How about being happy and hopeful as well as healthy?

The couple had been trying to conceive for 5 years unsuccessfully. The tension and anxiety in the relationship was palpable and strained. They had spent well into the 5 digits to have a child with test tube baby technology (IVF) and yet were still not pregnant. His vasectomy reversal had also failed them. And they were going to try one more time, just once, with me, before calling it quits.

When he came to me for care, he was frankly depressed. Out of money and full of debt, close to losing his job in this economy and in a strained relationship hanging on by a thread, he sat across from me. He looked terrible. “Can you help?” he asked me.

Well I did help. I reversed his vasectomy again and it worked. Fast-forward 9 months and a birth announcement arrives in the office from the couple with a long personal note of thanks on the back. But one line really struck me:

”Looking at her, sleeping quietly, I see her future as an astronaut, the President, a doctor, a lawyer or anything else that she wants to be. She can be or do anything!”

Absolutely unbridled hope and enthusiasm was infusing a mind once filled with almost unfathomable despair. All this change, nine months and one baby ago. Wow!

Talk about a biological drive. Reproduction easily ranks up there with breathing and eating. Not for everyone of course, but for many. I am quite sure that if you surveyed infertile couples about their quality of life with infertility, as has been done in patients with cancer, you would find these diagnoses equally impactful. I have no doubt many of my patients would give up five healthy years of their life to have a child. Maybe even 10. Just because it cannot be assessed by a blood pressure cuff, a blood test, or a scar does not make infertility any less important an affliction.

And yet, despite its profound impact, its ability to tear apart relationships, crush self-esteem and slow down an otherwise productive couple to a grinding halt, infertility is not really considered a disease in many societies, including ours.

Want a more productive and healthier society? Cure infertility. And what about something else that this world could use a lot more of, as expressed by my patient: the resurrection of those elemental feelings that lead us to live good lives and to make the world a better place for those who will follow us.

The best medicine for man is man...and good government

A couple sees a reproductive specialist for infertility. She gets a complete evaluation and he gets a semen analysis checked. It looks like his semen quality is low and they are recommended to pursue in vitro fertilization  (IVF) and intracytoplasmic sperm injection (ICSI) to conceive, the highest level of what is termed “assisted reproduction.” They try this at significant expense and it fails. They try again and it fails again. At this point, the man sees a urologist and, after a proper physical examination, he is told that he has a testis mass and is diagnosed with testis cancer.

The point: Male infertility can be a symptom of another medical condition.

The question: What would have happened to this man if they had successfully conceived with IVF-ICSI?

This scenario is not all that uncommon in our field. And it is why I gladly accepted the invitation to go Washington D.C. and consult with the National Institute of Health (NIH) last fall regarding where government research monies should be spent in the future in the field of male reproductive health. At that meeting, I suggested that we start calling infertility a medical disease, just like any other, and get men the medical care that they deserve. I expect several great grant initiatives to stem from this gathering and was honored to have participated in it.

This scenario is also why I am excited to have been more recently invited to join the Medical Advisory Board of the Cooperative Reproductive Medicine Network at the National Institute for Child Health and Diseases (NICHD) at the NIH. The RMN, established in 1989, is a cooperative effort of seven universities and the government and is charged with conducting and publishing high quality clinical research studies in reproductive medicine.  Thankfully, one of the areas of focus is on male infertility. So, I will be taking my “infertility as a disease” mantra to Washington quite a bit this year as I believe scenarios like the case outlined above should never happen in modern medicine.

Can we be DNA barcoded like a soup can in a grocery store?

How many of you would take a blood test to learn exactly how long you will live? How about whether or not you will become demented? Since the Human Genome Project ended, the genes and mutations associated with a vast array of diseases are being discovered daily and it is pretty easy to just put them on “chip” and make them available to the public.

Don’t get me wrong; gene testing already has already improved our lives. Such tests can clarify a diagnosis and better direct care, while others allow families to avoid having children with life-threatening or disabling conditions. They can be used to prevent disease before it happens, as with monitoring and removal of colon growths among those who have a gene for familial polyposis, and can diagnose common iron-storage diseases early enough to treat them and prevent them from becoming fatal. They can also help to positively identify murderers two decades after the crime.

