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Asian Journal of Andrology (2016) 18,
332–337
© 2016 AJA, SIMM & SJTU. All rights reserved 1008-682X
www.asiaandro.com; www.ajandrology.com
Open Access
INVITED REVIEW
Male Fertility
An overview of the management of post-vasectomy
pain syndrome
Wei Phin Tan, Laurence A Levine
Post-vasectomy pain syndrome remains one of the more challenging urological problems to manage. This can be a frustrating
process for both the patient and clinician as there is no well-recognized diagnostic regimen or reliable effective treatment. Many of
these patients will end up seeing physicians across many disciplines, further frustrating them. The etiology of post-vasectomy pain
syndrome is not clearly delineated. Postulations include damage to the scrotal and spermatic cord nerve structures via inflammatory
effects of the immune system, back pressure effects in the obstructed vas and epididymis, vascular stasis, nerve impingement, or
perineural fibrosis. Post-vasectomy pain syndrome is defined as at least 3 months of chronic or intermittent scrotal content pain.
This article reviews the current understanding of post-vasectomy pain syndrome, theories behind its pathophysiology, evaluation
pathways, and treatment options.
Asian Journal of Andrology
(2016)
18,
332–337; doi: 10.4103/1008-682X.175090; published online: 4 March 2016
Keywords:
epididymectomy; microdenervation; orchalgia; post-vasectomy pain management; post-vasectomy pain syndrome;
testicular pain; vasectomy reversal; vaso-vasostomy
INTRODUCTION
Vasectomies are one of the most common urological procedures performed
by urologists worldwide. It is the most effective male contraceptive method.
It is estimated that 500,000 vasectomies are performed in the United States
per annum.
1
This procedure involves dividing the vas deferens and is often
performed under local anesthesia in an outpatient setting. Traditionally,
the procedure involves making small bilateral scrotal incisions to expose
and visualize the vas deferens, excising at least 1 cm of the vas deferens,
followed by electrocautery fulguration of the ends of the vas deferens,
placing sutures or clips on each end and interposing tissue between the
two cut ends to further prevent recanalization. The success rate of the
procedure is estimated to be between 98% and 99%.
2,3
The most common
complications include bleeding, development of a hematoma and infection
of the scrotal incision sites.
Although rare, patients may experience chronic scrotal content
pain following a vasectomy. The 2012 American Urological
Association  (AUA) guideline for vasectomy which was updated in
2015 states that 1–2% of men who undergo a vasectomy will develop
chronic scrotal pain that is severe enough to interfere with their quality
of life and require medical attention.
4
This syndrome has been coined
by many terms including testialgia, chronic orchialgia, chronic scrotal
content pain, post-vasectomy orchialgia, congestive epididymitis, and
chronic testicular pain. At present, the syndrome is widely accepted
as post-vasectomy pain syndrome (PVPS).
5
In this article, we aim to
review the therapeutic intervention for this perplexing problem.
METHODOLOGY
Search strategy
We conducted a computerized bibliographic search of the PubMed,
Medline, Embase, and Cochrane databases for all reports pertaining
to PVPS using the Mesh Words “Post-vasectomy Pain Syndrome,”
“Post Vasectomy Pain Syndrome,” “Microdenervation of Spermatic
Cord,” “Epididymectomy,” “Vasectomy Reversal,” and “Orchiectomy”
through October 31, 2015.
Eligibility criteria and patients
We specifically reviewed all articles pertaining to PVPS and
microdenervation of the spermatic cord, epididymectomy, vasectomy
reversal or orchiectomy. We only included articles in the English
literature.
BACKGROUND
PVPS is different from acute post procedure pain. Acute post procedure
pain typically resolves 2–4  weeks postoperatively whereas PVPS
continues to persist or may occur months to years after the vasectomy.
PVPS can be an extremely frustrating problem to treat for both the
patient and the clinician, as there remains no widely accepted protocol
for evaluation and treatment of the problem. PVPS is defined as
constant or intermittent testicular pain for 3 months or longer with a
severity that interferes with daily activities prompting the patient to
seek medical treatment.
6
The exact incidence of PVPS is unknown but
was estimated to be very low (<1%) in the past.
4–7
However surveys
in recent years have found that almost 15% of men suffer from PVPS,
with 2% of men experiencing pain intense enough to impact their
quality of life.
8,9
One review reported that 1 in 1000 men who undergo a
vasectomy will sustain long-term pain requiring surgical intervention.
10
ETIOLOGY
The pathophysiology of PVPS remains unclear, but speculations
regarding the mechanism leading to pain include damage to the
scrotal and spermatic cord nerve structures via inflammatory effects
Department of Urology, Rush University Medical Center, Chicago, Illinois, USA.
Correspondence: Dr. LA Levine ([email protected])
Received: 17 September 2015; Revised: 17 December 2015; Accepted: 18 December 2015
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Post-vasectomy pain syndrome management
WP Tan and LA Levine
333
of the immune system, back pressure effects in the obstructed vas and
epididymis, vascular stasis, nerve impingement, or perineural fibrosis.
11
Histological findings within the proximal segment of the vas following
vasectomy include spermatid degeneration, thickened basement
membranes, and increased phagocytosis by Sertoli cells, which are
responsible for maintaining normal epididymal pressure.
12
Pressure
build-up that is too great for compensatory mechanisms eventually
occur, leading to the formation of sperm granulomas, epididymal
blowout, or vasitis nodosa.
4
Studies have reported that in vasectomized
men, testicular histology show dilation of the seminiferous tubules,
reduction in seminiferous cell population and interstitial fibrosis using
quantitative morphometric analysis.
