Posts Tagged ‘male infertility’

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Good Job Government!

Sunday, February 28th, 2010
The best medicine for man is man...and good government

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.

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Posted in male infertility, men's health | 1 Comment »

Your DNA Barcode

Sunday, February 21st, 2010
Can we be DNA barcoded like a soup can in a grocery store?

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…”

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Metabolomics: The Picture of Fatherhood

Sunday, February 7th, 2010
Cellular metabolites: woven together like a rug

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.

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The Quiet After the The Storm of Cancer

Sunday, January 17th, 2010
Throwing a wrench in the machinery of sperm production...

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.

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Posted in male infertility, men's health, sexual health | 2 Comments »

Weighing Your Options

Sunday, January 10th, 2010
Bacchus is no longer a role model...

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.

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Posted in male infertility, men's health, sexual health | 2 Comments »

Keeping the Family Jewels Shining

Saturday, January 2nd, 2010
Heirlooms for the species.

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!

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Posted in male infertility, men's health, testis cancer | 4 Comments »

A Short History of the Y Chromosome

Tuesday, September 22nd, 2009
The Y chromosome: diminutive but cool.

The Y chromosome: diminutive but cool.

Among the many chromosomes in a man’s body, the smallest one with the largest personality has to be the Y chromosome. With it, you are a male; without it, you are a female, with few exceptions. More than any other chromosome, it really defines who you are.

The Y chromosome controls other traits as well: hairy ears, tooth enamel, and stature to name a few. But for the longest time, the Y chromosome was also considered home to a lot of “junk DNA” that we thought had no purpose. We now know that much of this DNA has a purpose and that the Y is the home of many important male fertility genes.

Before its association with male fertility, the Y chromosome was widely considered a genetic black hole, a chromosome that evolved as a broken remnant of the X chromosome. We knew that the “maleness” gene was on the Y and a few other genes. However, since the Y chromosome has been fully undressed as a result of the human genome project, we now know that it is very unique, even special, and that it evolves in its own special way to keep men men.

The Y chromosome, and its neighbor the X chromosome, evolved into “sex” chromosomes hundreds of millions of years ago. This is important because many species do not have a chromosome for each sex like we do. Some species become male or female based simply on the environment in which they find themselves. Imagine that! A boy in the Artic but a girl in the Caribbean. At first, the original sex chromosomes probably evolved as a pair of two X chromosomes. Then, 150 million years ago, the Y chromosome made its break from the X chromosome. Basically, it stopped associating with it and this led to our current X-Y system of sex determination. I guess this is when men really became men.

As it works now, the single Y chromosome has no partner with which to swap genes when sperm are made (at a normal rate of 1200 sperm/heartbeat!) This “swap meet” of genes that occurs when new sperm are formed is an important repair process for the 22 other chromosomes and is absolutely critical for our evolution as a species. In fact, this is the source of our evolution. So, now that the Y chromosome has become isolated and less of a team player, is it doomed to extinction? More importantly, are men are doomed to extinction?  

So how does the Y chromosome survive and repair itself, living alone in isolation while the world is changing around it? Well, we now know that it manages very well on its own, thank you. And this has probably been true for about 5 million years. Although it no longer swaps genes with the X chromosome, from which it came, the human Y chromosome is able to swap genes with itself to discard bad genes. It’s called gene conversion and no other chromosome does it. Just the Y. How uniquely male.

Basically, essential Y chromosome genes are arranged in a series of eight “palindromes,” or mirror image sequences, each of which folds like a hairpin in which its two arms come together. Then the “DNA checkers” compare the two arms for any differences and convert a mutation back to the correct sequence, thus saving the Y’s genes from mutational decay. So, the older “junk DNA” thought to exist on the Y chromosome is now known to represent DNA that it critical for its survival. One man’s junk is another man’s treasure. And so it goes, the Y lives on, and men do too.

