Variococeles and Male Infertility
Introduction to Varicoceles and Their Potential Impact on Sperm Quality
Varicoceles, or abnormally dilated veins in the scrotum, are quite common in the general population, with studies showing them to be present in 5 to 25 percent of all men. Although the majority of these varicoceles are not clinically significant, they are one of the leading causes of male-factor infertility—about 20 to 40 percent of men with infertility issues have varicoceles.
Several factors can play a role in the development of varicoceles, including the smooth muscle content of the walls of the scrotal veins, how effectively the one-way venous valves are functioning, and increased pressure within the veins (because of their anatomic position).
Most varicoceles are small and do not cause problems with fertility: 80–85 percent of men with varicoceles experience no problems with conceiving children. However, if the veins get large enough, then the pooling of blood in these dilated vessels can interfere with the normal heat exchange mechanisms of the body which normally help to keep the testicles two to three degrees cooler than the rest of the body. The resulting elevations in scrotal temperature over time can lead to decreased sperm production and quality, low testosterone levels, decreased testicular size, elevated levels of sperm DNA fragmentation, and increased oxidative stress. [Clavijo, RI. FertSteril 2017]
A few important points to remember about varicoceles
1) Varicoceles typically first show up during adolescence. It is possible, in rare circumstances, that certain activities (like extreme powerlifting, which increases intra-abdominal pressures) can increase the chance of developing varicoceles. Typically, however, varicoceles are something that some men were born with a propensity to develop, and they are not a result of lifestyle choices or activities. Varicoceles can occasionally run in families.
2) Varicoceles can cause a progressive decrease in sperm counts over time, due to the progressive heat damage. Therefore, varicoceles are the most common cause of what is called secondary infertility. This is where a couple has progressively worsening problems with conceiving children over time.
3) Typically the larger the varicocele, the higher the chance of it causing fertility-related problems. Large varicoceles are not always associated with the presence of abnormal semen parameters, although these men are at an increased risk of developing fertility problems with time and should be followed closely if they wish to have further children.
4) A varicocele on one side can impact sperm production on both sides.
5) Varicoceles that are having a negative effect on sperm production are often associated with decreased testicular volumes on at least one side (although, as noted above, the effect on sperm production can impact both testicles).
6) Because of the structure of the venous system, varicoceles are more commonly found on the left side. Approximately 80–90 percent of men with varicoceles have them on the left side only, with the rest having them on both sides. If they are found on both sides (bilateral varicoceles), then the left-sided varicocele is usually larger.
In the past if only a right sided varicoceles were present (or bilateral varicoceles where the right side was larger) then there was a concern that an intra-abdominal mass may be present. Traditionally, abdominal imaging (such as CT or ultrasound) was recommended in these circumstances. These recommendations have changed over the years due to the very low probability of serious intra-abdominal pathology causing a right sided varicocele in the absence of other related symptoms. An example of this was a study of 4000 men with varicoceles, 8% of which were only on the right hand side. There was no difference in cancer diagnoses in these men. [DeWitt EM. Urol 2018] Therefore, otherwise asymptomatic men with isolated right sided varicoceles (or where the right side is larger than the left) do not warrant routine imaging. [Schlegal PN. FertSteril 2021] Imaging may be considered for new onset right varicoceles of if they are not reducible, especially if they are of large size.
7) Most varicoceles are completely asymptomatic, but in a minority of patients (2-10%) they can be associated with a dull aching discomfort or a dragging sensation in the scrotum. This discomfort tends to worsen after the man that gets worse with physical exertion and improves when he lies down. [Peterson AC. JUrol 1998]
Diagnosis of Varicoceles
Size matters with varicoceles. Small varicoceles are typically not considered to be clinically significant, but larger ones can be. Varicoceles are most commonly diagnosed in one of two ways: either by physical examination of the scrotum or by ultrasound imaging. An important rule for diagnosing varicoceles accurately is that the man must be in the standing position, both for physical exam and for any ultrasound evaluation. When a man lies down, the varicoceles tend to collapse (and therefore appear smaller on palpation and imaging) since the downward pressure exerted on them by gravity is decreased.
