Archives of Andrology, 51:225231, 2005

Copyright # Taylor & Francis Inc.

ISSN: 0148-5016 print/1521-0375 online
DOI: 10.1080/014850190884354

PROBABILITY OF SPERM RECOVERY IN NON-OBSTRUCTIVE

AZOOSPERMIC PATIENTS PRESENTING WITH TESTES VOLUME
LESS THAN 10 ml/FSH LEVEL EXCEEDING 20 mIU/ml

H. Hibi and T. Ohori & Department of Urology, Kyoritsu General Hospital,

Nagoya, Japan
Y. Yamada and N. Honda & Department of Urology, Aichi Medical University,
Nagakute, Japan
Y. Asada & Asada Ladys Clinic, Kasugai, Japan

& We evaluated the sperm recovery rate in non-obstructive azoospermia (NOA) patients presenting with bilateral testicular atrophy characterized by testes volume of less than 10 ml and FSH
levels exceeding 20 mIU=ml (group NOA-1), and compared the results to those NOA cases displaying unilateral testis volume exceeding 10 ml or FSH levels less than 20 mIU=ml (group NOA-2).
Sperm retrieval was conducted in 261 azoospermic patients from April 1995 to December 2002.
Forty-six NOA-1 and 37 NOA-2 individuals underwent microdissection TESE or 34 standard
biopsies. Sperm recovery was achieved in 11 (24%) and 12 (32%) cases in NOA-1 and NOA2, respectively. All couples received ICSI. Four clinical pregnancies (36.3%) in NOA-1 and two
(17%) in NOA-2 resulted. Five subsequent healthy deliveries were obtained. NOA patients presenting with bilateral severe atrophic testes volume and obviously elevated FSH levels exhibited approximately 24% probability of sperm recovery. On the other hand, NOA characterized by testicular
atrophy or elevated FSH levels displayed probability of approximately 32%. Differences in sperm
recovery were not evident between NOA-1 and NOA-2. No successful pre-operative predictors of
sperm recovery were identified.
Keywords NOA, non-obstructive azoospermia, FSH, sperm, TESE-ICSI, testis volume

INTRODUCTION
Patients presenting with non-obstructive azoospermia (NOA) caused by
germinal failure can be currently treated in terms of several objectives
employing testicular sperm extraction (TESE) and intracytoplasmic sperm
This paper was read at the 18th Congress of the European Association of Urology, Madrid, Spain,
1215 March 2003.
Address correspondence to Hatsuki Hibi, MD, Department of Urology, Kyoritsu General Hospital,
Goban-cho, Atsuta-ku, Nagoya, 456-8611, Japan. E-mail: hibih@quartz.ocn.ne.jp

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injection (ICSI). In NOA patients, diffuse distribution of spermatogenesis,

which is observed throughout the testis, is not limited to a specific region;
consequently, multiple biopsies or a recent microsurgical approach to
TESE is recommended. Successful sperm recovery has been achieved in
approximately 4060% of cases [3, 6, 8, 10, 13]. No precise definition exists
regarding FSH levels and testes volume in NOA; documented FSH values
and testicular volume vary widely. Furthermore, NOA patients displaying
normal FSH values, testicular volume and histopathology appear in the
literature [5, 6]. Identification of a successful predictor is difficult; however,
some differences may exist according to these values.
This study was conducted to evaluate the sperm recovery rate and subsequent ICSI results in NOA patients demonstrating bilateral testicular
atrophy (testes volume of less than 10 ml) and FSH levels exceeding
20 mIU=ml. These results were compared to NOA patients characterized
by unilateral testis volume exceeding 10 ml or FSH levels less than
20 mIU=ml.
MATERIALS AND METHODS
Patients
Sperm retrieval was conducted in 261 azoospermic patients from April
1995 to December 2002. Azoospermia was confirmed on at least three separate occasions on the basis of semen analyses, which included a centrifuged pellet. One hundred seventy-eight and 83 subjects were diagnosed
with obstructive azoospermia (OA) and NOA, respectively. Among the
NOA cases, 46 subjects displayed severe bilateral testicular atrophy characterized by testes volume of less than 10 ml and FSH levels in excess of
20 mIU=ml (group NOA-1). On the other hand, 37 individuals demonstrated unilateral testicular volume exceeding 10 ml or an elevated FSH
value, which was less than 20 mIU=ml (group NOA-2). These men showed
no evidence of major systemic illness or previous history of urogenital infection. Testicular volume was measured with an orchidometer. Fifteen NOA-1
patients had undergone previous diagnostic biopsy at other institutes.
Sertoli cellonly syndromes and maturation arrest were present in 12 and
two patients, respectively; mixed histological pattern was observed in one
individual.
Operation
The procedure was conducted under local anesthesia with spermatic
block; occasionally, sedatives were employed. In NOA-1, 28 subjects underwent 34 standard biopsies per testicle, whereas 18 individuals received

