Microsurgical varicocele ligation: surgical methodology and associated outcomes

The impact of clinical varicoceles on semen parameters and male infertility has long been established. In the era of assisted reproduction, clinical discussion has questioned the role of varicocelectomy, offering the potential to bypass, rather than treat, varicocele-associated male infertility. However, current literature supports improved semen parameters and reproductive outcomes following repair. This article presents the stepwise operative approaches to microsurgical varicocelectomy and discusses the recent publications on outcomes. The impact of clinical varicoceles on semen parameters and male infertility has long been established. In the era of assisted reproduction, clinical discussion has questioned the role of varicocelectomy, offering the potential to bypass, rather than treat, varicocele-associated male infertility. However, current literature supports improved semen parameters and reproductive outcomes following repair. This article presents the stepwise operative approaches to microsurgical varicocelectomy and discusses the recent publications on outcomes. Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/42040-27415 Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/42040-27415 It is widely accepted that varicoceles have a potential impact on male fertility. It is the most common correctable cause of infertility in men with primary and secondary infertility, with incidences of 35% and 80%, respectively (1Gorelick J.I. Goldstein M. Loss of fertility in men with varicocele.Fertil Steril. 1993; 59: 613-616Abstract Full Text PDF PubMed Google Scholar). There is less clarity on why only certain men with varicoceles are affected, what the true pathogenesis is, how we decide which men to treat, and how to treat them. Although the American Society for Reproductive Medicine (ASRM) Practice Committee (2Pfeifer S. Butts S. Catherino W. Davis O. Dumesic D. Fossum G. et al.Report on varicocele and infertility: a committee opinion.Fertil Steril. 2014; 102: 1556-1560Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar) has attempted to outline indications for repair, clinical practice is not as clear-cut given that all of the criteria for consideration are seldom met. Subclinical varicoceles identified on ultrasonography but not palpable on physical examination have not been found to affect fertility, and therefore repair is not currently the standard of care (3Kohn T.P. Ohlander S.J. Jacob J.S. Griffin T.M. Lipshultz L.I. Pastuszak A.W. The effect of subclinical varicocele on pregnancy rates and semen parameters: a systematic review and meta-analysis.Curr Urol Rep. 2018; 19: 53Google Scholar). Recent reports have questioned this practice, particularly in the setting of unilateral clinical varicocele with a contralateral subclinical varicocele, and whether we should perform unilateral or bilateral varicocelectomy (4Sun X.L. Wang J.L. Peng Y.P. Gao Q.Q. Song T. Yu W. et al.Bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele: a prospective randomized controlled study.Int Urol Nephrol. 2018; 50: 205-210Crossref PubMed Scopus (25) Google Scholar, 5Thirumavalavan N. Scovell J.M. Balasubramanian A. Kohn T.P. Ji B. Hasan A. et al.The impact of microsurgical repair of subclinical and clinical varicoceles on total motile sperm count: is there a difference?.Urology. 2018; 120: 109-113Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar). Prospective randomized studies are likely needed before making conclusions that warrant changes in clinical practice, although such studies are extremely difficult to achieve in fertility care. In addition, a dispute exists among reproductive physicians regarding the role of varicocelectomy in the current era of assisted reproduction, debating the applicability of bypassing rather than treating the male factor. Historical literature supports repair for the improvement of semen parameters, but more recent publications have advocated repair for testicular pain, hypogonadism, and azoospermia to avoid microsurgical testicular sperm extraction or to improve sperm retrieval rates (6Su L.M. Goldstein M. Schlegel P.N. The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles.J Urol. 1995; 154: 1752-1755Crossref PubMed Scopus (149) Google Scholar, 7Cayan S. Kadioglu A. Orhan I. Kandirali E. Tefekli A. Tellaloglu S. The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele.BJU Int. 1999; 84: 1046-1049Crossref PubMed Google Scholar, 8Tanrikut C. Goldstein M. Rosoff J.S. Lee R.K. Nelson C.J. Mulhall J.P. Varicocele as a risk factor for androgen deficiency and effect of repair.BJU Int. 2011; 108: 1480-1484Crossref PubMed Scopus (115) Google Scholar, 9Yaman Ö. Özdiler E. Anafarta K. Gögüş O. Effect of microsurgical subinguinal varicocele ligation to treat pain.Urology. 