Surgical Management

Male factor infertility is prevalent, impacting 7% of the population and potentially affecting half of all couples attempting to conceive. A range of surgical and reconstructive options offers opportunities for biological paternity, contingent upon the underlying causes of male factor issues. This article explores historical and contemporary treatments, examining the roles of traditional open surgery, microsurgery, robotic surgery, and interventional radiologic procedures in addressing male infertility.

What is Surgical Management for Male Infertility?

Infertility, typically defined as the inability of a couple to conceive after 12 months of unprotected intercourse, affects around 15% of individuals. Among these cases, approximately 50% are attributed to female reproductive factors, 30% to male factors, and about 20% involve contributions from both partners. It's crucial for both partners to undergo evaluation before considering further treatments, even if an abnormality is found in one partner's assessment.

Male factor infertility, characterized by abnormal semen analysis as per World Health Organization criteria, impacts roughly 7% of the population. A more severe form, azoospermia—where sperm is absent in multiple ejaculated samples—occurs in about 1% of men.

This article explores procedures aimed at improving suboptimal semen parameters, such as varicocele repair, or restoring fertility, including vasectomy reversal and relieving ejaculatory duct obstruction (EDO). When natural conception isn't viable, various techniques can aid in retrieving sperm for assisted reproductive technologies. Surgical interventions for male infertility have played a significant role in enabling previously infertile couples to conceive their biological children.

Varicocele

Varicocele, characterized by the dilation of the pampiniform plexus, stands as the most prevalent identifiable cause of male factor infertility. Clinically, varicoceles are graded based on physical examination findings: Grade I, palpable with the Valsalva maneuver; Grade II, palpable at rest without the Valsalva maneuver; and Grade III, visibly prominent. Subclinical varicoceles, detectable solely via scrotal sonogram, are commonly encountered, with reported prevalence rates ranging from 8% to 81%, contingent upon the patient population. Studies reveal varying incidence rates across different cohorts; for instance, a seminal study involving 275 military men reported clinical varicoceles in 8% of the population. Conversely, research involving 100 fertile men seeking vasectomy revealed varicocele in 61%, with 17% exhibiting clinical varicoceles. Notably, clinical varicocele prevalence was found to be 12% among men with normal semen analyses presenting for infertility evaluation, escalating to 25% among those with abnormal semen parameters. Furthermore, varicocele prevalence was notably higher among men with secondary infertility (81%) compared to those with primary infertility (35%).

Color Doppler ultrasonography (CDUS) serves as a highly sensitive and specific diagnostic tool for varicocele, assessing the maximum venous diameter in the pampiniform plexus alongside evidence of retrograde flow during the Valsalva maneuver. It offers more objective data, particularly regarding venous diameter in millimeters, compared to relying solely on physical examination. However, similar to physical exams, CDUS evaluation is subject to limitations stemming from patient positioning, relaxation level, ultrasonographer expertise, and probe placement. While there's general consensus among physicians regarding a cutoff value of multiple veins exceeding 3 mm in diameter with retrograde flow for varicocele diagnosis, there's debate over the pathological significance of veins larger than 1 mm or 5 mm (11). Although the Male Infertility Best Practice Policy committee doesn't routinely endorse CDUS for subfertile patients with suspected varicoceles, it can serve as a valuable adjunct for patients with challenging physical examinations, such as those who are obese, have a small scrotum, or present with scarring from previous surgeries.

The most prevalent semen abnormalities linked to clinical varicocele in men seeking fertility evaluation often include low sperm count (oligospermia), decreased motility (asthenospermia), and/or poor morphology (teratospermia). However, it's worth noting that semen parameters may also appear normal in some cases. Research on subclinical varicoceles yields mixed results; although they are common (up to 61%), few studies have assessed semen quality in this context.

The precise mechanism by which varicoceles may contribute to male factor infertility remains unclear. Several theories based on experimental models have been proposed, including increased testicular temperature leading to adverse effects on Sertoli cells and spermatogenesis, testicular hypoxia, reductions in intratesticular testosterone levels, venous stasis resulting in the accumulation of toxic metabolites and increased oxidative damage, and modifications of the androgen receptor. Additionally, Leydig cell dysfunction due to elevated testicular temperature may also contribute to hypogonadism. Despite various etiologic theories supported by some evidence, conclusive data explaining why some men present with infertility while the majority of varicocele patients do not are still lacking.

