Report on varicocele and infertility: a committee opinion

  • Practice Committee of the American Society for Reproductive Medicine
  • the Society for Male Reproduction and Urology
      This document discusses the evaluation and management of varicoceles in the male partners of infertile couples, and presents the controversies and recommendations regarding this condition. This document replaces the ASRM Practice Committee document titled “Report on Varicocele and Infertility,” last published in 2008, and was developed in conjunction with the Society for Male Reproduction and Urology (Fertil Steril 2008;90:S247–9).
      Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/asrmpraccom-varicocele-infertility/
      Varicoceles, defined as abnormally dilated scrotal veins, are present in almost 15% of the normal male population and in approximately 40% of men presenting with infertility (
      • Nagler H.M.
      • Luntz R.K.
      • Martinis F.G.
      Varicocele.
      ). Although the majority of men with varicoceles are fertile, varicocele remains the most common diagnosis seen in infertile men. The preponderance of experimental data from clinical and animal models demonstrates an adverse effect of varicoceles on spermatogenesis. Venous reflux and testicular temperature elevation appear to play important roles in varicocele-induced testicular dysfunction, although the exact pathophysiologic mechanisms involved are not yet completely understood. Despite the relationship between varicoceles and sperm production, irrefutable evidence for a clinical benefit of varicocele repair in improving fertility has been elusive. Therefore, the exact impact of varicoceles on male fertility is somewhat controversial.

      Detection of varicoceles

      Evaluation of a male patient with infertility should include a careful medical and reproductive history, a physical examination, and at least two semen analyses. The physical examination should be performed with the patient in both the upright and recumbent positions. A palpable varicocele feels like a “bag of worms” and disappears or is very significantly reduced when the patient is recumbent. When a suspected varicocele is not clearly palpable, the scrotum should be examined while the patient performs a Valsalva maneuver in a standing position.
      Only clinically palpable varicoceles have been clearly associated with infertility. Varicoceles are typically graded on a scale of 1 to 3, with grade 3 being present on visual inspection of the scrotum, grade 2 being easily palpable, and grade 1 only being palpable with Valsalva maneuver (
      • Dubin L.
      • Amelar R.D.
      Varicocele size and results of varicocelectomy in selected subfertile men with varicocele.
      ). These definitions are somewhat vague, as what may be easily palpable to one examiner may not be for another. However, there is agreement that varicoceles palpable by most examiners are considered “clinically significant.” Ancillary diagnostic measures, such as scrotal ultrasonography, thermography, Doppler examination, radionuclide scanning, and spermatic venography, should not be used for routine screening and detection of subclinical varicoceles in patients without a palpable abnormality. Scrotal ultrasonography is indicated for evaluation of an inconclusive physical examination of the scrotum. Although definitive evidence-based criteria are lacking, most investigators agree that multiple spermatic veins >2.5–3.0 mm in diameter (at rest and with Valsalva) tend to correlate with the presence of clinically significant varicoceles (
      • Stahl P.
      • Schlegel P.N.
      Standardization and documentation of varicocele evaluation.
      ). Spermatic venography may be useful to demonstrate the anatomic position of refluxing spermatic veins that recur or persist after varicocele repair. Although early studies did not demonstrate a difference in outcome based on varicocele size, more recent data suggest that larger varicoceles may have a greater impact on semen parameters, and correction may result in greater improvement (
      • Steckel J.
      • Dicker A.P.
      • Goldstein M.
      Relationship between varicocele size and response to varicocelectomy.
      ).