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Baby Making Tips

Wednesday, August 19th, 2009
The most fun he ever had without laughing

The most fun he ever had without laughing

You might have “practiced” the art of baby making for quite a while. But have you actually tried to make a real baby? What does it mean when a couple says they’re “trying”, besides jettisoning the condoms, scheduling free time, and practicing your “sore throat” voice for calling in sick to work. No one teaches you the nitty gritty of baby making in sixth grade sex ed classes. So, here are some of the finer points.

First of all, your chances of conceiving decrease if the two of you are under stress. Frequent travelling, major life changes, a long sickness, being vetted for the Supreme Court, running a start up with a gazillion hours weekly, are terrible for getting one “in the mood.” If the body is under stress, it’s in the primitive “fight or flight” response, and it’s not exactly in the mood to reproduce. So to improve your chances, decrease your stress level by eating well, sleeping well, staying healthy and relaxed, and treating your body right. If you are chronically overworked, you may consider decreasing or delegating your responsibilities. If this isn’t possible, force your body to relax with exercise, yoga, massage or acupuncture. Also, quit smoking, drink no more than two glasses of alcohol daily and avoid hot tubs and hot baths (showers are fine).

Like many things in life, timing is everything. Eighty percent of pregnancies occur when sex takes place before or during ovulation, which is the time when a woman’s ovary releases an egg for fertilization. But how to tell when ovulation is occurring? The most accurate way would be with an “ovulation predictor kit” purchased at any drugstore. Like a pregnancy test, it uses urine to determine if ovulation is about to occur. The old-fashioned method, which also works well, would be to pay attention to her basal body temperature. To do this, she should take her temperature first thing in the morning, for a string of consecutive days during the middle of her monthly cycle. There should be a dip in her temperature, followed by a rise. This indicates ovulation.

Once you know that the egg is on its way, intercourse is best performed every other day. Men need time between ejaculations to “reload”, and daily intercourse may not give a man enough time to do so (sorry guys). As for the act itself, studies have shown that no particular position is best. Research is suggesting that the two of you can bend yourselves into pretzels, if desired, with no effect on your chances of conceiving or on the gender of the child.

Baby making is a special experience. And, it’s fun! As Woody Allen said in the movie Annie Hall, ”…sex is the most fun I ever had without laughing.” If you think about it, what I am suggesting is that you and your partner make it a habit to take the best care of yourselves, just as you are going to take the best care of your child. Set the example for the new family and enjoy the ride!

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Sexual Health Pop Quiz #2

Monday, July 20th, 2009
Remember computer test bubble sheets? Get out the #2 pencils...

Remember computer test bubble sheets? Get out the #2 pencils...

You may call me a stern and demanding taskmaster, but because the last one was so much fun, it’s time for another pop quiz on men’s sexual health. This one is based on real-life, case-based questions.

1. In anticipation of a romantic encounter with his partner, and to help him be the best that he can be, a man takes Viagra. His next move should be:

A. Watch Law and Order, a stirring drama to stir the loins.
B. Go to the post office and renew his passport.
C. Eat tacos and drink beer.
D. Play strip poker with his romantic encounter.

Answer: D. Viagra and the other erection pills do not provide an instantaneous erection. They may take from 20-60 minutes to work. In addition, they won’t give you an erection unless you want it to occur. Engaging in stimulation and foreplay is an excellent way to spend your time waiting for the pill to kick in.

2. Good sex ALWAYS involves:

A. Multiple orgasms from your partner.
B. Whatever looks really freaky in the last pornographic film you saw.
C. Kinky stuff.
D. Leather of one sort or another
E. None of the above.

Answer: E. In our society, exceptions to any rule fascinate us. Here, extreme sex performance acts, characteristic of pornography, are the exception. Sex was designed by Mother Nature to be satisfying when undertaken in many different ways, and takes many different forms, all of which can be intimate and pleasurable without having to go to extremes.

