Turek On Men's Health » fertility restoration

A Year Without Answers II

Paul Turek, MD — Mon, 19 Mar 2012 15:00:18 +0000

Rug design courtesy of Rex Ray, San Francisco

This is the second of two guest posts from a patient who lives in Europe. He recently recontacted me about his experience with male infertility and how it affected him. Moved by his story and by his emotional fortitude, I asked him if he could share his remarkable journey with others. The first post is from March 12th.

I had to face the fact that I was my own worst enemy. This was an epiphany for me. By becoming a negative person, spontaneity and creativity had left me, high and dry. And gone with it was the ability to problem solve. For me, once of the hardest things that I have ever had to do in my life was to admit that I was the root of the problem, that I was responsible. The epiphany was that because I was the problem, I could also be the agent of change. I could own this. The rebuilding of me had to start with me.

It was at that point that I reached out to a psychiatrist, Our talks helped me find my way back. Honestly, I never knew that these sides of my character even existed, and was even less aware that they would belch from my soul as they did. These sessions allowed me to vent my feelings and, over time, I felt better and better. It felt like I could take the 800-pound gorilla to the doctor’s office and leave it there. And, funny enough, the “gorilla” began shrinking in size with each session, almost to the point of becoming a small, friendly monkey. And although even cute little monkeys can be annoying, these sessions helped me enormously by providing tools and methods to help me better understand, accept and manage such strong feelings.

Modern societies of any culture, Western or Eastern, are not great at raising men to be in touch with their emotions. And realizing that you are infertile is a very hard blow to one’s manhood on many levels. One of the most concerning issues was worrying about what others were thinking or knew about my situation. Early on, it bothered me to think that they would find out. As I began to heal, however, I began to care less and less about what others thought. I simply can´t control other people’s minds and have no interest in doing so. I also realized that those who are close to me all know about the infertility and nothing has changed between us and how the view me as a person. The rest I leave in God’s grace.

Another realization over the last year is that infertility is not a disability in life. It is in fact the way that I was created. It is part of me. It is who I am. And although I can’t change it easily like, say, losing weight or getting more exercise, I can certainly change how I view it. I can shape my future in any way that I wish. I am the master of me.

The road I took that year was no easy one, but I made it through the year. Leaving this behind me, I can now move forward in my life. I have faced the demons and have come to terms with my reality. I now look upon the future with renewed eyes and see a future filled with happiness despite the fact that I cannot have children.

Please let us know if you would like to continue a discussion of these issues in an on-line forum…

The Incredible (Renewable?) Egg

Paul Turek, MD — Mon, 05 Mar 2012 18:32:47 +0000

The human egg: a thing of beauty…now a renewable resource?

It’s hard to keep up anymore; things are changing so quickly in fertility medicine. Just in the last week, a Harvard researcher discovered stem cells in the human ovary and a 66 year old just became a mom to twins in Switzerland. There goes the rug, being pulled out from under our scientific feet yet again.

Testicular Stem Cells

A couple of years ago, we published a paper confirming the presence of cells in adult men that were long though to exist: testicular stem cells. These are “multipotent” cells unlike most other cells in the body: they not only renew themselves, but they can also become sperm and may even be coaxed into becoming other organs in the body. The really convenient thing is that they are not derived from embryonic stem cells (a political minefield) a fact that makes them prime candidates for stem cell-based treatments in the future.

The Dogma About Eggs and Ovaries

But eggs are not sperm. Sperm are made constantly throughout a man’s life, like blood cells, and therefore it makes sense that there are stem cells running the show. However, for at least as long as I have been in medicine, it has been thought that women are born with all of the eggs they will ever have, some 1-2 million, and lose them throughout life, most obviously through monthly ovulation, until they are gone. The basket empties of eggs somewhere in the 40’s for most women, about 10 years before menopause. This lack of new egg production has led to the belief that, unlike within the testicle, adult stem cells do not exist in the ovary.

Ovarian Stem Cells

But Dr. Jonathan Tilly at Harvard thinks otherwise. He believes that women indeed have adult stem cells in the ovary that might be able produce new eggs during a woman’s lifetime. And maybe even after her traditional reproductive window has closed.

Dr. Tilly first showed this in mice and published it in 2004. He recently extended this work to women by locating an incredibly scare biological resource: fresh ovaries donated by Japanese women undergoing sex change procedures. Within this tissue, he found cells that showed classic stem cell characteristics using genetic markers. But this only means that they “look” like stem cells. To prove that they can “act” like real stem cells, he isolated these cells in a Petri dish and watched them turn into real, live, immature eggs. More convincingly, he then transplanted them into mice and they continued to develop into even more mature eggs, passing through meiosis in some cases which is a characteristic process occurring only in eggs and sperm.

So what are the implications of this technologically mind-bending work? Hard to know, but down the line it may mean that women may be able to make new eggs when we thought that they couldn’t. Maybe their baskets never really empty of eggs and that their fertility can be extended beyond what we now think is possible.

Regarding the 66 year old women who just had twins…it’s not clear to me how many genetic parents were involved, how long it took, and how heroic the effort was, but I can guarantee you that she will have her hands way too full for the next several years to keep up with this science.

It’s in the Steak

Paul Turek, MD — Tue, 21 Feb 2012 16:00:48 +0000

Hope is a core value of children (Drawing courtesy Sophia Turek, age 7)

In quiet moment on the couch, I recently asked my 8-year old daughter what the word “hope” means to her. “If life were a meal, hope belongs in the steak,” she said.