      Indications for treatment of a varicocele

      When the male partner of a couple attempting to conceive has a varicocele, treatment of the varicocele should be considered when most or all of the following conditions are met: [1] the varicocele is palpable on physical examination of the scrotum; [2] the couple has known infertility; [3] the female partner has normal fertility or a potentially treatable cause of infertility, and time to conception is not a concern; and [4] the male partner has abnormal semen parameters. Varicocele treatment is not indicated in patients with either normal semen quality, isolated teratozoospermia, or a subclinical varicocele (
      • Stahl P.
      • Schlegel P.N.
      Standardization and documentation of varicocele evaluation.
      ).
      An adult male who is not currently attempting to achieve conception but has a palpable varicocele, abnormal semen analyses and a desire for future fertility, and/or pain related to the varicocele is also a candidate for varicocele repair. Young adult males with clinical varicoceles who have normal semen parameters may be at risk for progressive testicular dysfunction and should be offered monitoring with semen analyses every 1 to 2 years to detect the earliest sign of reduced spermatogenesis. More recently, there is increased evidence that larger varicoceles may impact testosterone production, and some advocate repair in the setting of diminished testosterone levels (
      • Schlegel P.N.
      • Goldstein M.
      Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction.
      ).
      Adolescent males who have unilateral or bilateral varicoceles and objective evidence of reduced testicular size ipsilateral to the varicocele may also be considered candidates for varicocele repair (
      • Okuyama A.
      • Nakamura M.
      • Namiki M.
      • Takeyama M.
      • Utsunomiya M.
      • Fujioka H.
      • et al.
      Surgical repair of varicocele at puberty: preventive treatment for fertility improvement.
      ,
      • Paduch D.A.
      • Niedzielski J.
      Repair versus observation in adolescent varicocele: a prospective study.
      ,
      • Yamamoto M.
      • Hibi H.
      • Katsuno S.
      • Miyake K.
      Effects of varicocelectomy on testis volume and semen parameters in adolescents: a randomized prospective study.
      ,
      • Sigman M.
      • Jarow J.P.
      Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles.
      ). If objective evidence of reduced testis size is not present, then adolescents with varicoceles should be followed with annual objective measurements of testis size and/or semen analyses to detect the earliest sign of varicocele-related testicular injury. Varicocele repair may be offered on detection of testicular or semen abnormalities, as catch-up growth has been demonstrated as well as reversal of semen abnormalities; however, data are lacking regarding the impact on future fertility.

      Management considerations

      Varicocele repair, intrauterine insemination (IUI), and in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) are options for the management of couples with male factor infertility associated with a varicocele. The decision to proceed with any of these management options is influenced by a number of factors. Varicocele repair has the potential to reverse a pathological condition, as opposed to IUI or IVF-ICSI, which are treatments that circumvent abnormal semen parameters and are required for each attempt at pregnancy. Other factors to be considered include associated symptoms attributed to the varicocele, age, fertility potential of the female partner, and time available for conception as improvement in semen parameters after varicocele repair may take 3 to 6 months. The potential cost-effectiveness of varicocele repair compared with IVF with or without ICSI is another aspect that may influence treatment (
      • Schlegel P.N.
      Is assisted reproduction the optimal treatment for varicocele-associated infertility? A cost-effective analysis.
      ). In addition, factors that may help to predict improvement including size of varicocele, follicle-stimulating hormone level, and preoperative total motile sperm count should be taken into consideration (
      • Fretz P.C.
      • Sandlow J.I.
      Varicocele: current concepts in pathophysiology, diagnosis, and treatment.
      ). Finally, failure to treat a varicocele may result in a progressive decline in semen parameters, which may further compromise future fertility (
      • Chehval M.J.
      • Purcell M.H.
      Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage.
      ,
      • Gorelick J.
      • Goldstein M.
      Loss of fertility in men with varicocele.
      ,
      • Witt M.A.
      • Lipshultz L.I.
      Varicocele: a progressive or static lesion?.
      ).
      Varicocele repair is not usually indicated when IVF or IVF-ICSI is otherwise required for the treatment of a female factor infertility, although some studies have also suggested a benefit (
      • Ashkenazi J.
      • Dicker D.
      • Feldberg D.
      • Shelef M.
      • Goldman G.A.
      • Goldman J.
      The impact of spermatic vein ligation on the male factor in in vitro fertilization-embryo transfer and its relation to testosterone levels before and after operation.
      ,
      • Esteves S.C.
      • Oliveira F.V.
      • Bertolla R.P.
      Clinical outcome of intracytoplasmic sperm injection in infertile men with treated and untreated clinical varicocele.
      ). However, there are certain circumstances in which treatment of a varicocele should be considered before assisted reproductive technology (ART), even when a significant female factor is present. Specifically, men with nonobstructive azoospermia have been shown to respond to varicocele repair, albeit in fairly low-quality observational studies. Several studies have suggested restoration of low numbers of sperm to the ejaculate in approximately 10% to 50% of men with nonobstructive azoospermia due to either hypospermatogenesis or late maturation arrest based on previous testicular biopsy (
      • Matthews G.J.
      • Matthews E.D.
      • Goldstein M.
      Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia.
      ,
      • Kim E.D.
      • Leibman B.B.
      • Grinblat D.M.
      • Lipshultz L.I.
      Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure.
      ). In such cases, varicocele repair is associated with return of sperm to the ejaculate, thus potentially making it possible to perform IVF-ICSI without testicular sperm aspiration or extraction. These studies have also shown that men with Sertoli-cell only or early maturation arrest histology did not have sperm return to the ejaculate. It is important to remember that men previously found to be azoospermic may also have sperm found in the ejaculate with no intervention (
      • Schlegel P.N.
      • Goldstein M.
      Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction.
      ,
      • Ron-El R.
      • Strassburger D.
      • Friedler S.
      • Komarovski D.
      • Bern O.
      • Soffer Y.
      • et al.
      Extended sperm preparation: an alternative to testicular sperm extraction in non-obstructive azoospermia.
      ). Therefore, testicular biopsy/testicular sperm extraction or varicocele repair may be offered to such men, although the value of varicocelectomy in all patients with nonobstructive azoospermia remains controversial (
      • Schlegel P.N.
      • Kaufmann J.
      Role of varicocelectomy in men with nonobstructive azoospermia.
      ).

