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
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.