One real problem is that many commercialized gene tests are targeted to healthy people who might be at high risk because of a strong family medical history for a disorder. Unfortunately, because of how complex we are as biological organisms, the tests give only a “probability” for developing the disorder. That means that some people who carry a mutation may never develop the disease. Another limitation is the possibility of laboratory errors. What this means is that the tests are not perfect and could be wrong.

And what happens to your job prospects and health (or life) insurance rates when it is learned through genetic testing that you might develop a significant disease? Well…nothing. Because of the federal GINA Law (Genetic Information Nondiscrimination Act) passed in May 2008, insurance companies and employers cannot discriminate on the basis of information derived from genetic tests. So, genetics has now been added to the list of characteristics first embodied by the Civil Rights Act of 1964, that states that U.S. employers cannot discriminate according to race, color, national origin, sex, or religion. And this is good.

So, go ahead and take the “23 and Me” “DeCode” or “Navigenics” genomic screens if you so desire. Get to know your DNA barcode. Maybe you will get an idea of what may be around the corner for you. And maybe, just maybe, you will take better care of yourself knowing more about your genes. Just understand that many in the medical community feel that uncertainties surrounding test results, the current lack of available treatment options, the tests’ potential for provoking anxiety and social stigmatization could outweigh the benefits of testing. You know the saying: “Too much information…”

Cellular metabolites: woven together like a rug

Call me a nerd, but I have to admit that I am pretty excited about metabolomic technology. Uh, what? Metabolomics is the study of the chemical fingerprints that cells leave behind. It does not look at genes, DNA, RNA or proteins, but is a peek into the products or metabolites that result from all this genetic orchestration. It is a “physiological snapshot” of a living cell.

This past week, we published a study that applies metabolomics to male infertility. If you have been reading this column, you are well aware of my interest in helping sterile men become fathers. Over the last decade, it has become clear that many men with azoospermia (no ejaculated sperm) may have small pockets of sperm in the testicle. The question is how to safely find that sperm without causing undo harm to the testicle. Current methods for evaluating whether sperm are present include somewhat invasive techniques such as testicular biopsy and microdissection and less invasive ones such as FNA Sperm Mapping that I invented 13 years ago. However, as I always say, there is always room for improvement.

Wouldn’t it be nice to find the “pockets” of sperm in the testis through a simple scan and avoid a biopsy? Maybe even a scan that involves no radiation exposure, like an MRI? Well, that is precisely what we have developed in this study.

We showed that magnetic resonance (MR) spectroscopy can measure metabolic activity in the testis. And given that most metabolic activity in the testis is concentrated on building sperm (remember, normally men produce 1200 sperm/heartbeat!), metabolic measurements in the testis generally reflect sperm production. The study showed that the metabolomic scanning is as accurate as a more invasive testis biopsy in reading several abnormal patterns of sperm production typically associated with infertility. It also showed that testes that contain sperm carry a distinct chemical “signature” that can be distinguished by MR Spectroscopy.

How does it work? Essentially, the scan looks for chemicals in the testis that are the building blocks for sperm production. The theory is if you see a pile of bricks in the yard, then there is a good chance that a house is being built. In the study, phosphocholine was observed as one of the building-block chemicals in the testis. The more there is, the more likely sperm are being made.

Not only that, MR Spectroscopy can evaluate for sperm in as many as 100-200 areas within the testis, significantly increasing the ability to sample for sperm well beyond any of the more invasive techniques commonly used today.

Are we ready to replace a testis biopsy with an MRI scan? Not yet, but give me some time to tweak the system a bit and perform clinical trials comparing it to current approaches. My motivation runs deep, as I know that men would rather have their picture taken than have a surgical procedure to understand whether they can be fathers.

Do you agree with the Ancients on the good of the hood?

To circumcise or not. A loaded subject to be sure. The practice of male circumcision is ancient, likely far older than the biblical account of Abraham in Genesis. The Jewish faith, but not that of the Greeks or Romans, routinely recommended circumcision of newborn males. In the past century, it became “medicalized” as a preventative procedure only to be debunked in the last decade. Well, it may be now a procedure on the rise once again.

Circumcision is the removal of some or all of the foreskin or prepuce from the penis. The august American Academy of Pediatrics continues to recommend that circumcision is medically unnecessary, that it lacks any proven benefit, and that it should not be performed routinely in neonates. Maybe that is why the incidence of neonatal circumcision in the U.S. has continued to decline, from 80% in the 1960’s to 60% in 1996, to 55% of boys in 2001.