      Treatment of varicoceles

      There are two approaches to varicocele repair: surgery and percutaneous embolization. Surgical repair of a varicocele may be accomplished by various open surgical methods, including retroperitoneal, inguinal, and subinguinal approaches, or by laparoscopy. Percutaneous embolization treatment of a varicocele is accomplished by percutaneous embolization of the refluxing internal spermatic vein(s). None of these methods has been proven superior to the others in its ability to improve fertility, although there are differences in recurrence rates (
      • Ding H.
      • Tian J.
      • Du W.
      • Zhang L.
      • Wang H.
      • Wang Z.
      Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials.
      ).

       Surgical Repair

      All surgical procedures entail ligation and division of the spermatic veins (pampiniform plexus) in the spermatic cord, thus leading to venous drainage of the testis via collaterals from the vasal veins. Most experts perform inguinal or subinguinal surgical repair employing loupes or an operating microscope for optical magnification. Some practitioners use a retroperitoneal (high ligation) approach, which consists of a small abdominal incision. Laparoscopy has been used for varicocele repair, but this approach is less commonly performed and may carry additional risks not associated with open surgical approaches. Techniques using optical magnification maximize preservation of arterial and lymphatic vessels while reducing the risk of persistence or recurrence of varicocele (
      • Ding H.
      • Tian J.
      • Du W.
      • Zhang L.
      • Wang H.
      • Wang Z.
      Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials.
      ,
      • Goldstein 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.
      ). High ligation approaches (retroperitoneal, laparoscopic) have higher rates of recurrence (up to 15%) compared with low inguinal/subinguinal techniques (1% to 2%) and thus are considered to be inferior to the lower approaches (
      • Ding H.
      • Tian J.
      • Du W.
      • Zhang L.
      • Wang H.
      • Wang Z.
      Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials.
      ,
      • Goldstein 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.
      ).

