Varicocelectomy before assisted

reproductive technology: are

outcomes improved?
Taylor P. Kohn, M.Phil.,a Jaden R. Kohn, B.S.,a and Alexander W. Pastuszak, M.D., Ph.D.b,c
a
Baylor College of Medicine; b Center for Reproductive Medicine, Baylor College of Medicine; and c Scott Department of
Urology, Baylor College of Medicine, Houston, Texas

Clinical varicoceles have been associated with impaired semen parameters and male-factor infertility. Varicocele repair can improve
live birth rates for men with clinical varicocele. Varicocelectomy is often combined with assisted reproductive techniques
(ART) such as intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). Here we review
the literature examining varicocelectomy before ART to evaluate whether improved pregnancy outcomes are realized. Although
insufficient evidence exists to determine if correcting a varicocele improves IUI outcomes, a clinical benefit is observed when correcting
a clinical varicocele in oligospermic and nonobstructed azoospermic men before IVF/ICSI. In couples seeking fertility with the use of
ART, varicocele repair may offer improvement in semen parameters and may decrease the level of ART needed to achieve successful
pregnancy. (Fertil SterilÒ 2017;108:385–91. Ó2017 by American Society for Reproductive Medicine.)
Key Words: Varicocele, varicocelectomy, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection
Discuss: You can discuss this article with its authors and with other ASRM members at https://www.fertstertdialog.com/users/
16110-fertility-and-sterility/posts/18170-24268

I
nfertility is defined as the inability to with only 11.7% of men with normal permitting retrograde blood flow and
conceive after 1 year of unprotected semen parameters (6). Although the pooling close to the testicle. The left
intercourse (1). It is estimated that mechanism of impaired sperm gonadal vein joins with the left renal
one in six couples experience infertility production resulting from varicocele vein at a perpendicular angle, leading
in their lifetime (2). Of these infertile has not been clearly established, poor to increased venous pressure compared
couples, a male factor plays a role in testicular drainage may result in with the right. Varicoceles can also
50% of cases (3). The most common varicocele-associated testicular result from left renal vein compression
and correctable cause of male-factor dysfunction (7). between the superior mesenteric artery
infertility is a varicocele. Although var- A varicocele is a pathologic dila- and the abdominal aorta (the
icoceles are present in 15%–20% of tion of the pampiniform venous plexus ‘‘nutcracker effect’’) (8–10).
postpubertal men, those presenting to of the spermatic cord, one of three Numerous theories have been pro-
infertility clinics have varicoceles at venous drainage pathways of the testi- posed for how poor testicular drainage
2–3 times the frequency found in the cle. Clinically, the dilated venous impairs fertility. An early study by
general population and in those with plexus is graded by size: subclinical Goldstein et al. in 1989 demonstrated
proven fertility (4, 5). In a World (detected by ultrasound only), grade I, that intratesticular and scrotal temper-
Health Organization study of 9,034 grade II, or grade III. Several etiologies atures were higher in men with a vari-
infertile men, a varicocele was for varicocele have been proposed. cocele compared with control subjects
identified in 25.4% of men with The veins of the pampiniform plexus without a varicocele, suggesting that
abnormal semen parameters compared may have dysfunctional valves, testicular hyperthermia induced by
varicocele may impair sperm produc-
Received April 29, 2017; revised May 25, 2017; accepted June 28, 2017.
T.P.K. has nothing to disclose. J.R.K. has nothing to disclose. A.W.P. is an advisor to and speaker for tion (11). Other studies have found
Endo Pharmaceuticals. that men with varicocele have more re-
Supported by a National Institutes of Health K12 Scholar grant (to A.W.P.) supported by a Male Repro-
ductive Health Research Career Development Physician-Scientist Award (HD073917-01) from the
flux of adrenal metabolites in penile
Eunice Kennedy Shriver National Institute of Child Health and Human Development Program. blood, testicular hypoxia, antisperm
Reprint requests: Alexander W. Pastuszak, M.D., Ph.D., Assistant Professor, Center for Reproductive antibodies, and reactive oxygen species
Medicine, Scott Department of Urology, Baylor College of Medicine, 6624 Fannin Street, Suite
1700, Houston, Texas 77030 (E-mail: pastusza@bcm.edu). in sperm compared with men without
varicoceles (12–14). These biochemical
Fertility and Sterility® Vol. 108, No. 3, September 2017 0015-0282/$36.00
Copyright ©2017 Published by Elsevier Inc. on behalf of the American Society for Reproductive
changes have been implicated in
Medicine testicular atrophy, higher levels of
http://dx.doi.org/10.1016/j.fertnstert.2017.06.033

