The AFA Blog

The Story of Testosterone

by Craig Niederberger, M.D., F.A.C.S.

When you think of what makes up the inside of the testes, think spaghetti. Imagine a bunch of spaghetti noodles squished together. Inside of the noodles are the developing sperm cells. Between the noodles are cells called “Leydig cells” whose job it is to make the male hormone testosterone. They start with cholesterol, and churn out testosterone.

Not only is testosterone critical to the factory inside the spaghetti that makes sperm, it is important for many parts of the male body to work well. Adequate testosterone is needed for bone and muscle strength, and men with low testosterone may experience low sex drive, problems with mental focus and depression.

The relationship between testosterone and how the penis works is less clear. Men with low testosterone can get erections, but of course sex drive can be a problem. And if a man’s testosterone is low, correcting it may improve the performance of drugs like Viagra, Levitra and Cialis.

Total testosterone doesn’t tell you the whole story. Testosterone circulates in the blood in two forms. Testosterone that is either free or loosely bound to blood protein is called “bioavailable”, and as the name implies, is available for the cells to work. Testosterone that is bound to sex hormone binding globulin (“SHBG”, but also called androgen binding protein,) is blocked from acting in cells. Although many labs offer to measure free testosterone, often the most reliable way to measure bioavailable testosterone is to have the blood tested for albumin, sex hormone binding globulin and testosterone, and then to use a calculator for bioavailable testosterone. One is available on the International Society for the Study of the Aging Male’s web site, and another for iPhones and iPod touches can be found in the iTunes store. A man may have adequate total testosterone, but still suffer from the ravages of low testosterone levels if his bioavailable testosterone is low.

Testosterone levels rise and fall during the day, with a peak in the early morning, and the lowest point in the late afternoon. That’s why many a man’s sex drive is highest in the morning, and it’s time for a nap in the afternoon.

Testosterone is converted to dihydrotestosterone, which makes the hair fall out of your hair follicles if your family tree has male pattern baldness. Dihydrotestosterone also enlarges the prostate. Drugs like finasteride (Propecia and Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone.

All men have a little estrogen, the female hormone. An enzyme called “aromatase” converts testosterone to estrogen. If the estrogen level is too high, it may interfere with the working of testosterone.

One last important point about the making of testosterone: levels in the testis are twenty times greater than in the blood. So if a man is given testosterone, his blood levels may increase, but the pituitary tells the testis, “hey, there’s enough testosterone around, so stop making it.” As a result, testosterone levels in the testis fall, sperm stop being made, and the testes shrink. That’s why many body builders who take testosterone and other similar chemicals experience shrinking testes. Testosterone can be great for men with low levels later in life, but for men who want to have children, it can really work against sperm production.

 

Antioxidants and Reproductive Health

By Harry Fisch, MD

Everybody knows that we need oxygen to live. In the body, oxygen is vital for many of the chemical reactions that keep us alive and healthy. But these reactions also produce "free radicals" – highly unstable molecules that can damage cells. Free radicals are produced when the body breaks down foods for use or storage. They are also produced when the body is exposed to tobacco smoke, radiation and environmental contaminants.
 
The body protects itself from free radicals by producing antioxidants – molecules that neutralize or destroy free radicals. We also get antioxidants from food. Antioxidants are abundant in vegetables and fruits and are also found in grain cereals, teas, legumes and nuts. Examples of antioxidants include anthocyanins, beta-carotene, flavonoids, lipoic acid, lutein, lycopene, selenium, and vitamins C and E.
 
In lab experiments, antioxidant molecules clearly block the damage that can be caused by free radicals. It is not as clear whether consuming antioxidants – in food or supplement form – actually benefits health. Many studies have now been conducted and the evidence is mixed. Interestingly, however, it may be that one area in which antioxidants play a key role is in supporting sexual health and fertility.  
 
