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Are sperm motion parameters influenced by varicocele ligation?
FERTILITY AND STERILITYt VOL. 71, NO. 5, MAY 1999 Copyright ©1999 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
Are sperm motion parameters influenced by varicocele ligation? Mohamed T. Ismail, M.D., John Sedor, M.S., and Irvin H. Hirsch, M.D. Department of Urology, Jefferson Medical College, Philadelphia, Pennsylvania
Objective: To document objectively, improvements in sperm motion parameters in subfertile men after varicocele ligation with the use of computer-aided sperm analysis. Design: Retrospective chart review. Setting: An academic clinical environment. Patient(s): Thirty-four men with varicocele as the primary cause of infertility who underwent a physical examination, hormonal profile, and Doppler ultrasound evaluation. Intervention(s): Computer-aided sperm analysis was performed before and after either subinguinal or laparoscopic varicocele ligation. Main Outcome Measure(s): Patients were followed up for 3–18 months after operation, and average computer-aided sperm analysis values were obtained before and after operation. Computer-aided sperm analysis values were analyzed by paired Student’s t-test, with special reference to motility and sperm motion parameters. Result(s): After varicocele ligation, patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although the increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level. Conclusion(s): Because progressive velocity has been a primary computer-aided sperm analysis parameter predictive of male fertility and the success of assisted reproductive techniques, we conclude that varicocele ligation results in improvements in semen parameters, especially the key parameter of progressive sperm velocity. (Fertil Sterilt 1999;71:886 –90. ©1999 by American Society for Reproductive Medicine.) Key Words: Varicocele, computer-aided sperm analysis (CASA), surgery, laparoscopy, outcome assessment
Received January 27, 1998; revised and accepted December 14, 1998. Presented at the 22nd Annual Meeting of The American Society of Andrology, Baltimore, Maryland, February 23–25, 1997. Reprint requests: Irvin Hirsch, M.D., Jefferson Medical College, 1025 Walnut Street, Room 1103, Philadelphia, Pennsylvania 19107 (FAX: 215-9231884). 0015-0282/99/$20.00 PII S0015-0282(99)00101-6
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The role of varicocele in male infertility has been the subject of much controversy. The World Health Organization clearly identifies varicocele as an important cause of male infertility (1). Although varicocele is observed in approximately 40% of infertile men, it also is observed in 15% of healthy men who father children (2– 4). Several studies have been carried out to establish the effect of varicocelectomy on male fertility, with conflicting results (5–7). Semen analysis has been considered the cornerstone of male fertility assessment and includes the measurement of sperm concentration, motility, and morphology. Of these parameters, sperm motility has been thought to correlate strongly with male fertility potential. However, routine semen analysis often has been criticized for its subjectivity, technician
dependence, and intersubject variability. Although sperm motility commonly is abnormal in the setting of varicocele, it usually improves after varicocele ligation. To define more specifically the response of motility characteristics to the presence and treatment of varicocele, we used computeraided sperm analysis (CASA) to evaluate objectively the effect of varicocelectomy on semen parameters, with special reference to sperm motion parameters.
MATERIALS AND METHODS Patient Evaluation A total of 42 varicocelectomies were performed in 34 consecutively seen patients. The characteristics of the patient population according to varicocele size are outlined in Table 1. All the patients had their fertility history and
TABLE 1 Patient characteristics according to varicocele size. Varicocele size I II III
No. of patients
Median age (y) (range)
Mean (6 SD) duration of infertility (y)
Right
Left
Bilateral
Mean (6 SD) testicular volume*
25 6 3
37 (32–46) 34.5 (31–38) 31 (30–32)
2.0 6 1.2 2.5 6 1.9 1.6 6 1.3
2 0 0
17 4 0
6 2 3
16.0 6 3.1 17.6 6 5.5 13.0 6 1.7
Location of varicocele
Note: Values are means 6 SD. * The average testicular volume was used in bilateral cases.
medical history evaluated and underwent a physical examination. Their female partners were evaluated by a reproductive endocrinologist who identified any associated female factors. Men who demonstrated concurrent causes of male infertility were excluded from the study. Varicocele was diagnosed by physical palpation and Doppler auscultation in the standing position with and without the use of Valsalva’s maneuver. The size of the varicocele was classified as large (grade III), moderate (grade II), or small (grade I). This retrospective study was approved by our multiinstitutional review board.