Why should circumcision be avoided? Issues of neonatal pain, behavioral changes and the potential for loss of sexual sensitivity from removal of the prepuce are age-old arguments for its discontinuation. However, a military study showing that there is a higher rate of urinary tract infections (UTIs) in non-circumcised boys and the fact that penile cancer tends to occur almost exclusively in uncircumcised men has kept the procedure alive and well.

In a somewhat radical departure from earlier recommendations, public health officials are now arguing that circumcision of men is a key weapon in the fight against human immunodeficiency virus (HIV) in Africa. Three recent, large, controlled studies have shown that circumcision reduces infection rates by 50 to 60% among heterosexual African. These studies stem from 3 different parts of the continent: South Africa, Uganda, and Kenya. In fact, two of the three clinical trials were stopped early because of overwhelmingly positive results. Experts now estimate that more than 3 million lives could be saved in sub-Saharan Africa alone if the procedure becomes widely used. And there is more recent data showing that the incidence of Herpes virus and HPV (Human Papilloma Virus) may also be reduced in circumcised men.

How circumcision prevents HIV transmission is not completely understood, but it is believed that the foreskin acts as a reservoir for HIV-containing secretions, increasing the contact time between the virus and target cells in the foreskin.

The problem with HIV and circumcision is that it is much more than a simple “behavior-based” intervention and this may ultimately be its biggest obstacle to wide acceptance. Changing social mores and behavior is one thing, but the “cold, hard steel” aspect of this public health initiative may not survive in the long run. If you don’t live in Africa, a clean penis and a clean life may be all that’s needed to replace the knife.

Is faster better? Not always.

What is the most common sexual health problem affecting men? That’s easy, it’s erectile dysfunction, right? Nope. Try premature ejaculation. Hands down more common than erection issues, affecting 25-40% of men in the U.S.

Variably called early ejaculation, or early or rapid climax, it is defined as male ejaculation earlier than the subject or his partner desires. It used to be defined as ejaculation within 2 minutes of sexual intercourse, until it was realized that 75% of men ejaculate within 2 minutes in over half of their sexual encounters. What the definition really implies is that is some element of poor control over ejaculation that is stressful and may result in interpersonal difficulty.

Is this a medical disorder? In some cases, yes. Think of ejaculation as a reflex, like sneezing. There is a point of no return and this is what comes too soon in men with early ejaculation. The problem has two forms: lifelong and recent. The former is believed to result from low levels of the neurotransmitter serotonin (5HT) that normally modulates the ejaculation reflex. The recent form does not have as clear a biological basis, but may occur from psychological stress or from the need to overcome an erection problem.

The good news is that there are treatments available, and more treatments being reviewed by the FDA. Currently, the most effective treatments are pills called SSRIs, which elevate 5-HT levels and include anti-depressants such as Prozac, Zoloft, Celexa, and Lexapro. A newer form of SSRI drug, called Priligy, is now available in nine countries but has still not been FDA approved in the states. Also, a metered-dose aerosol spray has been developed to increase time to ejaculation by numbing the skin on the penis and decreasing sensation. Maybe this will help. Unfortunately, with all drug treatments for this condition, when the drugs are stopped, the issue generally returns.

What I find interesting is that companies are vigorously trying to drum up sympathy and attention for premature ejaculation as a widespread medical disorder, when in many cases it may be only an occasional annoyance that does not need constant treatment. Treatment might be perfect for a few men with debilitating disease, but it appears that they are trying to create and market a whole new category of disease. Good idea: create a “huge unmet need,” an epidemic that is perfect for a blockbuster, quality of life drug. Well what about a pill for shyness, or talking too fast? Where does it end? The larger issue here might be the “medicalization” of our daily lives in which there is a healthy and wide variation of normal.

Do I believe that some men have debilitating early ejaculation? You bet, and I see them every day. Do I think that a pill will treat this issue? Sure, for many, but only while you take it. Will blockbuster pills be the cure-all for early ejaculation? No way. The cure will come with more holistic treatment, by empowering men through behavioral changes that teach them to control and “own” the problem. Works superbly for my patients, pill or no pill.

