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Serum testosterone levels in patients with nonmosaic Klinefelter syndrome after testicular sperm extraction for intracytoplasmic sperm injection
FERTILITY AND STERILITY威 VOL. 82, NO. 1, JULY 2004 Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Serum testosterone levels in patients with nonmosaic Klinefelter syndrome after testicular sperm extraction for intracytoplasmic sperm injection We measured testosterone levels in 24 patients with nonmosaic Klinefelter syndrome before and at 6 and 12 months after conventional or microdissection testicular sperm extraction. Testosterone levels decreased after surgery by either technique, and they did not recover to baseline concentrations, even when using less invasive microdissection techniques. (Fertil Steril威 2004;82:237– 8. ©2004 by American Society for Reproductive Medicine.) Key Words: Testicular sperm extraction, microsurgery, testosterone, assisted reproductive technology, Klinefelter syndrome Testicular sperm extraction (TESE) presently is applied to the most severe forms of male infertility, which represent nonobstructive azoospermia. Most notably, TESE has been performed successfully in patients with nonmosaic Klinefelter syndrome, who usually present with small testes and hypogonadism (1). In our first 2 years of performing TESE in patients with nonmosaic Klinefelter syndrome, we used a conventional multiple testicular biopsy technique (conventional TESE). We then adopted microdissection TESE, which is less invasive and minimizes the amount of testicular tissue removed and facilitates hemostasis (2). To our knowledge, no prospective study has evaluated serum testosterone concentrations in these patients after TESE. Between January 1997 and March 2002, we performed TESE in 24 patients with nonmosaic Klinefelter syndrome at our institution (7 by the conventional technique, 17 by microdissection TESE). We assayed testosterone in serum before and at 6 and 12 months after surgery. All blood specimens were obtained between 9 AM and 10 AM. All patients were fully informed about the study, and their prior consent was obtained. We statistically compared concentrations of testosterone at baseline, at 6 months, and at 12 months with Wilcoxon’s signed rank test. Testosterone concentrations ranged from 0.4 to 4.5 ng/mL (normal range, 2.4 –10.4). No difference was observed between the two groups at baseline (microdissection TESE patients, 2.43 ⫾ 1.54 ng/mL [mean ⫾ SD]); conventional TESE patients, 1.3 ⫾ 0.72 ng/mL, P⫽.0864]. Testosterone declined significantly from baseline concentrations in all patients undergoing either microdissection TESE or conventional TESE (microdissection, 1.94 ⫾ 1.32 ng/mL at 6 months, P⫽.003, and 2.07 ⫾ 1.37 ng/mL at 12 months, P⫽.003; conventional TESE, 0.74 ⫾ 0.45 ng/mL at 6 months, P⫽.018, and 0.79 ⫾ 0.51 ng/mL at 12 months, P⫽.018: Fig. 1).
Received June 19, 2003; revised and accepted November 25, 2003. Reprint requests: Hiroshi Okada, M.D., Ph.D., Department of Urology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 1738605, Japan (FAX: ⫹81-33964-8934; (E-mail: [email protected]). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2003. 11.047
Serum testosterone concentrations at 12 months had not improved significantly from those at 6 months in either microdissection or conventional TESE patients (% decrease from baseline at 6 months after microdissection, 24.1% ⫾ 10.3%; at 12 months, 17.7⫾8.5%, P⫽.058; and 42.6% ⫾ 12.8% at 6 months after conventional TESE, 39.1% ⫾ 18.0% at 12 months, P⫽.5002). Considering both nonmosaic cases and several forms of mosaicism, Klinefelter syndrome accounts for 5% of male-factor infertility and represents sterility caused by deficient spermatogenesis (3). The success rate for TESE in patients with nonmosaic Klinefelter syndrome at our institution is 56% (Okada, unpublished data), and numbers of TESE performed in this group are increasing rapidly. Although most patients with nonmosaic Klinefelter syndrome have serum testosterone concentrations below normal limits, testosterone replacement therapy is not indicated until retrieval of spermatozoa from the testes (3). Our data showed that the postoperative decline in Klinefelter patients’ testosterone was not followed by recovery to baseline concentrations, even when using less invasive microdissection TESE techniques.
