Does response to treatment of ejaculatory duct obstruction in infertile men vary with pathology?

FERTILITY AND STERILITY威 VOL. 76, NO. 1, JULY 2001 Copyright ©2001 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.

Does response to treatment of ejaculatory duct obstruction in infertile men vary with pathology? Ates Kadiogˇlu, M.D.,a Selahittin Cayan, M.D.,b Ahmet Tefekli, M.D.,a Irfan Orhan, M.D.,a Gulgun Engin, M.D.,c and Paul J. Turek, M.D.d Medical Faculty of Istanbul, University of Istanbul, Istanbul, and School of Medicine, University of Mersin, Mersin, Turkey; and University of California San Francisco School of Medicine, San Francisco, California

Received August 25, 2000; revised and accepted January 12, 2001. Presented at the 95th American Urological Association Annual Meeting, Atlanta, May 1–5, 2000. Reprint requests: Ates Kadiogˇlu, M.D., Department of Urology, Medical Faculty of Istanbul, University of Istanbul, 34390, Capa, Istanbul, Turkey (FAX: 90-212-23339-24; E-mail: [email protected]) a Department of Urology, Medical Faculty of Istanbul, University of Istanbul. b Department of Urology, University of Mersin, School of Medicine. c Department of Radiology, Medical Faculty of Istanbul, University of Istanbul. d Department of Urology, University of California San Francisco School of Medicine. 0015-0282/01/$20.00 PII S0015-0282(01)01817-9

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Objective: To describe the pathology-specific response to transurethral resection of ejaculatory ducts (TURED) in patients with complete or partial ejaculatory duct obstruction and to evaluate the role of TURED in light of powerful assisted reproductive technologies. Design: Retrospective clinical study. Setting: University hospital. Patient(s): Thirty-eight infertile men with obstruction of the ejaculatory ducts. Intervention(s): Diagnosis by transrectal ultrasonography or magnetic resonance imaging, and treatment with TURED. Main Outcome Measure(s): Changes in semen variables, pregnancy outcomes, and complication rates were analyzed before and after surgery. Result(s): Improvement in semen variables was significantly better in patients with partial obstruction (94%) of ducts than in those with complete obstruction (59%) (P⫽.04). Cystic obstruction, especially midline and eccentric cysts, responded best to TURED. Before surgery, all patients were candidates for IVF/ICSI; after surgery, 32% of azoospermic men and 81% of oligospermic men conceived spontaneously or were referred for IUI instead of IVF/ICSI. Conclusion(s): Ejaculatory duct obstruction due to cysts appears to respond best to TURED. In addition, TURED may decrease the need for IVF/ICSI as primary treatment in many cases. Finally, TURED may allow IVF/ICSI to be performed with ejaculated rather than surgically retrieved sperm. (Fertil Steril威 2001;76: 138 – 42. ©2001 by American Society for Reproductive Medicine.) Key Words: Infertility, ejaculatory duct, obstruction, pathology, transurethral resection, ICSI.

Ejaculatory duct obstruction, either complete or partial, affects 5% of infertile men (1, 2). High-resolution transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI) have been very helpful in the diagnosis of ejaculatory duct problems (3–7). Although ejaculatory duct obstruction is a surgically correctable cause of male infertility, the response to treatment with transurethral resection of ejaculatory duct (TURED) in relation to the presenting pathology of cyst, calcification, stone, or atresia has not been well elucidated (1, 3, 8). Likewise, the role of this treatment in the context of newer assisted reproductive technologies, such as ICSI, has not been well delineated. Low-volume azoospermia and oligoasthenozoospermia, often the presentation of

ejaculatory duct obstruction, qualifies many couples for IVF and ICSI. The power of these technologies to achieve pregnancies has led clinicians to reexamine treatment of male infertility. We sought to further delineate pathologyspecific response to TURED and to determine whether patients could be spared the need to undergo ICSI with surgical treatment of these pathologies.

MATERIALS AND METHODS Patients During a 5-year period, we enrolled 38 men undergoing TURED for ejaculatory duct obstruction. Patients were evaluated by using a

detailed history, complete physical examination, and hormone profiles (FSH and testosterone levels). At least three spermiograms were obtained from each patient. Semen samples were collected and evaluated in accordance with World Health Organization standards (9). The diagnosis of retrograde ejaculation was excluded in all patients with a postejaculate urine analysis. Men with other infertility diagnoses were excluded .

