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Electroejaculation before chemotherapy in adolescents and young men with cancer
FERTILITY AND STERILITY威 VOL. 75, NO. 4, APRIL 2001 Copyright ©2001 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
COMMUNICATIONS-IN-BRIEF
Electroejaculation before chemotherapy in adolescents and young men with cancer Yedidya Hovav, M.D., Mary Dan-Goor, Ph.D., Haim Yaffe, M.D., and Miriam Almagor, Ph.D. IVF and Fertility Laboratory, Department of Obstetrics and Gynecology, Bikur Cholim Hospital, Jerusalem, Israel
Objective: To evaluate the outcome of repeated electroejaculation for obtaining semen from adolescents and young men before initiation of anticancer therapies. Design: Retrospective clinical study. Setting: Bikur Cholim Hospital, Jerusalem, Israel. Patient(s): Six young male patients (average age, 18⫾3 years) with diagnosed cancer who underwent 12 procedures of electroejaculation before chemotherapy. Intervention(s): Transrectal electroejaculation. Semen was cryopreserved in small aliquots. Main Outcome Measure(s): Semen analysis. Result(s): In all patients, semen was obtained by electroejaculation. Sperm count and motility were relatively low; mean values were 16 ⫻ 106 (range, 0 – 45 ⫻ 106) and 14% (range, 0 –53%) respectively. Conclusion(s): If necessary, electroejaculation can be performed in adolescents, and sperm may be obtained by repeated treatments over a short period. (Fertil Steril威 2001;75:811–3. ©2001 by American Society for Reproductive Medicine.) Key Words: Adolescents, cancer, cryopreservation, electroejaculation, sperm
Received March 10, 2000; revised and accepted October 31, 2000. Reprint requests: Miriam Almagor, Ph.D., IVF and Fertility Laboratory, Department of Obstetrics and Gynecology, Bikur Cholim Hospital, 5 Strauss Street, Jerusalem 91004, Israel (FAX: 972-26464289; E-mail: [email protected]). 0015-0282/01/$20.00 PII S0015-0282(01)01680-6
Cancer therapies can impair sperm quality and lead to infertility. Cryopreservation of semen and ICSI offer cancer patients a chance to achieve biological paternity even with extremely poor sperm quality (1). Therefore, male patients with cancer are encouraged to preserve semen, preferably before initiation of anticancer treatments. In patients who are unable to produce semen by masturbation, transrectal electroejaculation is a treatment option (2, 3). To our knowledge, only one case of electroejaculation before cancer treatment in a pubertal boy has been reported (2), and data on the frequency of its use are lacking. We report the results of semen collection by repeated electroejaculation in a group of teenagers and young men with cancer.
MATERIALS AND METHODS Patients During 1998 –1999, six male patients with neoplastic diseases were referred from other hospitals to our unit for semen cryopreserva-
tion before initiation of chemotherapy. All were single, and their average age was 18⫾3 years. Five patients were Jews belonging to Orthodox communities, and one was an Arab Muslim. All patients attempted but failed to produce semen by masturbation, and they declined our suggestion to attempt penile vibratory stimulation. The study was approved by the institutional review board of our hospital. Written informed consent was obtained from all patients. For patients younger than 18 years of age, parental consent was received.
Electroejaculation Procedure Electroejaculation was performed under general anesthesia. The bladder was flushed with Ham F-10 medium (Sigma, St. Louis, MO), and 20 mL of medium was introduced for collection of retrograde emitted sperm. The patients were placed in the lateral decubitus position, and electroejaculatory stimulation was performed by using the Seager Model 14 Electroejaculator (Dazell Medical Systems, The Plains, VA). Initial stimulation was set at 4 811
TABLE 1 Patients characteristics and sperm quality after repeated electroejaculation in adolescents and men with cancer. Patient Age no. (y) 1 2
Disease
15 Ewing sarcoma 15 Osteosarcoma
3
17 Osteogenic sarcoma
4
18 Testicular germ-cell tumor
5
21 Hodgkin lymphoma
6
22 Testicular germ-cell tumor
Total sperm Sperm motility No. of count (%) treatments (⫻106) A:— R: 15 A: 0 R: 24 A: 0.65 R: 9 A: 35 R: — A: 38 R: 45 A: 6.5 R: 2
3 6 2 53 0 0 33 5 10 20 0
1 2
DISCUSSION
3
Modern therapies have greatly improved survival among patients with cancer. However, these treatments often impair fertility. Cryopreservation of semen before initiation of gonadotoxic therapy offers male patients the chance to achieve biological paternity in the future. With the availability of ICSI, even extreme oligoasthenospermia is considered treatable (1).
1
Note: Values are means. A ⫽ antegrade ejaculate; R ⫽ retrograde fraction. Hovav. Electroejaculation in young men with cancer. Fertil Steril 2001.