Physical Exam
With the man standing, the doctor palpates the spermatic cord structures above the testicles in the scrotum, to feel for dilation of the veins. During the exam the man can be asked to perform a Valsalva maneuver (it’s usually done by closing the mouth and pinching the nose shut, then trying to exhale), which increases the pressure in his abdominal area. If a varicocele is present, this increase in abdominal pressure can typically be felt as an “impulse” or bump against the examiner’s fingers, which are around the scrotal veins. [Clavijo, RI. FertSteril 2017]
(It is worth noting that every so often, a man can feel light-headed during the scrotal evaluation. This is due to a vasovagal response—essentially, the parasympathetic nerves in the scrotum are activated, causing the veins in the legs to dilate and blood to pool there. If this occurs, the exam should be stopped and the man should lie down. A drink of water and a damp, cold towel on the head often help.)
Varicocele Grading System
Varicoceles are assigned a grade by the physician doing the exam:
Subclinical: the varicocele cannot be felt on physical exam, and is only seen on ultrasound
Grade 1: an impulse can be felt during the Valsalva maneuver, but there are no veins that feel dilated on examination
Grade 2: scrotal veins feel dilated on examination.
Grade 3: scrotal veins are so dilated that they can be seen through the scrotal skin with visual inspection, and typically feel like a “bag of worms” on physical examination
Subclinical and Grade 1 varicoceles are usually not thought to be clinically significant (only minimal potential improvements with treatment), whereas Grade 2 and 3 varicoceles can adversely affect semen parameters. [Asafu-Adjei D. JUrol 2020]
Ultrasound
Most men with varicoceles are fine with just a physical exam and do not need to have scrotal ultrasonography. Grade 1 varicoceles on exam are clinicially insignificant and do not need further imaging. Grade 3 varicoceles are of clinicially significant size no matter what an ultrasound subsequently finds. I reserve scrotal ultrasounds for men with grade 2 varicoceles to see if the dilated veins are of clinically significant size (see below for further details on how this size is defined).
While the man is standing, the scrotal veins are evaluated in two ways. First, the diameter of the largest veins is measured. Second, while the man performs the Valsalva maneuver, the ultrasonographer looks for reversal of blood flow within the scrotal veins (consistent with faulty valve functioning).
The classic definition of the presence of a varicocele by ultrasound is a vein 3 mm or greater in diameter that shows reversal of blood flow by Doppler. I personally feel that a vein between 3.0 and 3.5 mm in size is consistent with a subclinical varicocele, one that cannot be felt on physical exam. Since larger varicoceles tend to have a larger impact on fertility, I feel that only dilated veins larger than 3.5 mm in size are likely to be clinically significant. When reversal of flow is seen in these veins with a Valsalva maneuver, it provides further evidence of the presence of a varicocele. Reversed blood flow is sometimes seen in dilated veins that are not of clinically significant size. When a large dilated vein (greater than 3.5 mm in diameter) is seen but the ultrasound shows no reversal of blood flow, I usually consider that to be clinically significant (as long as the vein is not clotted off, or thrombosed). This is because sometimes the Valsalva maneuver is not performed effectively during the ultrasound.
My definition of what I would consider to be a clinically significant varicocele by ultrasound is controversial. Many experts in the field consider any dilated vein 3.0 mm or larger in size that shows reversal of flow with Valsalva a clinically significant varicocele. Clinical studies have certainly shown significant improvements in semen parameters in men treated for varicoceles using the 3mm criteria. One such study showed improvements in sperm count from 28.3 to 37.1 million sperm/cc with motilities improving from 44.3% to 50.9%. [Punjani N. JUrol 2021]. However, these were not all 3.0mm varicoceles and invariably there were much larger varicoceles included in the treatment group. Not all varicocele repairs results in improved semen parameters, it is an invasive procedure, and the results can take 6+ months to be evident. If a couple is going to make the investment in time and money for a varicocele repair, I think that it is important that the potential improvements in semen parameters be worthwhile. If a man’s total motile count improves from 2 million to 4 million, then he has had a 100% increase in his numbers, but it still does not change the fact that he is probably still going to need IVF. Since larger varicoceles have the potential for bigger improvements in sperm counts and motility, I generally like to see standing varicocele sizes larger than 3.5mm for a recommendation to potentially treat.
