Management of Obstructive Azoospermia

Azoospermia in a patient with normal size testes (20-25 cc volume) and normal FSH suggest obstructive etiology. The sites of reproductive tract obstruction are epididymis, vas deferens and ejaculatory ducts. Rarely obstructive azoospermia is caused by congenital bilateral absence of vas deferens (CBAVD) or Young syndrome. The diagnosis of obstructive azoospermia (OA) requires confirmation of normal spermatogenesis by testicular biopsy (with the exception of CBAVD). The site of obstruction may be determined preoperatively by physical exam (CAV), transrectal ultrasound (ejaculatory duct obstruction in patients with low volume ejaculate without fructose) and intraoperatively by microscopic examination of intravasal fluid and vasography. Vasography is always deferred until time of planned reconstruction.

Reconstructable group includes patients with reproductive tract obstruction amenable to repair. The currently available treatment options for vasal, epididymal and ejaculatory ducts obstruction are microsurgical Vasovasostomy (VV) and vasoepididymostomy (VE), transurethral resection of the ejaculatory ducts.


Vasovasostomy

Vasectomy is the most common iatrogenic cause of obstructive azoospermia. About 2 to 6% of vasectomized men will ultimately seek vasectomy reversal. Furthermore, iatrogenic injuries to the vas deferens are found in 7.2% of men with obstructive azoospermia (most commonly after pediatric inguinal hernia repair). However, the level of obstruction (vas deferens or epididymis) is not known preoperatively. It is not uncommon, that preoperatively thought vasal obstruction intraoperatively appears to be an epididymal obstruction. The decision of performing Vasovasostomy or Vasoepididymostomy greatly depends on intraoperative findings of the quality of the intravasal fluid. Ideally, sperm have to be microscopically identified in the intravasal fluid from testicular end of the surgically exposed vas. This clinical scenario is invariably favorable for the Vasovasostomy. Otherwise, microsurgical vasoepididymostomy may be a better choice. It is appealing to be able to predict the presence of sperm in the intravasal fluid preoperatively which enables surgeon to plan reconstructive procedure better.

Certain physical signs and other factors have been propose as the predictive tools:

  1. Epididymis: An indurated irregular epididymis often predicts secondary epididymal obstruction, necessitating vasoepididymostomy.
  1. Sperm granuloma. The beneficial pressure releasing effect of sperm granuloma had been described. Sperm leakage from the testicular end at the vasectomy site may vent high back pressure and prevent rupture of the epididymal tubule and, therefore, and epididymal obstruction.
  2. The length of vasal remnant. A longer vasal remnant corresponds to higher volume of the reservoir and, therefore lower internal pressure. The pressure remains lower within long vasal remnants for a significantly longer time. This is an important factor in patient with iatrogenic injuries to the vas deferens, inguinal or retroperitoneal, resulting in a long vasal remnant and usually a long obstructive interval.
  3. The length of obstructive interval: longer time of obstruction is associated with higher risk of epididymal obstruction
  4. Presence of sperm in the pre-vasectomy reversal semen analysis spun pellet was confirmed in 10% of men before microsurgical reconstruction. At operation these men had sperm in the testicular end of the vas more frequently than preoperatively azoospermic men .

 

Bilateral high vertical scrotal incisions are preferred. These incisions may be easily extended up to external inguinal ring if additional length of the abdominal segment of the vas deferens is needed. This is not possible with midline incision recommended by some surgeons

Obstruction of the inguinal vas deferens should be suspected in men with the history of previous inguinal surgeries. The patient has to be carefully examined in order to identify possible inguinal scars since some patients do not remember any interventions in childhood. Such iatrogenic injuries to the vas deferens were found in 7.2% of patients with obstructive azoospermia Inguinal Incision through the previous scar usually leads directly to the site of the obstruction. Although vas deferens may not be completely transected, strictured segment is usually long since iatrogenic injuries usually significantly altered vasal blood supply due to scarring and damage to the small vasal vessels. If the obstruction turns out to be scrotal or epididymal, testis may be delivered into the inguinal wound.

After the vas has been freed, the testicular end of the vas is cut transversely (90ƒ) using an ultrasharp knife drawn through a slotted 2 to 3 mm diameter nerve clamp (Accurate Surgical and Scientific Instrument Corp., Westbury, NY).