A recent article in the respected Cochrane Database of Systematic Reviews found that among couples undergoing fertility treatments, men taking antioxidants were over fourfold more likely than men not taking supplements to get their partner pregnant and see a successful live birth.
 
"When trying to conceive as part of an assisted reproductive program, it may be advisable to encourage the male partner to take an oral antioxidant supplement to improve his partner's chance of conceiving," the authors concluded.
 
Further studies are needed to confirm these results, but the findings are certainly encouraging. They also make sense from a physiological perspective. Semen contains vitamins E and C and other antioxidants to scavenge free radicals, which can break down sperm membranes and damage sperm DNA. It may be that oxidative stress damage to sperm contributes significantly to male subfertility. Antioxidants are a key ingredient in a supplement I’ve developed called the Sexual Health Formula.

The clinical trials that were reviewed in the Cochrane paper used a wide range of antioxidant supplements, predominantly vitamin E, vitamin C, carotenoids, ubiquinol, folate and zinc. No one antioxidant seemed to be better than another.   
 
As with any type of supplement, you shouldn’t use antioxidants as a replacement for a healthful diet and lifestyle. Fresh fruits and vegetables contain a wealth of important nutrients in addition to antioxidants, and your overall sexual health is supported by many things such as getting enough exercise, sleep, and avoiding obviously unhealthy habits such as smoking.

It’s also a good idea to let your doctor know if you decide to take an antioxidant supplement and to avoid mega-doses, which might be harmful. The bottom line, though, is that antioxidants are very beneficial and they may be particularly helpful in maintaining sexual health and fertility.

 

How-To; Getting Sperm from the Testis

by Craig Niederberger, M.D., F.A.C.S.

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.

In short, a surgeon has many ways to retrieve sperm when necessary.  The choice depends on the preference of the surgeon and the couple, and what’s going on inside the testis.  I’ve listed the surgical techniques available, and my typical recommendations.

The New WHO

by Craig Niederberger, M.D., F.A.C.S.

A first test of male fertility is the semen analysis.  You do your thing, and a technician counts the sperm, sees how they’re moving, what they look like and whether they’re alive.  For decades, the World Health Organization has published criteria for these numbers to alert a man that he might have a problem when it comes to impregnating a woman.  Until recently, the numbers were a consensus of expert opinion, but in the latest edition, the WHO criteria changed substantially.

What the WHO is currently doing is to dispense with expert opinion, and just lay the numbers out for all to see.  Table II from the paper shows the numbers for men from couples who conceived within a year.  Take sperm concentration, for example.  For centile 5, the sperm concentration is 15 million per ml.  That means that only 5% of couples where the man had 15 million/ml sperm or less conceived within a year.  For centile 50, the concentration was 73 million/ml, meaning that 50% of couples conceived within a year when the sperm concentration was up to that number.  You get the idea.

The problem is that people like cutoffs, and in the latest edition, the WHO chose centile 5 as the line in the sand.  It’s a good number for thinking that below it, couple infertility likely involves the male.  But keep in mind that at centile 10, only 10% of couples conceived within a year.  In other words, having sperm numbers above the centile 5 cutoff doesn’t guarantee that the sperm are trouble free.

Frankly, I think the WHO numbers are most useful to get a ballpark idea of how fertility may be related to what’s inside the semen.  I prefer the approach David Guzick and colleagues took, where they applied a statistical method called Classification and Regression Tree (CART) analysis to sperm, which gives two cutoffs in a “green light, yellow light, red light” fashion.  For example, CART analysis came up with 13.5 million/ml and 48 million/ml for sperm concentration.  At 13.5 million/ml sperm or less, the “red light,” couple infertility likely involves the male.  At 48 million/ml or more, your sperm probably are “green light” good to go.  Between 13.5 million/ml and 48 million/ml, the “yellow light,” sperm may or may not be the problem.  You can find the Guzick CART cutoffs here.

A lot of people, including doctors and fertility specialists, are confused about the new WHO cutoffs.  Expect a little consternation about them for a bit.