The food metaphor didn’t surprise me, as with most kids her age, she thinks about it a lot. What did interest me was that, in her view, hope takes center stage. It’s not the cupcake for dessert. Or a sweet milk shake, or potato chips. To kids, hope is serious stuff, right smack in the middle of the main meal. Just a hunch, but I am convinced most adults would not put it there.

A Telling Telephone Call

He called from Kentucky. Having read about our recent research story about obtaining grant funding to build an artificial testicle, he wanted to know more. As a cancer survivor, he had no chance of fathering a child. He asked great questions about where the research was going and the expected time line for generating sperm from stem cells. I answered frankly as I am not a fan of dangling carrots or pipe dreams in front of others. He listened intently and thanked me kindly. I asked him to keep in touch, and that was that.

Little did he know such brief but meaningful conversations stokes my fire and fuels me to imagine, begin, execute and finish such far-fetched research projects.

Little did I know how that single, brief exchange also affected him. The next day, the Clinic received a new Yelp review (don’t get me started on this…just compare the visible reviews on the page with the invisible “filtered” accessed at the bottom). Curious, I read it. It blew me away. It went something like this (edited for brevity):

“H-O-P-E; that’s what Dr. Turek has given me; new found hope…..” After a 16-year nightmare with testicular cancer, once in 1996 and again in 2002, a good friend of mine forwarded me the most shocking, exciting, uplifting, inspiring article I had EVER read. I anxiously and carefully read it word for word, line for line, as I could not believe what my eyes were reading and my mind was comprehending. My instinct, was to call Dr. Turek’s office immediately as I was yearning for more information.”

“After talking with his office staff, a phone conference was scheduled for Dr. Turek and I within the next 3 days…Dr. Turek gave me “me” and he gave the rest of the testicular cancer world a vision that we never imagined possible… I will strive daily to do everything in my power to assist Dr. Turek in seeing this miracle discovery come to life. I will do whatever, whenever, whereever it takes to be a part of this life changing miracle. I am inspired, encouraged, and relieved with the hope of tomorrow for me and for others.”

For the first time in years, the man from Kenucky felt a ray of hope. And in some small way, his life is different today than yesterday.

Hope not Hype

So what is it about being an adult that takes the hope out of our “steak?” Why do long, strong doses of reality make it harder to dream the unimaginable? There is so much promise in hope that I, for the record, refuse to give it up. I agree with the old French Proverb that “hope is the dream of a soul awake.” You can expect more of the unimaginable out of me before my time is up on this good earth.

The Artificial Testicle: Funded!

Paul Turek, MD — Mon, 02 Jan 2012 16:00:01 +0000

Whole Earth Catalog: the old Google, according to Steve Jobs

It is the stuff of dreams in academic medicine: an NIH (National Institutes of Health) research grant. Get one of these and you’re pretty much assured of getting tenure and succeeding at any major U.S. university. It is the ultimate stamp of approval from the government and society that your thoughts and ideas have merit and value.

And I was just awarded one!

NIH Funds the Artificial Testicle

Yes, the federal grant that we submitted recently to build a human artificial testicle was funded. To be clear, this grant is not about creating a testicular implant for a man who is missing a real one. We did that a decade or so ago. This award is to develop a sperm making biological machine. I wrote it along with Dr. Connie John, CEO at MandalMed, Inc., a biotechnology company in the Bay Area. We now have a couple of years to create human artificial sperm in a dish, or more formally, a “bioreactor.” A fancy dish to be sure.

You’ve seen the posts on how successful this research has been in mice models using various stem cells as a starting point: embryonic stem cells, adult stem cells and early germ line (spermatogonial) stem cells. In labs all over the world, real, live, fertile sperm have been made in animal models from each of these stem cell precursors. Honestly, given this success over the past several years, surely we can figure out how to do the same in humans.

Why Do I Need NIH Funding?

Funny thing is, I am not in academic medicine anymore. No tenure to deal with and no need to prove anything to anyone but myself and to legions of loyal patients who depend on cutting edge innovation for their infertility care. Personally, feeling the suffering of patients with infertility is far more motivating than doing science for the sake of science, or for the sake of tenure.

Not to compare myself to Steve Jobs in any way, but I can’t help think one of his favorite mottos from the Whole Earth Catalog. This is what guided him in his quest to build a better computer for everyone: “Stay hungry; stay foolish.” It feels absolutely fabulous to be able to dream it, write it and finally to do it. The essence of science for the good of people.

Press Release

Effort to Build Artificial Testicle Awarded NIH Grant

Released: 1/9/2012 1:45 PM EST
Source: The Turek Clinic

Proposal to make human sperm from stem cells receives government funding

Newswise — SAN FRANCISCO, CA. January 9, 2012. Dr. Paul Turek, Director and Founder of The Turek Clinic, a men’s health medical practice, and Dr. Constance John, chief executive of MandalMed, Inc, a San Francisco-based biotech company, were recently awarded a Small Business Innovation Research (SBIR) grant from the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) to construct an artificial human testicle and research how sperm are made from stem cells.

“Fertile sperm can be made from various stem cells in mice, but making human sperm from these same sources has been elusive,” says Turek, a practicing male infertility specialist in San Francisco. In this project, they will try to produce mature human sperm in a live laboratory model of a human testicle.