Throwing a wrench in the machinery of sperm production...

I have to admit, the testis “mapping” procedure that I developed some years ago has truly been a workhorse technique for my male infertility practice. And for the practices of other male reproductive specialists around the world as well. Creating fertility from sterility. I bring it up again because it is gathering more attention in the press as this week we recently published another paper that highlights its utility—this time in cancer survivors.

In a related study from 2002, we published that the majority of men who had been exposed to chemotherapy for cancerous or non-cancerous disease and who were “sterile” afterwards have sperm in the testis that can be safely used for fatherhood with assisted reproduction. Fine needle aspiration (FNA) mapping was employed in this study and its potential to help cancer survivors to conceive was convincingly demonstrated. The recent paper expands that group of men to include those who received not only chemotherapy and radiation therapy but also a relatively extreme treatment for certain cancers termed bone marrow transplantation.

Let’s back up a minute for a biology lesson. How does chemotherapy affect a man’s fertility? Well, the basis of its effectiveness in curing cancer is that chemotherapy preferentially kills rapidly dividing cells more than slowly dividing cells. In general, cancer cells divide more rapidly than do normal body cells. The term for this difference in cell susceptibility is “therapeutic index”. Unfortunately, sperm are also produced very rapidly (about 1200 sperm are made every heartbeat) and therefore sperm precursor cells are also very sensitive to the effects of chemotherapy. Think of sperm production as a rapidly turning set of gears and chemotherapy as a wrench being thrown into them. Ka-chunk! Machine comes to a loud and crashing halt. Sperm production is over, or tremendously slowed down. The same action is true for radiation therapy treatment.

Now, imagine not just one small wrench being thrown into the gears, but a huge wrench (or many wrenches) being suddenly thrown into the machine of sperm production. The result? More damage to the sperm-making machinery and a much higher chance of sterility. This is the essential difference between the patients from the 2002 paper on mapping and the most recent one. The cancer survivors in this week’s paper got blasted with the heaviest doses of chemotherapy imaginable, and topped off with a dollop of radiation therapy just to be sure. Hard to believe, but they also had usable pockets of sperm in their testicles. And normal babies as a result.

So, with techniques like FNA sperm mapping, there continues to be hope and good news about fertility after the storm of cancer treatment has passed.

Bacchus is no longer a role model...

What you weigh affects how your sperm play. And your fertility. Overweight men tend to have lower semen volumes, less sperm and more oddly shaped sperm. The same is also true for men who are too thin. So, along with the many other health hazards associated with obesity, add poor semen quality to the list.

Obesity in both sexes is known to be associated with heart disease, diabetes, hypertension, and metabolic syndrome among other nasty conditions that can shorten your life. Typically, obesity is measured with BMI or body mass index, which looks at weight in relation to height. Not a perfect measure, but reasonably accurate. Using this tool, the ideal BMI for men (and women) is considered to be 20-25. A Danish study of 1600 men showed that overweight men with a BMI > 25 had a 22% lower sperm concentration compared with healthy weight men. Interestingly, a BMI of <20 was also associated with poor semen quality. For optimal sperm production, then, it helps to be not too fat and not too thin.

But what about fertility? Is it also affected by obesity? Yup. Another recent study showed that for every 20-pound increase in a man’s weight, there is a 10% increase in the chance of infertility. And this remained true when other factors that might influence the results were accounted for, including obesity status of the women, the man’s age, cigarette smoking, alcohol intake, and solvent and pesticide exposure. In addition, obesity was associated with infertility in both older and younger men.

So what is it about weight that influences men’s sperm production and fertility? One theory is that sex hormone metabolism is altered by changes in weight. Sex hormones are the “fuel” for the engine (testis) to make sperm. Obesity increases fat stores and fat converts male hormones (testosterone) into female hormones (estrogens). Too much estrogen in men is bad for sperm production. Another theory posits that normal 2-degree difference in testis temperature relative to the body is lost with obesity, as excessive fat provides too much insulation and results in overheating. On the other hand, when a man is too thin, he may take on a “catabolic” metabolic state. With a body in “starvation mode,” fertility is not the first thing on its mind and sperm production and fertility suffer.

So, is the epidemic of obesity the reason why sperm counts have been falling in Western countries over the last 50 years? Maybe. But this problem is unique in that it is utterly and entirely preventable. Eat well and in moderation, sleep well and treat your body like a temple. You used to it for your own health; now do it for the health of your future family.

