VARICOCELE: A REVIEW

Nevzat Can Sener,1 Ismail Nalbant,2 *Ufuk Ozturk2

1. Department of Urology, Numune Education and Research Hospital, Ministry of Health, Adana, Turkey
2. Department of Urology, Diskapi Yildirim Beyazid Education and Research Hospital,
Ministry of Health, Ankara, Turkey
*Correspondence to [email protected]

Disclosure: The authors have declared no conflicts of interest.

Received: 16.02.15 Accepted: 23.03.15
Citation: EMJ Repro Health. 2015;1[1]:54-58.

ABSTRACT
The link between varicocele and infertility was first reported by Celsius in the first century AD, but it was
not widely acknowledged until Tulloch and colleagues reported the improvement of sperm parameters
in 26 of 30 patients undergoing varicocelectomy. The World Health Organization also reported that
varicocele was present in 25% of patients with abnormal sperm parameters and 12% of patients with
normal sperm parameters. Varicocele is the most frequently encountered surgical disease causing
male infertility.

Keywords: Male infertility, varicocele, varicocelectomy.

INTRODUCTION blood pressure and relatively slower blood flow

compared with the right side. This is mainly
The link between varicocele and infertility was caused by the drainage of the left testicular
first reported by Celsius in the first century AD.1 vein to the left renal vein with a perpendicular
A varicocele was described as a bag of worms angle, whereas in the right testicular vein the
by Dubin and Amelar in 1970,2 although a more drainage is to the vena cava at a steeper angle.
scientific definition would be: an abnormal venous This causes less cranial venous drainage.
dilatation of the pampiniform plexus caused by Venous reflux: Reflux to the pampiniform
various aetiologies. The first usage of the word plexus is caused by the lack of valves in the
varicocele was by Curling in 1843.3 Varicocele internal spermatic vein and/or the reflux caused
remained out of the spotlight until Tulloch and by venous collateral flow. The lack of valves
colleagues4 reported the improvement of sperm in the junction of the left renal and internal
parameters in 26 of 30 patients undergoing spermatic veins was shown by Shiraishi and
varicocelectomy. The World Health Organization Naito.7 Braedel and colleagues6 demonstrated
reported that varicocele is present in 25% of a lack of venous valves in 73% of 659 male
patients with abnormal sperm parameters and patients with varicocele.
12% of patients with normal sperm parameters.5 Partial obstruction of testicular veins:
The condition is commonly encountered in the This phenomenon, called the nutcracker
left testicular side: 90% of cases are isolated in phenomenon, occurs when a specific vein is
the left side and only 2% are isolated in the right compressed by arteries. In proximal type, the
side; this phenomenon can be explained by the left renal vein is compressed by the aorta and
venous anatomy.6 the superior mesenteric artery. In distal type,
the left common iliac artery compresses the
AETIOLOGY left common iliac vein.

There are three commonly accepted theories: PATHOPHYSIOLOGY

Differences between left and right testicular
venous drainage anatomy: The left internal The underlying pathophysiology can be
spermatic vein has about 8-10 mm H2O higher summarised in the following hypotheses. It is

