Posts Tagged ‘reproduction’

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.

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.

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!

What Comes After the Pill?

Sunday, November 15th, 2009
Making the world a better place with modern technology.

Making the world a better place with modern technology.

In this forum, I’ve already talked about how erections occur and also about pills used to treat erectile dysfunction in men. But what if they don’t help? What comes after the pill?

There are about 30 million men in the U.S. affected by erectile dysfunction. For 20% or more of men, common prescription therapies – Viagra, Levitra or Cialis – are not effective. For these men, we have many things “up our sleeves” to help. Before reviewing this cornucopia of cures, I really need to emphasize again the idea that erectile dysfunction may be a message that your body is not perfectly healthy. Think of it as a loud noise coming from under the hood of the car. It may run fine if you keep going, but you never know. Similarly, medical conditions such as high blood pressure, heart disease, high cholesterol, diabetes and low testosterone are important “loud sounds” that are associated with erectile dysfunction; they should be treated first and foremost. Often, by treating these illnesses, not only will erections improve, but you might live better and longer too.

Ok, so your cholesterol is fine. How then can erections be improved? Well the answer may be to “go local.” Local therapies attempt to improve erections by going to the source to treat the problem: the penis itself. Help the big guy out without involving the rest of the body. Penile salves, creams and urethral pills are available in many forms and are often compounded by pharmacies. One of these is a pill (MUSE) that is inserted just inside the urethra (the urine tube within the penis) and is absorbed by the penis to stimulate an erection. A little unconventional, but very effective in some men.

Although more difficult to imagine, local therapy can also involve injecting the side of the penis with highly active erectogenic agents such as papaverine, phentolamine and prostaglandins. Not the most palatable way to get an erection, but highly effective for the vast majority of men who fail to respond to pills. A more inviting alternative is based on recent developments in transdermal technology and involves delivering the same three medications in a clear gel into the urethra (TriMix Gel). Rub it in for a minute or two and you are up and running.

Available for 30 years now, penile vacuum pumps will also work in the majority of men. By creating 6 atmospheres of negative suction pressure around the penis, these mechanical devices draw blood directly into the penis. Once filled, a rubber ring is placed around the base of the penis to keep the blood in and away you go. But please don’t keep the ring on too long (more than 45 minutes) as bad things could happen…

In the most resistant cases, surgical implants may be needed to resurrect the erection.  Reliable and realistic, implants are the most invasive kind of local therapy and are effective in virtually all men. They can be rigid but bendable, inflatable, antibiotic coated and can have other neat widgets and gadgets. But they do require surgery, which distinguishes them from other treatments. They are also irreversible in the sense that they permanently alter penile anatomy, rendering ineffective most other treatments discussed here. So, let it be known that “vee have vays” of getting those erections back in case the pill doesn’t work.

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.

Are We Replacing Ourselves?

Tuesday, September 8th, 2009
Where are you? Green means high and red means low.

Where are you? Green means high and red means low.

When a couple decides to have children, they rarely, if ever, contemplate the effect this has on the nation. But population scientists do. The effect that birth rates have on society is critical—as basic as knowing whether a nation is sustaining their population or not. But, trying to figure out if birth rates are going up or down is also complex, not unlike taking our temperature by feeling our foreheads.

A good barometer of birth rate assesses the average number of births per woman, and is generally noted by country. For a country to sustain its population in the future, the replacement rate is 2.1, or 2.1 births to every woman. What has occupied the minds of population scientists over the past 20 years is the fact that birth rates have dropped around the world, especially in Europe, but also in China and Japan. Interestingly, many countries in Africa do not have this problem, with birth rates well above 4. 

Also notable is the fact that in the past 20 years, the population of the world has dropped, falling an average of 1% per year. You can imagine how much this issue has occupied the minds of population scientists who seek to explain the phenomenon. Contributing factors include changing attitudes about family size, the cost of raising a child and the wider availability of contraceptives. The birth rate may also be dropping because child mortality on the whole has dropped. Or, because women who choose to have children later create a temporary lull in the birth rate. One concern with population drops is that countries whose populations become too small may not be able to afford to support its infrastructure, causing economic decline. So, on the one hand, it’s expensive to raise a child. On the other, it’s also expensive not to.

A recent study however, does show a change in these trends. Fertility rates now show a recent increase in developed nations. For years it has been thought that for some reason, developed nations, including most of Europe, have steadily dwindling populations. But this may not actually be the case. For example, in the 1970s, the US fertility rate was at a low of 1.74; lately it’s been relatively stable at 2.05. It appears that children are still wanted in a modernized world.

