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Sperm extraction at orchiectomy for testis cancer
FERTILITY AND STERILITY威 VOL. 75, NO. 2, FEBRUARY 2001 Copyright ©2001 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
Sperm extraction at orchiectomy for testis cancer Jack Baniel, M.D.,a and Avishai Sella, M.D.b Rabin Medical Center, Beilinson Campus, Sackler School of Medicine, Tel Aviv University, Petach Tikva, Israel
Objective: To evaluate the value of aspirating sperm from the vas and epididymis at orchiectomy in azoospermic patients. Design: Retrospective clinical study. Setting: Tertiary care academic hospital. Patient(s): Three patients with known azoospermia who presented with testicular masses suspected to be cancerous. Intervention(s): At orchiectomy, immediately after ligation of the spermatic cord, the contents of the epididymis and vas deferens were extracted into preserving media. Main Outcome Measure(s): Fertility rate. Result(s): Sperm retrieval was successful in all three patients. The mean total sperm count was 2.3 ⫻ 106/mL with 20% motility. Intracytoplasmic injection of sperm harvested by using this method was successful in two couples, one of which delivered a healthy infant. Conclusion(s): Sperm can be aspirated from the vas deferens and epididymis at orchiectomy for preservation. In azoospermic patients, this procedure may salvage enough sperm for successful use in micromanipulation techniques. It may be worthwhile to perform sperm aspiration during orchiectomy for testis cancer in any patient with known or suspected infertility. (Fertil Steril威 2001;75:260 –2. ©2001 by American Society for Reproductive Medicine.) Key Words: Testis cancer, sperm preservation, fertility, azoospermia
Testis cancer commonly occurs between the ages of 15 and 35 years. Because many men of this age are unmarried or in their early years of marriage, the issue of fertility is important.
Patients with infertility are at high risk for testis cancer, and they present a more complicated clinical problem. Several such patients have undergone orchiopexy and have small hypotrophic testes. When they present with a tumor, their only sperm-bearing testis may require resection.
From 1997 to 1998, three patients with azoospermia were managed for suspected testis cancer at the Beilinson Medical Center, Petach Tikva, Israel (Table 1). The cause of infertility was previously undescended testes and bilateral testis atrophy in two patients and primary azoospermia in one patient. All three patients were referred for suspected testis mass on physical examination and sonography. All patients had clinical stage I disease. All were aspermic on consecutive sperm counts performed before orchiectomy and were therefore scheduled for intraoperative sperm preservation. Institutional Review Board approval was obtained before initiation of procedures.
We present our experience with sperm retrieval by squeezing the epididymis and vas deferens at orchiectomy in azoospermic patients. We also discuss a role for this procedure in the management of testis cancer.
At orchiectomy, sperm was harvested from the vas deferens, epididymis, and testis tissue remote from the tumor. Immediately after ligation of the spermatic cord, the contents of the epididymis and vas deferens were extracted
Up to 60% of patients have impaired sperm counts when they present with testis cancer. Many of these patients will need adjuvant chemotherapy, surgery, or radiation, all of which have further negative effects on their fertility. Received April 13, 2000; revised and accepted August 21, 2000. Reprint requests: Jack Baniel, M.D., Urology Section,, Rabin Medical Center, Beilinson Campus, Petach Tikva, 49100 Israel (FAX: 03-9225108; E-mail: [email protected]). a Urology Section. b Genitourinary Oncology Unit. 0015-0282/01/$20.00 PII S0015-0282(00)01706-4
260
METHODS AND MATERIALS
TABLE 1 Data for three patients with azoospermia and testicular masses suspected to be cancerous.
Patient 1 2 3
Side of orchiectomy
Cause of infertility
Left Right Left
Undescended testis; right orchidopexy Undescended testes; bilateral orchidopexy Primary
Pathology
Preoperative sperm count (⫻106/L)
Vas deferens sperm count (⫻106/L)
Fertilization
Live birth
Seminoma Leydig cell tumor Seminoma
0 0 0
2.5 3.6 1.3
Yes Yes No
Yes No No
Baniel. Sperm extraction of orchiectomy. Fertil Steril 2001.
into appropriate preserving media. The testis was incised along the longitudinal axis and the tumor was circumscribed. Normal tissue distant to the tumor was harvested into media and scanned for viable sperm.
RESULTS Attempts to retrieve sperm were successful in all three patients. The mean amount of fluid collected was 1 mL. The mean total sperm count was 2.3 ⫻ 106/mL (range, 1.3–3.6 ⫻ 106/mL), and the average motility was 20% (Table 1). Samples were cryopreserved for further use. Mobile sperm was also found in the testis tissue, but in smaller amounts (average, 2.0 ⫻ 106/mL). Intracytoplasmic sperm injection with vasal sperm was performed in all three cases and was successful in two couples. On follow-up, one healthy infant was born from sperm salvaged by this method.