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microdissection TESE in the right testis and four biopsies in the left testis
through a scrotal median raphe incision. On the other hand, all subjects
underwent 34 standard biopsies per testicle in NOA-2. Control of bleeding
was achieved via bipolar cautery; however, application of this technique was
minimized so as to avoid local temperature elevation, which may be harmful to sperm. Excised tissue was collected in center-well organ culture dishes
(Becton Dickinson Labware, Franklin Lakes, NJ, USA) filled with spermwashing medium (modified human tubal fluid; Irvine Scientific Co., Santa
Ana, CA, USA); subsequently, these tissues were finely minced and shredded.
The specimens were cryopreserved for ICSI when sperm were evident.
Following termination of the retrieval process, the tunica vaginalis was
sutured and skin closure was effected with a stapler. Scrotal support was
provided despite the absence of a drainage tube.
Testicular volume and FSH value were compared in order to define
predictive parameters for successful sperm retrieval. Furthermore, successful sperm recovery rate in NOA-1 was compared to that of NOA-2. Postoperative testosterone level was re-tested one month later as a component
of post-operative evaluation in 19 consenting subjects.
Statistical analysis was performed using ANOVA. Results, which were
subjected to Fishers test, were considered significant at P < 0:05. All data
were expressed as mean
SEM.

RESULTS
Patient characteristics of NOA-1 and NOA-2 are presented in Table 1.
Chromosomal abnormality was detected in eight subjects (47XXY in seven
and 47XXY(96)=46XY(4) in one) in NOA-1. One individual among 12
NOA-1 cases demonstrated Y chromosome microdeletion. No chromosomal abnormalities were detected in NOA-2. Testicular sperm were
successfully recovered in 11 NOA-1 (23.9%) and in 12 NOA-2 (32.4%) subjects. Microdissection TESE enabled sperm recovery in only one individual
TABLE 1 Patient Characteristics

Age
Spouses age
Duration of infertility
Testis (right=left) ml
LH mIU=ml
FSH mIU=ml
Testosterone ng=ml

NOA-1 (n 46)

NOA-2 (n 37)

32
0.7
30
0.6
3.7
0.6
5.9
0.4=5.3
0.3
9.4
0.8
33
1.7
4.3
0.25

33
1.0
31
0.7
3.2
0.7
11.5
0.9=9.7
0.6
5.5
0.6
20
1.6
4.6
0.32

NOA: non-obstructive azoospermia

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H. Hibi et al.

TABLE 2 Preoperative Parameters and Outcome of Successful Sperm Retrieval in NOA-1

NOA-1 (n 46)

Testis (right=left) ml
FSH mIU=ml
Age

NOA-2 (n 37)

Sperm recovery (11)

No sperm (35)

Sperm recovery (12)

No sperm (25)

6.0
0.4=5.9
0.4

34
5.4
37
1.9#

5.8
0.5=5.1
0.4

33
2.1
31
0.8y

8.0
1.6=9
1.5

16
1.3
35
2.0

12
1.0=10
0.7
21
2.0
32
1.0

NOA: non-obstructive azoospermia;

#
vs; y P < 0.019
Testicular volume and FSH value were not significant.

displaying right testicular volume of 5 ml and FSH level of 76.7 mIU=ml.

Relative sperm recovery rates according to testicular volume and FSH value
failed to demonstrate benefit as potential predictive parameters. Curiously,
only patient age in NOA-1 was obviously higher in instances of successful
sperm retrieval (P < 0:019, Table 2).
All couples in which successful sperm retrieval was accomplished
received ICSI. Clinical pregnancy was observed in four (36%) and two
(17%) cases of NOA-1 and NOA-2, respectively. One pregnancy was discontinued by abortion; additionally, five subsequent healthy deliveries were
obtained. No statistical differences were evident regarding sperm recovery
rate and pregnancy rate between NOA-1 and NOA-2 (Table 3).
A single individual exhibited post-operative lump hematoma; however,
it subsided spontaneously within two weeks. All patients required analgesics
on the day of surgery. Testosterone was re-tested in 19 subjects (NOA-1; 12,
NOA-2; 7) one month later. Decreased testosterone levels consequent to
the operation were not observed (pre-operative=post-operative; 4:36

0:51=4:00
0:37 ng=ml in NOA-1, 4:53
0:50=4:66
0:40 ng=ml in
NOA-2, respectively).

