14.1 Introduction

Obstructive pathology is a common cause of male factor infertility, affecting up to 40% of men presenting with azoospermia [1]. A wide variety of etiologies can result in obstructive azoospermia (OA), ranging from iatrogenic to infectious to congenital causes. Today’s reproductive urologist has a multiple of treatment options to offer patients faced with a diagnosis of OA. We believe that reconstruction remains the gold standard for the appropriately selected couple, whereas a staged operative plan is required should sperm retrieval prove necessary. Just as important as facility resources and provider experience, a treatment plan must also consider the risks, benefits, and success rates of any planned intervention. Careful counseling and objective consideration of existing data will guide the urologist to a tailored treatment plan. In the review below, we will present the advantages and disadvantages for the various therapeutic options that can be employed for OA. Special attention will be paid to microdissection testicular sperm extraction (microTESE), as it serves as an important rescue procedure in difficult cases and is overall underutilized for the OA population.

14.2 Reconstruction Versus Sperm Retrieval

OA can now be successfully treated with a number of treatment options, ranging from definitive reconstruction to the myriad of sperm retrieval techniques (Table 14.1). Prior to the widespread use of intracytoplasmic sperm injection (ICSI), the only options for men with OA were vasovasostomy (VV) and/or vasoepididymostomy (VE). Before the ICSI era during the 1980s and 1990s, significant effort was spent optimizing both of these techniques. In experienced hands, it can now be expected that post-operative patency rates will approach at least 85% for a primary VV [2]. Outcomes following reconstruction have typically been reported as clinical pregnancy within a short term of follow-up, ranging up to 53% at 2 years post-procedure [3]. Success rates diminish if the patient requires a bilateral VE. It is difficult to predict which individuals may require bilateral VE, and just as important, how proximally along the epididymis a surgeon must anastomose the vas deferens. Though published outcomes still favor reconstruction in these scenarios, it is necessary to realize that fertility potential is a function of anastomosis location, with clinical pregnancy rates dropping precipitously for a VE near the efferent ducts.

Reconstruction has been shown to be cost-effective compared to upfront sperm retrieval for the purposes of ICSI [4,5]. Undertaking VV or VE may obviate the need for future procedures in the female partner, and as a result, prevent complications that are associated with assisted reproductive technology (ART) and the accompanying risk of negative perinatal outcomes. For couples that desire multiple children, reconstruction is particularly beneficial as it offers an established and reliable source of future sperm. Although data is limited regarding the long-term safety of ICSI, natural conception following VV or VE maintains the putative adaptations of natural fertilization of the oocyte, selecting against sperm that are suboptimal. To date, preliminary data suggests that ICSI is reasonably safe, at least in regard to the risks of congenital malformation and early childhood development [6]. Time will tell if the initial ICSI generation maintains comparable health outcomes to their naturally conceived peers.

For couples that face a significant female factor, reconstruction may not be the best initial option. One recent study established the kinetics of male reproductive potential following VV and VE [7]. It can take more than 6 months following reconstruction for sperm to return to the ejaculate in sufficient numbers, a duration that may be unacceptable for situations involving advanced maternal age. Additionally, certain clinical characteristics of the male partner will serve as contraindications to reconstruction, as is the case for congenital bilateral absence of the vas deferens. Nevertheless, a discussion of the risks and benefits of VV/VE is necessary in most couples presenting with OA, which is reflected in the most recent committee opinion by the American Society of Reproductive Medicine [8]. As always, treatment decisions must be adjusted to the individual needs and wishes of the couple.

14.3 Sperm Retrieval: Staged Intervention

The reproductive urologist can utilize a multitude of techniques and anatomical sources for sperm should the treatment plan progress to sperm retrieval. Appropriate pre-operative counseling of the male partner will include a description of these various techniques, success rates, risks, and benefits. Since no single surgical approach is ideal for all patients with OA, options for management including a staged approach should be outlined at the time of informed consent. Generally speaking, it is our opinion that microTESE should be used primarily as a back-up procedure in the event initial retrieval attempts fail.

We believe that the operative plan should ideally begin with an attempted retrieval from the epididymis. Early data for OA, in which use of epididymal sperm for assisted reproduction was compared against testicular sperm, suggested some limited benefit of epididymal sperm for ICSI outcomes, although cases were not directly matched [1]. However, in one of the largest OA cohorts where sperm source was evaluated, van Wely and colleagues demonstrated a statistically significant difference in live birth rates favoring an epididymal source [9]. In their retrospective analysis, 280 men who underwent microsurgical epididymal sperm aspiration (MESA) obtained a live birth rate of 39% compared to 24% in men who required testicular sperm extraction (TESE). After adjusting for maternal age and ovarian reserve, their data demonstrated an odds ratio of 1.82 (CI 1.05–3.67) supporting the use of MESA-derived sperm. It is possible that the MESA approach, where the epididymis is searched microscopically and the most promising regions of the epididymis are aspirated, provides for optimal sperm quality.

