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Scrotal Ultrasound in the Infertile Man: Detection of Subclinical Unilateral and Bilateral Varicoceles
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THE JOURNAL OF UROLOGY
Printed in
Copyright© 1986 by The Williams & Wilkins Co.
SCROTAL ULTRASOUND IN THE INFERTILE MAN: DETECTION OF SUBCLINICAL UNILATERAL AND BILATERAL VARICOCELES R DALE McCLURE*
AND
HEDVIG HRICAK
From the Departments of Urology and Radiology, University of California School of Medicine and Veterans Administration Medical Center, San Francisco, California
ABSTRACT
Clinical and laboratory studies have provided convincing evidence that varicoceles are detrimental to spermatogenesis and that this effect is unrelated to their size, Thus, physicians have used diagnostic techniques other than physical examination to find these small but clinically significant varicoceles, Because scrotal sonography has proved to be invaluable to detect many intrascrotal abnormalities, and has the unique ability to visualize the testicle and surrounding structures, we used it to evaluate 50 infertile men, Of our 50 patients 22 had a clinically palpable left varicocele and 3 additional patients had bilateral varicoceles, All clinical varicoceles were confirmed by sonography, However, sonography also demonstrated a left varicocele in an additional 12 patients (34 of 50 or 68 per cent) and a right varicocele in 21 (a total of 24 or 48 per cent), Reflux on the right side always occurred in conjunction with that on the left side, Thus, among our 50 infertile men 24 of 34 (70 per cent) had bilateral varicoceles as detected sonography, and 12 of 50 (24 per cent) had a subclinical varicocele on the left side, The high percentage of bilateral varicoceles detected by sonography may explain the pathophysiological mechanism by which what formerly was considered a unilateral anatomical abnormality may produce bilateral testicular dysfunction, It also may challenge us to change our present unilateral surgical approach to the patient with a clinically evident left varicocele. V aricocele, a dilatation of the pampiniform plexus resulting from incompetence or absence of valves in the internal spermatic vein, is now a well established cause of male infertility, The turning point in our appreciation of the varicocele as a pathological lesion occurred in 1952, when Tulloch reported successful impregnation after bilateral varicocelectomy in an azoospermic patient, 1 Since then, varicocelectomy has become the most common operation for male infertility, In 1970 Dubin and Amelar reported that the improvement in semen quality after varicocelectomy bears no relationship to the size of the varicocele on palpation. 2 Size also does not appear to correlate positively with testicular and seminal pathological conditions. Therefore, small, even subclinical, varicoceles may have significant pathological potentiaL It is possible that small but clinically significant varicoceles may be missed, even with careful examination of the patient in the upright position with the Valsalva maneuver if he has an active cremasteric reflex or thick scrotal skin, Therefore, physicians have used various diagnostic techniques other than physical examination to find these small varicoceles, One of the earlier, more sophisticated methods was the Doppler pencil-probe stethoscope with which Greenberg and associates reported confirmation of 75 palpable varicoceles, 3 In the same study physical examination was unsatisfactory in 33 of 216 men, and of these 33 the Doppler examination was positive for vein regurgitation during the Valsalva maneuver in 13, negative in 13 and equivocal in 7, Hirsh and associates were able to demonstrate Valsalva-induced reflux by Doppler sonography in 118 men but were unable to distinguish a different incidence between fertile and infertile men, 4 We found that questionable regurgitant sounds are a drawback with the Doppler stethoscope and it will not provide unequivocal anAccepted for publication November 25, 1985. Read at annual meeting of American Urological Association, New Orleans, Louisiana, May 6-10, 1984, * Requests for reprints: Department of Urology, U-518, University of California, San Francisco, California 94143. 711
swers in cases of questionable varicoceles. Also, this procedure is limited to use by those with extensive experience and the ability to recognize auditory venous pulse waves. Another diagnostic technique is scrotal thermography for testicular temperature differences, 5' 6 However, in patients with a single or atrophic testicle, a small valve or bilateral varicoceles this test is inadequate, since diagnosis relies on temperature differences in both sides of the scrotum, 6 Findings also appear to overlap with those of the normal population, At this point, scrotal thermography must be considered an equivocal diagnostic test for varicocele, More recently, radioisotopic angiography has been used, although exposing infertile individuals to radioisotopes is cause for concern, 7 Radionuclide angiography with static imaging appears to be ineffective with small varicoceles, since no blood pooling is found in the majority of these cases, 8 Venography appears to be the most specific method of identification9 • 10 but it is invasive and associated with some morbidity, requires specialized skills and equipment, and is expensive, We have sought a noninvasive, readily available and costeffective method to detect varicoceles, Because scrotal sonography has proved invaluable to detect many intrascrotal abnormalities and has the unique ability to visualize the testicle and surrounding structures, 11 - 13 we used it to evaluate our infertile men, PATIENTS AND METHODS
A total of 50 men with infertility more than 1 year in duration but with normal hormone levels (luteinizing and follicle-stimulating hormones, and serum testosterone) underwent scrotal ultrasonography, All of the patients had had at least 3 semen analyses that showed oligospermia (sperm count less than 20 X 106 /mL) and/or asthenospermia (sperm motility less than 40 per cent, grades 2 or 3). The results showed oligospermia in 34 patients and asthenospermia in 43 (that is 27 had oligoas-
712
MCCLURE AND HRICAK
thenospermia). To provide normal standards for scrotal sonography we studied a control population of 25 normal fertile men who were examined before vasectomy. All of the subjects ranged from 21 to 39 years old. The latest generation, gray-scale, real-time unit (a Picker LS 3000 linear array and a Diasonics DRF 400V sector scan) with 5 to 7.5 MHz. transducers was used. Both sides of the scrotum were examined with the subjects in the supine and upright positions. Studies were done during normal respiration and were repeated with the Valsalva maneuver. With the patient in the supine position the scrotum was elevated by a towel draped over the thigh, or by a rolled towel placed between the thighs if additional elevation was needed. The penis was placed on the abdomen and covered with a drape, resulting in minimal exposure of the patient and maximal access to the area of interest. Imaging was performed by direct contact approach of the transducer with the scrotal skin. Copious amounts of acoustic gel were used to facilitate scanning. The vessels were scanned on each side from the hilus of the testicle to the scrotal neck, accomplished by rotating the testicle slightly in its long axis to bring the vessels to the lateral aspect of the scrotum directly beneath the base of the transducer. Examination was repeated with the patient in the upright position during normal respiration and the Valsalva maneuver. The testicles again were supported by a towel placed between the thighs, with the side of the towel held by the patient. Scrotal ultrasound was analyzed for testicular size, echogenicity and internal homogeneity. Testicular volume, compared to that obtained at physical examination by a Prader orchidometer, was calculated by the formula: volume = anteroposterior diameter x width x length x 0.53. The comparison between the right and left testicles always was performed. The size of the epididymis and the presence of any epididymal pathological condition were recorded. The size and diameter of the vein within the spermatic cord, as well as identification of the spermatic veins at the mediastinum, always were analyzed. Venous diameter was measured during normal respiration with the patient in the supine and upright positions, and in the upright position during the Valsalva maneuver. Any detectable fluid collection or incidental scrotal abnormalities also were recorded.
