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Diagnosis and Management of Infertility Due to Ejaculatory Duct Obstruction: Summary Evidence ______ Vol. 47 (4): 868-881, July - August, 2021 doi: 10.1590/S1677-5538.IBJU.2020.0536 EXPERT OPINION Diagnosis and management of infertility due to ejaculatory duct obstruction: summary evidence _______________________________________________ Arnold Peter Paul Achermann 1, 2, 3, Sandro C. Esteves 1, 2 1 Departmento de Cirurgia (Disciplina de Urologia), Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brasil; 2 ANDROFERT, Clínica de Andrologia e Reprodução Humana, Centro de Referência para Reprodução Masculina, Campinas, SP, Brasil; 3 Urocore - Centro de Urologia e Fisioterapia Pélvica, Londrina, PR, Brasil INTRODUCTION tion or perineal pain exacerbated by ejaculation and hematospermia (3). These observations highlight the Infertility, defined as the failure to conceive variability in clinical presentations, thus making a after one year of unprotected regular sexual inter- comprehensive workup paramount. course, affects approximately 15% of couples worl- EDO is of particular interest for reproduc- dwide (1). In about 50% of these couples, the male tive urologists as it is a potentially correctable factor, alone or combined with a female factor, is cause of male infertility. Spermatogenesis is well- contributory to the problem (2). Among the several -preserved in men with EDO owing to its obstruc- male infertility conditions, ejaculatory duct obstruc- tive nature, thus making it appealing to relieve the tion (EDO) stands as an uncommon causative factor. obstruction and allow these men the opportunity However, the correct diagnosis and treatment may to impregnate their partners naturally. This review help the affected men to impregnate their partners aims to update practicing urologists on the current naturally due to its treatable nature. methods for diagnosis and management of EDO. A EDO’s reported incidence among men se- detailed analysis of each therapeutic modality is eking fertility varies between 1 and 5% (3, 4). provided, including the use of sperm retrieval and Azoospermia (lack of sperm in the ejaculate) or se- assisted reproductive technology. vere oligozoospermia (less than 5 million/sperm per mL), associated with low volume ejaculate (<1.5mL, Anatomy and Etiology termed hypospermia) can be indicative of EDO (5). Spermatozoa are produced in the semini- The typical clinical picture of bilateral and comple- ferous tubules under the influence of sexual hor- te EDO includes an acidic semen specimen, a low mones (testosterone and androstenedione) secre- volume azoospermic ejaculate, and low or absent ted by the interstitial cells. The epididymis is in fructose levels (5, 6). By contrast, oligo[astheno-te- continuity with the vas deferens, which in turn rato]zoospermia can be found in patients with par- join the emerging ducts from the seminal vesicles tial obstruction, in whom the ejaculate volume and to form the ejaculatory ducts (EDs). The EDs usu- fructose levels might be unremarkable. Nevertheless, ally penetrate the central zone of the prostate and both complete and partial obstructions can lead to empty into the prostatic urethra on either side of infertility (7, 8). While some patients are completely the seminal colliculus (9). While the prostatic fluid asymptomatic, others complain of painful ejacula- accounts for approximately 0.5mL of the ejacula- 868 IBJU | EXPERT OPINION te, the seminal vesicles (SVs) produce an alkaline ging exams. The typical patient complains of fluid with prostaglandins and fructose, which com- painful ejaculation, which can be associated with prises 1.5-2.0mL (~50-80%) of the seminal fluid. hematospermia, decreased ejaculatory volume, The ED derives from the Wolffian duct, like and infertility. Other possible symptoms are de- the epididymis body and tail, the vas deferens, and creased ejaculation force, perineal or lower back the seminal vesicles (SV). On the other hand, the pain, chronic scrotal pain, and dysuria. EDO prostate originates from the endoderm, which inva- symptoms might suggest prostatitis or epididy- ginates into its surrounding mesenchyme (10). Des- mitis, so it is essential to make the differential pite anatomic variations (11, 12), the ED usually runs diagnosis (17). The presence of tender and indu- obliquely for 1-2cm inside the prostate in a 75-angle rated epididymis, scrotal swelling and erythema degree (13). is indicative of epididymitis, whereas elevated Although the SVs and the EDs have similar PSA levels, dysuria, a painful prostate during histological features, with a cuboidal or pseudostra- digital rectal examination and an urinalysis tified columnar epithelium line and a middle colla- with infection suggest prostatitis. Early endos- genous layer, only the SVs present an inner muscular copic treatment may not only resolve the symp- layer. Eighty percent of the SVs wall thickness consists toms but also avoid progression to complete or of muscular layers (inner circular and outer longitu- bilateral ejaculatory duct obstruction (3, 5, 17). dinal fibers) (13). The typical SV measures 4.5-5.5cm Semen analysis plays a pivotal role in in length and 