Synonyms: acute varicocele = lover's nut
A varicocele is an abnormal dilatation of the testicular veins in the pampiniform venous plexus, caused by venous reflux. They are important because they are a well-recognised cause of reduced testicular function and are associated with male infertility. This link with infertility was first proposed by Barfield, a British surgeon, in the late 19th century.
Varicoceles are more common on the left for anatomical reasons:
- The angle at which the left testicular vein enters the left renal vein.
- Lack of effective valves between the testicular and renal veins.
- Increased reflux from compression of the renal vein (between the superior mesenteric artery and aorta). This is sometimes called the nutcracker syndrome or aorto-left renal vein entrapment syndrome.
Pathophysiology of effect on sperm quality
Randomised controlled trials and prospective studies assessing semen parameters clearly demonstrate that varicocele repair is associated with a significant increase in sperm concentration, motility and normal morphology. Furthermore, recent studies indicate that the pathophysiology is associated with seminal oxidative stress and sperm DNA damage.
Three protein spots have been identified whose expression was significantly lower in sperm samples before varicocelectomy compared with after surgery. They include heat shock protein A5 (HSPA5), superoxide dismutase 1 (SOD1) and the delta subunit of the catalytic core of mitochondrial adenosine triphosphate synthase (ATP5D). These proteins are all essential for normal sperm production and are affected by the heat generated by the existence of a varicocele.
Varicocelectomy helps to reverse these factors. Evidence supports the view that varicocelectomy will improve fertility in young men with impaired seminal parameters who are not yet interested in pregnancy. The operation also appears to improve the prospects of men with varicocele whose partner has experienced first-term recurrent miscarriage.
Testicular biopsy shows that hypospermatogenetic patients have a better chance of improvement in their semen analysis after varicocelectomy than non-obstructive azoospermia patients with Sertoli cell-only syndrome or maturation arrest.
- It is unusual in boys under the age of 10 years.
- Incidence increases after puberty.
- The incidence is 15% of the general population and is similar in adults and adolescents[5, 6].
- Varicocele has been implicated as a cause in 35-50% of patients with primary infertility and up to 81% of men with secondary infertility.
- It is usually asymptomatic (between 2% and 10% have symptoms) and only rarely causes pain.
- The scrotum is often described as feeling 'like a bag of worms'.
- Patients may report scrotal heaviness.
- It may be an incidental finding, being discovered at routine medical examinations or noticed in children by parents.
- Infertility investigations. The high prevalence of varicoceles in subfertile males emphasises that they are the most important cause of poor sperm production and reduced semen quality.
- Careful examination, with the patient standing, is the most important method of detection:
- The scrotum on the side of the varicocele hangs lower than on the normal side.
- Dilation and tortuosity of the veins increase with standing and usually decrease on lying down. The varicocele cannot usually be palpated with the patient lying down.
- Performing the Valsalva manoeuvre whilst standing increases the dilation.
- There may be a cough impulse.
- Most are in the left testicle (80-90%), some bilateral (as many as 35-40% radiologically) and very few just on the right side.
- Size. They vary in size and may be classified as:
- Large. Easily identified by inspection alone. Sometimes called grade III.
- Moderate. Identified by palpation but without performing the Valsalva manoeuvre. Grade II.
- Small. Identified only by 'bearing down' to increase intra-abdominal pressure (impedes varicocele drainage) and increase the size of varicocele. Grade I.
- However, examination is not the most accurate method of detection and, where detection is important (particularly in infertility), other methods of investigation are required.
The diagnosis is not usually difficult. However, beware of secondary varicocele. Varicocele can (rarely) be secondary to other pathological processes blocking the testicular vein. For example, tumours of the kidney and other retroperitoneal tumours may involve the renal vein and obstruction of the left testicular vein[11, 12]. If on the right, consider situs inversus.
- Sperm counts may be done as part of fertility investigations. They should also be offered to men in their 20s with varicocele, irrespective of presentation, as studies document a significant increase in abnormal semen parameters compared to controls.
- Colour Doppler studies. This is the method of choice to diagnose varicocele but is not indicated unless physical examination is inconclusive. They define both anatomical and physiological aspects of varicoceles by combining real-time ultrasonography with pulsed Doppler in the same scan. Colour demonstrates direction of blood flow, including reverse flow in the varicocele. Various ultrasonographic parameters, such as the spermatic cord diameter, diameter of the veins in the pampiniform plexus and venous retrograde flow in either supine or upright positions with or without Valsalva manoeuvre, have been investigated to assess patients suspected of having varicocele. There is as yet no consensus on which is the best method. The general consensus is that dilation of the pampiniform plexus veins to a width of 2 mm or more is diagnostic of varicocele.
- Other imaging methods used to evaluate varicoceles include:
- Venography - this was formerly the gold standard but is more expensive and more invasive than Doppler ultrasonography.
