought in ali-pafie nts seen because of infertility. The patient should a lways be examined after a few minutes in the upright position, since most varicoceles are undetectable with the patient supine . The pres ence of an impulse within the varicocele upon coughing or straining helps to confirm diagnosis . Correction of small varicoceles restores fe rtility potential in just as many p_atients as does that of large varicoceles . Therefore , the size of the"le§ion snould not affect the decision t o operate. Best postoperative results are noted in pat ients who had preoperative sperm counts in the 20 to 40,000,000 per cc range, with a typical st ress pattern on seminal cytology. However, significant improvement in semen quality and subsequent fatherhood occurred occasionally after operation in patients with virtual azoospermia. Many patients , after full discussion and t he knowledge that the varicocele does not constitute a serious health hazard, will elect no't to undergo operative correction of the varicocele . One can not argue with this philosophy but , on the basis of experience in this series of non-operated cases, one can at least advise such patients that their chance of subsequent fatherhood will be only 5 to 10 per cent, as compared to about 50 per cent in patients undergoing surgical repair .
RESULTS
SUMMARY
DISCUSSION
A varicocele is the most common surgically correctable cause of male infertility. Pa~ ith
A varicocele is the most common surgically correctable cause of male mfertihty, repair of wfoch gives better result s than standard medical therapy for oth er fo rms of m fertility . In a series of 48 oligospermic patients with varicocele, subse quent fatherhood was achieved in 55 per cent of 20 operated cases as compared to only 7 per cent of 28 non-operated cases . The presence of a varicocele, when associated witn the presence of t he st ress pattern on semmal cytology, constitut es a definite ind1cat10n for surgical t herapy in the infertile male patient.
9500 Euclid Avenue , Cleveland , Ohio 44106
:!
i
'J
l
THE JOURNAL OF U ROLOGY
Printed in U.S.A .
Copyright © 1974 by The Will iams & Wilkins Co.
~
VARICOCELE IN INFERTILITY: INCIDENCE AND RESULTS OF SURGICAL THERAPY BRUCE H. STEW ART
Correction of varicocele by ligation of t he internal spermatic vein has been standard therapy for more than half a century. 1 However, the causal role of the varicocele in male infertility has been a relatively recent d evelopment . 2 Significant improvement in semen quality in most infert ile patients with varicocele treated surgically has been demonstrated in several large series (table 1). 3- 7 A varicocele develops as a result of incompetency of the valves in the left internal spermatic vein and is probably enhanced by compression of t he left renal vein between the simultaneously pulsating aorta and superior mesenteric artery. Retrograde venous blood flow when the subject is in the erect position affects both testes, since there is extensive cross-venous circulation between the vasal and cremasteric systems. 8 • 9 The precise reason why spermatic vein backflow impairs spermatogenesis is still not clear. Various circulatory, t hermal and endocrine factors have been implicated but as yet have not been proved. 10- 18 HowAccepted for publication January 25, 1974. Read at annual meeting of North Central Section, American Urological Association, Acapulco, Mexico, November 11- 18, 1973. 1 Ivanissevich, 0 .: Left varicocele due to reflux, experience with 4,470 operative cases in 42 years. J. Int. Coll. Surg., 34: 742, 1960. 'Tulloch, W. S.: Consideration of sterility factors in light of subsequent pregnancies; subfertility in the male. Edinburgh Med. J., 59: 29, 1952. 'Tulloch, W. S.: Varicocele in subfertility, results of treatment. Brit . Med. J ., 2: 356, 1955. 'Scott, L. S. and Young, D.: Varicocele: a study of its effects on human spermatogenesis, and of the results produced by spermatic vein ligation. Fertil. Steril., 13 : 325, 1962. 5 Zorgniotti, A. W., MacLeod, J . and Hotchkiss, R. S.: Treatment and results of varicocelectomy in the subfertile male. Presented at annual meeting of The American Fertility Society, Chicago, Illinois, April 1966 . • Charny, C. W. and Baum, S.: Varicocele and infertility. J.A.M.A., 204: 1165, 1968 . 7 Dubin, L. and Amelar, R. D.: Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil. Steril., 21: 606, 1970. 'El-Sadr, A. R. and Mina, E.: Anatomical and surgical aspects in operative management of varicocele. Urol. & Cutan. Rev., 54: 257, 1950. 'Brown, J. S., Dubin, L., Becker, M. and Hotchkiss, R. S.: Venography in the subfertile man with varicocele. J. Urol., 98: 388, 1967. 1 0 Russell, J. K. : Varicocele in groups of fertile and subfertile males. Proc. Soc. Steril. Fertil., 5: 31, 1953. 11 Hanley, H . G. and Harrison, R. G.: Nature and surgical treatment of varicocele. Brit. J. Surg., 50: 64,
1962.