Although van Wely and colleagues obtained good results using MESA, percutaneous approaches remain a viable option for the initial technique in a staged operative plan. Percutaneous epididymal sperm aspiration (PESA) allows for office-based retrievals under local anesthetic, eliminating the costs and logistics of the operating room and anesthesia. A percutaneous approach is useful if a fresh sample is required for ART, or in the unexpected situation of a male partner unable to produce a semen sample. PESA does not require microsurgical equipment or microsurgical training. In a large series of 146 men, Esteves and colleagues were able to retrieve motile sperm with PESA alone in 78% of cases [10]. As a rescue, they preferred testicular sperm aspiration (TESA), which was successful in all but four patients. However, percutaneously retrieved sperm does not allow selection of the best region of epididymal sperm. Authors have suggested that percutaneously retrieved epididymal sperm may have increased sperm DNA fragmentation, thereby risking worse reproductive outcomes [11].

PESA is an initial option in sperm retrieval, if one accepts the limitation of sperm quality discussed above. If resources and timing permits, however, we recommend MESA for obtaining epididymal sperm. In terms of complications, open techniques tend to be safer than percutaneous approaches since bleeding can be recognized and controlled, thereby minimizing the risk of post-operative hematoma [8]. Another advantage of MESA is the direct visualization of the epididymis. It is common to observe under magnification macrophage-laden tubules that should be avoided, as sperm from these locations will often carry significant DNA fragmentation and will usually lack motility. It is also apparent that in obstructed systems, the macrophage concentration increases as one progresses distally along the epididymis. With PESA the surgeon is blinded to optimal tubule selection, whereas during MESA the yellowish tubules associated with poor sperm quality can easily be avoided [9]. An additional consideration is the ability to cryopreserve sperm following MESA. In the PESA series conducted by Esteves and colleagues, only 27% of cases yielded enough specimen to allow for freezing [10]. MESA reliably produces enough sperm to allow for cryopreservation, a notable advantage since most couples will require at least two cycles of IVF for one live birth. Thus, MESA will avoid subsequent sperm retrieval procedures, allows for optimal epididymal tubule identification for high-quality sperm, and offers the ability to escalate the operative intervention should TESE prove necessary. Although PESA can fall back on percutaneous testis sampling, these procedures expose the patient to the same risk of hematoma as PESA, although typically more reliable in terms of successful sperm retrieval in OA [11,12].

The role of microTESE becomes significant for the atypical presentation of nonobstructive azoospermia when the initial workup suggests OA. The seminal study by Schoor and colleagues established that a follicle-stimulating hormone (FSH) of less than 7.6 mIU/mL, in combination with a testicular long-axis dimension of at least 4.6 cm, predicted OA in 96% of cases, and will accurately diagnose nonobstructive azoospermia with a rate of 89% [13]. These preoperative rubrics have effectively eliminated the use of diagnostic testis biopsy in modern practice. However, it is apparent that approximately 1 in 20 men considered to have OA by these criteria will actually harbor a defect in sperm production. The initial presentation may further be clouded by accompanying risk factors for OA. For example, bilateral inguinal hernia repair is a common presenting history, and can be a cause for iatrogenic injury of both vasa. Unfortunately, other findings on physical examination, such as epididymal fullness or induration, are highly subjective, depend heavily on examiner experience, and perform poorly diagnostically for the average practitioner’s exam. Both men with nonobstructive azoospermia, and the approximate 15% of cases of OA secondary to obstruction at the rete testis, may have “flat” epididymides when examined by an experienced practitioner [1]. In both of these scenarios an epididymal source will fail, necessitating a testicular procedure.

Most men with impaired sperm production, low FSH, and preserved testicular size will have a form of maturation arrest on histology. Hung and colleagues conducted a retrospective case review of nonobstructive azoospermia evaluated at a single institution [14]. They identified 26 men out of 600 who demonstrated uniform maturation arrest, an FSH below 7.6 mIU/mL, and normal testis volume. The resulting rate of 26/600 (4.3%) was consistent with the earlier work conducted by Schoor and colleagues [13]. In another series by Tsai and colleagues, a normal FSH and testis volume was observed in 38% of cases when focusing only on patients with maturation arrest [15]. Given these data, it is clear that any high-volume reproductive urologist will periodically encounter occult maturation arrest despite a pre-operative diagnosis of OA. It is our opinion that these men benefit most from microTESE as compared to conventional TESE due to the maximal exposure for sampling favorable seminiferous tubules. Although a meta-analysis conducted by Deruyver and colleagues failed to demonstrate a statistical difference in sperm retrieval rates for maturation arrest comparing conventional TESE versus microTESE, it is notable that all included studies documented higher retrieval rates for the microTESE arm [16]. All of the included studies were unfortunately underpowered, with an average cohort of 30 maturation arrest subjects. Appropriately powered studies have yet to be conducted to differentiate the ideal TESE technique for this subpopulation. Just as important as sperm retrieval success, conventional TESE carries an increased complication rate compared to microTESE, a perspective that will be addressed in Section 14.4 of this chapter. For these reasons, we often prefer microTESE as the backup intervention should MESA fail to produce adequate quality or number of sperm.