This work extends on previously published research by Dr. Turek on human testicular stem cells, the forerunners of sperm. Dr. John is an expert on human Sertoli cells, which critically nurture sperm as they develop in the testicle. “This grant is quite an honor and comes after several years working together on this idea,” notes Turek. “We have assembled a great group of scientists who are very committed to its success.”

A functioning artificial testicle has important implications for the field of reproductive biology. It could shed enormous light on the intricate details behind the mysterious and complicated process of spermatogenesis or sperm production. Even further, it could be used to later develop patient-specific, fertile sperm for men who simply do not make sperm due to genetic or acquired causes.

About Paul Turek, MD
Paul Turek, MD is founder of The Turek Clinic and a former professor and endowed chair at the University of California San Francisco. As a men’s reproductive health expert, he has pioneered innovative techniques for treating male infertility, including Testicular Mapping. In addition to his appointment to the Cooperative Reproductive Network Advisory Board, Dr. Turek sits on the Advisory Board for the Men’s Health Network, Fertile Hope and is President-Elect of the Society of Male Reproduction and Urology. He is Chief Medical Officer at MandalMed, Inc, and is also Past-President of the American Society of Andrology and of the Northern California Urology Society and is an Editorial Board member of several journals including Systems Biology in Reproductive Medicine, the Asian Journal of Andrology and the International Brazilian Journal of Urology.

A complete biography of Dr. Turek is available on Wikipedia at http://en.wikipedia.org/wiki/Paul_J._Turek.

About The Turek Clinic
The Turek Clinic, founded in 2008, is a men’s reproductive health practice specializing in male infertility, vasectomy, vasectomy reversal, varicocele repair, and other minimally invasive procedures using innovative and cutting-edge techniques. For more information, visit www.TheTurekClinic.com, www.TurekVasectomy.com, or Dr. Turek’s blog (here).

About MandalMed, Inc.
MandalMed is a privately held biotechnology company located in San Francisco- the home of more bioscience companies than any other region in the world. MandalMed’s mission is to develop pharmaceutical products of worldwide significance. Areas where there is a great need for better treatments, including cancer and neurological conditions, are the targets of MandalMed’s research and development programs. For more information, see www.MandalMed.com.

Fertility from Sterility

Paul Turek, MD — Mon, 07 Nov 2011 16:00:55 +0000

What's inside of a coffee mug depends on how you look at it.

Do you think it is possible to have your own children with absolutely no sperm in the ejaculate?
Why yes. It happens on a daily basis in my practice.
Honestly, the word “sterility” has really lost much of its meaning nowadays with advances in reproductive technology.

The Affairs of Sperm

Azoospermia is the word used to describe the lack of any sperm in the ejaculate. It is a devastating thing for men to hear as they try to conceive. It comes in two forms: as a consequence of blockage in the sperm ducts outside the testis in the setting of normal sperm production in the testicle (i.e. vasectomy) or as a result of poorly functioning testicles and normal, open ducts beyond it. We routinely grab sperm from behind vasectomy sites to use with assisted reproduction to conceive. Finding sperm in men with poor sperm production, termed nonobstructive azoospermia, is a more complex matter.

One way to think about sperm production in men with poorly functioning testicles is to compare it to a mug with coffee in it. Say the mug is filled with ¼ cup of coffee. If you hold shake the mug, you may not see any coffee spill over the side. In this case, you might assume that the mug has no coffee inside. But, if you peer into the mug directly, you will see that there is actually coffee in the mug. Similarly, the testicle makes more sperm (coffee) than is found in the ejaculate (spilling over cup). There exists a threshold of sperm production, over which sperm shows up in the ejaculate and below which it will not. So, now you know the secret of making fathers out of “sterile” men with poorly functioning testicles.

Sperm from a Rock

Of course, it’s not quite that simple. There is one more layer of complexity here. Poorly functioning testicles may not make sperm evenly throughout their substance. In many cases, there are “pockets” or “islands” of sperm within a sea of otherwise empty tissue. Clinically, this makes sperm retrieval more difficult and has pushed this technology to a high art.

To find sperm, fertility specialists use several sophisticated approaches in men with nonobstructive azoospermia. The traditional testis biopsy works about 30% of the time to find sperm and, as a consequence, is no longer the de rigueur technique for this problem. Fine needle aspiration “mapping”, which I invented about 15 years ago, is easily twice as good as a biopsy in finding sperm and much less invasive. Lastly, “microdissection” of the testis another alternative and involves an all-out surgical assault on the testicle to find sperm making it the most invasive approach. The elegance and complication rates for these approaches vary widely, but their intent is the same: to find enough sperm to allow biological fatherhood. Importantly, when expertly performed, these techniques will find sperm in the majority of cases. For the remainder, there is hope as even newer “no touch” scanning technologies are on the horizon…

An Ounce of (Fertility) Prevention

Paul Turek, MD — Mon, 17 Oct 2011 15:00:19 +0000

Kokopelli, the ancient fertility symbol.

“I’ve been told that my cancer is now cured… how do I get my fertility back?

Patients ask me this question weekly all the time and I am glad to help. Some of the most satisfying medical moments I’ve had are associated with these patients.

But when I hear this call for help, it also reminds me how medicine has been remiss in preventing the infertility in the first place. We can do better and we can do it right now.