RESULTS
Testicular measurement by ultrasound was somewhat subjective because with the use of the real-time unit the measurement of the length is dependent on the skill of the operator and the testicular shape may be altered by the degree of pressure of the transducer. Testicular size will be smaller by ultrasound than with the orchidometer because the former does not measure the surrounding tissue. Testicular size was normal (length more than 4.5 cm., width more than 2.5 cm.) in 18 patients (36 per cent), the left testis was small in 9 (18 per cent), the right testis was small in 5 (10 per cent) and both testes were small in 18 (36 per cent). Testicular texture was homogeneous in 4 7 of the 50 patients (2 had a localized low intensity area subsequently found to be testicular atrophy, while 1 showed asymmetrical echogenicity, with the lower echogenicity being on the side of the smaller testis). The epididymis was identified in all patients and was normal in 48. Incidental small epididymal cysts were identified in the remaining 2 men as small, round areas of fluid collection that remained spherical regardless of the axis of scanning. Incidental fluid collection (that is a hydrocele) was present in 3 of the 50 patients. Identification of the spermatic vein in the spermatic cord at the neck of the scrotum was done in each patient. A total of 2 or 3 tubular structures was identified in the spermatic cord, 1 representing the spermatic artery, 1 the spermatic vein and 1 the ductus deferens. (The spermatic artery could be identified with the Doppler ultrasound probe.) In patients with subsequently proved varicocele the number of veins was more than 3 and at least 1 had a diameter more than 3 mm. (fig. 1). Although Rifkin 12 and Wolverson 13 and their associates have diagnosed varicocele with the presence of numerous dilated, tortuous vessels of various caliber when 1 was 2 or more mm., the majority of our control subjects as well as 5 infertile men with negative findings on venography had veins in the spermatic cord with a diameter of up to 3 mm. Therefore, we consider the diagnosis of varicocele by sonography if the veins in the pampiniform plexus are more than 3 mm., while the diagnosis is confirmed if they change in size with the patient in the upright position or during Valsalva's maneuver.
FIG. 1. Left varicocele. A, transverse scan demonstrates varicoceles (arrows) as tubular structures free of echoes and posterior to testis (T). B, longitudinal scan confirms presence of numerous varicoceles (arrows). T, testis.
713
SCROTAL ULTRASOUND IN INFERTILE MEN
Collateral veins in the region of the septum also could be identified in the patients with large bilateral varicoceles. Normal veins of the pampiniform plexus were visualized in all of the subjects. The veins were seen as small (less than 3 mm.) tubular structures in the region of the mediastinum testis, and they did not increase in size or change in appearance with the patient in the upright position or during Valsalva's maneuver (fig. 2). Of our 50 infertile patients 25 had clinical evidence of a palpable left varicocele that was confirmed by sonography. The sizes of these varicoceles could be measured accurately and compared favorably to the clinical classifications of grades 1 to 3 (or small, medium and large varicoceles). Of these 25 patients with a left varicocele 3 had a clinically palpable right varicocele (bilateral), which also was confirmed by sonography. Thus, ultrasound has an excellent clinical correlation with physical examination for a varicocele. The sperm count, percentage of motile sperm and testicular volume are shown in the table, differentiated into categories of clinical or subclinical varicocele. Because abnormalities of sperm morphology appear to be more related to diminished sperm count and motility than to the presence or absence of a varicocele, 14 this has not been included. Sonography revealed evidence of a left varicocele in 34 men (68 per cent) and a right varicocele in 24 (70 per cent). Reflux on the right side always occurred in conjunction with that on the left side (fig. 3). Thus, there was sonographic evidence of 12 subclinical varicoceles (24 per cent) on the left side and 21 (42 per cent) on the right side. The incidence appeared to be high on the right side because these were less detectable clinically than those on the left side. Of the 25 fertile control subjects physical examination revealed clinical evidence of a varicocele on the left side in 4 (16 per cent) and on the right side in none. Sonography revealed evidence of a varicocele on the left side in 8 men (32 per cent) on the right side in 2 (8 per cent).