Practical Tips for Diagnosing Varicoceles
As mentioned above, a physical exam is all you need if there is no palpable varicocele or a grade 1 or grade 3 varicocele. However, if a grade 2 varicocele is found, then I typically like to have the man get an ultrasound to check its size. Again, this is controversial, with some experts relying only on the physical exam in order to decide whether to treat varicoceles in the grade 2 size range. However, an interesting study published in 2014 found that when multiple urologists performed a physical exam on men with varicoceles, there was a 25 percent discrepancy in the grade of varicocele they thought that patient had. Thus, the grade a varicocele is assigned depends on who is doing the assessment. I prefer to use ultrasound, as I think it provides more objective measurement data for men with midsized varicoceles, helping inform treatment decisions.
If a good physical exam cannot be performed, then I recommend having an ultrasound. Reasons for an inconclusive physical exam include significant discomfort during examination, a vasovagal response (light-headedness) before the evaluation can be completed, and body structure reasons (e.g., a large hydrocele, extreme obesity).
Should A Varicocele Be Treated?
The treatment of varicoceles is a very controversial topic in the field of infertility. A review of the existing literature will yield a number of articles concluding that treating varicoceles has no impact whatsoever on improving male fertility, and a number of other articles that support treating them. However, it must be remembered that varicoceles have been recognized as a cause of decreased sperm production for hundreds of years, and a large number of studies have been performed over the past fifty years looking at various ways of treating varicoceles. Many of the review articles that have been published include outcomes for varicocele treatment techniques that are outdated and not very effective, or include large numbers of patients who were treated for clinically insignificant (subclinical or grade 1) varicoceles. After evaluating only the latest clinical data, both the American Urological Association and American Society of Reproductive Medicine concluded that treatment of varicoceles should be offered to infertile men with palpable lesions (grade 2 or 3) and abnormalities in their semen parameters. I personally agree that a varicocele repair can play an important role in restoring fertility to some couples, but I also think it is not necessary for the majority of men with varicoceles. I take into account overall semen parameters, the size of the varicocele, the age of the man’s partner, and any female-factor fertility issues to see if a varicocele repair is in the couple’s best interest from a fertility standpoint.
The minimum requirements to consider treatment of a varicocele (need all 3)
1) Clinically significant size (grade 2 or 3, or veins larger than 3.5 mm by ultrasound)
2) Abnormal semen parameters
3) Normal female fertility evaluation, or no irreversible problems
If the semen parameters are completely normal, then in most cases I do not think treatment of a varicocele is indicated. Possible exceptions to this include suspected varicocele-related scrotal pain or abnormal sperm DNA fragmentation (see below).
Another controversial area involves patients with varicoceles who have a sperm morphology abnormality (isolated teratospermia) but normal sperm counts and motility (isolated teratospermia). Since varicoceles seem to have a larger impact on sperm counts and motility, the American Society of Reproductive Medicine’s Practice Committee has issued guidelines suggesting that varicoceles of clinically significant size should not be treated in men who have isolated teratospermia.
Chances of Improved Semen Parameters After Varicocele Treatment
If a man has abnormal semen parameters and a varicocele of clinically significant size, then there is an approximately 65–70 percent chance of a significant improvement in sperm counts and motility if the varicocele is treated. As a general rule, the larger the size of the varicocele, the higher the chance of seeing improvements with treatment. If a man has a borderline-sized varicocele (for example, 3.5 mm) and associated testicular atrophy on that side, then I typically quote him a 50 percent chance of improved sperm count and motility with varicocele treatment.
A 65 to 70 percent chance of improved sperm count and quality is pretty good, but these statistics must be balanced with a couple of other considerations. One is that the treatment of varicoceles involves an invasive procedure (see below) requiring some degree of anesthesia. The second is that although improvements in semen parameters can be seen as early as three months after the repair is done, the average time to see significant improvements is 5-6 months (and it can take 12+ months in some circumstances).
Factors to consider when trying to decide whether to repair a varicocele
1) How long a couple has been trying to conceive. If a couple has been working on trying to have a baby for over a year, they may not want to wait another six to twelve months to see if a varicocele repair is going to work.
2) The age of the woman. If she is older (approaching forty or beyond), the average five-to-six month delay before seeing improvement in semen parameters becomes an even more important consideration.
