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17 Ultrasound in Male Infertility
Fig. 17.7 Orchitis: transverse color Doppler sonogram
shows both testes with
abnormally increased blood
fl ow in the symptomatic left
testis
Fig. 17.8 Testicular tumor:
transverse color Doppler
sonogram shows a large,
well-circumscribed
hypoechoic mass with
prominent blood fl ow in the
left testis and both testes with
numerous tiny hyperechoic
foci, characteristic of
microlithiasis. The mass
proved to be a seminoma
217
limited epidemiological data on the impact of
orchitis on overall infertility, previous reports
have demonstrated oligospermia and azoospermia occurring at follow-up among 15–33 % and
8–27 % of males with unilateral epididymoorchitis, respectively [ 84 , 85 ]. Subsequent
pathologic analysis of patients with prior epididymo-orchitis has demonstrated scarring of
the seminiferous tubules involving both the ipsilateral and contralateral testicles with chronic
infl ammatory changes noted [ 84 ].
Mumps orchitis is the most common complication of pubertal and postpubertal mumps and is
reported to occur in 5–37 % of patients with
mumps, with 16–65 % occurring bilaterally [ 86 ].
Among patients with a history of mumps orchitis,
approximately 50 % will demonstrate some
degree of testicular atrophy with one study demonstrating complete atrophy of seminiferous
tubules in 38 % of biopsies obtained [ 24 , 87 , 88 ].
These fi ndings may be persistent, even in the setting of appropriate acute phase treatment [ 88 ].
Testicular Masses
Males presenting with infertility are at increased
risk for both immediate and subsequent development of testicular malignancy (Fig. 17.8 ). The
reported incidence of testicular malignancy in
218
L.W. Trost et al.
infertile males ranges from 0.2 to 1 % and is estimated to be 20–100-fold more common than in the
general population [ 15 , 19 , 77 , 89 – 92 ]. Men with
abnormal semen parameters are also at an increased
risk of testicular malignancy with an incidence
ratio of 1.6 [ 93 ]. Additionally, infertile men con-
tinue to be at risk for malignancy following sterility
with one report of subsequent development of testicular cancer occurring 14 years after initial evaluation [ 78 ]. These fi ndings have led some authors to
advocate for the routine use of ultrasound during
the initial infertility evaluation [ 76 , 77 ].
The increasing utilization and improved resolution of scrotal ultrasonography have additionally resulted in an increased rate of detection of
testicular lesions with series reporting incidental
testicular masses in 1–6 % of infertile patients
[ 77 , 91 , 94 , 95 ]. When the criteria for an inciden-
tal testicular lesion are broadened to include
hypoechoic/hyperechoic regions, 34 % (49/145)
of azoospermic patients are found to have focal
abnormalities, with only one of the 49 cases subsequently found to represent malignancy [ 92 ].
This increased rate of detection has also led to
an altered ratio of benign versus malignant
lesions [ 96 ]. Carmignani and colleagues reported
on a series of patients undergoing scrotal ultrasonography for infertility evaluations as well as
multiple causes (varicoceles, testicular pain) with
benign pathology found at surgical excision in
75–80 % of incidentally discovered testicular
lesions [ 91 , 94 ]. Other groups have reported
higher ratios of malignancies occurring in 50 %
(2/4)–71 % (7/9) of incidental lesions, albeit
these series were comprised of relatively small
numbers [ 77 , 89 ]. When benign fi ndings are
reported on frozen section with later determination of malignancy on fi nal pathology, subsequent orchiectomy specimens were found to have
no residual malignancy detected [ 89 ].
Given the higher rate of incidental, benign
lesions, close observation with repeat physical
examinations and ultrasonography has been proposed for non-palpable testicular lesions, particularly those <1 cm [ 97 ]. Despite the increasing
rate of detection of benign testicular lesions, the
decision as to perform radical excision, testicular
sparing surgery, or active surveillance remains an
area of active debate.
Of interest, testicular ultrasound fi ndings following sperm retrievals including PESA, TESA,
and TESE demonstrate focal abnormalities which
persist in 77 and 54 % of patients at 5 days and
6 months, respectively [ 98 ]. These fi ndings are
not to be misinterpreted as concerning for malignancy in this otherwise at-risk population.
Microlithiasis
Microlithiasis is identifi ed on testicular ultrasonography as hyperechoic regions measuring
3 mm or smaller without defi nitive shadowing
present (Fig. 17.9 ). Among asymptomatic
patients undergoing screening scrotal sonography, testicular microlithiasis is reported in
2.4–6 % of individuals with a higher frequency
of testicular microlithiasis present in infertile
males (10 % vs. 2 % in controls) [ 99 – 101 ].