Heirlooms for the species.

As a living, breathing being on this good earth, we tend to take things for granted. The ability to have offspring can be one of them. That is, until the day that a serious medical condition like cancer rears it ugly head and puts childbearing at risk. In addition to the sterilizing effect of cancer treatments, the mad rush to treat the disease often marginalizes efforts to preserve fertility. Fire all the canons and check for collateral damage later.

Fertility preservation seeks to protect men, adolescents and children from a common, serious and impactful side effect of cancer treatment: infertility. The goal of fertility restoration is to empower patients who are cured and potentially infertile to bear children. These related fields have burgeoned recently because medical care is now shifting from curing cancer to improving the quality of life among survivors. And without a doubt, for many, fertility is a key quality of life issue at some point. Thankfully, exciting new methods of restoring fertility have already been developed and even newer technologies are under study.

Classic techniques for fertility preservation in men include gonadal shielding and sperm banking. Gonadal shielding uses lead-based devices to protect the testicles from being struck directly by sterilizing radiation treatment. Sperm banking is the process of freezing healthy sperm before cancer treatment begins for later use to conceive. But there is more. For patients who are too young to bank sperm, for those who have precious little time to bank sperm, or for those who have no ejaculated sperm to bank, testis sperm retrieval by biopsy (TESE) or needle aspiration (TESA) for banking is now possible before cancer treatment. In fact, in some cases of testis cancer, it is possible to remove only the cancerous nodule instead of the whole testis, or to freeze sperm from the testicle after it is surgically removed. These are now routine ways to preserve fertility in men.

Fertility restoration for men has also seen real advances lately. Sperm “mapping” is an innovation that I developed for men who survive cancer treatment but have no sperm in the ejaculate. It non-invasively and non-surgically deciphers whether there are small numbers of mature sperm in the testis, too few to get into the ejaculate, but usable nonetheless. In men who sustain nerve injury from cancer surgery and who are unable to ejaculate, a special medical instrument can produce an ejaculate for fertility purposes in a process termed electroejaculation. Techniques such as these are valuable tools to help men deemed “sterile” after cancer treatment to become fathers.

One of the most exciting areas of fertility restoration involves stem cell technology. Yes, the “promise” that we have all heard about stem cells curing disease will likely find its way into the fertility field as well. In pre-pubertal boys with cancer, ejaculated sperm is not present. Despite this, it may be possible to freeze the early stem cells from the testicles of boys before sterilizing treatment. After thawing, these “adult” stem cells may later be used to create sperm after further growth in a Petri dish or after transplantation back into the same individual. Also on the horizon is our ability to take skin cells from a sterile man, convert them into an embryonic-like stem cells and then “drive” these cells to become mature sperm in a dish–a true “artificial testicle.” So, with the belief that hope can cure misery, the world of science has taken fertility research from science fiction to reality. Not convinced? Stay tuned!

A woman whose independence lasted longer than most countries.

Excuse my diversion from men’s health, but a very important woman in my life has just passed away. My last grandmother (known as Oma) lived a fiercely independent life for over 99 years, longer than most countries.

She brought our family to America from what is now Czechoslovakia in 1950, after 1000 years of farming the land and a generation of recent persecution. She brought a husband, a son (my father) and her daughter, each with a single suitcase, to Connecticut to start life anew. And we have prospered here since. A typical immigrant story.

She lived in her own home for 56 years, preparing every meal from scratch, and died there. A simple humble, life and a simple humble death. If you got to her house too late in the morning after a winter storm, you would find her clearing the snow from her driveway well into her 90’s. I only knew her as a gray-haired grandmother, but she was a constant and a compass to the entire family: our north, our south, our east, and our west. Rooted, decisive and opinionated, she was usually right, but never wrong.

She was a woman of the land, a gardener and a grower. In the words or Rilke, she knew the sound that small flowers make when they open in the morning.

The Germans play a card game call Setback, like Bridge. If you played on her team, you usually won. It was something about those million fine wrinkles that gave her the perfect poker face.

She leaves to 6 grandchildren and 8 great-grandchildren on both coasts a spirited legacy of wisdom, willfulness and fortitude that will survive for generations.