Varicoceles

Background 

Varicoceles is the name given to varicose veins present in the scrotum. Varicose veins are dilated veins. They most commonly result from the failure of valves within veins which are meant to promote one-way flow of blood back to the heart. They most commonly occur in the legs but may occur just about anywhere in the body where the veins are subject to high hydrostatic pressures.

Every structure in the body requires blood flow - inflow of fresh blood through arteries and outflow of blood through veins. The testes are no different - there are 3 main groupings of arterial and venous drainage systems from the testicles, and 2 additional ‘collateral’ venous drainages: 

  1. Internal spermatic artery and vein (aka gonadal or testicular): the artery is the primary blood supply to the testis; the vein is longest vein draining the testis and the major culprit for varicoceles.

  2. Deferential artery and vein (aka vasal): these are closely associated with the vas deferens.

  3. Cremasteric artery and vein: these travel with the cremasteric muscle and terminates in the inferior epigastric veins.

  4. Collateral supply: these may become prominent if a very large varicocele is present.

    1. Gubernacular: drain to the superficial scrotal system.

    2. Sub-inguinal collaterals: drain to the superficial system.

The gonadal, deferential and cremasteric veins intertwine and intermix to form the pampiniform plexus. They separate into their named branches as they travel away from the testis and back towards the heart.

The pampiniform plexus acts as a heat exchange system in which the warm blood coming from the heart is cooled by the blood returning from the testicle back to the heart. This keeps the operating temperature of the testis below that of core body temperature by 1-2 degrees celcius. Sperm production works best when the temperature is a little lower than core temperature. Testicular hyperthermia is thought to be the primary mechanism of varicocele-related infertility. Failure of the valves meant to promote one way flow of blood back the heart is the underlying reason for the development of varicoceles though there are several other less common causes.

Varicoceles are very common: they occur in about 1 in every 5 to 7 males, hence approximately 450 million men on earth have a varicocele. Obviously, not all men with varicoceles have difficulty conceiving and most men with varicoceles are able to father children. However, varicoceles can cause subfertility or sterility in some men.

Left-sided varicoceles are more common than on the right. This is thought to be a result of the increased length of the left gonadal vein and the way that it inserts into the left renal vein.

Diagnosis & Evaluation 

Varicoceles can be classified based on physical examination  (the so called 'clinical varicocele') or based on ultrasound.

Physical exam by a skilled physician is considered the gold standard for detection of varicoceles. The reason is that the exam can be performed dynamically - in the standing position and with and without abdominal straining. If an ultrasound is done in this manner, it may be just as accurate but in many circumstances, the testing procedures are insufficient to detect a varicocele.

When a varicocele can be identified on ultrasound but not on physical exam it is called a 'subclinical varicocele'. Physical examination is usually more sensitive and relevant than ultrasound for diagnosis and classification. There are several classifications for varicoceles, both clinical and sonographic. Here are 2 commonly used classifications.

Clinical Ultrasound
Grade I (small): palpable with valsalva only Small: 2-3.4 mm
Grade II (moderate): palpable standing w/o valsalva Medium: 3.5-4.9 mm
Grade III (large): visible Large: ≥5 mm

Reasons to Treat Varicoceles

There are 3 basic reasons why men present for varicocele correction.

  1. They are having difficulty with having a child (infertility) or want to preserve future fertility

  2. They are having pain or discomfort (symptoms)

  3. They are having hormone dysfunction from the varicocele (hypogonadism) - this is rare

The most common reason for varicocele correction is infertility. It is worthwhile to examine the role of varicocele correction in infertility. There are multiple scenarios in which it may be of value. There are 3 primary issues to consider:

  1. How likely is it that the varicocele is having a negative effect on fertility?

  2. How likely is correction of the varicocele to improve the fertility outcome of interest under the specific circumstances?

  3. How should the varicocele be treated if it warrants treatment?

Probably the biggest issue is deciding if the varicocele is contributing to a couple's difficulty with fertility because there are usually multiple issues at play, varicocele being just one issue. Furthermore, the data on varicocele correction is limited - there are few randomized controlled trials (the gold standard of evidence in medicine) and those that exist have many confounding elements such that with rare exception some clinical judgement is necessary to chart the best course of action.