Despite the known association between testicular
microlithiasis and infertility, Yee and colleagues
reported no differences noted in semen analyses
between infertile males with microlithiasis versus those without microlithiasis [ 100 ].
Microlithiasis has additionally been associated with a relative risk of testicular malignancy
of 21.6, with testicular tumors occurring in
approximately 6 % of patients with microlithiasis
[ 102 , 103 ]. Patients with microlithiasis and uni-
lateral testicular germ cell tumors have an
increased incidence of carcinoma in situ in the
contralateral testicle, with some authors recommending routine biopsy of the contralateral testicle [ 104 , 105 ]. However, subsequent surveillance
of patients with isolated testicular microlithiasis
followed over a period of 7 years has not been
shown to develop malignancy [ 104 ].
Given the increased incidence of testicular
microlithiasis with malignancy and indeterminate clinical relevance of carcinoma in situ, routine surveillance is commonly recommended
with repeat self-testicular exams with or without
serial scrotal ultrasonography [ 102 , 103 ].
Testicular Torsion/Trauma
Scrotal ultrasonography is an excellent imaging
modality for the rapid assessment and triage of
testicular injuries. In the case of testicular trauma,
ultrasonography provides visualization of the
tunica albuginea and assessment of rupture of
17 Ultrasound in Male Infertility
Fig. 17.9 Microlithiasis:
transverse sonogram shows
multiple diffuse hyperechoic
foci with no acoustic
shadowing in both testes
Fig. 17.10 Torsion :
transverse color Doppler
sonogram shows absence of
blood fl ow in the symptomatic
left testis, which is slightly
enlarged and surrounded by a
small hydrocele. Note normal
color fl ow in the left
extratesticular soft tissues
( arrows )
219
seminiferous tubules, scrotal and testicular
hematomas, and incidental testicular lesions
[ 106 ]. In patients with an acute scrotum, Doppler
ultrasonography is able to differentiate between
infectious processes and testicular torsion [ 107 ].
Epididymitis and/or orchitis may present with
various imaging fi ndings including diffuse
hypoechogenicity, enlarged epididymis/testicle,
increased heterogeneity, increased Doppler fl ow,
or straightened spermatic cord. In contrast, early
or partial testicular torsion may present with
venous congestion and preserved arterial infl ow.
Complete torsion is characterized by the absence
of testicular blood fl ow, frequently with a proximal “whirlpool” sign (Fig. 17.10 ). Given the
occasional diffi culty in identifying early ischemic
injuries, alternative imaging techniques including pulse inversion ultrasound may eventually
220
L.W. Trost et al.
offer a superior assessment in cases of acute ischemia [ 108 ].
Multiple studies have examined hormonal and
semen profi les following unilateral testicular
loss. In patients undergoing orchiectomy secondary to testicular trauma, impaired hormonal and
semen characteristics were identifi ed including
decreased sperm density and elevated FSH/LH
compared to fertile controls [ 109 ]. Studies com-
paring outcomes following orchiectomy versus
orchiopexy for acute testicular torsion have
reported varied results. Arap and colleagues
reported decreased sperm counts and morphology with preserved hormonal levels in patients
undergoing either orchiectomy or orchiopexy
while a second study noted decreased inhibin B
levels in both groups, indicating possible persistent subclinical gonadal dysfunction [ 110 , 111 ].
Other studies demonstrate decreased inhibin B
levels, elevated FSH, and impaired sperm density
in patients undergoing orchiectomy compared to
orchiopexy [ 112 , 113 ].
Transrectal Ultrasonography
Transrectal ultrasonography (TRUS) is frequently utilized during the evaluation of male
infertility in cases of low-volume ejaculate, azoospermia on semen analysis, or palpable asymmetry on digital rectal exam in order to rule out
ejaculatory duct obstruction or to evaluate for the
presence/absence of seminal vesicles. TRUS
identifi es pathologic fi ndings (hypoplastic/atrophic SVs, vasal agenesis, among others) in 75 %
of azoospermic males, compared to no pathology
in 65 % of non-azoospermic males [ 114 ].
TRUS is frequently performed with a 6.5–
7.5 MHz probe with the bladder partially fi lled.
Patients are placed in the lateral decubitus and
knee-to-chest position and may alternatively be
placed in the prone jackknife or dorsolithotomy
positions depending on the surgical scenario.