54 REPRODUCTIVE HEALTH August 2015 EMJ EUROPEAN MEDICAL JOURNAL

 proposed that varicocele is associated with that patients should have at least one diagnostic
increased testicular blood flow; Grasso Laenza imaging modality combined with physical
and colleagues8 reported increased blood flow in examination. Through the use of Doppler USG,
patients with varicocele compared with healthy blood flow to the testes and reflux can be
controls in colour Doppler studies. An increase in evaluated. Hirsh et al.17 graded varicocele according
interstitial fluid was described in animal models of to the reflux observed in Doppler USG:
varicocele formation,9 with the increased number
of leukocytes potentially attributable to Grade 1: No spontaneous venous reflux.
this increase. In addition, a higher testicular
temperature may inhibit spermatogenesis. In Grade 2: Intermittent spontaneous venous reflux.
both animal models and humans, an increased Grade 3: Continuous spontaneous venous reflux.
intra and intertesticular temperature was shown
in the presence of varicocele.10,11 Increased venous However, an objective grading system is lacking
pressure caused by reflux may contribute to and a validated Doppler grading system is needed.
decreased testicular flow,12 while Tek et al.13 The most sensitive test for diagnosing varicocele
demonstrated a higher apoptotic index in patients is venography, but, due to its invasiveness and
with varicocele (0.693 versus 0.206; p<0.05). relatively high cost, it is no longer recommended
Varicocele also causes impairment of the blood
unless a therapeutic occlusion is planned. The
testis barrier,14 which leads to the formation of
success rate of the occlusion procedure is as
anti-sperm antibodies.15
high as 85% for recurrent varicoceles.18 Scrotal
thermography is another tool for diagnosis
DIAGNOSIS
although it is not a widely used method, mainly
Diagnosis is made using physical examination. due to the widespread use of Doppler USG.
Physical examination should be completed in This method can be used to document elevated
both sitting and standing positions inside a warm temperature of the scrotum due to varicocele.
and comfortable room. The scrotum should be
inspected first and then palpated to evaluate TREATMENT INDICATIONS
spermatic cord and testes. The diagnosis is finally
made by observing and/or palpating a dilated or Guidelines from the European Association of
tortuous segment.16 Varicocele can be classified as Urology19 recommend treatment in the case of
one of three grades: clinical varicocele, oligozoospermia, infertility
Grade 1: Dilated veins are palpable only with lasting longer than 2 years, and unexplained
Valsalva manoeuver. infertility. The American Urological Association
recommends treatment when the following
Grade 2: Dilated veins are seen whilst the patient criteria are met: palpable varicocele on physical
is standing but not without Valsalva manoeuver, examination (may be validated via ultrasound),
the physician can palpate dilated veins. known infertility, normal female fertility potential,
Grade 3: Tortuous and dilated veins can be seen in and abnormal semen parameters.20
scrotum skin.
TREATMENT OPTIONS
Radiology can assist in diagnosis: scrotal
ultrasonography (USG) is not indicated for The main aim of treatment is to disrupt internal
diagnosis of varicocele, but can be helpful if the spermatic venous drainage whilst preserving
diagnosis is inconclusive, such as in patients
arterial and lymphatic blood flow. There are several
with morbid obesity, previous scrotal surgery, or
defined methods, the most widely used of which
accompanying ipsilateral hydrocele. The spermatic
are the inguinal,21 subinguinal, and microscopic
cord and epididymis can be evaluated with
conventional USG. The assessment of testicular subinguinal approaches. Although not very
volume can also be helpful for indicating a need commonly used, retroperitoneal,22 scrotal,23 and
for intervention. Nowadays, because of the wide laparoscopic approaches24 have been described.
usage of Doppler USG and the subjectivity of Furthermore, a minimally invasive method,
physical examination, Doppler USG has become angiography, and embolisation for internal
a standard diagnostic tool. It is recommended spermatic veins, have also been defined.25

