Ejaculatory duct obstruction in subfertile males: analysis of 87 patients

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1 FERTILITY AND STERILITY Copyright o 1991 The American Fertility Society Vol. 56, No.4, October 1991 Printed on acid-free paper in U.S.A. Ejaculatory duct obstruction in subfertile males: analysis of 87 patients John P. Pryor, M.S. William F. Hendry, Ch.M. Institute of Urology, London, United Kingdom Objective: To study the causes, presentation, and treatment of ejaculatory duct obstruction in subfertile males. Design: Collaborative retrospective study of clinical experience collected by two urologists over a 15-year period. Setting: National Health Service and Private Care Hospitals. Patients, Participants: Subfertile males with azoospermia (n = 67), very severe oligozoospermia (n = 17), oligozoospermia (n = 1), or normal sperm concentration (n = 2) in small volume ejaculates with acid ph and little or no fructose. Interventions: Exploration of scrotum with vasogram and testicular biopsy, plus reconstruction if possible. Main Outcome Measures: Follow-up seminal analysis and occurrence of pregnancy in female partners. Results: The causes were: miillerian duct cyst (n = 17); wolffian duct malformation (n = 19); previous surgical trauma (e.g., imperforate anus) (n = 15); previous genital infection (n = 19); tuberculosis (n = 8); megavesicles (pathological dilatation of vesicles and ampullae of unknown cause) (n = 8); and carcinoma of prostate (n = 1). After incision of Mullerian duct cysts, five pregnancies were produced. Five pregnancies occurred in the other groups using a variety of surgical techniques. Conclusions: Routine vasography has shown that ejaculatory duct obstruction is not as rare as previously thought. The diagnosis should not be missed because the condition is simple to correct surgically in certain cases. Fertil Steril 56:725, 1991 The ejaculatory ducts are formed by the confluence of the vasa deferentia and the ducts of the seminal vesicles. They pass for 1 to 2 em downward and forward through the prostate gland, converging as they approach their termination at the verumontanum. The close proximity of the two ducts and their narrow caliber mean that a single local lesion in this area may produce bilateral obstruction. Situated at the crossroads of genital differentiation, they may be affected by congenital malformation; connected to the urethra, genital infection can lead to stricture; rectal surgery may damage the ducts, Received November 26, 1990; revised and accepted June 18, Reprint requests: William F. Hendry, Ch.M., 149 Harley Street, London WIN 2DE, United Kingdom. Vol. 56, No.4, October 1991 and prostatic disease can narrow them. Such obstructions are rare and usually the subject of single case reports. Some relate to problems such as pain on ejaculation or hemospermia, others to dysuria or difficulty with defecation, and few contain reports of successful restoration of fertility. The diagnosis of ejaculatory duct obstruction may be suspected on clinical grounds from the characteristic seminal analysis. The finding of a small volume of acid semen, which does not contain fructose, in a patient in whom the vasa are palpable is pathognomic. However, the typical clinical picture may be complicated by the obstruction being unilateral, partial, or functional. The diagnosis must, therefore, be confirmed by vasography, which revealed ejaculatory duct obstruction in 4.8% of 370 azoospermic men undergoing scrotal exploration. 1 In this report, Pryor and Hendry Ejaculatory duct obstruction 725