The important steps of vasal reanastomosis are:

  1. Examine intravasal fluid. Although the decision to proceed with Vasovasostomy or vasoepididymostomy has been attributed to the quality of intravasal fluid (scant, copious, opalescence, waterlike, thick/creamy) the only objective indicator of sperm presence in the intravasal fluid is microscopic findings. If no sperm are present in the fluid, the epididymis has to be examined for the site of obstruction and vasoepididymostomy performed only by experienced microsurgeon. Vasoepididymostomy should not be attempted without special training. If in doubt, VV should be performed. The vasal artery and vein are then clamped and ligated with 6-0 polypropylene. Small bleeders are controlled with a micro-bipolar forceps set at low power. Once a patent lumen has been established on the testicular end, the vas is milked and a clean glass slide is touched to its surface. The vasal fluid is immediately mixed with a drop or two of saline or Ringer's lactate and preserved under a cover slip for microscope examination. The abdominal end of the vas deferens is prepared in a similar manner and the lumen gently dilated with a microvessel dilator and cannulated with a 25-gauge angiocatheter sheath. Injection of saline e confirms its patency. A minimum of instrumentation of the mucosa should be performed.

After preparation, the ends of the vas are stabilized with a microspike approximating clamp (Goldstein, 1985) to remove all tension prior to performing the anastomosis. Isolating the field through a slit in a rubber dam prevents micro-sutures from sticking to the surrounding tissue. A sterile tongue blade covered with a large Penrose drain is placed beneath the ends of the vas to provide a platform on which to perform the anastomosis.

 

II. Certain microsurgical principles have to be strictly observed to achieve maximum success in creating functional vasal anastomosis: 

Accurate mucosa to mucosa approximation 

  

Meticulous atraumatic anastomotic technique

  

Leakproof and Tension-free anastomosis

  

Good vas mobilization and layered water-tight closure

  

Good blood supply

Preservation of the vasal sheath.

 

Presence of healthy bleeding from the mucosal surface of both vas ends

  

Healthy mucosa and muscularis

Clearly visible three vasal layers ( "bullseye")

 

A healthy white mucosal ring which springs back immediately after gentle dilation. Smooth and soft muscularis.


III. ( Pictures: Dr. Marc Goldstein, Cornell Medical center, with permission).We prefer the multilayered technique. The inner mucosal layer is approximated with 8 monofilament 10-0 polypropylene sutures, double-armed and bent into a fish hook configuration. Eight 9-0 polypropylene sutures are placed through the adventitia and muscularis The anastomosis is reinforced by approximating the vasal sheath with eight interrupted 6- 0 polypropylene sutures to provide strength and remove all tension from the anastomosis. We use a mictrotip marking pen to map out planned needle exit points. This method, introduced by Dr. Marc Goldstein from Cornell University Medical Center, allows precision suture placement and dramatically improves accuracy.  

 In rare cases of iatrogenic or congenital obstruction, a complex reconstruction such as a transseptal crossed ductal anastomosis to overcome massive vasal defects may be performed. The indications for crossover vasovasostomy are:

 

1.Unilateral large vasal defect associated with contralateral testicular atrophy (with histologic confirmation of maturation arrest) or epididymal obstruction.

2.Unilateral obstruction of the ejaculatory duct associated with contralateral testicular atrophy (with histologic confirmation of maturation arrest) or epididymal obstruction. The results are usually inferior to those reported for ipsilateral microsurgical vasectomy reversal due to longer obstructive interval, frequent impairment of blood supply associated with iatrogenic injuries and the presence of only one functional testiculo-ductal system. Crossover operations usually result in return of sperm that can be used for in vitro fertilization if natural pregnancy does not occur

3.Multiple vasal obstructions are occasionally present in vasectomized patients who also have iatrogenic injuries to the abdominal vas deferens. Simultaneous vasovasostomies at two separate sites may lead to devascularization of the intervening segment with fibrosis and necrosis and, therefore, not recommended. Sperm aspiration (vasal or epididymal) and assisted reproduction are better.

 

Varicocelectomy and Vasovasostomy

Simultaneous repair of varicocele and Vasovasostomy/vasectomy reversal remains a controversial issue. When varicocelectomy is properly performed all spermatic veins are ligated and the only remaining avenues for testicular venous return are the vasal veins. In men who have had vasectomy and are presenting for reversal, the vasal veins are likely to be compromised from either the original vasectomy or the reversal itself. Furthermore the integrity of the vasal artery in those men is also likely to be compromised. Varicocelectomy in such men requires preservation of the testicular artery as the primary remaining testicular blood supply as well as preservation of some avenue for venous return. Because of the significantly increased risk of testicular atrophy and varicocele recurrencevaricocelectomy should not be performed simultaneously with a vasovasostomy or a vasoepididymostomy. The vasovasostomy or vasoepididymostomy should be performed first. The semen quality should then be assessed post-operatively. If necessary, varicocelectomy can be safely performed 6 months or more later when venous and arterial channels have formed across the anastomotic line. This two stage delayed approach has been completed a dozen times with no atrophy or recurrence. The varicocelectomy should be performed microscopically to preserve the testicular artery, since atrophy can occur after testicular artery ligation even when the vasal blood supply to the testis is intact.