DISCUSSION Testis cancer and male infertility are closely associated. It has been estimated that 40%– 60% of patients with testis cancer are hypofertile at diagnosis (1–3). This lack of fertility is thought to be related to stage of disease, and patients with non-seminoma have lower counts than those with seminoma (4, 5). Many patients experience improvement in sperm counts after orchiectomy. Foster et al. (1) reported that 76% of patients who wished to have children after retroperitoneal lymph node dissection succeeded in doing so. Proposed explanations for improved spermatogenesis after orchiectomy include decreased production of antisperm antibodies, cessation of hormone production by the tumor (such as hCG), and improvement in psychological measures (1, 3, 6). Patients may have to undergo radiation, chemotherapy, or surgery as part of medical management. Each of these treatments has deleterious effects on sperm production or emission and thus contributes to infertility. It is therefore common practice to preserve sperm before initiation of therapy for testis cancer, in order to retain the potential for fertilization in case therapy results in azoospermia. However, it is FERTILITY & STERILITY威
not currently routine practice to preserve sperm before orchiectomy. An informal examination of current urology textbooks (7, 8) revealed no mention of sperm preservation in the algorithm of testis cancer management. There are several reasons for such an omission. Most patients with testis cancer are young, and the idea of having children often seems distant and irrelevant to the patient who must undergo immediate treatment of imminent cancer. Sperm banking facilities may not be available at every clinic, and the wait for a sperm count and proper sperm preservation may delay prompt management. Many orchiectomies are performed by primary care urologists, who treat few patients with testis cancer, and the need for sperm preservation may escape their attention. In the azoospermic patient with testis cancer, the problem of infertility is intensified. Sometimes only a single functioning testis is present, and if a tumor is suspected, the only chance for future fertility may be to preserve sperm before orchiectomy. This was demonstrated by Scher et al. (9), who retrieved sperm from testis tissue at orchiectomy for testis cancer in patients with a single testis and poor sperm counts. In these patients, one may find some sperm at orchiectomy but none after the procedure. However, a considerable number of patients with normal testes and no previous fertility problems may unknowingly have very low sperm counts; this problem has not yet been addressed. At present, even semen of the poorest quality and quantity (1–50 sperm) can produce pregnancy when used in modern IVF and micromanipulation techniques. It is therefore worthwhile to retrieve any amount of sperm available at orchiectomy before discarding the diseased testis. We show that in patients with sperm counts of zero before orchiectomy, a considerable amount of sperm was retrieved at orchiectomy by squeezing the contents of the vas deferens and epididymis into preserving media. This sperm was used in three couples to achieve fertilization, and in one couple, a healthy infant was delivered after a normal pregnancy. We propose that by making sperm aspiration from the vas deferens and epididymis a routine part of every orchiectomy for testis cancer, an immediate sperm count can be obtained and sperm can be preserved for further manipulation. This 261
may be the only chance for future fertilization in azoospermic patients. This technique may be used in a patient scheduled for orchiectomy who has clinical hypogonadism, known infertility, or a single testis or has had orchidopexy. References 1. Foster RS, McNulty A, Rubin LR, Bennet R, Rowland RG, Sledge DW, et al. The fertility of patients with stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection. J Urol 1994:152:1139 – 42. 2. Lange PH, Chang WY, Fraley EE. Fertility issues in the therapy of nonseminomatous testicular tumors. Urol Clin North Am 1987:14:731– 47. 3. Presti JC, Herr HW, Carrol PR. Fertility and testis cancer. Urol Clin North Am 1993:20:173–9.
262
Baniel and Sella
Sperm Extraction at Orchiectomy
4. Botchan A, Hauser R, Yogev L, Gamzu R, Paz G, Lessing JB, et al. Testicular cancer and spermatogenesis. Hum Reprod 1997:12:755– 8. 5. Agarwal A, Toletino MV, Sidu RS, Azyman I, Lee JC, Thomas AJ, et al. Effects of cryopreservation on semen quality in patients with testis cancer. Urology 1995:46:382–9. 6. Turek PJ, Lowther DN, Carrol PR. Fertility issues and their management in men with testis cancer. Urol Clin North Am 1998:25:517–31. 7. Rowland RG, Donohue JP: Scrotum and testis. In: Gillenwater JY, Grayhack JT, Howards SS, Duckett JW. Adult and pediatric urology. St. Louis: Mosby–Year Book, 1991:1565–98. 8. Richie J. Neoplasms of the testis. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s urology. Philadelphia: W.B. Saunders, 1998: 2411–36. 9. Scher D, Choi BB, Su L, Moomy M, Schlegel P, Goldstein M. Pregnancy after testicular sperm extraction at the time of radical orchiectomy for cancer in a solitary testis [abstract]. J Urol 1999;161(suppl):353.