Varicocele Correction for Infertility

Varicoceles are about 4x more common in men having difficulty conceiving than those without problems. Despite this, a varicocele may not be the major contributing factor to infertility nor does correction of the varicocele guarantee that a pregnancy will occur. What varicocele correction can do in select circumstances is increase the odds of a good outcome. What's a good outcome? Ultimately, having a healthy baby is the goal but there can be other goals that can be used as stepping stones to achieve that outcome. Things such as improving the sperm concentration (or facilitating the production of sperm where none can be identified) or even using a less intensive modalities to achieve a pregnancy (for example, intrauterine insemination rather than in vitro fertilization). 

Several medical societies publish guidelines on varicocele correction (NICE, AUA, EUA). They are all very similar. In general, ALL of the following criteria should be met before considering varicocele correction:

  1. Infertility: Difficulty obtaining a pregnancy after 1 year of trying.

  2. Low numbers of sperm: Oligospermia - sperm concentrations less than about 20 million per ml.

  3. Larger varicocele: generally defined as a Grade 2 or larger varicocele.

  4. There are no ‘female factors’ that would render varicocele correction futile.

One can appreciate that these indications cover virtually all the specific scenarios discussed below. Virtually all studies show that in the absence of these criteria, correction of a varicocele is unlikely to make any difference in the chances of obtaining a pregnancy. The guidelines do not recommend correction (or advise caution) if the varicocele is subclinical or there is a substantial female factor. This last element may make varicocele correction futile.

How much benefit is derived from correction of varicoceles?

When the above criteria are applied, varicocele correction improves the odds of a pregnancy by 2-4 times. (Ficarra et al Current Urology Opinion 2010).

Varicocele correction results in an improvement in semen analysis parameters in 80% of men and about 40% of couples will conceive with intercourse following varicocele correction (Marmar et al. Fertil Steril 2007).

Specific Scenarios for Varicocele Correction

The question of varicocele correction may come up in some very specific circumstances, usually in the setting of various types of assisted reproduction.

  • Men who have no sperm (azospermia) or few sperm (oligospermia = less than 20 million per mL) can benefit from correction of their varicocele. A review of all the published studies on the subject showed a clinically relevant improvement in multiple scenarios with different outcomes (Kirby et al. Fertility and Sterility November 2016). 

    The improved odds of having success following varicocele correction compared to leaving the varicocele untreated in specific groups was as follows: 

    • 1.7x improved odds of live birth in oligospermic men using IUI/IVF

    • 2.3x improved odds of live birth in azospermic men using IUI/IVF

    • 1.8x improved odds for pregnancy in oligospermic/azospermic men as a whole using IUI/IVF

    • 2.3x improved odds for prgenancy in azsopermic men

    • 8.4x improved odds of a live birth in oligospermic/azospermic men as a whole using IUI

    • 2.5x increased odds of retrieving sperm in azospermic men using testicular sperm extraction (TESE)

    Groups in which varicocele correction demonstrated questionable, limited or no benefit:

    • Varicocele correction in azospermia prior to testicular sperm extraction (TESE) before planned IVF/ICSI. The pooled analysis showed an 2.2 times improved odds ratio for live birth rate and a 2.3 times improved odds ratio for pregnancy but this was not statistically significant. One of the 2 studies did show a substantial increase in the sperm retrieval rate with TESE (53% vs. 30%, odds ratio 2.63) but there was no statistically significant difference in the fertilization rate (64% vs. 54%) or the pregnancy rate (31% vs. 22%). (Inci et al J Urology October 2009)

    • When the ICSI variant of IVF is being used, pregnancy rates, implantation and miscarriage rates do not seem to be improved by varicocele correction. (Pasqualotto et al Journal of Andology 2012)

  • By definition, couples who have conceived are considered fertile even if the pregnancy did not result in a live birth. First trimester loss (miscarriage) is a devastating event for couples. There are a myriad of causes which can be challenging to identify and treat. The question of whether treatment of a varicocele might be beneficial, even in the absence of abnormalities in the semen analysis based on WHO criteria, was addressed in this study. (Ghanaie et al Urology Journal Spring 2012) The short answer is that varicocele correction should be considered under these circumstances, even if the sperm concentration is well within normal range to start. 

