IVF and Infertility Unit, Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, Israel
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: ICSI/non-obstructive azoospermia/TESE/testicular sperm
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Patients in whom mature testicular sperm were found after the first TESE were grouped as sperm positive (sp+). Those in whom TESE yielded no sperm for ICSI were grouped as sperm negative (sp).
When no cryopreserved testicular tissue was available to allow further ICSI cycles, repetition of the TESE procedure was offered to the patients. A minimum interval of 6 months between the surgical sperm retrievals was recommended, a policy that was later verified (Schlegel and Su, 1997). Twenty-two patients chose to undergo at least one repetitive TESE cycle, and eight, six and three patients underwent three, four and five surgical retrievals respectively. Patients' characteristics, including female and male partners' age, male patients' serum FSH and testosterone levels are presented in Table I
.
|
Methodology of the TESE procedure
The technique of surgical testicular sperm retrieval in patients with NOA, sperm preparation and ICSI have been described in detail elsewhere (Friedler et al., 1997). Once sperm were found, the surgical procedure was terminated. If sperm were not observed, up to three biopsies were taken, in different areas in the same testicle and also from the contralateral one. During repetitive TESE, the scrotum was opened and adhesions, if present, were dissected. No specific technical problems were encountered in the repetitive TESE cases that could disturb the exposure of testicular tissue.
Ovarian stimulation was performed using the routine long protocol of pituitary suppression followed by ovarian stimulation. Oocytes were retrieved by vaginal ultrasound-guided follicular puncture. Embryo transfer was performed on day 2 or 3 following oocyte retrieval. Recently, the policy of transferring fewer embryos has been emphasized at our Unit. However, in our population, when a couple go through a complete IVF cycle including surgical sperm aspiration, they frequently ask to have more embryos transferred and prefer to take the risk of multiple pregnancy, despite our explanations concerning the risks involved. However, no more than three embryos were transferred, except in women >38 years old or in cases with recurrent failures of implantation, where up to five embryos were transferred if available. Following embryo transfer, all patients received luteal support, including i.m injections of hCG, or of progesterone in oil. Only clinical pregnancies including ultrasonographic demonstration of a gestational sac were counted.
Statistical analysis
Statistical evaluation was performed using Student's t-test, 2-test and Fisher's exact test, where appropriate. Differences were considered significant at P < 0.05.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Successful testicular sperm retrieval rate, enabling performance of ICSI, according to the TESE trial is presented in Table IIac. Twenty-two patients underwent a second TESE (Table IIa
). Altogether, during the second TESE procedure, in 1/4 patients from the sp group and in 16/18 from the sp+ group, sperm was found to enable ICSI (Table IIb
). Further trials were performed on patients from the sp+ group only. At the third trial, in all eight patients, at the fourth trial in 5/6 and at the fifth trial in all three patients, testicular sperm was obtained enabling ICSI, as presented in Table IIa,b
. Overall, in repetitive TESE, 33/39 procedures were sp+ (85%) (Table IIc
).
|
|
|
|
Complications included 4/83 (4.8%) cases with self-resolved extratunical haematomata, all occurring at the first trial. During the performance of repetitive TESE, adhesions were rarely found, in contrast with the findings of another study (Amer et al., 1999), and no specific technical problems or post-operative complications were encountered. Follow-up of the patients was performed on a clinical basis. Testicular sonography was not performed on a routine basis.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our policy of repetition of TESE at intervals of 6 months seems in concordance with the reported experience in the literature. The result of 85% success of testicular sperm retrieval is in the range appearing in these earlier reports. Furthermore, performance of three biopsies per testicle will screen the majority of the positive cases for sperm presence in testicles of men with NOA (Hauser et al., 1998
; Amer et al., 1999
). It should be mentioned that in NOA, testicular sperm may be retrieved also by performing testicular sperm aspiration (TESA); however, as sperm is produced focally, the chance of finding sperm is related to the amount of testicular tissue extracted. Therefore, in several comparative studies TESE was found to be more efficient compared with TESA in successfully of extracting sperm in these cases (Friedler et al., 1997
; Ezeh et al., 1998
; Mercan et al., 2000
). Alternative methods of testicular sperm retrieval that avoid open biopsy were also proposed, including testicular biopty gun needle (Tuuri et al., 1999
) or Trucut needle and milking of seminiferous tubules (Steele et al., 2000
). Presently there is no consensus over the ultimate method of testicular sperm retrieval in NOA and each centre tends to specialize in its method of preference. Regarding repeated surgical sperm retrievals, experience with repeated TESA has been reported (Westlander et al., 2001
). Out of 34 patients with NOA, 34, 14, five, three and one patients underwent a second, third, fourth, fifth and sixth TESA procedure respectively. The fertilization rate remained similar, and pregnancies were achieved up to the fifth attempt, but only five men underwent more than three retrievals. There were no sperm recovery failures in any of the repeated TESA procedures and the time interval did not seem to affect the outcome. No post-operative complications were reported. Whether these presumably less aggressive sperm retrieval methods should be proposed in repeated cases is to be evaluated by a different study.