reflex or thickened scrotal skin, were diagnosed easily by sonography. Twelve subclinical varicoceles were detected on the left side (24 per cent) and 21 (42 per cent) on the right side. The high incidence of bilateral varicoceles (70 per cent) was surprising but was comparable to that reported by Chatel and associates, who found radiological evidence of bilateral varicoceles in 60 per cent of 178 patients, 20 and to the 61 per cent incidence found by Gonzalez and associates in 39 patients evaluated by venography. 21 Their use of this more invasive technique may explain their greater reported incidence than that found by Rifkin and associates, who noted bilateral varicoceles in only 2 of 21 patients. 12 Bilaterality was not specified among the 13 patients studied by Wolverson and associates. 13 With retrograde venography in 350 patients, Bigot and Chatel found spermatic venous insufficiency to be almost as frequent on the right as on the left side (60 versus 76 per cent). 22 In our control population the incidence of varicocele by physical examination (16 per cent on the left side and none on the right side) was compatible with the 8 to 23 per cent incidence in men over-all. 23 Recent investigators have revised upward their previous opinion that varicoceles occur bilaterally in only 15 per cent of the individuals: among 870 varicocelectomies performed between 1980 and 1981 bilateral varicoceles were found in 57 per cent of the patients. 17 This apparently high incidence may explain the failure of left varicocelectomy to restore spermatogenesis to normal and improve fertility in some patients. Cockett and associates found that 65 per cent of new patients presenting with a left varicocele had a right varicocele and they believed that this finding may explain the only moderate impregnation rate (30 to 35 per cent) after left varicocelectomy. 24 With selective phlebography in subjects in the upright position, Ahlberg and associates reported retrograde left internal spermatic vein filling in 22 patients with varicoceles. 9 Some Correlation between varicocele, and sperm count, motility and testicular volume
DISCUSSION
Clinical studies and laboratory research18 have provided convincing evidence that varicoceles are detrimental to spermatogenesis in some men. The incidence of varicocele is several-fold higher in the infertile male population. 19 Therefore, it behooves the physician to use diagnostic techniques more sophisticated than careful physical examination to detect scrotal varicosities. In our experience ultrasonography has confirmed all clinical varicoceles, and detected small subclinical and bilateral varicoceles. Our report demonstrates that in the presence of clinically palpable varicoceles scrotal ultrasonography will not demonstrate false negative results. Varicoceles that easily escaped detection on physical examination alone, especially in patients with an active cremasteric 15 - 17
Testicular Volume (cc) Varicocele
Sperm Count Motile Sperm (%) (106/ml.)
Orchidometer Rt.
Clinical It., 22 pts. Clinical bilat., 3 pts.* Subclinical It., 12 pts. Subclinical bilat., 21 pts.*
Lt.
Ultrasound Rt.
Lt.
19 ± 17
41 ± 11
18± 3 17 ± 5 17 ± 6 14 ± 4
11 ±8
32 ± 8
12 ± 2 11 ± 3 11 ± 1
14 ± 13
37 ± 15
17 ± 3 14± 3 15 ± 4 11 ±4
19 ± 18
28 ± 11
17 ± 5 15 ± 4 15 ± 6 13 ± 6
9±2
Values are given in mean± standard deviation. * No patient had right varicocelesonly. Reflux on the right side always occurred in conjunction with reflux on the left side.
FIG. 2. Large left varicocele extends into spermatic cord. A, longitudinal scan shows numerous dilated vessels (varicocele) superior to testis. B, longitudinal scan through spermatic cord demonstrates extension of varicocele (curved arrows) to spermatic cord.
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MCCLURE AND HRICAK
FIG. 3. Bilateral varicoceles. A, transverse scan with patient in supine position demonstrates bilateral varicoceles (curved arrows). B, transverse scan repeated during Valsalva's maneuver shows increase in size of left varicocele (curved arrow). C, long section scan obtained with patient in supine position shows varicoceles (arrows) posterior to testis (T). Incidental finding is hydrocele (H) seen superior to testis.
patients had no valves and in others the valves appeared incompetent. In 10 of the patients the right scrotal vein filled with contrast medium via collateral veins between the spermatic veins and other venous systems of the pelvis, lumbar and perirenal regions. Others suggested that these collaterals may be present in superficial vessels in the lower pelvis or scrotum. 25·26 These findings might explain the bilateral effects of the presumed unilateral varicoceles. Although no adequate clinical trials have been conducted to determine whether reflux of blood without a palpable varicocele has a role in the pathogenesis of infertility or whether the correction leads to improvement in semen quality, the concept of a subclinical varicocele as a cause of infertility has obvious appeal in patients in whom no other cause is evident. In 1975 Fogh-Andersen and associates reported fertility after ligation of the left spermatic vein in infertile men with oligospermia without clinical evidence of a varicocele. 27 Semen profiles improved in 50 per cent of the 22 patients and in 7 (31.8 per cent) impregnation was achieved within 16 months. Sperm quality and impregnation rate were significantly greater than in the 44 controls. Unfortunately, diagnostic tests, such as sonography, thermography and Doppler studies, were not performed to confirm the presence of a subclinical varicocele. Greenberg and associates used the Doppler stethoscope to diagnose subclinical varicoceles in 5 men with oligoasthenospermia and performed varicocelectomy in all 5.3 In 2 of these patients semen quality improved and each subsequently fathered a child. Lewis and Harrison diagnosed subclinical varicoceles with thermography in 6 patients and did varicocelectomies in all 6. 28 In 5 patients semen analysis improved and 2 achieved impregnation. More recently, Tinga and associates used sonography to detect subclinical varicoceles in 12 men. 16 Although there was no significant improvement in semen quality in these patients after varicocelectomy, there was no difference in the incidence of impregnation (33 per cent) between them and patients with various grades of palpable varicoceles. The high percentage of bilateral varicoceles in our infertile population may explain the pathophysiological mechanism by which what formerly was considered a unilateral anatomical abnormality bilateral testicular dysfunction is produced. Surprising also was the number of subclinical varicoceles detected by sonography. Although there is no conclusive evidence to date that repair of subclinical varicoceles improves semen quality and, consequently, fertility their presence may explain some of the previously unknown causes of idiopathic infertility. This high incidence of bilateral subclinical varicoceles may challenge us to change our present unilateral surgical approach to the patient with a clinically evident left varicocele.