13
Another possible explanation of PVPS is that the epididymis is
trapped between two opposing forces when ejaculation occurs. The
epididymal duct and vas deferens are lined with smooth muscle cells
which contract rhythmically during ejaculation to facilitate sperm
movement through the duct. However, in the setting of a vasectomized
patient, this contraction results in testicular fluid being discharged into
the caudal epididymis leading to increase pressure, causing epididymal
fibrosis, and blowout within the epididymis.
14
In vasectomized patients, the blood-testes barrier is also disrupted,
causing detectable levels of serum antisperm antibodies in 60%–80% of
men.
8
About 7%–30% of vasectomized patients will also have antisperm
antibodies within the epididymis.
15,16
Animal studies have found that
these antibodies can result in agglutination of sperm and activation
of the complement cascade, with immune complex formation and
deposition of these complexes in the basement membrane.
17
All the
above mechanisms together or individually may result in PVPS.
CLINICAL PRESENTATION
The mean time of the onset of PVPS is reported to be 7–24 months.
9,18
Demographics (age, socioeconomic status, race) and operative
techniques have not been shown to have a correlation to the
development of PVPS.
13
Signs and symptoms of PVPS include a
tender vas deferens and/or epididymis, fullness of the vas deferens,
orchialgia, dyspareunia, pain with ejaculation, premature ejaculation,
and pain with straining. Scrotal ultrasound may show engorgement or
thickening of the epididymis.
EVALUATION
The evaluation includes a thorough history and physical examination.
The history should include the duration and nature of the pain, severity
(on a 0–10 scale), location, radiation, aggravating factors, associated
symptoms, and previous therapeutic maneuvers. The physician should
also determine if voiding, bowel movements, sexual or physical
activities or prolonged sitting aggravate the pain. Previous surgery to
the spine, inguinal, scrotal, pelvic, and retroperitoneal space should also
be recorded. Psychosocial questions to rule out depression, history of
sexual abuse, Munchausen syndrome or other somatoform disorders
should also be included.
19
Physical examination focusing on the genitalia is essential. The
patient should be examined while standing and supine, beginning on
the normal/less painful side. A thorough examination of the testes,
epididymides, vas deferens and a 360° rectal exam is also recommended
to evaluate abnormalities of the prostate and hypertonicity or
tenderness of the pelvic floor structures. A neurological examination
of the lower limbs and genitals should also be performed to rule out
radicular pain syndromes and neurosensory deficits. Laboratory
investigations include a urinalysis, urine and semen culture to rule
out infection when indicated.
4
Should microscopic hematuria be
identified, computed tomography  (CT) scan of the abdomen and
pelvis is indicated as stones in the ureter can cause scrotal pain. All
men with chronic orchialgia should also undergo a high-resolution
scrotal ultrasound with color-flow Doppler to evaluate the contents of
the scrotum to rule out any pathological processes such as testicular
tumor, varicocele or infection.
4
Magnetic resonance imaging (MRI)
scan of the spine or hips is suggested when there is a history of back
or hip pain to rule out nerve impingement. A spermatic cord block
should also be considered to determine if the pain is being generated
from within the scrotum. We recommend that this block should
be performed by injecting 20  ml of 0.25% bupivacaine/ropivacaine
without epinephrine, into the spermatic cord at the level of the pubic
tubercle.
19
If the pain is conducted via the spermatic cord nerves, the
pain should be temporarily relieved after performing the cord block.
A saline control to exclude malingering remains controversial as it has
not been found to be a reliable tool to rule out malingering behavior.
20
Differential diagnoses for PVPS include varicocele, hydrocele,
infection, tumor, intermittent testicular torsion, inguinal hernia,
trauma, pelvic floor myalgia, referred pain, and psychogenic causes.
20
PVPS is a diagnosis of exclusion and the diagnosis should only be made
after all these investigative studies have been performed.
TREATMENT
Currently, there are no published data with good evidence regarding
non-surgical intervention for PVPS. However, pharmacotherapy
should be considered the first line followed by a series of spermatic cord
blocks. Pelvic floor physical therapy, acupuncture, and a psychological
evaluation may also be beneficial. Failing non-surgical treatment,
repeating the vasectomy with wide excision of the severed ends,
microdenervation of the spermatic cord, epididymectomy, vasectomy
reversal or orchiectomy should be considered (Figure 1).
Pharmacological treatment
Antibiotics should be initiated if the patient shows any signs of orchitis
or epididymitis. Trimethoprim/sulfamethoxazole or quinolone
antibiotics for 2–4  weeks are preferred due to their lipophilic
nature which penetrates the testis and epididymis well. It would be
inappropriate to empirically treat men for an infection in the absence
of any signs or symptoms of an infection, which may in fact be more
harmful than good.
Figure 1:
Treatment algorithm for patient with postvasectomy pain syndrome.
59
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Post-vasectomy pain syndrome management
WP Tan and LA Levine
334
Initial pharmacological therapy should include non-steroidal
anti-inflammatory drugs (NSAIDs) over a period of 2–4 weeks. In our
experience, NSAIDs typically work best in patients who experience
PVPS  <1  year from their vasectomy. Failing NSAIDs therapy, we
recommend using a tricyclic antidepressant (TCA). There has been
no clinical trial showing any efficacy in using a TCA for PVPS.
Sinclair
et al.
found that 66.6% of patients with idiopathic testicular
pain had improvement of pain in a trial of six patients after 3 months
with nortriptyline therapy.
21
However, a subgroup analysis of patients
with PVPS did not show the same improvement.
21
Limiting factors
of this study include a small sample size and its retrospective nature.
However, TCA has been shown to treat nerve pain in patients with
diabetic neuropathy as well as postherpetic neuralgia.
22,23
TCA works
by inhibiting the reuptake of norepinephrine and serotonin in the brain.