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reactive oxygen species, and decreased testosterone semen parameters is unclear, because several studies and
production by Leydig cells (13,15–17). A recent study from meta-analyses have demonstrated improvement in only one
Mostafa et al. found that men with varicoceles have semen parameter or no improvement at all after varicocelec-
elevated levels of apoptosis-associated microRNA in seminal tomy, despite increases in pregnancy and live birth rates (22,
fluid (18). Ultimately, it may be a combination of these factors 23). However, several studies have demonstrated
that result in impaired fertility. improvements in sperm DNA fragmentation and in the
The correction of a varicocele can be performed in presence of reactive oxygen species after surgical correction
numerous ways, microsurgical ligation being the most effec- of varicocele (24–28). These molecular-level improvements
tive; venous embolization is another common option. Several may explain why varicocelectomy results in improved preg-
randomized controlled trials and meta-analyses have found nancy rates although traditional semen parameters remain
that in men with both a varicocele and abnormal semen pa- relatively unchanged.
rameters, varicocelectomy improves the chances of achieving Assisted reproductive techniques (ART), such as intra-
a pregnancy (17,19–21). Although the studies demonstrated a uterine insemination (IUI), in vitro fertilization (IVF), and in-
benefit in pregnancy outcomes, whether improvement tracytoplasmic sperm injection (ICSI), can be used to help
in pregnancy outcomes after surgical correction of a infertile couples achieve a pregnancy. In the United States
clinical varicocele is due to improvement in typical and Europe, more than 348,000 cycles of IVF and 400,000

FIGURE 1

Summary of possible assisted reproductive techniques and range of pregnancy rates and sperm recovery rates for men with a clinical varicocele and
oligospermia or azoospermia. ICSI ¼ intracytoplasmic sperm injection; IUI ¼ intrauterine insemination; IVF ¼ in vitro fertilization.
Kohn. Impact of varicocelectomy on IUI or IVF/ICSI. Fertil Steril 2017.