The topic of fertility preservation is the substance of my recent lecture at the annual meeting of the American Society of Reproductive Medicine (ASRM) in Orlando, Florida. This well-attended course focused on the prevention, treatment and restoration of male fertility in the setting of sterilizing treatments typical of cancer therapy.

The goal of my lecture was to review and update providers on current and future strategies for the preservation and restoration of male fertility. Here are some of the ideas discussed. I’ve also included a link to the lecture slides if you are so inclined.

Preserving Male Infertility

Sperm banking. A 200-year old technique that is the purest form of preventative medicine, it is vastly underutilized, not covered by insurance, and not routinely offered to many cancer patients before treatment. What gives? Here is where we need to do the most work in this field.
Sperm Harvest. For 15 years, it has been possible, nay routine, to harvest sperm from men who want children after having a vasectomy without reversing the vasectomy. This same technology is easily applied to men before, during and after sterilizing cancer treatments. One very successful example of this in my practice is fine needle aspiration “mapping” of testicles for sperm in cancer survivors. Indeed, no-touch, metabolic imaging for sperm may be the ultimate iteration of this concept.
Electroejaculation. Based on decades of successful use in spinal cord injured men, artificial stimulation of ejaculation can be a very effective way to bank sperm or restore fertility in men or post pubertal teens who have had nerve damage to reproductive organs from cancer surgery.
Shielding Sperm Production. Physical shields are routinely used to block the effects of aberrant X-rays from hurting sperm production during treatment. In animal models, hormonally induced shut down of sperm production can protect the testicle during the storm of chemotherapy as well.

Restoring Male Infertility

Stem cell transplantation. Currently possible in animal models, this involves taking the delicate testicle stem cells from either pre- or post-pubertal boys or men and freezing the cells before cancer treatment. Subsequently, the stem cells are thawed and replaced back into the testicle to restore sperm production after the cancer is cured.
Sperm Maturation in a Dish. A variant of the above, also demonstrated in animal models, this technique involves maturing stem cells harvested from the testicle before cancer treatment in the laboratory all the way to their final form: a sperm with a tail.
Sperm from Stem Cells. Yet another variant of the above that has been demonstrated in animals, this involves growing usable sperm from early, pluripotent stem cells such as embryonic or adult pluripotent stem cells. One example would be to take a skin biopsy from a sterile man, coercing them to become adult stem cells and then push those cells to sperm in a dish. Truly, a fantastic outcome of America’s investment in stem cell technology.

Fertility Restoration after Cancer: Current and Future Therapies by Paul J. Turek MD, FACS, FRSM Director, TheTurek Clinic, San Francisco (WARNING: Images in slides not appropriate for all audiences due to subject matter)

View more presentations from Dr. Paul Turek | The Turek Clinic

The Secret Life of Varicoceles

Paul Turek, MD — Mon, 26 Sep 2011 15:00:19 +0000

Celsus, an expert at heat and varicoceles.

What’s squishy, worm-like, fills the space in the scrotum above your left testicle, can ache after a run and wreak havoc on your fertility? No it’s not your Johnson; it’s a varicocele. A very-what? A vari-ko-seal.

What is a Varicocele?

Varicoceles are dilated, tortuous veins that drain the testosterone-rich blood from the testicles. They come in three sizes: small, medium and large and are diagnosed on physical examination, generally by a specialist. Varicoceles exist when blood travels in the wrong direction through these veins. Normally, blood leaves the testicle and travels uphill to drain to the upper back, near the kidney. This is a long way to go and it’s all uphill. Since we stand as a species, good ol’ gravity, clearly our enemy as we age, acts over time here too and pulls the blood back down the veins and causes it to pool around the testicle.

Developing at puberty in active boys, varicoceles are an evolutionary consequence of man’s upright posture. Our quadriped ancestors and pets do not get them. They are common, occurring in one in every six adult men, and are generally nothing to worry about as they are often asymptomatic.

Why Do Varicoceles Matter?

The fact is, though, that varicoceles are not always innocent. In an odd way, they remind me of my dog Pretzel (my daughter named him) who will sit at your side all day when you’re home, but will grab that half eaten burger off the table as soon as nobody’s looking. Although varicoceles don’t cause cancer, they can hurt and they can cause male infertility. Also, a few others think that varicoceles can cause testosterone levels to drop.

The discomfort they cause is again due to gravity. It is usually mild and is worsened with physical activity and relieved by lying down, which neutralizes the effect of gravity. So, men can have varicocele pain after a long day of standing, but it never hurts in the morning upon awakening.

It’s role in male infertility actually dates back to the 1^st century AD. Celsus, a Greek physician, described them in De Medicina: “The veins are swollen and twisted over the testicle, which becomes smaller than its fellow, in as much as nutrition has become defective.” In reality, 40% of men who are having trouble conceiving their first child will have a varicocele, a rate almost three times higher than in the general population.

How varicoceles cause infertility is not entirely clear, but the most popular theory is that warm blood from the body that is flowing downhill into the scrotum heats up the testicles to the point that sperm production and quality are affected. Basically, the factory (testicle) is overheated and the workers aren’t putting out as many, or as good, a product.

Away with Thee, Varicocele

Fortunately, there are several ways to treat varicoceles and they work well to relief the pain and to improve semen quality. My favorite is to spend an hour with the patient and an operating microscope and tie off all of the enlarged veins. This stops the reverse flow of blood. Elegant, simple and safe. I do this a lot. In fact, varicocele is the single most correctable abnormality found among infertile men.