2 we have analyzed our experience of ejaculatory duct obstruction and reviewed the relevant literature. Patients MATERIALS AND METHODS Ejaculatory duct obstruction was diagnosed in 87 subfertile males investigated by the authors during the past 15 years. The patients all underwent full clinical investigation and had at least one normal sized testis and normal serum follicle-stimulating hormone levels. Serum antisperm antibodies were measured by sperm agglutination tests. They all had scrotal exploration under general anaesthesia when the epididymes were inspected and the testes were biopsied. Vasography was performed at this time by the injection of 3 to 5 ml of 25% or 45% Hypaque (Sterling Research Laboratories, Guildford, United Kingdom) using either direct puncture with 25-gauge needle (J.P.P.) or incision and cannulation with 2 French gauge (FG) Portex (Portex Ltd; Hythe, Kent, United Kingdom) cannula (W.F.H.). A few ml of 0.1% solution of methylene blue was injected into the vasa before cystourethroscopy when an attempt was to be made to relieve the obstruction endoscopically, with the patient placed in the lithotomy position. Obstructed cystic congenital lesions in the region of the verumontanum were treated by incision ofthe verumontanum with the optical urethrotome. Obstruction of the ducts was treated by resecting the verumontanum until methylene blue gushed out. This was often facilitated by placing a gloved finger in the rectum to squeeze the seminal vesicle. Deeper resection was carried out if necessary, sometimes with transrectal ultrasound (US) or radiologic control but often to no avail. A catheter was always left in the bladder overnight in case of hemorrhage. When the dilated vas contained spermatozoa but communication to the urethra could not be re-established, treatment was by implantation of a sperm reservoir in the groin (12 patients) 2 or operative aspiration of spermatozoa and assisted fertilization (1 patient). 3 Coexisting epididymal obstruction was treated by epididymovasostomies when indicated. Follow-up in appropriate cases was by serial seminal analyses or reservoir aspirations. RESULTS Sperm concentrations on presentation, grouped according to the underlying etiologic condition are shown in Table 1: 67 of the 87 patients had azo- 726 Pryor and Hendry Ejaculatory duct obstruction Table 1 Classification by Cause of Obstruction With Sperm Concentration on Presentation Sperm concentration Group 0 <1 1 to 10 >10 M/mL Congenital Mullerian (n = 17) Wolffian (n = 19) Traumatic (n = 15) 15 Postinfective (n = 19) 14 5 Tuberculous (n = 8) 8 Megavesicles (n = 8) Neoplastic (n = 1) 1 Total (n = 87) ospermia, and 17 had very severe oligozoospermia ( <1 X 10 6 sperm/ml). A small volume ejaculate, with acid ph and low or absent fructose content was noted in 65 (89%) of 75 patients in whom this information was available. The patients are classified according to the main etiologic factor, although it is recognized that there may be some overlap between the various groups. Congenital Mullerian Duct (Prostatic Utricle) Cyst In 17 patients, vasography showed a single midline cyst 1 to 2 em diameter with dilatation of seminal vesicles and vasa deferentia (Fig. 1b) that often contained blood-stained fluid. Three men were previously fertile and had themselves noted a deterioration in semen volume and sperm concentration. Endoscopic incision of the cyst produced an improvement in seminal quality in 10 of 12 cases with adequate follow-up, and 5 partners conceived. In 3 cases, the incision in the cyst wall closed over and was successfully reopened with a resectoscope at a second operation. Bilateral epididymovasostomies were done in 3 patients for secondary epididymal obstruction, and sperm appeared in the ejaculate of 1. Wolffian Malformations This was the largest group of patients (n = 19), and there was a wide range of associated abnormalities of those elements of the urogenital tract derived from the mesonephric (wolffian) duct (Fig. 1c). In 10 patients, there was an absent vas, and in 7 of these there were associated renal abnormalities. When there was an absent vas, the opposite vas Fertility and Sterility

Surgical treatment was largely unsuccessful, patency being restored in only 1 patient.

3 Figure 1 (A), Normal vasogram. (B), Typical miillerian duct cyst. (C), Malformation of right vas; absent left vas with pelvic left kidney. (D), Malformation of left vas with absent left kidney (normal right side). High-titer antisperm antibodies subsided after left orchidectomy. usually crossed the midline in a characteristic manner. Surgical treatment was largely unsuccessful, patency being restored in only 1 patient. In one case, however, the contralateral vas deferens was normal, and the existence of the vasal abnormality was only suspected because of the known absence of the ipsilateral kidney discovered during investigation of epididymitis. After orchidectomy, antisperm antibody levels fell, and his wife conceived (Fig. 1d). 4 Traumatic In 15 patients, the ejaculatory ducts had been damaged or removed at the time of previous surgery. There were two common causes. The first group of 5 patients resulted from transabdominal excision of seminal vesicle cysts, which had expanded sufficiently to cause urinary difficulties, usually acute urinary retention. The cyst was usually associated with ipsilateral renal abnormalities, and the contralateral (normal) ejaculatory duct was damaged or removed (Fig. 2a). The second group occurred after rectal surgery in childhood, such as correction of imperforate anus (5 patients) or other rectal convol. 56, No.4, October 1991 ditions (2 patients). An example is shown in Figure 2b of a young man who suffered recurrent bilateral epididymitis, the cause of which was ultimately tracked down to stenosis of the ejaculatory ducts. After insertion of sperm reservoirs, one pregnancy was produced by artificial insemination of aspirated spermatozoa. One patient had bilateral ejaculatory duct obstruction after repair of bladder exstrophy in childhood. Two followed military perineal injuries with a bullet wound or explosion complicated by prolonged catheterization: both regained normal sperm counts after reconstruction by transvasovasostomy, but neither produced a pregnancy. Postinfective In 19 patients, there was a history of previous genital, urinary, or tuberculous infection, prostatic abscess (n = 1) or prolonged catheterization (n = 1). In 8 patients, the duct itself was narrowed, whereas in 6 patients there was no filling of the seminal vesicle, indicating obstruction at the union of the vas deferens and the seminal vesicles at the upper end of the ejaculatory duct. There were multiple vasal blocks in 5 patients. Patency was restored in 4 papryor and Hendry Ejaculatory duct obstruction 727

Figure 2 (A), Obstruction after open removal of left seminal vesicle cyst causing urinary retention. (B), Partial ejaculatory duct obstruction after surgery for imperforate anus in infancy.

