Review Article

Surgical management of male infertility: an update

Monica Velasquez1,2, Cigdem Tanrikut1,2
1
Department of Urology, Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, Massachusetts, USA
Correspondence to: Cigdem Tanrikut, MD. MGH Fertility Center, Massachusetts General Hospital, 55 Fruit Street, YAW 10A, Boston, MA 02114,
USA. Email: ctanrikut@partners.org.

Abstract: Male factor infertility is common, affecting 7% of the total population and up to half of couples
who are trying to conceive. Various surgical and reconstructive options allow biological paternity depending
on the etiology of the male factor issues. This article describes historical treatments and newer approaches,
discussing the role for traditional open surgery, microsurgery and robotic surgery, as well as interventional
radiologic procedures in the management of male infertility.

Keywords: Male infertility; azoospermia; nonobstructive; varicocele; microsurgery; sperm retrieval; vasovasostomy (VV)

Submitted Nov 08, 2013. Accepted for publication Jan 21, 2014.
doi: 10.3978/j.issn.2223-4683.2014.01.05
Scan to your mobile device or view this article at: http://www.amepc.org/tau/article/view/3518/4364

Introduction As such, the surgical management of male infertility has

allowed many previously infertile couples to parent their
Infertility, classically defined as the inability of a couple
own biological children.
to conceive after 12 months of intercourse without
contraception, affects approximately 15% of the population.
Of these couples, 50% of cases are thought to be due to Varicocele
female reproductive factors alone, 30% secondary to male
Varicocele refers to dilatation of the pampiniform plexus
factor alone, and about 20% with a contribution from
and is the most common identifiable cause of male factor
both partners. Even if an abnormality is found during one infertility. Clinical varicoceles are rated on a grading
partner’s evaluation, both members of an infertile dyad system based on physical examination findings: Grade I,
should undergo assessment prior to proceeding with further palpable with Valsalva maneuver; Grade II, palpable at
treatments (1). rest without Valsalva maneuver; and Grade III, grossly
Male factor infertility, delineated by abnormal semen visible. Subclinical varicoceles are detected only via scrotal
analysis according to World Health Organization manual sonogram (5). They are a common finding with reported
criteria, is thought to affect approximately 7% of the ranges in the literature from 8-81% depending on patient
total population (2). The most severe form of infertility, population. The seminal study of 275 military men reported
azoospermia—the absence of sperm in at least two separate clinical varicoceles in 8% of their population (6), but one
ejaculated samples with examination of centrifuged samples— study of 100 fertile men presenting for vasectomy identified
affects approximately 1% of the general population (3), and up 61% of men with varicocele, 17% of which were clinical (7).
to 20% of the population who present to an infertility clinic (4). A clinical varicocele was reported in 12% of men with
This article discusses procedures that may improve normal semen analyses presenting for infertility evaluation,
suboptimal semen parameters, such as varicocele repair, and in 25% of men with abnormal semen parameters (8),
or restore normal fertility potential, such as vasectomy while another study population showed that varicocele was
reversal and relief of ejaculatory duct obstruction (EDO). present in 35% of men with primary infertility and 81% of
In circumstances when natural conception efforts are not men with secondary infertility (9).
possible, a number of techniques can facilitate the retrieval Color Doppler ultrasonography (CDUS) is both
of sperm for use in assisted reproductive technologies. highly sensitive and specific in the diagnosis of varicocele,

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Translational Andrology and Urology, Vol 3, No 1 March 2014 65