237
FIGURE 1 Serum testosterone concentrations before and at 6 and 12 months after TESE were measured. Seven patients (No. 1–7) underwent conventional TESE, and 17 patients (No. 8 –24) underwent microdissection TESE. The red circle, green square, and blue triangle indicate testosterone concentration before and at 6 and 12 months after TESE, respectively.
Postoperative testosterone concentrations should be assayed regularly, and testosterone replacement therapy is indicated in patients whose serum testosterone concentrations remain low. Hiroshi Okada, M.D., Ph.D.a,c Toshiro Shirakawa, M.D., Ph.D.a Tomomoto Ishikawa, M.D.a Kazumasa Goda, M.D.a Masato Fujisawa, M.D., Ph.D.b Sadao Kamidono, M.D., Ph.D.a Division of Urology, Department of Organ Therapeutics, Faculty of Medicine,a Kobe University Graduate School of Medicine, Kobe, Japan; and Department of Urology,b Kawasaki Medical University, Kurashiki, Japan; Present address: Department of Urology,c Teikyo University School of Medicine, Tokyo, Japan
References
Okada. T levels after TESE in Klinefelter patients. Fertil Steril 2004.
238
Okada et al.
Correspondence
1. Tournaye H, Camus M, Vandervorst M, Nagy Z, Joris H, Van Steirteghem A, et al. Surgical sperm retrieval for intracytoplasmic sperm injection. Int J Androl 1997;20:69 –73. 2. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue extraction. Hum Reprod 1999;14:131–5. 3. Okada H, Fujioka H, Tatsumi N, Kanzaki M, Okuda Y, Fujisawa M, et al. Klinefelter’s syndrome in the male infertility clinic. Hum Reprod 1999;14:946 –52.
Vol. 82, No. 1, July 2004
Serum testosterone levels in patients with nonmosaic Klinefelter syndrome after testicular sperm extraction for intracytoplasmic sperm injection We measured testosterone levels in 24 patients with nonmosaic Klinefelter syndrome before and at 6 and 12 months after conventional or microdissection testicular sperm extraction. Testosterone levels decreased after surgery by either technique, and they did not recover to baseline concentrations, even when using less invasive microdissection techniques. (Fertil Steril威 2004;82:237– 8. ©2004 by American Society for Reproductive Medicine.) Key Words: Testicular sperm extraction, microsurgery, testosterone, assisted reproductive technology, Klinefelter syndrome Testicular sperm extraction (TESE) presently is applied to the most severe forms of male infertility, which represent nonobstructive azoospermia. Most notably, TESE has been performed successfully in patients with nonmosaic Klinefelter syndrome, who usually present with small testes and hypogonadism (1). In our first 2 years of performing TESE in patients with nonmosaic Klinefelter syndrome, we used a conventional multiple testicular biopsy technique (conventional TESE). We then adopted microdissection TESE, which is less invasive and minimizes the amount of testicular tissue removed and facilitates hemostasis (2). To our knowledge, no prospective study has evaluated serum testosterone concentrations in these patients after TESE. Between January 1997 and March 2002, we performed TESE in 24 patients with nonmosaic Klinefelter syndrome at our institution (7 by the conventional technique, 17 by microdissection TESE). We assayed testosterone in serum before and at 6 and 12 months after surgery. All blood specimens were obtained between 9 AM and 10 AM. All patients were fully informed about the study, and their prior consent was obtained. We statistically compared concentrations of testosterone at baseline, at 6 months, and at 12 months with Wilcoxon’s signed rank test. Testosterone concentrations ranged from 0.4 to 4.5 ng/mL (normal range, 2.4 –10.4). No difference was observed between the two groups at baseline (microdissection TESE patients, 2.43 ⫾ 1.54 ng/mL [mean ⫾ SD]); conventional TESE patients, 1.3 ⫾ 0.72 ng/mL, P⫽.0864]. Testosterone declined significantly from baseline concentrations in all patients undergoing either microdissection TESE or conventional TESE (microdissection, 1.94 ⫾ 1.32 ng/mL at 6 months, P⫽.003, and 2.07 ⫾ 1.37 ng/mL at 12 months, P⫽.003; conventional TESE, 0.74 ⫾ 0.45 ng/mL at 6 months, P⫽.018, and 0.79 ⫾ 0.51 ng/mL at 12 months, P⫽.018: Fig. 1).