REFERENCES 1. Tulloch, W. S.: A consideration of sterility factors in the light of subsequent pregnancies. II. Subfertility in the male. Edinburgh Med. J., 59: 29, 1952. 2. Dubin, L. and Amelar, R. D.: Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil. Steril., 21: 606, 1970. 3. Greenberg, S. H., Lipshultz, L. I. and Wein, A. J.: A preliminary report on 'subclinical varicocele': diagnosis by Doppler ultrasonic stethoscope. Examination and initial results of surgical therapy. J. Reprod. Med., 22: 77, 1979. 4. Hirsh, A. V., Cameron, K. M., Tyler, J. P., Simpson, J. and Pryor, J. P.: The Doppler assessment of varicoceles and internal spermatic vein reflux in infertile men. Brit. J. Urol., 52: 50, 1980. 5. Lewis, R. W. and Harrison, R. M.: Contact scrotal thermography: application to problems of infertility. J. Urol., 122: 40, 1979. 6. Comhaire, F., Monteyne, R. and Kunnen, M.: The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of "subclinical" varicocele. Fertil. Steril., 27: 694, 1976. 7. Harris, J. D., McConnell, B. J., Lipshultz, L. I., McConnell, R. W. and Conoley, P. H.: Radioisotope angiography in diagnosis of varicocele. Urology, 16: 69, 1980. 8. Comhaire, F. H.: Varicocele infertility: an enigma. Int. J. Androl., 6: 401, 1983. 9. Ahlberg, N. E., Bartley, 0., Chidekel, N. and Fritjofsson, A.: Phlebography in varicocele scroti. Acta Rad., 4: 517, 1966. 10. Comhaire, F. and Kunnen, M.: Selective retrograde venography of the internal spermatic vein: a conclusive approach to the diagnosis of varicocele. Andrologia, 8: 11, 1976. 11. Hricak, H. and Filly, R. A.: Sonography of the scrotum. Invest. Rad., 18: 112, 1983. 12. Rifkin, M. D., Foy, P. M., Kurtz, A. B., Pasto, M. E. and Goldberg, B. B.: The role of diagnostic ultrasonography in varicocele evaluation. J. Ultrasound Med., 2: 271, 1983. 13. Wolverson, M. K., Houttuin, E., Heiberg, E., Sundaram, M. and Gregory, J.: High-resolution real-time sonography of scrotal varicocele. Amer. J. Roentgen., 141: 775, 1983. 14. Rodriguez-Rigau, L. J., Smith, K. D. and Steinberger, E.: Varicocele and the morphology of spermatozoa. Fertil. Steril., 35: 54, 1981. 15. Johnsen, S. G. and Agger, P.: Quantitative evaluation of testicular biopsies before and after operation for varicocele. Fertil. Steril., 29: 58, 1978. 16. Tinga, D. J., Jager, S., Bruijnen, C. L. A. H., Kremer, J. and Mensink, H. J.: Factors related to semen improvement and fertility after varicocele operation. Fertil. Steril., 41: 404, 1984. 17. Cockett, A. T. K., Harrison, R. M., Comhaire, F. and Dubin, L.: The varicocele and its effect on fertility. Contemp. Surg., 24: 111, April 1984. 18. Saypol, D. C., Howards, S. S., Turner, T. T. and Miller, E. D., Jr.: Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs. J. Clin.
SCROTAL ULTRASOUND IN INFERTILE MEN
Invest., 68: 39, 1981. 19. Saypol, D. C.: Varicocele. J. Androl., 2: 61, 1981. 20. Chatel, A., Bigot, J.M., Helenon, C., Dectot, H., Rotman, J. and Salat-Baroux, J.: Interet de la phlebographie spermatique dans le diagnostic des sterilites d'origine circulatoire (varicocele). Comparaison avec les donnees cliniques, thermographiques et anatomiques. Ann. Rad., 21: 565, 1978. 21. Gonzalez, R., Reddy, P., Kaye, K. W. and Narayan, P.: Comparison of Doppler examination and retrograde spermatic venography in the diagnosis of varicocele. Fertil. Steril., 40: 96, 1983. 22. Bigot, J. M. and Chatel, A.: The value of retrograde spermatic phlebography in varicocele. Eur. Urol., 6: 301, 1980. 23. de Castro, M. P. P. and Mastrorocco, D. A. M.: Reproductive history and semen analysis in prevasectomy fertile men with and without varicocele. J. Androl., 5: 17, 1984.
24. Cockett, A. T. K., Takihara; H. and Cosentino, M. J.: The varicocele. Fertil. Steril., 41: 5, 1984. 25. Etriby, A. A.-E., Ibrahim, A.-A. A., Mahmoud, K. Z. and Elhaggar, S.: Subfertility and varicocele. I. Venogram demonstration of anastomosis sites in subfertile men. Fertil. Steril., 26: 1013, 1975. 26. Sayfan, J., Adam, Y. G. and Soffer, Y.: A natural "venous bypass" causing postoperative recurrence of a varicocele. J. Androl., 2: 108, 1981. 27. Fogh-Andersen, P., Nielsen, N. C., Rebbe, H. and Stakemann, G.: The effect on fertility of ligation of the left spermatic vein in men without clinical signs of varicocele. Acta Obst. Gynec. Scand., 54: 29, 1975. 28. Lewis, R. W. and Harrison, R. M.: Diagnosis and treatment of varicocele. Clin. Obst. Gynec., 25: 501, 1982.