Currently, there are no clinical or laboratory methods that can predict reliably and accurately the presence of sperm on TESE. It was shown that even the presence of sperm in a preliminary testicular biopsy may fail to predict the presence of mature testicular sperm at the actual TESEICSI in up to 30% of cases (Vanderzwalmen et al., 1997). According to our results and those of others (Amer et al., 1999
), consultation prior to repetitive TESE should consider that even performing TESE after the recommended interval may fail to produce mature sperm for ICSI in up to 10% of cases. Our results indicate that for patients with available sperm (sp+) at their first TESE, failure to obtain sperm may occur during repetitive TESE [in our experience at a rate of 11% (2/28) up to 33% (2/6) during the second and fourth TESE respectively]. Therefore, finding of mature sperm for ICSI in the first fresh TESE offers a good prognosis of an 85% chance of finding sperm in the following trial, but patients should be cautioned that it still may not completely assure success in further TESE trials. On the other hand, in our experience 1/4 sp patients at the first trial did become sp+ at their second trial. When testicular sperm are found, performance of ICSI after a repetitive TESE using the fresh testicular sperm results in a similar outcome with regards to fertilization, embryo cleavage and implantation rates. However, in our study, no pregnancies were achieved using sperm from patients with MA as their main testicular histological diagnosis. Others have reported normal pregnancies resulting from such cases (Silber et al., 1996
), and therefore repetition of TESE in these patients may still be considered with caution, as lack of success may result from other contributing factors. Also, no pregnancies were achieved among the three patients who chose to undergo a fifth TESE in spite of transfer of 14 embryos.
In conclusion, repetition of TESE has clinical value because pregnancies may be achieved in each repetitive trial. Special difficulties or complications during or after performing the procedure were not encountered at any higher rate than after the first TESE, based on clinical examination and judgement. Due to the group's size it is difficult to draw significant conclusions regarding recommendations to perform more than four repetitive TESE procedures. New clinical tools to predict testicular mature sperm availability with proven accuracy are awaited ardently. New sperm retrieval techniques, such as micro-TESE (Schlegel, 1999) should also be tested in repeated TESE procedures in patients with NOA.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Amer, M., Ateyah, A., Hany, R. and Zohdy, W. (2000) Prospective comparative study between microsurgical and conventional testicular sperm extraction in non-obstructive azoospermia: follow-up by serial ultrasound examinations. Hum. Reprod., 15, 653656.
Devroey, P., Liu, J., Nagy, Z., Goossens, A., Tournaye, H., Camus, M., Van Steirteghem, A. and Silber, S. (1995) Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia. Hum. Reprod., 10, 14571460.[Abstract]
Ezeh, U.I.O, Moore, H.D.M. and Cooke, I.D. (1998) A prospective study of multiple needle biopsies versus open biopsy for testicular sperm extraction in men with non-obstructive azoospermia. Hum. Reprod., 13, 30753080[Abstract]
Friedler, S., Raziel, A., Strassburger, D., Soffer, Y., Komarovsky, D. and Ron-El, R. (1997) Testicular sperm retrieval by percutaneous fine needle sperm aspiration compared with testicular sperm extraction by open biopsy in men with non-obstructive azoospermia. Hum. Reprod., 12, 14881493.[Abstract]
Harrington, T.G., Schauer, G. and Gilbert, B.R. (1996) Percutaneous biopsy: an alternative to open testicular biopsy in the evaluation of the subfertile man. J. Urol., 156, 16471651.[ISI][Medline]
Hauser, R., Botchan, A., Amit, A., Ben Yosef, D., Gamzu, R., Paz, G., Lessing, J.B., Yogev, L. and Yavetz, H. (1998) Multiple testicular sampling in non-obstructive azoospermia: is it necessary? Hum. Reprod., 13, 30813085.[Abstract]
Kahraman, S., Ozgur, S., Alatas, C., Aksoy, S., Balaban, B., Evrenkaya, T., Nuhoglu, A., Tasdemir, M., Biberoglu, K., Schoysman, R. et al. (1996) High implantation and pregnancy rates with testicular sperm extraction and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia. Hum. Reprod., 11, 673676.[Abstract]
Mercan, R., Urman, B., Alatas, C., Aksoy, S., Nuhoglu, A., Isiklar, A. and Balaban, B. (2000) Outcome of testicular sperm retrieval procedures in non-obstructive azoospermia: percutaneous aspiration versus open biopsy. Hum. Reprod., 15, 15481551.