It also inhibits sodium channel blockers and L-type calcium channels
that are thought to be responsible for its analgesic effect by modulating
first order neuron synapses with second order neuron synapses in the
dorsal horn of the spinal cord. Tertiary amines  (amitriptyline and
clomipramine) are reported to be more effective for neuropathic pain
compared to secondary amines (desipramine and nortriptyline).
24,25
However, tertiary amines are also associated with more sedation and
postural hypotension.
26
TCA may take 2–3 weeks from initiation of
therapy to be effective.
Anticonvulsants have also been shown to work for neuropathic
pain. The two mainstays of anticonvulsants used for neuropathic
pain are gabapentin and pregabalin due to the paucity of side effects
in the older generation anticonvulsants. There has been no clinical
trial showing any efficacy in using anticonvulsants for PVPS. Sinclair
et al.
found that 61.5% of patients with idiopathic testicular pain had
improvement of pain in a trial of 13  patients after 3  months with
gabapentin therapy.
21
However, a subgroup analysis of patients with
PVPS also did not show any improvement of pain.
21
Limiting factors
of this study have been discussed above and include a small sample
size with only 13 patients on gabapentin having complete data and
an even smaller PVPS group of four patients. However, gabapentin
has also been shown in large, randomized, placebo-controlled trials
to relieve pain in patients with diabetic polyneuropathy, postherpetic
neuralgia, and other types of neuralgia.
27–29
The proposed mechanism
of gabapentin as an analgesic is that it modulates the
α-2-d
subunit of
N-type calcium channels which affects the afferent pain fibers.
Long-term treatment with narcotic agents is not recommended
as this does not address the underlying pathological condition and
carries the risk of addiction. We occasionally offer a short duration of
narcotics for temporary relief of PVPS.
Nonsurgical treatment
Originating around 100 BC in China, acupuncture is regarded as the
earliest form of neuromodulation. It is considered a form of alternative
medicine and continues to remain a key component of traditional
Chinese medicine. This modality may be recommended for patients
with chronic genitourinary pain. There are no published trials on
acupuncture for PVPS.
Pelvic floor therapy may also benefit patients with pelvic floor
dysfunction. This is particularly beneficial in patients who have muscle
dysfunction or myofascial trigger points. In our practice, we routinely
recommend specialized pelvic floor physical therapy to patients with
PVPS if a positive 360° digital rectal exam is identified.
A series of spermatic cord blocks with local anesthetic agents with
or without steroids to disrupt the afferent pain pathway may also relieve
testicular pain. Studies have demonstrated that this technique rarely
Asian Journal of Andrology
provides long-term relief and usually only lasts the duration of the
local anesthetic.
19
The block is performed by isolating the spermatic
cord at the inguinal-scrotal junction. A 25–27-gauge needle is then
introduced into the spermatic cord at the level of the pubic tubercle.
We typically use 20 cc of 0.25% Bupivacaine Hydrochloride for our
initial cord block. The patient is instructed to call the office in 24 hours
to report the duration and level of relief if any from the block. Should
he experience >90% temporary pain relief, we offer a series of cord
blocks every 2 weeks for 4–5 blocks using 9 cc of 0.75% Bupivacaine
Hydrochloride combined with 1 cc (10 mg) of triamcinolone acetonide.
If there is no alleviation of pain with a well-placed injection, we do not
recommend repeating this treatment. In our experience, this technique
is rarely successful with long-term pain relief, especially when the
duration of chronic pain exceeds 6 months.
Other nonsurgical techniques include pulsed radiofrequency of the
spermatic cord and genital branch of the genitofemoral nerve for PVPS
if the patient receives temporary relief from a spermatic cord block.
30,31
This technique has only been reported in small non-randomized trials.
Surgical treatment
Patients who fail medical therapy should be considered for surgical
intervention. Surgical intervention includes excision of sperm
granuloma, microdenervation of the spermatic cord  (MDSC),
epididymectomy, vasectomy reversal or orchiectomy. The success rates
of these procedures remain unclear due to the availability of only small
case series of men undergoing surgical treatment for PVPS.
Table 1
depicts the published success rates of surgical treatments for men with
chronic orchialgia. No clear predictors of success for any procedure
have been reported except as listed below.
Table 1: Surgical treatment of orchialgia in the literature
33
References
Number Follow‑up
of units (months)
Number of success (%)
Complete Partial No relief
2 (100)
4 (100)
7 (88)
13 (76)
25 (76)
34 (96)
7 (70)
N/A
6 (100)
N/A
9 (69)
7 (50)
N/A
66
6
1 (10)
N/A
4 (100)
0
0
1 (12)
4 (24)
3 (9)
1 (4)
2 (20)
7 (78)
0
4 (31)
6 (43)
9 (90)
14 (88)
0
0
0
0
0
5 (15)
0
1 (10)
2 (22)
0
0
1 (7)
N/A
N/A
0
Microsurgical denervation
Devine and Schellhammer
51
Choa and Swami
Levine
et al.
53
34
54
52
2
4
8
17
33
35
95
10
9
6
32
13
14
10
16
4
N/A
18.5
16.6
N/A
20
31.5
20.3
24
25.1
N/A
29
18
Ahmed
et al.
Levine and Matkov
Heidenreich
et al.
35
Strom and Levine
33
Oliveira
et al.
55
67 (71) 17 (17) 11 (12)
Laparoscopic denervation
Cadeddu
et al.
56
Vasectomy reversal
Shapiro and Silber
47
Myers
et al.
46
Nangia
et al.
18
Horovitz
et al.
Davis
et al.
20
West
et al.
43
50
24 (75) 8 (25)
Epididymectomy
Resection of genitofemoral nerve
Ducic and Dellon
57
Orchiectomy
Davis
et al.
20
Inguinal orchiectomy
Scrotal orchiectomy
Yamamoto
et al.