2000; 55: 107-108Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 10Matthews G.J. Matthews E.D. Goldstein M. Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia.Fertil Steril. 1998; 70: 71-75Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar). Recently, a meta-analysis supported repair to improve outcomes of intrauterine insemination (IUI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (11Kirby E.W. Wiener L.E. Rajanahally S. Crowell K. Coward R.M. Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis.Fertil Steril. 2016; 106: 1338-1343Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar). The present review does not focus on the pathophysiology or the decision to repair, but rather on the operative techniques and their associated outcomes. The search strategy in this review was constructed in accordance with Cochrane guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). In November 2018, a search for randomized controlled trials, systematic reviews, and meta-analyses with the terms "varicocele," varicocelectomy," and "varicocele repair" was conducted in Medline (www.pubmed.gov) and the Cochrane electronic databases and yielded 269 different articles. Publications were reviewed by the authors and, after carefully screening all titles and abstracts, articles were excluded that were not published in English, were focused on a different topic, were about varicocele in the adolescent, or did not use microsurgery as the method of choice. Articles were selected for final inclusion in this review on the basis of relevance to the subtopics detailed below, and additional articles were selected after review of the references from the initial articles identified. The basis of varicocele repair is the disruption of venous pooling and retrograde flow while preserving arterial inflow and lymphatic drainage. The American Urological Association Best Practice Policy Committee advocates that optical magnification should be used during varicocele repair because it allows identification of all spermatic cord structures either with inguinal or subinguinal approaches (12Sharlip I.D. Jarow J.P. Belker A.M. Lipshultz L.I. Sigman M. Thomas A.J. et al.Best practice policies for male infertility.Fertil Steril. 2002; 77: 873-882Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). The use of microscopy reduced postoperative complications, including hydrocele and varicocele recurrence, compared with both loupe-assisted and unassisted techniques and is accepted as the criterion standard of therapy (13Çayan S. Acar D. Ülger S. Akbay E. Adolescent varicocele repair: long-term results and comparison of surgical techniques according to optical magnification use in 100 cases at a single university hospital.J Urol. 2005; 174: 2003-2006Crossref PubMed Scopus (71) Google Scholar). It appears to be important that all internal and external spermatic veins be ligated to avoid varicocele recurrence. It was demonstrated by phlebography that recurrences were due to dilated external spermatic veins in the presence of total internal spermatic vein occlusion (14Sayfan J. Adam Y.G. Soffer Y. A new entity in varicocele subfertility: The "cremasteric reflux".Fertil Steril. 1980; 33: 88-90Abstract Full Text PDF PubMed Scopus (37) Google Scholar). A microsurgical approach is associated with recurrence rates of <1% and virtual elimination of postoperative hydrocele formation (15Goldstein M. Gilbert B.R. Dicker A.P. Dwosh J. Gnecco C. Microsurgical inguinal varicocelectomy with delivery of the testis: An artery and lymphatic sparing technique.J Urol. 1992; 148: 1808-1811Crossref PubMed Scopus (377) Google Scholar). The microsurgical technique offers two incision sites. The inguinal approach begins by identifying the level of the external ring after invaginating the scrotal skin up to the inguinal canal. The ring is marked and a 2.5–3.5-cm skin incision is made extending laterally from this point along the Langer lines. The subcutaneous tissue is hemostatically dissected until the Camper and Scarpa fasciae are exposed and incised