Ron-El, R., Strassburger, D., Friedler, S., Komarovski, D., Bern, O., Soffer, Y. and Raziel, A. (1997) Extended sperm preparation: an alternative to testicular sperm extraction in non-obstructive azoospermia. Hum. Reprod., 12, 12221226.[ISI][Medline]
Ron-El, R., Strauss, D., Friedler, S., Strassburger, D., Komarovsky, D. and Raziel, A. (1998) Serial sonography and colour flow Doppler imaging following testicular and epididymal sperm extraction. Hum. Reprod., 13, 33903393.[Abstract]
Rosenlund, B., Kvist, U., Ploen, L., Rozell, B.L., Sjoblom, P. and Hillensjo, T. (1998) A comparison between open and percutaneous needle biopsies in men with azoospermia. Hum. Reprod., 13, 12661271.[Abstract]
Schlegel, P.N. ( 1999) Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum. Reprod., 14, 131135.
Schlegel, P.N. and Su, L.M. (1997) Physiological consequences of testicular sperm extraction. Hum. Reprod., 12, 16881692.[Abstract]
Schlegel, P.N., Palermo, G.D., Goldstein, M., Menendez, S., Zaninovic, N., Veeck, L.L. and Rosenwaks, Z. (1997) Testicular sperm extraction with intracytoplasmic sperm injection for non-obstructive azoospermia. Urology, 49, 435440.[ISI][Medline]
Silber, S.J., Van Steirteghem, A., Nagy, Z., Liu, J., Tournaye, H. and Devroey, P. (1996) Normal pregnancies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azoospermia due to maturation arrest. Fertil. Steril., 66, 110117.[ISI][Medline]
Silber, S.J., Nagy, Z., Devroey, P., Camus, M. and Van Steirteghem, A.C. (1997) The effect of female age and ovarian reserve on pregnancy rate in male infertility: treatment of azoospermia with sperm retrieval and intracytoplasmic sperm injection. Hum. Reprod., 12, 26932700.[Abstract]
Steele, E.K., Kelly, J.D., Lewis, S.E., McNally, J.A., Sloan, J.M. and McClure, N. (2000) Testicular sperm extraction by Trucut needle and milking of seminiferous tubules: a technique with high yield and patient acceptability. Fertil. Steril., 74, 380383.[ISI][Medline]
Tournaye, H., Verheyen, G., Nagy, P., Ubaldi, F., Goossens, A., Silber, S., Van Steirteghem, A.C. and Devroey, P. (1997) Are there any predictive factors for successful testicular sperm recovery in azoospermic patients? Hum. Reprod., 12, 8086.[ISI][Medline]
Tuuri, T., Moilanen, J., Kaukoranta, S., Makinen, S., Kotola, S. and Hovatta, O. (1999) Testicular biopty gun needle biopsy for collecting spermatozoa for intracytoplasmic injection, cryopreservation and histology. Hum. Reprod., 14, 12741278.
Vanderzwalmen, P., Zech, H., Birkenfeld, A., Yemini, M., Bertin, G., Lejeune, B., Nijs, M., Segal, L., Stecher, A., Vandamme, B. et al. (1997) Intracytoplasmic injection of spermatids retrieved from testicular tissue: influence of testicular pathology, type of selected spermatids and oocyte activation. Hum. Reprod., 12, 12031213.[ISI][Medline]
Westlander, G., Hamberger, L., Hanson, C., Lundin, K., Nilsson, L., Söderlund, B., Werner, C. and Bergh, C. (1999) Diagnostic epididymal and testicular sperm recovery and genetic aspects in azoospermic men. Hum. Reprod., 14, 118122.
Westlander, G., Rosenlund, B., Soderlund, B., Wood, M. and Bergh, C. (2001) Sperm retrieval, fertilization and pregnancy outcome in repeated testicular sperm aspiration. J. Assist. Reprod. Genet., 18, 171177.[ISI][Medline]
Submitted on July 7, 2000; resubmitted on April 16, 2002; accepted on May 10, 2002.