Semen Analysis All patients were instructed to abstain from sexual intercourse for 2–3 days before their semen was collected. A minimum of 2 semen analyses were performed before operation, and 2–3 semen analyses were performed at 3, 6, and 9 months after operation. A 5-mL aliquot of the semen sample was placed in a 20-mm Cell-VU chamber (Fertility Technologies, Natick, MA), and the sperm concentration and motility parameters were analyzed with the Hamilton Thorne IVOS Motility Analyzer. Patients were stratified into four groups according to their preoperative sperm concentration: Group 1: sperm concentration of ,10 3 106/mL (n 5 9). Group 2: sperm concentration of 10–19 3 106/mL (n 5 7). Group 3: sperm concentration of 20–40 3 106/mL (n 5 8). Group 4: sperm concentration of .40 3 106/mL (n 5 10).
Varicocelectomy The patients were offered the option of open subinguinal or laparoscopic varicocelectomy. Twenty-two patients elected to undergo an open procedure, and the remaining 12 elected to undergo a laparoscopic varicocelectomy. All the procedures were performed by the same urologist in an outpatient surgical setting. A modified subinguinal varicocelectomy with preservation of the spermatic artery and lymphatics was used in patients who elected to undergo an open procedure. When present, external venous collaterals were ligated. Under loupe magnification (33.5), the dilated internal spermatic FERTILITY & STERILITYt
veins were doubly ligated with 2-0 silk suture. No attempt was made to deliver the testis. A standard insufflative intraperitoneal varicocele ligation with preservation of the spermatic artery was used in patients who elected to undergo a laparoscopic procedure.
Statistical Analysis The mean preoperative and postoperative CASA semen parameters were analyzed statistically. The preoperative and postoperative motion parameters were compared using the paired Student’s t-test. In addition, the data were stratified according to the surgical technique used, the size of the varicocele (Table 1), the age of the patient, the duration of infertility, the volume of the testicles, and the preoperative sperm concentration; the influence of these variables on semen parameters was determined.
RESULTS Of the 34 men who underwent varicocelectomy, 23 had a unilateral varicocele and 11 had a bilateral varicocele. The median age of these patients was 36 years (range, 30 – 46 years), and the mean (6 SD) duration of infertility was 2.1 6 1.3 years. A comparison of preoperative and postoperative CASA parameters is provided in Table 2. After varicocelectomy, the patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although these increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level (t-test 5 2.84, P5.008). Stratification of the data according to the size of the varicocele, the age of the patient, the duration of infertility, and the volume of the testicles revealed no statistically significant differences between the mean preoperative and postoperative CASA parameters. However, when the data were analyzed according to the type of procedure performed and the mean preoperative sperm concentration, statistically significant differences were noted (Table 3, Fig. 1). In the 887
TABLE 2 Mean CASA parameters before and after varicocelectomy. CASA parameter Volume (mL) Total concentration (3 106/mL) Motility (%) Progressive motility (%) Rapid velocity (%) Medium velocity (%) Slow velocity (%) Static velocity (%) Path velocity (mm/s) Progressive velocity (mm/s) Track speed (mm/s) Lateral amplitude (mm/s) Beat frequency (Hz) Straightness (%) Linearity (%)
Before varicocelectomy
After varicocelectomy
2.7 6 1.5 40.8 6 40.2 38.8 6 19.3 12.2 6 7.8 21.0 6 13.1 12.6 6 7.5 4.0 6 3.5 62.3 6 20.6 32.3 6 7.5 24.1 6 6.2 50.1 6 10.4 4.2 6 1.2 13.4 6 2.3 71.4 6 6.5 48.7 6 6.1
3.0 6 1.7 46.2 6 39.8 38.8 6 20.0 12.6 6 8.7 23.0 6 15.0 12.5 6 6.5 3.2 6 2.0 59.1 6 22.8 32.1 6 7.0 27.6 6 8.9* 54.6 6 19.4 4.2 6 1.2 13.4 6 3.8 73.1 6 5.1 49.2 6 7.0
Note: Values are means 6 SD. CASA 5 computer-aided sperm analysis. * t-test 5 2.84, P5.008.