Interestingly, the marked increase in recurrences when the cremasteric veins and peri-arterial venous network were left intact suggest that these veins contribute to a significant proportion of varicocele recurrences.

 

Vasoepididymostomy 

Vasoepididymostomy (anastomosis between vas deferens and epididymal tubule) is the most technically difficult microsurgical procedure.

The decision to perform vasoepididymostomy is made intraoperatively since in most cases preoperative evaluation cannot indicate the level of obstruction of the excurrent duct system. The indications to perform vasoepididymostomy are based usually on certain intraoperative findings: 1. Presence and type of intravasal fluid, presence or absence of the sperm in the intravasal fluid. 3. Microsurgical training and experience

1. Vasoepididymostomy is recommended when intravasal fluid is thick, toothpaste-like, and creamy. This fluid is usually devoid of sperm. If copious watery and clear fluid is pouring from the testicular end of the vas deferens, vasovasostomy may be performed even in the absence of the sperm in this fluid. Successful vasovasostomies with return of the sperm in the ejaculate have been documented in this clinical situation. Overall, up to 30% of men with bilateral absence of sperm in the vasal fluid will have sperm return to the ejaculate after vasovasostomy. Occasionally, no intravasal fluid is found intraoperatively. Gentle barbotage of the testicular end of the vas with 0.1 ml of normal saline may reveal sperm in the expressed fluid.

2. The absence of sperm in the intravasal fluids at the time of surgery indicates the epididymal obstruction. Epididymis should be evaluated for the presence of the dilated tubule, demarcation line or granuloma and vasoepididymostomy performed by an experienced microsurgeon

The principles of microsurgical Vasoepididymostomy are mainly the same as of Vasovasostomy: accurate, tension free mucosal reapproximation with maximal preservation of the blood supply. In general, vasoepididymostomy is performed by approximation of the

  1. epididymal tubule and vasal mucosa with 3-4 double-armed 10-0 Prolene or Nylon sutures applied always inside out to minimize the injury to the tubule.
  2. approximation of muscularis and adventitial layers of vas deferens and epididymal tunic. 
     
  1. End to-end and vasoepididymostomy is performed in cases of distal epididymal obstruction. Another indication is compromised vasal length. The epididymis may be dissected of the testis, which provide additional length necessary for tension-free anastomosis. The epididymis is dissected at the Vasoepididymal junction and serially transected at 1-2 mm intervals until a tubule with high fluid flow abundant sperm is found. Since coiled epididymal tubule may be transected tangentially, it is extremely important to identify real end tubule appropriate for the anastomosis. This tubule should have a clear round opening with continuous flow. Sometimes the epididymis has to be recut to obtain clear tubule. Subsequent anastomotic technique generally resembles multilayered vasovasostomy.
  2.  End to side vasoepididymostomy. This is the preferred technique for proximal epididymal obstruction and when vasal length is not compromised.
  3. The end-to-side technique minimally disturbs the epididymal blood supply. Single dilated epididymal tubule is visualized through the epididymal tunic under the operating microscope. A 3-4 mm round opening (buttonhole) is made in the tunic with microscissors corresponding roughly with the outer diameter of the previously prepared vas deferens. The dilated loops of tubule are clearly exposed with blunt and sharp dissection. A tiny round window is performed in the epididymal tubule with small blunt scissors. Epididymal fluid is examined under the light microscope aspirated and cryopreserved. Methylene blue or indigocarmine can be used to outline tubular opening. It is recommended to use these agents after aspiration of the fluid since they may affect sperm motility. The mucosal anastomosis performed with double armed, 10-0 Prolene or Nylon sutures on fishhook bent needle. The epididymal tunic is approximated with and muscularis and adventitial layers of the vas deferens.

    Results of the vasoepididymostomy are best when anastomosis performed lower at the epididymis.  

    In every case of vasoepididymostomy epididymal fluid with sperm has to be aspirated and cryopreserved for possible future use in the assisted reproduction. 

    Vasoepididymostomy should only be performed at the level where sperm is present in the epididymal tubule.