THE JOURNAL OF UROLOGY
Printed in
Copyright© 1986 by The Williams & Wilkins Co.
SCROTAL ULTRASOUND IN THE INFERTILE MAN: DETECTION OF SUBCLINICAL UNILATERAL AND BILATERAL VARICOCELES R DALE McCLURE*
AND
HEDVIG HRICAK
From the Departments of Urology and Radiology, University of California School of Medicine and Veterans Administration Medical Center, San Francisco, California
ABSTRACT
Clinical and laboratory studies have provided convincing evidence that varicoceles are detrimental to spermatogenesis and that this effect is unrelated to their size, Thus, physicians have used diagnostic techniques other than physical examination to find these small but clinically significant varicoceles, Because scrotal sonography has proved to be invaluable to detect many intrascrotal abnormalities, and has the unique ability to visualize the testicle and surrounding structures, we used it to evaluate 50 infertile men, Of our 50 patients 22 had a clinically palpable left varicocele and 3 additional patients had bilateral varicoceles, All clinical varicoceles were confirmed by sonography, However, sonography also demonstrated a left varicocele in an additional 12 patients (34 of 50 or 68 per cent) and a right varicocele in 21 (a total of 24 or 48 per cent), Reflux on the right side always occurred in conjunction with that on the left side, Thus, among our 50 infertile men 24 of 34 (70 per cent) had bilateral varicoceles as detected sonography, and 12 of 50 (24 per cent) had a subclinical varicocele on the left side, The high percentage of bilateral varicoceles detected by sonography may explain the pathophysiological mechanism by which what formerly was considered a unilateral anatomical abnormality may produce bilateral testicular dysfunction, It also may challenge us to change our present unilateral surgical approach to the patient with a clinically evident left varicocele. V aricocele, a dilatation of the pampiniform plexus resulting from incompetence or absence of valves in the internal spermatic vein, is now a well established cause of male infertility, The turning point in our appreciation of the varicocele as a pathological lesion occurred in 1952, when Tulloch reported successful impregnation after bilateral varicocelectomy in an azoospermic patient, 1 Since then, varicocelectomy has become the most common operation for male infertility, In 1970 Dubin and Amelar reported that the improvement in semen quality after varicocelectomy bears no relationship to the size of the varicocele on palpation. 2 Size also does not appear to correlate positively with testicular and seminal pathological conditions. Therefore, small, even subclinical, varicoceles may have significant pathological potentiaL It is possible that small but clinically significant varicoceles may be missed, even with careful examination of the patient in the upright position with the Valsalva maneuver if he has an active cremasteric reflex or thick scrotal skin, Therefore, physicians have used various diagnostic techniques other than physical examination to find these small varicoceles, One of the earlier, more sophisticated methods was the Doppler pencil-probe stethoscope with which Greenberg and associates reported confirmation of 75 palpable varicoceles, 3 In the same study physical examination was unsatisfactory in 33 of 216 men, and of these 33 the Doppler examination was positive for vein regurgitation during the Valsalva maneuver in 13, negative in 13 and equivocal in 7, Hirsh and associates were able to demonstrate Valsalva-induced reflux by Doppler sonography in 118 men but were unable to distinguish a different incidence between fertile and infertile men, 4 We found that questionable regurgitant sounds are a drawback with the Doppler stethoscope and it will not provide unequivocal anAccepted for publication November 25, 1985. Read at annual meeting of American Urological Association, New Orleans, Louisiana, May 6-10, 1984, * Requests for reprints: Department of Urology, U-518, University of California, San Francisco, California 94143. 711
swers in cases of questionable varicoceles. Also, this procedure is limited to use by those with extensive experience and the ability to recognize auditory venous pulse waves. Another diagnostic technique is scrotal thermography for testicular temperature differences, 5' 6 However, in patients with a single or atrophic testicle, a small valve or bilateral varicoceles this test is inadequate, since diagnosis relies on temperature differences in both sides of the scrotum, 6 Findings also appear to overlap with those of the normal population, At this point, scrotal thermography must be considered an equivocal diagnostic test for varicocele, More recently, radioisotopic angiography has been used, although exposing infertile individuals to radioisotopes is cause for concern, 7 Radionuclide angiography with static imaging appears to be ineffective with small varicoceles, since no blood pooling is found in the majority of these cases, 8 Venography appears to be the most specific method of identification9 • 10 but it is invasive and associated with some morbidity, requires specialized skills and equipment, and is expensive, We have sought a noninvasive, readily available and costeffective method to detect varicoceles, Because scrotal sonography has proved invaluable to detect many intrascrotal abnormalities and has the unique ability to visualize the testicle and surrounding structures, 11 - 13 we used it to evaluate our infertile men, PATIENTS AND METHODS
A total of 50 men with infertility more than 1 year in duration but with normal hormone levels (luteinizing and follicle-stimulating hormones, and serum testosterone) underwent scrotal ultrasonography, All of the patients had had at least 3 semen analyses that showed oligospermia (sperm count less than 20 X 106 /mL) and/or asthenospermia (sperm motility less than 40 per cent, grades 2 or 3). The results showed oligospermia in 34 patients and asthenospermia in 43 (that is 27 had oligoas-
712
MCCLURE AND HRICAK
thenospermia). To provide normal standards for scrotal sonography we studied a control population of 25 normal fertile men who were examined before vasectomy. All of the subjects ranged from 21 to 39 years old. The latest generation, gray-scale, real-time unit (a Picker LS 3000 linear array and a Diasonics DRF 400V sector scan) with 5 to 7.5 MHz. transducers was used. Both sides of the scrotum were examined with the subjects in the supine and upright positions. Studies were done during normal respiration and were repeated with the Valsalva maneuver. With the patient in the supine position the scrotum was elevated by a towel draped over the thigh, or by a rolled towel placed between the thighs if additional elevation was needed. The penis was placed on the abdomen and covered with a drape, resulting in minimal exposure of the patient and maximal access to the area of interest. Imaging was performed by direct contact approach of the transducer with the scrotal skin. Copious amounts of acoustic gel were used to facilitate scanning. The vessels were scanned on each side from the hilus of the testicle to the scrotal neck, accomplished by rotating the testicle slightly in its long axis to bring the vessels to the lateral aspect of the scrotum directly beneath the base of the transducer. Examination was repeated with the patient in the upright position during normal respiration and the Valsalva maneuver. The testicles again were supported by a towel placed between the thighs, with the side of the towel held by the patient. Scrotal ultrasound was analyzed for testicular size, echogenicity and internal homogeneity. Testicular volume, compared to that obtained at physical examination by a Prader orchidometer, was calculated by the formula: volume = anteroposterior diameter x width x length x 0.53. The comparison between the right and left testicles always was performed. The size of the epididymis and the presence of any epididymal pathological condition were recorded. The size and diameter of the vein within the spermatic cord, as well as identification of the spermatic veins at the mediastinum, always were analyzed. Venous diameter was measured during normal respiration with the patient in the supine and upright positions, and in the upright position during the Valsalva maneuver. Any detectable fluid collection or incidental scrotal abnormalities also were recorded.