386 VOL. 108 NO. 3 / SEPTEMBER 2017

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cycles of IUI are performed per year (29). Some couples in pregnancy success in this early study may be explained by
which the male partner presents with a varicocele elect to the lack of ovarian stimulation in women undergoing IUI.
use ART with or without undergoing varicocelectomy first. In 2001, Daitch et al. published a retrospective study that
Multiple studies have explored the potential benefit of varico- followed 58 men with both clinical varicocele and abnormal
celectomy in addition to ART; here we examine and summa- semen parameters (31). However, the duration of follow-up
rize the evidence assessing the efficacy of varicocelectomy in was not specified. Within that cohort, 34 men underwent sur-
combination with ART in achieving a pregnancy (Fig. 1). gical varicocelectomy and 24 were untreated. Varicocelec-
tomy did not improve semen parameters, but was associated
SEARCH STRATEGY with higher pregnancy and live birth rates after IUI. Couples
with surgically corrected varicocele achieved 12 pregnancies
To identify articles for this review, the following search terms
after 101 IUI cycles (11.9%), all of which resulted in live births
were used in Medline: ‘‘varicocele repair,’’ ‘‘varicocele correc-
(11.9%). Couples with untreated varicocele achieved only four
tion,’’ ‘‘varicocelectomy,’’ ‘‘varicocele treatment,’’ ‘‘assisted
pregnancies after 63 IUI cycles (6.3%), of which only one
reproductive techniques,’’ ‘‘in vitro fertilization,’’ ‘‘intrauter-
pregnancy resulted in a live birth (1.6%). That paper unfortu-
ine insemination,’’ or ‘‘intracytoplasmic sperm injection.’’
nately did not report female age, which is a prominent
Relevant articles were identified and presented in this review.
confounder when assessing pregnancy rates.
In 2008, Boman et al. retrospectively reviewed 118 cou-
INTRAUTERINE INSEMINATION AFTER ples presenting with clinical varicocele and asthenospermia
VARICOCELECTOMY followed for a mean of 41.6 months (32). Among the men,
Intrauterine insemination is often the first ART tried for an 69 underwent varicocelectomy and 49 did not. Significant
infertile couple. In a study of 251 infertile men with a clinical improvements in sperm motility and total motile count were
varicocele, Zini et al. found that 28% of men who underwent observed in men after varicocelectomy, with a significant
varicocelectomy went on to try IUI and 34% of men who did decrease in sperm concentrations from 48.0 to 36.6 million/
not have varicocele correction used IUI (29). Although couples mL. The authors did not report the number of IUI cycles per-
often undergo a combination of varicocele correction and IUI, formed or live birth rates. However, the ten couples with var-
the efficacy of this combination has not been well studied. icocelectomy achieved five pregnancies after IUI (50%),
Only three controlled studies have been published examining whereas the ten couples with uncorrected varicocele achieved
pregnancy rates with the use of IUI after varicocelectomy, and only one pregnancy after IUI (10%). However, that difference
those studies demonstrated a wide range of results. was not statistically significant, likely because of the small
In 1992, Marmar et al. published a retrospective study sample size. Several other studies have reported pregnancy
investigating the effectiveness of IUI after varicocelectomy rates after IUI for men with corrected varicoceles, but did
(30). In that study, the authors followed a cohort of 71 infertile not use a control group with untreated varicocele for compar-
men with ultrasound-confirmed varicocele for a mean dura- ison. In those case series of men with corrected varicocele, the
tion of 42 months (Table 1). The exposure of interest was vari- IUI pregnancy rates per couple ranged from 10% to 27% (33–
cocele treatment, and the outcome was rate of conception 35).
after IUI. Of the 52 men with a surgically corrected varicocele, Overall, the literature examining the effectiveness of IUI
145 cycles of IUI resulted in four pregnancies (2.8%). In 14 after varicocelectomy is suboptimal, with all existing studies
men with untreated varicoceles, 30 cycles of IUI resulted in being retrospective and underpowered. No meta-analysis has
two pregnancies (6.7%). Finally, five men were medically specifically examined the efficacy of IUI after varicocelec-
managed with antioxidant therapy, but no pregnancies tomy, owing to the dearth of studies and the poor quality of
resulted after four IUI cycles per couple. Of the six pregnancies existing studies, as noted by Kirby et al. in a 2016 meta-
that occurred, five resulted in live birth and one in a miscar- analysis examining the effect of ART on pregnancy and live
riage; the authors did not indicate live birth rate by varicocele birth rates after varicocele repair (36). Within the existing
treatment group. That early study found a higher rate of literature, after varicocele correction, the per-couple preg-
IUI success in men with untreated varicocele than in men nancy rate after IUI ranges from 7.7% to 50%, making it a
undergoing varicocelectomy (30). The overall low rates of challenge to establish the true rate, and most of the studies

TABLE 1

Pregnancy outcomes following intrauterine insemination for men with treated and untreated varicoceles.
Statistically
Treated varicocele Untreated varicocele significant?
Study Pregnancies Couples Pregnancy rate Pregnancies Couples Pregnancy rate P<.05
Marmar et al. 1992 (30) 4 52 7.7% 2 14 14.3% No
Daitch et al. 2001 (31) 12 34 35.3% 4 24 16.7% No
Boman et al. 2008 (32) 5 10 50.0% 1 10 10.0% No
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VIEWS AND REVIEWS