So, if you find yourself having trouble conceiving with an abnormal semen analysis and just can’t figure out why its happening, see a specialist as you might just be the average guy with a varicocele.

Insider’s Guide to Vasectomy Reversal

Paul Turek, MD — Tue, 06 Sep 2011 15:00:17 +0000

Beauty (and results) are in the eye of the practiced beholder…

Something like 25,000 American men a year want more children after having a vasectomy. The more popular of two options for fatherhood after vasectomy is a vasectomy reversal; the other choice is sperm retrieval for men and in vitro fertilization (IVF, “test tube baby”) for their partners. Even though it is a surgical procedure that is technically quite challenging and not generally covered by medical insurance plans, clearly reversals have a major leg up on high-tech, IVF conceptions: you can do what you do best and do it at home, the old-fashioned way, to conceive.

Who Does Vasectomy Reversals?

Among the 10,000 or so practicing urologists in the U.S., maybe 5-10% of them are interested in performing vasectomy reversals and far fewer than 1% are fellowship trained microsurgeons who specialize in this procedure. So, how do you decide to whom you should go to have this done?

Deciding on a Surgeon

Not all doctors are same. If you didn’t know this before, you heard it here first. Some are average run-of-the-mill, some are better, and others are truly gifted and talented at what they do. And the difference between an average doctor and a great doctor is the quality of the product. Did you actually get what you asked for, or what you expected to get?

You can read all over the Internet about ways to choose your reversal surgeon. These parcels of advice are helpful and may lead you to find a good surgeon instead of an average one. But if you want the highest quality surgeon, here are six key issues to consider as you search and shop:

Does the surgeon enjoy doing vasectomy reversals? I’ve met countless surgeons who are pleasant enough in or out of the office but who are simply miserable in the operating room. I can’t explain why. Personally, reversals are my favorite thing to do (at work). It is a craft and an art form of the highest caliber, the elixir of a surgical life. A surgeon who loves what he does will do a better job of it.
Does the surgeon pay attention to details? I can’t recall who said this, but life really is in the details. And microsurgery, performed at 1/25 normal scale, is the ultimate detail-oriented surgical procedure. Has the surgeon gotten all of your details? How about your medications? Habits? Your partner’s issues? How neat is their office? How comprehensive and detail-oriented are the staff?
How long will you have to wait to get the procedure done? You may think that if you have to wait a long time to get the reversal performed that the surgeon is very busy at doing reversals. Honestly, it could mean that (s)he doesn’t operate very much or that (s)he spends a lot of time out of the office or doing other procedures. In other words, reversals may not be a priority for the surgeon (see #1 above). Or, the office itself may be disorganized (see #2 above). The better way to assess “busy” is to look them in the eye and ask them how many vasectomy reversal cases they do each year.
What are your surgeon’s success rates? You see success rates of surgeons on every website. And they all look the same and are all very high. What does this mean? How do you decide? Frankly, many surgeons quote the published rates of other surgeons, kind of like selling “knock offs” instead of the real thing. This may be fine for buying purses but not for vasectomy reversals. Peer-reviewed and journal-published data is an excellent measure of quality: it is the certified seal of authenticity. So, ask that simple question: Has the surgeon published their success rates in trade journals?
How many reversals does the surgeon perform annually? Do Olympic athletes or concert musicians win competitions through talent alone? Of course not. It’s all about the training. Similarly, a good predictor of reversal success is surgical volume or the number of cases. Volume means practice and practice makes perfect. This is true for almost all surgical procedures in medicine and is also true with reversals.
Does your surgeon want what you want? You don’t really want a reversal, you really want a kid, right? And you don’t want to sell that old car or mortgage a property to get it. Let’s say that the cost matters a lot for you. If IVF is covered by insurance and a reversal is not, then IVF may be the cheaper way to go. In this case, the surgeon should not keep giving the hard sell for vasectomy reversal. There are several paths to fatherhood. Make sure that your surgeon shares your goals. For me, it’s the holiday card that matters the most.

A Well Lived Life

Paul Turek, MD — Mon, 22 Aug 2011 15:00:59 +0000

Walking barefoot on green moss..one of life's simple pleasures.

Dear William,

You called several months ago from across the country to talk with me, as many others do. The story you told moved me as many others do. But the way your story ends is different from many others and, because of this, is now etched in my memory.

You broke your back at age 16 and you were paralyzed from the neck down. I can’t remember exactly how it happened, a diving accident, skateboarding fall, car accident or a gunshot wound. And for 6 years you had been trying to conceive. I remember telling you that although you cannot move any of your limbs with purpose, remarkably enough, the part of the spinal cord responsible for the ejaculation reflex is still intact and that your fertility potential is very high. Penile vibratory stimulation or electroejaculation are techy ways in which I can routinely stimulate this reflex, much like a sneeze, and offer you the opportunity of fatherhood. Several interesting issues made your case unique but did not pose insurmountable obstacles.

I may have even mentioned that the most rewarding moments of my career have occurred while watching giggling children running around their father’s wheelchairs. The satisfaction of helping spinal cord injured men become fathers is immense and continually motivates me to help.

We had a plan to optimize you medically and then bring you out to California where the sun always shines to make your dream of fatherhood come true.