Vol. 75, No. 2, February 2001
Sperm extraction at orchiectomy for testis cancer Jack Baniel, M.D.,a and Avishai Sella, M.D.b Rabin Medical Center, Beilinson Campus, Sackler School of Medicine, Tel Aviv University, Petach Tikva, Israel
Objective: To evaluate the value of aspirating sperm from the vas and epididymis at orchiectomy in azoospermic patients. Design: Retrospective clinical study. Setting: Tertiary care academic hospital. Patient(s): Three patients with known azoospermia who presented with testicular masses suspected to be cancerous. Intervention(s): At orchiectomy, immediately after ligation of the spermatic cord, the contents of the epididymis and vas deferens were extracted into preserving media. Main Outcome Measure(s): Fertility rate. Result(s): Sperm retrieval was successful in all three patients. The mean total sperm count was 2.3 ⫻ 106/mL with 20% motility. Intracytoplasmic injection of sperm harvested by using this method was successful in two couples, one of which delivered a healthy infant. Conclusion(s): Sperm can be aspirated from the vas deferens and epididymis at orchiectomy for preservation. In azoospermic patients, this procedure may salvage enough sperm for successful use in micromanipulation techniques. It may be worthwhile to perform sperm aspiration during orchiectomy for testis cancer in any patient with known or suspected infertility. (Fertil Steril威 2001;75:260 –2. ©2001 by American Society for Reproductive Medicine.) Key Words: Testis cancer, sperm preservation, fertility, azoospermia
Testis cancer commonly occurs between the ages of 15 and 35 years. Because many men of this age are unmarried or in their early years of marriage, the issue of fertility is important.
Patients with infertility are at high risk for testis cancer, and they present a more complicated clinical problem. Several such patients have undergone orchiopexy and have small hypotrophic testes. When they present with a tumor, their only sperm-bearing testis may require resection.
From 1997 to 1998, three patients with azoospermia were managed for suspected testis cancer at the Beilinson Medical Center, Petach Tikva, Israel (Table 1). The cause of infertility was previously undescended testes and bilateral testis atrophy in two patients and primary azoospermia in one patient. All three patients were referred for suspected testis mass on physical examination and sonography. All patients had clinical stage I disease. All were aspermic on consecutive sperm counts performed before orchiectomy and were therefore scheduled for intraoperative sperm preservation. Institutional Review Board approval was obtained before initiation of procedures.
We present our experience with sperm retrieval by squeezing the epididymis and vas deferens at orchiectomy in azoospermic patients. We also discuss a role for this procedure in the management of testis cancer.
At orchiectomy, sperm was harvested from the vas deferens, epididymis, and testis tissue remote from the tumor. Immediately after ligation of the spermatic cord, the contents of the epididymis and vas deferens were extracted
Up to 60% of patients have impaired sperm counts when they present with testis cancer. Many of these patients will need adjuvant chemotherapy, surgery, or radiation, all of which have further negative effects on their fertility. Received April 13, 2000; revised and accepted August 21, 2000. Reprint requests: Jack Baniel, M.D., Urology Section,, Rabin Medical Center, Beilinson Campus, Petach Tikva, 49100 Israel (FAX: 03-9225108; E-mail: [email protected]). a Urology Section. b Genitourinary Oncology Unit. 0015-0282/01/$20.00 PII S0015-0282(00)01706-4
260
METHODS AND MATERIALS
TABLE 1 Data for three patients with azoospermia and testicular masses suspected to be cancerous.
Patient 1 2 3
Side of orchiectomy
Cause of infertility
Left Right Left
Undescended testis; right orchidopexy Undescended testes; bilateral orchidopexy Primary
Pathology
Preoperative sperm count (⫻106/L)
Vas deferens sperm count (⫻106/L)
Fertilization
Live birth
Seminoma Leydig cell tumor Seminoma
0 0 0
2.5 3.6 1.3
Yes Yes No
Yes No No
Baniel. Sperm extraction of orchiectomy. Fertil Steril 2001.
into appropriate preserving media. The testis was incised along the longitudinal axis and the tumor was circumscribed. Normal tissue distant to the tumor was harvested into media and scanned for viable sperm.
RESULTS Attempts to retrieve sperm were successful in all three patients. The mean amount of fluid collected was 1 mL. The mean total sperm count was 2.3 ⫻ 106/mL (range, 1.3–3.6 ⫻ 106/mL), and the average motility was 20% (Table 1). Samples were cryopreserved for further use. Mobile sperm was also found in the testis tissue, but in smaller amounts (average, 2.0 ⫻ 106/mL). Intracytoplasmic sperm injection with vasal sperm was performed in all three cases and was successful in two couples. On follow-up, one healthy infant was born from sperm salvaged by this method.
