Page 145 - Remedial Andrology

The exact association between reduced male fertility and varicocele is unknown. Increased scrotal
temperature, hypoxia and reflux of toxic metabolites can cause testicular dysfunction and infertility due to
increased overall survival and DNA damage [1694].

A meta-analysis showed that improvements in semen parameters are usually observed after surgical correction
in men with abnormal parameters [1695]. Varicocelectomy can also reverse sperm DNA damage and improve
OS levels [1694, 1696].

10.4.3.3.2 Varicocelectomy
Varicocele repair has been a subject of debate for several decades. A meta-analysis of RCTs and observational
studies in men with only clinical varicoceles has shown that surgical varicocelectomy significantly
improves semen parameters in men with abnormal semen parameters, including men with NOA with hypo-
spermatogenesis or late maturation (spermatid) arrest on testicular pathology [1693, 1697-1700]. Pain
resolution after varicocelectomy occurs in 48-90% of patients [1701]. A recent systematic review has shown
greater improvement in higher-grade varicoceles and this should be taken into account during patient
counselling [1702].

In RCTs, varicocele repair in men with a subclinical varicocele was ineffective at increasing the chances
of spontaneous pregnancy [1703]. Also, in randomised studies that included mainly men with normal
semen parameters no benefit was found to favour treatment over observation. A Cochrane review from
2012 concluded that there is evidence to suggest that treatment of a varicocele in men from couples
with otherwise unexplained subfertility may improve a couple’s chance of spontaneous pregnancy [1704].
Two recent meta-analyses of RCTs comparing treatment to observation in men with a clinical varicocele,
oligozoospermia and otherwise unexplained infertility, favoured treatment, with a combined OR of 2.39-4.15
(95% CI: 1.56-3.66) (95% CI: 2.31-7.45) [1700, 1704]. Average time to improvement in semen parameters
is up to two spermatogenic cycles [1705, 1706] and spontaneous pregnancy between 6 and 12 months
after varicocelectomy [1707, 1708]. A further meta-analysis has reported that varicocelectomy may improve
outcomes following ART in oligozoospermic men with an OR of 1.69 (95% CI: 0.95-3.02) [1709].

10.4.3.3.3 Prophylactic varicocelectomy
In adolescents with a varicocele, there is a significant risk of over-treatment because most adolescents with a
varicocele have no problem achieving pregnancy later in life [1710]. Prophylactic treatment is only advised in
case of documented testicular growth deterioration confirmed by serial clinical or Doppler US examinations
and/or abnormal semen analysis [1711, 1712].

More novel considerations for varicocelectomy in patients with NOA, hypogonadism and DNA damage are
described below:

Varicocelectomy and NOA
Several studies have suggested that varicocelectomy may lead to sperm appearing in the ejaculate in men with
azoospermia. In one such study, microsurgical varicocelectomy in men with NOA led to sperm in the ejaculate
post-operatively with an increase in ensuing natural or assisted pregnancies [1713]. There were further
beneficial effects on sperm retrieval rates (SRRs) and ICSI outcomes. Meta-analyses have further corroborated
these findings; 468 patients diagnosed with NOA and varicocele underwent surgical varicocele repair or
percutaneous embolisation. In patients who underwent varicocelectomy, SRRs increased compared to those
without varicocele repair (OR: 2.65; 95% CI: 1.69-4.14; P < 0.001). In 43.9% of the patients (range: 20.8%-
55.0%), sperm were found in post-operative ejaculate. These findings indicate that varicocelectomy in patients
with NOA and clinical varicocele is associated with improved SRR, and overall, 44% of the treated men have
sperm in the ejaculate and may avoid sperm retrieval. However, the quality of evidence available is low and
the risks and benefits of varicocele repair must be discussed fully with the patient with NOA and a clinically
significant varicocele prior to embarking upon treatment intervention [1698]. This must necessarily take into
consideration the infertile couple together, especially considering the time needed for a possible SRR and the
baseline characteristics of the female partner (i.e., age, medical history, anti-Müllerian hormone (AMH) levels =
good ovarian reserve, etc.).

Varicocelectomy and hypogonadism
Evidence also suggests that men with clinical varicoceles who are hypogonadal may benefit from varicocele
intervention. One meta-analysis studied the efficacy of varicocele intervention by comparing the pre-operative
and post-operative serum testosterone of 712 men. The combined analysis of seven studies demonstrated
that the mean post-operative serum testosterone improved by 34.3 ng/dL (95% CI: 22.57-46.04, P < 0.00001,

144 SEXUAL AND REPRODUCTIVE HEALTH - MARCH 2021