(C), Typical megavesicles in insulin-dependent diabetic with severe oligozoospermia. (D), Distortion of seminal vesicles and ejaculatory ducts caused by carcinoma of prostate.

4 Figure 2 (A), Obstruction after open removal of left seminal vesicle cyst causing urinary retention. (B), Partial ejaculatory duct obstruction after surgery for imperforate anus in infancy. Patient had azoospermia because of secondary epididymal obstruction after recurrent epididymo-orchitis. Note distortion of ejaculatory ducts and dilatation of vasa. (C), Typical megavesicles in insulin-dependent diabetic with severe oligozoospermia. (D), Distortion of seminal vesicles and ejaculatory ducts caused by carcinoma of prostate. tients, with one pregnancy after transurethral surgery. The lesion was too high for such surgery in 4 patients, and sperm reservoirs were inserted; one pregnancy was produced by artificial insemination of aspirated spermatozoa.2 In seven patients with proven tuberculous disease, extensive damage was found, including ejaculatory duct obstruction that was irreparable. In an eighth tuberculous case, however, sperm retrieval by open operation was combined with assisted fertilization, and this resulted in pregnancy. 3 Neoplastic One patient, medically qualified, noted progressive diminution of the ejaculate volume and complained of inability to impregnate his second wife (having previously produced children with his first wife). Vasography showed gross distortion of the ejaculatory ducts (Fig. 2d). Biopsy showed endometrioid carcinoma of prostate; he remains well after bilateral orchidectomy. Overall Outcome Megavesicles In eight cases, very marked dilatation of the seminal vesicles was noted; two of these patients were diabetic (Fig. 2c). In one of these patients, dye was still present in the vesicles on x ray 1 month after vasography. Sperm reservoirs were inserted, and numerous poorly motile sperm were obtained by aspiration, but no pregnancy resulted. In another patient, the sperm count improved after transurethral resection of the verumontanum and bilateral epididymovasostomies. 728 Pryor and Hendry Ejaculatory duct obstruction Among those suitable for treatment, patency was restored in 25 of 43 patients with adequate followup, and 10 female partners became pregnant (Table 2). Treatment was primarily surgical in 31, of whom 18 achieved patency and 6 produced pregnancies. Reservoirs were inserted in 12; spermatozoa were obtained in 7, and 2 produced pregnancies. One pregnancy was produced using spermatozoa retrieved from the convoluted part of the vas by open operation, and one was produced after subsidence of antisperm antibodies after removal of a testicle Fertility and Sterility

Table 2 Number of Patients Successfully Treated/Number With Adequate Follow-up in the Various Groups Pregnancies Group Patency Reservoirs produced Congenital Mullerian (n = 17) 10/12 5 Wolffian (n =