       Percutaneous Embolization Treatment

      Percutaneous embolization of varicoceles uses either metal coils or sclerosants (e.g., as pure alcohol) to obstruct the dilated spermatic veins. These are accessed percutaneously under fluoroscopic guidance. Percutaneous embolization requires a physician with experience in interventional radiologic techniques. This technique may be associated with less pain than occurs after the standard inguinal surgical approach. Moreover, in some patients, interventional access to the internal spermatic veins cannot be achieved because of technical problems (up to 20%). Recurrence rates are higher than microscopic approaches and are similar to high ligation surgical approaches (15%). The results of percutaneous embolization are variable and depend on the experience and skill of the interventional radiologist performing the procedure.

       Complications

      The potential complications of surgical varicocele repair occur infrequently and are usually mild. Overall, complications may occur in 1% to 5%, based on the approach used (
      • Baazeem A.
      • Belzile E.
      • Ciampi A.
      • Dohle G.
      • Jarvi K.
      • Salonia A.
      • et al.
      Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.
      ). All approaches to varicocele surgery are associated with a small risk of wound infection, hydrocele, persistence or recurrence of varicocele, and, rarely, testicular atrophy. Potential additional complications from an inguinal incision for varicocele repair include scrotal numbness and prolonged pain, although these are somewhat rare.

      Results of varicocele treatment

      Surgical treatment successfully eliminates over 90% of varicoceles, with some series reporting over 99% success (
      • Schlegel P.N.
      • Kaufmann J.
      Role of varicocelectomy in men with nonobstructive azoospermia.
      ). Improvement in semen parameters after varicocele repair is somewhat difficult to measure, as there is no standard definition for what constitutes significant improvement. Furthermore, improvement needs to be interpreted in the context of the presurgical and postsurgical parameters. Most studies have reported that semen quality improves in a majority of patients after varicocele repair, as defined by a comparison of pretreatment and posttreatment semen parameters. In a meta-analysis of studies that examined infertile men who underwent varicocele repair, sperm concentration increased by a mean of 12 million sperm/mL with a mean 11% increase in motility and variable effects on sperm morphology (
      • Baazeem A.
      • Belzile E.
      • Ciampi A.
      • Dohle G.
      • Jarvi K.
      • Salonia A.
      • et al.
      Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.
      ). In addition to the improvement in semen parameters, varicocele repair may allow a couple with severely impaired semen parameters to have less invasive treatment. Men with severe oligospermia who would otherwise require IVF-ICSI to conceive may have adequate improvement in semen analysis to allow IUI instead of IVF-ICSI, and those with oligospermia may have sufficient improvement in semen parameters to allow natural conception in some cases (
      • Cayan S.
      • Erdemir F.
      • Ozbey I.
      • Turek P.J.
      • Kadioğlu A.
      • Tellaloğlu S.
      Can varicocelectomy significantly change the way couples use assisted reproductive technologies?.
      ). Time to improvement is typically 3 to 6 months, which corresponds to one to two spermatogenic cycles. This period of time may be a concern for the female partner with age-related infertility or decreased ovarian reserve.
      There are several randomized, controlled published studies examining the impact of varicocele repair on pregnancy rates for men with palpable varicoceles, abnormal semen parameters, and normal female evaluation (
      • Madgar I.
      • Weissenberg R.
      • Lunenfeld B.
      • Karasik A.
      • Goldwasser B.
      Controlled trial of high spermatic vein ligation for varicocele in infertile men.
      ,
      • Nieschlag E.
      • Hertle L.
      • Fischedick A.
      • Abshagen K.
      • Behre H.M.
      Update on treatment of varicocele: counseling as effective as occlusion of the vena spermatica.
      ) (Table 1). Two of the studies showed an improved pregnancy rate after varicocele repair compared with controls. The first study observed a statistically significant improvement in fertility following varicocele repair (
      • Madgar I.
      • Weissenberg R.
      • Lunenfeld B.
      • Karasik A.
      • Goldwasser B.
      Controlled trial of high spermatic vein ligation for varicocele in infertile men.
      ). This study, a randomized, controlled study of infertile men with varicoceles, observed a natural conception rate of 60% in treated patients compared with 10% in untreated patients. The untreated patients then underwent repair and had a natural conception rate of 66% (44% in the first year and 22% in the second year). Although the second study observed no greater likelihood of pregnancy after varicocele repair, it did demonstrate significant improvement in testis volume and semen parameters compared with those in untreated controls (
      • Abdel-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.
      ). The most recent study examined 145 couples who were randomized to varicocelectomy (study) versus observation (control). The control group had a natural conception rate of 13.9%, while the study group had a rate of 32.9% with an odds ratio (OR) 3.04 (95% confidence interval [CI], 1.33–6.95). The baseline characteristics of both groups were statistically similar. No crossover was done (
      • Abdel-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.
      ).
      Table 1Summary of data from three randomized, controlled trials involving treatment of varicoceles in subfertile men.
      StudyType of studyNo. of total patientsClinical grade of varicoceleInclusion criteria of semen parameters (106/mL)Semen parameter improvement with interventionPregnancy rateComments
      Madgar et al., 1995
      • Madgar I.
      • Weissenberg R.
      • Lunenfeld B.
      • Karasik A.
      • Goldwasser B.
      Controlled trial of high spermatic vein ligation for varicocele in infertile men.
      Randomized, crossover control trial45