Design and Methods of Evaluation Suspicion of ejaculatory duct obstruction was based on at least one of four findings on semen evaluation: [1] low ejaculate volume (⬍2.0 mL) azoospermia, [2] low ejaculate volume with a sperm concentration ⬍20 ⫻ 106/mL of semen, [3] low ejaculate volume with sperm motility ⬍30%, and [d] low ejaculate volume with a sperm concentration of ⬍20 ⫻ 106/mL and motility ⬍30%. All patients underwent TRUS performed by the same radiologist using a Hitachi scanner ultrasound unit equipped with a 6.5-MHz endorectal probe, as described elsewhere (10). The diagnosis of ejaculatory duct obstruction was confirmed in patients by at least one of the following four findings on TRUS: [1] seminal vesicle dilatation with a transverse diameter ⬎1.5 cm, [2] a dilated ejaculatory duct, [3] calcification or stones in the ejaculatory duct or verumontanum, and [d] presence of a midline or eccentric cyst near the verumontanum (2, 3, 7, 8). Magnetic resonance imaging scans (Siemens 1 Tesla; Medrad, Pittsburgh, PA) were obtained for patients who had equivocal results on TRUS. Several images were obtained by using an endorectal coil. Hyperintense lesions on T2weighted MRI scans were diagnosed as ejaculatory duct cysts. An increase in the width of seminal vesicles on MRI was considered diagnostic of ejaculatory duct obstruction (6).

Surgical Procedure Transurethral surgery was performed by resecting the proximal verumontanum as described by Farley and Barnes (11). A standard 24-French transurethral resectoscope loop was used for resection of the ejaculatory duct. Intraoperative observation of fluid efflux from the ejaculatory ducts after resection and detection of sperm in the bladder irrigation fluid were used to judge the success of the procedure. Electrocauterization was not performed in most cases so as to avoid iatrogenic obstruction; in cases of excessive bleeding, it was used gently. A urethral catheter was placed after the procedure and left in place for 24 hours. All patients received a single dose of broad-spectrum antibiotic before the procedure and continued to take oral antibiotics for 3 days. Ejaculation was started 2 to 4 weeks after the procedure. Telephone interviews were conducted to garner information about pregnancy rates. FERTILITY & STERILITY威

Statistical Analysis Semen analyses were obtained at 1-month intervals until semen variables stabilized after surgery. Statistical analysis was done by using the paired Student t-test to compare semen variables before and after surgery and the ␹2 test to compare proportions. Improvement in semen quality was defined as at least a 50% increase in postoperative sperm concentration or motility.

RESULTS Clinical Characteristics

The mean age of patients was 34.5 ⫾ 4.1 years (range, 26 –51 years). Related symptoms, such as hemospermia (n ⫽ 4), painful ejaculation (n ⫽ 5), and perineal or testicular pain and discomfort (n ⫽ 8), were present in 45% of patients. Physical examination was normal in all but four patients (10%), who had dilated seminal vesicles on rectal examination. Testicular size was normal and the vas deferens was bilaterally palpable in all men. Mean serum hormone levels (FSH and testosterone) were within the normal range in all patients.

Complete ejaculatory duct obstruction was considered in 22 patients (58%) with low-volume (⬍2.0 mL) azoospermia. Among patients with partial ejaculatory duct obstruction, 3 had oligozoospermia (sperm count ⬍20 ⫻ 106 sperm/mL), 3 had asthenozoospermia (motility ⬍30%) ,and 10 had oligoasthenozoospermia (sperm count ⬍20 ⫻ 106 sperm/mL and motility ⬍30%).

Radiologic Findings Midline cysts were diagnosed by TRUS in 12 men (32%). However, midline cysts in the presence of dilated seminal vesicles were observed in only 4 men (10%). Calcifications along the ejaculatory ducts were found in 11 patients (29%), and 6 patients (16%) had both eccentric cysts and dilated seminal vesicles. No patient had dilated ejaculatory duct on TRUS. Nine patients (23%) had no pathognomonic features for ejaculatory duct obstruction. These 9 patients were further evaluated by using MRI, which demonstrated a midline cyst in 3 (8%), eccentric cyst in 2 (5%), and cystic dilatation of seminal vesicles in 4 (10%) patients.