But then, just like that, it got ugly.

I will never forget the day your wife called to tell me that you were in the intensive care unit at Johns Hopkins Hospital, the worlds best, with a very serious pneumonia. So serious that it had eaten up most of your precious lungs and forced you to be on maximal life support, with little chance of making it out of the hospital.

Yet through all of this, through weeks and weeks of deteriorating health and increasing suffering, you made it crystal clear that your ultimate wish was to be a father and, through the newness of life, be remembered by those who you loved and those who loved you.

My life is now somehow different after knowing you. With your grace, will power and singularity of purpose, you have taught me something about life, and living, that I did not know before. You have clarified once again, what really matters in a well-lived life. You have reminded me of the sound that small flowers make as they open in the morning.

So, William, I salute you. And, in the words of Nobelist Thomas Mann, may you always walk on the greenest of mosses.

Your friend,

Paul

Cancer’s Second Hit

Paul Turek, MD — Mon, 15 Aug 2011 15:00:15 +0000

A holder of "two hit wonders" of a different kind

“This is as hard on me as having cancer was. The difference is that being infertile is not life threatening; having cancer is.”

These are the words of a young cancer survivor sitting in my office who is now dealing with infertility, a common consequence of cancer treatment. Yes, he is very happy to be alive. Yes, he is grateful for each new day and knows exactly what it feels like to look death in the face and skirt it. But, what is also clear is that the infertility hurts, hurts a lot, and hurts all over (again).

Surviving Cancer: The Numbers

Thankfully, surviving cancer is now quite common. Over 80% of childhood cancers are overcome and well over a million people in the U.S. are alive 25 years after cancer treatment. This means two things: 1) cancer defines quality of life among many of us, and 2) cancer and reproduction are bed partners in younger survivors.

The Effect of Infertility on Life

It is my belief that infertility affects a man’s quality of life as profoundly as cancer does. My patient’s statement is simply another reminder of this truth. But this is hard to prove, because the “tools” and “instruments” used to assess the impact of cancer on quality of life do not exist for infertility. And, for academic reasons, they are hard to compare mano e mano.

As a start, we studied how infertility affected men who were not necessarily cancer survivors. In 357 infertile couples, we looked at the “strain” (personal, social, sexual, and marital) caused by having a male factor infertility diagnosis. Importantly, these men underwent formal face-to-face interviews and filled out questionnaires as they were battling the infertility problem. In this way, the immediate impact of having the diagnosis was assessed in couples and not the memory of infertility, which is often softened by time.

What we learned was that infertile male partners had a lower personal and sexual quality of life compared to men without male infertility. Examples of how we defined personal issues are: lack of control, missing something in life, inability to meet life goals, or feeling defective. Examples of sexual issues are: level of sexual enjoyment, perceived attractiveness to partner, failure with sex because of fertility problems, and persistent thoughts of having a child during intercourse. I would wager that cancer affects personal and sexual quality of life in similar ways.

Infertility: An Owner’s Checklist

So, being infertile matters to men. And it matter a lot, sometimes more than anything else. What can you do about it? Here’s the checklist for surviving infertility:

Get information. It helps control of the situation. You need to “own” it.
Talk openly with your partner and trusted others. Get the support you need.
Keep the lines of communication open with your partner. This may be the most significant threat your relationship will ever see.
Keep doing the things that you do best. They are not likely the cause of infertility and can keep the routine in your life.
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.

The Recipe for Man Made Sperm

Paul Turek, MD — Mon, 08 Aug 2011 15:00:32 +0000

Will stem cell "recipes" become as tried and true as the ones in this book?

Stem cells rock. While the stock market tumbles, stem cell science is sizzling. I know, you’re thinking: what is he talking about? No diseases have been cured with new stem cell technologies. But, from what’s being discovered almost weekly now, I can tell you that male infertility is likely to be one of the earliest boxes ticked on the “Diseases to Cure” list for stem cells.

Sperm from Stem Cells

Honestly, stem cells appear to be great to use to create sperm. Just a few posts ago, I shared the exciting findings from a group in Japan who took stem cells from newborn mouse testicles, placed them in an “organ culture” system (basically Jell-O), and grew mature, fertile sperm in the laboratory. Over the past 2 years, my colleagues at Stanford have also shown that human embryonic stem cells can be pushed along the path toward sperm in a dish. They also showed that adult stem cells from places like skin can also be driven in the same direction. Not all the way to mature sperm, but certainly more than half the way.

Overcoming Sterility in Mice

Last week, researchers at Kyoto University in Japan brought man made sperm closer to reality…at least in mice. I know many of you aren’t really worried about infertility in mice, but we have to start somewhere.

In a study published this past week, they took embryonic stem cells from mice, the mother of all cells, and watched them closely as they began to develop into other cell types (i.e. differentiate) in a dish. After several days, they plucked out rare and transient downstream stem cells called the primordial germ cells and transplanted these cells back into sterile baby mouse testicles. And sperm were made. Good sperm. Genetically intact and fertile sperm. Sperm that led to offspring that were also naturally fertile. And they did the same experiments with adult stem cells and got the same result, eliminating the need to use embryos at the start.

Please realize that this success did not happen overnight, but was the result of good, wholesome science and lots of sweat equity. And not all the results were rosy: primordial germ cells are rare, short lived and inefficient. In addition, when slightly different cells were injected into testicles, benign tumors formed, the scourge of stem cell science. So now you understand why mice experiments come first.