patients who underwent laparoscopic varicocelectomy, the changes in progressive velocity and track speed were not significantly different. In contrast, in the patients who underwent subinguinal varicocelectomy, there were significant increases in both progressive velocity and track speed (P5.001 and P5.006, respectively). The mean (6 SD) preoperative sperm concentration in the open surgery group (49.6 6 45.9 3 106/mL) was significantly higher than that in the laparoscopic surgery group (P5.035, t-test 5 2.21); this was the only statistically significant difference between the two groups before operation. Moreover, stratification of the patients according to their preoperative sperm concentration yielded several findings. The increase in the mean postoperative sperm concentration (Fig. 1), reached statistically significant levels in patients with a preoperative sperm concentration of ,10 3 106/mL (group 1) and in those with a preoperative sperm concentration of 20 – 40 3 106/mL (group 3) (P5.028 and P5.041, respectively). Progressive velocity increased postoperatively to statistically significant levels (Fig. 2) in patients with a preoperative sperm concentration of .40 3 106/mL (group
4) (P5.04). In patients with a preoperative sperm concentration of 10 –19 3 106/mL (group 2), several motion parameters improved postoperatively (Fig. 3). The percentages of motility, progressive motility, and rapidly moving sperm increased to statistically significant levels, whereas the percentage of sluggish sperm decreased (P5.006, P,.001, P,.001, and P5.010, respectively). In addition, path velocity increased, although not significantly, in the same group (P5.40).
DISCUSSION The precise mechanism by which varicoceles cause infertility is unknown. Several hypotheses have been suggested, but none has been proven conclusively. Most widely accepted among these is elevation in scrotal temperature (8, 9). Also cited is the reflux of toxic metabolites from the renal and/or adrenal vein (10, 11). In a study of 425 subfertile men, Greenberg et al. (12) noted abnormal semen parameters in 83% of 159 men with varicoceles. Baker et al. (6) noted abnormal semen parameters in 92% of 651 men with varicoceles. Similar rates of impaired semen quality in men with varicoceles have been observed by other investigators (13–17). The finding of semen abnormalities presently constitutes the main indication for varicocele surgery in infertile patients. However, because there are infertile patients who have semen abnormalities in association with varicocele but who demonstrate no improvements in these parameters after varicocele ligation, debate has continued regarding the efficacy of surgery. In a review encompassing 15 published reports of 2,466 infertile men with varicoceles, Pryor and Howards (18) noted improvement in semen parameters in 66% of patients after varicocele ligation. Moreover, pregnancy rates of 30%–55% have been reported (5). The benefits of CASA evaluation of male reproductive function in patients with infertility are currently under study. Mathur et al. (19) observed that fertile men can be distinguished best from infertile men on the basis of the CASA parameter of sperm velocity, with 30 mm/s being the dividing point between these groups. In addition, the discriminatory ability of sperm progressive velocity has been confirmed by others (20, 21). Our finding that progressive
TABLE 3 Changes in CASA parameters with laparoscopic vs. open subinguinal varicocelectomy. Progressive velocity (mm/s) Procedure Laparoscopic varicocelectomy Open subinguinal varicocelectomy
Track Speed (mm/s)
Preoperative
Postoperative
P value
Preoperative
Postoperative
P value
24.1 6 5.5 24.1 6 6.6
23.1 6 5.9 30.0 6 9.4
NS .001
50.5 6 10.1 49.9 6 10.8
45.1 6 10.9 59.9 6 21.2
NS .006
Note: Values are means 6 SD unless otherwise indicated. CASA 5 computer-aided sperm analysis; NS 5 not significant.
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Vol. 71, No. 5, May 1999
FIGURE 1 Mean sperm concentrations before and after operation. See text for group definitions. NS 5 not significant.
velocity increased significantly after varicocele ligation (P5.001) supports these studies. Thus, the observation of significant improvement in sperm progressive velocity after varicocele ligation lends additional support to the role of varicocele ligation in maximizing male fertility potential. Fuse et al. (22), studying the effect of varicoceles on fertility, noted improved sperm velocity after operation in patients whose partners became pregnant. Although they observed no change in linearity, Parikh et al. (23), using CASA assess-
FIGURE 2
ment of sperm characteristics before and after varicocelectomy, noted improvements in additional motion parameters. Although we noticed increases in mean sperm density and in the percentage of sperm with rapid velocity, as well as in mean measures of linearity and track speed after operation, these were not statistically significant. This may be because
FIGURE 3 Motion parameters before and after operation in patients with a preoperative sperm concentration of 10 –19 3 106/mL. h 5 preoperative; ■ 5 postoperative.