V and was increased gradually until ejaculation occurred. The maximum voltage used was 20 V. Current, voltage, and temperature of the rectal probe were monitored continuously throughout the procedure. The antegrade fraction of the ejaculate was obtained by manual expression of seminal fluid along the perineal and penile urethra. The retrograde portion was recovered by draining the bladder. Both were collected in sterile containers. In two patients, prostatic massage was performed before stimulation by electroejaculation.
Semen Cryopreservation Sperm concentration and motility were evaluated according to World Health Organization guidelines for semen analysis (4). The retrograde portion of the ejaculate was centrifuged at room temperature (5 minutes at 1800 g) to yield 1–2 mL of concentrate. The antegrade and retrograde fractions were processed separately. Cryopreservation was performed as described elsewhere (3) by using test-yolk freezing solution (Irvine Scientific, Santa Ana, CA). The samples were frozen in liquid nitrogen in ampules containing 0.1-mL aliquots.
RESULTS Six young male patients with cancer underwent a total of 12 sessions of transrectal electroejaculation under general anesthesia. In patients 1, 2, 4, and 5, treatments were performed 48 hours apart. All procedures were accomplished without complications. Each patient produced semen with similar sperm parameters in each treatment session. Total sperm counts were relatively low (mean, 16 ⫻ 106 [range, 0 – 45 ⫻ 106]); higher sperm densities were obtained in the retrograde ejaculates (Table 1). In four patients, sperm mo812
Hovav et al.
tility was impaired, and in patients 1 and 4, antegrade or retrograde ejaculates could not be obtained (Table 1). The mean value for sperm motility was 14% (range, 0 –53%). In patients 4 and 5, prostatic massage was performed before electroejaculation. Patient 4 ejaculated 0.04 mL of semen, with 10 ⫻ 103 spermatozoa and 60% motility. During his second treatment, no semen was obtained. In patient 5, prostatic massage was attempted each time. He produced 0.1 of mL semen with few spermatozoa in the second session only. In view of these unsatisfactory results, we performed transrectal electroejaculation.
Electroejaculation in young men with cancer
In our study, semen was obtained by transrectal electroejaculation before chemotherapy was started. Our patients were unable to produce semen by masturbation, perhaps because of the heavy psychologic and emotional stress associated with their disease. Another strong stress factor may have been the contravening of strongly held convictions. Islam, Catholicism, and Judaism consider masturbation as a sin, and the boys in our study absorbed their cultural environment from a very young age. All patients refused psychological counseling; the Jewish patients preferred to consult their rabbis. Regardless of whether they had received dispensation to masturbate, their attempts to do so failed. All patients also declined treatment by penile vibratory stimulation. Retrieval of sperm from nocturnal emissions was not feasible because time was limited. Because initiation of anticancer therapy could not be postponed, we had to perform electroejaculations within a short period. In four patients, the procedure was successfully performed 2 to 3 times every 48 hours, and no complications occurred. It is therefore suggested that in adolescents and young men with cancer who cannot produce semen by masturbation or penile vibratory stimulation, electroejaculation may be successfully repeated in a short time. For practical purposes, the sperm should be frozen in small aliquots. If electroejaculation is not available or has not been successful, testicular sperm extraction may be a further option. In 80% of our patients, the quality of sperm was diminished in terms of both concentration and motility. A previous report on penile vibratory stimulation and a single attempt of electroejaculation in two boys 14 and 15 years of age also demonstrated impaired semen variables (2). Vol. 75, No. 4, April 2001
The possibility that rectal probe electrostimulation has detrimental effects on semen quality or causes only partial emission cannot be ruled out (3). However, it is an efficient technique for sperm retrieval, especially when simpler methods fail (2, 3). Even in the case of patient 3, lack of sperm motility does not necessarily imply a lack of fertilizing potential. Although the outcome of future ICSI procedures cannot be predicted, it seems reasonable to assume that cryopreserved sperm obtained by electroejaculation can potentially produce live births. The established success of electroejaculation in combination with ICSI offers young male patients with cancer a reasonable chance of fertility in the future.
FERTILITY & STERILITY威
Acknowledgment: The authors thank Mrs. June Sher for help in revising the manuscript.
References 1. Palermo GD, Cohen J, Alikani M, Adler A, Rosenwaks Z. Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility. Fertil Steril 1995;63:1231– 40. 2. Schmiegelow ML, Sommer P, Carlsen E, Sonksen JOR, Schmiegelow K, Muller JR. Penile vibratory stimulation and electroejaculation before anticancer therapy in two pubertal boys. J Pediat Hematol Oncol 1998; 20:429 –30. 3. Hovav Y, Shotland Y, Yaffe H, Almagor M. Electroejaculation and assisted fertility in men with psychogenic anejaculation. Fertil Steril 1996;66:620 –3. 4. World Health Organization. Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 3rd ed. New York: Cambridge University Press, 1993.
