IVF Unit, Department of Obstetrics and Gynecology, Hadassah Medical Center, Hebrew University, Ein-Kerem, Jerusalem, Israel
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Abstract |
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Key words: fine needle aspiration/histology/non-obstructive azoospermia/predictive value/testicular sperm
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Introduction |
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Although ICSI using testicular sperm offers men with non-obstructive azoospermia the possibility of fathering their own genetic children, the recovery of sperm may not always be successful in these patients, an event that encompasses important emotional and financial implications. Despite that, before turning to the alternative treatment with donor sperm, many couples request the performance of a repeated sperm recovery attempt. Determining factors which may predict the outcome of such a repeated TEFNA attempt allow objective counselling, offering thus realistic expectations for both the couple and the physician. This study aims to analyse the predictive value of the first TEFNA attempt in patients with non-obstructive azoospermia for sperm recovery in the subsequent attempt.
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Materials and methods |
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Methods
The pretreatment evaluation comprised karyotyping, sonographic and physical examination of the testes, serum FSH and testosterone, testicular biopsy, as well as repeated semen analysis following high velocity centrifugation (1800 g for 5 min). In all patients, TEFNA was used for the recovery of testicular sperm as previously described (Lewin et al., 1999). A positive TEFNA was defined as the recovery of any number of mature sperm. In order to rule out testicular malignancy and corroborate the pretreatment histological evaluation, after searching for the presence of sperm, tissue specimens retrieved from each TEFNA attempt were sent for histopathological examination. Based on testicular histology as determined in the pretreatment testicular biopsy, patients were classified as having Sertoli cell-only (germ cell aplasia) in 21 cases, maturation (spermatogenic) arrest in 12 cases, hypospermatogenesis (germ cell hypoplasia) in 11 cases, and tubular hyalinization due to non-mosaic Klinefelter's syndrome in seven cases.
Statistical analysis
Positive predictive value (the probability that sperm will be recovered) and negative predictive value (the probability that sperm will not be found) were calculated.
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Results |
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The sperm recovery results of the second TEFNA attempt performed in patients with either positive or negative first TEFNA classified by the histological findings are summarized in Table IIa and b
. In the 33 patients with a positive first TEFNA, sperm recovery rates in the second TEFNA attempt by testicular histology were respectively 10/11 (90.9%) in hypospermatogenic patients, 8/11 (72.7%) in Sertoli cell-only patients, 2/7 (28.6%) in patients with maturation arrest and 3/4 (75%) in patients with tubular hyalinization. In the 18 patients with a negative first TEFNA, the second attempt succeeded in retrieving sperm in only 2/10 (20%) of patients with Sertoli cell-only, whereas no sperm were recovered in the five patients with maturation arrest and the three patients with tubular hyalinization. The predictive value of the first to the second TEFNA attempt for sperm recovery by testicular histology is shown in Figure I
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Discussion |
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Considering the reported average sperm recovery rate is <50% in patients with testicular failure, and the fact that testicular biopsy is an invasive procedure that may be associated with significant complications (Harrington et al., 1996), the need to restrict testicular sperm search to those with a high chance of yielding testicular sperm was widely acknowledged. As a result, several, mainly retrospective, studies examined possible predictive factors for successful testicular sperm recovery in azoospermic patients (Tournaye et al., 1996
; Ezeh et al., 1998
; Jezek et al., 1998
). Although the roles of various parameters as predictors were previously evaluated, including testicular volume, serum FSH, serum inhibin B, the presence of at least one single spermatozoon in any preliminary semen analysis, and the histological results of testicular biopsy, studies failed to show any strong predictors except for testicular histopathology for successful testicular sperm recovery (Tournaye et al., 1997
; Schultze et al., 1999
).
The correlation between testicular histology and successful testicular sperm recovery was corroborated by others (Jow et al., 1993), who reported testicular sperm retrieval to be successful in seven out of 11 (64%) patients with hypospermatogenesis, two out of nine (22.2%) patients with maturation arrest and none of nine patients with Sertoli cell-only. On the other hand, high sperm retrieval rates for all histological categories in obstructive and non-obstructive azoospermia patients were reported (Tournaye, 1999
), although showing that the number of testicular sperm retrieved decreases as the histological pattern changes from normal spermatogenesis (100%) to different degrees of maturation arrest (4862%) and Sertoli cell-only patterns (1986%). Ezeh et al. similarly reported testicular sperm retrieval in all patients with hypospermatogenesis, 91% of patients with focal spermatogenesis, none of the patients with maturation arrest and 67% of patients with Sertoli cell-only pattern (Ezeh et al., 1998
).
Thus far, to our knowledge, the possible predictive value of the results of the first testicular biopsy in counselling patients interested in undergoing a second attempt has not been evaluated by any study. This study was performed in an effort to offer appropriate counselling to patients suffering from non-obstructive azoospermia turning to our IVF clinic for a second TEFNA attempt. In accordance with the results of previous studies showing testicular histopathology to be the only valid predictor for successful testicular sperm recovery by testicular biopsies (Tournaye et al, 1997; Schultze et al., 1999
), the parameters used in this study for evaluation included only the sperm recovery and the testicular histopathological classification. In examining the relationship between the results of the first and second TEFNA attempt, a high predictive value of the first TEFNA attempt has been found in patients with non-obstructive azoospermia for sperm recovery at the subsequent attempt, with a mean positive predictive value (PPV) of 69.7%, with the highest probability being 90.9% in patients with hypospermatogenesis, 72.7% in patients with Sertoli cell-only, 75% in patients with tubular hyalinization, and the lowest being 28.6% in patients with maturation arrest. The negative predictive value (NPV) was found to be high in all categories (80% in Sertoli cell-only, 100% in maturation arrest and 100% in tubular hyalinization), with the mean NPV being 88.9%. None of the patients with hypospermatogenesis had two subsequent negative TEFNA attempts.
Our results corroborate those reported by others (Tournaye et al., 1997), in which a positive histopathology of a preliminary single-specimen testicular biopsy would correctly predict successful testicular sperm recovery in 83.3% of cases, whereas a negative result would predict recovery failure in 68.7% of cases. Furthermore, in the study by Tournaye et al. (1997), similar to our results, the probability that sperm would be recovered was 86% with focal hypospermatogenesis, whereas the probability that sperm would not be recovered was as high as 80% with Sertoli cell-only. For complete and incomplete maturation arrest the results were less encouraging for successful sperm recovery and included 52.5 and 66.6% respectively.
One of the primary considerations regarding repeated TEFNA attempts might be the possible consequences on testicular function. While several studies evaluating the effects of testicular sperm extraction (TESE) on the testis reported possible side-effects, which in the majority were transient and resolving within 6 months (Schlegel and Su, 1997), our experience with TEFNA in over 110 attempts has shown a very low rate of minor complaints, and has been proven thus far to be safe and well tolerated by all patients (Lewin et al., 1999
).
In conclusion, considering the important psychological and financial implications of a subsequent TEFNA/ICSI treatment, some guidelines for patient counselling may be proposed. At present, we therefore suggest that repeated TEFNA may be offered to all non-obstructive azoospermic patients with a positive first TEFNA. In view of the poor (11%) prognosis of sperm recovery following a negative result, patients are strongly advised to use donor back-up if a second attempt is planned, but such an attempt should not be denied should the patient decide not to use donor sperm and face the consequences of a negative result.
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Notes |
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References |
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Submitted on April 9, 2001; accepted on September 4, 2001.