DISCUSSION
Treatment of infertile couples requires coordinated management of
both the man and the woman. Effective teamwork by the gynecologist
TABLE 3 Sperm Recovery Rate and ICSI Outcome

Sperm recovery rate

Pregnancy rate

NOA-1 (n 46)

NOA-2 (n 37)

11=46 (23%)
4=11 (36%)

12=37 (32%)
2=12 (16%)

ICSI: intracytoplasmic sperm injection

NOA: non-obstructive azoospermia

NS
NS

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229

and the urologist is essential. The primary objective should involve attempts
to restore fertility, rather than to proceed immediately to ART. Moreover,
the couple should be advised regarding the risks and probable success rates
of the various treatment options. However, the only treatment available for
patients with NOA is testicular sperm retrieval. At present, sperm may be
harvested from these men who were previously considered infertile and
untreatable. ICSI has allowed some NOA patients to father offspring using
a small number of sperm.
NOA is typically characterized by atrophic testes and elevated FSH
value. Successful sperm recovery rate employing multiple TESE or microsurgical TESE was reported in 4060% of men exhibiting NOA. No precise
definition in terms of NOA exists; consequently, FSH value and testicular
size, which varied widely, were often not described [5, 6, 16]. Furthermore,
examples of normal histology were included with documented NOA
cases [1], which might affect differences with respect to success rate.
Consequently, data with which to inform individual NOA patients were
insufficient.
The major difficulty encountered in NOA patients is the inability to
predict reliably and accurately the presence of sperm by TESE based on testis size, FSH level and clinical history. Mean testicular size was 5.8=5.3 ml
(right=left) in NOA-1; larger size up to 1216 ml has been reported in
NOA [1, 6]. On the other hand, FSH is inhibited by the total number of
spermatogenic cells, and, FSH is not inhibited specifically by the number
of mature sperm or spermatids. Thus, the level of FSH in no way indicates
whether any normal sperm are present in the testis [11]. Apparently, no
upper limit for FSH concentration exists above which no spermatogenetic
activity can be expected. Reported FSH values in NOA patients were relatively low [5, 6]; mean FSH value was 33.7 mIU=ml in the NOA-1. Microdissection TESE enabled the recovery of sufficient numbers of sperm for ICSI
in an individual displaying testicular volume of 5 ml and FSH level of
76.7 mIU=ml. This condition is consistent with results of previous studies
[3]. Unfortunately, this couple was unable to achieve a successful outcome.
Testicular damage can be minimized on occasion via utility of a fine
needle in lieu of open biopsy to obtain spermatozoa for ICSI. Approximately 10% of men presenting with NOA will experience successful sperm
retrieval via the percutaneous approach; however, in excess of 50% will
experience successful retrieval with open biopsy [2]. It would appear that
open sperm extraction permits sperm retrieval and examination of larger
tissue fields in comparison to needle aspiration [12]. Furthermore, we recommend application of bilateral testicular biopsy in order to obtain sperm
whenever possible.
When spermatogenesis is extremely limited, a small biopsy will not
detect a tubule displaying spermatogenesis. TESE was conducted by open

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biopsy, frequently in four-part biopsies or microdissection per testicle.

Ostad et al. also reported that the average number of biopsy sites necessary
to retrieve spermatozoa in NOA was 6.4 [8].
TESE is not without adverse effects involving a permanent, or at least a
transient, influence on spermatogenesis. Tash et al. described a relevant
decrease in seminiferous tubular volume upon histological examination
of testicular biopsy specimens obtained from patients who had undergone
two consecutive TESE procedures [14]. Microsurgical approach permits
the removal of smaller samples of testicular tissue with minimum damage
and secondary testicular atrophy [9]. Microdissection TESE affords an
advantage regarding successful retrieval upon comparison with multiple
TESE [1, 7, 15]. We previously described the application of microdissection
TESE under circumstances identical to those of this study [4]. Although
excised tissue weight was obviously reduced, successful retrieval was limited.
In this series, microdissection TESE played a diminished role with respect
to successful sperm recovery. The small number of patients and the heightened severity of the condition may have influenced this situation.
Decreased testosterone levels were not observed in relation to the procedure in the present investigation; however, the small sample of patients
later receiving endocrine evaluation might be related to the poor results
associated with sperm retrieval.
In conclusion, NOA patients presenting with testes volume of less than
10 ml and FSH levels in excess of 20 mIU=ml exhibited 23.9% probability
of sperm recovery, whereas NOA patients displaying testicular atrophy or
elevated FSH levels displayed probability of 32.4%. No successful preoperative predictors of sperm recovery were identified.
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