Progressive velocity before and after operation. See text for group definitions. NS 5 not significant; h 5 preoperative; ■ 5 postoperative.
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we compared mean preoperative and postoperative CASA parameters, whereas Parikh et al. (23) compared preoperative CASA parameters with postoperative CASA parameters at 3, 6, and 9 months separately. Although no correlation between postoperative motion parameters and such variables as the size of the varicocele, the age of the patient, the duration of infertility, and the volume of the testicles was found, the degree of postoperative improvement in motion parameters correlated with the surgical approach used. Patients who elected to undergo subinguinal varicocelectomy demonstrated significantly increased progressive velocity and track speed (P5.001 and P5.006, respectively). In contrast, all 12 patients who elected to undergo laparoscopic varicocelectomy had no change in either parameter. Although lower preoperative sperm concentrations in the laparoscopic surgery group may account for this discrepancy, it also may be related to the more complete venous ligation afforded by the subinguinal approach that included collaterals external to the spermatic cord. Beck et al. (24) noted that these veins are present in approximately 74% of patients and recommended that they be ligated. These results lend more support to the superiority of the subinguinal approach to varicocele ligation. In a recent study (25), we found that laparoscopic techniques offered no advantage over the standard open subinguinal approach with respect to hospital stay, analgesic requirements, or return to work. Moreover, laparoscopic techniques require excessive operative time, may have attendant complications, and require general anesthesia, limitations that preclude their routine application in varicocele ligation. Several attempts have been made to define preoperatively the subset of patients who would benefit from varicocelectomy (4, 14, 15, 26). In our study, all patients—irrespective of their preoperative sperm concentration—showed improvement in at least one CASA parameter after operation. The mean sperm concentration increased in patients who had a preoperative sperm concentration of ,10 3 106/mL. In contrast, progressive sperm velocity increased in patients who had a high preoperative sperm concentration. Several motion parameters increased in patients who had an intermediate preoperative sperm concentration, which may reflect treatment of the pathophysiology induced by varicoceles. In conclusion, varicocelectomy results in improved se-
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men parameters, especially the key parameter of progressive sperm velocity. Computer-aided sperm analysis may allow for more accurate quantitative evaluation of semen samples before and after varicocelectomy. References 1. World Health Organization. Etiologic factors in 1,294 consecutive cases of male infertility. Fertil Steril 1971;22:469 –74. 2. Saypol DC. Varicocele. J Androl 1973;2:61–5. 3. Stewart BH, Montie JE. Male infertility: an optimistic report. J Urol 1973;110:216 – 8. 4. Dubin L, Amelar RD. Varicocelectomy: 986 cases in a 12 year study. Urology 1977;10:446 –9. 5. Hanley HG, Harrison RG. The nature and surgical treatment of varicocele. Br J Surg 1962;50:64 –7. 6. Baker H, Burger H, De Krester D, Hudson B, Rennie G, Straffon W. Testicular vein ligation and fertility in men with varicocele. Br Med J 1985;291:1678 – 80. 7. Vermeulen A, Vandeweghe M. Improved fertility after varicocele correction: fact or fiction. Fertil Steril 1984;42:249 –56. 8. Zorgniotti AW, Macleod J. Studies in the temperature, human semen quality and varicocele. Fertil Steril 1974;24:854 – 63. 9. Yamagushi M, Sakatoku J, Takihara H. The application of intrascrotal deep body temperature measurement for the noninvasive diagnosis of varicocele. Fertil Steril 1989;52:295–301. 10. Comhaire F, Vermeulen A. Varicocele sterility: cortisol and catecholamines. Fertil Steril 1974;25:88 –95. 11. Ito H, Fuse H, Minagawa H, Kawamura K, Murakami M, Shimazaki J. Internal spermatic vein prostaglandins in varicocele patients. Fertil Steril 1982;38:218 –22. 12. Greenberg SH, Lipshultz LI, Wein AJ. Experience with 425 subfertile male patients. J Urol 1978;119:507–10. 13. Aafjes JH, Van Der Vijver JC. Fertility of men with and without varicocele. Fertil Steril 1985;43:901– 4. 14. Cockett AT, Urry RL, Dougherty KA. The varicocele and semen characteristics. J Urol 1979;121:435– 6. 15. Marks JL, McMahon R, Lipshultz LI. Predictive parameters of successful varicocele repair. J Urol 1986;136:609 –12. 16. Newton R, Schienfield JS, Schiff I. The effect of varicocelectomy on sperm count, motility and conception rate. Fertil Steril 1980;34:250 – 4. 17. Nilsson S, Edvinsson A, Nilsson B. Improvement of semen and pregnancy rate after ligation and division of the internal spermatic vein: fact or fiction? Br J Urol 1979;51:591– 6. 