REPRODUCTIVE HEALTH August 2015 EMJ EUROPEAN MEDICAL JOURNAL 55

 TREATMENT OUTCOMES PROGNOSTIC FACTORS

In 2009, a meta-analysis suggested that Not all patients improve after a successful
varicocele repair did not improve the likelihood varicocelectomy. Patients with a disease history
of conception.26 After the meta-analysis <2 years and who have high-grade varicoceles are
was published, it was greatly criticised for more likely to improve following varicocelectomy.
heterogeneity among enrollment and having Patients with a total motile sperm count <5 million,
who have genetic disorders, altered follicle-
normal semen parameters of patients suffering
stimulating hormone (FSH)/testosterone levels,
from infertility.27-29 Furthermore, the study included
small testis volume, or concomitant metabolic
one of the most debatable topics in urology, the
syndrome have worse treatment outcomes.44-46
subclinical varicocele, which will be discussed in
more detail below. In contrast to this meta-analysis, COMPLICATIONS
several papers published in subsequent years
advocated the use of varicocelectomy to improve Recurrence rates can be as high as 29% with
sperm parameters and reported improvement of high ligations and about 2% with microscopic
sperm parameters and paternity rates.30 techniques. When optical enhancement is not an
option, hydrocele may be observed in 7-10% of
Subinguinal varicocelectomy can yield high cases following varicocelectomy. Following the
improvement rates: 75.2% improvement in semen improvement of the technique with microscopy,
parameters and 45.5% in pregnancy rates.31 one of the most feared complications, testicular
Abdel-Meguid et al.30 treated patients with atrophy, is encountered at a rate of only 1%.
varicocelectomy and followed their progress. They Ilioinguinal nerve damage may be seen with the
revealed a significant improvement in the treatment loss of sensation in the scrotum and inner thigh.
arm of the study, and a 3.04-times higher rate of Haematoma and infections may be encountered
spontaneous pregnancy.30 There is a debate as in about 2-5% of cases.46,47
to whether varicocele repair improves pregnancy
Patients with Non-Obstructive Azoospermia
rates. Nilsson et al.32 reported the first comparative
study of varicocele repair and did not reveal a The need for varicocelectomy in patients
significant difference in pregnancy rates among with non-obstructive azoospermia is debatable.
patients treated with varicocele repair. Krause and Palpable varicocele can be found in approximately
colleagues33 conducted a study of 65 men treated 4-14% of cases.48 Even after varicocele repair, most
with sclerotherapy and revealed no significant of these men will be subfertile.48 One of the most
comprehensive meta-analyses was conducted
improvement compared with those who received
by Weedin and colleagues,49 and stated that
no treatment. However, both studies have been
39% of a total of 233 patients had motile
criticised for low cohort size and poor follow-up.
sperm in semen analysis performed after
On the other hand, Okuyama et al.34 compared successful varicocelectomy. They concluded that
patients treated using Palomo repair with histopathological examination was a key factor
those who received no treatment and revealed in treatment success, with those with maturation
arrest being the most likely to benefit from
significantly higher pregnancy rates in the
surgery, whereas Sertoli-cell-only syndrome had
treatment arm (30% versus 18%; p<0.05). Schlegel35
the worst outcome (p<0.001). Daitch et al.50
wrote a review on varicocele treatment outcomes
proposed a higher rate of pregnancy following
and revealed a 33% pregnancy rate in patients surgical repair. Esteves et al.51 reported
with varicocele repair compared with 16% in the better outcomes following intracytoplasmic sperm
no-treatment group. Varicocele can cause scrotal injection therapy.
pain and some surgeons prefer surgery to treat
this painful disease. In several studies pain Patients with Subclinical Varicocele
was shown to be resolved with conservative Subclinical varicocele is defined as varicocele
treatment (e.g. oral anti-inflammatory medicine that is only diagnosed radiologically. Several
and limiting physical activity) in 5-15% of investigators have conducted trials concerning
patients.36,37 Several studies reported success rates treatment of subclinical varicocele and do not
between 75-91%.38-44 recommend treatment.28,29,52 Both the European

56 REPRODUCTIVE HEALTH August 2015 EMJ EUROPEAN MEDICAL JOURNAL

 and American Urological Associations do not that patients should have at least one
recommend treatment of subclinical varicocele.20 diagnostic imaging modality combined with
physical examination.
Paediatric and Adolescent Varicocele The main aim of treatment is to disrupt internal
Indications for treatment are: varicocele associated spermatic venous drainage while preserving
with small testis, additional testicular condition arterial and lymphatic blood flow. There are
affecting fertility, bilateral palpable varicocele, several methods defined, with the most widely
pathological sperm quality, and symptomatic used being the inguinal, subinguinal, and
varicocele.53 ayan and colleagues54 compared microscopic subinguinal approaches.
studies of paediatric varicocelectomy and Patients with a disease history <2 years and
proposed that a 10% volume difference in the with high-grade varicoceles are more likely to
affected testis should be the indication for surgical improve following varicocelectomy.
repair; they reported that 53% of patients gained Not all patients improve after a successful
normal sperm volume following the operation varicocelectomy. Patients with a total motile
before 14 years of age. With the subinguinal sperm count <5 million, who have genetic
microscopic approach, recurrence rates are disorders, altered FSH/testosterone levels,
usually <10%.55-57 small testis volume, or concomitant metabolic
syndrome have worse treatment outcomes.
KEY MESSAGES Both European and American Urological
Associations do not recommend the treatment
The WHO reported that varicocele was present of subclinical varicocele.
in 25% of patients with abnormal sperm Following the improvement of the technique
parameters and 12% of patients with normal with microscopy, one of the most feared
sperm parameters. complications, testicular atrophy, is encountered
Diagnosis is made using physical examination. at a rate of only 1%.
Nowadays, because of the wide usage of Several papers advocate for varicocelectomy
Doppler USG and subjectivity of physical in improving sperm parameters, and report
examination, Doppler USG has become a improvement of sperm parameters and
standard diagnostic tool. It is recommended paternity rates.

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