Varicocele and male infertility – diagnosis and prospects

In this session, Arie Parnham, MBChB, FRCS (Urol), urologist and a national expert in surgery for penile cancer, Consultant Urologist & Andrologist at The Christie NHS Foundation Trust. Mr Parnham has discussed varicocele, diagnosis, symptoms, and treatment options. Varicocele is in the scrotum and the cord, which supplies blood to and from the testis itself. It’s in the veins that take away the blood from the testis. Why does it happen? Essentially, normal veins have valves that ensure that your blood flow continues in one direction, but in people with varicose veins or varicocele, those valves that ensure that one-way direction do not operate as they should. As a consequence, you get a pooling of blood. How common are varicose veins? About 1 in 7 men will have a varicocele, and around 1 in 4 men with a varicocele will have some degree of infertility. Therefore, around 40% of infertile men will have a varicocele, so it is something that is associated with infertility.

Varicocele – diagnosis

How do you diagnose a varicocele? There are many ways of checking it, starting with a subclinical examination, they should look at your testes, and they will look for a varicocele. There are lots of different ways to look for varicocele. It’s possible to grade them to some degree. For instance, varicocele can be subclinical, it has to be found during an ultrasound scan. You can have grade 1, and you can feel the varicocele, but only during special manoeuvres called a Valsalva manoeuvre. Then there’s grade 2, and those are the ones that are palpable at rest. The grade is a visible varicocele, and you don’t need to do anything, you can see it without touching it.

The slight problem with examination is that if you go to one doctor, he may say that he feels something and then you might go to another doctor who does the same thing and say that he is not convinced. If it’s visible, then it’s visible, that’s quite easy, but the ones with a grade 1 or maybe even grade 2 where you get a bit of discrepancy, and people struggle. Therefore, the best thing to do is to get an ultrasound scan where the parameters can be measured and checked.

The EAU (European Association of Urology) Guidelines classify as a varicocele a maximum diameter of more than 3 millimetres in the upright position. In other words, standing during the Valsalva manoeuvre with some reflux (the blood is going the wrong way) for more than 2 seconds. An ultrasound scan is a bit more accurate than an examination. If there’s a suspicion of a varicocele, an ultrasound scan would be advised, and it should be done by someone who’s used to scanning testes and looking for varicocele and would do something similar to what’s described in EAU guidelines.

Varicocele – male fertility

Varicocele are associated with certain things, for instance, they’re associated with male subfertility or problems with fertility in men. They are also associated with people whose testicles didn’t grow, they go through adolescence or puberty, but their testicles have failed to grow, so they haven’t developed quite as they should. Varicocele can cause some pain and discomfort, and often that pain is kind of a dull, dragging, heavy sensation. It’s also associated with low testosterone levels. Men who undergo an infertility investigation will have a semen analysis and if you’ve identified to have an abnormal semen analysis and you’ve got a low sperm count, then that may be improved by removing varicocele. There were 15 studies put together, reported in one of the papers, that looked at men who’ve got azoospermia with palpable varicocele. They performed surgery on them to correct their varicocele, and then they looked to see if they can find sperm in the ejaculate whereas previously they didn’t have any actually in this 45% of men or roughly about 43.9% of men, ended up having sperm within the ejaculate at a later date and that sperm could then be used for IVF or ICSI. The success rates for that were around 15%. Another study looked at men with no sperm when they were ejaculating and had a palpable varicocele. In this study, they compared people who had a varicocele repair versus those that didn’t have a varicocele repair. One group had surgery on their testes that were opened to see if they could pick out sperm, the success rate in finding sperm in these patients was better than in those who hadn’t had a varicocele repair. It was 60% versus 40%, and the live birth rates were better, 75% versus 50%. This shows that a varicocele might help in people who’ve got low sperm counts, and even maybe in those people who have no sperm in the ejaculate. Another thing worth mentioning is DNA Fragmentation. One of the studies was performed on 41 patients who had high DNA fragmentation, and then they looked at their chances of IVF and ICSI. They found that with IVF those that had high DNA fragmentation had a reduced chance of IVF at 1.92 and those with ICSI less successful at 1.49. Therefore, if you have DNA damage, your chances of IVF or IVF success are reduced. What’s that got to do with varicocele? Another study compared men who have got varicocele and those that didn’t. They looked at 55 patients with clinical varicocele. They found that those patients who had a clinical varicocele had a higher DNA fragmentation rate than those who didn’t have a varicocele, at 5 to 10% versus 35%. Having a varicocele means that you’re more likely to have a higher DNA fragmentation rate. That suggests that if a varicocele repair is performed, your DNA fragmentation can also be improved. One more study looked at 37 men who underwent a microsurgical varicocelectomy. They looked at their DNA fragmentation, and they found that it went from around 30% and it improved to about 25%. They had reduced DNA fragmentation after their microsurgical varicocele.

Varicocele – treatment options

There are 2 options to treat varicocele. The first is to perform surgery, and the other is to have a radiological procedure called embolization. Surgical options involve cutting some way and then using either a camera put into the amp into the tummy to kind of find the veins and tie them off and sometimes using a microscope to identify the dilated veins or the varicocele and then tying those abnormal veins off. There are also different surgical approaches, there is a scrotal approach which is going through the scrotum, the inguinal approach, which means going in the groin, Open Retroperitoneal high ligation, which goes a bit higher, laparoscopic which is a keyhole and then Microsurgical subinguinal, which is probably a gold standard of surgical options. This has got the best results in terms of the surgical option. The radiological options are also Antegrade sclerotherapy and Retrograde sclerotherapy and the other option is retrograde Embolisation, which is the gold standard and is most often performed. In a radiological department, they would put a tiny little access port into your neck in the most common circumstance and then feed a tiny wire down into the testicular vein and then block it off with a tiny metal coil which will then cause that vein to shrink away, it’s minimally invasive.

Surgery vs Radiology

Comparing the rates between a microsurgical subinguinal varicocele repair, the chances of it coming back are somewhere between 1-4%, while with radiological embolization, the chances of it coming back are around about 3-12%. The benefits of the surgery are that the rates of complications are low, it has the lowest recurrence rate, and it probably has the strongest evidence as there were a lot of studies performed on that. The benefits of Radiological embolization are that your complication rate is low, and you can rapidly return to normal activity, while with surgery, you usually need a couple of weeks off and to take painkillers. With an embolization, you can treat both sides, whereas, with surgery, you would often be very cautious about doing both sides in case something went wrong on one side. With embolization, you have a lower risk of damaging the blood vessels in the testicle. You can repeat it after an embolization as well and it’s also fairly readily available.

Summary

• Varicocele should not be treated in infertile men who have normal semen analysis and in men with subclinical varicocele.
• Infertile men with a clinical varicocele, abnormal semen parameters and otherwise unexplained infertility in a couple where the female partner has good ovarian reserve should be treated to improve fertility rates.
• Varicocelectomy may be considered in men with raised DNA fragmentation with otherwise unexplained infertility or who have suffered from failed IVF/ICSI techniques, including recurrent pregnancy loss, failure of embryogenesis and implantation