(inguinal)
N/A: not available
58
15
9
4
N/A
N/A
N/A
11 (73)
5 (55)
3 (75)
4 (27)
3 (33)
1 (25)
0
1 (22)
0
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Post-vasectomy pain syndrome management
WP Tan and LA Levine
335
Microdenervation of the spermatic cord (MDSC)
MDSC is a relatively new surgical option which became more
popular over the last two decades. The goal of the procedure involves
transecting all the nerves in the spermatic cord while preserving
all the arteries  (testicular, cremasteric, and deferential) along with
several lymphatic channels to reduce the likelihood of developing a
hydrocele  (Figure 
2).
32
Informed consent is imperative as the pain
may persist, and in some situations worsen following surgery.
33
This
may be due to accessory fibers from the pudendal nerve, incomplete
cord denervation, central nervous system sensitization or malingering.
Other risks include the development of a hydrocele and testicular
atrophy. Patients with bilateral pain are advised to undergo surgery
for the more painful side first as the contralateral site may occasionally
resolve following MDSC.
There has only been one study to date that has specifically
evaluated the success rate of MDSC for PVPS. Ahmed
et al.
conducted
a retrospective survey of 560 post-vasectomy patients to which
396 patients replied. A total of 17 patients underwent MDSC for PVPS
with 13 (76.5%) reporting complete relief of pain at their first follow-up
visit. The other four patients had significant improvement in terms of
pain and were satisfied with the results.
34
Multiple studies have shown
good success with MDSC for chronic testicular pain due to a variety
of etiologies including idiopathic pain (Table 1). A total of 152 out of
191 men (81.2%) based on all cases of MDSC in the English literature
had complete resolution of scrotal content pain (Table 1). Heidenreich
et al.
reported a series of 35 patients with 96% of patients experiencing
complete resolution of pain following MDSC.
35
Strom and Levine
reported that durable relief was noted in 71% of men following MDSC.
A total of 17% of patients reported partial relief, whereas 12% reported
no change in pain but no patient reported worsening pain.
33
Men with
PVPS were included in these studies but were not specifically addressed.
Larsen
et  al.
also reported our institution’s results on MDSC,
showing that patients who had not undergone a prior attempt at
surgical correction for scrotal content pain had a mean post-MDSC
visual analog pain scale (VAPS) score of 2 (range 0–10) with an average
pain decrease of 79%.
36
Whereas, patients who failed prior surgical
procedure including epididymectomy, varicocelectomy, and vas
reversal who then underwent MDSC reported a mean postoperative
VAPS score of 3 (range 0–10) with an average decrease in pain of 67%.
36
There was a complete response in 64% of patients in the surgery naïve
group compared to 50% in patients whom prior surgical correction
for pain had failed. In a separate study, we also found that a positive
response to a spermatic cord block defined as at least a 50% temporary
reduction of pain was an independent predictor of a successful MDSC.
37
Please refer to the
Supplementary Appendix
section on our
technique for performing MDSC.
Epididymectomy
Epididymectomy continues to remain a more popular approach
compared to MDSC especially in Europe. A  survey among Swiss
urologists in 2005 concluded that 74% of urologists would perform an
epididymectomy, 7% would perform an inguinal orchiectomy and 6%
would perform a MDSC for PVPS.
38
The reported success rates with
epididymectomy range from 50% to 92% and have been reported to
produce a better result in relieving pain if a structural abnormality (cyst,
granuloma or mass) was noted in the epididymis on examination or
with ultrasonography.
39–42
When diffuse pain in the cord and/or testicle
is noted during physical examination, this should lead to a MDSC being
performed rather than epididymectomy.
There are multiple small series in the literature on epididymectomy
for PVPS. West
et  al.
reviewed 16  patients that underwent
epididymectomy for pain after vasectomy (3 bilateral, 13 unilateral).
A  total of 14  patients had excellent initial symptomatic benefit
following epididymectomy. Ten patients were followed up for at
least 3  years and 90% of patients had sustained improvement in
their scrotal pain.
43
Lee
et  al.
reviewed 22  patients who underwent
epididymectomy and 16 who underwent vasectomy reversal  (VR)
for PVPS. The difference in the mean preoperative and postoperative
VAPS scores was 6.00  ±  1.34  (range 3–8) in the epididymectomy
group and 5.50  ±  1.03  (range 4–8) in the VR group. There was no
significant difference in pain reduction or patient satisfaction between
epididymectomy and vasectomy reversals; hence selection of the
procedure should be determined based on physician and patient
preference.
44
Chung
et  al.
published a multicenter, randomized controlled,
single-blind study in 2013 where 21 patients underwent epididymectomy
alone and 22  patients underwent epididymectomy with concurrent
administration of hyaluronic acid and carboxymethyl cellulose to
inhibit adhesion and fibrosis for PVPS.
45
At postoperative week 24,
15.8% of patients from the epididymectomy only group were pain
free and 57.1% of patients from the epididymectomy with concurrent
administration of hyaluronic acid and carboxymethyl cellulose group
were pain free. A  total of 31.6% from the epididymectomy only
group exhibited limited pain relief and 9.5% of patients from the
epididymectomy with concurrent administration of hyaluronic acid
and carboxymethyl cellulose group, exhibited limited pain relief.
Please refer to the
Supplementary Appendix
section on our
technique for performing epididymectomy.
Vasectomy reversal
Vaso-vasostomy appears to be an intuitive solution to PVPS. The goal
of the procedure is to relieve the pressure from the obstruction, hence
decreasing pain levels. Only data from small single-center studies are
available. However, these studies show that up to 100% of patients
experience some improvement in pain scores, and complete resolution
Asian Journal of Andrology
a
b
c
d
e
Figure 2:
Microdenervation of the spermatic cord. (a) Marking of inguinal
site. (b) Dissection to expose spermatic cord. (c) Spermatic cord supported by
5/8 inch Penrose drain with cord fascia opened. (d) Arteries secured by blue
Vessel loop. (e) After completion of dissection, only the cremasteric artery,
testicular artery, deferential artery, lymphatics remain (top to bottom).