1.5cm in width (14). The proximal lumi- EDO diagnosis. While patients with complete nal diameter is larger than the distal counterpart and EDO are azoospermic, those with partial EDO ranges from 1.7mm narrowing down to 0.3mm (12). show severe oligozoospermia with decreased The high accuracy of transrectal ultrasound (TRUS) sperm motility. Other typical findings on the se- to determine the dimensions of both the SVs and EDs men analysis of a patient with complete EDO makes this method a useful tool to investigate obs- includes a low volume ejaculate (<1.5mL) with a tructions at the ED level. EDO should be suspected if low pH (<7.2), and low (<13µmol per ejaculate) TRUS shows an enlargement of the SVs, which can be or absent fructose in the seminal fluid (6, 18). congenital, acquired, or functional. The finding of palpable vasa deferentia and SVs In 1914, the Zinner’s syndrome was first des- can help differentiate EDO from the congenital cribed as a triad of unilateral renal agenesis, ipsila- bilateral absence of vas deferens (CBAVD). The teral seminal vesicle cyst, and EDO as a consequence presence of an acidic and low volume azoosper- of a Wolffian duct abnormality (15). To date, less mic ejaculate, associated with absent seminal than 200 cases of this rare congenital abnormali- fructose, and palpable vas deferens is pathog- ty have been reported in the literature. Agenesis or nomonic for the EDO diagnosis (18). However, atresia of the ejaculatory ducts, mutations in the the absence of one or more of these features cystic fibrosis transmembrane regulator (CFTR) gene, cannot exclude EDO. and ectopic ureteral orifice opening directly into the ejaculatory duct are other examples of congenital Vasography causes of EDO. By contrast, acquired EDO may be Vasography is carried out by incising or secondary to trauma, infection/inflammation, or cal- puncturing the vas, followed by the injection of culus. Lastly, a functional obstruction may occur as a contrasting agent. The obstruction is confir- a consequence of spinal cord injury, pelvic surgery, med by radiologic/fluoroscopic observation of post-retroperitoneal lymph node dissection, medica- normal vasa deferentia, enlarged seminal vesi- tion use, and systemic disorders (diabetes mellitus cles, and lack of contrast in the bladder and ure- and multiple sclerosis) (3, 16). thra. Despite being historically considered the gold standard method for EDO diagnosis, scrotal Diagnosis vasography has been replaced by TRUS. Even The diagnosis of EDO includes history, though the former may allow sperm collection physical examination, semen analysis, and ima- for cryopreservation, is an invasive method that 869 IBJU | EXPERT OPINION requires injection of a contrast agent, and there (24). They found that only half of the patients are risks of iatrogenic vasal stenosis or stricture. with obstructive findings on TRUS had sperm The TRUS high accuracy and no invasiveness on SV aspiration. The authors suggested that have made this method the standard imaging SV aspiration should be added to the TRUS to diagnostic tool (3, 4, 19). improve its diagnostic accuracy (24). It has also been reported that viable sperm collected from Transrectal Ultrasonography (TRUS) the SV can be used for assisted reproductive The endorectal 5-7MHz biplanar trans- technology (ART) (25). ducer has high accuracy in measuring the SVs and the ED internal diameter (3, 5). TRUS ena- Seminal Vesicle Chromotubation bles the evaluation of midline cysts, ED cal- In this procedure, a 5mL diluted dye so- cification, and hyperechoic SV calculi, all of lution (e.g., indigo carmine or methylene blue) which can obstruct the EDs (4, 10, 19, 20). EDO is injected into the SV after TRUS-guided SV should be suspected when an enlarged SVs with aspiration. The dye efflux from the prostatic a cross-section width greater than 1.5cm and/or urethra is monitored with cystourethroscopy. an ED diameter >2.3mm are seen. Despite being Moreover, the method can be used to confirm currently advocated by many as the method of obstruction resolution after endoscopic transu- choice for evaluating infertile men suspected of rethral resection of the ED (TURED) (3, 21). having EDO-related obstructive azoospermia, TRUS has limitations. In one study, Purohit et Seminal Vesiculography al. performed TRUS and duct chromotubation The TRUS-guided injection of a non-io- followed by SV aspiration and seminal vesicu- nic contrast agent into the vesicles combined lography in men suspected of having EDO (21). with fluoroscopy enables the evaluation of the Of 25 patients with findings suggestive of EDO ED anatomical and functional aspects. The lack on TRUS, only 12 patients (48%) had the obs- of contrast within the urethra and bladder, as- truction confirmed by SV aspiration and vesi- sociated with an enlarged SV, suggest obstruc- culography. The authors concluded that if the tion (26). In about two-thirds of patients, this diagnosis had been based on TRUS alone, only imaging exam provides information concerning about half of the treated patients would have the vas patency by assessing the retrograde va- shown improvements in symptoms or semen sogram (4).
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