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Scrotal US for Evaluation of Infertile Men with Azoospermia¹

¹ From the Departments of Radiology (M.H.M., J.Y.C.), Urology (J.T.S.), and Pathology (Y.K.C.), Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; and Department of Radiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea (S.H.K.). Received February 17, 2005; revision requested April 14; revision received May 10; final version accepted June 13. Address correspondence to S.H.K.(e-mail: kimsh{at}radcom.snu.ac.kr).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Purpose: To evaluate prospectively the accuracy of scrotal ultrasonography (US) in distinguishing obstructive azoospermia from nonobstructive azoospermia in infertile men by using histologic findings as the reference standard.

Materials and Methods: The institutional review board approved the study, and informed consent was obtained from each patient. Twenty infertile men (mean age, 34.7 years; 40 testes) with azoospermia were evaluated at scrotal US, with an emphasis on the course of the proximal genital duct: mediastinum testis, epididymal head, epididymal body, and epididymal tail. Testicular volumes were calculated by using the formula: length x height x width x 0.71. On the basis of histologic results, azoospermia was divided into two groups (obstructive vs nonobstructive) in all cases except one. Scrotal US findings between obstructive and nonobstructive azoospermia were compared. The Fisher exact and Wilcoxon signed rank sum tests were used to assess differences between both groups.

Results: Of 20 infertile men with azoospermia, 14 were proved to have obstructive azoospermia; the others had nonobstructive azoospermia. According to US findings, epididymal abnormalities in the head, body, and tail were significantly associated with obstructive azoospermia (17 [61%], 18 [64%], and 20 [71%] of 28 testes, respectively; P < .001 for all), while abnormalities of the mediastinum testis between both groups were not significant (P > .05). By taking epididymal abnormalities into account, sensitivity, specificity, and accuracy of scrotal US for differentiation of obstructive from nonobstructive azoospermia were 82.1% (23 of 28 scrota), 100% (12 of 12 scrota), and 87.5% (35 of 40 scrota), respectively. The median testicular volume in obstructive azoospermia was 11.6 mL (range, 7.7–25.8 mL) and that in nonobstructive azoospermia was 8.3 mL (range, 1.2–16.4 mL) (P < .05).

Conclusion: Evaluation of the epididymis and measurement of testicular volume with scrotal US are important in distinguishing obstructive azoospermia from nonobstructive azoospermia in infertile men.

© RSNA, 2006

	INTRODUCTION

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According to World Health Organization, infertility is defined as the inability to initiate a pregnancy after 1 year of unprotected intercourse. In approximately 50% of infertile couples, a variety of male factors are responsible for difficulty in conception (1). Of these, azoospermia, complete absence of the sperm in the ejaculate, accounts for about 5%–10% of male infertility (2,3). In azoospermic patients, it is important to distinguish nonobstructive azoospermia from obstructive azoospermia, because infertile men with obstructive azoospermia may be amenable to surgical or interventional correction. On the other hand, in those with primary testicular failure, it may be reasonable to proceed directly to an advanced assisted reproductive technique such as intracytoplasmic sperm injection.

In infertile men with azoospermia, transrectal ultrasonography (US) has been conventionally used as a first-line diagnostic modality to document the absence of the vas deferens or obstruction in the ejaculatory duct (4). Although scrotal US is routinely performed to check for nonpalpable varicocele, it also may be helpful in distinguishing testicular failure from obstruction in an azoospermic patient in that it can directly demonstrate abnormalities in the proximal (mediastinum testis, epididymis, and intrascrotal portion of the vas deferens) genital duct and may also depict secondary changes of the proximal genital duct caused by distal (terminal vas deferens, ampulla of the vas deferens, seminal vesicle, and ejaculatory duct) genital duct obstruction. The purpose of our study, therefore, was to evaluate prospectively the accuracy of scrotal US in helping distinguish obstructive azoospermia from nonobstructive azoospermia in infertile men by using histologic findings as the reference standard.

	MATERIALS AND METHODS

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Study Population
From October 2003 to January 2005, 20 infertile men with azoospermia were included consecutively in this study. The mean age of these patients was 34.7 years (range, 21–44 years). Patients with the diagnosis of retrograde ejaculation were excluded from the study population on the basis of postejaculation urine analysis. Our institutional review board approved the study, and informed consent was obtained from each patient.

US Technique
Scrotal US was performed by an investigator (M.H.M.) with 8 years of experience in genitourinary US. The scrota were scanned (HDI 5000; Advanced Technology Laboratories, Bothell, Wash) with a 5–12-MHz linear-array transducer. Scanning was performed with the patient in the supine position. The scrota were supported by a towel between the thighs. Testicular volumes were calculated by using the empiric formula of Lambert (5): length x height x width x 0.71. Then, the testis and paratesticular area—mediastinum testis, epididymal head, epididymal body, and epididymal tail—were examined sequentially along the course of the proximal genital duct. Additional techniques such as the use of Valsalva maneuver or upright positioning were used if needed for venous evaluation.