22,43
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Post-vasectomy pain syndrome management
WP Tan and LA Levine
336
of pain have been reported to be as high as 50%–69%.
18,46,47
The benefits
of this approach are the potential resolution of pain and preservation
of all intrascrotal structures. However, this contradicts the purpose
of the vasectomy, may be costly and may not be covered by health
insurance. Reasons that this approach may not succeed include any
nonobstructive etiologies such as nerve entrapment.
Polackwich
et  al.
identified 26  patients who underwent
a vaso-vasostomy and seven patients who under went an
epididymo-vasostomy for PVPS. A  total of 34% of patients had
complete resolution of pain and 59% of patients reported improvements
in pain scores.
48
Lee
et  al.
identified 32  patients who underwent a
vasectomy reversal for PVPS and noted that the improvement in the
mean preoperative and postoperative VAPS was 6.00 ± 1.25 (4–8) in
the patency group (sperm in the ejaculate) and 4.43 ± 0.98 (3–6) in
the no patency group (P = 0.011).
49
The authors concluded that there
was a significant difference in pain reduction in patients who had
patency following vasectomy reversal compared to patients who remain
obstructed. However, patients who remain obstructed had a decrease
in VAPS suggesting that the mechanism of action to which PVPS may
not be due to the obstructed vas deferens alone.
Horovitz
et al.
also published a series of 14 patients who underwent
vasectomy reversal for PVPS.
50
Fifty percent of patients were rendered
pain-free whereas 93% of patients had improvement in pain. Myers
et al.
reviewed the records of 32 patients undergoing vasectomy reversal
for PVPS and found that 24 patients had relief of symptoms after the
initial procedure. Of the eight men with recurrent pain, six underwent
the second reversal where 50% of these men subsequently had relief
of symptoms.
46
Please refer to the
Supplementary Appendix
section on our
technique for performing vasectomy reversal.
Orchiectomy
Orchiectomy is considered the last resort in patients who do not
respond to other means of therapy. Davis
et al.
reviewed 24 patients with
chronic unilateral or bilateral orchialgia not necessarily for PVPS who
underwent inguinal orchiectomy.
20
A total of 15 patients underwent
inguinal orchiectomy where 11  (73%) reported complete relief of
pain while 4 had partial relief. Of the nine patients who underwent
scrotal orchiectomy, 5 (55%) reported complete relief of pain, 3 (33%)
had partial relief and 1 (11%) denied improvement.
20
On the basis of
these results, the authors recommended inguinal orchiectomy as the
procedure of choice for the management of chronic testicular pain
when other management is unsuccessful.
Please refer to the
Supplementary Appendix
section on our
technique for performing orchiectomy.
OUR PROTOCOL
Once a diagnosis of PVPS has been established, our protocol involves
a trial of oral ibuprofen 600–800 mg every 4–6 hours or oral celecoxib
200 mg daily for 10–14 days. Failing NSAIDs therapy, we recommend
10–20  mg of amitriptyline nightly. After 1  month of TCA therapy
without success, we recommend adding pregabalin 75 mg 3 times a
day. A patient is considered to have failed pharmacology therapy should
pain persist after initiating pregabalin for 4 weeks.
Our next step is to perform a spermatic cord block with local
long-acting anesthetic agents  (bupivacaine or ropivacaine) with or
without steroids which aims to disrupt the pain cycle in men with
PVPS. This is both therapeutic and diagnostic as patients who respond
to a cord block are more likely to respond to MDSC. Should the
patient experience >90% relief, we offer a series of cord blocks every
2 weeks for 4–5 blocks using 9 cc of 0.75% Bupivacaine Hydrochloride
Asian Journal of Andrology
injection combined with 1 cc (10 mg) of triamcinolone acetonide. If
there is no reduction of pain with a well-placed injection, we do not
repeat the cord block.
Failing pharmacotherapy, the next step is to consider excision
of granuloma, MDSC, epididymectomy or a vasectomy reversal.
We recommend surgical excision of a granuloma if a tender mass is
palpable at the site of the transected vas deferens. We typically perform
MDSC in patients with diffuse pain involving the cord, epididymis,
and/or testicle. An epididymectomy is beneficial in patients with pain
isolated solely to the epididymis especially in those with structural
abnormalities noted on examination or ultrasound. Epididymectomy
is rarely performed in our practice as most patients present with
more diffuse pain rather than just the epididymis. Should MDSC fail
to relieve the pain and the testicle is still sensate on examination, we
recommend orchiectomy via an inguinal approach particularly if a
cord block results in temporary relief of pain. Vasectomy reversal is
rarely offered except in circumstances when the pain is localized to the
vasectomy site, and/or epididymis and the patient understands the risk
of failure and restoration of fertility (Figure 1).
CONCLUSIONS
PVPS remains a challenge to clinicians due to its poorly understood
pathophysiology. Large multicenter, well-constructed trials are
essential in hopes of establishing level one evidence to facilitate a
standardized algorithm to approach this disease. Our evaluation
and treatment algorithm for patient with PVPS is listed in
Figure 1.
A  multidisciplinary approach including pain clinic services,
psychologist/psychiatrist and pelvic floor physical therapist along
with the urologist is warranted before considering surgery. When
nonsurgical treatments fail, MDSC remains a valuable approach
with high success rates and should be considered for PVPS that are
refractory to medical therapy. MDSC appears to have the most success
for patients who experience a temporary relief from a cord block, and
can significantly improve the patient’s quality of life and ability to
return to daily activities.