The effectiveness of varicocele repair in improving fertility outcomes is heavily influenced by several factors, including the initial indication for repair (clinical versus subclinical varicocele, normal versus abnormal semen parameters) and the measured outcome (improvement in semen parameters versus pregnancy and live birth). The diverse data available, even within randomized clinical trials, along with high dropout rates, pose challenges in generalizing conclusions from any single study. A meta-analysis of seventeen studies indicated that repair of clinical varicoceles in men with abnormal semen analyses improves sperm concentration and motility, yet its impact on pregnancy remains less clear. Another recent meta-analysis of four randomized controlled trials focusing on pregnancy outcomes after varicocele repair in oligospermic men revealed that although individual studies reported improved pregnancy rates, considering the heterogeneity within the treatment population, the results were not statistically significant.

The conclusions drawn from meta-analyses vary depending on the inclusion criteria of the studies analyzed. For instance, a 2004 Cochrane meta-analysis involving eight studies found no evidence supporting varicocele treatment as beneficial for increasing conception rates. However, Ficarra et al. highlighted in 2006 that this analysis included patients with both normal semen analyses and subclinical varicocele. Upon reevaluation, focusing solely on three studies involving patients with abnormal semen analyses and clinical varicoceles, they observed a statistically significant difference in pregnancy rates, even accounting for intention-to-treat analysis and a notable rate of loss of follow-up after 12 months. A more recent Cochrane meta-analysis of ten studies also included patients with normal semen analyses and subclinical varicocele, but planned subgroup analysis of five studies excluded these patients. Both initial and subgroup analyses indicated potential improvements in pregnancy chances following varicocele treatment, yet highlighted significant heterogeneity and advocated for further research.

Current guidelines on varicocele treatment come with significant qualifiers: The Practice Committee of the American Society for Reproductive Medicine suggests varicocele repair for adolescents with reduced ipsilateral testicular size and infertile adult men with a clinical varicocele, abnormal semen analysis, and a partner with normal or correctible fertility. Meanwhile, the European Association of Urology's 2012 update recommends varicocele repair for infertile couples with clinical varicocele, oligospermia, infertility lasting over two years, and otherwise unexplained infertility.

Controversy persists regarding the benefits of repairing subclinical varicocele in subfertile patients without other identifiable causes. Studies show mixed results, with some indicating improved semen parameters postoperatively, while others show worsening. Various repair methods, including surgical and percutaneous embolization, have been employed. While some randomized clinical trials demonstrate improved semen parameters post-treatment, they do not consistently show an increase in pregnancy rates. However, a recent small nonrandomized retrospective study showed significant improvement in sperm count and pregnancy rates with surgical correction compared to medical management and observation groups.

Regardless of the treatment modality, the principle of varicocele repair remains consistent: occlusion of veins to eliminate the varicocele, preservation of testicular blood supply, and prevention of post-procedural hydrocele formation by preserving lymphatic vessels.

Surgery

Surgical intervention remains the primary method for varicocele repair and can be accomplished through various techniques:

(I) Open approach via retroperitoneal, inguinal, or subinguinal routes.
(II) Microsurgical technique through an inguinal or subinguinal incision.
(III) Laparoscopic procedure utilizing three, two, or single-port incisions.
(IV) Robotic-assisted surgery, employing either a transperitoneal approach or a subinguinal incision.

Varicocelectomy entails the ligation of abnormally dilated veins within the spermatic cord while preserving arterial and lymphatic supply, as well as the deferential veins. The specific location of vein ligation depends on the chosen approach. For instance, during varicocelectomy via an inguinal or subinguinal incision, the cremasteric and internal spermatic veins are ligated, whereas retroperitoneal varicocelectomy involves ligating the testicular vein. Open and laparoscopic retroperitoneal techniques may involve intentionally dividing the testicular artery above the internal inguinal ring, with collateral arterial inflow compensating for blood supply to the testis. Conversely, in inguinal and subinguinal approaches, all encountered arteries are preserved.