with electrocautery. The wound is deepened with blunt dissection with the use of Army/Navy or Richardson retractors until the level of the external oblique aponeurosis. The aponeurosis is opened sharply by means of a proximal stab incision and then sliding Metzenbaum scissors in the direction of its fibers through the external inguinal ring. Care is taken to identify the ilioinguinal nerve and the genital branch of the genitofemoral nerve and to isolate them from the spermatic cord. A vessel loop may be used to assist in retraction of the nerves away from the spermatic cord structures to allow free blunt dissection of the cremasteric attachments and mobilization of the cord. The spermatic cord is encircled with a Babcock clamp, or with one's index finger and thumb, and elevated out of the incision. We do not routinely deliver the testicle. A Penrose drain is then passed around the mobilized spermatic cord for ease in manipulation, and the floor of the canal is inspected to assure complete isolation of the spermatic cord and its vasculature. The operative microscope is brought over the operative field, and under ×20 magnification the spermatic cord is inspected for the presence of external spermatic veins. The external and internal spermatic fasciae are opened by blunt puncture with the use of Gerald forceps and needle-tip Bovie electrocautery, and then spread to flatten and expose the internal spermatic cord contents (16Beck E.M. Schlegel P.N. Goldstein M. Intraoperative varicocele anatomy: a macroscopic and microscopic study.J Urol. 1992; 148: 1190-1194Crossref PubMed Scopus (87) Google Scholar). The exposed cord is then set on a tongue depressor sheathed with a Penrose drain or draped over the surgeon's nondominant index finger, the later requiring a skilled microsurgical assistant, given a greater need for the assistance in micromanipulation. A 3-mm micro-Doppler is used for differentiation of vascular structures throughout the procedure exposing the internal spermatic vessels. As previously advocated by Tatum and Brannigan, we request that the patient's blood pressure be maintained at or above their baseline, typically preferring systolic blood pressure >100 mm Hg, to assure audible arterial signal (17Tatem A.J. Brannigan R.E. The role of microsurgical varicocelectomy in treating male infertility.Transl Androl Urol. 2017; 6: 722-729Google Scholar). Additional measures for vascular identification consist of irrigation with 1% lidocaine without epinephrine or a 1:5 dilution of papaverine (30 mg/mL) to combat vasospasm (17Tatem A.J. Brannigan R.E. The role of microsurgical varicocelectomy in treating male infertility.Transl Androl Urol. 2017; 6: 722-729Google Scholar). The systematic use of intraoperative vascular micro-Doppler allows more arterial branches to be identified and preserved and more internal spermatic veins to be ligated (18Cocuzza M. Pagani R. Coelho R. Srougi M. Hallak J. The systematic use of intraoperative vascular Doppler ultrasound during microsurgical subinguinal varicocelectomy improves precise identification and preservation of testicular blood supply.Fertil Steril. 2010; 93: 2396-2399Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar). If the testicular artery is immediately identified, then it is dissected free and isolated with a vessel loop. If the artery is not clearly identified, the spermatic cord is carefully dissected starting with the largest vein. The veins are individually mobilized and stripped of adventitia to avoid injury to possible underlying lymphatics or artery (16Beck E.M. Schlegel P.N. Goldstein M. Intraoperative varicocele anatomy: a macroscopic and microscopic study.J Urol. 1992; 148: 1190-1194Crossref PubMed Scopus (87) Google Scholar). A Jacobson clamp provides fine dissection and easy passage behind the isolated vessel for placement of ligation microclips or 4-0 silk ties. Grasping the silk tie at the midpoint, before cutting the tie, allows for a single passage posterior to the isolated vein. Once passed, the midpoint is cut, allowing two points of ligation. Limiting posterior passage limits inadvertent trauma to the isolated vessel. One should confirm an absence of an arterial pulse from the isolated vessel as well as assure that the vessel is not occluded by tension before formally ligating the vessel. All veins within the spermatic cord except the vasal vessels are double-ligated and divided. All identified lymphatics are