Image Interpretation
Without knowledge of histologic findings, the testis and paratesticular area were evaluated prospectively with an emphasis on the course of the proximal genital duct. In the testis, the mediastinum testis was sonographically classified as normal and abnormal. Appearance of anechoic tubular structures or cysts suggesting ectasia of the rete testis was considered abnormal. In the paratesticular area, careful attention was paid to the head, body, and tail of the epididymis. The epididymal heads were classified according to their appearance as normal, absent, tubular ectasia, or inflammatory masslike lesion. Tubular ectasia was defined as multiple anechoic tubular or round structures representing the dilated epididymal duct. Simple cysts in the epididymal head, whether spermatocele or epididymal cyst, were excluded from being considered as tubular ectasia. When the epididymal head was enlarged due to formation of a heterogeneous mass, it was regarded as an inflammatory masslike lesion. The epididymal body was classified as normal, absent, tapering, or an inflammatory masslike lesion. Tapering was defined as abrupt narrowing of the epididymal body without tracing to the distal epididymis. The diameter of the epididymal body was not assessed because it showed different values along the course. Finally, we classified the epididymal tail as normal, absent, or an inflammatory masslike lesion. We did not evaluate the vas deferens because it could not be reliably identified on scrotal US scans.

Standard of Reference
In all cases except one, biopsy of the testis was performed for diagnostic purposes or sperm harvesting. Histologic results were prospectively provided by each of five staff pathologists (Y.K.C., with 14 years of experience; the others with 28, 22, 14, and 7 years of experience) at our institution as part of their daily practice. Formally designated diagnoses were as follows; (a) normal spermatogenesis, (b) mild hypospermatogenesis, (c) severe hypospermatogenesis, (d) maturation arrest, and (e) germ cell aplasia (6). For the purpose of this study, these diagnoses were divided into two groups: obstructive and nonobstructive azoospermia. Normal spermatogenesis and mild hypospermatogenesis were included in the obstructive azoospermia category, and the other diagnoses were included in the nonobstructive azoospermia category. In one patient in whom biopsy of the testis was not performed because he did not desire sperm harvesting, grouping was performed with cytogenetic analysis.

Statistical Analysis
The value of scrotal US in helping distinguish nonobstructive from obstructive azoospermia was assessed by using a commercially available software package (SPSS, version 10.0; SPSS, Chicago, Ill). For the assessment of the proximal genital duct, the differences between obstructive and nonobstructive azoospermia were evaluated by using the Fisher exact test. Sensitivity, specificity, and accuracy were calculated as follows: sensitivity = (IO/PO) x 100, where IO is the number of correct imaging-based diagnoses of obstructive azoospermia and PO is the number of proved obstructive azoospermia; specificity = (IN/PN) x 100, where IN is the number of correct imaging-based diagnoses of nonobstructive azoospermia and PN is the number of proved nonobstructive azoospermia; and accuracy = [(IO + IN)/(PO + PN)] x 100. In addition, testicular volume in nonobstructive azoospermia was compared with that in obstructive azoospermia by means of Wilcoxon signed rank sum test. For all statistical tests, P .05 was considered to indicate a significant difference.

	RESULTS

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Study Groups
Of the 20 men with azoospermia, 14 were proved to have obstructive azoospermia and were given the following diagnosis: congenital bilateral absence of the vas deferens (CBAVD) (n = 9) and inflammatory-associated obstruction (n = 5). Six had nonobstructive azoospermia, and their diagnoses included Klinefelter syndrome (n = 1), Y microdeletion (n = 1), and unexplained testicular failure (n = 4).

Scrotal US Findings in Obstructive Azoospermia
A total of 14 infertile men with obstructive azoospermia (28 testes) were studied with US. Twenty-four (86%) testes had abnormal US imaging findings in the epididymis or mediastinum testis. The abnormalities in the epididymal head (61%) were tubular ectasia (n = 11), absence (n = 4), and inflammatory masslike lesion (n = 2) (Fig 1). The abnormalities in the epididymal body were tapering (n = 8), absence (n = 7), and inflammatory masslike lesion (n = 3) (Fig 2) and were present in 64% of cases of obstructive azoospermia. The epididymal tail was absent (n = 15) or showed inflammatory masslike lesion (n = 5) in 71% of cases of obstructive azoospermia (Fig 3). The mediastinal abnormality was found in three testes, which manifested as multiple cysts in the mediastinum testis (Fig 4a).