Stem Cells and Human Male Infertility

Imagine this: A boy has cancer and gets cured by being pounded with chemotherapy. Easily enough treatment to sterilize him for life. After that, his testicles could make sperm, but the “seeds” (early germ cells) that develop into sperm have been wiped out. Solution? A skin biopsy. Turn it into an adult stem cell and inject it right back into his testicles. And ta da! Sperm. I can’t stop thinking about how possible all of this is, as stem cell recipes are perfected. As Ted Allen, The Iron Chef once said: “There are two words to improve any dish: Ba-Con.”

Timing (And Position) Are Everything

Paul Turek, MD — Mon, 18 Jul 2011 15:00:39 +0000

Does timing and position matter for sex like it does for surfing?

Missionary? Doggie? Cowgirl? Kneeling Lotus? Quarter moon? Full moon? No moon? Is there really a best lovemaking time or position to have a girl or boy?

History of Designing Sex for a Boy or Girl

Methods for determining baby gender are ancient, even prehistoric, and range from astrological, to dietary to positional. One of the earliest references to this concept is the Chinese Birth Gender Chart, said to have been discovered in a tomb near Beijing for where it lay for 700 years. It supposedly now resides in the Institute of Science in Beijing. It claims to predict the sex of the child from the month of conception and the age of the mother.

It has also been said the many myths about sex position and timing determining baby gender resulted from the mad rush of lovemaking that followed the end of the World Wars and the return home of soldiers. I’m sure this influx of war torn yet triumphant, and testosterone laden yet depraved men gave new meaning to the term “Honey, I’m home!” for many mid-century modern couples.

The Lovemaking Myths

Here are the most common myths regarding sexual position and timing to help get that boy or girl. Sorry, no pictures. I hear these from patients all the time, as they look at me bright eyed, with heads nodding, searching for my blessing.

Eat meat and salty food to get a boy.
Splurge on desserts to get a girl.
Both partners eat lots of fish and vegetables for a girl.
Make love standing or doggy style and during a quarter moon or at night for a son.
Use the missionary or cowgirl position and during a full moon for a daughter.
The Shettle method suggests having sex as close to ovulation as possible, for a boy, as boy sperm are less robust than girl sperm. Do the opposite for a girl.
If the male partner climaxes first, then a boy will be conceived. The opposite is suggested for a girl.

The Lovemaking Truths

Sorry to be the bearer of bad news. Despite all that you may have heard, there is no real data supporting the idea of a “best” position or time for sex to conceive a boy or girl. In fact, a prospective study of couples starting to conceive was actually published in 1995 in the New England Journal of Medicine that reported no relationship between the timing of intercourse and baby gender. Ah, but they did not study lovemaking position, thus keeping that myth and folklore alive! Come to think of it, that would be an interesting study to do, and one that I imagine would have no trouble enrolling subjects…

The Secret Life of a Microsurgeon

Paul Turek, MD — Sat, 23 Apr 2011 15:09:50 +0000

Try doing this with suture much smaller than the finest human hair…

A recent study on hungover surgeons suggests that they are slower and sloppier after a night on the town. Get them toasted, let them sleep it off and they can’t perform surgery on par the next day. Not surprising findings, given the physical and mental demands of many surgeries. But quite alarming for patients who will quickly forgive a heart surgeon for having a terrible personality, but expect and demand that a surgeon be at the top of their game when operating.

Study of Sloshed Surgeons

Eight experienced surgeons and a bunch of medical students were treated to dinner in a restaurant and were instructed to drink until they felt intoxicated. They were then driven home and picked up again the next morning. Brought to a laboratory, they performed virtual reality (fake) surgeries at 9am, 1pm and 4pm. At 1pm, their skills were the worst, but at all three time points, they performed simulated surgeries below baseline, even though they were technically sober at the time of testing. So, surgeons are people too. The problem is that they wield scalpels.

As a microsurgeon, I shuttered when I read this study. It violates the mantra of centeredness that many of us adhere to religiously in practicing such a high art. And although any surgery can be challenging and take years to master, microsurgery places a unique demand on the surgeon: to fix things that are utterly invisible to the naked eye.

The Microcosm of Microsurgery

How demanding is microsurgery? Demanding enough that you would certainly not want your microsurgeon to rave all night before your procedure. In vasectomy reversal surgery, we routinely reconnect tubes that are less than 1/10th of a millimeter in size, slightly bigger than the absolute limit of human hand-eye coordination. For perspective, here are a variety of other dimensions in this subatomic universe:

Thickness, credit card 0.76 mm
Diameter, human egg 0.12 mm
Diameter, average human hair 0.1 mm
Diameter, human vas deferens opening 0.1 mm
Average thickness, plain sheet of paper 0.09 mm
Length, human sperm cell tail 0.04 mm
Limit of human motion 0.03 mm
Wavelength of light emitted by a carbon dioxide laser 0.0011 mm

What’s the Surgeon’s Secret?

The secret of expert surgeons is the same as that of any Olympic-caliber athlete. Natural skill and experience are assumed. If your outstretched hand has a visible tremor, you should probably avoid microsurgery. More importantly, however, are consistency and discipline, which are the true hobgoblins of great surgeons. With this Tao in mind, drinking binges are unacceptable for a master surgeon. Regarding coffee, its allowed, but just drink the same amount every day. Stay consistent. Play sports and keep fit but don’t expect to be Picasso if you’ve thrown a shoulder, your back or sprained a finger-playing ball. Pain diverts critical mental and neuromuscular energy away from the task at hand. Best to heed the words of Aristotle on this: “We are what we repeatedly do. Excellence… is not an act, but a habit.”