measured as maximum venous diameter in the pampiniform rate in these reports can make it difficult to generalize
plexus with evidence of retrograde flow during Valsalva from the conclusions of any one study. A meta-analysis
maneuver (10). It may provide more objective data (venous of seventeen studies confirmed that repair of clinical
diameter in mm) than physical exam alone. However, just varicoceles in men with abnormal semen analyses improves
as physical exam is limited by subjectivity and examiner sperm concentration and motility (14), but outcomes on
experience, varicocele assessment via CDUS is also affected pregnancy are less clear. Another recent meta-analysis of
by patient position and relaxation, experience of the four randomized controlled trials reporting on pregnancy
ultrasonographer, and location of the probe placement. outcomes after repair of clinical varicoceles in oligospermic
Furthermore, while most physicians agree with a cutoff men found that while each of the studies individually
value of multiple veins of greater than 3 mm diameter with noted improved pregnancy rates as an outcome, when the
retrograde flow in the diagnosis of varicocele, some suggest treatment population heterogeneity was taken into account
that any vein larger than 1 mm is pathologic, while others the results were not statistically significant (20).
suggest that only veins larger than 5 mm are clinically The meta-analysis results and recommendations have
significant (11). Currently the Male Infertility Best Practice varied depending upon which studies were included for meta-
Policy committee does not routinely recommend CDUS analysis. A 2004 Cochrane meta-analysis of eight studies,
in subfertile patients with suspected varicoceles (12), but it with pregnancy as the outcome of interest, concluded that
may be a useful adjunct for patients with a difficult physical there was no evidence that treatment of varicocele improved
exam, such as those who are obese, have a small scrotum, or the chance of conception (21). However, Ficarra et al. noted
scarring from prior surgery (13). in 2006 that this meta-analysis included both patients with
The most common semen abnormalities associated with normal semen analyses and subclinical varicocele. Their
a clinical varicocele in men presenting for fertility evaluation reanalysis of the data using only the three studies with
include low sperm count (oligospermia), decreased motility patients who had abnormal semen analyses and clinical
(asthenospermia), and/or poor morphology (teratospermia), varicoceles showed a statistically significant difference in
but as noted above semen parameters may also be normal (14). pregnancy rates even based on intention-to-treat analysis
The evidence regarding subclinical varicoceles is mixed: as and a high rate of loss of follow-up after 12 months (36.4%
previously noted, they are common (up to 61%) with few treatment group, 20% control group) (22). The most recent
studies assessing semen quality. The mechanism by which Cochrane meta-analysis of ten studies also included patients
varicoceles may contribute to male factor infertility is not with normal semen analyses and subclinical varicocele, but
yet well-understood. There are a number of theories based with a planned subgroup analysis of five studies which did
on experimental models, including increased testicular not include these patients. Initial and subgroup analyses both
temperature with subsequent negative impact on Sertoli cells suggested that varicocele treatment may improve chance
and spermatogenesis (15), testicular hypoxia (11), decreases of pregnancy, but they again noted high heterogeneity and
in levels of intratesticular testosterone (16), venous stasis suggested the need for further research (23).
leading to accumulation of toxic metabolites and increased The current recommendations regarding treatment
oxidative damage (17), and modifications of the androgen of varicocele remain heavily qualified: the Practice
receptor (18). Leydig cell dysfunction due increased testicular Committee of the American Society for Reproductive
temperature may also contribute to hypogonadism (19). Medicine recommends repair of varicocele in adolescents
While there are multiple etiologic theories supported by with reduced ipsilateral testicular size, and, in the infertile
some contributory data, there are no conclusive data to date couple attempting to conceive, in adult men with a
as to why some men present with infertility but the majority clinical varicocele, abnormal semen analysis, and a partner
of patients with varicocele do not. with normal or correctible fertility (24). The European
The data on whether varicocele repair improves fertility Association of Urology 2012 update on male infertility
outcomes depend heavily on the initial indication for recommends varicocele repair in infertile couples with
repair (clinical versus subclinical varicocele, normal versus clinical varicocele, oligospermia, infertility of more than
abnormal semen parameters) and the measured outcome two years duration, and otherwise unexplained infertility (5).
(improvement in semen parameters versus pregnancy and There remains, as noted above, significant controversy
live birth). Furthermore, the heterogeneous data available over whether repair of subclinical varicocele in a subfertile
even in randomized clinical trials and the high dropout patient with no other identifiable cause is beneficial; one

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66 Velasquez and Tanrikut. Surgical management of male infertility

Table 1 Outcomes of varicocele treatment

Type of repair Pregnancy rate (%) Recurrence rate (%) Hydrocele rate (%)
Open (all types) (22) 29 14 0.1
Open (inguinal) (21) 31 11 3
Laparoscopic (22) 30 17 0.08
Open microsurgical (22) 40 2 0 (0.005)
Sclerotherapy (antegrade) (30) 42 11 0
Sclerotherapy (retrograde) (30) 30 11 0

