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Male accessory gland infection and subfertility: a diagnostic challenge
Trum, J.W.
Publication date
1999
Link to publication
Citation for published version (APA):
Trum, J. W. (1999). Male accessory gland infection and subfertility: a diagnostic challenge.
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Chapter
J W Trum, FM Gubler, R Laan, F van der Veen.
Abstract
Three non-invasive methods for the detection of a varicocele were evaluated in 63 men presenting with infertility. Physical examination, Varicoscreen contact thermography and colour Doppler ultrasound were compared with spermatic venography as reference strate-gy. Physical examination had a sensitivity of 71 %. Whether the non-palpable varicoceles are all subclinical is questionable since the specificity of physical examination was 69%. Varicoscreen proved to be quick, easy and cheap but of no clinical value (sensitivity 97%, specificity 9%). Colour Doppler ultrasound using strict criteria was a good diagnostic tool (sensitivity 97%, specificity 94%). No imaging difference was seen with colour Doppler ultrasound among clinical and subclinical varicoceles. Since the debate on treating all degrees of varicoceles is ongoing, we suggest that Doppler sonography should be a routine examination in infertile men.
Introduction
The prevalence of palpable varicocele is presumed to be higher among infertile men (21-41%) than in the general male population (4.4-22.6%) (Saypol, 1981). Some authors think a varicocele to be an etiological factor in male infertility (Nagler and Zippe, 1991 ; Takihara et al.,1991). A varicocele is present in a significantly higher percentage of men with secondary (81%) as compared with primary infertility (35%) (Gorelick and Goldstein, 1993). Gorelick and Goldstein (1993) state that the detrimental effect of a varicocele on spermatogenesis is a progressive phenomenon and that it is a matter of time before testicular damage becomes clinically evident. This explanation is questionable, since it may be simply a sign of aging. Subclinical varicocele is defined as reflux in the internal spermatic vein without palpable distention of the pampiniform plexus (Comhaire et al., 1976). Published data suggest that subclinical varicocele is present in 24-83% of infertile men (Comhaire et at, 1976; Hirsh et ai, 1980; Dale McLure and Hricak, 1986). Treatment of primary varicocele has been the subject of much debate. When the results of treatment of patients with subclinical varicocele are compared with those of patients with clinical varicocele there seem to be no notable differences (Dhabuwala et ai,\992; Marsman and Schats, 1994). Literature data covering 5471 surgically treated patients show pregnancy rates of 0-50% with an average of 36% (Mordel ^^/.,1990). None of the reviewed studies, however, was performed according to the strict criteria of a randomized controlled clinical trial. One randomized clinical trial comparing different treatments of varicocele showed surgical ligation and radiological embolization to be equally effective in terms of pregnancies following treatment (Nieschlag et al., 1993). In a recently published randomized clinical trial no significant difference in pregnancy rate between occlusion of the vena spermatica and counseling was seen; however, the authors emphasized the need for further controlled studies (Nieschlag et al., 1995).
Selection of patients with both clinical and subclinical varicoceles is mandatory before such a study can be carried out. Various non-invasive methods for diagnosing a varicocele have been described. Contact thermography using a thermo-vision infra red camera is a reliable diagnostic test with a sensitivity of 84-98% and a specificity of 81-100% [World Health Organization (WHO), 1985; Hamm et al., 1986]. As an alternative to the infra red came-ra an easier, quicker and cheaper method using liquid crystal contact colour thermo-gcame-ra- thermo-gra-phy was developed. The test had a sensitivity of 100% and a specificity of 50%, but the sample size was too small to draw firm conclusions (Pochaczevsky et ai, 1986). Another larger study concluded that contact thermography had a sensitivity of only 20% and the use was limited to quantification of a clinical varicocele (Basile-Fasole et ai, 1986). Reports on colour Doppler scrotal ultrasound describe varying results; some found a high sensitivity and specificity up to 95% (Gonda et ai, 1987; Fobbe et al, 1989), one reported a high sensitivity of 9 3 % but a specificity of only 3 3 % (Petros et al, 1991) and in one study both sensitivity and specificity were low (Eskew et al, 1993). This may in part be explained by varying degrees of skillfulness of the examiners.
In view of these discrepancies, three non-invasive methods for the detection of a varicocele were evaluated in our institute. We compared liquid crystal contact colour ther-mography (Varicoscreen®), colour Doppler ultrasound as well as physical examination, with spermatic venography as reference strategy.