AUTHOR CONTRIBUTIONS
WPT drafted the manuscript and LAL reviewed and edited the
manuscript. All authors read and approved the final manuscript.
COMPETING INTERESTS
The authors declare that they have no competing interests.
Supplementary information is linked to the online version of the paper
on the
Asian Journal of Andrology
website.
REFERENCES
1
2
3
Barone MA, Hutchinson PL, Johnson CH, Hsia J, Wheeler J. Vasectomy in the United
States, 2002.
J Urol
2006; 176: 232–6.
Schwingl PJ, Guess HA. Safety and effectiveness of vasectomy.
Fertil Steril
2000;
73: 923–36.
Jamieson DJ, Costello C, Trussell J, Hillis SD, Marchbanks PA,
et al.
US collaborative
review of sterilization working group. The risk of pregnancy after vasectomy.
Obstet
Gynecol
2004; 103: 848–50.
Sharlip ID, Belker AM, Honig S, Labrecque M, Marmar JL,
et al.
American urological
association. Vasectomy: AUA guideline.
J Urol
2012; 188: 2482–91.
Christiansen CG, Sandlow JI. Testicular pain following vasectomy: a review of
postvasectomy pain syndrome.
J Androl
2003; 24: 293–8.
Valencic M. Re: Granitsiotis P, Kirk D. Chronic testicular pain: an overview. Eur Urol
2004;45:430-6.
Eur Urol
2005; 47: 720.
McMahon A, Buckley J, Taylor A, Lloyd S, Deane R,
et al.
Chronic testicular pain
following vasectomy.
Br J Urol
1992; 69: 188–91.
Manikandan R, Srirangam SJ, Pearson E, Collins GN. Early and late morbidity
after vasectomy: a comparison of chronic scrotal pain at 1 and 10 years.
BJU Int
2004; 93: 571–4.
4
5
6
7
8
 SUU, Alm.del - 2016-17 - Bilag 234: Henvendelse af 17/3-17 fra Steen Vinum vedr. mandlig sterilisation
1734189_0006.png
[Downloaded free from http://www.ajandrology.com on Monday, August 08, 2016, IP: 217.74.141.215]
Post-vasectomy pain syndrome management
WP Tan and LA Levine
337
9
10
Leslie TA, Illing RO, Cranston DW, Guillebaud J. The incidence of chronic scrotal
pain after vasectomy: a prospective audit.
BJU Int
2007; 100: 1330–3.
Sandlow JI, Winfield HN, Goldstein M. Surgery of the scrotum and seminal vesicles.
In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, editors. Campbell-Walsh Urology.
9
th
ed. Philadelphia: WB Saunders; 2006. p. 1103–9.
Scherger JE, Ellis AR. Post-Vasectomy Pain Syndrome: Common But Hidden;
2012. p. 1–8. Available from: http://www.vasectomy-information.com/moreinfo/
pvps.htm. [Last accessed on 2015 Oct 25].
Tandon S, Sabanegh E. Chronic pain after vasectomy: a diagnostic and treatment
dilemma.
BJU Int
2008; 102: 166–9.
Sabanegh ES Jr., Thomas A Jr. Microsurgery in male infertility. In: Lipshultz L,
Howards S, Niederberger C, editors. Infertility in the Male. 4
th
ed. Cambridge:
Cambridge University Press; 2008.
Chen TF, Ball RY. Epididymectomy for post-vasectomy pain: histological review.
Br
J Urol
1991; 68: 407–13.
Linnet L, Hjort T. Sperm agglutinins in seminal plasma and serum after vasectomy:
correlation between immunological and clinical findings.
Clin Exp Immunol
1977;
30: 413–20.
Linnet L, Hjort T, Fogh-Anderson P. Association between failure to impregnate after
vasovasostomy and sperm agglutinins in semen.
Lancet
1981; 1: 117–9.
Alexander NJ. Vasectomy: long-term effects in the rhesus monkey.
J Reprod Fertil
1972; 31: 399–406.
Nangia AK, Myles JL, Thomas AJ Jr. Vasectomy reversal for the post-vasectomy
pain syndrome: a clinical and histological evaluation.
J Urol
2000; 164:1939–42.
Levine L. Chronic orchialgia: evaluation and discussion of treatment options.
Ther
Adv Urol
2010; 2: 209–14.
Davis BE, Noble MJ, Weigel JW, Foret JD, Mebust WK. Analysis and management
of chronic testicular pain.
J Urol
1990; 143: 936–9.
Sinclair AM, Miller B, Lee LK. Chronic orchialgia: consider gabapentin or nortriptyline
before considering surgery.
Int J Urol
2007; 14: 622–5.
Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK,
et al.
Recommendations
for the pharmacological management of neuropathic pain: an overview and literature
update.
Mayo Clin Proc
2010; 85: S3–14.
Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B,
et al.
Effects of desipramine,
amitriptyline, and fluoxetine on pain in diabetic neuropathy.
N Engl J Med
1992;
326: 1250–6.
Jackson KC, St. Onge EL. Antidepressant pharmacotherapy: considerations for the
pain clinician.
Pain Pract
2003; 3: 135–43.
Gallagher RM. Management of neuropathic pain: translating mechanistic advances
and evidence-based research into clinical practice.
Clin J Pain
2006; 22: S2–8.
Sansone RA, Sansone LA. Pain, pain, go away: antidepressants and pain
management.
Psychiatry (Edgmont)
2008; 5: 16–9.
Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V,
et al.
Gabapentin for
the symptomatic treatment of painful neuropathy in patients with diabetes mellitus:
a randomized controlled trial.
JAMA
1998; 280: 1831–6.
Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin
for the treatment of postherpetic neuralgia: a randomized controlled trial.