study noted 41% of patients with improvement in semen relying on collateral arterial inflow to provide blood supply
parameters postoperatively, but also an equal number with to the testis (10). However, in the inguinal and subinguinal
worsening of their semen parameters (25). Repair methods approaches, all encountered arteries are preserved (32).
were both surgical and percutaneous embolization. Two A large 2009 meta-analysis supports microsurgical
randomized clinical trials (26,27) showed improvement in varicocelectomy as the gold standard for varicocele repair,
semen parameters but not pregnancy rate, while one (28) with the lowest rate of hydrocele formation (0.4%) and
showed neither an improvement in semen parameters the lowest rate of recurrence (1%) compared to other
nor pregnancy rate. However, a more recent small modalities (33). A more recent comparison of only
nonrandomized retrospective study (29) showed significant randomized controlled trials comparing microsurgical
improvement in sperm count and pregnancy rate (12/20) varicocelectomy to open and laparoscopic varicocelectomy
with surgical correction compared to their medical performed for infertility confirmed these results. Two of the
management (19/55) and observation (3/16) groups. four studies compared all three surgical approaches (open,
The principle of varicocele repair remains the same laparoscopic, and microsurgical) whereas the remaining
regardless of treatment modality: occlusion of veins to two studies compared open and microsurgical repairs only.
eliminate the varicocele, identification and preservation of The study found a statistically significant difference in
testicular blood supply, and preservation of the lymphatic the reduction of hydrocele formation and recurrence in
vessels to prevent post-procedural hydrocele formation. microsurgery compared to laparoscopic and open surgery,
with no statistically significant difference in hydrocele or
recurrence for laparoscopic versus open surgery (34) (See
Surgery
Table 1). Two small studies demonstrated little difference in
Surgical treatment remains the mainstay of varicocele outcomes between subinguinal versus inguinal microsurgical
repair and can be performed through a number of surgical varicocelectomies, but showed conflicting results regarding
techniques: (I) open via retroperitoneal, inguinal, or postoperative pain. Shiraishi et al. noted increased scrotal
subinguinal approaches; (II) microsurgically through an pain with a subinguinal incision (35), while Pan et al.
inguinal or subinguinal incision; (III) laparoscopically attributed increased pain found in the inguinal group in
using three, two (30), or single-port sites (31); or (IV) their study to division of muscle and fascia (36).
robotically, employing either a transperitoneal approach or No studies have compared robotic transperitoneal
a subinguinal incision. varicocelectomy to laparoscopic varicocelectomy, and
Varicocelectomy involves ligation of the aberrantly only one report in two patients demonstrates its use in the
dilated veins within the spermatic cord while preserving literature. However, several small studies have studied the
arterial and lymphatic supply and the deferential veins. The use of robot-assisted microsurgical varicocelectomies. Shu
site of vein ligation depends on the approach used. For et al. performed the pilot study comparing operative time
example, if varicocelectomy is performed via an inguinal or in microsurgical subinguinal varicocelectomy with robotic
subinguinal incision the cremasteric and internal spermatic subinguinal varicocelectomy, and found no difference (37).
veins are ligated, whereas if it is performed retroperitoneally It is unclear what the indications were for varicocelectomy,
the testicular vein is ligated. The open and laparoscopic and whether operative time took into account setup time
retroperitoneal techniques may include intentional division for the daVinci ® robot system. Semen parameters were
of the testicular artery above the internal inguinal ring, not measured. A more recent non-randomized, non-

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Translational Andrology and Urology, Vol 3, No 1 March 2014 67