A comprehensive 2009 meta-analysis underscores microsurgical varicocelectomy as the premier choice for varicocele repair, boasting the lowest rates of hydrocele formation (0.4%) and recurrence (1%) compared to alternative methods. Recent evaluations focusing solely on randomized controlled trials have reaffirmed these findings. In these comparisons, two studies evaluated all three surgical approaches (open, laparoscopic, and microsurgical), while the remaining two studies scrutinized open and microsurgical repairs exclusively. Results indicate a statistically significant superiority of microsurgery over laparoscopic and open techniques in reducing hydrocele formation and recurrence, with no notable disparity in these outcomes between laparoscopic and open surgery (Refer to Table 1). Although two smaller studies found little variance in outcomes between subinguinal and inguinal microsurgical varicocelectomies, they yielded conflicting results concerning postoperative pain. Shiraishi et al. reported heightened scrotal discomfort with subinguinal incisions, whereas Pan et al. attributed increased pain in the inguinal group to muscle and fascia.

No comparative studies have been conducted between robotic transperitoneal varicocelectomy and laparoscopic varicocelectomy, with only one report found in the literature demonstrating its application in two patients. However, several small-scale studies have explored the efficacy of robot-assisted microsurgical varicocelectomies. Shu et al. conducted a pilot study comparing operative times between microsurgical subinguinal varicocelectomy and robotic subinguinal varicocelectomy, revealing no significant differences. Nonetheless, it remains unclear what specific indications prompted varicocelectomy and whether the operative time accounted for setup time involving the daVinci® robot system. Furthermore, semen parameters were not assessed. In a more recent non-randomized, non-controlled study involving 154 patients (including 106 with chronic orchialgia, some exhibiting oligospermia, and 77 with oligo- or azoospermia), it was found that 77% of patients with oligospermia and 18% of those with azoospermia experienced improvements in semen parameters.

Nonobstructive azoospermia (NOA)

Non-Obstructive Azoospermia (NOA), a condition marked by impaired sperm production leading to a lack of sperm in the ejaculate, can manifest as primary or secondary, congenital or acquired. In a study involving 1,583 azoospermic patients, 12% exhibited no discernible cause, though this figure is lower than previously reported in literature. Sex chromosome abnormalities accounted for 21% of cases, with Klinefelter's Syndrome prevalent in 14% and Y chromosome microdeletions in 1.7%. Urogenital infections were attributed to ten percent of cases, while chronic unspecified diseases and malignancies without gonadotoxic treatment contributed seven percent and six percent, respectively.

While correction of endocrinopathies may restore fertility in cases of hypogonadotropic hypogonadism, most NOA patients lack medically or surgically correctable options. Traditionally, donor insemination or adoption were necessary for family building. However, the advent of intracytoplasmic sperm injection (ICSI) in the early 1990s revolutionized treatment possibilities. Testicular sperm retrieved via standard testicular sperm extraction (TESE) or microdissection testicular sperm extraction (microTESE) can now be used with in vitro fertilization (IVF) and ICSI to fertilize oocytes successfully. Some centers have even introduced robotic-assisted microsurgical TESE procedures.

Open Testicular Sperm Extraction (TESE) involves creating a small incision or multiple incisions in the tunica albuginea, allowing the surgeon to extract tubules from the testis using surgical scissors. In contrast, microTESE, pioneered by Schlegel, follows a more standardized approach. This technique entails a transverse hemispheric incision in the tunica albuginea, enabling the surgeon, under magnification, to selectively collect larger, more opaque seminiferous tubules. Recent studies have demonstrated the superiority of microTESE over traditional TESE in sperm retrieval rates. For instance, one study reported a 56.9% success rate with microTESE compared to 38.2% with standard TESE. Moreover, certain patient subsets, including those with Klinefelter Syndrome, chemotherapy-induced azoospermia, post-orchidopexy azoospermia, and Y microdeletions in the AZFc region, are found to benefit optimally from microTESE. These populations often exhibit limited areas of sperm production in the testes, necessitating the use of optical magnification for identifying dilated, opaque seminiferous tubules. Ongoing efforts include the development of a predictive nomogram to assess the likelihood of successful sperm retrieval before microdissection, with preliminary findings highlighting factors such as Klinefelter Syndrome and cryptorchidism history as significant predictors.

