Has it really been over three months since my last post?  Between becoming one of the next Co-Editors in Chief of Fertility and Sterility, preparing for a review of our urology training program and finishing my latest book (Thank You, Chapter Authors!) I guess that I’ve let my blogging slip a bit.  Fortunately, thanks to my Italian co-faculty’s discovery of the Saeco Vienna Plus espresso maker at Costco, I’m back at the keyboard.

I turned off the two-week limit for comments, and so far, that’s been a good idea.  People are commenting on older posts (like How Clomid Works in Men) with good questions and thoughtful points.  For new commenters, please read the FAQ.  I can’t answer questions about specific patients.  Those are best left to a live visit with a doctor with an interest in male reproductive medicine.  One great resource is the American Society for Reproductive Medicine’s Society for Male Reproduction and Urology page and the ASRM’s find a doctor search page, (just click on the “Society for Male Reproduction and Urology (SMRU)” button in the “Find Member by Affiliated Society:” section.)  Another excellent way to find a specialist who treats men with reproductive issues is to use the American Urological Association’s Society for the Study of Male Reproduction’s search engine.

This blog post was inspired by several patients who asked after I explained surgical sperm retrieval, if there was somewhere they could go for more information.  I realized that I hadn’t written about such a common issue.

Just as a carpenter has many ways to make a cabinet, a surgeon can tackle a problem in a number of ways.  And just as two cabinets may differ, different surgical problems demand different approaches.  Such is the case in retrieving sperm from the testis.

Most of the time, taking sperm directly from the testis is necessary when a man has azoospermia, where no sperm is found in the ejaculate.  Azoospermia takes two basic forms, obstructive and non-obstructive.  As the name implies, obstructive azoospermia is due to a blockage in the tubes and structures that convey sperm from the testis to the outside world.  In the best case, a surgeon can fix the errant anatomy, allowing a couple to conceive children without further ado.  But because the tubes are so tiny, sometimes the tubes can’t be reconnected with surgery, and the alternative is to take sperm from the testis for it to be used in in-vitro fertilization.

The other form of azoospermia, non-obstructive, arises when the factory making sperm in the testis isn’t working quite right.  Sometimes, the cells starting sperm are missing entirely, a condition known as “Sertoli cell only syndrome”.  Occasionally, sperm may be rolling along their assembly line, a process that takes two to three months to complete, and stop mid-production.  When that happens, it’s called “maturation arrest“.  But frequently, sperm can be found in small amounts in the testis and can be retrieved using surgery.

Because it isn’t mature, sperm from the testis can only be used with in-vitro fertilization and intra-cytoplasmic sperm injection.

How can a surgeon remove sperm?  He or she can take it from the testis itself, or the epididymis, the tiny coiled tube lying on the back of the testis where sperm mature.  The surgeon can insert a needle into the testis or epididymis, he or she may make one or several small incisions into the testis or use microsurgery to retrieve sperm from either the testis or epididymis.  In the case of obstructive azoospermia, it doesn’t seem to matter which technique is used.  There’s plenty of sperm wherever it’s sought, and any method will do to retrieve it.  When a man has obstructive azoospermia, I usually recommend taking a small piece from the testis, as the sperm may be frozen and is good for a number of in-vitro fertilization cycles so that the man doesn’t need to go through a procedure for every cycle, and can be there for his wife during her procedures.

We’ve found that frozen sperm is just as good as fresh.  in fact, the chances for fertilization are the same for fresh and frozen sperm, and the chance for pregnancy may even be a little better for frozen sperm than for fresh.

Frozen sperm should literally last forever.  It’s in liquid nitrogen, which is so cold that the building blocks making sperm don’t decay.  Freezing sperm gives a couple time to plan when in-vitro fertilization is done.

When he has non-obstructive azoospermia, a man’s options are more limited.  A surgeon can use the operating microscope to comb through the testis looking for areas that may contain sperm, a procedure known as “microsurgical testis sperm extraction“.  Other techniques include making several small incisions in the testis or piercing the testis with a needle in a dozen or so different spots.  When a man has non-obstructive azoospermia, I usually recommend microsurgical testis sperm extraction.  More areas of the testis can be examined, and I can see the places that most likely contain sperm.

We’ve observed that prescribing a man with non-obstructive azoospermia clomiphene citrate for a few months before surgical retrieval seems to increase the chance to retrieve sperm.  In many men, sperm appears in the ejaculate and surgery isn’t needed.  If a couple has a few months, taking clomiphene before surgical sperm retrieval might be a good idea.

You may have heard the news that British biologist Robert Edwards won the Nobel prize in Medicine for his work developing in-vitro fertilization. Gynecologist Patrick Steptoe pioneered advances in retrieving and replacing a woman’s eggs without open surgery, and Edwards made breakthrough discoveries in keeping sperm and eggs alive outside of the body. Together, their work resulted in the first “test tube” baby born in 1978. She’s now a healthy adult with children of her own.

I clearly remember the breaking news of that first IVF baby. I was headed to college, and it read like science fiction. All sorts of horrors were imagined and published, alongside articles expressing the thrill of bringing children to childless couples. More than four million IVF babies have been born since that remarkable first, four million people who otherwise wouldn’t be here with us today.