5 Table 2 Number of Patients Successfully Treated/Number With Adequate Follow-up in the Various Groups Pregnancies Group Patency Reservoirs produced Congenital Mullerian (n = 17) 10/12 5 Wolffian (n = 19) 1/6 1/3 1 Traumatic (n = 15) 2/6 4/4 1 Postinfective (n = 19) 4/6 1/4 2 Tuberculous (n = 8) 1 Megavesicles (n = 8) 1/1 1/1 Neoplastic (n = 1) Total (n = 87) 18/31 7/12 10 whose outflow was obstructed by wolffian abnormality. DISCUSSION The diagnosis of ejaculatory duct obstruction may be overlooked for a number of reasons. First, the patient may be referred with azoospermia or severe oligozoospermia but without details of volume and chemical composition of the semen. In such patients, a small volume ejaculate with low ph and absent fructose but with palpable vasa (and often some epididymal thickening) is virtually pathognomic. Surgically, the epididymes at scrotal exploration may not show the characteristic distention of tubules that is observed in obstruction because of blocks at the tail of the epididymis or after vasectomy. Presumably, the dilatation of the ampullary parts of the vasa and seminal vesicles takes the pressure off the epididymes. Finally, the capacity of the distended system may be sufficient to accommodate a little saline injected up the vas and thus the diagnosis may be missed if vasography is omitted. Transrectal US provides an accurate image of this area, but the images may be difficult to interpret and subject to observer variation. 5 Nevertheless, this procedure should be done before scrotal exploration in cases in which there is a high suspicion of this diagnosis, and abdominal US should also be done to define any coexisting abnormalities of the urinary tract, particularly ectopic kidneys. Vasography permits much better definition of the ejaculatory ducts and seminal vesicles and will indicate where transurethral relief of the obstruction is possible. Hence the patient should be in the lithotomy position on an x ray lucent operating table, suitably draped to allow intraoperative digital examination per rectum so that ejaculatory duct or cyst contents can be expressed. Vol. 56, No. 4, October 1991 Congenital disorders are the most common causes of ejaculatory duct obstruction. Englisch 6 in 1874 pointed out the difference between midline cysts that are usually of miillerian origin, and lateral swellings usually of wolffian duct origin. Clearly, there is a spectrum of disorders that can affect this area. 7 The lesion that is the most correctable single cause of ejaculatory duct obstruction is probably best called Mullerian duct cyst 8 and is well defined by vasogram (Fig. lb) because it fills easily from vasal injection. The cyst expands and appears to compress the ejaculatory ducts by distorting them. The resulting obstruction may be complete or incomplete, that is, the patient may present with azoospermia or severe oligozoospermia. Hemospermia is common, 9 and the cyst and one vas back to the epididymis often contain blood although where it comes from is unknown.10 Injection of methylene blue into one vas may be seen to descend down the contralateral vas, implying that both open into the cyst, a phenomenon also noted by others.u 12 Surgical correction is relatively easy. The cyst is inflated with methylene blue diluted tenfold, and the roof of the cyst is longitudinally incised with the optical urethrotome or resected with the resectoscopep- 17 If no fluid flows out, it should be expressed digitally per rectum. Secondary epididymal obstruction is common and may require epididymovasostomy. 18 The lateral, wolffian abnormalities give a rather variable appearance. The seminal vesicles may be cystic, and ipsilateral or contralateral renal and/or vasal agenesis often coexists (sometimes called Zinner's syndrome). 19 Endoscopic incision is often rather unsatisfactory perhaps because of the considerable distance between the blind ending termination of the ductal system and the urethra; nonetheless, one such cyst spontaneously emptied into the back of the bladder. 20 Another cause of failure may be cystic dilatation of the vas and ejaculatory duct, and such adynamic segments may fail to contract and transport sperm. The long-standing nature of the obstruction and associated preceding epididymitis may be the reason that sperm reservoirs have given little success. Traumatic damage to the ejaculatory ducts usually occurred after removal of seminal vesicle cysts or after pull-through operations for imperforate anus. However, other examples were seen after military injuries caused by bullets or mines, complicated by infection. Many of these cases could be classified elsewhere on an etiologic basis but are considered separately to highlight the extreme care that is re- Pryor and Hendry Ejaculatory duct obstruction 729

