ANDROLOGY/UROLOGY. Why cancer patients request disposal of cryopreserved semen specimens posttherapy: a retrospective study

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1 FERTILITY AND STERILITY VOL. 69, NO. 5, MAY 1998 Copyright 1998 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A. ANDROLOGY/UROLOGY Why cancer patients request disposal of cryopreserved semen specimens posttherapy: a retrospective study Jorge Hallak, M.D., Rakesh K. Sharma, Ph.D., Anthony J. Thomas, Jr., M.D., and Ashok Agarwal, Ph.D. Andrology Research and Clinical Laboratories, Department of Urology, The Cleveland Clinic Foundation, Cleveland, Ohio Received July 14, 1997; revised and accepted December 13, Supported in part (J.H.) from Conselho Nacional de Desenvolvimento Cientifico e Technologico, Ministry of Science and Technology of Brazil, Brasilia, Brazil. Presented at the VIth International Congress of Andrology, Salzburg, Austria, May 25 29, Reprint requests: Ashok Agarwal, Ph.D., Andrology Research and Clinical Laboratories, Department of Urology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, A19.1, Cleveland, Ohio (FAX: ; agarwaa@cesmtp. ccf.org) /98/$19.00 PII S (98) Objective: To determine why patients with cancer stop storing semen in a sperm bank program. Design: Retrospective study. Setting: Hospital andrology laboratory. Patient(s): Cancer patients (n 56) who discontinued sperm storage. Intervention(s): A database of 342 patients with cryopreserved sperm was searched for disease diagnosis, marital status before and after diagnosis, type of therapy, number of specimens banked, interval between diagnosis and sperm banking, and postthaw semen characteristics. Patients discontinuing storage were surveyed. Main Outcome Measurement(s): Reasons for discontinuing storage and clinical correlation of the decision. Result(s): Reasons included patient death (n 21); fertility but no plans for more children (n 23); good sperm quality (n 8); and no plans to have children (n 4). Patients were similar in age, number of specimens, and interval between diagnosis and treatment, but they showed significant differences in type of treatment and time in the program. Cost of cryopreservation and specimen storage was not cited. Conclusion(s): Most patients decided to discontinue sperm banking because either they regained fertility or had improved semen quality. Sperm banking should be strongly recommended for all patients with malignant diseases who may wish to have children, even if they eventually decide that the specimens are not needed. (Fertil Steril 1998;69: by American Society for Reproductive Medicine.) Key Words: Spermatozoa, cryopreservation, cancer, infertility, sperm bank, posttreatment fertility Testicular cancer, Hodgkin s disease, and leukemia are among the most prevalent malignancies in young men of reproductive age. Testicular cancer represents 1% 2% of all neoplasms in the male (1). Hodgkin s disease is the second most common malignancy affecting young men between the ages of 20 and 40 (2). Receiving a diagnosis of cancer is both emotionally and physically stressful. Infertility is often the price for the curative, aggressive treatment of the cancer. Although improved treatment regimens have resulted in a high degree of recovery of fertility (1, 2), the incidence of azoospermia in patients after treatment for malignant diseases is still high. It is not possible to predict which patients, after cancer treatment, will become sterile and which will recover adequate spermatogenic function (3 5). Cryopreservation decreases sperm quality and the numbers of motile sperm in both normal healthy men and cancer patients (6, 7). Sperm cryopreservation for cancer patients who will be treated by surgery, radiation, or chemotherapy is available in many institutions to safeguard the patient s chances of later procreation (8, 9). Initially, only a high-quality sperm sample could be used because simple IUI was the only method available. However, advances in assisted reproductive technology have improved the chances of pregnancy with few sperm of lesser quality (10 12). Some patients (or surviving family members) decide to dispose of the cryopreserved samples for a variety of reasons, such as having enough children or regaining good sperm quality after the cancer treatment. Our study examines the reasons for the disposal of sperm spec- 889