Materials and methods
Male partners of couples with at least 12 months' infertility who had abnormal semen ana-lyses according to the W H O guidelines (WHO, 1987) were included in the study. The study was approved by the ethics committee and all patients gave informed consent prior to examination. All men were given a general physical and genital examination by the first author, resident in obstetrics and gynecology with a longstanding experience in this field. The scrotal contents were examined with patients in standing position. Volume, position and consistency of testes and epididymes as well as presence of the vasa deferentia were noted. Palpation of the pampiniform plexus was done with and without the patient per-forming a Valsalva manoeuvre. Direct visible varicoceles were graded class III. Direct pal-pable varicoceles were graded class II. Varicoceles only palpal-pable during Valsalva manoeu-vre were graded class I. Men with Klinefelter's syndrome, inflammation or infection of the scrotal and/or inguinal skin, or elevated follicular stimulating hormone (FSH) and/or thy-roid stimulating hormone (TSH) were excluded. All men underwent Varicoscreen ther-mography performed by the same physician. Therther-mography was performed using a flexi-ble thermostrip Varicoscreen (Amsaten, De Pinte, Belgium) containing heat sensitive liquid crystals calibrated at different temperatures varying from 31.3 to 35.3°C. The patient had to stand for 5 min with the lower part of his body uncovered to cool the scro-tum in a room where the temperature did not exceed 22°C. The Varicoscreen was applied to the scrotum with the patient standing. The test was considered negative when the tem-perature of the skin was symmetrical and did not exceed 32.5°C. The test was positive when there was a uni- or bilateral colour change corresponding to temperatures of 32.8°C or higher Because the purpose of each non-invasive screening method was to select patients in whom a varicocele was suspected, we considered all cases with bilateral
temperature rise as true positives if venography demonstrated at least a unilateral (left or right sided) varicocele.
Colour Doppler scrotal ultrasound was carried out by the second author, a skilled radiologist, and was performed using a 7.5 MHz high-resolution linear array transducer (Acuson, Mountain View, California) with pulsed and colour Doppler capabilities. The patient was examined supine and the scrotal contents on both sides were visualized. On gray-scale sonography the presence of any paratesticular anechoic, tortuous tubular struc-tures, i.e. widened spermatic veins, was noted. On colour Doppler ultrasound scans visu-alization of augmentation of venous flow during a Valsalva manoeuvre was noted.
Doppler samples of the spermatic vein were obtained during Valsalva maneuvers and while breathing normally. Reflux, whether Valsalva-induced or spontaneous, defined as caudate flow in the internal spermatic vein, was considered abnormal if it lasted longer than 1 s.
In this study we used pathological reflux as the only diagnostic criterion for a vari-cocele. Patients without reflux, or with Valsalva- induced reflux for a time period <1 s were considered normal. Patients showing reflux >1 s were considered to have a varicocele. After the above-mentioned diagnostic tests, all patients underwent internal spermatic venography using the Seldinger technique through the right femoral vein. Both the left and right renal vein were catheterized, and contrast material was infused while the patient performed the Valsalva manoeuvre in the upright position. Retrograde flow of contrast material, through the internal spermatic vein, toward the testis was the venographic crite-rion for the diagnosis of a varicocele. Clinicians were blinded for the results of the diffe-rent diagnostic tests.
The results of the comparison of the various diagnostic tests are expressed in terms of sen-sitivity, specificity, and likelihood ratios.
Sensitivity is defined as a true positive test result. Specificity is defined as a true negative test result. The likelihood ratio of a positive test is the sensitivity divided by (1-specifici-ty). The likelihood ratio of a negative test is (1-sensitivity) divided by the specificity.
Results
Out of 63 subjects included in the study a varicocele was determined by spermatic veno-graphy in 31 of them, correspond-ing to a prevalence of 49%. A left-sided varicocele was seen in 26 cases (84%), a right-sided varicocele in two cases (6%) and a bilateral varicocele in three cases (10%).
Table I shows the results of clinical palpation compared with presence or absence of reflux with retrograde venography. Sensitivity of clinical examination was 7 1 % [95% confidence limit (CI) 0.52-0.86] and specificity 69% (95% CI 0.50-0.84). In nine cases a varicocele was present with venography but not demonstrated clinically and considered subclinical. In 10 cases clinical findings were false positive (left-sided seven, right-sided two, bilateral one).
Table I. Accuracy of physical examination, compared with presence or absence of reflux with retrograde venography
Physical Venography Examination
Reflux present Reflux absent Totaal
IDistention present 22 10 32
Distention absent 9 22 31
Total 31 32 6
CI= confidence interval.
Sensitivity 7 1 % (95% CI 0.52-0.86); specificity 69% (95% CI 0.50-0.84); likelihood ratio positive test 2.3 (95% CI 1.3-4.0);
Table II shows the results of Varicoscreen compared with spermatic venography. Sensitivity of Varicoscreen was 97% (95% CI 0.83-1.0), specificity 9% (95% CI 0.02-0.25). In 54 cases there was a bilateral temperature rise >32.8°C. In four cases the tempe-rature rise was on the left side only and in one case on the right side only.