RESULTS
Testicular measurement by ultrasound was somewhat subjective because with the use of the real-time unit the measurement of the length is dependent on the skill of the operator and the testicular shape may be altered by the degree of pressure of the transducer. Testicular size will be smaller by ultrasound than with the orchidometer because the former does not measure the surrounding tissue. Testicular size was normal (length more than 4.5 cm., width more than 2.5 cm.) in 18 patients (36 per cent), the left testis was small in 9 (18 per cent), the right testis was small in 5 (10 per cent) and both testes were small in 18 (36 per cent). Testicular texture was homogeneous in 4 7 of the 50 patients (2 had a localized low intensity area subsequently found to be testicular atrophy, while 1 showed asymmetrical echogenicity, with the lower echogenicity being on the side of the smaller testis). The epididymis was identified in all patients and was normal in 48. Incidental small epididymal cysts were identified in the remaining 2 men as small, round areas of fluid collection that remained spherical regardless of the axis of scanning. Incidental fluid collection (that is a hydrocele) was present in 3 of the 50 patients. Identification of the spermatic vein in the spermatic cord at the neck of the scrotum was done in each patient. A total of 2 or 3 tubular structures was identified in the spermatic cord, 1 representing the spermatic artery, 1 the spermatic vein and 1 the ductus deferens. (The spermatic artery could be identified with the Doppler ultrasound probe.) In patients with subsequently proved varicocele the number of veins was more than 3 and at least 1 had a diameter more than 3 mm. (fig. 1). Although Rifkin 12 and Wolverson 13 and their associates have diagnosed varicocele with the presence of numerous dilated, tortuous vessels of various caliber when 1 was 2 or more mm., the majority of our control subjects as well as 5 infertile men with negative findings on venography had veins in the spermatic cord with a diameter of up to 3 mm. Therefore, we consider the diagnosis of varicocele by sonography if the veins in the pampiniform plexus are more than 3 mm., while the diagnosis is confirmed if they change in size with the patient in the upright position or during Valsalva's maneuver.
FIG. 1. Left varicocele. A, transverse scan demonstrates varicoceles (arrows) as tubular structures free of echoes and posterior to testis (T). B, longitudinal scan confirms presence of numerous varicoceles (arrows). T, testis.
713
SCROTAL ULTRASOUND IN INFERTILE MEN
Collateral veins in the region of the septum also could be identified in the patients with large bilateral varicoceles. Normal veins of the pampiniform plexus were visualized in all of the subjects. The veins were seen as small (less than 3 mm.) tubular structures in the region of the mediastinum testis, and they did not increase in size or change in appearance with the patient in the upright position or during Valsalva's maneuver (fig. 2). Of our 50 infertile patients 25 had clinical evidence of a palpable left varicocele that was confirmed by sonography. The sizes of these varicoceles could be measured accurately and compared favorably to the clinical classifications of grades 1 to 3 (or small, medium and large varicoceles). Of these 25 patients with a left varicocele 3 had a clinically palpable right varicocele (bilateral), which also was confirmed by sonography. Thus, ultrasound has an excellent clinical correlation with physical examination for a varicocele. The sperm count, percentage of motile sperm and testicular volume are shown in the table, differentiated into categories of clinical or subclinical varicocele. Because abnormalities of sperm morphology appear to be more related to diminished sperm count and motility than to the presence or absence of a varicocele, 14 this has not been included. Sonography revealed evidence of a left varicocele in 34 men (68 per cent) and a right varicocele in 24 (70 per cent). Reflux on the right side always occurred in conjunction with that on the left side (fig. 3). Thus, there was sonographic evidence of 12 subclinical varicoceles (24 per cent) on the left side and 21 (42 per cent) on the right side. The incidence appeared to be high on the right side because these were less detectable clinically than those on the left side. Of the 25 fertile control subjects physical examination revealed clinical evidence of a varicocele on the left side in 4 (16 per cent) and on the right side in none. Sonography revealed evidence of a varicocele on the left side in 8 men (32 per cent) on the right side in 2 (8 per cent).