813
COMMUNICATIONS-IN-BRIEF
Electroejaculation before chemotherapy in adolescents and young men with cancer Yedidya Hovav, M.D., Mary Dan-Goor, Ph.D., Haim Yaffe, M.D., and Miriam Almagor, Ph.D. IVF and Fertility Laboratory, Department of Obstetrics and Gynecology, Bikur Cholim Hospital, Jerusalem, Israel
Objective: To evaluate the outcome of repeated electroejaculation for obtaining semen from adolescents and young men before initiation of anticancer therapies. Design: Retrospective clinical study. Setting: Bikur Cholim Hospital, Jerusalem, Israel. Patient(s): Six young male patients (average age, 18⫾3 years) with diagnosed cancer who underwent 12 procedures of electroejaculation before chemotherapy. Intervention(s): Transrectal electroejaculation. Semen was cryopreserved in small aliquots. Main Outcome Measure(s): Semen analysis. Result(s): In all patients, semen was obtained by electroejaculation. Sperm count and motility were relatively low; mean values were 16 ⫻ 106 (range, 0 – 45 ⫻ 106) and 14% (range, 0 –53%) respectively. Conclusion(s): If necessary, electroejaculation can be performed in adolescents, and sperm may be obtained by repeated treatments over a short period. (Fertil Steril威 2001;75:811–3. ©2001 by American Society for Reproductive Medicine.) Key Words: Adolescents, cancer, cryopreservation, electroejaculation, sperm
Received March 10, 2000; revised and accepted October 31, 2000. Reprint requests: Miriam Almagor, Ph.D., IVF and Fertility Laboratory, Department of Obstetrics and Gynecology, Bikur Cholim Hospital, 5 Strauss Street, Jerusalem 91004, Israel (FAX: 972-26464289; E-mail: [email protected]). 0015-0282/01/$20.00 PII S0015-0282(01)01680-6
Cancer therapies can impair sperm quality and lead to infertility. Cryopreservation of semen and ICSI offer cancer patients a chance to achieve biological paternity even with extremely poor sperm quality (1). Therefore, male patients with cancer are encouraged to preserve semen, preferably before initiation of anticancer treatments. In patients who are unable to produce semen by masturbation, transrectal electroejaculation is a treatment option (2, 3). To our knowledge, only one case of electroejaculation before cancer treatment in a pubertal boy has been reported (2), and data on the frequency of its use are lacking. We report the results of semen collection by repeated electroejaculation in a group of teenagers and young men with cancer.
MATERIALS AND METHODS Patients During 1998 –1999, six male patients with neoplastic diseases were referred from other hospitals to our unit for semen cryopreserva-
tion before initiation of chemotherapy. All were single, and their average age was 18⫾3 years. Five patients were Jews belonging to Orthodox communities, and one was an Arab Muslim. All patients attempted but failed to produce semen by masturbation, and they declined our suggestion to attempt penile vibratory stimulation. The study was approved by the institutional review board of our hospital. Written informed consent was obtained from all patients. For patients younger than 18 years of age, parental consent was received.
Electroejaculation Procedure Electroejaculation was performed under general anesthesia. The bladder was flushed with Ham F-10 medium (Sigma, St. Louis, MO), and 20 mL of medium was introduced for collection of retrograde emitted sperm. The patients were placed in the lateral decubitus position, and electroejaculatory stimulation was performed by using the Seager Model 14 Electroejaculator (Dazell Medical Systems, The Plains, VA). Initial stimulation was set at 4 811
TABLE 1 Patients characteristics and sperm quality after repeated electroejaculation in adolescents and men with cancer. Patient Age no. (y) 1 2
Disease
15 Ewing sarcoma 15 Osteosarcoma
3
17 Osteogenic sarcoma
4
18 Testicular germ-cell tumor
5
21 Hodgkin lymphoma
6
22 Testicular germ-cell tumor
Total sperm Sperm motility No. of count (%) treatments (⫻106) A:— R: 15 A: 0 R: 24 A: 0.65 R: 9 A: 35 R: — A: 38 R: 45 A: 6.5 R: 2
3 6 2 53 0 0 33 5 10 20 0
1 2
DISCUSSION
3
Modern therapies have greatly improved survival among patients with cancer. However, these treatments often impair fertility. Cryopreservation of semen before initiation of gonadotoxic therapy offers male patients the chance to achieve biological paternity in the future. With the availability of ICSI, even extreme oligoasthenospermia is considered treatable (1).
1
Note: Values are means. A ⫽ antegrade ejaculate; R ⫽ retrograde fraction. Hovav. Electroejaculation in young men with cancer. Fertil Steril 2001.