    III. Dr. Richard Berger (University of Washington, Seattle) has recently introduced the Triangulation end- to- side technique. The three 10-0 double-armed nylon sutures are placed in triangulating fashion through the epididymal superficially. This maneuver usually associated with the leakage of epididymal fluid, which can be examined and aspirated. The opening of the epididymal tubule is made with a microknife or microcutting needle. Then each needle of 10-0 nylon sutures is passed equidistantly inside the lumen of the vas deferens to three quarters of the way out of the muscularis layer (3 and 5 o'clock position, 7 and 9 o'clock position and 1 and 11 o'clock position). Preplacement sutures make this procedure somewhat easier but presence of sperm in the epididymal tubule cannot be evaluated before sutures placement. Also, opening the tubule after sutures placement sometimes leads to cutting of the preplaced the suture. Invagination of the epididymal tubule may help to prevent sperm leakage and scarring of the anastomosis.

     

    Results of microsurgical reconstructive procedures.


Procedure

     

Patency

     

Pregnancy

     

Late stricture

     

Vasovasostomy

     

73-99%

     

50-65%

     

12%

     

Vasoepididymostomy

     

50-80%

     

31-65%

     

21%

     


    Complications of microsurgical reconstructive procedures

    Hematoma

    Sperm Granuloma

    Stricture of the anastomosis

    Wound Infection

     

     

    Transurethral resection of the ejaculatory ducts(TURED). Azoospermia or oligospermia with decreased ejaculate volume (<1.5ml), PEU negative for sperm, negative fructose test in patients with normal testicular size and palpable vas deferens indicate the possibility of ejaculatory duct obstruction (EDO). Vasography is mostly replaced by transrectal ultrasound as a primary diagnostic imaging modality. Aspiration of seminal vesicles confirms the absence of epididymal obstruction if sperm are present in the aspirate. Treatment involves surgical unroofing of ejaculatory duct region using transurethral resection. If scrotal exploration and vasography are performed, both vasa injected with Methylene blue to facilitate efflux and determine efficacy of resection. Methylene blue can also be injected directly into the seminal vesicles before surgery during transrectal ultrasound examination. Transurethral resection performed at the area of verumontanum with 1-2 cuts until blue efflux is observed. Cauterization to the area should be mainly avoided to prevent scarring.

    TURED results in increased semen volume about 2/3 of the time and appearance of sperm in the ejaculate in about 50% of azoospermic men

    Complications

    Rectal injury

    Hematuria

    Epididymitis secondary to reflux of urine

    Restenosis 

    Retrograde ejaculation

    Nonreconstructable Obstructive Azoospermia

    Sperm retrieval with ART (IVF-ICSI) is the treatment of choice for group of men with reproductive tract obstruction when restoration of genital tract continuity is not possible or associated with extremely low success rates (congenital anomalies e.g. CAV, severe loss of vasal length, failed multiple reconstructive procedures). It is difficult sometimes to differentiate between these groups preoperatively, therefore the microsurgeon needs to be skilled in different reconstructive procedures and sperm retrieval techniques.

     

    Microsurgical Autogenous Sperm Reservoir was first described by Moni and Lalita( 1992). The reservoir is created by the marsupialization of epididymal tubule to the visceral layer of the tunica vaginalis. Sperm subsequently may be aspirated from the reservoir under sonographic guidance by fine needle percutaneous technique and used for assisted reproduction. However, this method is not widely accepted because of advances in direct sperm retrieval techniques and cryopreservation.

    Although sperm retrieval techniques may be universally applied to any patient with obstructive azoospermia, microsurgical reconstruction plays an important role for men who desire to conceive naturally.

    After diagnosis of obstructive azoospermia is established, treatment options results and complications have to be fully discussed to help couples choose the best therapy for their particular situation. ART may not be advised when simpler, more cost-effective treatment is available.

    Selected Bibliography

 

  1. Lemack GE, Goldstein M. Presence of sperm in the prevasectomy reversal semen analysis: Incidence and implications. Jurol 1996;155:167-169
  2. Moni VN, Lalitha PA. Moni's window operation: a new surgical technique to create a sperm reservoir in congenital vasal agenesis. J Urol 1992;148:834-844
  3. Zini A., Girardi S., Goldstein M. Complex vasal reconstruction. Advances in Urology, 1997; vol 10 121-141
  4. Pryor JP, Hendry WF. Ejaculatory duct obstruction in subfertile males: analysis of 87 patients. Fertil Steril 1991;56:725-730
  5. Sheynkin YR., Hendin BN.,Schlegel PN., Goldstein M. Microsurgical repair of iatrogenic injury to the vas deferens. J Urol 1998;159:139-141
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