    There was a 2 fold difference in the pregnancy rate - from about 20% to 40% in the year following treatment favoring those couples in which the men had their varicocele corrected. Furthermore, the probability of miscarriage was about 70% vs. 15% in the couples where the man had undergone varicocele correction. There are several issues with this study including the small number of patients in the study and these results have not been reproduced elsewhere.

  • DNA fragmentation and its measurement is a controversial subject in male infertility to say the least. Overlooking those controversies, the question of whether men with varicoceles and an increased DNA fragmentation index (DFI) might see some measurable benefit in fertility by correction of the varicocele has been asked.

    In many ways, the current data does not advance clinical management. The data for improvement in DFI and other parameters such as sperm concentration following varicocele correction is reasonably strong. (Roque et al Int Urol Nephrol 2018) The issue is that the men who underwent varicocele correction could have been selected for varicocele repair based on the 3 criteria above (infertility + large varicocele + oligospermia) without ever having done the DNA fragmentation testing in the first place. Ultimately, one would like to know if the DFI independently predicts benefit from varicocele correction even when the sperm counts are high (since we already know that doing varicocele correction with low sperm counts is beneficial). What these studies show is that one of the basic mechanisms by which varicoceles cause infertility is by injuring the DNA.

  • Adolescents may present with varicoceles. While they may not actively be attempting to achieve a pregnancy, preservation of fertility is important. Consideration to repair should be given to teenages with varicoceles grade 2 or larger associated with a significant discrepancy in testicular volume or consistency. The fact that there may be a normal discrepancy in testicular volume and consistency as a male progresses through puberty can make a decision difficult. In such cases, repeated examination every 6-12 months is warranted.

Checking for Success After Varicocele Correction

After your varicocele is treated, follow-up is required. In general:

  1. Physical examination and follow-up ultrasound to ensure satisfactory treatment

  2. Semen analysis to check for improvement in parameters. Usually done every 3 months or so following treatment until a pregnancy is achieved

A sperm takes roughly 3 months to make from scratch. As a consequence, the earliest that any beneficial effect of varicocele correction would be seen is 3 months. This is when the first semen analysis should be done. There is little improvement in results after 6 months. Therefore, if a change in strategy is being contemplated following varicocele correction (e.g. moving from IUI to IVF), this can be safely made at 6 months without concern that the semen analysis might improve further. On average, a 10 million/mL improvement in sperm concentration is expected - but results are highly variable with about 1/5 of men seeing less than 5 million/mL of improvement (this includes no improvement) and another 1/5 seeing greater than 15 million/mL improvement.

Varicocele Correction for Symptoms

Varicocele-related pain is not a common presentation. The mechanism is poorly understood that may be related to back pressure, hypoxia or compression of surrounding neural fibers by the dilated veins.

Varicocele-related pain is uncommon and therefore pain in the scrotum should not routinely be attributed to a varicocele if one is present. The vast majority of men who have varicoceles did not have any symptoms and it is thought that in a substantial number of man who had discomfort in the presence of varicoceles that the discomfort is completely unrelated to the varicocele. In short, when should not assume the varicoceles causing pain. Scrotal pain include testis tumors, fluid collections, pain following vasectomy or hernia repair, nerve entrapment syndromes, infection, referred pain from hernia or even ureteral stones. In a large number of cases the scrotal pain may not have an identifiable cause.

It’s recommended that a period of observation of at least a few months following onset of symptoms to determine if the discomfort will spontaneously resolve.

Conservative methods to address the pain can include limiting physical activities, scrotal elevation and nonsteroidal anti-inflammatory drugs. There is no known medication that can specifically help with varicocele-related pain.

Most studies demonstrate that varicocele-related pain only occurs in men with large varicoceles (grade 3) and that repair is unlikely to help unless the pain is worse with prolonged standing and is a 'dull ache'.  There are no head-to-head studies which can guide one in determining if surgery or embolization is more effective in addressing varicocele related pain. The success rates for resolution of pain following surgery averages approximately 90% for improvement in pain and 50% for complete resolution in pain (Paick et al. Review The World Journal of Men's Health 2019 January 37(1): 4-11).