controlled study of 154 patients (chronic orchialgia in Complications specific to percutaneous embolization,
106 pts, including some with oligospermia, and oligo- or aside from the risks of infection, contrast reaction and those
azoospermia in 77 pts) found that 77% of the patients with risks inherent to venous puncture, include phlebitis and
oligospermia and 18% of patients with azoospermia had migration of embolization materials. Furthermore, a study
improvement in semen parameters (38). of radiation exposure in varicocele embolization noted
that radiation exposure can be significant: generally low
(estimated fatal cancer risk 0.1% in a retrospective series)
Sclerotherapy
but in some exceptional cases as high as 100 mSv (estimated
Percutaneous retrograde embolization of the gonadal risk of fatal radiation-induced cancer 3%) (48). The authors
vein for the treatment of varicocele was first described noted that the radiation dose could be substantially reduced
in the 1970s (39). It is less invasive than traditional open with careful technique.
retroperitoneal surgery and does not require general A few studies compare sclerotherapy to open and
anesthesia; for these reasons, some authors have proposed laparoscopic surgery. May et al. (49) and Beutner et al. (50)
that it be the initial treatment of varicocele (40). It is both compared laparoscopic surgery to sclerotherapy, and
performed under fluoroscopic guidance with percutaneous found a higher failure rate (16% vs. 5%) with sclerotherapy,
access to the spermatic vein obtained in a retrograde but a higher complication rate with laparoscopy (13-15%).
fashion via the right femoral vein. It requires significant It is important to note that neither study was done in the
experience by a vascular interventional radiology team or infertile population, and Beutner’s study included both
an appropriately trained urologist, but may allow return to adults and adolescents. Zucchi et al. compared inguinal
physical activity more quickly than antegrade sclerotherapy varicocelectomy under loupe magnification to antegrade
approaches or surgical treatments given the lack of sclerotherapy in patients with abnormal semen parameters
incision (41). Current techniques may include alternate and clinical unilateral left varicocele and found a statistically
venous access sites, such as transjugular and transbrachial significant improvement in number of motile sperm and
approaches, in order to compensate for the difficulty of fast progressive spermatozoa in the antegrade sclerotherapy
obtaining access to the spermatic vein and those with group compared to the inguinal varicocelectomy group,
complex anatomy (42). with 40% global improvement in semen parameters across
Antegrade sclerotherapy was described in 1988 by Tauber, both groups and no significant difference in complications
and can be used either as an initial treatment method or or recurrence rates (51). Pregnancy rate was not measured.
after attempted retrograde sclerotherapy with complex One small, prospective, randomized study compared the use
anatomy (41). The antegrade technique can be performed via of retrograde sclerotherapy, antegrade sclerotherapy, and
either inguinal or subinguinal access. After spermatic cord open inguinal varicocelectomy in infertile men, and found
exposure, a single dilated vessel of the pampiniform plexus improvement in sperm count and total motility across all
is exposed and distally ligated. This vein is then cannulated three groups, with no significant difference in pregnancy rate
in an antegrade fashion. Drainage to the internal spermatic among the groups (52). Currently, there are no randomized
vein can be confirmed by contrast fluoroscopy. The vein is controlled trials comparing sclerotherapy to microsurgery.
then sclerosed by antegrade injection of a sclerosing agent Given the radiation exposure and lack of superior outcomes
and ligated proximally (43). One new technique involves to surgery, many urologists reserve sclerotherapy for when
temporary clamping of the spermatic cord proximally prior other surgical options have failed (53).
to injection of the sclerosing agent in order to prevent
proximal diffusion and less effective sclerosis (44).
Nonobstructive azoospermia (NOA)
Percutaneous embolization of varicocele is performed
with a variety of materials, including angiographic coils (45), NOA—a problem of sperm production with resultant
venous sclerosis chemical agents, transcatheter foam (46), and azoospermic ejaculate—can be primary or secondary,
more recently, liquid embolic agents (47). The theoretical congenital or acquired. A large series of 1,583 azoospermic
advantage of foams and liquid agents over the traditional patients found 12% to have no identifiable cause, although
angiographic coils is that they may occlude collateral this is a lower estimate when compared with prior reports in
pathways which, in turn, may translate to decreases in the the literature (54). Known sex chromosome abnormalities
reported 11% recurrence rate (42). formed 21% of this patient population, with Klinefelter’s

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68 Velasquez and Tanrikut. Surgical management of male infertility

Syndrome in 14% and Y chromosome microdeletions in retrieval prior to microdissection given known patient
1.7%. Urogenital infections were thought to be the cause of characteristics. Preliminary results suggest that in their
azoospermia in ten percent, with chronic unspecified disease nomogram model, the presence of Klinefelter Syndrome
causing seven percent, and malignancy without gonadotoxic or a history of cryptorchidism had the largest modifying
treatment constituting six percent. effect on successful sperm retrieval, with the contribution of
Correction of endocrinopathies in the uncommon case varicocele minor and not statistically significant (61).
of hypogonadotropic hypogonadism can result in return of There have been several attempts to further refine the
fertility (55), but for most patients NOA is not medically microdissection technique given that one of the critiques
or surgically correctable. Historically, most patients with of the procedure is its long operative time compared to
NOA needed donor insemination or adoption in order traditional TESE. A recent retrospective study of 900 patients
to build their families. However, the introduction of found sperm on initial unilateral microdissection in 474 men,
intracytoplasmic sperm injection (ICSI) in the early 1990s but with only 8% success in finding sperm in the contralateral
and the discovery that testicular sperm could be used with testis in those who underwent bilateral microdissection for
in vitro fertilization (IVF) and ICSI to successfully fertilize failure to find sperm on initial exploration. They concluded
oocytes (56) changed this. Sperm may be retrieved from that two specific populations—patients with Klinefelter
men with NOA by standard testicular sperm extraction Syndrome or those with hypospermatogenesis—may benefit
(TESE), or microdissection testicular sperm extraction from contralateral dissection in the event that unilateral
(microTESE) (57). One center is now performing robotic- sperm retrieval is unsuccessful (62). One small study
assisted microsurgical TESE, as well. of systematic upper, middle, and lower pole biopsies in
Open TESE involves a small incision (or multiple conjunction with microTESE suggests that the combination
incisions) in the tunica albuginea at a location of the may be more successful in retrieving sperm (66.2%) than
surgeon’s choice. The testis is squeezed to extrude either technique alone (63).
tubules, and the biopsy specimen(s) obtained using a A contemporary modification of microsurgical technique
pair of surgical scissors. The technique for microTESE incorporates the use of robotic assistance. One group has
is more standardized, as first described by Schlegel: a noted that they have performed twelve robotic-assisted
transverse hemispheric incision in the tunica albuginea microsurgical TESEs, but have not published their outcomes
allows the surgeon to bivalve the testis and, under 20× to other than to state that the procedure is feasible and there
40× magnification with the operating microscope, one were no complications in their study population (38).
attempts to identify and selectively collect larger, more An interesting adjunct to TESE is the role of varicocelectomy
opaque seminiferous tubules (58). A biopsy specimen is also then subsequent TESE in the patient with NOA and a
obtained for histologic analysis. clinical varicocele. A recent small observational study of
Numerous recent studies have confirmed the success of 36 patients examined the timing of varicocelectomy: 19
microTESE in obtaining sperm compared to traditional patients with grade 3 unilateral left varicocele and NOA
TESE. One nonrandomized trial of 133 men noted a underwent microsurgical inguinal varicocelectomy three
56.9% sperm retrieval rate in microTESE versus a 38.2% months prior to magnified (loupe) TESE and 16 underwent
success rate with standard TESE (59). One meta-analysis it at the same time as TESE (64). They showed significant
noted four particular subsets of patients who may optimally improvement in sperm retrieval rate during TESE with
benefit from microTESE rather than random open biopsy: earlier varicocelectomy (57.8% vs. 25%). However,
patients with mosaic or nonmosaic Klinefelter Syndrome, interestingly, in semen analyses six months after TESE, both
patients with chemotherapy-induced azoospermia, patients groups also had sperm present in ejaculated samples (57.8%
with azoospermia after orchidopexy for cryptorchidism, vs. 37.5%). No semen analysis was done in the interval
and patients with Y microdeletions in the AZFc region. period prior to TESE in the patients who had undergone
These populations are thought to represent men with previous varicocelectomy. By contrast, Inci retrospectively
small, limited areas of sperm production in the testes, studied 96 nonrandomized patients with any grade clinical
with sperm found in dilated, opaque seminiferous varicocele and NOA, 66 of whom underwent microsurgical
tubules that can best be identified with the aid of optical inguinal/subinguinal varicocelectomy one year prior to
magnification (60). One group is currently in the process of microTESE (65). On the day of microTESE a semen
developing a nomogram to predict the likelihood of sperm analysis was performed to confirm persistent azoospermia