Table II Accuracy of varicoscreen, compared with presence or absence of reflux with retrograde venography
Varicoscreen Venography
Reflux present Reflux absent Total
Temperature 30 29 59 >32.8°C Temperature 1 3 4 <32.8°C Total 31 32 63 Sensitivity 9 7 % (95% CI 0.83-1.0); specificity 9% (95% CI 0.02-0.25); likelihood ratio positive test 1.1 (95% CI 0.94-1.2);
likelihood ratio negative test 0.33 (95% CI 0.04-3.1).
Table III shows the results of colour Doppler ultrasound compared with spermatic veno-graphy. Sensitivity of colour Doppler ultrasound was 97% (95% CI 0.83-1.0) and specifi-city was 94% (95% CI 0.79-0.99). There was one false negative case where a bilateral vari-cocele demonstrated with venography was missed by ultrasound. In two false positive cases, one bilateral and one left-sided varicocele were suspected sono-graphically but not confirmed with venography. In one case a bilateral varicocele was suspected sonographi-cally while only a left-sided varicocele was seen with venography. This case was recorded as true positive.
Table III Accuracy of colour Doppler ultrasound, compared with presence or absence of reflux with retrograde venography
Colour Doppler Venography Ultrasound
Reflux present Reflux absent Total
Reflux present 30 2 32
Reflux absent 1 30 31
Total 31 32 63
Sensitivity 9 7 % (95% CI 0.83-1.0); specificity 94% (95% CI 0.79-0.99); likelihood ratio positive test 16 (95% CI 4.0-59);
likelihood ratio negative test 0.03 (95% CI 0.005-0.24).
Discussion
In the diagnosis of varicocele, spermatic venography is generally considered the reference strategy. It is an invasive technique offering prompt treatment in case a varicocele is pre-sent. The prevalence of varicocele in - 4 0 % of an infertility population implies that large numbers of patients might be submitted to this invasive diagnostic procedure. For this reason, various non-invasive diagnostic tests have been developed. We compared three non-invasive tests; physical examination, Varicoscreen and colour Doppler ultrasound using strict criteria, with the spermatic venography. Our results show that physical exami nation has a sensitivity of 7 1 % (95% CI 0.52-0.86) and a specificity of 69% (95% CI 0.50-0.84).
A low sensitivity could be explained by the presence of subclinical varicoceles. These are depicted with venography but not palpated on physical examination. In our study this occurred in 29% of the cases. Reviewing the literature comparing results of venography with physical examination, the presence of subclinical varicoceles varied from 24 to 50% (Comhaire et al., 1976; Tremblay et al., 1980; W H O , 1985; Basile-Fasole et al., 1986; Pochaczevsky et al., 1986; Petros et al, 1991).
In the same studies the false positive rate, i.e. a varicocele palpated on physical examina-tion but not demonstrated with venography, varied from 24 to 60% and in only one study was as low as 5% (Comhaire et ai, 1976). In our study the false positive rate was 3 1 % . It is impossible to consider all false negative findings on palpation to be subclin-ical varicoce-les, without taking into account the high number of false positive findings. In view of these results, we think that the existence of a subclinical varicocele is questionable. Palpation of the pampiniform plexus is therefore not a good screening test.
The Varicoscreen (liquid crystal contact thermo-graphy) was used, conforming to the instruc- tions for use, and had a sensitivity of 97% (95% CI 0.83-1.0) but a specificity of only 9% (95% CI 0.02-0.25). A specificity of 9% means that almost all subjects have to undergo a spermatic venography. Varicoscreen as a screening method is therefore of no value whatsoever.
Colour Doppler ultrasound proved to be a good screening method with a sensiti-vity of 97% (95% CI 0.83-1.0) and a specificity of 94% (95% CI 0.79-0.99), providing our criterion of pathological reflux for the diagnosis of a varicocele was used as described in an earlier report (Dol et ai, 1993). With an accuracy of 9 5 % we accomplished better results than previous studies (Gonda et al., 1987; Fobbe et al., 1989; Petros et al., 1991; Eskew et al., 1993).
We suggest that all infertility patients undergo a Doppler sonography. Those presenting with a varicocele could be randomized for a clinical trial comparing the results of treat-ment of varicocele versus no treattreat-ment.
Acknowledgement
We thank B.W.J. Mol of the Department of Clinical Epidemiology, Academic Medical Center, for his assistance in producing the tables.
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