V and was increased gradually until ejaculation occurred. The maximum voltage used was 20 V. Current, voltage, and temperature of the rectal probe were monitored continuously throughout the procedure. The antegrade fraction of the ejaculate was obtained by manual expression of seminal fluid along the perineal and penile urethra. The retrograde portion was recovered by draining the bladder. Both were collected in sterile containers. In two patients, prostatic massage was performed before stimulation by electroejaculation.
Semen Cryopreservation Sperm concentration and motility were evaluated according to World Health Organization guidelines for semen analysis (4). The retrograde portion of the ejaculate was centrifuged at room temperature (5 minutes at 1800 g) to yield 1–2 mL of concentrate. The antegrade and retrograde fractions were processed separately. Cryopreservation was performed as described elsewhere (3) by using test-yolk freezing solution (Irvine Scientific, Santa Ana, CA). The samples were frozen in liquid nitrogen in ampules containing 0.1-mL aliquots.
RESULTS Six young male patients with cancer underwent a total of 12 sessions of transrectal electroejaculation under general anesthesia. In patients 1, 2, 4, and 5, treatments were performed 48 hours apart. All procedures were accomplished without complications. Each patient produced semen with similar sperm parameters in each treatment session. Total sperm counts were relatively low (mean, 16 ⫻ 106 [range, 0 – 45 ⫻ 106]); higher sperm densities were obtained in the retrograde ejaculates (Table 1). In four patients, sperm mo812
Hovav et al.
tility was impaired, and in patients 1 and 4, antegrade or retrograde ejaculates could not be obtained (Table 1). The mean value for sperm motility was 14% (range, 0 –53%). In patients 4 and 5, prostatic massage was performed before electroejaculation. Patient 4 ejaculated 0.04 mL of semen, with 10 ⫻ 103 spermatozoa and 60% motility. During his second treatment, no semen was obtained. In patient 5, prostatic massage was attempted each time. He produced 0.1 of mL semen with few spermatozoa in the second session only. In view of these unsatisfactory results, we performed transrectal electroejaculation.
Electroejaculation in young men with cancer
In our study, semen was obtained by transrectal electroejaculation before chemotherapy was started. Our patients were unable to produce semen by masturbation, perhaps because of the heavy psychologic and emotional stress associated with their disease. Another strong stress factor may have been the contravening of strongly held convictions. Islam, Catholicism, and Judaism consider masturbation as a sin, and the boys in our study absorbed their cultural environment from a very young age. All patients refused psychological counseling; the Jewish patients preferred to consult their rabbis. Regardless of whether they had received dispensation to masturbate, their attempts to do so failed. All patients also declined treatment by penile vibratory stimulation. Retrieval of sperm from nocturnal emissions was not feasible because time was limited. Because initiation of anticancer therapy could not be postponed, we had to perform electroejaculations within a short period. In four patients, the procedure was successfully performed 2 to 3 times every 48 hours, and no complications occurred. It is therefore suggested that in adolescents and young men with cancer who cannot produce semen by masturbation or penile vibratory stimulation, electroejaculation may be successfully repeated in a short time. For practical purposes, the sperm should be frozen in small aliquots. If electroejaculation is not available or has not been successful, testicular sperm extraction may be a further option. In 80% of our patients, the quality of sperm was diminished in terms of both concentration and motility. A previous report on penile vibratory stimulation and a single attempt of electroejaculation in two boys 14 and 15 years of age also demonstrated impaired semen variables (2). Vol. 75, No. 4, April 2001
The possibility that rectal probe electrostimulation has detrimental effects on semen quality or causes only partial emission cannot be ruled out (3). However, it is an efficient technique for sperm retrieval, especially when simpler methods fail (2, 3). Even in the case of patient 3, lack of sperm motility does not necessarily imply a lack of fertilizing potential. Although the outcome of future ICSI procedures cannot be predicted, it seems reasonable to assume that cryopreserved sperm obtained by electroejaculation can potentially produce live births. The established success of electroejaculation in combination with ICSI offers young male patients with cancer a reasonable chance of fertility in the future.
FERTILITY & STERILITY威
Acknowledgment: The authors thank Mrs. June Sher for help in revising the manuscript.
References 1. Palermo GD, Cohen J, Alikani M, Adler A, Rosenwaks Z. Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility. Fertil Steril 1995;63:1231– 40. 2. Schmiegelow ML, Sommer P, Carlsen E, Sonksen JOR, Schmiegelow K, Muller JR. Penile vibratory stimulation and electroejaculation before anticancer therapy in two pubertal boys. J Pediat Hematol Oncol 1998; 20:429 –30. 3. Hovav Y, Shotland Y, Yaffe H, Almagor M. Electroejaculation and assisted fertility in men with psychogenic anejaculation. Fertil Steril 1996;66:620 –3. 4. World Health Organization. Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 3rd ed. New York: Cambridge University Press, 1993.
813