Efforts to enhance the microdissection technique have been ongoing, particularly addressing concerns regarding its prolonged operative duration compared to traditional TESE. A recent retrospective analysis involving 900 patients revealed sperm retrieval success during initial unilateral microdissection in 474 individuals. However, the success rate for locating sperm in the contralateral testis during bilateral microdissection after initial exploration failure was merely 8%. This study suggests that specific patient groups, such as those with Klinefelter Syndrome or hypospermatogenesis, might benefit from contralateral dissection if initial unilateral sperm retrieval proves unsuccessful. Additionally, a small-scale investigation incorporating systematic upper, middle, and lower pole biopsies alongside microTESE demonstrated potentially higher success rates (66.2%) in sperm retrieval compared to individual techniques.

Furthermore, contemporary advancements in microsurgical procedures have introduced robotic assistance. While limited data are available, one study group reported conducting twelve robotic-assisted microsurgical TESE procedures, noting feasibility without complications among their study population.

A noteworthy supplement to TESE (Testicular Sperm Extraction) is the incorporation of varicocelectomy, particularly in patients with Non-Obstructive Azoospermia (NOA) and clinical varicocele. A recent observational study involving 36 patients shed light on the optimal timing of varicocelectomy. Among them, 19 individuals with grade 3 unilateral left varicocele and NOA underwent microsurgical inguinal varicocelectomy three months before magnified (loupe) TESE, while 16 underwent both procedures simultaneously. The study revealed a significant enhancement in sperm retrieval rates during TESE when varicocelectomy was performed earlier (57.8% vs. 25%). Interestingly, six months post-TESE, both groups exhibited the presence of sperm in ejaculated samples (57.8% vs. 37.5%), even though no semen analysis was conducted during the interval period before TESE in patients who had undergone prior varicocelectomy.

In another study, Inci retrospectively analyzed 96 nonrandomized patients with any grade clinical varicocele and NOA, 66 of whom underwent microsurgical inguinal/subinguinal varicocelectomy one year before microTESE. A semen analysis was conducted on the day of microTESE to confirm persistent azoospermia prior to the attempt at surgical sperm extraction. The findings indicated a significant improvement in surgical sperm retrieval rates (53% vs. 30%). This improvement was also validated by Haydardedeoglu et al. (60.8% vs. 38.5%), who observed enhancements in implantation, clinical pregnancy, and live birth rates among men with NOA and a history of grade 3 varicocele repair. Unlike Zampieri's study, they observed higher pregnancy rates in patients with a shorter interval since varicocelectomy, although the time intervals were considerably longer (an average of 40 months since the prior varicocelectomy in the shorter group). These studies contrast with Schlegel's initial 2004 study, which found comparable microTESE retrieval rates (60%) between varicocelectomy and non-varicocelectomy groups. It's worth noting that this population included patients with subclinical varicocele.

Over the past two decades, the utilization of surgically-retrieved sperm for IVF-ICSI has become increasingly common, prompting some men to opt for repeat procedures. One retrospective study, examining 126 cases of repeat microTESE following 963 initially successful microTESE procedures, reported a sperm retrieval rate of 82%. In this cohort, the pregnancy rates after initial and repeat microTESE were 42% and 39%, respectively (68). Another retrospective analysis of 216 patients who had undergone prior TESE revealed varying success rates based on their history: 81% success in patients with NOA and a previously successful TESE, contrasted with a mere 27% success rate in those with a history of unsuccessful initial TESE (69).

It's important to note that neither TESE nor microTESE procedures are devoid of risks. Both carry the potential for complications such as bleeding, hematoma, infection, and scar formation within the testicles, along with the possibility of excessive tissue removal leading to hypogonadism. Following microTESE, serum testosterone levels may decrease to 80% of baseline within 3-6 months, with subsequent recovery to 95% by 18 months (70). However, the long-term impacts of TESE, whether microdissection or standard, on testicular histology and spermatogenesis remain uncertain.