that compare IUI success in men with treated versus untreated pregnancy rate of 45.0% and a live birth rate of 31.4%. The
varicocele fail to find a statistically significant difference. In authors found that when using IVF/ICSI, the odds ratio (OR)
addition, many studies do not report semen parameters, fe- for live birth after varicocele repair was 1.87 (95% confidence
male age, duration of follow-up, number of cycles attempted interval [CI] 1.08–3.25). Importantly, the female age in each
in total or per couple, or ovulation induction protocol, all of group was similar: 32.6 years for the men with treated varico-
which can significantly affect IUI success. Finally, most celes versus 32.2 years for the men with untreated varicocele.
studies do not report how soon after varicocelectomy preg- This association between varicocelectomy and IVF/ICSI
nancy occurred, which is relevant given that conception success was challenged when another large retrospective
3 months after surgery is different than conception occurring study demonstrated no difference in IVF/ICSI success be-
40 months after surgery. Given these limitations, the current tween men who did or did not undergo repair of a grade III
literature is inadequate to draw any firm conclusion regarding varicocele. Pasqualotto et al. analyzed IVF/ISCI results from
the impact of varicocele repair on IUI success. Future large- 248 men with oligospermia: 169 who had undergone varico-
scale studies are necessary to determine if the correction of celectomy and 79 with untreated varicoceles (38). Both groups
a varicocele affects IUI pregnancy success rates. were similar in average female and male ages, testicular size
and volume, and semen parameters. Pregnancy via IVF/ICSI
was achieved by 30.9% of couples with corrected varicoceles
IVF/ICSI AFTER VARICOCELECTOMY IN MEN and 31.1% of couples without corrected varicoceles (P¼ .97).
WITH OLIGOSPERMIA The miscarriage rate was similar between the two groups:
In men with severe oligospermia, IVF may be required to 23.9% vs. 21.7%, respectively. Although pregnancy rates
achieve a pregnancy. Four studies have examined the effect were not significantly different between the two groups, the
of varicocelectomy combined with either IVF or ICSI in oligo- time to pregnancy for couples who had undergone varicoce-
spermic men (Table 2). In 1989, Ashkenazi et al. first demon- lectomy was 6.0  0.5 years, whereas the time to pregnancy
strated that correcting a varicocele resulted in improved for couples with uncorrected varicoceles was 2.7  0.4 years
pregnancy rates when combined with IVF (40). In a cohort (P< .001). This discrepancy in time to pregnancy between
of 22 men with clinical varicoceles, oligospermia, and infer- groups biases the null findings of that study, because couples
tility followed for more than 2 years, no couples achieved a with a longer duration of infertility (apparently the varicoce-
pregnancy with IVF before varicocelectomy, whereas 20% lectomy group) may have had other factors contributing to
of couples achieved a pregnancy using IVF after varicocelec- greater difficulty in achieving a pregnancy. Had these factors
tomy. The study also found that in six of the seven men whose been accounted for, pregnancy rates with IVF/ICSI may have
partners got pregnant after varicocele repair, significant in- been favorably altered among men who had undergone vari-
creases in testosterone levels were observed. The authors cocele repair. Unfortunately, a regression analysis to deter-
theorized that this increase in testosterone levels may predict mine whether time to pregnancy or other factors may have
varicocelectomy success. That initial study, though small, confounded pregnancy outcomes between men and couples
demonstrated a unique synergy between varicocele repair who had undergone varicocelectomy and those that had not
and IVF (40). was not performed (38).
It was 20 years before another study explored the rela- In the most recent and the largest study to date, Gokce
tionship between IVF success and varicocelectomy. Esteves et al. confirm the conclusions of Ashkenazi et al. and Esteves
et al. compared IVF/ICSI outcomes in 80 oligospermic men et al., demonstrating that varicocelectomy prior to IVF/ICSI
with clinical varicoceles who underwent elective microsur- improves pregnancy rates in oligospermic men (39). In a
gical varicocelectomy and in 162 men with clinical varico- retrospective study of 306 infertile couples undergoing IVF/
celes who did not (37). Each group had a similar mean ICSI, 168 men underwent varicocelectomy before IVF/ICSI
duration of infertility, a similar number of grade I, II, and III and 138 men had untreated varicocele. The two groups were
varicoceles, and an equal proportion of men with bilateral similar in male and female ages, proportion of women with
varicoceles. Men with surgically corrected varicocele concurrent infertility diagnosis, and proportions of varicocele
achieved clinical pregnancy with the use of IVF with or grades. Couples with men who had undergone varicocelec-
without ICSI in 60.0% of cases, with a live birth rate of tomy had a higher pregnancy rate compared with those
46.2%, and men with untreated varicocele achieved a clinical with uncorrected varicocele (62.5% vs. 47.1%; P¼ .01). Live

TABLE 2

Pregnancy outcomes following IVF/ICSI for oligospermic men with treated and untreated varicoceles.
Statistically
Treated varicocele Untreated varicocele significant?
Study Pregnancies Couples Pregnancy rate Pregnancies Couples Pregnancy rate P<.05
Esteves et al. 2010 (37) 48 80 60.0% 73 162 45.0% Yes
Pasqualotto et al. 2012 (38) 52 169 30.9% 25 79 31.1% No
Gokce et al. 2013 (39) 105 168 62.5% 65 139 47.1% Yes
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TABLE 3