3. The problem with porn on the Internet is that:

A. There is no problem! It’s good fun and free!
B. The video is fuzzy and far too pixilated.
C. I can’t watch it at work without getting caught.
D. I can get too used to it, and sex with my own partner could become unsatisfying.

Answer: D. With the increasing availability of porn, a serious problem is arising. Men who are without partners become accustomed to that kind of sexual stimulation and then end up needing that same kind of stimulation to become aroused with a partner. So, when they find themselves face to face with an honest-to-goodness, flesh-and-blood woman, they may have trouble performing. This is an increasingly common issue for sex therapists.

4. TRUE or FALSE: You and your partner have a night in together. You turn off the television, go upstairs, and tenderly give each other long, leisurely massages with body oil in a room lit only by candles. You have a great time. This constitutes a satisfying sexual experience.

Answer: True. “Sex” does not have to involve sexual intercourse and climax and orgasm. The point is to feel satisfaction and closeness with your partner. Of course sex can involve pure carnal pleasure, but that definition should be broadened to include other emotional and physical intimacy.

5. TRUE or FALSE: Since the advent of free love, we’ve become liberated from the sexual taboos of our mothers and  fathers.

Answer: Profoundly False. Although we’d like to think so, sex therapists still see tales of embarrassment and lack of communication between couples, now more than ever. Being able to express our needs, both emotional and physical, without embarrassment or shame, is a problem of the ages.

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Infertility: Window into Men’s Minds

Monday, July 13th, 2009

It's true...it hurts to be infertile. Like any other disease.

It's true...it hurts to be infertile. Like any other disease.

Recently, sitting face to face with an infertile patient, I asked him what the first thing was that came to his mind after being told that he had no sperm count. After a short silence in which his eyes gazed downward and then back again toward me, he stated, quietly “I thought it might be the end of my family lineage.”

Facing a diagnosis of infertility is one of the loneliest experiences a man can have, as evidenced by a study I recently co-authored with Drs. James Smith and Patty Katz at UCSF. Published in The Journal of Sexual Medicine this week, it found that men with a diagnosis of male infertility suffer intense negative sexual, personal and social strains that might be considered typical for other medical illnesses, including cancer. It affects not only their self esteem, but their sexual confidence and sexual function. Think about it. Men find the inability to sire children a real and palpable blow to their manhood and self-identity. The impact of this diagnosis is easily comparable to the mortal challenge associated with a cancer diagnosis. Infertility causes an immense strain to their relationships both with their partners and socially. Adding to the strain, this diagnosis is as taboo as syphilis or AIDS. The ramifications for the rest of his life are significant, especially if his lifelong assumption was that having kids is normal, expected, eventually, would not be a problem. Infertility is often one big secret that is kept from the rest of the world, making the patient, and his partner, feel isolated and desperate.

I have seen this distress in my practice, day in and day out, for years. Finally, through this study, some proof has surfaced that male infertility is one of the toughest challenges a man can face in life. The funny thing is, male infertility is not as uncommon as one might think. It affects 10% to 15% of reproductive aged couples worldwide. About half as common as diabetes. But far more silent a disease than diabetes. The bright side is that it is treatable in many cases.

So what should men do if they have a diagnosis of infertility? First, get information so that you can make decisions and get control of the situation. You need to “own” it, and this is a great start. Learn through websites such as ASRM.org and SSMR.org, or TheTurekClinic.com and see a urologist or specialist. Also, talk openly with your partner and people you trust, and get the support that you need. Decide with your partner who needs to know about this and who doesn’t. Keep the lines of communication open with your partner, as this can be the most significant threat your relationship will ever see. Keep doing the things that you do best, as these are not likely the cause of infertility and can keep the balance in your life. Importantly, take time to “blow off” stress through exercise, sports, yoga, massage or whatever works for you. Maintain that critical balance as you tackle this issue like you have tackled others, and as you will tackle future issues.

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