Obstructive azoospermia (OA)

Obstructive azoospermia (OA), characterized by a blockage in the reproductive tract resulting in the absence of sperm in the ejaculate, is less prevalent compared to non-obstructive azoospermia (NOA), with reported rates ranging from 11% to 40%. Surgical intervention serves as the primary treatment approach, either through sperm extraction procedures or by addressing the obstruction through reconstruction or alleviation. The causes of OA can be either congenital, such as congenital bilateral absence of the vasa deferentia (CBAVD), or acquired, including factors like vasectomy, scarring from past infections, or iatrogenic injuries stemming from previous inguinal surgeries.

Sperm retrieval

Sperm retrieval methods serve as the ultimate recourse for patients with obstructive azoospermia (OA) who either opt against reconstructive procedures, have experienced failed reconstructions, or possess anatomies unsuitable for reconstruction. These techniques encompass the aspiration of sperm from either the epididymis (percutaneously or via open surgery, with or without microscopic assistance) or the testis (percutaneously or via open surgery).

Percutaneous epididymal sperm aspiration (PESA) entails the percutaneous insertion of a small-gauge needle into the epididymis, followed by the aspiration of epididymal fluid. PESA offers the advantage of being technically straightforward and obviates the need for an operating room, general anesthesia, or specialized microsurgical expertise. In the largest study conducted on PESA thus far, which involved 255 patients with various etiologies of OA, such as congenital bilateral absence of the vas deferens (CBAVD), vasectomy, unsuccessful vasovasostomy (VV), and iatrogenic vasal injuries, researchers reported success rates of 75% in obtaining abundant motile sperm, 9% in finding rare motile sperm, 11% in locating nonmotile sperm, and 5% in yielding no sperm. Nineteen percent of patients subsequently underwent testicular sperm extraction (TESE), with mature spermatozoa identified in all cases. The study authors noted a notable tendency for older patients and those with smaller testicular volumes to necessitate progression to testicular sperm retrieval procedures.

The microsurgical epididymal sperm aspiration (MESA) procedure was initially introduced in 1994 for patients with CBAVD. This technique involves a small incision to access the epididymis, where individual tubules are isolated and punctured to aspirate fluid. MESA offers the advantage of directly identifying tubules, which is particularly beneficial in cases of extensive scarring or proximal obstruction. It can also be attempted following unsuccessful PESA procedures. However, studies directly comparing MESA and PESA are lacking, with only a few initial studies investigating sperm retrieval rates in MESA.

In cases where epididymal sperm extraction fails or at the practitioner's discretion, patients may opt for testicular sperm extraction (TESE) for use in intracytoplasmic sperm injection (ICSI). TESE can be performed via percutaneous or open methods. Percutaneous needle aspiration, performed with different numbers of passes and needle gauges, shows some evidence suggesting that larger needles (18- or 19-gauge) may be more successful in sperm retrieval compared to smaller (21-gauge) needles. Limited older studies describe percutaneous testicular biopsy using a biopsy gun, indicating increased yield and consistent preservation of testicular architecture compared to needle biopsy. However, these studies also report avascular areas in the testes post-gun biopsy on ultrasound, likely due to small arterial rupture.

Percutaneous techniques for obstructive azoospermia (OA) typically yield successful sperm retrieval rates suitable for intracytoplasmic sperm injection (ICSI), with numerous studies reporting success rates exceeding 95% for both epididymal and testicular sperm extraction (118). In one investigation, testicular sperm extraction (TESE) achieved a 100% sperm recovery rate, coupled with ICSI fertilization rates of 66% and live delivery rates of 62% (119). Furthermore, a comprehensive analysis involving 1,121 men diagnosed with OA, who underwent either epididymal or TESE procedures for ICSI, revealed that neither the origin nor the cause of the obstruction significantly impacted fertilization or pregnancy rates.

A Note from Kamakhya Andro-Uro Care & Fertility Clinic:

In today's era of advanced reproductive technologies, microsurgery, and robotic procedures, the surgical treatment of male infertility presents a complex yet promising landscape. These interventions offer biological fatherhood to men who, in the past, may have only considered adoption or sperm donation as options for parenthood.