Pregnancy outcomes following IVF/ICSI for nonobstructed azoospermic men with treated and untreated varicoceles.
Statistically
Treated varicocele Untreated varicocele significant?
Study Pregnancies Couples Pregnancy rate Pregnancies Couples Pregnancy rate P<.05
Inci et al. 2009 (42) 21 66 31.4% 7 30 22.2% No
Haydardedeoglu et al. 2012 (43) 23 31 74.2% 34 65 52.3% Yes
Kohn. Impact of varicocelectomy on IUI or IVF/ICSI. Fertil Steril 2017.

birth rates were also higher in couples with men who had un- examined the efficacy of varicocelectomy before TESE and
dergone varicocele repair (47.6% vs. 29.0%; P< .001) (39). IVF/ICSI. In 2009, Inci et al. retrospectively examined 96
Though retrospective, these large studies convincingly sug- men who had undergone TESE and IVF/ICSI (42). Of those
gest that varicocelectomy improved IVF/ICSI pregnancy men, 66 had previously undergone varicocelectomy and 30
rates. had uncorrected varicocele. The mean time between
The time between varicocelectomy and IVF/ICSI cycles varicocelectomy and micro-TESE was 23.6 months. The two
varied in the above studies. Sperm counts have the greatest groups were similar regarding FSH levels, testicular volume,
improvement from 3 to 6 months after varicocelectomy duration of infertility, female age, and proportion of couples
with no to little improvement after 6 months (41). The mean with female-factor infertility. In men who had undergone
time between surgical correction of the varicocele and IVF/ varicocele repair, 53% had successful testicular sperm
ICSI cycles was 7.2 months in the Gokce et al. study and retrieval, whereas only 30% of the control subjects had suc-
6.2 months in the Esteves et al. study (37, 39). cessful sperm retrieval (P¼ .04). However, pregnancy rates
Unfortunately, neither the Pasqualotto et al. nor the were higher, albeit not significantly, in men with treated
Ashkenazi et al. study reported the time between versus untreated varicocele (31.4% vs. 22.2%; P>.05). These
varicocelectomy and IVF/ICSI (38, 40). It is important to findings suggest that varicocele repair may be beneficial in
note that those studies were performed in couples in which men with NOA before TESE with IVF/ICSI (42).
the female partner was younger, and the improvement in In 2010, Haydardedeoglu et al. published a similar retro-
IVF/ICSI success after varicocelectomy had not been spective study affirming many of Inci et al.’s findings (43). In
demonstrated in couples with advanced maternal age. that study of 96 men with NOA and grade III varicoceles, 31
The 2016 meta-analysis by Kirby et al. examining the ef- men had surgical correction and 65 men were untreated.
fect of ART on pregnancy rates and live birth rates after vari- The two groups were similar regarding male age, FSH levels,
cocele repair analyzed the Gokce et al., Esteves et al., and testicular volume. Sperm retrieval rates were higher in
Pasqualotto et al., and Ashkenazi et al. studies to determine men with treated versus untreated varicoceles (60.8% vs.
whether varicocelectomy enhances these variables when 38.5%; P¼ .01), as were pregnancy and live birth rates
used with IVF/ICSI (36). Meta-analysis demonstrated that (74.2% and 64.5% for treated vs. 52.3% and 41.5% for un-
varicocele repair did not significantly improve pregnancy treated varicocele, respectively). Furthermore, there was a
rates (OR 1.70, 95% CI 0.95–3.02) but did improve live birth greater duration of time between varicocelectomy and TESE
rates (OR 1.70, 95% CI 1.02–2.72). for couples who failed to conceive. Mean time to pregnancy
Although the above studies were retrospective, they were was 42.2 months between varicocele repair and TESE in cou-
adequately powered to detect differences between treatment ples who achieved a pregnancy, whereas couples who did not
groups. Nevertheless, prospective studies are needed to iden- conceive had a mean time of 80.0 months between varicocele
tify the subgroups of men that may most benefit from varico- repair and TESE (43). Of note, men were excluded from this
celectomy, because existing studies have not examined study if they canceled embryo transfer because of fertilization
whether other factors, such as female age, male age, duration failure, which may explain the slightly higher pregnancy rates
of infertility, grade of varicocele, and semen parameters, compared with other studies.
contribute to outcomes. The Kirby meta-analysis further affirms the promising re-
sults of varicocelectomy for men with NOA. Compared with
NOA men with an uncorrected varicocele, those with a surgi-
IVF/ICSI AFTER VARICOCELECTOMY IN MEN cally corrected varicocele had higher rates of sperm retrieval
WITH NONOBSTRUCTIVE AZOOSPERMIA (OR 2.51), pregnancy (OR 2.34, 95% CI 1.02–5.34), and live
Early studies demonstrated that varicocele repair could birth (OR 2.21, 95% CI 0.99–4.90) (36). Although these clinical
improve semen parameters in men with nonobstructive azoo- outcomes are important, couples should be counseled
spermia (NOA; Table 3) (44, 45). Combining varicocelectomy regarding the expected length of time between varicocelec-
with testicular sperm extraction (TESE) or microdissection tomy and TESE/ICSI; the Inci et al. and Haydardedeoglu
TESE (micro-TESE) followed by IVF/ICSI, urologists are now et al. studies observed a mean duration to successful concep-
able to offer fertility treatment to couples in which the male tion ranging from 2 to 3.5 years between procedures, and
partner has NOA (46, 47). Two controlled studies have those who failed to conceive had a mean duration of 6 years