WHO Table II Distribution of values, lower reference limits and their 95% CI for semen parameters from fertile men whose partners had a time-to-pregnancy of 12 months or less

N Centiles 2.5 (95% CI) 5 (95% CI) 10 25 50 75 90 95 97.5 Semen volume (ml) 1941 1.2 (1.0–1.3) 1.5 (1.4–1.7) 2 2.7 3.7 4.8 6 6.8 7.6 Sperm concentration (106/ml) 1859 9 (8–11) 15 (12–16) 22 41 73 116 169 213 259 Total number (106/Ejaculate) 1859 23 (18–29) 39 (33–46) 69 142 255 422 647 802 928 Total motility (PR + NP, %)* 1781 34 (33–37) 40 (38–42) 45 53 61 69 75 78 81 Progressive motility (PR, %)* 1780 28 (25–29) 32 (31–34) 39 47 55 62 69 72 75 Normal forms (%) 1851 3 (2.0–3.0) 4 (3.0–4.0) 5.5 9 15 24.5 36 44 48 Vitality (%) 428 53 (48–56) 58 (55–63) 64 72 79 84 88 91 92

*PR, progressive motility (WHO, 1999 grades a + b); NP, non-progressive motility (WHO, 1999 grade c).

Varicose Veins in the Scrotum: What's the Deal?

by Craig Niederberger, M.D., F.A.C.S.

The testes must be kept cool for the proper production of sperm.  One way the human body achieves this is to house them outside the body.  Another is to have a network of veins surrounding the artery pumping blood into the testis: the veins take the heat away in a “counter-current” heat exchange similar to a radiator.  (The human body is an amazing piece of engineering.)

Arteries don’t need to worry about moving blood; there’s a huge amount of pressure coming from the heart to help with that.  But once the blood goes through the capillaries and into the veins, getting back to the heart isn’t easy.  Veins have little valves to help hold the blood while it pulses its way back.  If those little valves start to separate, the vein expands, causing the condition known as a “varicose vein.”  Varicose veins can happen in many places in the body, often visibly in the skin of the legs, but, believe it or not, also in the scrotum.  And if varicose veins develop in the scrotum, they can disturb the counter-current heat exchange.  The testes then get hot, posing a problem for developing sperm cells.

Varicose veins in the scrotum are called a “varicocele,” and there are three kinds.  A grade I varicocele can’t be felt or seen without equipment like ultrasound.  Almost all experts now consider grade I varicoceles to be unimportant.  Varicoceles that can be felt (grade II) or visible by the naked eye (grade III) are the ones that may cause problems with sperm production.

Some men have such high sperm production that their varicoceles don’t significantly alter their chance of making women pregnant.  But many men’s testes are affected by grade II or III varicoceles.

What can be done about a varicocele that may be throwing a wrench into the sperm factory?  A urologist can tie or clip the veins in a procedure called “varicocelectomy,” or an interventional radiologist can inject material into the veins to block the flow of blood.

Craig Niederberger, M.D., F.A.C.S. is a highly published author and editor, and head of the Department of Urology, University of Illinois at Chicago. His blog, Male Health, and other writings will be syndicated on this page for The American Fertility Association's readership 

Combating Infertility

By: Stephanie Himel-Nelson

 You may read me on the Attainblog and on the Attain Fertility Facebook page.  If so, you  probably have this picture in your head of what I look like and how I sound, so I thought I’d share the real me with you in my first Video Blog for Attain Fertility.  In this video, I tell you a bit about the Attain Great Expectations Fertility Trivia Challenge!

I’m pretty excited about this because I love anything that might possibly be considered a contest and I know a boat load (that’s a technical term) about infertility. I’m not competitive at all. Just ignore my nose growing by leaps and bounds….