3) Sperm counts can go down before they go back up. When a varicocele is treated, the result is increased inflammation in the area which often results in transient decreases in semen parameters before they later rebound. Therefore if a couple is planning on doing an IUI or IVF cycle in the near future, they should postpone treatment of their varicocele until they are done with their treatments from the female side.
4) The baseline semen parameters. If the sperm density if very low to start with, then treatment of the varicocele may not have a clinically significant impact, even if it is successful. For example, a couple with a very low sperm count may still need IVF despite improvement in the semen parameters (i.e. sperm counts and motility may rise after varicocele treatment, but not to the point where the couple is now a candidate for IUI, and can avoid IVF).
How Much Improvement Is Typically Seen with a Successful Varicocele Repair
Technically (according to the literature), a successful procedure is described as one that leads to at least a 50 percent increase in sperm count and quality, although I have regularly seen much higher levels of improvement in some men. In general, if the varicocele is bigger, then the improvements tend to be larger after repair, though this is not always the case. Review articles report an average overall increase in sperm density of about 10–12 million sperm per cc, an 11 percent improvement in motility, and a variable impact on morphology. However, what we can expect in terms of improvement does tend to correlate with baseline semen parameters. To take an example, if a man has a pre-treatment total motile count (TMC) of 6 million sperm, then treatment of a clinically significant varicocele would have a decent chance of getting his TMC to above 10 million making him a potential candidate for IUI. However, if a man is starting out with a TMC of <1 million, then the odds of getting his TMC count to the point where IUI is an option is quite low.
Virtual Azoospermia
Men with virtual azoospermia typically have a small number of sperm in the ejaculate, less than 100,000 per cc (see “Virtual Azoospermia” section). Sometimes men with virtual azoospermia do not have enough sperm to even comfortably proceed with IVF/ICSI because the lab is concerned that they will not be able to find enough viable sperm to inject all of the eggs (typically 5 to 20 egg are retrieved, so this many live sperm are needed). In these circumstances, getting enough sperm for intrauterine insemination (IUI) following a varicocele repair is not a reasonable expectation. For men with virtual azoospermia, successful varicocele treatment would be defined as having a great enough improvement in sperm counts to comfortably allow for IVF/ICSI.
Azoospermia
In complete azoospermia (where there is no sperm in the ejaculate), repair of a significant varicocele can sometimes result in the return of some sperm to the ejaculate. If no genetic abnormalities are found (such as Y chromosome microdeletion or karyotype abnormalities), the literature has reports of a wide range of results, with some studies reporting rates of sperm return as high as 43% but there were questions regarding the patient population. [Esteves SC. AsJAndrol 2016] However, most clinicians feel that the success rates are much lower for any usable sperm returning in men with true NOA after varicocele repair. [Lipshultz LL. FertSteril 2019]. In my experience you can expect sperm to return in <5-10% of NOA men following varicocele repair. The official 2020 AUA/ASRM guidelines recommend that varicocele repair should not be expected to have usable sperm return to the ejaculate, but the success of subsequent microTESE procedures may be higher in men who have had a clinically significant varicocele treated beforehand. [Farooq S. AUAUpdate 2022]. Those who do see some sperm return usually have an average post-treatment sperm density in the range of 1–2 million sperm per cc, so IVF/ICSI would still need to be used. (see “Azoospermia” section for more information on microTESE).
If a man with virtual or complete azoospermia has had a successful varicocele repair and sees significant improvements in semen parameters, I strongly recommend that he promptly freeze several semen specimens, as (for unclear reasons) many of these men will eventually go back to having lower (or absent) sperm counts with time. The time it takes for this regression to occur can range from a few months up to several years.
Suggestions for Managing Significant Varicoceles
The decision whether to treat a clinically significant varicocele should be made while looking at the couple as a whole. The first step is to see how much improvement in semen parameters can be made through non-invasive means (e.g., hormonal treatments, lifestyle changes, supplements, etc.). If semen abnormalities are still present following these conservative measures, then the decision about treatment can be made based upon the wishes of the couple as well as the starting sperm count:
Virtual azoospermia and azoospermia
If there are so few sperm that IVF is not even an option, then treating a varicocele is probably a good idea, as long as the couple is able and willing to have IVF (and if genetic testing of the man reveals no genetic abnormalities). The goal would be to get enough sperm to be able to proceed with IVF using ejaculated sperm. Of course, other factors can play a role as well such as female age. If an azoospermic man with large varicoceles has a wife who is 40 years old, they may be best served by proceeding straight to microTESE and avoid the long delays often associated with waiting for repeat semen analysis testing following varicocele repair.