      C: n = 20

      T: n = 25
      2, 3>5–20YesC: 2/20 (10%)

      T: 15/25 (60%)
      Significant dropout and exclusion rate (>75%)
      Nieschlag et al., 1998
      • Nieschlag E.
      • Hertle L.
      • Fischedick A.
      • Abshagen K.
      • Behre H.M.
      Update on treatment of varicocele: counseling as effective as occlusion of the vena spermatica.
      Randomized, controlled trial125

      C: n = 63

      T: n = 62
      1–30–<20YesC: 16/63 (25.4%)

      T: 18/62 (29%)
      Significant dropout rate (38%)

      Treatment group included embolization and surgical ligation

      No significant difference in pregnancy rates between treatment and control

      Regardless of treatment modality, females who achieved pregnancy were younger (P<.05)
      Abdel-Meguid et al., 2011
      • Abdel-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.
      Randomized control trial145

      C: n = 72

      T: n = 73
      1–3>8–<20YesC: 10/72 (13.9%)

      T: 24/73 (32.9%)
      Low dropout rate (1%)

      Treatment group underwent microsurgical subinguinal ligation

      Pregnancy rates higher in treatment arm
      Note: C = control, T = treatment.
      A number of meta-analyses have been performed to analyze the existing data on varicocele repair and pregnancy rates. One recent report included randomized, controlled trials and observational studies of infertile men with clinical varicoceles and abnormal semen analyses (
      • Marmar 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.
      ). The spontaneous pregnancy rate in the treated group (33%) was statistically significantly higher than in the untreated group (15.5%). The calculated OR of spontaneous pregnancy after varicocele repair was 2.87 (95% CI, 1.33–6.20; P=.007). The most recent Cochrane review, which included the two studies mentioned here, concluded that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy (
      • Kroese A.C.J.
      • de Lange N.M.
      • Collins J.
      • Evers J.L.H.
      Surgery or embolization for varicoceles in subfertile men.
      ). This supersedes previous versions of Cochrane reviews which did not demonstrate this effect; however, it should be noted that even this most recent Cochrane review commented on the low quality of the studies reviewed.
      Most trials have observed improved semen parameters and fertility after varicocele treatment, and only a few have concluded that varicocele treatment has little or no effect on fertility. However, most published studies regarding fertility outcomes after varicocele repair have had a low number of patients, were not randomized, and lacked consideration of female factors, and/or controls. In addition many studies have not limited their analysis to men with clinical varicoceles, abnormal semen parameters, and normal and age-restricted female partners. Despite these limitations, varicocele treatment should be considered an option for appropriately selected infertile couples.