2 TABLE 1 Reasons for disposal of semen specimens in patients with cancer participating in a sperm bank program. Reason for disposal of specimen Patient death (group I; n 21) Enough children (group II; n 23) Good sperm quality (group III; n 8) Do not want children (group IV; n 4) Diagnosis Testicular cancer 2 (9.5) 14 (60.9) 5 (62.5) 2 (50) Hodgkin s disease 8 (38.1) 7 (30.4) 2 (25) 2 (50) Other cancers 11 (52.4) 2 (8.7) 1 (12.5) 0 (0) Marital status Before treatment Single 14 (66.7) 7 (30.4) 7 (87.5) 2 (50) Married 7 (33.3) 16 (69.6) 1 (12.5) 2 (50) After treatment Single 1 (4.4) 8 (100) 3 (75) Married 22 (95.6) 0 (0) 1 (25) Treatment type Chemotherapy 19 (90.5) 13 (56.5) 2 (25) 0 (0) Radiation 5 (25) 9 (39.1) 2 (25) 4 (100) Surgery 7 (33.3)** 19 (82.6) 7 (87.5)** 4 (100) Note: All values represent no. of patients (%). * P value for the overall group comparison. If the P value was statistically significant, pairwise comparisons with Bonferroni corrections were used. P (group I versus group II). P 0.01 (group II versus group III). Patients in group II were significantly different from those in both group III (P 0.001) and group IV (P ). Patients in group I were significantly different from those in both group III (P ) and group IV (P ). Patients in group I were significantly different from those in group IV (P 0.012). ** Patients in group I were significantly different from those in group II (P 0.002). imens at our sperm-banking facility and whether it was associated with a specific type of cancer, treatment, or posttreatment fertility. MATERIALS AND METHODS Patients This study was approved by our institutional review board. We reviewed records of all cancer patients (n 342) referred to our andrology laboratory from 1984 to 1996 for cryobanking. Patients who had their sperm specimens banked before initiating cancer treatment were included. Among them, 56 patients had their specimens disposed and were placed in three groups according to the type of cancer: testicular (n 23), Hodgkin s disease (n 19), and other cancers (n 14). Included in this latter group were those with leukemia (n 8), colon cancer (n 2), sarcoma (n 2), and lung cancer (n 2). Review of medical records revealed that all 21 families of patients who died requested disposal of their semen specimens. All living patients (n 35) were interviewed by phone regarding the type of treatment (chemotherapy, radiation, or surgery), the time between the diagnosis and banking of first sperm specimen, impact of treatment on fertility status, posttreatment fertility status, and finally, reasons for disposal of their banked specimens. The cost of cryopreserving three semen specimens at our center averages about $800. A long-term storage fee of $70 is assessed annually for each frozen ejaculate. Statistical Analysis The categorical factors were analyzed by Fisher s exact tests and the continuous factors by the Kruskal-Wallis test. A P value of 0.05 was considered statistically significant. Pairwise comparisons were performed for any significant overall results, and Bonferroni corrections were used to control for the type I error rate. All statistical analyses were performed with the SAS statistical package (SAS Institute, Inc., Cary, NC). RESULTS Patients who discontinued their sperm banking were subdivided into four major groups based on their reasons of disposal, and information from the phone survey was categorized (Table 1). Of the 342 cancer patients who participated in the study, 157 were diagnosed with testicular cancer, 123 for Hodgkin s disease, 30 with leukemia, and 32 with other types of cancer. Of the 56 requests (16.4%) to opt out of the sperm banking program, 21 (37.5%) were made 890 Hallak et al. Semen disposal by patients with cancer Vol. 69, No. 5, May 1998

3 TABLE 2 Reasons for disposal of semen specimens in patients with cancer participating in a sperm bank program. Reason for disposal of specimen Patient death (group I; n 21) Enough children (group II; n 23) Good sperm quality (group III; n 8) Do not want children (group IV; n 4) Mean ( SD) age (y) No. of specimens banked 3.0 (2.0, 4.0) 3.0 (2.0, 4.0) 3.5 (2.5, 5.5) 1.0 (1.0, 2.0) 0.10 Mean ( SD) length of storage (mo) Mean ( SD) diagnosis and treatment interval (d) Postthaw characteristics Total sperm count ( 10 6 /ml) 24.0 (6.5, 63.0) 23.5 (6.6, 67.0) 7.4 (3.1, 23.0) 31.5 (6.7, 86.5) 0.66 Motile sperm count ( 10 6 /ml) 3.3 (1.8, 13.0) 6.0 (1.9, 17.0) 2.5 (0.65, 5.8) 8.6 (2.5, 19.0) 0.66 Percent motility 17.0 (12.0, 37.0) 20.0 (12.0, 31.0) 16.5 (10.0, 27.5) 25.0 (12.0, 30.5) 0.99 Note: Numbers in parentheses represent the median and interquartile range (25%, 75%). * P value for the overall group