The Great Expectations Fertility Trivia Challenge is running through the end of January and you can enter every. single. day.  Every time you take the challenge, you’ll be entered into a random drawing for some really cool prizes.  Attain will be giving away $1000 that you can use for a shopping spree or a spa getaway and is also giving away 25 Kindles with Amazon gift certificates, to celebrate Attain Fertility’s 25th anniversary!

You can enter every day. I’m pretty sure you’ll learn something too.  Despite my insistence that I know everything, I’ve gotten quite a few questions wrong.  (Don’t tell!)  But, I’ve also learned the correct answers about quite a few fertility topics.

You can take the challenge every day at http://attainfertility.com/challenge.

A Baby at Last

 

by Carolyn Berger, L.C.S.W.

As those of you who religiously follow the AFA Blog know, Wednesday night’s

Illuminations NYC fundraiser was a remarkable success.

 My favorite part of the evening was giving Dr. Zev Rosenwaks, Dr. Marc Goldstein, and Mark Fuerst our Media Award for their recent book, A Baby at Last.

 If truth be told, I was just a bit anxious before getting up in front of our 170 guests. Would I suffer from “brain freeze,” forget someone’s name, or, even worse, trip on the step up to the stage?  To make matters even more dicey, I decided a minute before I went up that I wouldn’t follow my script, but would speak from my heart instead.  I just didn’t feel that what I had written was enough.

 So I got up there and told people that after I finished reading the first chapter of the book, “You Are Not Alone,” I knew I had to get a second copy.  I counsel fertility patients in two separate offices, and I wanted this book by my side in both places. It would make me a better therapist.

 I’ll tell you why.  The book takes the very complex world of fertility treatment and simplifies it—something that patients and clinicians alike can appreciate.  It intersperses scientific information with vignettes of true-to-life couples struggling to have babies—and it imparts hope.  Each chapter ends with “Take-Home Messages,” which cull the essential ideas and can act as quick reference points for busy patients who don’t have time to re-read chapters looking for one important piece of information.

 Something else I like about the book…. In a world where female fertility issues often take center stage, Dr. Zev Rosenwaks and Dr. Marc Goldstein, both of Weill Cornell Medical Center, have joined together to give male and female fertility equal play, including chapters on both male and female fertility evaluations and treatments. (This is all to the good since while male and female factors each count for 40% of cases of infertility, male-factor infertility has not gotten the attention it deserves.)

 So, my introduction of our Media Honorees went just fine in the end.  Dr. Zev Rosenwaks took out a sheaf of papers when he reached the podium—and then put them aside.  He spoke from his heart instead.  Dr. Marc Goldstein did the same. And Mark Fuerst followed suit.

 It was just that kind of evening, hopeful and celebratory all at once, and when I went home I was smiling.

 Carolyn Berger, LCSW, is Founding Board Chair of The AFA.  She has a practice devoted to Fertility, All Forms of Family Building and Adoption in Westchester and Manhattan.

 

The Mysteries of Funny Looking Sperm

by Craig Niederberger, M.D., F.A.C.S.

I was at a meeting recently, and one of the hottest topics of discussion was sperm shape. We call it “morphology”, and it’s how sperm look under the microscope. A technician counts up the number of normal looking sperm, and reports the percentage of the total. Here’s the odd part: with fairly generous criteria, (like normal means one oval head with one tail,) only about a third of a man’s sperm look normal. That means, for most men, most of their sperm are funny looking.

Is that a bad thing? Well, we all managed to get here with fathers that had for the most part funny looking sperm. Was it the best looking sperm that found its way into the egg and made you? That’s the million dollar question, and one for which we don’t yet entirely know the answer.

There are two ways to measure the look of sperm. One is using the World Health Organization (WHO) criteria, which for the most part say that if a third of sperm look fairly normal, the whole lot are O.K. These criteria have been around for a while, about a half century. The new kid on the block is about twenty years old, and uses a much stricter definition to call a sperm ‘normal’. Thinus Kruger invented this stricter system, and so it’s often called ‘Kruger morphology’ or ‘strict morphology’. To calculate strict morphology, the technician takes measurements of the sperm, and if any are outside the normal range, the sperm is counted as abnormal. The usual cutoff for strict morphology is 4%, which means that 95% of your sperm can be funny looking, and you’d still be considered to have normal morphology. That should give you an idea of how oddly shaped most sperm are in the typical male.