reflex or thickened scrotal skin, were diagnosed easily by sonography. Twelve subclinical varicoceles were detected on the left side (24 per cent) and 21 (42 per cent) on the right side. The high incidence of bilateral varicoceles (70 per cent) was surprising but was comparable to that reported by Chatel and associates, who found radiological evidence of bilateral varicoceles in 60 per cent of 178 patients, 20 and to the 61 per cent incidence found by Gonzalez and associates in 39 patients evaluated by venography. 21 Their use of this more invasive technique may explain their greater reported incidence than that found by Rifkin and associates, who noted bilateral varicoceles in only 2 of 21 patients. 12 Bilaterality was not specified among the 13 patients studied by Wolverson and associates. 13 With retrograde venography in 350 patients, Bigot and Chatel found spermatic venous insufficiency to be almost as frequent on the right as on the left side (60 versus 76 per cent). 22 In our control population the incidence of varicocele by physical examination (16 per cent on the left side and none on the right side) was compatible with the 8 to 23 per cent incidence in men over-all. 23 Recent investigators have revised upward their previous opinion that varicoceles occur bilaterally in only 15 per cent of the individuals: among 870 varicocelectomies performed between 1980 and 1981 bilateral varicoceles were found in 57 per cent of the patients. 17 This apparently high incidence may explain the failure of left varicocelectomy to restore spermatogenesis to normal and improve fertility in some patients. Cockett and associates found that 65 per cent of new patients presenting with a left varicocele had a right varicocele and they believed that this finding may explain the only moderate impregnation rate (30 to 35 per cent) after left varicocelectomy. 24 With selective phlebography in subjects in the upright position, Ahlberg and associates reported retrograde left internal spermatic vein filling in 22 patients with varicoceles. 9 Some Correlation between varicocele, and sperm count, motility and testicular volume
DISCUSSION
Clinical studies and laboratory research18 have provided convincing evidence that varicoceles are detrimental to spermatogenesis in some men. The incidence of varicocele is several-fold higher in the infertile male population. 19 Therefore, it behooves the physician to use diagnostic techniques more sophisticated than careful physical examination to detect scrotal varicosities. In our experience ultrasonography has confirmed all clinical varicoceles, and detected small subclinical and bilateral varicoceles. Our report demonstrates that in the presence of clinically palpable varicoceles scrotal ultrasonography will not demonstrate false negative results. Varicoceles that easily escaped detection on physical examination alone, especially in patients with an active cremasteric 15 - 17
Testicular Volume (cc) Varicocele
Sperm Count Motile Sperm (%) (106/ml.)
Orchidometer Rt.
Clinical It., 22 pts. Clinical bilat., 3 pts.* Subclinical It., 12 pts. Subclinical bilat., 21 pts.*
Lt.
Ultrasound Rt.
Lt.
19 ± 17
41 ± 11
18± 3 17 ± 5 17 ± 6 14 ± 4
11 ±8
32 ± 8
12 ± 2 11 ± 3 11 ± 1
14 ± 13
37 ± 15
17 ± 3 14± 3 15 ± 4 11 ±4
19 ± 18
28 ± 11
17 ± 5 15 ± 4 15 ± 6 13 ± 6
9±2
Values are given in mean± standard deviation. * No patient had right varicocelesonly. Reflux on the right side always occurred in conjunction with reflux on the left side.
FIG. 2. Large left varicocele extends into spermatic cord. A, longitudinal scan shows numerous dilated vessels (varicocele) superior to testis. B, longitudinal scan through spermatic cord demonstrates extension of varicocele (curved arrows) to spermatic cord.
714
MCCLURE AND HRICAK
FIG. 3. Bilateral varicoceles. A, transverse scan with patient in supine position demonstrates bilateral varicoceles (curved arrows). B, transverse scan repeated during Valsalva's maneuver shows increase in size of left varicocele (curved arrow). C, long section scan obtained with patient in supine position shows varicoceles (arrows) posterior to testis (T). Incidental finding is hydrocele (H) seen superior to testis.
patients had no valves and in others the valves appeared incompetent. In 10 of the patients the right scrotal vein filled with contrast medium via collateral veins between the spermatic veins and other venous systems of the pelvis, lumbar and perirenal regions. Others suggested that these collaterals may be present in superficial vessels in the lower pelvis or scrotum. 25·26 These findings might explain the bilateral effects of the presumed unilateral varicoceles. Although no adequate clinical trials have been conducted to determine whether reflux of blood without a palpable varicocele has a role in the pathogenesis of infertility or whether the correction leads to improvement in semen quality, the concept of a subclinical varicocele as a cause of infertility has obvious appeal in patients in whom no other cause is evident. In 1975 Fogh-Andersen and associates reported fertility after ligation of the left spermatic vein in infertile men with oligospermia without clinical evidence of a varicocele. 27 Semen profiles improved in 50 per cent of the 22 patients and in 7 (31.8 per cent) impregnation was achieved within 16 months. Sperm quality and impregnation rate were significantly greater than in the 44 controls. Unfortunately, diagnostic tests, such as sonography, thermography and Doppler studies, were not performed to confirm the presence of a subclinical varicocele. Greenberg and associates used the Doppler stethoscope to diagnose subclinical varicoceles in 5 men with oligoasthenospermia and performed varicocelectomy in all 5.3 In 2 of these patients semen quality improved and each subsequently fathered a child. Lewis and Harrison diagnosed subclinical varicoceles with thermography in 6 patients and did varicocelectomies in all 6. 28 In 5 patients semen analysis improved and 2 achieved impregnation. More recently, Tinga and associates used sonography to detect subclinical varicoceles in 12 men. 16 Although there was no significant improvement in semen quality in these patients after varicocelectomy, there was no difference in the incidence of impregnation (33 per cent) between them and patients with various grades of palpable varicoceles. The high percentage of bilateral varicoceles in our infertile population may explain the pathophysiological mechanism by which what formerly was considered a unilateral anatomical abnormality bilateral testicular dysfunction is produced. Surprising also was the number of subclinical varicoceles detected by sonography. Although there is no conclusive evidence to date that repair of subclinical varicoceles improves semen quality and, consequently, fertility their presence may explain some of the previously unknown causes of idiopathic infertility. This high incidence of bilateral subclinical varicoceles may challenge us to change our present unilateral surgical approach to the patient with a clinically evident left varicocele.