DISCUSSION Testis cancer and male infertility are closely associated. It has been estimated that 40%– 60% of patients with testis cancer are hypofertile at diagnosis (1–3). This lack of fertility is thought to be related to stage of disease, and patients with non-seminoma have lower counts than those with seminoma (4, 5). Many patients experience improvement in sperm counts after orchiectomy. Foster et al. (1) reported that 76% of patients who wished to have children after retroperitoneal lymph node dissection succeeded in doing so. Proposed explanations for improved spermatogenesis after orchiectomy include decreased production of antisperm antibodies, cessation of hormone production by the tumor (such as hCG), and improvement in psychological measures (1, 3, 6). Patients may have to undergo radiation, chemotherapy, or surgery as part of medical management. Each of these treatments has deleterious effects on sperm production or emission and thus contributes to infertility. It is therefore common practice to preserve sperm before initiation of therapy for testis cancer, in order to retain the potential for fertilization in case therapy results in azoospermia. However, it is FERTILITY & STERILITY威
not currently routine practice to preserve sperm before orchiectomy. An informal examination of current urology textbooks (7, 8) revealed no mention of sperm preservation in the algorithm of testis cancer management. There are several reasons for such an omission. Most patients with testis cancer are young, and the idea of having children often seems distant and irrelevant to the patient who must undergo immediate treatment of imminent cancer. Sperm banking facilities may not be available at every clinic, and the wait for a sperm count and proper sperm preservation may delay prompt management. Many orchiectomies are performed by primary care urologists, who treat few patients with testis cancer, and the need for sperm preservation may escape their attention. In the azoospermic patient with testis cancer, the problem of infertility is intensified. Sometimes only a single functioning testis is present, and if a tumor is suspected, the only chance for future fertility may be to preserve sperm before orchiectomy. This was demonstrated by Scher et al. (9), who retrieved sperm from testis tissue at orchiectomy for testis cancer in patients with a single testis and poor sperm counts. In these patients, one may find some sperm at orchiectomy but none after the procedure. However, a considerable number of patients with normal testes and no previous fertility problems may unknowingly have very low sperm counts; this problem has not yet been addressed. At present, even semen of the poorest quality and quantity (1–50 sperm) can produce pregnancy when used in modern IVF and micromanipulation techniques. It is therefore worthwhile to retrieve any amount of sperm available at orchiectomy before discarding the diseased testis. We show that in patients with sperm counts of zero before orchiectomy, a considerable amount of sperm was retrieved at orchiectomy by squeezing the contents of the vas deferens and epididymis into preserving media. This sperm was used in three couples to achieve fertilization, and in one couple, a healthy infant was delivered after a normal pregnancy. We propose that by making sperm aspiration from the vas deferens and epididymis a routine part of every orchiectomy for testis cancer, an immediate sperm count can be obtained and sperm can be preserved for further manipulation. This 261
may be the only chance for future fertilization in azoospermic patients. This technique may be used in a patient scheduled for orchiectomy who has clinical hypogonadism, known infertility, or a single testis or has had orchidopexy. References 1. Foster RS, McNulty A, Rubin LR, Bennet R, Rowland RG, Sledge DW, et al. The fertility of patients with stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection. J Urol 1994:152:1139 – 42. 2. Lange PH, Chang WY, Fraley EE. Fertility issues in the therapy of nonseminomatous testicular tumors. Urol Clin North Am 1987:14:731– 47. 3. Presti JC, Herr HW, Carrol PR. Fertility and testis cancer. Urol Clin North Am 1993:20:173–9.
262
Baniel and Sella
Sperm Extraction at Orchiectomy
4. Botchan A, Hauser R, Yogev L, Gamzu R, Paz G, Lessing JB, et al. Testicular cancer and spermatogenesis. Hum Reprod 1997:12:755– 8. 5. Agarwal A, Toletino MV, Sidu RS, Azyman I, Lee JC, Thomas AJ, et al. Effects of cryopreservation on semen quality in patients with testis cancer. Urology 1995:46:382–9. 6. Turek PJ, Lowther DN, Carrol PR. Fertility issues and their management in men with testis cancer. Urol Clin North Am 1998:25:517–31. 7. Rowland RG, Donohue JP: Scrotum and testis. In: Gillenwater JY, Grayhack JT, Howards SS, Duckett JW. Adult and pediatric urology. St. Louis: Mosby–Year Book, 1991:1565–98. 8. Richie J. Neoplasms of the testis. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s urology. Philadelphia: W.B. Saunders, 1998: 2411–36. 9. Scher D, Choi BB, Su L, Moomy M, Schlegel P, Goldstein M. Pregnancy after testicular sperm extraction at the time of radical orchiectomy for cancer in a solitary testis [abstract]. J Urol 1999;161(suppl):353.
Vol. 75, No. 2, February 2001