18. Pryor JL, Howards SS. Varicocele. Urol Clin North Am 1987;14:499 – 513. 19. Mathur S, Carlton M, Ziegler J, Rust PF, Williamson HO. A computerized sperm motion analysis. Fertil Steril 1986;46:484 – 8. 20. Holt WV, Moore HD, Hillier SG. Computer-assisted measurement of sperm swimming speed in human semen: correlation of results with in-vitro fertilization. Fertil Steril 1985;44:112–9. 21. Aitkin RJ, Best FS, Richardson DW, Djahanbakhch D, Mortimer D, Templeton AA, et al. An analysis of sperm function in cases of unexplained infertility. Conventional criteria, movement characteristics and fertilizing capacity. Fertil Steril 1982;38:212–21. 22. Fuse H, Akashi T, Fujishiro Y, Kazama T, Katayama T. Effect of varicocele on fertility potential: comparison between impregnating and nonimpregnating groups. Arch Androl 1995;35:143– 8. 23. Parikh FR, Kamat SA, Kodwaney GG, Balaiah D. Computer-assisted semen analysis parameters in men with varicocele: is surgery helpful? Fertil Steril 1996;66:440 –5. 24. Beck EM, Schlegel PN, Goldstein M. Intraoperative varicocele anatomy: a macroscopic and microscopic study. J Urol 1992;148:1190 – 4. 25. Hirsch IH, Abdel-Meguid TA, Gomella LG. Postsurgical outcomes assessment following varicocele ligation: laparoscopic versus subinguinal approach. Urology 1998;51:810 –5. 26. Brown JS. Varicocelectomy in the subfertile male: a 10-year experience with 295 cases. Fertil Steril 1976;27:1046 –53.
Vol. 71, No. 5, May 1999
Are sperm motion parameters influenced by varicocele ligation? Mohamed T. Ismail, M.D., John Sedor, M.S., and Irvin H. Hirsch, M.D. Department of Urology, Jefferson Medical College, Philadelphia, Pennsylvania
Objective: To document objectively, improvements in sperm motion parameters in subfertile men after varicocele ligation with the use of computer-aided sperm analysis. Design: Retrospective chart review. Setting: An academic clinical environment. Patient(s): Thirty-four men with varicocele as the primary cause of infertility who underwent a physical examination, hormonal profile, and Doppler ultrasound evaluation. Intervention(s): Computer-aided sperm analysis was performed before and after either subinguinal or laparoscopic varicocele ligation. Main Outcome Measure(s): Patients were followed up for 3–18 months after operation, and average computer-aided sperm analysis values were obtained before and after operation. Computer-aided sperm analysis values were analyzed by paired Student’s t-test, with special reference to motility and sperm motion parameters. Result(s): After varicocele ligation, patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although the increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level. Conclusion(s): Because progressive velocity has been a primary computer-aided sperm analysis parameter predictive of male fertility and the success of assisted reproductive techniques, we conclude that varicocele ligation results in improvements in semen parameters, especially the key parameter of progressive sperm velocity. (Fertil Sterilt 1999;71:886 –90. ©1999 by American Society for Reproductive Medicine.) Key Words: Varicocele, computer-aided sperm analysis (CASA), surgery, laparoscopy, outcome assessment
Received January 27, 1998; revised and accepted December 14, 1998. Presented at the 22nd Annual Meeting of The American Society of Andrology, Baltimore, Maryland, February 23–25, 1997. Reprint requests: Irvin Hirsch, M.D., Jefferson Medical College, 1025 Walnut Street, Room 1103, Philadelphia, Pennsylvania 19107 (FAX: 215-9231884). 0015-0282/99/$20.00 PII S0015-0282(99)00101-6
886
The role of varicocele in male infertility has been the subject of much controversy. The World Health Organization clearly identifies varicocele as an important cause of male infertility (1). Although varicocele is observed in approximately 40% of infertile men, it also is observed in 15% of healthy men who father children (2– 4). Several studies have been carried out to establish the effect of varicocelectomy on male fertility, with conflicting results (5–7). Semen analysis has been considered the cornerstone of male fertility assessment and includes the measurement of sperm concentration, motility, and morphology. Of these parameters, sperm motility has been thought to correlate strongly with male fertility potential. However, routine semen analysis often has been criticized for its subjectivity, technician
dependence, and intersubject variability. Although sperm motility commonly is abnormal in the setting of varicocele, it usually improves after varicocele ligation. To define more specifically the response of motility characteristics to the presence and treatment of varicocele, we used computeraided sperm analysis (CASA) to evaluate objectively the effect of varicocelectomy on semen parameters, with special reference to sperm motion parameters.