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VIEWS AND REVIEWS

between procedures (42, 43). Thus, older couples with NOA 7. Pathak P, Chandrashekar A, Hakky TS, Pastuszak AW. Varicocele manage-
and varicocele should be cautioned against delaying any ment in the era of in vitro fertilization/intracytoplasmic sperm injection.
Asian J Androl 2016;18:343–8.
attempts to conceive with IVF/ICSI after varicocelectomy.
8. Sheehan MM, Ramasamy R, Lamb DJ. Molecular mechanisms involved in
Finally, prospective studies remain necessary to determine varicocele-associated infertility. J Assist Reprod Genet 2014;31:521–6.
which couples are most likely to benefit from 9. Eisenberg ML, Lipshultz LI. Varicocele-induced infertility: Newer insights into
varicocelectomy before IVF/ICSI. its pathophysiology. Indian J Urol 2011;27:58–64.
10. Masson P, Brannigan RE. The varicocele. Urol Clin North Am 2014;41:
129–44.
COST-EFFECTIVENESS OF VARICOCELECTOMY 11. Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface tem-
BEFORE ART perature in men with varicocele. J Urol 1989;142:743–5.
12. Ozbek E, Yurekli M, Soylu A, Davarci M, Balbay MD. The role of adrenome-
Although varicocelectomy can improve IVF/ICSI outcomes,
dullin in varicocele and impotence. BJU Int 2000;86:694–8.
cost-effectiveness remains a consideration in today's health
13. Hendin BN, Kolettis PN, Sharma RK, Thomas AJ Jr, Agarwal A. Varicocele is
care environment. Penson et al. compared the cost- associated with elevated spermatozoal reactive oxygen species production
effectiveness of four strategies for varicocele-related infer- and diminished seminal plasma antioxidant capacity. J Urol 1999;161:
tility: observation, gonadotropin-stimulated IUI followed by 1831–4.
IVF if IUI conception fails, varicocelectomy followed by IVF 14. Gilbert BR, Witkin SS, Goldstein M. Correlation of sperm-bound immuno-
if natural conception fails, and immediately proceeding to globulins with impaired semen analysis in infertile men with varicoceles. Fer-
til Steril 1989;52:469–73.
IVF. The probabilities of live delivery and costs were based
15. Mieusset R, Bujan L. Testicular heating and its possible contributions to male
on a literature search covering the years 1995–2000. Ranked infertility: a review. Int J Androl 1995;18:169–84.
from most to least expensive, Penson et al. calculated that im- 16. Simsek F, Turkeri L, Cevik I, Bircan K, Akdas A. Role of apoptosis in testicular
mediate IVF costs $33,686 per live birth, gonadotropin- tissue damage caused by varicocele. Arch Esp Urol 1998;51:947–50.
stimulated IUI followed by IVF costs $22,122 per live birth, 17. Abdel-Meguid TA, Farsi HM, Al-Sayyad A, Tayib A, Mosli HA,
and varicocelectomy followed by IVF costs $22,114 per live Halawani AH. Effects of varicocele on serum testosterone and changes
birth (48). Although observation alone did not incur costs to of testosterone after varicocelectomy: a prospective controlled study.
Urology 2014;84:1081–7.
the patient, it was the least effective method and contributed
18. Mostafa T, Rashed LA, Nabil NI, Osman I, Mostafa R, Farag M. Seminal
additional delays in time to conception. Although that cost- miRNA relationship with apoptotic markers and oxidative stress in infertile
effectiveness analysis is helpful when choosing between men with varicocele. Biomed Res Int 2016;2016:4302754.
method of ART and varicocelectomy, no studies have deter- 19. Freire Gde C. Surgery or embolization for varicoceles in subfertile men. Sao
mined the cost-effectiveness of varicocelectomy before ART. Paulo Med J 2013;131:67.
20. Breznik R, Vlaisavljevic V, Borko E. Treatment of varicocele and male fertility.