- Radionucleotide angiography - offers no advantage over ultrasonography.
- Thermography - a useful non-invasive technique. One study found that it was more sensitive than sonography.
- CT scans - may be required to identify tumours obstructing the testicular vein.
- Serum follicle-stimulating hormone (FSH), luteinising hormone (LH) levels and response to luteinising hormone-releasing hormone (LHRH). Testicular injury can be assessed by a supranormal LH and FSH response to LHRH.
- There are no established effective medical treatments. There is some evidence that bioflavinoids slow the progress from subclinical to palpable varicoceles but they have no effect on the onset of testicular growth arrest.
- Surgical repair of subclinical varicoceles is not usually recommended, although opinions differ.
- Not all varicoceles require surgery. Surgery has the potential to cause testicular damage.
However, the primary treatment of varicoceles is surgery and indications include:
- Infertility possibly (controversy surrounds this recommendation).
- To prevent testicular atrophy.
Approaches to surgery include:
- Infra-inguinal or subinguinal
All methods involve ligation of veins to prevent abnormal blood flow. The recurrence rate is usually less than 10%. Lymphatic-sparing microscopic surgery has the advantage of minimising the risk of recurrence and of the development of hydrocele. Embolisation of the gonadal vein has a higher technical failure rate than that of surgery but is a better option for the treatment of post-surgical recurrence[19, 21].
It was common practice to recommend referral for repair of varicoceles if:
- Varicocele was palpable.
- The couple had documented infertility.
- The female partner had normal fertility or correctable infertility.
- The male partner had one or more abnormal semen parameters or sperm function test results.
There is evidence suggesting that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However the quality of the available evidence is very low. It is not advocated by the National Institute for Health and Care Excellence (NICE). Overall, one suspects that future research will identify a subset of men likely to benefit, based on factors such as testicular morphology and histology, venous anatomy and duration of infertility. (See also 'When to refer', below).
When to refer
- Refer urgently to a urologist to exclude a tumour:
- If a varicocele appears suddenly, especially if the man is older than 40 years of age and the varicocele remains tense when lying down.
- If there is a solitary right-sided varicocele.
- Refer to a urologist if there is uncertainty about the nature of a scrotal swelling.
- Refer routinely to a urologist for consideration of varicocele ablation:
- If it is causing distress or embarrassment.
- If there is pain or discomfort.
- Refer adolescents with a varicocele to a urologist if:
- There are concerns about reduced ipsilateral testicular volume.
- There is an additional testicular condition affecting fertility.
- There is a bilateral palpable varicocele.
- There is pathological sperm quality (in older adolescents).
- The varicocele is causing symptoms.
- Do not routinely refer men with a left-sided varicocele for ultrasonography to look for an underlying tumour.
- If a varicocele is found in the male partner of an infertile couple referral should be considered. See 'Prognosis after surgery', below.
Prognosis after surgery
NICE recommends that men should not be offered surgery for varicoceles as a form of fertility treatment because it does not improve pregnancy rates. However, this is based on 2004 evidence and does not take into account more recent research. Studies suggest that surgical treatment should be considered when the semen analysis shows oligospermia, asthenozoospermia (reduced sperm motility), teratospermia (abnormal morphology) or co-existence of these abnormalities even if the total sperm count is normal.
Varicoceles can recur after surgery. There is evidence that recurrence can be associated with low body metabolic index.
Some have also questioned the need for surgery with the advent of intracytoplasmic sperm injection (ICSI) techniques. However, further research is needed to clarify the effectiveness of this on conception rates in infertile couples.
Repair in children and adolescents
There is no evidence that early operation in adolescents gives better andrological results. Referral is recommended as above.
Further reading and references
Samplaski MK, Yu C, Kattan MW, et al; Nomograms for predicting changes in semen parameters in infertile men after varicocele repair. Fertil Steril. 2014 May 10. pii: S0015-0282(14)00301-X. doi: 10.1016/j.fertnstert.2014.03.046.
Kumanov P, Robeva R, Tomova A; Does an Association between the Idiopathic Left-Sided Varicocele and Eye Colour Exist? Adv Urol. 20142014:524570. doi: 10.1155/2014/524570. Epub 2014 Apr 7.
Rudloff U, Holmes RJ, Prem JT, et al; Mesoaortic compression of the left renal vein (nutcracker syndrome): case reports and review of the literature. Ann Vasc Surg. 2006 Jan20(1):120-9.
Ficarra V, Crestani A, Novara G, et al; Varicocele repair for infertility: what is the evidence? Curr Opin Urol. 2012 Nov22(6):489-94. doi: 10.1097/MOU.0b013e328358e115.
Hosseinifar H, Sabbaghian M, Nasrabadi D, et al; Study of the effect of varicocelectomy on sperm proteins expression in patients with varicocele and poor sperm quality by using two-dimensional gel electrophoresis. J Assist Reprod Genet. 2014 Apr 24.