6 quired to operate in this area and to avoid injury to these delicate structures. After genital or urinary infection, prostatic abscess or even prolonged catheterization, the ducts may become stenosed or completely closed off Distinction should be made between distal obstruction, easily cleared by transurethral resection, and more proximal blocks that may be associated with blockage of the seminal vesicles. Tuberculosis produces devastation that may be quite uncorrectable, but the diagnosis must be established so that appropriate chemotherapy can be given. The seminal vesicles and ampullary parts of the vasa may be distended, often quite grossly so. 23 Although this may be because of mechanical obstruction in some cases, there are others in whom cystic dilatation of the seminal vesicle occurs, even though no ductal obstruction can be demonstrated. One such example (Fig. 2c) occurred in a severe diabetic and may be the end result of autonomic neuropathy. In others, the etiology is unclear, and this may represent a variant of congenital wolffian abnormality. The seminal characteristics point to ejaculatory disturbance, possibly as a form of dyskinesia. Colpi et al. 24 calls this "functional voiding disturbance of the ampullo-vesicular seminal tract" and described six examples that were refractory to medical treatment. In some of our patients, we found ephedrine 30 mg or desipramine 25 mg 1 hour before intercourse corrected the ejaculatory abnormality, improving the seminal quality. This little-recognized syndrome is clearly worthy of diagnosis and treatment, and we are conducting further studies. Finally, prostatic carcinoma can present by causing ejaculatory duct obstruction. Interestingly, we have seen two patients who were medically qualified and had documented serial reduction in ejaculate volume and semen quality. One patient had an "endometrioid" carcinoma, which typically started at the prostatic utricle. This tumor has been shown to stain strongly for acid phosphates and has ultrastructural features of prostatic ductal origin, so it probably is not a true endometrial carcinoma. 25 Ejaculatory duct obstruction is a fascinating condition for the andrologist to discover because of the wide variety of etiologic factors and differing treatment possibilities. Previously thought to be exceedingly rare, this study shows that this is not the case. Therapeutically, it provides an opportunity not to be missed because endoscopic incision, sperm retrieval from the vasa, or drug stimulation of ejaculation in carefully selected cases can restore the man's fertility. REFERENCES 1. Hendry WF, Levison D, Parkinson CM, Parslow JM, Royle MR: Testicular obstruction: clirtico-pathological studies. Ann R Coli Surg Eng! 72:396, Brindley GS, Scott GI, Hendry WF: Vas cannulation with implanted sperm reservoirs for obstructive azoospermia or ejaculatory failure. Br J Urol 58:721, Pryor JP: Surgical retrieval of epididymal spermatozoa. Lancet 2:1341, Hendry WF: Clinical significance of unilateral testicular obstruction in subfertile males. Br J Urol 58:709, Littrup PJ, Lee F, McLeary RD, Wu D, Lee A, Kumasaka GH: Transrectal US of the seminal vesicles and ejaculatory ducts: clinical correlation. Radiology 168:625, Englisch J: Ueber cysten an der hinteren blasenwand bei mannern. Wien Med Jahrbucher 1874, p Morgan RJ, Williams DI, Pryor JP: Mullerian duct remnant in the male. Br J Urol 51:488, Stanley KE: Mullerian duct cyst variant: utriculocele and inclusion of ejaculatory ducts. report of a case. J Urol 102: 233, Van Poppe! H, Vereecken R, de Geeter P, Verduyn H: Hemospermia owing to utricular cyst: embryological summary and surgical review. J Urol129:608, Fanous H, Elist J, Edson M: Spontaneous bleeding into epididymis and vas. Urology 20:186, Elder JS, Mostwin JL: Cyst of the ejaculatory duct/urogenital sinus. J Urol 132:768, Sharlip ID: Obstructive azoospermia or oligozoospermia due to Mullerian duct cyst. Fertil Steril 41:298, Hassler RD, Werer CH: Oligospermia secondary to Mullerian duct cyst: simple surgical cure. Urology 11:386, Porch PP: Aspermia owing to obstruction of ductal ejaculatory duct and treatment by transurethral resection. J Urol 119: 141, Dunetz GN, Krane RJ: Successful treatment of aspermia secondary to obstruction of ejaculatory duct. Urology 27:529, Farley S, Barnes R: Stenosis of the ejaculatory ducts treated by endoscopic resection. J Urol 109:664, Vicente J, Del Portillo L, Pomerol MM: Endoscopic surgery in distal obstruction of the ejaculatory ducts. Eur Urol9:338, Silber SJ: Ejaculatory duct obstruction. J Urol124:294, Zinner A: Ein fall von intravesikaler samenblasenzyste. Wien Med Wochenschr 64:605, Hart JB: A case of cyst or hydrops of the seminal vesicle. J Urol 86:137, Carson CC: Transurethral resection for ejaculatory duct stenosis and oligospermia. Fertil Steril 41:482, Goldwasser BZ, W einerth JL, Carson CC: Ejaculatory duct obstruction: the case for aggressive diagnosis and treatment. J Urol134:964, W eintraube CM: Transurethral drainage of the seminal tract for obstruction, infection and infertility. Br J Urol 52:220, Colpi GM, Casella F, Zanollo A, Ballerini G, Balerna M, Campana A, Lange A: Functional voiding disturbances of the ampullo-vesicular seminal tract: a cause of male infertility. Acta Eur Fertil 18:165, Zalouder C, Williams JW, Kempson RL: "Endometrial" adenocarcinoma of the prostate. C(lncer 37:2255, Pryor and Hendry Ejaculatory duct obstruction Fertility and Sterility

Evaluation and treatment of ejaculatory duct obstruction in the infertile male

FERTILITY AND STERILITY Copyright 99 The American Fertility Society Vol. 59, No,, February 99 Printed on acid4ree paper in U.S.A. Evaluation and treatment of ejaculatory duct obstruction in the infertile