Arch Androl 1993;30:157–60.
CONCLUSION 21. Kroese AC, de Lange NM, Collins J, Evers JL. Surgery or embolization for var-
Clinical varicocele can impair semen parameters and increase icoceles in subfertile men. Cochrane Database Syst Rev 2012:CD000479.
22. Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelec-
sperm DNA damage. Varicocele repair can improve semen pa-
tomy. A critical analysis. Urol Clin North Am 1994;21:517–29.
rameters, pregnancy rates, and live birth rates for most infer-
23. Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, Salonia A, et al. Varicocele
tile men with clinical varicocele. Although most available and male factor infertility treatment: a new meta-analysis and review of the
studies demonstrate a clinical benefit when correcting a clin- role of varicocele repair. Eur Urol 2011;60:796–808.
ical varicocele in oligospermic and NOA men before IVF/ICSI, 24. Zini A, Azhar R, Baazeem A, Gabriel MS. Effect of microsurgical varicocelec-
sufficient evidence has not demonstrated clinical advantages tomy on human sperm chromatin and DNA integrity: a prospective trial. Int J
to correcting a varicocele before IUI. In couples seeking Androl 2011;34:14–9.
25. Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, Weber RF, Dohle GR.
fertility using ART, varicocele repair may offer improvement
Decreased sperm DNA fragmentation after surgical varicocelectomy is asso-
in semen parameters and may decrease the level of ART ciated with increased pregnancy rate. J Urol 2013;189:S146–50.
needed to achieve successful pregnancy. Future investigation 26. Li F, Yamaguchi K, Okada K, Matsushita K, Ando M, Chiba K, et al. Signifi-
is needed to evaluate the cost-effectiveness of varicocele cant improvement of sperm DNA quality after microsurgical repair of varico-
treatments globally and to identify which couples would cele. Syst Biol Reprod Med 2012;58:274–7.
most benefit from varicocelectomy before ART. 27. Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between
varicocele and sperm DNA damage and the effect of varicocele repair: a
meta-analysis. Reprod Biomed Online 2012;25:307–14.
REFERENCES 28. Chen SS, Huang WJ, Chang LS, Wei YH. Attenuation of oxidative stress
1. World Health Organization. WHO laboratory manual for the examination and after varicocelectomy in subfertile patients with varicocele. J Urol 2008;
processing of human semen. Geneva: World Health Organisation Press; 2010. 179:639–42.
2. Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, et al. 29. Calhaz-Jorge C, de Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E,
Best practice policies for male infertility. Fertil Steril 2002;77:873–82. et al. Assisted reproductive technology in Europe, 2012: results generated
3. Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod 1998; from European registers by ESHRE. Hum Reprod 2016;31:1638–52.
13(Suppl 1):33–44. 30. Marmar JL, Corson SL, Batzer FR, Gocial B. Insemination data on men with
4. Redmon JB, Carey P, Pryor JL. Varicocele—the most common cause of male varicoceles. Fertil Steril 1992;57:1084–90.
factor infertility? Hum Reprod Update 2002;8:53–8. 31. Daitch JA, Bedaiwy MA, Pasqualotto EB, Hendin BN, Hallak J, Falcone T,
5. Pryor JL, Howards SS. Varicocele. Urol Clin North Am 1987;14:499–513. et al. Varicocelectomy improves intrauterine insemination success rates in
6. The influence of varicocele on parameters of fertility in a large group of men pre- men with varicocele. J Urol 2001;165:1510–3.
senting to infertility clinics. World Health Organization. Fertil Steril 1992;57: 32. Boman JM, Libman J, Zini A. Microsurgical varicocelectomy for isolated as-
1289–93. thenospermia. J Urol 2008;180:2129–32.