It’s quite hard to see these trends in my daily medical practice, as I perform as many vasectomies as I do vasectomy reversals. It’s even harder to render an opinion when the information is so diffuse and generational. So, to population scientist, I am a professionally “neutral contributor” to fertility rates. Like to think I do more good than that though…

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!

The Ailing Male Pill

Thursday, August 6th, 2009
What shape will the male pill take?

What shape will the male pill take?

A male birth control pill certainly sounds like a good idea. But after 25 years and millions of dollars of research, there’s still no pill. We put a man on the moon faster than we’ve invented a male pill.

The question isn’t really whether it can be done, because it can. The production of sperm is linked to testosterone levels in the body. When testosterone levels are too high, the body stops producing sperm. Witness the testis shrinking (atrophy) that occurs with anabolic steroid use. Such pills have been tested, and are successful. One problem, though, is that the ability of hormone-based male pills to work perfectly (which they really need to do) varies with a man’s ethnicity. Works for some, but not all. This issue alone may prove fatal for the male hormone pill.

Besides this, there is a litany of concerns regarding the physical side effects of a hormone-based male pill. Immediate concerns have been a big issue in past trials- adult acne, weight gain, moodiness and the like. But what about possible long term effects? The female contraceptive pill has been linked with higher rates of heart disease and breast and liver cancer in women. Although not completely comforting, at least we know these issues in women. But little to no research has addressed similar issues with long term “pill” use in men.

Despite all of this, there is still a healthy interest in a male birth control pill. Studies have shown that men in committed relationships are more interested than single men in a pill– no surprise here. Single men are interested in using condoms for the added bonus of protection against STDs. A male birth control pill might also be a better contraceptive alternative for men who want more control over family planning than that offered by vasectomy. That said, there is still the eternal question of whether or not a pill would sell successfully– would women, in the end, trust their partners to be consistent and compliant in taking the pill? The answer to this question varies from couple to couple, but to get a sense of things, ask yourself how often you fail to take something as simple and uneventful as a daily multivitamin to get an idea of the magnitude of this problem.

There simply aren’t enough options for male contraception on the market today. The main ones are abstinence, rhythm method, withdrawal, condoms, and vasectomy. Given this lineup, there is certainly room for more, and more reliable, contraceptives for men. One thing seems reasonable clear: given the safety and effectiveness of vasectomy, and fact that daily compliance is not needed to keep it effective, anything new has to be this good or better. How about a truly reversible vasectomy? Or a long term, implantable hormonal device? In the end, these are likely to become tasty alternatives to a male pill.

Pulling Out is In

Thursday, July 30th, 2009
Barrier contraception faces stiff competition...

Barrier contraception faces stiff competition...

Hold on now. Wait a minute. Don’t get too excited. If you thought “pulling out” was a feeble and ineffective method of contraception for the reckless and unprepared, well it is. At least at first glance. But given that at least 38 million couples use it worldwide, coitus interruptus warrants a second look. 

Coitus interruptus, with its ancient yet undistinguished history, is very easily dismissed as an effective contraceptive because of the widely accepted belief that the pre-ejaculate contains sperm. There is actually no conclusive evidence that this is the case. No one has actually found sperm in pre-ejaculatory fluid. In addition, it is all-natural, organic, hormone- and side effect-free, and affordable. It needs no tool that nature hasn’t already given us, except rigorous and unerring self-control. Well, in fact this is the big downside. Who has rigorous and unerring self-control? We are men, not robots. Pulling out doesn’t protect you from sexually transmitted diseases, either.

That said, a recently published study has shown for the first time in the modern era that withdrawal is more effective a contraceptive than one might think. Maybe we should look at the pull-out with a little more respect. The withdrawal method, when used with perfect technique, has a 4% failure rate. This falls behind vasectomy (0.1%), birth control pills (0.3%), IUDs (0.6%), and condoms (2%), but not by much. The actual (real life) failure rate is likely somewhere between 15-25%, which is really not far behind the actual failure rate of condoms, at 10-18%.  So withdrawal is not that bad after all, only a little less effective than condoms. Perhaps men deserve a pat on the back for this. Well done. 

However, if this were a contraceptive pill, a 15% failure rate would send its inventors back to the drawing board. For coitus interruptus is inherently flawed, and women who seek more control over whether or not they become pregnant are more likely to reject this method over the long term. One study revealed that women of higher economic status and education are more likely to insist upon a more surefire method of contraception. It appears that women simply don’t trust men’s timing, their control, and perhaps even the male sense of responsibility when it comes to contraception. They want more control in the matter. What does this mean for a male contraceptive pill? More on that next week.

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.