      Follow-up evaluation

      Patients should be evaluated after varicocele treatment for persistence or recurrence of the varicocele. If the varicocele persists or recurs, internal spermatic venography may be performed to identify the site of persistent venous reflux and be followed by either surgical ligation or percutaneous embolization of the refluxing veins. Semen analyses should be performed at approximately 3-month intervals during the first year after varicocele treatment or until pregnancy is achieved. Intrauterine insemination and ART should be considered for couples with persistent infertility despite an anatomically successful varicocele repair.

      Summary

      • The diagnosis of varicoceles is based primarily on physical examination.
      • Imaging studies are not indicated for the standard evaluation unless physical examination is inconclusive.
      • Only clinically palpable varicoceles have been clearly associated with infertility.
      • Adolescents and young men not actively trying to conceive who have a varicocele and objective evidence of reduced ipsilateral testicular size may be offered varicocele repair.
      • Treatment options include surgical approaches or percutaneous embolization techniques.
      • Low microsurgical approaches (inguinal/subinguinal) have been demonstrated to have lower recurrence and complication rates than high non-microsurgical approaches (retroperitoneal and laparoscopic).
      • Varicocele repair is associated with a low risk of complications.
      • Although data are limited and of lower quality, most studies show improvement in semen parameters and fertility after repair of varicocele.
      • Time to improvement in semen parameters is approximately 3 to 6 months.

      Conclusions

      • Treatment of a clinically palpable varicocele may be offered to the male partner of an infertile couple when there is evidence of abnormal semen parameters and minimal/no identified female factor, including consideration of age and ovarian reserve.
      • In vitro fertilization with or without ICSI may be considered the primary treatment option when such treatment is required to treat a female factor, regardless of the presence of varicocele and abnormal semen parameters.
      • The treating physician's experience and expertise, including evaluation of both partners, together with the options available, should determine the approach to varicocele treatment.

      Acknowledgments

      This report was developed under the direction of the Practice Committee of the American Society for Reproductive Medicine and the Society for Male Reproduction and Urology as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. The Practice Committee and the Board of Directors of the American Society for Reproductive Medicine and the Board of the Society for Male Reproduction and Urology have approved this report.
      This document was reviewed by ASRM members and their input was considered in the preparation of the final document. The following members of the ASRM Practice Committee participated in the development of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document.
      Samantha Pfeifer, M.D., Samantha Butts, M.D., M.S.C.E., William Catherino, M.D., Ph.D., Owen Davis, M.D., Daniel Dumesic, M.D., Gregory Fossum, M.D., Jeffrey Goldberg, M.D., Clarisa Gracia, M.D., M.S.C.E., Andrew La Barbera, Ph.D., Mark Licht, M.D., Roger Lobo, M.D., Randall Odem, M.D., Margareta Pisarska, M.D., Robert Rebar, M.D., Richard Reindollar, M.D., Mitchell Rosen, M.D., Jay Sandlow, M.D., Rebecca Sokol, M.D., M.P.H., Kim Thornton, M.D., Michael Vernon, Ph.D., Eric Widra, M.D.