"Tessler, A. N. and Krahn, H. P.: Varicocele and testicular temperature. Fertil. Steril., 17: 201, 1966. 13 Brown, J. S., Dubin, L. and Hotchkiss, R. S.: Varicocele as related to fert ility. Fertil. Steril. , 18: 46, 1967. 14
Amelar, R. D. and Dubin, L.: Male infertility: 222
ever, we do know t h at the size of the varicocele bears no relation to the effi cacy of surgical therapy and that ligation of the left internal spermatic vein alone is usually sufficient to correct the condition. 7 Although some patients with virtual azoospermia achieve fat herhood followin g an operation, best results have been obtained in atients who have mo erate oligospermia, a decrease in sperm motility and the stress pattern on seminal cytology . This pattern was first described by MacLeod and consists of an increase in the percentage of tapering, amorphous and immature forms as seen on Papanicolaou stain. 19 D u bin and Hotchkiss have since reported results of testis biopsy in patients with varicocele and found bilateral germinal hypoplasia with premature sloughing of immature cells into the lumina of the seminiferous tubules . 20 These immature cells, combined with spermatids and tapering forms, are similar to the abnormal cells found in the ejaculate. Encouraging results in patients with surgically treated varicoceles provided the stimulus that led to the present study. An attempt has been made to determine the incidence of a surgically correctable varicocele in the general infertile m a le population, to establish the percentage of properly selected patients t hat can achieve fatherhood after ligation of the internal spermatic vein and to establish the expected fertility rate in untreated patients with varicocele. MATERIAL AND METHODS
A total of 195 patients were evaluated for male infertility between 1965 and 1970. These patients were u nselected and constituted a relatively small fraction of a general urology practice . A varicocele was found in 48 patients and 20 were treated subsequently by ligation of the internal spermatic vein. Of the operated cases, 18 had only a left varicocele and were treated by ligation of the left internal current diagnosis and treatment. Urology, l: 1, 1973. 1 5 Donohue, R. E. and Brown, J. S.: Blood gases and pH determinations in t he internal spermatic veins of subfertile men with varicocele. Fertil. Steril. , 20: 365, 1969. 16
Agger, P.: Plasma cortisol in t he left spermatic vein
in patients with varicocele. Fertil . Steril. , 22: 270, 1971. 17 Comhaire, F. and Vermeulen, A.: Varicocele sterility: cortisol and catecholamines. Fertil. Steril., 25: 88,
1974. 18 Zorgniotti, A. W. and MacLeod, J.: St udies in temperature, human semen quality, and varicocele. Fertil. Steril. , 24: 854, 1973. 19 MacLeod, J. : Seminal cytology in the presence of varicocele. Fertil. Steril., 16: 735, 1965. 20 Dubin, L. and Hotchkiss, R. S. : Testis biopsy in subfertile men with varicocele. Fertil. Steril., 20: 50,
1969.
I
223
VARICO CELE IN INFERTILITY
.\ :1
TABLE
1. Results following internal spermatic vein
TABLE
ligation in subfertile men with varicocele
n
Reference
Semen Improved Pregnancy (%) ( %)
Tulloch' Scott and Young ' Zorgniotti and assoc iates' Charny and Baum' Dubin and Amelar'
~ ., '
No. Pts. 30 166 117 104 111
67 70 70 62 81
30 27 40 24 48
l
2. Varicocele in 48 patients No. P ts.
No operation Ligation of internal spermatic vein: Postoperative pregnancies, 11 Postoperative improvement in semen qual ity , 6 No change in semen quality postoperatively, 3
28 20
spermatic vein , 1 had a right varicocele and was treated by ligation of the right internal spermatic vein and 1 had bilateral varicoceles and was treated by bilateral spermatic vein ligation. The remainder received no treatment and served as a control series . All patients were considered subfertile on the basis of multiple semen analyses. A decrease in sperm count to less than 40 ,000,000 per cc, a decrease in motility to less than 60 per cent 3 plus activity at 2 hours and an increase in immature and tapering forms on seminal cytology exceeding 5 and 10 per cent, respectively, were considered factors in declaring a particular specimen subfer tile. Most patients were deficient in all 3 cate gories , although some had only a decrease in motility or an increase in the percentage of abnormal forms on cytologic exa mination . General physical examination, routine laboratory studies and a complete endocrine profile were within normal limits in all patients . The wives of these patients had all been examined by competent gynecologists and we re considered fertile . Followup semen analyses were obtained at 3month intervals in all operated cases. Most pa tients in the non-operative series were not treated or followed medically but were contacted by mail to determine their clinical status and whether their wives had become pregnant .
surgically treated varicocele indeed achieve the htgnest percentage of fatherhood of an y groug of 011gosperm1c patients. For these reasons the 12resence 6f av aricocele should be di ligently sought in ali-pafie nts seen because of infertility. The patient should a lways be examined after a few minutes in the upright position, since most varicoceles are undetectable with the patient supine . The pres ence of an impulse within the varicocele upon coughing or straining helps to confirm diagnosis . Correction of small varicoceles restores fe rtility potential in just as many p_atients as does that of large varicoceles . Therefore , the size of the"le§ion snould not affect the decision t o operate. Best postoperative results are noted in pat ients who had preoperative sperm counts in the 20 to 40,000,000 per cc range, with a typical st ress pattern on seminal cytology. However, significant improvement in semen quality and subsequent fatherhood occurred occasionally after operation in patients with virtual azoospermia. Many patients , after full discussion and t he knowledge that the varicocele does not constitute a serious health hazard, will elect no't to undergo operative correction of the varicocele . One can not argue with this philosophy but , on the basis of experience in this series of non-operated cases, one can at least advise such patients that their chance of subsequent fatherhood will be only 5 to 10 per cent, as compared to about 50 per cent in patients undergoing surgical repair .
RESULTS
SUMMARY
DISCUSSION
A varicocele is the most common surgically correctable cause of male infertility. Pa~ ith
A varicocele is the most common surgically correctable cause of male mfertihty, repair of wfoch gives better result s than standard medical therapy for oth er fo rms of m fertility . In a series of 48 oligospermic patients with varicocele, subse quent fatherhood was achieved in 55 per cent of 20 operated cases as compared to only 7 per cent of 28 non-operated cases . The presence of a varicocele, when associated witn the presence of t he st ress pattern on semmal cytology, constitut es a definite ind1cat10n for surgical t herapy in the infertile male patient.
9500 Euclid Avenue , Cleveland , Ohio 44106
:!
i
'J
l