View larger version (81K): [in this window] [in a new window] [Download PPT slide]   Figure 1a: Epididymal head abnormalities in obstructive azoospermia. (a) Longitudinal (left) and transverse (right) US images in a 31-year-old man with proved CBAVD show tubular ectasia (arrowheads) in the epididymal head. (b) Longitudinal US image in a 34-year-old man with proved inflammatory-associated azoospermia. Cranial portion of the right hemiscrotum shows enlarged, coarsely hypoechoic epididymal head (arrowheads) suggestive of an inflammatory mass. A few echogenic spots (arrows) are possibly due to calcifications.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 1b: Epididymal head abnormalities in obstructive azoospermia. (a) Longitudinal (left) and transverse (right) US images in a 31-year-old man with proved CBAVD show tubular ectasia (arrowheads) in the epididymal head. (b) Longitudinal US image in a 34-year-old man with proved inflammatory-associated azoospermia. Cranial portion of the right hemiscrotum shows enlarged, coarsely hypoechoic epididymal head (arrowheads) suggestive of an inflammatory mass. A few echogenic spots (arrows) are possibly due to calcifications.

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Longitudinal US images of epididymal body abnormalities in obstructive azoospermia. (a) Image through the epididymal body in a 32-year-old man shows abrupt tapering (arrow) in the middle to distal portion of epididymal body. The patient was proved to have CBAVD. (b) In a 31-year-old patient with CBAVD, abrupt tapering (arrow) is seen between epididymal head and body. Note tubular ectasia in epididymal head (). (c) Image in a 32-year-old man with proved inflammatory-associated azoospermia proximal to midportion of epididymal body shows ill-defined hypoechoic area (solid arrows) and calcified plaque (open arrow) within enlarged epididymal body, suggestive of inflammatory mass.

View larger version (75K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Longitudinal US images of epididymal body abnormalities in obstructive azoospermia. (a) Image through the epididymal body in a 32-year-old man shows abrupt tapering (arrow) in the middle to distal portion of epididymal body. The patient was proved to have CBAVD. (b) In a 31-year-old patient with CBAVD, abrupt tapering (arrow) is seen between epididymal head and body. Note tubular ectasia in epididymal head (). (c) Image in a 32-year-old man with proved inflammatory-associated azoospermia proximal to midportion of epididymal body shows ill-defined hypoechoic area (solid arrows) and calcified plaque (open arrow) within enlarged epididymal body, suggestive of inflammatory mass.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 2c: Longitudinal US images of epididymal body abnormalities in obstructive azoospermia. (a) Image through the epididymal body in a 32-year-old man shows abrupt tapering (arrow) in the middle to distal portion of epididymal body. The patient was proved to have CBAVD. (b) In a 31-year-old patient with CBAVD, abrupt tapering (arrow) is seen between epididymal head and body. Note tubular ectasia in epididymal head (). (c) Image in a 32-year-old man with proved inflammatory-associated azoospermia proximal to midportion of epididymal body shows ill-defined hypoechoic area (solid arrows) and calcified plaque (open arrow) within enlarged epididymal body, suggestive of inflammatory mass.

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 3: Longitudinal US image in a 32-year-old man with proved inflammatory-associated azoospermia. Caudal portion of left hemiscrotum shows enlarged, coarsely hypoechoic epididymal tail (arrowheads) with multiple echogenic spots presumed to be calcification. This finding suggests inflammatory mass involving the epididymal tail.

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: Transverse US images in (a) a 41-year-old man and (b) a 36-year-old man show multiple cysts (arrows), presumed to be ectasia of the rete testis, in the mediastinum testis. Diagnosis was ejaculatory duct obstruction in a and Klinefelter syndrome in b. Note that the testis (arrowheads) is small in volume (1.2 mL).

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: Transverse US images in (a) a 41-year-old man and (b) a 36-year-old man show multiple cysts (arrows), presumed to be ectasia of the rete testis, in the mediastinum testis. Diagnosis was ejaculatory duct obstruction in a and Klinefelter syndrome in b. Note that the testis (arrowheads) is small in volume (1.2 mL).

Scrotal US Abnormalities in Obstructive Azoospermia Compared with Those in Nonobstructive Azoospermia
Our comparison of the scrotal US findings in obstructive and nonobstructive azoospermia is summarized in the Table. Among the US criteria analyzed, abnormalities in the epididymal head, body, and tail were more common in obstructive azoospermia than in nonobstructive azoospermia. The differences in an epididymal abnormality between the two groups were significant (P < .001). An abnormality in the mediastinum testis, however, was encountered without a significant difference in frequency (P > .05). If scrotal US scans were considered abnormal when they showed any of the epididymal abnormalities, sensitivity, specificity, and accuracy for the differentiation of obstructive azoospermia from nonobstructive azoospermia were 82.1% (23 of 28 scrota), 100% (12 of 12 scrota), and 87.5% (35 of 40 scrota), respectively.