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Translational Andrology and Urology, Vol 3, No 1 March 2014 69

prior to surgical sperm extraction attempt. They found Ejaculatory duct obstruction (EDO)
significant improvement in surgical sperm retrieval rate (53%
EDO is rare: there are few recent studies describing its
vs. 30%). This was confirmed by Haydardedeoglu et al. (60.8%
prevalence, but older studies suggest that it occurs in less
vs. 38.5%) who also noted an improvement in implantation,
than 5% of men with OA (72). The classic presentation
clinical pregnancy, and live birth rates in a population of men
of EDO is low-volume, acidic ejaculate with oligo- or
with NOA and a history of grade 3 varicocele repair (66). In
azoospermia, a normal hormonal profile, and palpable
contrast to Zampieri’s study, they found higher pregnancy rates
vasa deferentia. Imaging findings suggest dilated seminal
in patients with a shorter interval since varicocelectomy, but
vesicles (SVs), prostatic cysts or calcifications, or dilated
the time intervals were much longer (an average of 40 months
ejaculatory ducts on transrectal ultrasound (TRUS) (73).
since prior varicocelectomy in the shorter group). These
However, patient presentation may vary considerably, as they
studies are in contrast to Schlegel’s initial 2004 study, which
may present with functional or partial obstruction rather
found equivalent microTESE retrieval rates (60%) between
than complete obstruction, and with complaints unrelated to
varicocelectomy and nonvaricocelectomy groups; of note, that
fertility such as pain or dysuria (74).
population included patients with subclinical varicocele (67).
In the twenty years since the advent of using surgically- Multiple studies of imaging modalities have been
retrieved sperm for IVF-ICSI, it is hardly surprising that conducted, primarily with small numbers of patients due to
some men may choose to undergo a repeat procedure. the rarity of the disease. TRUS is cheap, convenient, and
One retrospective study of 126 repeat microTESEs after does not require an incision. It is effective in the diagnosis
963 initial successful microTESEs reported a sperm retrieval of dilated SVs, but this finding is neither sensitive nor
rate of 82%. In their study population, the pregnancy rate after specific to EDO. Given the constraints of the rectal probe,
initial microTESE was 42%, and after repeat microTESE was TRUS may be limited in its ability to localize the level of
39% (68). Another retrospective study of 216 patients who obstruction (75). Purohit et al. (76) compared the use of
had had prior TESE (40 with successful microTESE, 72 with three invasive measures in 25 patients (8 of whom were
successful TESE, and 104 with unsuccessful TESE) showed infertile) suspected of having EDO both clinically and on
an 81% success rate in patients with NOA and successful prior TRUS: (I) SV sperm aspiration; (II) seminal vesiculography
TESE, but only a 27% success rate in patients with NOA and using a 30-gauge spinal needle placed under TRUS
a history of unsuccessful initial TESE (69). guidance and contrast patterns confirmed by fluoroscopy;
Neither TESE nor microTESE are risk-free, and both and (III) chromotubation of the ejaculatory ducts through
come with risks of bleeding, hematoma, infection, and transrectal injection of methylene blue into the SVs and
intratesticular scar formation, as well as excessive harvest of visual confirmation of obstruction with no dye efflux
testicular tissue leading to hypogonadism. Serum testosterone noted during urethroscopy. The authors hypothesized that
levels after microTESE may decrease to 80% of baseline appropriate patient selection through dynamic imaging
at 3-6 months, but recover to 95% by 18 months (70). The (such as vesiculography and chromotubation) may improve
longer-term effects of TESE, microdissection or standard, on outcomes after surgical management, but it is important
testicular histology and spermatogenesis are unknown. to note that in their study population, only the patients
who had positive dynamic imaging findings progressed to
surgical management.
Obstructive azoospermia (OA)
One recent study of the use of magnetic resonance
OA—a blockage of the reproductive tract leading to absence imaging (MRI) in the diagnosis of EDO in 18 patients
of sperm from the ejaculate—is less common than NOA, identified ejaculatory duct cysts in five patients, unilateral
with studies reporting rates of 11-40% (5,54,71). The or bilateral ejaculatory duct dilatation in nine patients, and
mainstay of treatment is surgical management via sperm Müllerian duct cysts in four patients. These findings were
extraction or restoration of outflow of the reproductive tract confirmed at surgery and the authors concluded that MRI,
via reconstruction or alleviation of blockage. The etiologies in allowing more accurate determination of the location,
of OA may be congenital [e.g., congenital bilateral degree, and cause of obstruction, could help facilitate
absence of the vasa deferentia (CBAVD)] or acquired, as preoperative planning regarding the depth of resection
in vasectomy, scarring caused by previous infection, or needed to clear the obstruction (77).
iatrogenic injury from prior inguinal surgeries. The classic treatment for EDO, transurethral resection

