Abstract
Objectives—Sonography is a noninvasive, office-based
diagnostic tool often used for evaluation of subfertile men. Previous studies
have suggested that a resistive index (RI) greater than 0.6 is associated with
impaired spermatogenesis. We sought to validate this threshold in a urologic
patient population presenting for infertility evaluation.
Methods—We retrospectively reviewed 99 consecutive patients seen for
nonobstructive male infertility at our institution. Patient demographics, semen
analysis parameters, hormone profiles, lipid profiles, and penile and scrotal
sonographic measurements were recorded. The RI was calculated from measurements
of the peak systolic velocity and end-diastolic velocity. Ninety-one patients
fit the inclusion criteria and were subsequently divided into 2 groups based on
RI: group 1 with RI values of 0.6 or less (n = 49) and group 2 with RI values
greater than 0.6 (n = 42).
Results—Variables that were significantly different between the groups included
age, total sperm count, percent motile sperm, total motile sperm,
follicle-stimulating hormone, high-density lipoprotein, and testis volume. On
the other hand, body mass index, forward progression, World Health Organization
score, total testosterone, free testosterone, estradiol, total cholesterol,
low-density lipoprotein, and triglycerides were not significantly different
between the groups. A receiver operating characteristic curve revealed an area
under the curve of 0.64 (confidence interval, 0.52–0.75; P = .025). At the threshold of
greater than 0.6, the RI had specificity of 63.27% and a 1.56 likelihood ratio
to predict total motile sperm less than 20 × 106 at spermatogenesis.
Conclusions—An intratesticular RI greater than 0.6 is
associated with impaired spermatogenesis. This finding supports the use of
testicular spectral Doppler sonography as a noninvasive tool for evaluation of
testicular function
Discussion
The RI is calculated from
measurements of the PSV and EDV. However, the PSV and EDV are dependent on the
angle of incidence given by the Doppler formula. The Doppler angle is the angle
of incidence between the ultrasound beam and the estimated flow direction.
Doppler sonography accurately measures velocity (speed and direction of the
movement) only at Doppler angles of 0° and 180°. Angles greater than 60°
produce too large of an error in velocity and should not be used. Therefore,
variation in the angle of incidence substantially influences the PSV and EDV.
The RI, in contrast, is an angle- and operator-independent ratio, making it a
reliable indicator. We used the average RI from both testes as an indicator,
assuming that both testes contribute equally to semen parameters in
spermatogenesis.
The standard RI of the testes
was categorized in several animal studies. Carrillo et al11 examined 5 dogs over a 6-month period to
determine that PSV, EDV, and RI measurements remained stable. Tarhan et al12 showed that the RI did not change in the
contralateral artery after unilateral testicular torsion in a study of 24
canines, suggesting that unilateral testicular torsion does not alter
contralateral testicular blood flow. Pozor and McDonnell13 evaluated 52 stallions to determine
reference values for the PSV, EDV, and RI in nonpathogenic testes and found
that obtaining the RI was feasible and that RI measurements for left and right
testes were similar.
The testicular arterial RI
has also has been studied for its predictive values in testicular disease. Jee
et al14 studied the RI in scrotal inflammatory
disease. They found that the RI could provide a diagnostic criterion for
scrotal inflammatory disease if the values for the intratesticular and
epididymal arteries were less than 0.5 and less than 0.7, respectively. Lefort
et al15 studied the RI in 5 patients with testicular
infarction caused by epididymo-orchitis. They found that an elevated RI can be
suggestive of ischemia.
Further studies have examined
the role of the RI in testicular microcirculation. Unsal et al16 examined RI values of 49 healthy patients.
Fifteen were classified by sonography as having left-sided varicoceles and were
compared to the other group of 34. The RI values were found to be significantly
higher in the varicocele group compared to the control group (0.68 versus 0.64,
respectively; P < .05).