There is less data on the use of varicocele embolization to treat varicocele-related pain. Sonographic resolution of the varicocele has been estimated at about 70% with improvement in pain described in roughly 90% of patients. Approximately 5% of patients could not have the procedure completed because of technical issues (Puche-Sanz et al. Andrology 014;2:716-20.)

Varicocele Correction for Hormone Dysfunction

This is only seen in the most severe cases of large varicoceles with severe testicular atrophy. Low testosterone, often accompanied by high FSH and LH, are observed. Low sperm counts are almost always present when the varicocele is severe enough to cause hormone dysfunction. The Leydig cells responsible for testosterone production are usually much more resilient than the germinal cells responsible for sperm production.

Options to Treat Varicoceles

If you have a varicocele and are not having any problems, they can usually just be left alone. Some follow-up may be appropriate in men who have not completed their family. If you meet criteria for correction, there are 2 primary options for repair. Each has it own pros and cons.

Both approaches to repair aim to correct the reflux of blood from the gonadal vein into the pampiniform plexus. They go about it in different ways.

Subinguinal microscopic varicocelectomy is considered the gold-standard for varicocele correction. The offending veins are addressed just below the external inguinal ring. Varicocele embolization address the veins in the retroperitoneum (within the abdomen). Varicocele embolization can provide excellent results in skilled hands though with a slightly higher failure rate which is more pronounced with bilateral varicoceles.

The trade off for a higher success rate for surgery is a longer recovery time (weeks rather than days). Surgery can be utilized after embolization and the opposite is also true.

  • Not all varicoceles merit treatment. The indications for correction are noted above - infertile men who meet ALL of the criteria above, pain or hormone issues.

    Varicoceles may progress over time and in men who have not completed their families, it may be prudent to follow-up with a combination of ultrasound, exam and lab testing (i.e. semen analysis).

    Some couples may also elect to forego varicocele correction even if infertility is present in order to avoid delaying IVF or other treatments.

  • A urologist performs this procedure.

    Subinguinal microscopic varicocelectomy is the most effective way to repair a varicocele because not only can it correct the veins that are the major contributors to the varicocele (the gonadal and cremasteric veins) but also can address the collateral veins to the superficial system (the gubernacular and subinguinal veins). Note that the deferential vein is left intact so that some venous drainage from the testis is preserved.

    The same approach be used both children and adults since this has the highest efficacy and best preservation of testicular function.

    Approaches that are generally inadvisable include a scrotal approach as the risk of injury to the testicular blood supply is higher. High ligation approaches are associated with an increased failure rate and are much more invasive in the subinguinal approach - the success rates are similar to embolization but with a less favorable risk profile. The inguinal approach is also associated with more pain than the subinguinal approach.

  • Gonadal vein embolization is performed by an interventional radiologist (IR).

    An IR can access the internal ‘plumbing’ of the venous system and block off the gonadal vein - usually with a combination of a metal coil (a thin wire) combined with ‘crazy glue’ (sometimes with a foam). This prevents the reflux and pooling of blood around the testis.

    Patients have a quicker recovery but the procedure is slightly less likely to be successful for unilateral varicoceles and much less likely to be successful if both sides need to be corrected.

    Embolization only addresses the gondal vein and cannot address the collateral vessels - which may not be important for smaller varicoceles. Having said that, since the gonadal veins are the main contributing factor to a varicocele, embolization will correct the majority of varicoceles.

  • Surgery and embolization share many similar risks. There are risks specific to each approach.

    Common Risks.

    1. Failure (persistence) or recurrence. Persistence occurs in 1-2% of patients after surgery and 5-10% of patients after embolization - the risk is higher for bilateral varicoceles. Recurrence occurs in 1-2% of patients.

    2. Fluid collections: hydroceles and lymphoceles. 1-2% with either approach.

    3. Numbness or pain. The nerves adjacent to the spermatic cord may be injured with surgery. Transient numbness may occur and is rarely permanent. In patients undergoing varicocele embolization, any of the 2-3 nerves which pass under the gonadal vein may be irritated by the embolized gonadal vein.

    4. Loss of the testis. Injury to the testicular (gonadal) artery. This is the most devastating complication with a risk of much less than 1%.

    Specific Risks

    1. Surgery: infection and significant bleeding are rare.

    2. Embolization. Contrast reaction or hematoma at the puncture site.