MATERIALS AND METHODS Patient Evaluation A total of 42 varicocelectomies were performed in 34 consecutively seen patients. The characteristics of the patient population according to varicocele size are outlined in Table 1. All the patients had their fertility history and
TABLE 1 Patient characteristics according to varicocele size. Varicocele size I II III
No. of patients
Median age (y) (range)
Mean (6 SD) duration of infertility (y)
Right
Left
Bilateral
Mean (6 SD) testicular volume*
25 6 3
37 (32–46) 34.5 (31–38) 31 (30–32)
2.0 6 1.2 2.5 6 1.9 1.6 6 1.3
2 0 0
17 4 0
6 2 3
16.0 6 3.1 17.6 6 5.5 13.0 6 1.7
Location of varicocele
Note: Values are means 6 SD. * The average testicular volume was used in bilateral cases.
medical history evaluated and underwent a physical examination. Their female partners were evaluated by a reproductive endocrinologist who identified any associated female factors. Men who demonstrated concurrent causes of male infertility were excluded from the study. Varicocele was diagnosed by physical palpation and Doppler auscultation in the standing position with and without the use of Valsalva’s maneuver. The size of the varicocele was classified as large (grade III), moderate (grade II), or small (grade I). This retrospective study was approved by our multiinstitutional review board.
Semen Analysis All patients were instructed to abstain from sexual intercourse for 2–3 days before their semen was collected. A minimum of 2 semen analyses were performed before operation, and 2–3 semen analyses were performed at 3, 6, and 9 months after operation. A 5-mL aliquot of the semen sample was placed in a 20-mm Cell-VU chamber (Fertility Technologies, Natick, MA), and the sperm concentration and motility parameters were analyzed with the Hamilton Thorne IVOS Motility Analyzer. Patients were stratified into four groups according to their preoperative sperm concentration: Group 1: sperm concentration of ,10 3 106/mL (n 5 9). Group 2: sperm concentration of 10–19 3 106/mL (n 5 7). Group 3: sperm concentration of 20–40 3 106/mL (n 5 8). Group 4: sperm concentration of .40 3 106/mL (n 5 10).
Varicocelectomy The patients were offered the option of open subinguinal or laparoscopic varicocelectomy. Twenty-two patients elected to undergo an open procedure, and the remaining 12 elected to undergo a laparoscopic varicocelectomy. All the procedures were performed by the same urologist in an outpatient surgical setting. A modified subinguinal varicocelectomy with preservation of the spermatic artery and lymphatics was used in patients who elected to undergo an open procedure. When present, external venous collaterals were ligated. Under loupe magnification (33.5), the dilated internal spermatic FERTILITY & STERILITYt
veins were doubly ligated with 2-0 silk suture. No attempt was made to deliver the testis. A standard insufflative intraperitoneal varicocele ligation with preservation of the spermatic artery was used in patients who elected to undergo a laparoscopic procedure.
Statistical Analysis The mean preoperative and postoperative CASA semen parameters were analyzed statistically. The preoperative and postoperative motion parameters were compared using the paired Student’s t-test. In addition, the data were stratified according to the surgical technique used, the size of the varicocele (Table 1), the age of the patient, the duration of infertility, the volume of the testicles, and the preoperative sperm concentration; the influence of these variables on semen parameters was determined.
