Semen analysis: At least two examinations must be performed with an interval between their of 2-3 months, according to WHO (see above Andrological investigations and spermatology). Azoospermia means absence of spermatozoa after centrifugation at X 400.
Careful repeat observation of several smears after semen liquefaction is necessary. Finding no spermatozoa in wet preparation involves the centrifugation of aliquots or of the whole semen sample (600 rpm for 15 minutes). The pellet must be examined for spermatozoa.
A semen volume of less than 1.5 ml_, acid pH and low fructose suggest ejaculatory duct obstruction or CBAVD. When semen volume is low, spermatozoa in urine after ejaculation must always be searched for, as their presence confirms an ejaculation disorder.
Absence of spermatozoa and immature germ cells in semen smears suggest complete proximal or distal seminal duct obstruction.
Clinical history
Clinical history taking should follow the suggestions for investigation of infertile men (see above Andrological investigations and spermatology), including questions about the presence of haematospermia, post-ejaculatory pain, previous or present urethritis, prostatitis, obstructive or irritative urinary symptoms, previous scrotal enlargement or pain or surgery, previous inguinal herniorrhaphy or traumas, and chronic sinopulmonary infections.
Clinical examination
This follows the suggestions for investigation of infertile men. The following are particularly importent:
? at least one testis > 15 ml volume (although a smaller testicular volume may be found in some patients
with obstructive azoospermia and concomitant partial testicular failure)
? enlarged and hardened cauda or caput epididymidis
? nodules
? absence or partial atresia of the vas
? present urethritis
? prostatic deformations
Hormone levels
Serum FSH levels may be normal but do not exclude a testicular cause of azoospermia (e.g. spermatogenic arrest). On the contrary, a serum FSH of less than twice the upper limit of normal may be present in patients with one normal testis, associated with contralateral seminal tract obstruction [4].
Transrectal ultrasonography
TRUS has to be performed on all patients in whom proximal or distal obstruction is suspected, if possible with high resolution and high frequency (7 MHz) biplanar transducers and in standard sexual abstinence conditions (e.g. immediately after ejaculation, for better definition of the ejaculatory ducts). Seminal vesicle enlargement (anterior-posterior diameter > 15 mm) [17] and seminal vesicle roundish anechoic areas [20] are TRUS anomalies more often associated with ejaculatory duct obstruction, especially when semen volume is < 1.5 ml. Other known anomalies in cases of obstructive azoospermia are Mullerian duct cysts or urogenital sinus/ejaculatory duct cysts [16] and ejaculatory duct calcifications [21]. TRUS may also be applied to aspirate seminal vesicle fluid [22].
Invasive diagnosis, including testicular biopsy, scrotal exploration and distal seminal duct evaluation, should be mandatory in all patients with azoospermia in whom a mechanical obstruction of the seminal ducts cannot be excluded. It is advisable to perform explorative and recanalization surgery at the same time.
Testicular biopsy
This is necessary when a concomitant secretory pathology is suspected. The same surgical procedure may also be used to extract testicular spermatozoa (TESE) for cryopreservation and subsequent ICSI, when surgical recanalization cannot be performed or has failed (for details see above Primary spermatogenetic failure).
Distal seminal tract evaluation
Distal seminal tract has to consider the anatomical perviousness of the seminal ducts downstream to the proximal vas deferens.
One technique involves cannulating each vas deferens and injecting a saline solution mixed with 0.5 mL of 10% methylene blue is injected. If the saline solution passes through easily, radiographic contrast and X-ray evaluation (vasography) are not needed. The injected solution passed into the bladder is recovered through a Foley catheter, and spermatozoa are searched for and counted (seminal tract washout) [23]. In an alternative method, the proximal vas deferens is microsurgically hemitransected (X 15 power magnification) and any fluid from the lumen is placed on a slide and mixed with a drop of saline solution. Absence of spermatozoa on microscopic examination indicates epididymal obstruction (if testicular biopsy is normal or only slightly altered). However if spermatozoa are found inside the proximal vas deferens of an azoospermic patient this suggests a distal seminal duct obstruction. In this case, antegrade cannulation of the vas deferens and injection of saline solution plus methylene blue are performed. If the solution passes easily, vasography is not necessary [24]. If injection is difficult or impossible, an anatomical ejaculatory duct obstruction or vas deferens obstruction, respectively, are suspected. In both cases, vasography is indicated to identify the nature and site of obstruction. At the end of the procedure a microsurgical suture of the vas deferens is required [24].
Treatment
Intratesticular obstruction:
Since seminal duct recanalization at this level is impossible, TESE or fine needle aspiration are recommended (see above Primary spermatogenetic failure). The spermatozoa retrieved may be immediately used for ICSI or may be cryopreserved.
Both TESE and fine needle aspiration allow sperm retrieval in nearly all obstructive azoospermic patients.
Epididymal obstruction:
Microsurgical Epididymal Sperm Aspiration (MESA) [25] is mandatory in CBAVD. Retrieved spermatozoa are
usually used for ICSI. In general, one MESA procedure provides sufficient material for several ICSI cycles [26].