comparison. If the P value was statistically significant, then the pairwise comparisons with Bonferroni corrections were used. P (group I versus group II). because the patients were no longer alive. Twenty-three patients (41.1%) had regained their fertility and had fathered all the children they had planned. Eight patients (14.3%) had good-quality sperm but as yet had no children, and four patients (7.1%) had no children and did not want to have children in the future. No patient cited cost as a reason for opting out of the sperm-banking program. Most patients with a history of testicular cancer were alive after treatment (21 of 23 [91.3%]) and 14 of these 21 (67%) had regained their fertility but already had the desired number of children after treatment. Of the patients with Hodgkin s disease, 11 of 19 (57.9%) were alive after treatment. Of these, 7 of 19 (36.8%) had caused a pregnancy after treatment. In patients with other types of cancer, 11 of 14 (78.6%) died. Of the survivors, 2 of 3 (66.7%) fathered children after treatment (Table 2). All of these patients spouses achieved natural pregnancy, except for one, who had a successful third-cycle IUI. Two thirds of the patients with testicular cancer (14 of 21) discontinued participation in the program because they had the desired number of offspring. Patients in the three cancer groups did not differ in age, number of cryopreserved specimens, or interval between diagnosis and treatment (Table 3). DISCUSSION Our study shows that most requests for disposal of specimens were made because the patients had regained fertility or died. Cost was not a factor. Information on the outcome of pregnancies achieved with cryopreserved sperm from cancer patients is limited. However, existing data suggest no apparent increase in birth defects after inseminations using sperm from men with Hodgkin s disease, testicular cancer, and other malignancies (13, 14). Evidence of the recovery of spermatogenic function after chemotherapy in patients with testicular cancer is convincing (15). Posttreatment fertility was seen in approximately 50% 64% of the patients with testicular cancer after 1 3 years (16). A fertility rate of 67% (14 of 21) also was seen in our study in patients with testicular cancer. The probability of return of spermatogenic function after treatment was 48% after 2 years and 80% after 5 years (17). Results of fertility in patients with Hodgkin s disease after treatment are scarce. Persistent azoospermia 17 years after chemotherapy or radiation therapy has been reported in 85% of children (18) and in 69% of children 7 years after chemotherapy (19). These results indicate a high degree of damage to the germinal epithelium even when the treatment is given during the prepubertal age. Spontaneous pregnancies can occur with sperm counts of /ml (20). Most patients in our study did not undergo a semen analysis before requesting disposal of their semen specimens. In all but one instance they impregnated their wives by natural intercourse, the exception being one couple who used IUI. Data on posttreatment fertility are meager and differ for each patient. In conclusion, we found that most patients discontinued FERTILITY & STERILITY 891

4 TABLE 3 s associated with different kinds of cancer. Type of cancer Testicular cancer Hodgkin s disease Other cancers Marital status Before treatment Single 13 (56.5) 11 (57.9) 6 (42.9) 0.74 Married 10 (43.5) 8 (42.1) 8 (57.1) After treatment Single 7 (33.3) 4 (36.4) 1 (33.3) 0.99 Married 14 (66.7) 7 (63.6) 2 (66.7) Treatment Chemotherapy 6 (26.1) 15 (79.0) 13 (92.9) Radiation 9 (39.1) 10 (52.6) 1 (7.7) 0.03 Surgery 23 (100) 10 (52.6) 4 (28.6) Mean age (y) 28 (25, 34) 25 (21, 29) 30 (25, 32) 0.25 No. of specimens banked 3.0 (3, 4) 3.0 (2, 4) 2.5 (2, 4) 0.36 Length of storage (mo) 52.0 (38, 72) 62.0 (35, 82) 16.5 (10, 42) 0.02 Diagnosis and treatment interval (d) 14 (5, 27) 14 (9, 26) 27 (5, 32) 0.64 Postthaw characteristics Total sperm count ( 10 6 /ml) 13.0 (4.9, 50.0) 62.0 (6.4, 85.0) 16.1 (5.5, 29) 0.28 Motile sperm count ( 10 6 /ml) 3.6 (1.9, 13) 11 (0.9, 24.0) 3.75 (0.7, 9.0) 0.62 Percent motility 20.0 (15, 33) 30.0 (3, 38) 15.5 (12, 18) 0.29 Note: Numbers in parentheses represent the median and interquartile values (25%, 75%) or the percentage. * P value for the overall group comparison. If the P value was statistically significant, then the pairwise comparisons with Bonferroni corrections were used. Patients with testicular cancer were significantly different from both Hodgkin s disease (P ) and other