But should we define recommendations for alcohol use by surgeons before procedures as the study authors suggest? Fine with me. But what about pilots, school bus drivers and cabbies, to name a few other professions, who also take other’s lives in their hands?

Mice Sperm in a Dish

Paul Turek, MD — Sat, 09 Apr 2011 15:11:11 +0000

If they just would have included a photo of the finished product…

It’s not the mother load of discoveries in our field, but it’s pretty close. It tells us that the mother load is definitely out there…and within reach. Yup, the good news is that real. live, old-fashioned sperm were made in a dish… at least for mice.

The Holy Grail: Artificial Sperm

For the 55,000 reproductive age cancers survivors annually in the U.S. and a host of other men who are sterile due to injury, genetics, exposures and the like, this is good news. Despite the availability of utterly fantastic reproductive technologies like sperm mapping, in vitro fertilization and intracytoplasmic sperm injection, some men still do not have sperm to use them. The standard of care in reproductive medicine today is a sperm: a mature one, with a tail, and hopefully moving or at least alive.

And the sperm can come from anywhere. Often, men with no sperm in the ejaculate will have sperm within the reproductive organs such as the testicle or epididymis. These sperm work great to help them become fathers. But there are many other men do not have any sperm, anywhere, especially men with childhood cancers who were blasted with sterilizing treatments before they even reached puberty and made their first sperm. Clinically, I see these patients all the time and this is the crowd of men I am very motivated to help in my short time on this good earth.

The Finding: Functional Sperm for Mice

The recipe to produce functional sperm from stem cells precursors has eluded researchers for 50 years. There have been many false starts, including the last one in 2009 out of Newcastle that was published and then retracted from print by the editors one week later. But, a group from Yokohama City Japan nailed it and recently published functional mouse sperm from testis stem cell precursors.

From reading the paper, it is clear that it took several years of constant, diligent work to find the key ingredients to make it happen. In my opinion, the secret sauce was that our recent, vastly improved understanding of stem cell biology really enlightened the science. They took testicular tissue from newly born mice that contained only stem cells (no sperm, just sperm precursors) and put them in a jello-like environment. Getting them to grow was the trickiest part and finding the right food was also critical.

How is This Sperm Different?

What made this paper great was that the scientists made reproductively “competent” sperm. They took the artificially created sperm and used them with high technology approaches to create baby mice. Then, they let the baby mice grow up and mate. Remarkably, the offspring of these mated mice were normal. Can’t ask for much more from a sperm now can we? Many have tried, including some of my closest colleagues, but no one has gone this far before. Bravo!

So now, all we have to do is replicate this in humans, something that I have been pursuing for several years with colleagues. What is so uplifting for me about this paper is that it seems that making human sperm in a dish is really more evolutionary than revolutionary science. I better go buy some more of that midnight oil….

Busy as Birds and Bees

Paul Turek, MD — Sat, 12 Mar 2011 16:04:21 +0000

Birds do it, bees do it. Even educated fleas do it…

I paused and peered over the microphone at the audience. My first words were “I thought you’d never ask.” And I mean’t it. My lecture at Stanford Universitywas not conceivable two decades ago. But last week was different.

The Most Common Genetic Disorder in America

The audience was filled with cystic fibrosis patients. Cystic fibrosis is a common inherited disorder that is due to a defective gene that results in abnormally thick and sticky mucus. The mucus builds up in lung passages and elsewhere and results in life-threatening lung infections and digestion problems. Cystic fibrosis is uniformly disabling and deadly.

In 1959, a child with cystic fibrosis survived an average of 6 months. In 2008 cystic fibrosis patients lived an average of 37.4 years. Recent data also shows that 40% of adults with cystic fibrosis are married or partnered. As they live healthier and longer, the minds of cystic fibrosis patients have naturally wandered to thoughts of the birds and the bees.

The Birds and the Bees: Fertility and Cystic Fibrosis

The Stanford Cystic Fibrosis Center asked me to speak about fertility and cystic fibrosis. Absolutely my honor. The fact that these patients are now old enough and strong enough to contemplate having children is a testament to advances in medical care and their personal fortitude. The message of my talk was that fertility is possible in both sexes and is even pretty close to normal in affected women. In fact, 240 American women with CF were pregnant in 2008. Men with cystic fibrosis tend to be missing parts of their reproductive tracts and require sperm retrieval(and their partners assisted reproduction) to become fathers.

Dying for What You Believe

As I was preparing my talk, I was overcome when I learned that simple childhood sniffles or sleepness nights can be life threatening to cystic fibrosis parents. The fabled nurturing instinct to care for their young, the sheer essence of parenthood, present throughout animaldom, can be a lethal reflex for cystic fibrosis parents. Add this to the normal heroic effort needed to raise children and your find yourself staring down the very definition of the words “commitment” and “courage.” That’s why I was honored, and frankly inspired, to speak that day and will be honored to speak again. Because, in the words of Lao Tzu, the ancient Taoist philosopher: “being deeply loved by someone gives you strength, while loving someone deeply gives you courage.”