	DISCUSSION

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In azoospermic patients, it is important to distinguish nonobstructive azoospermia from obstructive azoospermia because not all men with azoospermia are ideal candidates for intracytoplasmic sperm injection (7). For obstructive azoospermia, surgical correction such as vasoepididymostomy should be considered as initial treatment because it has a lower cost burden per each birth than does intracytoplasmic sperm injection (8), and natural pregnancy initiated with surgical correction may filter some chromosomal or genetic abnormalities. Moreover, epididymal damage that can happen during sperm retrieval could be prevented. In case an intracytoplasmic sperm injection is considered, it is also important to distinguish nonobstructive azoospermia from obstructive azoospermia. In contrast to testicular failure, a genital duct such as the epididymis or seminal vesicle can be used to retrieve sperm in obstructive azoospermia. In addition, only a single small testis biopsy specimen is adequate in obstructive azoospermia, but in nonobstructive azoospermia multiple or larger samplings for sperm harvesting or diagnosis are needed (9,10).

The role of imaging in the evaluation of azoospermia has been somewhat limited. Vasography has been considered the reference standard for the evaluation of the distal genital duct, but its invasiveness and the risk of genital duct scarring have narrowed its clinical use in azoospermia. Instead, transrectal US, which can easily depict the distal genital duct, has become the most popular alternative to vasography because of its noninvasiveness and relatively low cost. Although transrectal US has greatly reduced the need for more invasive open vasography, anatomic abnormalities, except CBAVD, depicted at transrectal US do not have a consistent causal relationship with obstructive azoospermia (11). Moreover, vasography and transrectal US do not cover the whole length of the genital duct, and therefore the proximal genital duct, which might be a blockage site, cannot be evaluated with these modalities.

In the evaluation of male infertility, scrotal US has been traditionally performed only to check nonpalpable varicocele. However, recent advances in US equipment make detailed anatomic evaluation of the proximal genital duct possible and therefore enable scrotal US to play an important role in the evaluation and management of a blockage of the proximal genital duct. In addition, scrotal US may be helpful even if a blockage is present in the distal genital duct, because obstruction in the distal genital duct may lead to pathologic changes in the more proximal genital duct (12).

There have been several reports regarding pathologic changes of the proximal genital duct in obstructive azoospermia. In men, CBAVD is a common condition manifesting as azoospermia. In a series of 11 men with congenital absence of the vas deferens, Jequier et al (13) reported that absence or atrophy of the distal portion of the epididymis was demonstrated in four of the eight men who underwent surgical exploration. Some changes may be also manifest in the epididymis or mediastinum testis. Although there are no specific reports about proximal duct changes linked with isolated absence of the vas deferens, a few reports have described cystic changes associated with cystic fibrosis in the mediastinum testis or epididymis (14,15). In cases of inflammatory-associated obstruction, cystic changes in the rete testis have been described, usually in association with epididymal obstruction (12,16,17). To our knowledge, however, there are no specific reports about the proximal genital duct abnormalities linked specifically with ejaculatory duct obstruction.

The results of our prospective study are limited by the small number of patients, but the results confirm previous reports regarding pathologic changes of the proximal genital duct in the obstructive azoospermia. Although the present study does not include all known causes for azoospermia, which is another limitation of our results, we have shown that it is possible to distinguish obstructive azoospermia from nonobstructive azoospermia by means of scrotal US.

In conclusion, epididymal abnormalities depicted with scrotal US are significantly associated with obstructive azoospermia (P < .001). Testicular volume is higher for obstructive than for nonobstructive azoospermia. Thus, evaluation of the epididymis and testicular volume with scrotal US are important in distinguishing obstructive azoospermia from nonobstructive azoospermia in infertile men.

	ADVANCES IN KNOWLEDGE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

• Scrotal US can directly demonstrate abnormalities in the proximal portion of the genital duct and can also depict secondary changes of the proximal genital duct caused by obstruction in the distal part of the genital duct.
  
• Testicular volume measured at scrotal US is higher for obstructive azoospermia than for nonobstructive azoospermia.
  
• Evaluation of the proximal genital duct and measurement of testicular volume with scrotal US are helpful in distinguishing obstructive azoospermia from nonobstructive azoospermia in infertile men.
  

	FOOTNOTES

 

Abbreviations: CBAVD = congenital bilateral absence of the vas deferens

Author contributions: Guarantors of integrity of entire study, M.H.M., S.H.K.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.H.M., S.H.K., J.Y.C.; clinical studies, M.H.M., S.H.K., J.Y.C., J.T.S.; statistical analysis, M.H.M.; and manuscript editing, M.H.M., S.H.K., J.T.S., Y.K.C.

Authors stated no financial relationship to disclose.

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

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This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2391050272v1 239/1/168    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moon, M. H. Articles by Chun, Y. K. Search for Related Content PubMed PubMed Citation Articles by Moon, M. H. Articles by Chun, Y. K.