One big challenge in assessing morphology is that even though it appears to be an objective way to describe sperm shape, it still includes a great deal of subjectivity on the part of the technician. The technician is like a referee. Sometimes he or she will let a sperm pass the shape test, sometimes not. From some labs, almost no sperm are called normal in shape. So the first thing you’ll want to do if you’re told that your sperm are especially strangely shaped is to have the test repeated, preferably at a lab that does a lot of semen analyses.

For as many scientific studies that say morphology predicts how sperm do, there are those that say it doesn’t. You might think, as I did, that if a man has especially odd looking sperm, it would affect the chances of sperm getting into the egg and be a good reason to have the sperm injected into the egg using intracytoplasmic sperm injection (ICSI). ICSI is a technique used in in-vitro fertilization (IVF) where the sperm is injected directly into the egg. But in 2007, Keegan and colleagues published a study which reported that there was no advantage to using ICSI for semen with an abundance of funny looking sperm, meaning they did just as well getting inside the egg by themselves as men with “normal” looking sperm.

What does this all mean? Well, it could mean that sperm shape counts, but we don’t yet know how to measure it correctly. Or it could mean that the sperm shape doesn’t have much to do with its function–in other words, the shape of the boat doesn’t say much about how good the captain is that’s piloting it. I don’t know which is right, and I don’t think anyone does yet. So if someone tells you that your sperm is funny looking, don’t despair. It might not be the thing keeping you from becoming a father.

Craig Niederberger, M.D., F.A.C.S. is a highly published author and editor, and head of the Department of Urology, University of Illinois at Chicago. His blog, Male Health, and other writings will be syndicated on this page for The American Fertility Association's readership 

Varicocele, a Common Form of Male Factor Infertility

by Corey Whelan

According to recent estimates, roughly six million Americans are affected by infertility today and need medical support in order to have their family.  In 20% of these cases, the underlying cause is male factor infertility.  In 30-40% of these cases, infertility results from both the male and female partner.

A common type of male factor infertility is called a varicocele.  Varicocele refers to enlarged and twisted veins along the cord that holds up a man's testicles.  Varicocele is most common in men 15-25 years of age and sometimes presents itself with  no external symptoms.  Sometimes however, one testicle will appear to be larger in size than the other.  Other symptoms may include a painless testicle lump, scrotal swelling, or bulge within the scrotum.   You may also experience an aching pain within the scrotum, a feeling of heaviness, or visibly enlarged veins.   Varicocele is caused when the valves found inside the veins of the spermatic cord stop blood from flowing properly, resulting in a blood back up.

If you suspect that you have a varicocele, or are undergoing a routine infertility workup, your urologist will conduct a full body physical exam.  Diagnosis of the varicocele will be done through the use of  an ultrasound of the groin area, scrotum and testicles.

In and of itself a varicocele is harmless.  If however, infertility results from the varicocele, treatment may be required to correct the problem.  Your urologist may recommend a varicocelectomy, which is the surgical correction of the varicocele.  Varicocelectomy is done on an outpatient basis.  A possible alternative to surgery is embolization, which is a minimally invasive treatment usually performed by a radiologist.  Insurance generally covers these procedures.  

Men may not settle around the TV set watching the world series and talking about varicoceles.  Bonding issues aside, male factor infertility is very common and in any group of men you find it is likely that several guys are grappling with this issue. 

If fatherhood is your goal, seek out the support of a reliable board certified urologist.  The American Fertility Association has a free referral service that  is a great place to start.  Get yourself to the right doctor, and get on the road to family.  

Reprinted with permission from www.examiner.com