In patients with azoospermia due to acquired epididymal obstruction, end-to-end or end-to-side microsurgical epididymovasostomy must be performed.
Reconstruction may be done uni- or bilaterally; patency and pregnancy rates are usually higher with bilateral reconstruction. Before performing microsurgery, it is important to check that there is full patency downstream of the epididymis. Anatomical recanalization following surgery may require 3-18 months. Before performing microsurgery (and also in all cases where recanalization is impossible), epididymal spermatozoa should be aspirated and cryopreserved to be used for ICSI in case of surgical failure [26].
Patency rates range between 60% and 87% [27-29] and cumulative pregnancy rates between 10% and 43%. Recanalization failures occur in 10% [30] to 21 % [27]. Recanalization success rates may be adversely affected by pre-operative and operative findings such as concomitant abnormal testicular histology, absence of sperm in the spermatic fluid on sectioning the epididymis small epididymal tubules and wide fibrosis of the epididymis.
The finding of motile or immotile spermatozoa at the level of the anastomosis does not appear to be related to the patency rate. Conversely, moving from the corpus to the caput epididymidis involves a significant adverse effect upon patency and pregnancy outcome. The same adverse effect occurs with the concomitant presence of ultrasonographic abnormalities in the prostate and seminal vesicles [31].
In terms of delivery rate, vasoepididymostomy in patients with epididymal obstruction secondary to vasectomy has proved more successful and more cost-effective than MESE and ICSI [32] (see also below Vasectomy and vasectomy reversal).
Proximal vas obstruction
Proximal vas obstruction after vasectomy requires microsurgical vasectomy reversal (see below Vasectomy and vasectomy reversal). Vasovasostomy must also be performed in the rare cases of proximal vasal obstructions (iatrogenic, post-traumatic, post-inflammatory). When spermatozoa are absent in the intraoperative vas fluid bilaterally, a concomitant secondary epididymal obstruction is usually present, and microsurgical vasoepididymostomy is mandatory.
Distal vas deferens obstruction:
Large bilateral vas defects resulting from involuntary vas excision during hernia surgery in early childhood or previous orchidopexy are usually untreatable [12]. In these cases, one can resort to proximal vas deferens sperm aspiration [33] orTESE/MESA in cases of concomitant epididymal obstruction. In large monolateral vas defects associated with contralateral testicular atrophy, the vas of the atrophic testis can be used for a crossover vasovasostomy or vasoepididymostomy.
Sperm reservoirs fixed onto epididymis or proximal vas deferens have been used during the past decade with poor results [34]. This type of surgery is not recommended.
Ejaculatory duct obstruction
The treatment of ejaculatory duct obstruction depends on aetiology. In large post-inflammatory obstruction and when one or both ejaculatory ducts empty into an intraprostatic midline cyst, transurethral resection of the ejaculatory ducts (TURED) [16,35] is recommended. Resection may remove part of the verumontanum. In case of obstruction due to a midline intraprostatic cyst, incision or unroofing of the cyst is required [16]. Intraoperative TRUS makes this procedure safer and more effective. If distal seminal tract evaluation is carried out at the time of the procedure, installation of methylene blue into the vas may be helpful to document opening of the ducts. Intraoperative haemostasis is advisable to avoid postoperative bleeding, which could result in rescarring of the ducts. Complications following TURED include retrograde ejaculation due to bladder neck injury, reflux of urine into ducts, seminal vesicles and vasa (causing poor sperm motility, acid semen pH and epididymitis). Although rectal injury, urine incontinence secondary to sphincteric injury, urethral injury, bladder neck contracture and erectile dysfunction have never been described to date, patients should be informed preoperatively about possible complications associated with this type of surgery [35].
Alternatives to TURED are MESA, TESE, proximal vas deferens sperm aspiration, seminal vesicle aspiration and direct ultrasonically-guided cyst aspiration.
In cases of functional obstruction of the distal seminal ducts, TURED often fails to improve the sperm output. Spermatozoa may then be retrieved by antegrade seminal tract washout [36].
Spermatozoa retrieved by any of the aforementioned surgical techniques should always be cryopreserved for assisted reproductive procedures.
4.5 Conclusions
1) Obstructive lesions of the seminal tract should be suspected in azoospermic or severely oligozoospermic patients with normal-sized testes.
2) Results of reconstructive microsurgery depend on the cause and location of the obstruction and the expertise of the surgeon. Standardized procedures include vasovasostomy, epididymovasostomy and TURED.
3) Sperm retrieval techniques such as MESA, TESE and testicular fine needle aspiration can be applied additionally. The consensus is that these methods should only be performed with the facility for cryostorage of the material obtained.
References
PryorJP.
Indications for vasovesiculography and testicular biopsy. An update; in Colpi GM, Pozza D (eds): Diagnosing Male Infertility: New Possibilities and Limits. Basel, Karger: Basel, 1992, pp 130-135.