Oligospermia with total motile count under 10 million sperm
With a total motile count of less than 10 million, there are plenty of sperm for IVF but probably not enough to be useful for IUI. If the couple would like to avoid IVF if possible and wants to pursue IUI, then treatment of the varicocele would be reasonable. Again, other factors such as female age should help play a role in making these types of decisions.
A common approach that I often recommend for couple who have been trying to conceive for a long time (and who want more than one child) is to proceed with IVF now, and once the woman is pregnant and through her first trimester, then the man could get his varicocele repaired. If it takes six to twelve months to see full improvement, that is not a problem, since the woman will be pregnant through most of that time, and potentially the next child could then be conceived through IUI or natural intercourse. [Samplaski MK. FertSteril 2017]
Oligospermia with total motile count over 10 million sperm
With a slightly higher count, this can be a tough decision. If immediate IUI is successful, then treatment of the varicocele may not be necessary. However, IUI has a higher chance of success with increased sperm count and quality—but it can take six to twelve months to see that improvement, with a 30 to 35 percent chance that the couple waits that long and no improvement even occurs. There is no correct answer here.
As mentioned before, most couples I am seeing have already been trying to conceive for over a year, so it makes sense to consider proceeding with treatments from the female side (IUI or IVF). Then once the woman is pregnant, elective varicocele repair can be undertaken if the couple wants more children, in the hopes that the next child may be conceived naturally or more easily.
INSURANCE COVERAGE OF VARICOCELE REPAIRS
Varicocele repairs are one of the few fertility treatments that are often (but not always) covered by insurance. Of course, regulations for coverage vary from state to state, as well as between different insurance companies and policies. Check with your insurance company prior to proceeding with treatment.
Diagnosis codes that can be used for varicocele treatment:
Diagnosis ICD-10
Varicocele I86.1
Testicular atrophy N50.0
Scrotal pain N50.9 and R10.2
Surgery procedure codes that can be used for varicocele treatment:
Varicocelectomy: 55530
Use of operating microscope: 69990
Embolization procedure codes that can be used for varicocele treatment:
Vascular catheter placement: 36011 and 36012
Vascular embolization for varicocele: 37241
Note that in some states insurance coverage for fertility is limited, but treatment of varicoceles for scrotal pain is often covered.
Management of Future Fertility if a Varicocele Is Not Treated
Many couples will achieve a pregnancy (either naturally or through IUI or IVF) without treating a clinically significant varicocele. If the couple would like to have more children in the future, they have the option of either treating the varicocele while the woman is pregnant or just observing the varicocele. The potential advantage of treating the varicocele electively while the woman is pregnant is that the next pregnancy might be easier to establish. However, given that a pregnancy was achieved the first time, the varicocele might not need to be treated. One point to consider regarding untreated varicoceles is that varicoceles can be associated with a progressive decrease in sperm counts and quality over time. I therefore recommend that when a man with a significant varicocele wants more children, he should get a semen analysis every 1-2 years to make sure that his numbers are not decreasing significantly over time.
Treatment Options for Varicoceles
There are two main techniques for treating varicoceles: surgical repair (varicocelectomy) and embolization (clotting the veins off using a minimally invasive approach). [Johnson D. FertSteril 2017][Pagani RL. FertSteril 2019]
Surgical Repair
The goal of varicocelectomy surgery is to tie off or clip the dilated veins, which then scar down over time. The remaining smaller, non-dilated surrounding veins effectively drain away the blood from the testicles, so there is no concern about blocking all blood flow from the scrotum.
Varicocelectomy procedures are considered minor surgery and are typically performed under general anesthesia on an outpatient basis. Most people are off work for five to seven days, though this period of time may be shorter for people with exclusively desk jobs, or longer for people whose jobs require more strenuous activity (construction, law enforcement, firefighting, etc.).
Keys to a Successful Surgery
1) Adequate visualization of the veins. Ideally, an operating microscope is used to minimize the chance that significant veins are missed, which can increase the risk that the varicocele will persist or recur.