preserved. Hemostasis is maintained throughout with the use of fine-tipped bipolar electrocautery for cord bleeding and needle-tip Bovie electrocautery for any hemostasis external to the cord. Before returning the cord to its inguinal lie, patency of the internal spermatic artery is confirmed and the vas deferens is inspected for signs of trauma. Once confirmed, the spermatic cord is dropped back into its natural position. A cord block may be administered for postoperative pain control. The external oblique aponeurosis is closed with a running 3-0 absorbable suture. Scarpa and Camper fasciae are approximated with a continuous 4-0 absorbable monofilament suture. The skin is closed with the use of a running subcuticular suture (16Beck E.M. Schlegel P.N. Goldstein M. Intraoperative varicocele anatomy: a macroscopic and microscopic study.J Urol. 1992; 148: 1190-1194Crossref PubMed Scopus (87) Google Scholar). Inguinal microsurgical varicocelectomy has the advantages of fewer internal spermatic veins, given the proximal coalescing of vessels, and fewer distal arterial tributaries, which enables the surgeon to encounter fewer vascular branches, shortening the operating time and facilitating the simplification of the operation. However, the main disadvantage of the inguinal approach is the need to open the aponeurosis of the external oblique muscle, which may result in more pain and a longer time before the patient can return to activity (19Hopps C.V. Lemer M.L. Schlegel P.N. Goldstein M. Intraoperative varicocele anatomy: a microscopic study of the inguinal versus subinguinal approach.J Urol. 2003; 170: 2366-2370Crossref PubMed Scopus (125) Google Scholar). When utilizing the subinguinal approach, the location of the external inguinal ring is identified in the same way as the inguinal approach by invaginating the scrotal skin with an index finger in a cephalad direction over the pubic tubercle and marking on the skin. A 2–3-cm skin incision is made ∼1 cm below the external inguinal ring. Camper and Scarpa fasciae are incised with the use of electrocautery. The wound is deepened with blunt dissection with the use of Army/Navy or Richardson retractors until the level of the spermatic cord is reached. The spermatic cord is identified, encircled with a Babcock clamp, or one's index finger and thumb, and elevated out of the incision, and then surrounded with a Penrose drain. Identification of vascular structures proceeds in the same way as the inguinal approach. Again, operative microscope and micro-Doppler are paramount for complete venous ligation. At the completion of the procedure, the spermatic cord is returned to the subinguinal level. The Scarpa fascia is closed with the use of an interrupted 4-0 absorbable monofilament, and the skin is closed with the use of a running subcuticular suture (19Hopps C.V. Lemer M.L. Schlegel P.N. Goldstein M. Intraoperative varicocele anatomy: a microscopic study of the inguinal versus subinguinal approach.J Urol. 2003; 170: 2366-2370Crossref PubMed Scopus (125) Google Scholar, 20Marmar J.L. DeBenedictis T.J. Praiss D. The management of varicoceles by microdissection of the spermatic cord at the external inguinal ring.Fertil Steril. 1985; 43: 583-588Abstract Full Text PDF PubMed Scopus (119) Google Scholar). Open microsurgical inguinal or subinguinal varicocelectomy techniques have demonstrated higher spontaneous pregnancy rates and fewer recurrences and postoperative complications than conventional varicocelectomy techniques. Table 1 presents the findings of a recent meta-analysis by Çayan et al. comparing outcome parameters of management techniques. The authors identified significant differences in spontaneous pregnancy rates, recurrence rates, and hydrocele rates favoring microsurgical repair (21Çayan S. Shavakhabov S. Kadioǧlu A. Treatment of palpable varicocele review in infertile men: a meta-analysis to define the best technique.J Androl. 