JAMA
1998; 280: 1837–42.
Rice AS, Maton S; Postherpetic Neuralgia Study Group. Gabapentin in postherpetic
neuralgia: a randomised, double blind, placebo controlled study.
Pain
2001;
94: 215–24.
Misra S, Ward S, Coker C. Pulsed radiofrequency for chronic testicular pain – A
preliminary report.
Pain Med
2009; 10: 673–8.
Terkawi AS, Romdhane K. Ultrasound-guided pulsed radiofrequency ablation of the
genital branch of the genitofemoral nerve for treatment of intractable orchalgia.
Saudi J Anaesth
2014; 8: 294–8.
Levine LA. Microsurgical denervation of the spermatic cord.
J Sex Med
2008;
5: 526–9.
Strom KH, Levine LA. Microsurgical denervation of the spermatic cord for chronic
orchialgia: long-term results from a single center.
J Urol
2008; 180: 949–53.
Ahmed I, Rasheed S, White C, Shaikh NA. The incidence of post-vasectomy
testicular pain and the role of nerve stripping (denervation) of the spermatic cord
in its management.
Br J Urol
1997; 79: 269–70.
35 Heidenreich A, Olbert P, Engelmann UH. Management of chronic testalgia by
microsurgical testicular denervation.
Eur Urol
2002; 41: 392–7.
36 Larsen SM, Benson JS, Levine LA. Microdenervation of the spermatic cord for
chronic scrotal content pain: single institution review analyzing success rate after
prior attempts at surgical correction.
J Urol
2013; 189: 554–8.
37 Benson JS, Abern MR, Larsen S, Levine LA. Does a positive response to spermatic
cord block predict response to microdenervation of the spermatic cord for chronic
scrotal content pain?
J Sex Med
2013; 10: 876–82.
38 Strebel RT, Leippold T, Luginbuehl T, Muentener M, Praz V,
et al.
Chronic scrotal pain
syndrome: management among urologists in Switzerland.
Eur Urol
2005; 47: 812–6.
39 Kavoussi PK, Costabile RA. Orchialgia and the chronic pelvic pain syndrome.
World
J Urol
2013; 31: 773–8.
40 Granitsiotis P, Kirk D. Chronic testicular pain: an overview.
Eur Urol
2004;
45: 430–6.
41 Sweeney CA, Oades GM, Fraser M, Palmer M. Does surgery have a role in management
of chronic intrascrotal pain?
Urology
2008; 71: 1099–102.
42 Calleary JG, Masood J, Hill JT. Chronic epididymitis: is epididymectomy a valid
surgical treatment?
Int J Androl
2009; 32: 468–72.
43 West AF, Leung HY, Powell PH. Epididymectomy is an effective treatment for scrotal
pain after vasectomy.
BJU Int
2000; 85: 1097–9.
44 Lee JY, Cho KS, Lee SH, Cho HJ, Cho JM,
et al.
A comparison of epididymectomy
with vasectomy reversal for the surgical treatment of postvasectomy pain syndrome.
Int Urol Nephrol
2014; 46: 531–7.
45 Chung JH, Moon HS, Choi HY, Jeong TY, Ha US,
et al.
Inhibition of adhesion
and fibrosis improves the outcome of epididymectomy as a treatment for chronic
epididymitis: a multicenter, randomized controlled, single-blind study.
J Urol
2013;
189: 1730–4.
46 Myers SA, Mershon CE, Fuchs EF. Vasectomy reversal for treatment of the
post-vasectomy pain syndrome.
J Urol
1997; 157: 518–20.
47 Shapiro EI, Silber SJ. Open-ended vasectomy, sperm granuloma, and postvasectomy
orchialgia.
Fertil Steril
1979; 32: 546–50.
48 Polackwich AS, Tadros NN, Ostrowski KA, Kent J, Conlin MJ,
et al.
Vasectomy
reversal for postvasectomy pain syndrome: a study and literature review.
Urology
2015; 86: 269–72.
49 Lee JY, Chang JS, Lee SH, Ham WS, Cho HJ,
et al.
Efficacy of vasectomy reversal
according to patency for the surgical treatment of postvasectomy pain syndrome.
Int J Impot Res
2012; 24: 202–5.
50 Horovitz D, Tjong V, Domes T, Lo K, Grober ED,
et al.
Vasectomy reversal provides
long-term pain relief for men with the post-vasectomy pain syndrome.
J Urol
2012;
187: 613–7.
51 Devine CJ, Schellhammer PF. The use of microsurgical denervation of the spermatic
cord for orchalgia.
Trans Am Assoc Genitourin Surg
1978; 70: 149–51.
52 Choa RG, Swami KS. Testicular denervation. A new surgical procedure for intractable
testicular pain.
Br J Urol
1992; 70: 417–9.
53 Levine LA, Matkov TG, Lubenow TR. Microsurgical denervation of the spermatic
cord: a surgical alternative in the treatment of chronic orchialgia.
J Urol
1996;
155: 1005–7.
54 Levine LA, Matkov TG. Microsurgical denervation of the spermatic cord as primary
surgical treatment of chronic orchalgia.
J Urol
2001; 165: 1927–9.
55 Oliveira RG, Camara C, Alves Jde M, Coelho RF, Lucon AM,
et al.
Microsurgical
testicular denervation for the treatment of chronic testicular paininitial results.
Clinics (Sao Paulo)
2009; 64: 393–6.
56 Cadeddu JA, Bishoff JT, Chan DY, Moore RG, Kavoussi LR,
et al.
Laparoscopic
testicular denervation for chronic denervation.
J Urol
1999; 162: 733–6.
57 Ducic I, Dellon AL. Testicular pain after inguinal hernia repair: an approach to
resection of the genital branch of the genitofemoral nerve.