RESULTS Of the 34 men who underwent varicocelectomy, 23 had a unilateral varicocele and 11 had a bilateral varicocele. The median age of these patients was 36 years (range, 30 – 46 years), and the mean (6 SD) duration of infertility was 2.1 6 1.3 years. A comparison of preoperative and postoperative CASA parameters is provided in Table 2. After varicocelectomy, the patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although these increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level (t-test 5 2.84, P5.008). Stratification of the data according to the size of the varicocele, the age of the patient, the duration of infertility, and the volume of the testicles revealed no statistically significant differences between the mean preoperative and postoperative CASA parameters. However, when the data were analyzed according to the type of procedure performed and the mean preoperative sperm concentration, statistically significant differences were noted (Table 3, Fig. 1). In the 887
TABLE 2 Mean CASA parameters before and after varicocelectomy. CASA parameter Volume (mL) Total concentration (3 106/mL) Motility (%) Progressive motility (%) Rapid velocity (%) Medium velocity (%) Slow velocity (%) Static velocity (%) Path velocity (mm/s) Progressive velocity (mm/s) Track speed (mm/s) Lateral amplitude (mm/s) Beat frequency (Hz) Straightness (%) Linearity (%)
Before varicocelectomy
After varicocelectomy
2.7 6 1.5 40.8 6 40.2 38.8 6 19.3 12.2 6 7.8 21.0 6 13.1 12.6 6 7.5 4.0 6 3.5 62.3 6 20.6 32.3 6 7.5 24.1 6 6.2 50.1 6 10.4 4.2 6 1.2 13.4 6 2.3 71.4 6 6.5 48.7 6 6.1
3.0 6 1.7 46.2 6 39.8 38.8 6 20.0 12.6 6 8.7 23.0 6 15.0 12.5 6 6.5 3.2 6 2.0 59.1 6 22.8 32.1 6 7.0 27.6 6 8.9* 54.6 6 19.4 4.2 6 1.2 13.4 6 3.8 73.1 6 5.1 49.2 6 7.0
Note: Values are means 6 SD. CASA 5 computer-aided sperm analysis. * t-test 5 2.84, P5.008.
patients who underwent laparoscopic varicocelectomy, the changes in progressive velocity and track speed were not significantly different. In contrast, in the patients who underwent subinguinal varicocelectomy, there were significant increases in both progressive velocity and track speed (P5.001 and P5.006, respectively). The mean (6 SD) preoperative sperm concentration in the open surgery group (49.6 6 45.9 3 106/mL) was significantly higher than that in the laparoscopic surgery group (P5.035, t-test 5 2.21); this was the only statistically significant difference between the two groups before operation. Moreover, stratification of the patients according to their preoperative sperm concentration yielded several findings. The increase in the mean postoperative sperm concentration (Fig. 1), reached statistically significant levels in patients with a preoperative sperm concentration of ,10 3 106/mL (group 1) and in those with a preoperative sperm concentration of 20 – 40 3 106/mL (group 3) (P5.028 and P5.041, respectively). Progressive velocity increased postoperatively to statistically significant levels (Fig. 2) in patients with a preoperative sperm concentration of .40 3 106/mL (group
4) (P5.04). In patients with a preoperative sperm concentration of 10 –19 3 106/mL (group 2), several motion parameters improved postoperatively (Fig. 3). The percentages of motility, progressive motility, and rapidly moving sperm increased to statistically significant levels, whereas the percentage of sluggish sperm decreased (P5.006, P,.001, P,.001, and P5.010, respectively). In addition, path velocity increased, although not significantly, in the same group (P5.40).