cancer group (P ). Patients with Hodgkin s disease were significantly different from the other cancer group (P 0.011). Patients with testicular cancer were significantly different from both Hodgkin s disease (P ) and the other cancer group (P 0.001). Patients with other cancers were significantly different from both testicular cancer (P 0.017) and Hodgkin s disease (P 0.013). participation in the sperm-banking program either because they had regained fertility or had improved semen quality. The cost of continued storage was not cited as a reason by any patient. Compared with other groups of cancer patients, the testicular cancer group had a better fertility status. Because it is difficult to predict which category of cancer patients will survive or become sterile after treatment, sperm banking should be strongly recommended for all patients with malignant diseases who may wish to have children in the future. Acknowledgment: The authors thank Karen Seifarth, M.T., Andrology Laboratory, for technical assistance, and Jar-Chi Lee, M.S., Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, for statistical analysis of the results. References 1. Drasga RE, Einhorn LH, Williams SD, Patel DN, Stevens EE. Fertility after chemotherapy for testicular cancer. J Clin Oncol 1983;31: Meirow D, Schenker JG. Cancer and male infertility. Hum Reprod 1995;10: Nijman JM, Schraffordt Koops H, Kremer J, Sleijfer DT. Gonadal function after surgery and chemotherapy in men with stage II and III non-seminomatous testicular tumors. J Clin Oncol 1987;5: Fossa SD, Ous DS, Aybyholm T, Norman N, Loeb M, Jetne V. Post-treatment fertility in patients with testicular cancer. II. Influence of cisplatin-based combination chemotherapy and of retroperitoneal surgery on hormone and sperm cell production. Br J Urol 1985;57: Padron OF, Sharma RK, Thomas AJ Jr, Agarwal A. Effects of cancer on spermatozoa quality after cryopreservation: a 12-year experience. Fertil Steril 1997;67: Agarwal A, Tolentino MV, Sidhu RS, Ayzman A, Lee JC, Thomas AJ Jr, et al. Effect of cryopreservation on semen quality in patients with testicular cancer. Urology 1995;46: Shekarriz M, Tolentino MV, Ayzman I, Lee JC, Thomas AJ Jr, Agarwal A. Cryopreservation and semen quality in patients with Hodgkin s disease. Cancer 1995;75: Sanger WG, Olson JH, Sherman JK. Semen cryobanking for men with cancer criteria change. Fertil Steril 1992;58: Davis OK, Bedford JM, Berkely AS, Graf MJ, Rosenwaks Z. Pregnancy achieved through in vitro fertilization with cryopreserved semen from a man with Hodgkin s lymphoma. Fertil Steril 1990;53: Khalifa E, Oehninger S, Acosta AA, Morshedi M, Veeck L, Bryzski RG, et al. Successful fertilization and pregnancy outcome using cryopreserved/thawed spermatozoa from patients with malignant diseases. Hum Reprod 1992;7: Tournaye H, Camus M, Bollen N, Wisanto A, Van Steirteghem AC, Devroey P. In vitro fertilization techniques with frozen-thawed sperm: a method for preserving the progenitive potential of Hodgkin s patients. Fertil Steril 1991;55: Hakim LS, Lobel SM, Oates RD. The achievement of pregnancies using assisted reproductive technologies for male factor infertility after retroperitoneal lymph node dissection for testicular carcinoma. Fertil Steril 1995;64: Swerdlow AJ, Jacobs PA, Marks A, Maher EJ, Young T, Barber JCK, et al. Fertility, reproductive outcomes, and health of offspring of patients treated for Hodgkin s disease: an investigation including chromosome examinations. Br J Cancer 1996;74: Hallak et al. Semen disposal by patients with cancer Vol. 69, No. 5, May 1998

5 14. Engel W, Murphy D, Schmid M. Are there genetic risks associated with microassisted reproduction? Hum Reprod 1996;11: Fossa SD, Aabyholm T, Vespestad S, Norman N, Ous S. Semen quality after treatment for testicular cancer. Eur Urol 1993;23: Berthelsen JG. Testicular cancer and fertility. Int J Androl 1987;10: Lampe H, Horwich A, Norman A, Nicholls J, Dearnaley DP. Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol 1997;15: Shafford EA, Kingston JE, Malpas JS, Plowman PN, Pritchard J, Savage MO, et al. Testicular function following the treatment of Hodgkin s disease in childhood. Br J Cancer 1993;68: Dhabhar BN, Malhotra H, Joseph R, Garde S, Bhasin S, Sheth A, et al. Gonadal function in prepubertal boys following treatment for Hodgkin s disease. Am J Pediatr Hematol Oncol 1993;15: Marmor D, Duyck F. Male reproductive potential after MOPP therapy for Hodgkin s disease: a long-term survey. Andrologia 1995; 27: FERTILITY & STERILITY 893