2) Preservation of the arterial blood supply. Only veins should be ligated (that is, clipped or tied). It is very important that the arterial blood supply of the testicle be maintained, or else testicular damage and atrophy can occur. The use of an intraoperative Doppler probe can effectively distinguish which vessels are veins and which are arteries.
3) Preservation of the vas deferens. This structure must be carefully identified and not damaged, as it carries the sperm from the testicle to the penis.
4) Preservation of lymphatic vessels. These small, delicate vessels have a characteristic translucent appearance under the operating microscope. Lymphatic channels should be preserved to decrease the risk of developing a significant hydrocele (a collection of fluid around the testicle that might require surgical drainage if it gets large enough).
Microscopic Inguinal or Subinguinal Varicocelectomy
The best surgical technique for treating varicoceles in adults is the inguinal or subinguinal microscopic varicocelectomy. In this technique, the spermatic cord (which contains the dilated veins) is approached through a small incision in the inguinal (groin) area. The inguinal ring is where the spermatic cord emerges from the abdomen into the scrotum. Incisions placed either at the inguinal ring (inguinal) or just below the ring (subinguinal) are effective, providing good access to the various veins that can branch off from the main testicular veins in this area. The inguinal approach tends to be associated with somewhat increased pain and longer recovery times, as opposed to the subinguinal technique. In both approaches, the dilated veins are identified and either tied off with permanent sutures or ligated with surgical clips, while the vas deferens, lymphatic channels, and arteries are identified and preserved.
Potential Complications of Varicocelectomy Procedures
1) Hydrocele. A hydrocele—a collection of fluid around the testicle that might require surgical draining—occurs in only 1 percent of cases when microsurgery is employed, versus 7 percent when an operating microscope is not used. Fifty percent of hydroceles grow to a size large enough to eventually require an outpatient surgical treatment for drainage (called hydrocelectomy).
2) Recurrence of the varicocele. Rates of recurrence of the varicocele in the surrounding veins range from 0 to 35 percent. Lower rates (around 1 to 2 percent) are seen with microscopic techniques using either the subinguinal or inguinal approach.
3) Testicular artery injury. Seen in approximately 1 percent of cases, this can lead to testicular atrophy and loss of function.
Other Varicocele Surgical Techniques
Several other surgical approaches used for varicocelectomy exist but are not typically used in adults by male fertility specialists. These include:
1) Open retroperitoneal (Ivanessevich) approach. This is an older surgical technique that accesses the testicular veins higher in the abdominal region. The problem with this approach is that it misses many of the lower venous branch points (external iliac branches) that are found in the inguinal (groin) region. Therefore, rates of persistent or recurrent varicoceles are much higher. These techniques are also typically not performed using operating microscopes, which increases the risk of complications such as hydroceles.
2) Laparascopic approach. A laparoscope is used to locate and clip off the dilated veins high up in the abdomen near the kidneys. This approach is more common in young children, in whom the inguinal vessels are much smaller and therefore harder to accurately visualize even with an operating microscope (and therefore the risk of arterial blood supply injury is greater). When used in adults, however, the laparoscopic approach has the same drawbacks as the open retroperitoneal approach in that the lower venous (external iliac) branches are not addressed, leading to a potentially higher recurrence rate. Rates of post-procedure hydroceles are low, but the laparoscopic approach through the abdomen does present the small but possible risk of intestinal or major vascular injuries.
Conclusion: when assessing potential urologists to use for the treatment of varicoceles, I would recommend finding one who utilizes an operating microscope and does an open inguinal or subinguinal approach. This will generally result in better outcomes and fewer complications for patients.
Varicocele Embolization
Embolization of varicoceles is a minimally invasive procedure performed by an interventional radiologist (a radiologist who specializes in doing procedures under X-ray imaging guidance). Embolizations are typically performed under IV sedation, in which the patient is made drowsy and essentially sleeps while the procedure is performed. To perform the embolization, the interventional radiologist gains access to the venous system with a needle stick, typically in either the upper leg or neck region. A special small catheter is then placed into the venous system and guided to the area of the dilated veins under X-ray guidance. The dilated veins are then embolized (clotted off), typically using small metal coils or other embolic materials.
The success of embolization must be assessed in three ways:
1) Technical success. Was the procedure successful in gaining access to the correct veins and effectively clotting them off?