DISCUSSION The precise mechanism by which varicoceles cause infertility is unknown. Several hypotheses have been suggested, but none has been proven conclusively. Most widely accepted among these is elevation in scrotal temperature (8, 9). Also cited is the reflux of toxic metabolites from the renal and/or adrenal vein (10, 11). In a study of 425 subfertile men, Greenberg et al. (12) noted abnormal semen parameters in 83% of 159 men with varicoceles. Baker et al. (6) noted abnormal semen parameters in 92% of 651 men with varicoceles. Similar rates of impaired semen quality in men with varicoceles have been observed by other investigators (13–17). The finding of semen abnormalities presently constitutes the main indication for varicocele surgery in infertile patients. However, because there are infertile patients who have semen abnormalities in association with varicocele but who demonstrate no improvements in these parameters after varicocele ligation, debate has continued regarding the efficacy of surgery. In a review encompassing 15 published reports of 2,466 infertile men with varicoceles, Pryor and Howards (18) noted improvement in semen parameters in 66% of patients after varicocele ligation. Moreover, pregnancy rates of 30%–55% have been reported (5). The benefits of CASA evaluation of male reproductive function in patients with infertility are currently under study. Mathur et al. (19) observed that fertile men can be distinguished best from infertile men on the basis of the CASA parameter of sperm velocity, with 30 mm/s being the dividing point between these groups. In addition, the discriminatory ability of sperm progressive velocity has been confirmed by others (20, 21). Our finding that progressive
TABLE 3 Changes in CASA parameters with laparoscopic vs. open subinguinal varicocelectomy. Progressive velocity (mm/s) Procedure Laparoscopic varicocelectomy Open subinguinal varicocelectomy
Track Speed (mm/s)
Preoperative
Postoperative
P value
Preoperative
Postoperative
P value
24.1 6 5.5 24.1 6 6.6
23.1 6 5.9 30.0 6 9.4
NS .001
50.5 6 10.1 49.9 6 10.8
45.1 6 10.9 59.9 6 21.2
NS .006
Note: Values are means 6 SD unless otherwise indicated. CASA 5 computer-aided sperm analysis; NS 5 not significant.
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Vol. 71, No. 5, May 1999
FIGURE 1 Mean sperm concentrations before and after operation. See text for group definitions. NS 5 not significant.
velocity increased significantly after varicocele ligation (P5.001) supports these studies. Thus, the observation of significant improvement in sperm progressive velocity after varicocele ligation lends additional support to the role of varicocele ligation in maximizing male fertility potential. Fuse et al. (22), studying the effect of varicoceles on fertility, noted improved sperm velocity after operation in patients whose partners became pregnant. Although they observed no change in linearity, Parikh et al. (23), using CASA assess-
FIGURE 2
ment of sperm characteristics before and after varicocelectomy, noted improvements in additional motion parameters. Although we noticed increases in mean sperm density and in the percentage of sperm with rapid velocity, as well as in mean measures of linearity and track speed after operation, these were not statistically significant. This may be because
FIGURE 3 Motion parameters before and after operation in patients with a preoperative sperm concentration of 10 –19 3 106/mL. h 5 preoperative; ■ 5 postoperative.
Progressive velocity before and after operation. See text for group definitions. NS 5 not significant; h 5 preoperative; ■ 5 postoperative.
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we compared mean preoperative and postoperative CASA parameters, whereas Parikh et al. (23) compared preoperative CASA parameters with postoperative CASA parameters at 3, 6, and 9 months separately. Although no correlation between postoperative motion parameters and such variables as the size of the varicocele, the age of the patient, the duration of infertility, and the volume of the testicles was found, the degree of postoperative improvement in motion parameters correlated with the surgical approach used. Patients who elected to undergo subinguinal varicocelectomy demonstrated significantly increased progressive velocity and track speed (P5.001 and P5.006, respectively). In contrast, all 12 patients who elected to undergo laparoscopic varicocelectomy had no change in either parameter. Although lower preoperative sperm concentrations in the laparoscopic surgery group may account for this discrepancy, it also may be related to the more complete venous ligation afforded by the subinguinal approach that included collaterals external to the spermatic cord. Beck et al. (24) noted that these veins are present in approximately 74% of patients and recommended that they be ligated. These results lend more support to the superiority of the subinguinal approach to varicocele ligation. In a recent study (25), we found that laparoscopic techniques offered no advantage over the standard open subinguinal approach with respect to hospital stay, analgesic requirements, or return to work. Moreover, laparoscopic techniques require excessive operative time, may have attendant complications, and require general anesthesia, limitations that preclude their routine application in varicocele ligation. Several attempts have been made to define preoperatively the subset of patients who would benefit from varicocelectomy (4, 14, 15, 26). In our study, all patients—irrespective of their preoperative sperm concentration—showed improvement in at least one CASA parameter after operation. The mean sperm concentration increased in patients who had a preoperative sperm concentration of ,10 3 106/mL. In contrast, progressive sperm velocity increased in patients who had a high preoperative sperm concentration. Several motion parameters increased in patients who had an intermediate preoperative sperm concentration, which may reflect treatment of the pathophysiology induced by varicoceles. In conclusion, varicocelectomy results in improved se-
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