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70 Velasquez and Tanrikut. Surgical management of male infertility

of the ejaculatory ducts (TURED), was first described assessment of fluid from the testicular vasal segment to
in 1973. Using a 24 French cystourethroscope and an confirm presence of sperm or other features reassuring for
electrocautery resectoscope loop, the urethra is resected in patency, and confirmation of patency of the abdominal vasal
the midline over the proximal verumontanum for bilateral segment. If both proximal and distal patency is confirmed,
obstruction or more laterally for unilateral obstruction, the freshly-cut ends of the vas are then reapproximated to
with successful resection determined by visualization of complete vasovasostomy (VV). If secondary epididymal
fluid expression intraoperatively from the ejaculatory ducts. obstruction is suspected, vasoepididymostomy (VE) is
Indigo carmine may be instilled under TRUS guidance into warranted (85).
the SVs to observe for efflux of blue dye from the opened Currently, vasectomy reversal is most commonly
ejaculatory ducts for confirmation of patency. The most performed microsurgically, although it has been performed
common complications of TURED include hematuria and without the aid of the microscope and recent studies
epididymoorchitis (78). explore the utility of robotic-assistance. The principles
Newer technologies are being applied to the transurethral of a successful anastomosis include mucosa-to-mucosa
management of EDO. Bipolar electrocautery was used in apposition, a tension-free and watertight reconstruction,
42 infertile patients with azoospermia or severe oligospermia and preservation of the blood supply. There are patient-
due to EDO. The investigators used pure cutting current related qualities that affect the success of a vasectomy
with no electrocautery to perform the resection and reversal aside from the procedure type chosen: a 1991
confirmed relief of obstruction through prostate massage multicenter retrospective study of 1,469 microsurgical
to express seminal fluid under cystoscopic visualization. Of vasectomy reversals noted improved patency and pregnancy
the azoospermic patients, 60% had return of sperm to the rates with shorter interval since vasectomy and when sperm
ejaculate. In the whole study cohort, 38% of patients had could be aspirated from the testicular end of the vas (86).
return to normal semen parameters, with a 31% pregnancy Most microsurgical series report patency rates of 85-98%
rate at 18-month follow-up (79). Lee et al. described the use (using variable definitions of patency) and live birth rates of
of the holmium: YAG laser in combination with monopolar 38-84% (87).
TUR in a case report of a patient with a midline prostatic The quality of vasal fluid from the testicular segment
cyst. They elected to use the laser, with its much smaller is a marker of proximal patency: thick, creamy fluid with
diameter, due to the degree of prostatic urethral narrowing no sperm or no fluid can signify secondary epididymal
imposed by this cyst. They unroofed the cyst with the laser, obstruction. In these cases, VE—end-to-side anastomosis
and then completed the resection via monopolar TUR (80). of the vas to a patent epididymal tubule—is indicated (85).
Other recently-described techniques for relief of EDO Patency and live birth rates are lower than in VV (70-90%
include direct ejaculatory duct recanalization using retrograde and 32-56%, respectively) due to technical difficulty and
balloon dilation (81) or retrograde insertion of 6F/6.5F possible epididymal dysfunction secondary to pressure-
vesiculoscopes (82,83). However, the use of these techniques related changes and inflammation. VE is more often
cannot necessarily be generalized to the infertile population necessary with longer duration of obstruction (87-89).
as study sizes are very small, indications for treatment are Open single-layer spatulated VV was first described in
heterogeneous, and semen analyses were not performed in the 1919, and in the subsequent historic literature a variety of
majority of these study populations. Nonetheless, preliminary suture materials and temporary stents to aid in visualization
results are encouraging and bear further investigation. of the vasal lumen were employed. The reported success rates
were up to 60%, with success not being clearly defined (90).
The use of the operating microscope was introduced in the
Vasal obstruction
1970s (91).
The most common cause of OA is vasectomy. In a recent Early animal studies in the 1980s exploring the use of
sampling of more than 10,000 men ages 15-45 through the fibrin glue for a sutureless or few-suture technique were
National Survey for Family Growth, approximately 7% of promising, including macroscopic rabbit studies with fibrin
men reported having had a vasectomy in their lifetime, but glue and temporary splints (92) and microscopic rat studies
nearly 20% of that population stated that they desire future using fibrin glue alone (93) or fibrin glue combined with
children (84). The basic steps of vasectomy reversal involve two or three sutures (94). By contrast, another rat model
excision of the obstructed segment of vas, microscopic showed that a biomaterial wrap improved operating time