390 VOL. 108 NO. 3 / SEPTEMBER 2017

 Fertility and Sterility®

33. Kamal KM, Jarvi K, Zini A. Microsurgical varicocelectomy in the era of assis- 41. Al Bakri A, Lo K, Grober E, Cassidy D, Cardoso JP, Jarvi K. Time for improve-
ted reproductive technology: influence of initial semen quality on pregnancy ment in semen parameters after varicocelectomy. J Urol 2012;187:227–31.
rates. Fertil Steril 2001;75:1013–6. 42. Inci K, Hascicek M, Kara O, Dikmen AV, Gurgan T, Ergen A. Sperm
34. Hudson RW. Free sex steroid and sex hormone–binding globulin levels in oli- retrieval and intracytoplasmic sperm injection in men with nonobstruc-
gozoospermic men with varicoceles. Fertil Steril 1996;66:299–304. tive azoospermia, and treated and untreated varicocele. J Urol 2009;
35. Grober ED, Chan PT, Zini A, Goldstein M. Microsurgical treatment of persis- 182:1500–5.
tent or recurrent varicocele. Fertil Steril 2004;82:718–22. 43. Haydardedeoglu B, Turunc T, Kilicdag EB, Gul U, Bagis T. The effect of prior
36. Kirby EW, Wiener LE, Rajanahally S, Crowell K, Coward RM. Undergoing varicocelectomy in patients with nonobstructive azoospermia on intracyto-
varicocele repair before assisted reproduction improves pregnancy rate plasmic sperm injection outcomes: a retrospective pilot study. Urology
and live birth rate in azoospermic and oligospermic men with a varicocele: 2010;75:83–6.
a systematic review and meta-analysis. Fertil Steril 2016;106:1338–43. 44. Kim ED, Leibman BB, Grinblat DM, Lipshultz LI. Varicocele repair improves
37. Esteves SC, Oliveira FV, Bertolla RP. Clinical outcome of intracytoplasmic semen parameters in azoospermic men with spermatogenic failure. J Urol
sperm injection in infertile men with treated and untreated clinical varico- 1999;162:737–40.
cele. J Urol 2010;184:1442–6. 45. Matthews GJ, Matthews ED, Goldstein M. Induction of spermatogenesis
38. Pasqualotto FF, Braga DP, Figueira RC, Setti AS, Iaconelli A Jr, Borges E Jr. and achievement of pregnancy after microsurgical varicocelectomy in men
Varicocelectomy does not impact pregnancy outcomes following intracyto- with azoospermia and severe oligoasthenospermia. Fertil Steril 1998;70:
plasmic sperm injection procedures. J Androl 2012;33:239–43. 71–5.
39. Gokce A, Demirtas A, Ozturk A, Sahin N, Ekmekcioglu O. Association of left 46. Schoysman R, Vanderzwalmen P, Nijs M, Segal L, Segal-Bertin G, Geerts L,
varicocoele with height, body mass index and sperm counts in infertile men. et al. Pregnancy after fertilisation with human testicular spermatozoa. Lan-
Andrology 2013;1:116–9. cet 1993;342:1237.
40. Ashkenazi J, Dicker D, Feldberg D, Shelef M, Goldman GA, Goldman J. The 47. Schlegel PN. Testicular sperm extraction: microdissection improves sperm
impact of spermatic vein ligation on the male factor in in vitro fertilization- yield with minimal tissue excision. Hum Reprod 1999;14:131–5.
embryo transfer and its relation to testosterone levels before and after oper- 48. Penson DF, Paltiel AD, Krumholz HM, Palter S. The cost-effectiveness of
ation. Fertil Steril 1989;51:471–4. treatment for varicocele related infertility. J Urol 2002;168:2490–4.

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