J Am Coll Surg
2004;
198: 181–4.
58 Yamamoto M, Katsuno S, Miyake K. Management of chronic orchialgia of unknown
etiology.
Int J Urol
1995; 2: 47–9.
59 Levine LA, Hoeh MP. Evaluation and management of chronic scrotal content pain.
Curr Urol Rep
2015; 16: 1–8.
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
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SUPPLEMENTARY APPENDIX
1. MICRODENERVATION OF THE SPERMATIC
CORD (MDSC) TECHNIQUE
We typically perform the procedure in an outpatient setting under
general anesthesia with the aid of an operating microscope at
4–8 × power. The patient is placed in a supine position and following
skin preparation, an oblique 3–4  cm inguinal incision is centered
over the external inguinal ring. The spermatic cord is then isolated
circumferentially and the ilioinguinal nerve is identified. The
ilioinguinal nerve typically runs along the lateral surface of the cord.
A 2–3 cm segment of the nerve is excised and the cut ends are ligated.
Subsequently, the nerve is buried under the external inguinal ring to
decrease the risk of neuroma formation. Fibers of the genital branch
of the genitofemoral nerve are reported to run along the floor of the
inguinal canal. Cautery is used to divide those rarely visible fibers.
The spermatic cord is then elevated and a Penrose drain (5/8 inch) is
placed underneath the cord.
The operating microscope is brought to the field and the anterior
spermatic cord fascia is incised to expose the cord contents. A 20 MHz
Microvascular Doppler System ultrasound  (Vascular Technology,
Inc.,  [VTI] Nashua, NH, USA) is used to identify the testicular,
cremasteric and deferential arteries. The arteries are secured with
micro-vessel loops. All identifiable lymphatics are spared to decrease
the risk of hydrocele formation. The internal spermatic veins are
subsequently divided then ligated. The cremasteric musculature and
spermatic cord fascia are divided using electrocautery (Figure 2).
Prior to closure, the micro-Doppler is used to check for pulsatile
flow within the preserved arteries. Topical papaverine is applied to the
vessel surface to encourage vasodilation if poor flow is noted. The cord
is then returned to its original position and 10 cc of 0.25 bupivacaine
without epinephrine is injected around the wound. The incision is
closed in layers.
2. EPIDIDYMECTOMY TECHNIQUE
The surgical procedure is typically performed in an outpatient setting
under local or general anesthesia. We utilize an anterior ipsilateral
or median raphe scrotal incision to deliver the testicle. The tunica
vaginalis is incised to allow access to the vas deferens and epididymis.
The testicular end of the vasectomy and the convoluted vas is identified.
The entire vas deferens from the severed vasectomy site back through
the convoluted vas and epididymis is excised using blunt and sharp
dissection to dissect the vas from the spermatic cord and testis. The
epididymal arteries and testicular arteries are typically located at the
middle and distal third of the epididymis. Care should be taken to
preserve the vessels to the testis. A spermatic cord block is performed
using 10 cc of 0.25% bupivacaine followed by electrocautery to achieve
hemostasis prior to closing the tunica vaginalis defect and the skin with
absorbable sutures. We typically do not leave a drain unless there is
persistent oozing of blood.
3. VASECTOMY REVERSAL TECHNIQUE
The surgical procedure is typically performed in an outpatient setting
under general anesthesia. The incision may be through the median
raphe, traverse scrotal or vertical incision on the anterior scrotal wall.
We typically prefer a lateral vertical incision for unilateral reversal. The
vas deferens is identified, both proximally and distally to the vasectomy
site. Care is taken to preserve the periadventitial sheath of the vas
deferens to ensure its blood supply remains intact. A 90° transection
of healthy vas is performed at both ends, using slotted nerve-holding
clamp (Accurate Surgical and Scientific Instruments Corp., Westbury,
NY, USA). The obstructed segments along with any sperm granuloma
and or sutures/clips are excised. Fluid from the testicular side of the
vas is then examined microscopically for spermatozoa. The distal side
of the vas is then cannulated with a 24-gauge angiocatheter and 10 cc
of saline is injected through to confirm distal patency.
We utilize a microspike approximator  (Accurate Surgical and
Scientific Instruments Corp., Westbury, NY, USA) to stabilize both
ends of the vas during reanastomosis. We start by placing full thickness
9-0 nylon double-armed sutures  (Ethicon Sharpoint Nylon Black,
Somerville, NJ, USA) at the 12, 3, 6 and 9 o’ clock positions beginning
within the lumen, through the muscularis and exiting the adventitia.
The mucosal lumen may be dilated with a micro-vessel dilator to
ease suture placement. Interrupted 9-0 nylon sero-muscular sutures
are then placed between the full thickness sutures for a modified
two-layer technique. The incision is closed in layers and 10 cc of 0.25%
bupivacaine without epinephrine is injected around the wound.
4. ORCHIECTOMY TECHNIQUE
We prefer the inguinal approach when performing an orchiectomy.
A 4–5 cm sub-inguinal incision is made, the spermatic cord is isolated
and secured with a Penrose drain. The ilioinguinal nerve is sharply
dissected off the spermatic cord and divided. The cord is dissected down
to the level of the pubic tubercle. The testicle is delivered through the
wound and the gubernaculum is divided with cautery while ensuring
that button-holing of the scrotal skin does not occur. Suture ligation
of the gubernacular attachments may be necessary.
The spermatic cord is isolated up to the internal inguinal ring by
opening the external oblique fascia. The cord is separated into 2–3
packets which are ligated with 2-0 silk ties and divided. We typically
isolate and tie the vas deferens separately from the cord. Meticulous
hemostasis is achieved using electrocautery and the external oblique
fascia is reapproximated using 3-0 dissolvable sutures followed by 4-0
monocryl for the skin.