2) Clinical success. In men in whom the veins were successfully treated, what was the impact on their fertility parameters?
3) Recurrence rate. What is the rate of varicocele recurrences, which can increase the risk of persistent fertility problems?
Technical Success
The internal spermatic (testicular) veins are the targets of the embolization procedure, and their anatomy differs between the left and right sides. On the left side, the internal spermatic vein typically comes off straight down (at a 90° angle) from the left renal vein, while on the right side the vein comes off at a sharper (more acute) angle from the vena cava. Because of this sharper angle, the spermatic veins on the right side are more difficult to access than those on the left side. Some radiologists feel that if a neck vein instead of a leg vein is used, the right side might be easier to get access to, coming at it from above instead of from below. Each radiologist has his or her personal preference regarding the best approach to use. In general, however, the rate of failure (that is, failure to gain access) is 3–5 percent on the left side and 15–20 percent on the right side. Most significant varicoceles are on the left, but large right varicoceles may be more difficult to treat with embolization in some cases.
Clinical Success
If the dilated veins are successfully embolized, then success rates in terms of fertility improvement are generally in the same range as those of surgical varicocele repair, with about 65–70 percent of patients experiencing significant improvement in sperm counts and quality.
Recurrence Rates
Rates of recurrence are felt to be higher with embolization than with surgical repair. This, however, does seem to be related to the type of embolization material that is used. Two primary types of techniques can be used: liquid sclerosing agents or specially designed embolic devices.
Sclerosing agents (e.g., sodium tetradecyl sulfate, polydocanol, dextrose solution) are injected into the internal spermatic veins and cause the veins to scar down. Late recurrence rates (significant varicoceles which return after an extended period of time following treatment) with sclerosing agents are 1–2 percent. The advantage of sclerosing agents is that they can be delivered through smaller veins that can be difficult to maneuver a small catheter into. The sclerosing agents can also enter into nearby smaller collateral veins that are connected to the main spermatic veins, thereby causing these smaller vessels to scar down and preventing them from dilating later and resulting in a recurrent varicocele. One disadvantage of sclerosing agents, however, is that they can be associated with more procedure-related discomfort than embolic devices, including thrombophlebitis (vein inflammation related to a blood clot).
There are two primary types of embolic devices, and both have a late recurrence rate of about 10 percent. Embolic coils can be released into the veins, where they expand and clot off the vein. The clotted-off vein eventually scars down over time. Detachable balloons can also be released into the veins, where they lodge and cause clotting off of the vein and eventual scar tissue formation.
Complications
The overall complication rate for varicocele embolization is about 10 percent. Most complications are minor, transient, and do not require treatment. However, there are several rare types of serious complications, including those that can result from the sclerosing or embolic agent accidentally traveling to other areas of the body.
Potential complications include:
1) Problems with venous access leading to bleeding or damage to nearby structures (less than 1 percent): pneumothorax or mediastinal hematoma with the neck (jugular) approach, and groin hematoma with the leg (femoral) approach
2) Severe allergic reactions to the contrast medium used (less than 1 percent)
3) Pulmonary embolism due to agent migration (less than 2 percent)
4) Renal vein thrombosis (less than 1 percent)
5) Testicular atrophy due to thrombophlebitis (less than 1 percent): the risk of this is higher with use of sclerosing agents than with embolic devices
Potential Advantages of Embolization
Compared to surgical repair, embolization has several potential advantages:
1) Minimally invasive procedure. Embolization involves only venous access (a needle stick) instead of an incision. Therefore, men typically only have to take one or two days off after the procedure instead of the five to seven days necessary with open surgery. They can usually return to full physical activity four to seven days after embolization, compared to two to three weeks with surgery. Generally, men experience a dull ache in the groin or back that last a few days. Less than 5 percent of men undergoing embolization experience more severe pain requiring analgesics or anti-inflammatory medications; if present, this pain can last an average of two days.
2) Less anesthesia needed. IV sedation is usually adequate for embolization, instead of the full general anesthesia needed for surgery.
3) Potentially faster time to improved semen parameters with a successful procedure. The minimally invasive embolization procedure is typically associated with less physiologic stress on the body, and there is evidence that in some men sperm counts and sperm quality may rebound faster than with open surgical repair.
