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Male Factor Infertility

Lesson 6 of 9


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More Common Than You’d Think

Approximately 25 – 35% of men who have primary male factor infertility (they’ve never fathered a child) have a varicocele, as do 80% of men who have secondary male infertility (fathered previously and now struggle to conceive). So varicocele is prevalent in men with male factor issues, but that doesn’t mean it’s always causative of male factor issues.

What Is Varicocele?

Varicocele is an enlargement of the veins in the scrotum as a result of a breakdown in the blood drainage system in the testicles. If a varicocele does play a role in male factor infertility, it’s likely because the varicocele helps drive up the heat and pressure damage in the testes, which impinges sperm production.

Diagnosing Varicocele

Urologists diagnose a varicocele in a pretty rudimentary fashion. If the doctor can feel the varicocele by pressing on the skin, the varicocele is considered “clinical” and the doctor may want to begin treatment. About 85% of varicoceles are on the left side of the body. For men who are obese, or have a small scrotum, an ultrasound is often needed to detect the varicocele.

Candidates for Surgical Varicocele Repair

Varicocele is present in many male factor patients and, after years of treatment, the field has established that only treating certain types of varicoceles improves semen analysis parameters or live birth rates.

Generally speaking, here are the criteria whereby a urologist should consider treating the varicocele:

  • Clinical: The varicocele is large enough in size & severity to be felt upon examination. Men with large varicoceles tend to benefit most from any intervention.
  • Symptomatic: Semen quality is impaired, the man is experiencing scrotal pain, or there’s evidence of atrophy (more common in children).

Nature of Varicocele Surgery

There are two types of varicocele surgeries, and both involve closing the veins where blood is pooling. Both treatments have relatively short recovery times and modest rates of adverse events. We generally hear from patients they managed to get both covered by insurance, though men who have already been given an infertility diagnosis may face more challenges than men that have yet to be given a fertility diagnosis. As with most aspects of this field, there is conflicting data on which of the two surgical approaches is better.

  • Varicocelectomy is a surgery performed by a urologist that takes 30 – 60 minutes per side and involves tying off the veins below the varicocele. Most believe a microscopic approach offers better outcomes while inflicting less damage to the arteries. Around 90% of patients who have treatment on their varicocele, in the US, have a varicocelectomy. This may be because the urologist does this form of varicocele surgery and is reluctant to send the patient to a different doctor to have the varicocele treated.

  • Embolization is a less invasive form of varicocele surgery and is performed by an interventional radiologist. It involves placing an artificial blockage in the problematic vein. The principal fear is that patients treated with embolization have a higher likelihood that the varicocele reappears than patients treated with varicocelectomy.

Varicocele Surgical Outcomes

The field is frankly at a loss to declare how effective varicocele surgery is in addressing male factor infertility.

In the “pro surgery” camp is data that averages the pregnancy rates in 11 studies that compared varicocele surgery and no surgery. The populations that underwent surgery clearly had superior pregnancy rates (33% vs 16%).

On the other hand, nearly every one of these studies was small, retrospective, looked only at pregnancy rates (instead of live birth rates), and, between them, saw such wildly different outcomes that it’s hard to determine how much credence to lend the rundown (one study’s “surgery population” had an 8% success rate, while another one had 60%).

A similar review of 10 studies found “evidence to suggest” that varicocele surgery drove higher pregnancy rates for infertile couples who, apart from the varicocele, appeared normal. Yet, the authors called the observation “inconclusive” because most of the studies it reviewed were not rigorously carried out.

What we’re left with are two prospective, randomized trials that cleanly looked at couples where only a male factor issue existed. They’re both small studies (each under a 150 patients), old (done in 1995), and both showed surgery clearly improves semen parameters. However, only one of the two studies demonstrated a statistically significant improvement in pregnancy rates (which, as you know, still falls short of the better benchmark of live birth rates).

At this point, it’s almost impossible to study whether having varicocele surgery improves fertility rates. The NIH tried to enroll a trial to test just this, but few men would enlist in the trial at the risk they would be selected to join the “no surgery” arm of the trial. Ultimately, while the evidence suggests surgery is probably of help, especially in certain sub-segments of patients (e.g. those with a larger varicocele), the topic has not been rigorously studied.

IUI Alone vs. IUI Plus Varicocele Surgery

Some patients might consider avoiding varicocele surgery and doing IUI (Intrauterine Insemination). As you may recall from an earlier lesson, IUI involves injecting sperm directly into the woman’s uterus in a relatively minor, often painless procedure that costs $300 - $3,000.

One study looked at how couples with only male factor infertility, with varicocele, fared with IUI, and the results were uninspiring. Just 6% of the couples conceived after one attempt and only 1% delivered.

However, the investigators also enrolled couples who had varicocele surgery before IUI and the results were better--12% of couples conceived after the IUI, and all of them delivered a live birth. This is clearly a marked improved compared with the couples who just did IUI with no surgery beforehand.

IVF With ICSI vs. Varicocele Surgery

If a couple has both poor semen parameters and a female infertility challenge, most reproductive urologists and reproductive endocrinologists agree advancing this couple to IVF makes sense. The rationale is that varicocele surgery could take months to restore semen parameters and for a woman with, say, diminished ovarian reserve, that’s not time the couple can afford to lose.

But if the issue resides solely with the male, possibly on account of a varicocele, there is disagreement on whether IVF with ICSI is better than just performing surgery alone. At the moment, there are few good studies that compare IVF with ICSI to varicocele surgery by itself.

IVF With ICSI After Varicocele Surgery vs. Without Surgery

There are two reasonably well done studies that evaluate whether doing varicocele surgery before IVF with ICSI is better than doing IVF with ICSI without surgery. This is for men with varicocele and some sperm (we’ll address men with a varicocele and no sperm below). The two studies that measured live birth rates (our strong preference for an endpoint) showed that varicocele surgery before IVF with ICSI clearly made an impact, increasing the live birth rate from 29% to 48% in one study, and from 31% to 46% in another.

In the case where the man is azoospermatic (has no sperm) and has no blockages, it appears the same approach works. In a very small study, investigators noted that when this group had varicocele surgery before IVF with ICSI, the IVF was far more likely to lead to a live birth than if they just did IVF with ICSI alone. Live birth rates increased from 42% to 65%.

Pro Tips

  • If you have a varicocele that’s large enough to be felt by your urologist during a physical exam, it will likely warrant a discussion of whether surgical repair of varicocele makes sense for you

  • When weighing varicocele surgery options, be aware that urologists may be inclined to recommend varicocelectomy and interventional radiologists will suggest embolization

  • If you’re planning to do IUI, the data shows meaningful improvement in doing varicocele repair surgery first

  • If you plan to do IVF with ICSI, the data is very compelling that doing varicocele repair surgery first will help your outcomes