Prostate
Transrectal ultrasonography is an excellent
modality to assess obstructive etiologies of
infertility including prostatic cysts and ejaculatory duct obstruction (EDO) and may be used as
an adjunctive measure in cases of suspected prostatic infections or abscesses. Infertile males with
EDO or prostatic cysts may present with varied
accompanying symptoms including perineal
pain, low-volume ejaculate, hematospermia,
painful ejaculation, or epididymal tenderness,
among others [ 6 , 23 , 24 ].
Cysts
Prostatic cysts are frequently identifi ed in cases
of obstructive azoospermia/severe low-volume
oligospermia and may be further classifi ed based
on location including peripheral/parenchymal,
midline, or paramedian. Midline cysts are typically of a Mullerian embryologic origin and usually do not contain sperm, while paramedian
cysts are typically of Wolffi an duct origin and
may contain sperm upon aspiration [ 115 , 116 ].
Midline cysts may further be differentiated into
utricular cysts which are typically 15 mm in
diameter or true Mullerian cysts which may be
larger and extend posteriorly beyond the prostatic
base (Fig. 17.11 ). Peripheral cysts may be
acquired following infectious processes or rarely
may represent benign or malignant processes
including multilocular cystadenoma/cystadenocarcinoma [ 117 , 118 ].
Ejaculatory Duct Obstruction
The ejaculatory duct is minimally visualized on
ultrasonography in the absence of obstruction
and enters the urethra at the level of the verumontanum with standard lengths of approximately
4–8 mm and a lumen of 2 mm. In contrast, ejaculatory duct obstruction (EDO) is often well demonstrated in the sagittal view and is commonly
associated with dilation of the ejaculatory duct,
seminal vesicles, and occasional ejaculatory ductal calcifi cations.
Ejaculatory duct obstruction may occur secondary to congenital processes including compression by prostatic cysts or ejaculatory duct
atresia/stenosis or may be acquired from infections (UTI, sexually transmitted diseases, tuberculosis), infl ammatory conditions, traumatic
strictures, or stone formation or following prior
surgical procedures (transurethral resection of
17 Ultrasound in Male Infertility
a
a
221
b
Fig. 17.11 Mullerian duct cyst: sagittal T1-weighted,
post-contrast ( a ), and coronal T2-weighted ( b ) MR
images show a midline, large Mullerian duct cyst ( arrows )
arising from the verumontanum and extending above the
prostate ( p ). The cyst does not enhance but has high signal
intensity on the T1-weighted image because of hemorrhagic or proteinaceous content
the prostate, exstrophy repair, colorectal surgery)
[ 119 – 122 ] (Fig. 17.12 ). Partial EDO may result
from any of the above etiologies and has a variable presentation including low volume with varied sperm densities/total sperm on semen analysis
and dilation of one or both of the SVs [ 123 , 124 ].
Although TRUS fi ndings may suggest EDO,
confi rmatory tests are commonly required given
the relatively low specifi city of TRUS alone. In
males with azoospermia/severe oligospermia
suspected of having EDO, TRUS with concurrent
SV aspiration demonstrating the presence of
sperm (common defi nition requiring three or
more per high power fi eld) confi rmed obstruction
in 49.1 % of cases [ 114 , 125 – 127 ]. Similarly,
Purohit and colleagues compared adjunctive testing including chromotubation, SV aspiration, and
seminal vesiculography with confi rmation of
b
Fig. 17.12 Stone in dilated ejaculatory duct: transverse
( a ) and longitudinal ( b ) transrectal sonograms show a
very small hyperechogenic stone ( arrows ) in the dilated
right ejaculatory duct
EDO in 52, 48, and 36 % of cases, respectively
[ 128 ]. An additional measure which is less com-
monly utilized includes ejaculatory ductal
manometry which identifi es higher opening pressures in men with EDO compared to fertile controls [ 129 ].
The treatment of EDO is frequently performed in combination with TRUS to confi rm
treatment success and assist in localization or
extent of obstruction where indicated. Isolated
cysts resulting in compression of the ejaculatory
duct may be treated with aspiration alone when
not in communication with the ejaculatory system or with transurethral resection of the ejaculatory duct (TURED) when communication
exists [ 120 , 130 ]. Results of TURED for com-
plete EDO demonstrate improved semen quality
in 50–92 % of patients with complete EDO with
subsequent spontaneous (without need for ART)
paternity rates of 13–29 % [ 131 – 135 ]. An
alternative therapy for the treatment of EDO
222
L.W. Trost et al.
includes ejaculatory ductal dilation utilizing
seminal vesicoscopy, with one study demonstrating equal effi cacy and fewer complications compared to TURED [ 136 ].