      References

        • Nagler H.M.
        • Luntz R.K.
        • Martinis F.G.
        Varicocele.
        in: Lipshultz L.I. Howards S.S. Infertility in the male. Mosby Year Book, St. Louis, MO1997: 336-359
        • Dubin L.
        • Amelar R.D.
        Varicocele size and results of varicocelectomy in selected subfertile men with varicocele.
        Fertil Steril. 1970; 21: 606-609
        • Stahl P.
        • Schlegel P.N.
        Standardization and documentation of varicocele evaluation.
        Curr Opin Urol. 2011; 21: 500-505
        • Steckel J.
        • Dicker A.P.
        • Goldstein M.
        Relationship between varicocele size and response to varicocelectomy.
        J Urol. 1993; 149: 769-771
        • Schlegel P.N.
        • Goldstein M.
        Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction.
        Fertil Steril. 2011; 96: 1288-1293
        • Okuyama A.
        • Nakamura M.
        • Namiki M.
        • Takeyama M.
        • Utsunomiya M.
        • Fujioka H.
        • et al.
        Surgical repair of varicocele at puberty: preventive treatment for fertility improvement.
        J Urol. 1988; 139: 562-564
        • Paduch D.A.
        • Niedzielski J.
        Repair versus observation in adolescent varicocele: a prospective study.
        J Urol. 1997; 158: 1128-1132
        • Yamamoto M.
        • Hibi H.
        • Katsuno S.
        • Miyake K.
        Effects of varicocelectomy on testis volume and semen parameters in adolescents: a randomized prospective study.
        Nagoya J Med Sci. 1995; 58: 127-132
        • Sigman M.
        • Jarow J.P.
        Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles.
        J Urol. 1997; 158: 605-607
        • Schlegel P.N.
        Is assisted reproduction the optimal treatment for varicocele-associated infertility? A cost-effective analysis.
        Urology. 1997; 49: 83-90
        • Fretz P.C.
        • Sandlow J.I.
        Varicocele: current concepts in pathophysiology, diagnosis, and treatment.
        Urol Clin North Am. 2002; 29: 921-937
        • Chehval M.J.
        • Purcell M.H.
        Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage.
        Fertil Steril. 1992; 57: 174-177
        • Gorelick J.
        • Goldstein M.
        Loss of fertility in men with varicocele.
        Fertil Steril. 1993; 59: 613-616
        • Witt M.A.
        • Lipshultz L.I.
        Varicocele: a progressive or static lesion?.
        Urology. 1993; 42: 541-543
        • Ashkenazi J.
        • Dicker D.
        • Feldberg D.
        • Shelef M.
        • Goldman G.A.
        • Goldman J.
        The impact of spermatic vein ligation on the male factor in in vitro fertilization-embryo transfer and its relation to testosterone levels before and after operation.
        Fertil Steril. 1989; 51: 471-474
        • Esteves 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: 1442-1446
        • Matthews 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: 71-75
        • Kim 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: 737-740
        • Ron-El R.
        • Strassburger D.
        • Friedler S.
        • Komarovski D.
        • Bern O.
        • Soffer Y.
        • et al.
        Extended sperm preparation: an alternative to testicular sperm extraction in non-obstructive azoospermia.
        Hum Reprod. 1997; 6: 1222-1226
        • Schlegel P.N.
        • Kaufmann J.
        Role of varicocelectomy in men with nonobstructive azoospermia.
        Fertil Steril. 2004; 81: 1585-1588
        • Ding H.
        • Tian J.
        • Du W.
        • Zhang L.
        • Wang H.
        • Wang Z.
        Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials.
        BJU Int. 2012; 110: 1536-1542
        • Goldstein 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: 1808-1811
        • Baazeem A.
        • Belzile E.
        • Ciampi A.
        • Dohle G.
        • Jarvi K.
        • Salonia A.
        • et al.
        Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.
        Eur Urol. 2011; 60: 796-808
        • Cayan S.
        • Erdemir F.
        • Ozbey I.
        • Turek P.J.
        • Kadioğlu A.
        • Tellaloğlu S.
        Can varicocelectomy significantly change the way couples use assisted reproductive technologies?.
        J Urol. 2002; 167: 1749-1752
        • Madgar I.
        • Weissenberg R.
        • Lunenfeld B.
        • Karasik A.
        • Goldwasser B.
        Controlled trial of high spermatic vein ligation for varicocele in infertile men.
        Fertil Steril. 1995; 63: 120-124
        • Nieschlag E.
        • Hertle L.
        • Fischedick A.
        • Abshagen K.
        • Behre H.M.
        Update on treatment of varicocele: counseling as effective as occlusion of the vena spermatica.
        Hum Reprod. 1998; 13: 2147-2150
        • Abdel-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: 455-461
        • Marmar 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: 639-648
        • Kroese A.C.J.
        • de Lange N.M.
        • Collins J.
        • Evers J.L.H.
        Surgery or embolization for varicoceles in subfertile men.
        Cochrane Database Syst Rev. 2012; 10: CD000479