2009; 30: 33-40Crossref PubMed Scopus (265) Google Scholar). The findings were supported by subsequent meta-analyses comparing open nonmicrosurgical, laparoscopic, and open microsurgical varicocelectomy (22Ding H. Tian J. Du W. Zhang L. Wang H. Wang Z. Open nonmicrosurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials.BJU Int. 2012; 110: 1536-1542Crossref PubMed Scopus (104) Google Scholar, 23Yuan R. Zhuo H. Cao D. Wei Q. Efficacy and safety of varicocelectomies: a meta-analysis.Syst Biol Reprod Med. 2017; 63: 120-129Crossref PubMed Scopus (23) Google Scholar).Table 1Outcomes of varicocele repair techniques.TechniquePregnancy ratesRecurrenceHydroceleHigh retroperitoneal ligation37.69%14.97%8.24%Laparoscopic30.07%4.3%2.84%Open inguinal36%2.63%7.3%Microsurgical (inguinal or subinguinal)41.97%1.05%0.44%Radiologic embolization32.2%12.7%P=.001P=.001P=.001Note: From: Çayan et al. Treatment of palpable varicocele review in infertile men: a meta-analysis to define the best technique. J Androl 2009;30:33–40. Open table in a new tab Note: From: Çayan et al. Treatment of palpable varicocele review in infertile men: a meta-analysis to define the best technique. J Androl 2009;30:33–40. A series of Cochrane Review manuscripts published in the early 2000s failed to show a significant difference in pregnancy rates for patients undergoing varicocelectomy (24Evers J.L.H. Collins J.A. Assessment of efficacy of varicocele repair for male subfertility: a systematic review.Lancet. 2003; 361: 1849-1852Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar, 25Evers J.L.H. Collins J. Clarke J. Surgery or embolisation for varicoceles in subfertile men.Cochrane Database Syst Rev. 2009; : CD000479Google Scholar). The studies included patients submitted to embolization and patients with subclinical varicocele in whom varicocelectomy has not proven to be successful (3Kohn T.P. Ohlander S.J. Jacob J.S. Griffin T.M. Lipshultz L.I. Pastuszak A.W. The effect of subclinical varicocele on pregnancy rates and semen parameters: a systematic review and meta-analysis.Curr Urol Rep. 2018; 19: 53Google Scholar), thus limiting broad generalizability and clinical applicability. Moreover, the same group that published the first studies against varicocele repair has recently published an update concluding that varicocelectomy in men with infertility and clinical varicocele may be of benefit (26Kroese A.C.J. Lange N.M.D. Collins J.A. Evers J.L.H. Varicocele surgery, new evidence.Hum Reprod Update. 2013; 19: 317Crossref PubMed Scopus (17) Google Scholar). Several subsequent studies focused on the impact of varicocelectomy on semen parameters and pregnancy rates in men with clinically relevant varicoceles. Agarwal et al. (27Agarwal A. Deepinder F. Cocuzza M. Agarwal R. Short R.A. Sabanegh E. et al.Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach.Urology. 2007; 70: 532-538Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar) published a meta-analysis showing a significant improvement in sperm concentration and motility after varicocelectomy. Investigators have demonstrated that significant improvements in total motile sperm count (TMSC) is seen by 3 months after surgery (28Fukuda T. Miyake H. Enatsu N. Matsushita K. Fujisawa M. Assessment of time-dependent changes in semen parameters in infertile men after microsurgical varicocelectomy.Urology. 2015; 86: 48-51Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar). Another meta-analysis, by Marmar et al., concluded that surgical varicocelectomy is an effective treatment for improving the natural pregnancy rate for couples with an infertile male partner who has low semen parameters and a palpable varicocele. Compared with nonintervention, patients who underwent varicocelectomy were 2.87 (95% confidence interval [CI] 1.33–6.20) times more likely to achieve a natural pregnancy (29Marmar J.L. Agarwal A. Prabakaran S. Agarwal R. Short R.A. Benoff S. et al.Reassessing the value of varicocelectomy as a treatment for male subfertility with a new meta-analysis.Fertil Steril. 2007; 88: 639-648Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar). In a randomized controlled trial, Abdel-Meguid et al. (30Abdel-Meguid T.A. Al-Sayyad A. Tayib A. Farsi H.M. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial.Eur Urol. 2011; 59: 455-461Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar) reported that treatment of palpable varicoceles in men with at least one abnormal semen parameter resulted in a 15% improvement in sperm count and a 15% improvement in sperm motility compared with the control group. Natural pregnancy was achieved for 32.9% of patients who underwent varicocelectomy whereas only 13.9% of patients in the observation group achieved a natural pregnancy (odds ratio [OR] 3.04, 95% CI 1.33–6.95). It also has been shown that varicocelectomy improves sperm variables (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology (31Baazeem A. Boman J.M. Libman J. Jarvi K. Zini A. Microsurgical varicocelectomy for infertile men with oligospermia: Differential effect of bilateral and unilateral varicocele on pregnancy outcomes.BJU Int. 2009; 104: 524-528Crossref PubMed Scopus (22) Google Scholar, 32Smit M. Romijn J.C. Wildhagen M.F. Veldhoven J.L.M. Weber R.F.A. Dohle G.R. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate.J Urol. 2010; 183: 270-274Crossref PubMed Scopus (117) Google Scholar, 33Zini A. Azhar R. Baazeem A. Gabriel M.S. Effect of microsurgical varicocelectomy on human sperm chromatin and DNA integrity: a prospective trial.Int J Androl. 2011; 34: 14-19Crossref PubMed Scopus (72) Google Scholar, 34Reichart M. Eltes F. Soffer Y. Zigenreich E. Yogev L. Bartoov B. Sperm ultramorphology as a pathophysiological indicator of spermatogenesis in males suffering from varicocele.Andrologia. 2000; 32: 139-145Crossref PubMed Scopus (29) Google Scholar). The role of varicocelectomy in the era of assisted reproductive technology (ART) has been a point of debate. The ASRM Practice Committee concluded that ART may be considered as the primary treatment option when such treatment is required to treat a female factor, regardless of the presence of varicocele and abnormal semen parameters (2Pfeifer S. Butts S. Catherino W. Davis O. Dumesic D. Fossum G. et al.Report on varicocele and infertility: a committee opinion.Fertil Steril. 2014; 102: 1556-1560Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). However, Esteves et al. (35Esteves S.C. Oliveira F.V. Bertolla R.P. Clinical outcome of intracytoplasmic sperm injection in infertile men with treated and untreated clinical varicocele.J Urol. 2010; 184: 1442-1446Crossref PubMed Scopus (80) Google Scholar) published a retrospective study comparing the outcomes in 80 men with abnormal semen parameters submitted to microsurgical varicocelectomy and 162 men with clinical varicoceles who elected to go directly to IVF/ICSI. In the latter group, couples with female-factor infertility were included. Each group had a similar mean duration of infertility, similar distribution in varicocele grades, equal proportion of men with bilateral varicoceles, and similar female age. Men with surgically corrected varicocele achieved clinical pregnancy with the use of IVF/ICSI in 60% of cases, with a live birth rate of 46.2%, and men with untreated varicocele achieved a clinical pregnancy rate of 45% and a live birth rate of 31.4%. The odds for live birth rate after varicocele repair were 1.87 (95% CI 1.08–3.25) times higher, suggesting that varicocelectomy should be indicated even when there is a clear indication for ART. In the largest retrospective study conducted to date evaluating the role of varicocele repair before IVF/ICSI, Gokce et al. (36Gokce M.I. Gülpinar Ö. Süer E. Mermerkaya M. Aydos K. Yaman Ö. Effect of performing varicocelectomy before intracytoplasmic sperm injection on clinical outcomes in nonazoospermic males.Int Urol Nephrol. 2013; 45: 367-372Crossref PubMed Scopus (18) Google Scholar) repaired the varicoceles in 168 patients before assisted reproduction (group A), whereas 138 patients with varicoceles went to IVF/ICSI directly (group B). Varicocele grade distribution, mean male age, mean female age, and female-factor infertility were similar across the groups. Patients in the treated group had significantly higher sperm count, sperm motility, sperm morphology than the untreated group before the IVF/ICSI procedure. They observed that patients of group A had a higher pregnancy rate (62.5% vs. 47.1%; P=.001) and higher live birth rate (47.6% vs. 29%; P=.0002) than patients of group B. In the logistic regression analysis, varicocelectomy was found to increase pregnancy and live birth rate: OR 2.02, 95% CI 1.25–3.87; and OR 2.12, 95% CI 1.26–3.97; respectively. A more recent meta-analysis (37Esteves S. Roque M. Agarwal A. Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis.Asian J Androl. 2016; 18: 254Crossref PubMed Scopus (58) Google Scholar) included four studies comprising 438 IVF cycles with prior varicocelectomy and 432 IVF cycles without prior varicocelectomy (35Esteves S.C. Oliveira F.V. Bertolla R.P. Clinical outcome of intracytoplasmic sperm injection in infertile men with treated and untreated clinical varicocele.J Urol. 2010; 184: 1442-1446Crossref PubMed Scopus (80) Google Scholar, 36Gokce M.I. Gülpinar Ö. Süer E. Mermerkaya M. Aydos K. Yaman Ö. Effect of performing varicocelectomy before intracytoplasmic sperm injection on clinical outcomes in nonazoospermic males.Int Urol Nephrol. 