The potential alteration of
the RI in dyspermia has been investigated in 2 studies.5,6 Biagiotti et al5 assessed whether sonographic values such as
the PSV, EDV, and RI may be useful in distinguishing the various causes of
dyspermia compared to FSH and testicular volume. They recruited 161 patients: 9
with obstructive azoospermia, 20 with nonobstructive azoospermia, 17 with
oligoasthenospermia, 38 with undetermined oligoasthenospermia, 19 with male
accessory gland inflammation, 11 with clinical varicoceles, 32 with normal
sperm analysis results plus recent paternity, and 15 with normal sperm analysis
results plus recent paternity and varicoceles. They found that only the RI and
PSV were correlated with the sperm production rate score, whereas FSH,
testicular volume, and the EDV were not. In our study, we found that FSH does
correlate with total motile sperm, whereas the PSV does not. The PSV is limited
by its angle-dependent characteristic. Follicle-stimulating hormone has been
shown to correlate with sperm production in previous studies.17,18
Pinggera et al6 also examined whether the RI can be used to
predict dyspermia. They recruited 160 patients and divided them into 2 groups
of 80. One group had mild oligoasthenozoospermia on semen analysis, whereas the
control group had normal semen analysis results as well as paternity within 14
months of recruitment. The control group had a mean RI of 0.54 ± 0.05, whereas
the cohort had a mean RI of 0.68 ± 0.06. The upper RI limit for a patient with
normal semen analysis results was 0.6. They concluded that an RI greater than
0.6 may be indicative of a pathologic sperm count in urologic patients.
Therefore, the objective in our study was to validate whether this conclusion
was true in a urologic population presenting for a subfertility or infertility
workup. We also sought to determine whether a lower RI threshold can be
associated with impaired spermatogenesis.
When comparing the groups
with an RI greater than 0.6 and an RI of 0.6 or less, we found a significant
difference in total motile sperm (P < .01). This finding
confirms the hypothesis by Pinggera et al6 that an RI greater than 0.6 is associated
with dyspermia. Furthermore, we found that at an RI greater than 0.6, the
sensitivity for total motile sperm less than 20 × 106 was 57.14%, and specificity
was 63.27%, with a 1.56 likelihood ratio. An RI of 0.56 or greater was also
significantly associated with lower total motile sperm (P = .04). At that level, the
sensitivity for total motile sperm less than 20 × 106 was 69.05%, and specificity was
46.94%, with a likelihood ratio of 1.3.
Patients with obstructive
azoospermia were excluded from the study, since we do not know the effect of
tubal obstruction on the RI, and we wanted to examine the relationship between
the RI and semen analysis. However, it was noted that in patients with
nonobstructive azoospermia, the average Johnsen score was 2.5, and the average
RI was 0.63. This RI was higher than the RI recorded for the excluded patients
from our study who had obstructive azoospermia. Their collective average RI was
0.5, and their average Johnsen score was 10. Additional study is needed to
determine whether this observation of a higher RI in nonobstructive azoospermia
is valid, whether the RI varies in testes with nonobstructive azoospermia, and
whether the RI can be used to identify localized pockets of spermatogenesis.
The explanation behind the
association of testicular blood flow and spermatogenesis has yet to be fully
elucidated. Testicular arteries are targets for androgens,19 and a study by Jezek et al20 showed that the testicular blood vessels in
hyalinized human testes had an enlarged endothelial layer. More research is
needed to clarify whether the impaired testicular microcirculation as reflected
by an elevated RI is secondary to systemically impaired vascular functioning or
a consequence of decreased testicular function.
A correlation of the RI with
testicular biopsy is needed to state that an altered RI identifies
spermatogenic dysfunction. Nonetheless, spectral Doppler analysis of the
subfertile man has several present and potential clinical applications.
Presently, available studies suggest that the RI should be used together with
semen analysis and hormonal studies as part of the clinical evaluation of the
subfertile man. It is a direct method of evaluating intratesticular blood flow
and, as suggested by this and prior articles, yields reproducible data.
Spectral Doppler sonography is a noninvasive technique that adds unique
information about the intratesticular vasculature that can guide the physician
in counseling the subfertile couple. Future studies will define the association
of spectral Doppler findings and spermatogenesis as well as determine the
spectral Doppler changes occurring with medical and/or surgical therapy and, by
extension, spermatogenesis.
In conclusion, an
intratesticular RI greater than 0.6 is associated with decreased total motile
sperm, decreased testicular size, and increased FSH, supporting its use as an
independent indicator of testicular function. Although further correlation with
testis biopsy is needed, our data support the use of testicular sonography, and
in particular spectral Doppler imaging, as a noninvasive tool for evaluation of
testicular function in the subfertile man.