Postoperative Results

Mean duration of follow-up was 26 ⫾ 8.5 months (range, 12– 63 months). Mean ejaculate volume, sperm concentration, and motility before and after surgery in men with partial and complete ejaculatory duct obstruction are shown in Table 1. In both groups, the mean value of ejaculate volume, sperm concentration and percent motility increased significantly after surgery. Outcomes of TURED in men with partial and complete ejaculatory duct obstruction, classified according to TRUS or MRI findings, are shown in Table 2. Overall, a minimum 50% increase in postoperative sperm concentration or mo139

TABLE 1 Preoperative and postoperative seminal variables after transurethral resection of ejaculatory ducts in patients with partial complete ejaculatory duct obstruction. Semen variable Patients with complete ejaculatory duct obstruction (n ⫽ 22) Ejaculate volume (mL) Sperm concentration (⫻106 sperm/mL of semen) Sperm motility (%) Patients with partial ejaculatory duct obstruction (n ⫽ 16) Ejaculate volume (mL) Sperm concentration (⫻ 106 sperm/mL of semen) Sperm motility (%) All patients (n ⫽ 38) Ejaculate volume (mL) Sperm concentration (⫻ 106 sperm/mL of semen) Sperm motility (%)

Before surgery

After surgery

P value

0.8 ⫾ 0.2 0 0

2 ⫾ 1.2 12 ⫾ 11 25 ⫾ 15

.000 .000 .000

1.4 ⫾ 0.7 9.7 ⫾ 6.3 23 ⫾ 19

2.5 ⫾ 1.2 23 ⫾ 10 43 ⫾ 26

.004 .000 .019

1 ⫾ 0.5 4 ⫾ 3.6 9.7 ⫾ 6.5

2.2 ⫾ 1.2 17 ⫾ 12 32 ⫾ 27

.000 .000 .000

Note: Values are means (⫾SD). Kadiogˇlu. Treatment of ejaculatory duct obstruction. Fertil Steril 2001.

prolonged antibiotic and antiinflammatory treatment. One patient developed acute urinary retention after removal of the urethral catheter, which resolved with recatheterization. One patient with partial obstruction became completely azoospermic after surgery. No patient had watery ejaculate or ejaculate that smelled of urine after TURED.

tility was noted in 28 patients (74%). Improvement in sperm variables was observed in 59% (n ⫽ 13) of patients with complete obstruction and in 94% of pathologies (n ⫽ 15) with partial obstruction (P⫽.04). The diseases associated with the best improvement in semen quality were midline cyst (n ⫽ 9), midline cyst and dilated seminal vesicle (n ⫽ 9), and eccentric cyst (n ⫽ 7). The finding of calcifications as a cause of ejaculatory duct obstruction was associated with the lowest rates of successful TURED.

Figure 1 shows pregnancy rates and use of assisted reproductive technologies among patients with ejaculatory duct obstruction. Spontaneous pregnancies were achieved in 5 (13%) cases. Two men with complete obstruction and 3 with partial obstruction initiated spontaneous pregnancy after a mean postoperative follow-up of 10.5 ⫾ 3.5 months. In addition, 15 (40%) patients who were candidates for IVF or ICSI before surgery achieved sufficient postoperative total

Preoperative symptoms, such as hemospermia and painful ejaculation, disappeared after surgery. Five patients (13%) experienced complications. Three patients developed urinary tract infections despite perioperative antibiotic prophylaxis. Two of these patients had recurrent epididymitis requiring

TABLE 2 Outcomes of transurethral resection of ejaculatory ducts pathologic findings on transrectal ultrasonography (TRUS) or magnetic resonance imaging.

Pathology

Patients with complete ejaculatory duct obstruction

Patients with partial ejaculatory duct obstruction

Total

7 5 (71) 4 3 (75) 8 3 (38) 3 2 (67) 22 13 (59)

4 4 (100) 4 4 (100) 3 2 (66) 5 5 (100) 16 15 (94)

11 9 (82) 8 7 (88) 11 5 (45) 8 7 (88) 38 28 (74)

No. with midline cyst No. with improvement (%)a No. with midline cyst and dilated seminal vesicle No. with improvement (%)a No. with calcification along ejaculatory duct No. with improvement (%)a No. with eccentric cyst No. with improvement (%)a Total No. with improvement (%)a a

At least 50% increase in postoperative sperm concentration or motility.

Kadiogˇlu. Treatment of ejaculatory duct obstruction. Fertil Steril 2001.

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Treatment of ejaculatory duct obstruction

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FIGURE 1 Treatment algorithm in patients with ejaculatory duct obstruction. TURED ⫽ transurethral resection of ejaculatory ducts.

obstruction. Successful results of TURED have been reported in patients with low-volume azoospermia and those with oligoasthenozoospermia (3, 8, 11–14). Previous published data have shown improvement of semen variables in 50%– 65% of cases and initiation of spontaneous pregnancy in 20%–29% of cases after TURED (8, 13). In our study, 74% of patients had improvement in postoperative sperm variables after a mean follow-up of 26 months after TURED. Spontaneous pregnancy was initiated in 13% of cases. Our findings further indicate that improvement of semen variables and initiation of spontaneous pregnancy is better in men with partial obstruction than in those with complete obstruction. This difference may be explained by the hypothesis that testicular or seminal biology are less affected by partial obstruction than complete obstruction. In addition, the greatest improvement in semen variables was seen in men with midline cysts and dilated seminal vesicles and those with eccentric cysts. These findings are in agreement with those of Netto et al. (15), who reported seminal improvement in 83% and spontaneous pregnancy in 66% of patients with midline cysts. Likewise, they found lower success rates in patients with calcification or trauma as a cause of ejaculatory duct obstruction (37% had seminal improvement and 12% achieved pregnancy).