Received June 19, 2003; revised and accepted November 25, 2003. Reprint requests: Hiroshi Okada, M.D., Ph.D., Department of Urology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 1738605, Japan (FAX: ⫹81-33964-8934; (E-mail: [email protected]). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2003. 11.047
Serum testosterone concentrations at 12 months had not improved significantly from those at 6 months in either microdissection or conventional TESE patients (% decrease from baseline at 6 months after microdissection, 24.1% ⫾ 10.3%; at 12 months, 17.7⫾8.5%, P⫽.058; and 42.6% ⫾ 12.8% at 6 months after conventional TESE, 39.1% ⫾ 18.0% at 12 months, P⫽.5002). Considering both nonmosaic cases and several forms of mosaicism, Klinefelter syndrome accounts for 5% of male-factor infertility and represents sterility caused by deficient spermatogenesis (3). The success rate for TESE in patients with nonmosaic Klinefelter syndrome at our institution is 56% (Okada, unpublished data), and numbers of TESE performed in this group are increasing rapidly. Although most patients with nonmosaic Klinefelter syndrome have serum testosterone concentrations below normal limits, testosterone replacement therapy is not indicated until retrieval of spermatozoa from the testes (3). Our data showed that the postoperative decline in Klinefelter patients’ testosterone was not followed by recovery to baseline concentrations, even when using less invasive microdissection TESE techniques.
237
FIGURE 1 Serum testosterone concentrations before and at 6 and 12 months after TESE were measured. Seven patients (No. 1–7) underwent conventional TESE, and 17 patients (No. 8 –24) underwent microdissection TESE. The red circle, green square, and blue triangle indicate testosterone concentration before and at 6 and 12 months after TESE, respectively.
Postoperative testosterone concentrations should be assayed regularly, and testosterone replacement therapy is indicated in patients whose serum testosterone concentrations remain low. Hiroshi Okada, M.D., Ph.D.a,c Toshiro Shirakawa, M.D., Ph.D.a Tomomoto Ishikawa, M.D.a Kazumasa Goda, M.D.a Masato Fujisawa, M.D., Ph.D.b Sadao Kamidono, M.D., Ph.D.a Division of Urology, Department of Organ Therapeutics, Faculty of Medicine,a Kobe University Graduate School of Medicine, Kobe, Japan; and Department of Urology,b Kawasaki Medical University, Kurashiki, Japan; Present address: Department of Urology,c Teikyo University School of Medicine, Tokyo, Japan
References
Okada. T levels after TESE in Klinefelter patients. Fertil Steril 2004.
238
Okada et al.
Correspondence
1. Tournaye H, Camus M, Vandervorst M, Nagy Z, Joris H, Van Steirteghem A, et al. Surgical sperm retrieval for intracytoplasmic sperm injection. Int J Androl 1997;20:69 –73. 2. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue extraction. Hum Reprod 1999;14:131–5. 3. Okada H, Fujioka H, Tatsumi N, Kanzaki M, Okuda Y, Fujisawa M, et al. Klinefelter’s syndrome in the male infertility clinic. Hum Reprod 1999;14:946 –52.
Vol. 82, No. 1, July 2004