2013; 45: 367-372Crossref PubMed Scopus (18) Google Scholar, 38Pasqualotto F.F. Braga D.P.A.F. Figueira R.C.S. Setti A.S. Iaconelli A. Borges E. Varicocelectomy does not impact pregnancy outcomes following intracytoplasmic sperm injection procedures.J Androl. 2012; 33: 239-243Crossref PubMed Scopus (40) Google Scholar, 39Shiraishi K. Matsuyama H. Takihara H. Pathophysiology of varicocele in male infertility in the era of assisted reproductive technology.Int J Urol. 2012; 19: 538-550Crossref PubMed Scopus (102) Google Scholar). Overall, there was a significant increase in the clinical pregnancy rate (OR 1.59, 95% CI 1.19–2.12) and live birth rate (OR 2.17, 95% CI 1.55–3.06) with prior varicocelectomy compared with no varicococelectomy. Samplaski et al. (40Samplaski M.K. Lo K.C. Grober E.D. Zini A. Jarvi K.A. Varicocelectomy to "upgrade" semen quality to allow couples to use less invasive forms of assisted reproductive technology.Fertil Steril. 2017; 108: 609-612Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar) further supported the importance of varicocele management in couples pursuing ART by investigating the degree of improvement in semen parameters. They retrospectively reviewed data on 373 men that underwent varicocele repair and found that the TMSC increased from 18.22 ± 38.22 million to 46.72 ± 210.92 million (P=.007), with the most profound increase in men with a baseline TMSC <5 million: from 2.32 ± 1.50 million to 15.97 ± 32.92 million (P=.0000002). However, what may have been their greatest finding was that 58.8% of men were "upgraded" from IVF candidacy (TMSC <5 million) to IUI (TMSC 5–9 million) or natural pregnancy (TMSC >9 million). Several studies have been able to demonstrate that varicocelectomy has a positive effect in men with azoospermia due to spermatogenic dysfunction, with a return of sperm to the ejaculate in a range of 20.8%–56% of their patients (10Matthews G.J. Matthews E.D. Goldstein M. Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia.Fertil Steril. 1998; 70: 71-75Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar, 41Kim E.D. Leibman B.B. Grinblat D.M. Lipshultz L.I. Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure.J Urol. 1999; 162: 737-740Crossref PubMed Scopus (173) Google Scholar, 42Cocuzza M. Pagani R. Lopes R.I. Athayde K.S. Lucon A.M. Srougi M. et al.Use of subinguinal incision for microsurgical testicular biopsy during varicocelectomy in men with nonobstructive azoospermia.Fertil Steril. 2009; 91: 925-928Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 43Kadioǧlu A. Tefekli A. Cayan S. Kandirali E. Erdemir F. Tellaloǧlu S. Microsurgical inguinal varicocele repair in azoospermic men.Urology. 2001; 57: 328-333Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 44Gat Y. Bachar G.N. Everaert K. Levinger U. Gornish M. Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele.Hum Reprod. 2005; 20: 1013-1017Crossref PubMed Scopus (67) Google Scholar, 45Zampieri N. Bosaro L. Costantini C. Zaffagnini S. Zampieri G. Relationship between testicular sperm extraction and varicocelectomy in patients with varicocele and nonobstructive azoospermia.Urology. 2013; 82: 74-77Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). In 2009, Inci et al. (46Inci K. Hascicek M. Kara O. Dikmen A.V. Gürgan T. Ergen A. Sperm retrieval and intracytoplasmic sperm injection in men with nonobstructive azoospermia, and treated and untreated varicocele.J Urol. 2009; 182: 1500-1505Google Scholar) retrospectively examined 96 patients who had undergone testicular sperm extraction (TESE) and IVF/ICSI (66 had prior varicocelectomy and 30 had elected to perform IVF/ICSI without varicocele repair). The two groups had similar FSH levels, testicular volume, and female age. In the first group, 53% had successful testicular sperm retrieval, whereas only 30% of the control subjects had successful sperm retrieval (P=.04). These findings suggest that varicocelectomy not only can obviate the need for TESE, but also improves the rate of sperm retrieval in patients who remained azoospermic after varicocele repair. In the subsequent years, other studies were able to corroborate similar findings, with higher sperm retrieval rates, pregnancy rates, and live birth rates in men treated with varicocelectomy before TESE (45Zampieri N. Bosaro L. Costantini C. Zaffagnini S. Zampieri G. Relationship between testicular sperm extraction and varicocelectomy in patients with varicocele and nonobstructive azoospermia.Urology. 