Aboutaleb HA, Elsherif EA, Omar MK, et al; Testicular Biopsy Histopathology as an Indicator of Successful Restoration of Spermatogenesis after Varicocelectomy in Non-obstructive Azoospermia. World J Mens Health. 2014 Apr32(1):43-9. doi: 10.5534/wjmh.2014.32.1.43. Epub 2014 Apr 25.
EAU Paediatric Urology Guidelines. Edn. presented at the EAU Annual Congress Copenhagen; European Association of Urology, 2018
Karami M, Mazdak H, Khanbabapour S, et al; Determination of the best position and site for color Doppler ultrasonographic evaluation of the testicular vein to define the clinical grades of varicocele ultrasonographically. Adv Biomed Res. 2014 Jan 93:17. doi: 10.4103/2277-9175.124647. eCollection 2014.
Milone M, Musella M, Fernandez ME, et al; Varicocele repair in severe oligozoospermia: A case report of post-operative azoospermia. World J Clin Cases. 2014 Apr 162(4):94-6. doi: 10.12998/wjcc.v2.i4.94.
Gat Y, Bachar GN, Zukerman Z, et al; Varicocele: a bilateral disease. Fertil Steril. 2004 Feb81(2):424-9.
Gat Y, Bachar GN, Zukerman Z, et al; Physical examination may miss the diagnosis of bilateral varicocele: a comparative study of 4 diagnostic modalities. J Urol. 2004 Oct172(4 Pt 1):1414-7.
Aswani Y, Hira P; Secondary varicocele caused by pancreatic pseudocyst obstructing testicular venous drainage. JOP. 2013 Nov 1014(6):674-5. doi: 10.6092/1590-8577/1974.
El-Saeity NS, Sidhu PS; "Scrotal varicocele, exclude a renal tumour". Is this evidence based? Clin Radiol. 2006 Jul61(7):593-9.
Espinosa Bravo R, Lemourt Oliva M, Perez Monzon AF, et al; Renal cell carcinoma and simultaneous left varicocele. Arch Esp Urol. 2003 Jun56(5):533-5.
Lang F; Encyclopedia of Molecular Mechanisms of Disease: 2009.
Kwon CS, Lee JH; Is semen analysis necessary for varicocele patients in their early 20s? World J Mens Health. 2014 Apr32(1):50-5. doi: 10.5534/wjmh.2014.32.1.50. Epub 2014 Apr 25.
Patiala B; Role of color doppler in scrotal lesions. Indian J Radiol Imaging. 2009 Jul-Sep19(3):187-90. doi: 10.4103/0971-3026.54874.
Hamm B, Fobbe F, Sorensen R, et al; Varicoceles: combined sonography and thermography in diagnosis and posttherapeutic evaluation. Radiology. 1986 Aug160(2):419-24.
Zampieri N, Pellegrino M, Ottolenghi A, et al; Effects of bioflavonoids in the management of subclinical varicocele. Pediatr Surg Int. 2010 May26(5):505-8. doi: 10.1007/s00383-010-2574-9. Epub 2010 Feb 17.
Seo JT, Kim KT, Moon MH, et al; The significance of microsurgical varicocelectomy in the treatment of subclinical varicocele. Fertil Steril. 2010 Apr93(6):1907-10. doi: 10.1016/j.fertnstert.2008.12.118. Epub 2009 Feb 26.
Cassidy D, Jarvi K, Grober E, et al; Varicocele surgery or embolization: Which is better? Can Urol Assoc J. 2012 Aug6(4):266-8. doi: 10.5489/cuaj.11064.
Ding H, Tian J, Du W, et al; Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials. BJU Int. 2012 Nov110(10):1536-42. doi: 10.1111/j.1464-410X.2012.11093.x. Epub 2012 May 29.
Jargiello T, Drelich-Zbroja A, Falkowski A, et al; Endovascular transcatheter embolization of recurrent postsurgical varicocele: anatomic reasons for surgical failure. Acta Radiol. 2014 Jan 10. pii: 0284185113519624.
Kroese AC, de Lange NM, Collins J, et al; Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst Rev. 2012 Oct 1710:CD000479. doi: 10.1002/14651858.CD000479.pub5.
Fertility - Assessment and treatment for people with fertility problems; NICE Guidance (February 2013, updated Aug 2016)
Cakiroglu B, Sinanoglu O, Gozukucuk R; The effect of varicocelectomy on sperm parameters in subfertile men with clinical varicoceles who have asthenozoospermia or teratozoospermia with normal sperm density. ISRN Urol. 2013 Oct 212013:698351. doi: 10.1155/2013/698351. eCollection 2013.
Gorur S, Candan Y, Helli A, et al; Low body mass index might be a predisposing factor for varicocele recurrence: a prospective study. Andrologia. 2014 May 9. doi: 10.1111/and.12287.