Calcifi cations of the prostate are commonly
visualized on transrectal ultrasonography and are
of unlikely signifi cance in regards to infertility.
Increasing calcifi cations are associated with age
and are present in 23 % of asymptomatic males
aged 20–29 versus 83 % in males 60–69 years
old [ 137 ].
Seminal Vesicles
The SVs are clearly visualized on TRUS cephalad to the prostate and posterior to the bladder
and may result in decreases to semen volume,
pH, and fructose concentration when abnormalities are present. Although there is variability in
reported standard SV lengths, normal, hypoplastic, and atrophic are commonly classifi ed as
occurring at >24, 17–24, and <17 mm, respectively, without signifi cant change following ejaculation [ 137 – 139 ]
Dilation of the SVs resulting from mechanical
obstruction, particularly when >15 mm, is most
commonly associated with EDO as described
previously. Dilation may also be seen in patients
with adult polycystic disease and infertility, ipsilateral upper urinary tract agenesis (Zinner syndrome), or diabetes mellitus and is felt to be
secondary in these cases to SV hypotonicity
rather than anatomic obstruction [ 140 – 142 ].
Absence of the SVs is associated with cystic
fi brosis and unilateral/bilateral absence of the vas
deferens as well as renal anomalies including
renal agenesis, ectopia, and horseshoe, among
others [ 49 , 51 , 54 , 55 ]. Infections of the seminal
vesicles may also be visualized on ultrasound and
have been reported to impact fertility with
improved semen parameters following antibiotic
therapy [ 143 ].
ARTs. Several studies have examined the use of
power Doppler at the time of TESE to identify
regions with increased sperm density to improve
the likelihood of sperm retrieval.
Herwig and colleagues reported on the use of
a laser Doppler scanner to determine perfusion
rates and noted higher sperm quality and quantity
based on underlying tissue perfusion. In patients
with at least 70 tissue perfusion units (TPU),
72.3 % of biopsies identifi ed progressive sperm
compared to 13.3 % among those with ten or
fewer TPUs [ 65 , 144 ]. A similar study performed
in patients with nonobstructive azoospermia
demonstrated successful sperm extractions in 38
and 14 % of patients with subjective good versus
poor vascularity, respectively [ 145 ]. A more
recent Cochrane review evaluating the effi cacy
of various techniques for sperm aspiration demonstrated no statistically signifi cant improvement
in ultrasound-guided testicular sperm aspiration
versus aspirations performed without ultrasound
[ 146 ]. It is not clear, however, how these tech-
niques compare to the results reported by Herwig
and colleagues, and therefore the role for ultrasound at the time of sperm extraction remains
unclear.
Further techniques to enhance extraction of
sperm at the time of TESE are being developed
with Ramkumar and colleagues recently reporting their initial experience with microdissection
probe-TESE (MP-TESE) [ 147 ]. The procedure
utilizes a microfabricated silicon microprobe
with an ultrasonic horn actuator and strain gauges
to detect tissue interface boundaries between
seminiferous tubules. This reportedly improves
size discrimination of seminiferous tubules with
the average diameter of sperm containing tubules
noted to be 41.2 +/− 1.6 μm per report. Although
this technology reports intriguing fi ndings, it has
yet to be validated by other groups and remains
experimental at the present time.
Assisted Reproductive Techniques
In addition to the initial evaluation of the infertile
male, ultrasound has been increasingly utilized in
the performance of sperm retrieval for use in
Conclusion
Ultrasonography, including adjunctive tech-
niques of power and duplex Doppler, is
increasingly utilized in the evaluation and
management of male-factor infertility. Scrotal
and transrectal ultrasonographies provide
17 Ultrasound in Male Infertility
223
both anatomic and functional information to
assist in identifying underlying etiologies for
infertility including infectious processes and
varicoceles as well as differentiating between
obstructive (EDO, epididymal obstruction,
absence of the vas deferens) and nonobstructive causes. Ultrasonography may additionally
detect associated fi ndings including testicular/
paratesticular lesions, upper tract renal anomalies, testicular microlithiasis, hydroceles,
and cysts. Although ultrasound currently has
a limited role with ARTs, an emerging body
of investigative literature suggests that its use
at the time of TESE may enhance the yield of
sperm obtained and therefore improve overall
outcomes. As ultrasound technology continues to improve, it will likely play an increasingly prominent role in the evaluation and
treatment of male-factor infertility.
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