Kadiogˇlu. Treatment of ejaculatory duct obstruction. Fertil Steril 2001.

motile sperm counts (⬎5 million) to allow referral for IUI. In vitro fertilization and ICSI was considered in 8 (21%) cases with insufficient postoperative improvement in semen variables (total motile sperm count ⱕ5 million). Men with isolated increases in ejaculate volume (16%) were reevaluated for vasoepididymal obstruction. The remaining 4 patients (10%) did not benefit from surgical treatment and were referred for IVF/ICSI.

DISCUSSION Ejaculatory duct obstruction is a relatively rare but surgically treatable cause of male infertility. Complete ejaculatory duct obstruction is reported in 1% of all infertile men; low-volume ejaculate with low pH in the presence of palpable vas deferens is suggestive of the diagnosis (1–3). In partial ejaculatory duct obstruction, the clinical presentation is highly variable; standard diagnostic criteria have therefore not been well defined (1, 3, 7, 8, 12). Transurethral resection of ejaculatory ducts is the accepted treatment for complete and partial ejaculatory duct FERTILITY & STERILITY威

Transrectal ultrasonography is considered the optimal imaging method for ejaculatory duct obstruction (1– 4, 7, 8, 12, 16). Patients with equivocal findings on TRUS can be further evaluated by using MRI. In our study, MRI detected pathologic lesions characteristic of ejaculatory duct obstruction in all patients with negative results on TRUS. Lesions detected by MRI but missed by TRUS included midline (Mu¨llerian) cysts, eccentric (Wolfian) cysts, and cystic dilatation of the seminal vesicles. However, patients with cystic lesions on MRI did not necessarily have dilated seminal vesicles, as diagnosed by increased organ width. Thus, it may be true that dilatation on MRI is not essential for the diagnosis of ejaculatory duct obstruction, as proposed by Schnall et al. (17). Although MRI can accurately identify cystic lesions and clearly demonstrate the relation between pelvic genital tract organs (5, 6, 17), the cost and difficulty of MRI limits its widespread use (5). Furthermore, MRI is notoriously poor at visualizing stones and calcification (5, 10). Of note, patients with ejaculatory duct obstruction are also candidates for IVF/ICSI. Transurethral resection of ejaculatory ducts can spare some of these patients the need for IVF/ICSI and allow IVF/ICSI to be performed with ejaculated instead of surgically retrieved sperm. In our study, half of the patients who were candidates for IVF/ICSI preoperatively were referred for IUI after TURED. Another 13% of patients conceived spontaneously. Among couples referred for IUI or IVF/ICSI, the outcome of these assisted reproductive cycles is under current study. In conclusion, patients with low-volume azoospermia and 141

oligoasthenozoospermia should be carefully evaluated for ejaculatory duct obstruction. In our study, TURED significantly improved sperm variables in more than two of every three patients. Of the various causes of ejaculatory duct obstruction, cysts appear to respond best to TURED. Use of TURED may decrease the need for IVF/ICSI as a primary treatment in many men who qualify for IVF/ICSI before surgery and may allow IVF/ICSI to be performed with ejaculated rather than surgically retrieved sperm. 1. Schlegel PN. Management of ejaculatory duct obstruction. In: Lipshultz LI, Howards SS (eds). Infertility in the male. St. Louis: Mosby–Year Book, 1997:385–94. 2. Jarow JP. Seminal vesicle aspiration in the management of patients with ejaculatory duct obstruction. J Urol 1994;152:899 –901. 3. Goluboff ET, Stifehnan MD, Fisch H. Ejaculatory duct obstruction in the infertile male. Urology 1995;45:925–31. 4. Jarow JP. Transrectal ultrasonography of infertile men. Fertil Steril 1993;60:1035–9. 5. Weintraub MP, De Mouy E, Hellstrom JGW. Newer modalities in the diagnosis and treatment of ejaculatory duct obstruction. J Urol 1993; 150:1150 – 4. 6. Nguyen HT, Turek PJ. Variability of seminal vesicle size in healthy men measured by magnetic resonance [abstract]. J Urol Suppl 1996; 155:367A. 7. Orhan I, Onur R, Cayan S, Koksal IT, Kadioglu A. Seminal vesicle

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