4) No risk of damage to the testicular blood supply. Embolization procedures stay within the venous system, and therefore inadvertent damage to the arterial blood supply of the testicle is not a concern.
Potential Disadvantages of Embolization
Embolization also has some potential disadvantages when compared to surgical repair:
1) Inability to gain adequate venous access. Due to variations in venous anatomy, about 10 percent of the time (3–5 percent on the left and 15–20 percent on the right), the interventional radiologist cannot get the specially designed catheter to the dilated testicular veins that need to be treated.
2) Recurrence rates. Rates of recurrent varicoceles can be higher with embolization, as the lower venous channels (external spermatic veins) may not be treated as effectively, especially if sclerosing agents are not used. Overall, with embolization the rates of recurrence are still quite low (1–10 percent), but they are higher than the rates with microsurgical varicocelectomy procedures (1–2 percent).
3) Potential migration of embolic material. The chance that a coil, balloon, or sclerosing agent will migrate a significant distance away from where it is inserted is low (less than 1–2 percent), but if this migration occurs, it can have potentially severe consequences. Some people have concerns about coils becoming dislodged and traveling to other parts of the body years down the road. However, the risk for migration is generally present only at the time of the procedure. Once the coils or balloons are in place, the veins scar down, thereby entrapping the clips in the area, so that they generally cannot move.
Optimizing Success with Embolization
One of the keys to success with varicocele embolization is working with an interventional radiologist who routinely performs these procedures. If you are working with a male fertility specialist, he or she should know the names of nearby interventional radiologists who are good at the procedure. Otherwise, you can call a large interventional radiology group and ask them which doctor in their group performs the most varicocele embolization procedures. Ask the interventional radiologist how many varicocele embolizations he or she performs each year. If you live in a fairly big town and the radiologist does at least a few a month, then he or she is probably fairly well experienced. If you work with an interventional radiologist who rarely performs these procedures, you may have a higher chance of an unsuccessful treatment outcome or complications.
Other Potential Health and Fertility Concerns Associated with Varicoceles
Varicoceles and DNA Fragmentation
Clinically significant varicoceles have been associated with elevated levels of DNA fragmentation in some men. Varicocele repair has been associated with improvements in sperm DNA fragmentation in up to 90 percent of men, although the degree of improvement was quite modest in most studies. One study showed a 14% improvement in the sperm DNA fragmentation index (DFI) [from 35 percent to 30 percent] in a group of men following varicocele repair, and another showed a 25 percent decrease in DFI by three to six months after the repair.
See the "Advanced Sperm Testing" section of this website for more information on DNA fragmentation.
Varicoceles and Hypogonadism
In addition to changes in their sperm production, men with clinically significant varicoceles have been shown to have lower testosterone levels. In general, the Leydig cells, which make testosterone, are more resistant to damage than the spermatogenic cells, but if the varicocele is large enough, then testosterone levels may be impacted as well. Several studies have shown improvements in testosterone levels in men undergoing varicocele repair for fertility problems. One meta-analysis showed that testosterone levels rose by an average of 87.5 ng/dL following varicocele repair. Another study showed that increases in testosterone were generally higher in men with larger and bilateral varicoceles. For example, in men with bilateral large (grade 3) varicoceles, 86 percent of them showed improvement, with an average testosterone increase of 160 ng/dL. In contrast, in men with only a left-sided, moderate-sized (grade 2) varicocele, 73 percent showed an elevation of testosterone, with an average rise of 103 ng/dL.
It is therefore widely believed that in men with hypogonadism and fertility problems, treatment of a clinically significant varicocele can improve both semen parameters and testosterone levels. However, what remains controversial is the treatment of men with varicoceles who do not have any fertility problems, in an attempt to treat or prevent hypogonadism. A few centers in the country currently treat varicoceles in men with low testosterone and no fertility problems. A potential advantage of this approach is the hope that the man can increase his own endogenous testosterone production and not have to rely on medications to increase testosterone levels.
To date, most urologists do not feel that the scientific evidence is compelling enough to offer invasive varicocele treatment solely for the reason of treating low testosterone levels, although this opinion seems to be slowly evolving with time, with more clinicians considering taking a more aggressive approach. [Lipshultz LI. FertSteril 2019]