2013; 82: 74-77Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 47Haydardedeoglu B. Turunc T. Kilicdag E.B. Gul U. Bagis T. The effect of prior varicocelectomy in patients with nonobstructive azoospermia on intracytoplasmic sperm injection outcomes: a retrospective pilot study.Urology. 2010; 75: 83-86Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar). The only prognostic factor that seems to consistently predict chances of finding sperm in the ejaculates of men with azoospermia due to spermatogenic dysfunction is testicular histopathology (48Weedin J.W. Khera M. Lipshultz L.I. Varicocele repair in patients with nonobstructive azoospermia: a meta-analysis.J Urol. 2010; 183: 2309-2315Crossref PubMed Scopus (83) Google Scholar). In 2016, a systematic review revealed that sperm was found in ejaculates after varicocelectomy in 9.7% of patients with germinal aplasia, 35.3% of patients with maturation arrest, and 56.2% of patients with hypospermatogenesis (49Esteves S. Miyaoka R. Roque M. Agarwal A. Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis.Asian J Androl. 2016; 18: 246Crossref PubMed Scopus (76) Google Scholar). Varicoceles are typically asymptomatic, but ∼10% of patients will present with a chief complaint of scrotal pain and varicocelectomy has been suggested when conservative measures fail and other causes of orchialgia are excluded. The pain associated with varicocele is typically greater when the patient is standing or submitted to heavy activity, and is described as a "dull" or "throbbing" pain in the ipsilateral testicle or inguinal region. For these patients, microsurgical subinguinal varicocelectomy has proven to be more effective than other approaches (50Han D.Y. Yang Q.Y. Chen X. Ouyang B. Yao B. Liu G.H. et al.Who will benefit from surgical repair for painful varicocele: a meta-analysis.Int Urol Nephrol. 2016; 48: 1071-1078Google Scholar). Owen et al. (51Owen R.C. McCormick B.J. Figler B.D. Coward R.M. A review of varicocele repair for pain.Transl Androl Urol. 2017; 6: S20-S29Google Scholar) summarized results from several studies and concluded that with careful patient selection, more than 90% of patients would experience benefit from varicocele repair. The idea of varicocelectomy as a treatment for hypogonadism is an emerging concept. Tanrikut et al. (8Tanrikut C. Goldstein M. Rosoff J.S. Lee R.K. Nelson C.J. Mulhall J.P. Varicocele as a risk factor for androgen deficiency and effect of repair.BJU Int. 2011; 108: 1480-1484Crossref PubMed Scopus (115) Google Scholar) found that men with palpable varicoceles have lower testosterone levels at every age than a control group of vasectomy reversal patients without varicoceles. Furthermore, they reported an increase in serum testosterone levels from 358 to 454 ng/dL after microsurgical repair. Recently, Abdel-Meguid et al. (52Abdel-Meguid T.A. Farsi H.M. Al-Sayyad A. Tayib A. Mosli H.A. Halawani A.H. Effects of varicocele on serum testosterone and changes of testosterone after varicocelectomy: A prospective controlled study.Urology. 2014; 84: 1081-1087Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar) published a prospective controlled study where they reported that men with varicocele have lower baseline testosterone than men without varicocele, and varicocelectomy yielded significant testosterone levels among hypogonadal men but insignificant changes in eugonadal men. A meta-analysis including only subfertile patients with clinical varicoceles and hypogonadism reached similar results, with significant testosterone improvement only in patients with hypogonadism (53Chen X. Yang D. Lin G. Bao J. Wang J. Tan W. Efficacy of varicocelectomy in the treatment of hypogonadism in subfertile males with clinical varicocele: a meta-analysis.Andrologia. 2017; 49Google Scholar). Many questions surrounding varicoceles remain. Although we think that the data presented here firmly support the role of varicocelectomy in not only isolated male-factor infertility, but also in couples needing ART for combined male and female factors, ultimately each couple must be approached uniquely. Factors such as female age are often controlled in clinical studies, but must be strongly considered in clinical practice. In the hands of a skilled microsurgeon, both techniques of microsurgical varicocelectomy offer excellent potential for reproductive success.