REFERENCES 1. Tulloch, W. S.: A consideration of sterility factors in the light of subsequent pregnancies. II. Subfertility in the male. Edinburgh Med. J., 59: 29, 1952. 2. Dubin, L. and Amelar, R. D.: Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil. Steril., 21: 606, 1970. 3. Greenberg, S. H., Lipshultz, L. I. and Wein, A. J.: A preliminary report on 'subclinical varicocele': diagnosis by Doppler ultrasonic stethoscope. Examination and initial results of surgical therapy. J. Reprod. Med., 22: 77, 1979. 4. Hirsh, A. V., Cameron, K. M., Tyler, J. P., Simpson, J. and Pryor, J. P.: The Doppler assessment of varicoceles and internal spermatic vein reflux in infertile men. Brit. J. Urol., 52: 50, 1980. 5. Lewis, R. W. and Harrison, R. M.: Contact scrotal thermography: application to problems of infertility. J. Urol., 122: 40, 1979. 6. Comhaire, F., Monteyne, R. and Kunnen, M.: The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of "subclinical" varicocele. Fertil. Steril., 27: 694, 1976. 7. Harris, J. D., McConnell, B. J., Lipshultz, L. I., McConnell, R. W. and Conoley, P. H.: Radioisotope angiography in diagnosis of varicocele. Urology, 16: 69, 1980. 8. Comhaire, F. H.: Varicocele infertility: an enigma. Int. J. Androl., 6: 401, 1983. 9. Ahlberg, N. E., Bartley, 0., Chidekel, N. and Fritjofsson, A.: Phlebography in varicocele scroti. Acta Rad., 4: 517, 1966. 10. Comhaire, F. and Kunnen, M.: Selective retrograde venography of the internal spermatic vein: a conclusive approach to the diagnosis of varicocele. Andrologia, 8: 11, 1976. 11. Hricak, H. and Filly, R. A.: Sonography of the scrotum. Invest. Rad., 18: 112, 1983. 12. Rifkin, M. D., Foy, P. M., Kurtz, A. B., Pasto, M. E. and Goldberg, B. B.: The role of diagnostic ultrasonography in varicocele evaluation. J. Ultrasound Med., 2: 271, 1983. 13. Wolverson, M. K., Houttuin, E., Heiberg, E., Sundaram, M. and Gregory, J.: High-resolution real-time sonography of scrotal varicocele. Amer. J. Roentgen., 141: 775, 1983. 14. Rodriguez-Rigau, L. J., Smith, K. D. and Steinberger, E.: Varicocele and the morphology of spermatozoa. Fertil. Steril., 35: 54, 1981. 15. Johnsen, S. G. and Agger, P.: Quantitative evaluation of testicular biopsies before and after operation for varicocele. Fertil. Steril., 29: 58, 1978. 16. Tinga, D. J., Jager, S., Bruijnen, C. L. A. H., Kremer, J. and Mensink, H. J.: Factors related to semen improvement and fertility after varicocele operation. Fertil. Steril., 41: 404, 1984. 17. Cockett, A. T. K., Harrison, R. M., Comhaire, F. and Dubin, L.: The varicocele and its effect on fertility. Contemp. Surg., 24: 111, April 1984. 18. Saypol, D. C., Howards, S. S., Turner, T. T. and Miller, E. D., Jr.: Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs. J. Clin.
SCROTAL ULTRASOUND IN INFERTILE MEN
Invest., 68: 39, 1981. 19. Saypol, D. C.: Varicocele. J. Androl., 2: 61, 1981. 20. Chatel, A., Bigot, J.M., Helenon, C., Dectot, H., Rotman, J. and Salat-Baroux, J.: Interet de la phlebographie spermatique dans le diagnostic des sterilites d'origine circulatoire (varicocele). Comparaison avec les donnees cliniques, thermographiques et anatomiques. Ann. Rad., 21: 565, 1978. 21. Gonzalez, R., Reddy, P., Kaye, K. W. and Narayan, P.: Comparison of Doppler examination and retrograde spermatic venography in the diagnosis of varicocele. Fertil. Steril., 40: 96, 1983. 22. Bigot, J. M. and Chatel, A.: The value of retrograde spermatic phlebography in varicocele. Eur. Urol., 6: 301, 1980. 23. de Castro, M. P. P. and Mastrorocco, D. A. M.: Reproductive history and semen analysis in prevasectomy fertile men with and without varicocele. J. Androl., 5: 17, 1984.
24. Cockett, A. T. K., Takihara; H. and Cosentino, M. J.: The varicocele. Fertil. Steril., 41: 5, 1984. 25. Etriby, A. A.-E., Ibrahim, A.-A. A., Mahmoud, K. Z. and Elhaggar, S.: Subfertility and varicocele. I. Venogram demonstration of anastomosis sites in subfertile men. Fertil. Steril., 26: 1013, 1975. 26. Sayfan, J., Adam, Y. G. and Soffer, Y.: A natural "venous bypass" causing postoperative recurrence of a varicocele. J. Androl., 2: 108, 1981. 27. Fogh-Andersen, P., Nielsen, N. C., Rebbe, H. and Stakemann, G.: The effect on fertility of ligation of the left spermatic vein in men without clinical signs of varicocele. Acta Obst. Gynec. Scand., 54: 29, 1975. 28. Lewis, R. W. and Harrison, R. M.: Diagnosis and treatment of varicocele. Clin. Obst. Gynec., 25: 501, 1982.