Patrick Steptoe couldn’t share the Nobel prize with Robert Edwards, although he most certainly would have if he could. He died in 1988, ten years after his great success, and the prize isn’t awarded posthumously. Congratulations, Drs. Edwards and Steptoe. You not only brought us great science, you brought children into our homes.

I hear that Mel Gibson allegedly blamed what he called depressed and “whacky” behavior on “male menopause.” Putting aside the question of whether he actually wrote the note circulating on the internet, (and that’s a big if,) is there a male menopause?  If the answer is yes, can it affect behavior and cause depression?

Testosterone levels do decrease, especially as a man gets older.  In one study, testosterone fell on average 110 ng/dL each decade in men over sixty.  As the FDA puts the normal line for testosterone in men at 300 ng/dL, that’s a big drop.  But it’s happening over ten years.

That’s the essential problem with calling the decline in testosterone as men age “menopause.” The word refers to the rapid plummet of women’s reproductive hormones around age fifty.  When a woman’s hormones drop in a short timespan, it’s fairly obvious to her that they’re changing .  But male hormones fall more gradually, though the decline is substantial.

Worse, a blood protein called “sex hormone binding globulin,” SHBG for short, is on the rise in the older man.  As its name implies, SHBG binds testosterone and renders it useless.  The drop in testosterone as men age is magnified by the climb in SHBG.

If testosterone was unnecessary, its decline would go unnoticed, but it’s one of the most important hormones a man has.  Low testosterone in older men is associated with muscle wasting, thinning of bones, loss of sex drive, depression and other problems.  Testosterone isn’t the only reason for these ailments, but it can be a big part of the puzzle.

If Mel did blame depression on “male menopause,” meaning a low testosterone, it’s possible that the 54 year old actor is feeling a drop in his hormones.  If he hasn’t already, he’ll want to get his testosterone checked.

You can’t fault a man for thinking his penis a single use tool.  But it’s more like a Leatherman or a good Swiss Army knife.  One great use is as a barometer for gauging the health of a man’s heart and blood vessels.

The structure of the penis is basically a sponge with a tiny artery that supplies blood.  The sponge fills with blood, and the penis becomes erect.  (It’s actually a really impressive piece of engineering, with veins at the outer edge of the sponge that are pressed closed as the penis fills, trapping the blood and holding the erection.)  The artery supplying the sponge is very small, only about half the diameter of the coronary blood vessels supplying the heart.  If the arteries are getting clogged, the arteries in the penis go before the heart ones do, giving a man a two to five years heads-up that something bad is happening, not just to the penis, but that may be life-threatening.

Recently published guidelines recommend that if a man is experiencing problems with erections, that he be evaluated for high cholesterol and other artery clogging problems, and that if the labs are out of whack, he be treated aggressively with medication.

As important as the penis is, the heart’s kind of necessary.

Doctor’s Corner

Ever so often, I get asked questions from doctors, and I figure that here is a reasonable place to put how I answer the frequently asked ones.  As with everything I write, it’s my opinion, and doctors opinions vary.

One question I get asked a lot is how to prescribe clomiphene for a male.  Here’s how I do it.

First, clomiphene works by stimulating the pituitary.  If the pituitary’s already in overdrive, clomiphene won’t help.  So if a man’s LH is high, like 25 IU/L, I don’t prescribe clomiphene.

The next decision to make is what the target for therapy will be.  If it’s augmenting a low testosterone level, then I’ll use the bioavailable testosterone calculation described in a previous post.  As a reasonable threshold for total testosterone is 300 ng/dL and the portion of bioavailable testosterone ranges between 52% and 70%,¹ I use the range between 156 ng/dL to 210 ng/dL as a lower limit of what is likely an adequate bioavailable testosterone level for a man.  If the target for clomiphene therapy is stimulating the testis to make sperm, I use a higher threshold.  If possible we try for twice as much, about 400 ng/dL for bioavailable and 600 ng/dl for total testosterone.  It’s not always possible to achieve those levels.

I start with 25 mg clomiphene a day.  As the pills come in 50 mg, and the half-life is relatively long, patients can take a pill every other day.  Some prefer talking half a 50 mg pill daily.  After two weeks, I have the patient get tests for testosterone, LH, albumin, SHBG (sex hormone binding globulin) and estradiol.  In some instances, the estradiol will increase, but as long as the ratio of total testosterone to estradiol is greater than ten-to-one, that shouldn’t be a problem.  If the estradiol increases substantially, other therapy, like an aromatase inhibitor, is preferred.  If the testosterone is still low, then we’ll increase the clomiphene by 25 mg every other day or daily, and repeat the tests.  I’ll increase the clomiphene to a maximum of 100 mg daily.

I believe that clomiphene works better if a man’s testosterone is low.  That’s a good indication that there is a problem that may be corrected.  If the testosterone is reasonable at the start, 400 ng/dL or more, then pushing it higher may not be as effective.  But that’s my opinion, and as of present, scientific studies don’t definitively prove it right or wrong.

It’s important to note that clomiphene is “off-label” for use in the male.  I explain this in a previous post.

¹S. Bhasin. Chapter 18: Testicular disorders.  In: Kronenberg H. M., Melmed S., Polonsky K. S., and Reed Larsen P., eds. Williams Textbook of Endocrinology 11th ed. Philadelphia, W.B. Saunders Company, 2008; 647.