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Translational Andrology and Urology, Vol 3, No 1 March 2014 71

without compromising patency. Patency rates in the sealant either fertility or chronic orchialgia after vasectomy) to
group were 70% compared with a 92% patency rate in 45 standard two-layer microsurgical reversals. VV or VE
the biomaterial wrap group (95). One human study using was performed as clinically indicated for both approaches.
Tisseel® with three bolstering sutures in 42 patients reported They found a significant increase in patency rates, defined
nine pregnancies in 21 patients actively trying to conceive, as greater than one million sperm/ejaculated sample, for
and suggested that the procedure was less time-consuming robotic versus microsurgical procedures (96% vs. 80%
and technically easier compared to microsurgical or open at 17-month follow-up) but no significant difference in
vasectomy reversal (96). However, the study has several flaws pregnancy rates at one year (65% vs. 55%). They also noted
that make it difficult to recommend this technique, including that their initial operative duration was significantly longer
a high failure rate and very low rates of follow-up. for robotic compared to microsurgical procedures, but
The microsurgical approach can be performed with one, median operative time was significantly decreased (103).
two, or three layers (97). The advantages of a three-layer However, the reported operative duration did not take into
technique over the two- or one-layer techniques include account the extra 30-60 minutes needed for robotic setup
the ability to bring markedly discrepant luminal diameters and preparation at the beginning of the case.
together with prevention of dog-ears and a more watertight Although vasectomy reversal is expensive, a number
anastomosis, but operative time is longer and the procedure is of studies have shown via various modeling methods that
more technically difficult. In 1998, Goldstein et al. described vasectomy reversal may be more cost-effective than sperm
the microdot technique in effort to reduce degree of technical retrieval performed in conjunction with IVF-ICSI (104-106).
difficulty of the procedure. A total of six evenly-spaced Complications are rare, with scrotal hematoma among the
microdots are placed on the cut ends of the vas using a pen most common. Rate of return of sperm to the ejaculate is
in order to mark the needle exit points. This pre-placement variable, with slower return of sperm with VE (67). Late failure
planning allows for more precise and evenly spaced suture is also possible. One study of 823 patients who had return of
placement (98). sperm to the ejaculate after VV noted reocclusion in 1% (97).
There have been no studies comparing the three-layer VV may also be used as a treatment approach for repair
closure to the one- or two-layer reapproximations. A single of iatrogenic vasal obstruction. The vas deferens may
retrospective study compared the modified one-layer be damaged by inadvertent intraoperative transection
approach to the two-layer approach in a single institution or compression during inguinal surgery. The incidence
and found no difference in patency postoperatively (99), of injury varies between 0.3% and 7.2% in adult hernia
but characteristics of the testicular vasal fluid were not repair, but is reported in as high as 27% in patients with a
measured, and neither were postprocedural pregnancy rates. history of pediatric inguinal hernia repair (107). It may be
One-layer and two-layer outcome comparisons had been associated with injury to the ipsilateral blood supply and
previously studied by the Vasovasostomy Study Group in a long obstructive interval. A 1998 study of 36 procedures
1991, with the same results (86). noted that microsurgical repair of iatrogenic vasal injury is
There are no randomized controlled trials comparing both possible and successful (108). Crossed VV or VE, with
open to microsurgical vasectomy reversal; most studies anastomosis to the contralateral side for patent outflow,
are single-institution retrospective reviews. Given the is indicated in three circumstances: (I) large vasal defects
lack of head-to-head comparative studies, critics of the where an ipsilateral tension-free anastomosis is not possible;
microsurgical technique note that operative time is (II) unilateral inguinal vasal obstruction with a contralateral
significantly increased and there is an unclear benefit in obstructed or atrophic testis; or (III) unilateral epididymal
pregnancy outcomes. One small, recent, retrospective obstruction with a contralateral atrophic testis.
study suggests that in the hands of a surgeon experienced
with both modalities, a single-layer macroscopic approach
Sperm retrieval
can provide decreased operative time and cost without
compromising results (100). Sperm retrieval methods provide a final common pathway
The first animal studies on robot-assisted VV were for patients with OA who either elect not to undergo
performed in 2004 (101) with the first human study reconstruction, have failed reconstruction, or have anatomy
published by Parekattil et al. in 2010 (102). They compared not conducive to reconstruction. Harvest techniques include
110 two-layer robotic-assisted reversals (performed for aspiration of sperm from the epididymis (percutaneously or

© Translational Andrology and Urology. All rights reserved. www.amepc.org/tau Transl Androl Urol 2014;3(1):64-76
72 Velasquez and Tanrikut. Surgical management of male infertility

open with or without the aid of the microscope) or the testis studies noting upwards of 95% success rate for either
(percutaneous or open). epididymal or testicular extraction of sperm (118).
Percutaneous epididymal sperm aspiration (PESA) One study found that sperm recovery in TESE was 100%
involves percutaneous cannulation of the epididymis with with ICSI fertilization rates of 66% and live delivery rates
a small-gauge needle and aspiration of the epididymal of 62% (119). A cohort of 1,121 men with OA who had
fluid. PESA has the advantage of being technically easy and undergone either epididymal or TESE for ICSI found that
does not require an operating room, general anesthetic, or the source and etiology of the obstruction did not affect
microsurgical training (109). The largest study of PESA fertilization or pregnancy rate (120).
to date is a retrospective study of 255 patients undergoing
PESA for OA of various etiologies, including CBAVD,
Conclusions
vasectomy, failed VV, and iatrogenic injury to the vas (110).
The investigators were successful in obtaining abundant In an era of assisted reproductive technology, microsurgery,
motile sperm in 75% of cases, rare motile sperm in 9%, and robotic surgery, the surgical management of the
nonmotile sperm in 11%, and no sperm in 5%. A total infertile male is both complex and encouraging, offering
of 19% of patients proceeded to TESE techniques, with biologic paternity to men who historically would have had
mature spermatozoa found in all of these patients. The to resort to adoption or donor sperm in order to parent.
authors observed a significant need for progression to
testicular sperm retrieval in older patients and patients with
Acknowledgements
smaller testicular volumes.
Microsurgical epididymal sperm aspiration (MESA) None.
was first described in 1994 in the setting of a patient with
CBAVD, and involves exposure of the epididymis through
Footnote
a small incision with isolation and puncture of individual
epididymal tubules to aspirate fluid (111). It has the Conflicts of Interest: The authors have no conflicts of interest
advantage of allowing direct identification of the tubules, to declare.
which can be particularly advantageous in the setting of
extensive scarring or proximal obstruction. It can also be Disclaimer: This article does not contain any studies with
performed after failed PESA. However, there have been human or animal subjects performed by either of the
no studies directly comparing the use of MESA and PESA, authors.
and very few studies other than the initial studies (109,112)
studying the rate of sperm retrieval in MESA.
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Cite this article as: Velasquez M, Tanrikut C. Surgical
aspirated epididymal spermatozoa and intracytoplasmic
management of male infertility: an update. Transl Androl Urol
sperm injection in azoospermic men. Hum Reprod
2014;3(1):64-76. doi: 10.3978/j.issn.2223-4683.2014.01.05
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