Turek On Men's Health » FNA mapping

Assisted Reproduction: A Two-Edged Sword

Paul Turek, MD — Mon, 14 May 2012 15:00:28 +0000

Double-edged swords cut both ways.

Almost 2 decades ago, just about the time when my fellowship ended and I was starting on the faculty of UCSF, along came ICSI. Short for intracytoplasmic sperm injection, ICSI involves using a single sperm and manually injecting it into an egg. Voila, the egg fertilizes and becomes an embryo, and later, with the help of mother, a real live baby. No God or Darwin needed to decide on the chosen sperm; in one fell swoop, natural selection is replaced by the judgment of a laboratory technician.

How Good is ICSI?

Make no mistake, ICSI is good. It can go where IVF alone fails to go. The fact is that sperm from any organ can be used with ICSI to create a baby. My medical practice relies on it daily to help azoospermic men become biological fathers. ICSI is also popular. In the latest available data, it was used in 66% of 146,693 U.S. IVF cycles in 2010. That’s 96,817 times a year. Pretty popular by any measure.

The Downside of ICSI

Fortunately for science, the center that invented ICSI (accidentally by the way) has done a great job of following up on kids born with the technique. In fact, they were the first to report that children born with ICSI have higher rates of sex chromosomal issues when compared to naturally conceived children. Since then, concerns have been raised that ICSI kids may also be associated with higher rates of developmental delay and birth defects as well.

What has confused much of this story is our inability to decipher whether the added risk is due to the injection procedure itself or whether it is driven by the genetic risk introduced by infertile parents who require it to conceive. It’s a chicken-or-the-egg issue but in different garb.

The Latest and Greatest

The latest entry in this informational fray about ICSI and birth defects was published last week in the New England Journal of Medicine, the world’s most revered medical journal. An Australian study of 308,974 pregnancies and births over 16 years, both assisted and unassisted, found that birth defect rates were almost 2 fold higher in ICSI infants (9.9%) compared to naturally conceived (5.8%) children. The kinds of birth defects examined were not controversial and included heart, spinal, urinary tract, limb and cleft palate abnormalities, among others, but not minor defects unless they were disfiguring. This study was impressive for the following reasons:

1. It was robust. The sheer numbers of births examined was in excess of 300K+.
2. It was uniform. A single population registry available in Australia was used. Birth defects were clearly defined on a national level.
3. It was comprehensive. Detailed information on children was available from pregnancy to a child’s fifth birthday!
4. It was dissectable. Details and outcomes from various assisted reproduction treatments were available for analysis.
5. It was rigorous. State of the art analytic techniques were used to assess the findings.

One question I had when reading the paper was whether the analysis could help us figure out whether the birth defect risk stems from the ICSI technique or incoming parental risk that is brought to bear on offspring. Here are some observations from the paper that address this issue:

1. The rate of birth defects associated with treatments other than IVF and ICSI were not different from natural conception.
2. The risk of birth defects was also increased among infertile women who did NOT use IVF-ICSI.
3. The risk of birth defects was also increased among women who conceived naturally AFTER using assisted reproduction in the past.
4. Determining the role of paternal issues was not possible, as no information on paternal age or semen quality was included in this study.

In the absence of good information about paternal factors, these observations point out that maternal issues or the technique itself may play role in the higher rate of birth defect findings observed with ICSI.

A Changed World View

So, what to think now? Remember there are dozens of papers addressing this issue over the last 15 years. Given the variation in their quality, to date, I have withheld my opinion on the matter. However, with this study the balance has now shifted for me to truly believe that the birth defect rates are higher with IVF-ICSI than with natural conception. Our national fertility organization agrees. Clearly, the “sword” of ICSI cuts both ways.

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…

A Year Without Answers

Paul Turek, MD — Mon, 12 Mar 2012 15:00:30 +0000

"Elemental" Courtesy of the Artist: A.J. Russell

This is a guest post 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 day we met with Dr. Turek was a week filled with hope and happiness. Almost a year earlier, on the same day, I went through a biopsy with the result that there were no sperm. So when we found out about Dr Turek, this really felt like the last chance, the last hope. Therefore the decision to travel across the world to see him was an easy one. The visit and procedure went well, but, again, the result from mapping showed no sperm. And no answer as to why this is.

It has been a year since I spoke with Dr. Turek about these results, a year characterized by disappointment, anger, sadness and worst of all, no answers. There were simply no answers to be found. Why me? Why now? What now? Literally a thousand questions ran through my head interfering with my daily life, keeping me up at night and affecting my relationships. I had never felt anything like this before.

I wanted so badly to not feel alone in this. I wanted someone to understood my plight, without me having to explain every small detail, because you can´t explain this feeling.

I needed to talk about it. I just couldn’t bury it. But, who was I going to talk to? And what would I talk about? I felt isolated as there appeared to be a big taboo regarding this topic. Anyone I spoke to told me focus on other things in life. But how are you supposed to do that when all you think about is the fact that you can’t have your own children? I knew no one with a similar experience who would step forward and talk about his experiences and feelings. Google searches were pointless, as the Internet does not care and information on coping is useless.

That year was best characterized by the feeling of being lost and trying to find my way in darkness without a map or light. I felt that I was in a deep, dark place, especially when I tried to look forward into the future.

Feeling alone, I began suppressing everything. All feelings, thoughts and discussions were avoided. I told my close family that I did not want talk about this matter anymore. It was a buried subject for me, never to see the light of day again. The reason for this was that talking about this issue within the family only made things worse. One problem with this approach was that the bright spots in my life also suffered along side. The subject became an 800-pound gorilla that, although ignored, never left the room. Maybe the gorilla was bigger than 800-pounds as the family dynamics changed greatly.

Then I became angry, sometimes uncontrollably. This was when I could see that I was approaching rock bottom. The slightest annoyance, comment or action sent me into a furious rage where I often exploded at whomever was next to me. Many times it was my wife, which led us to the brink of divorce. We were both tired of fighting and there appeared to no other solution to end the fighting but dissolving the marriage. This moment was a real eye opener for me.

What helped keep me going to some degree during this time was my job. As a futures trader, my work was very involving and in the moment. Believe it or not, it was also logical and predictable, in a mathematical sort of way. It could be explained and reasoned with and while doing it, I could leave all my troubles behind. But I couldn´t hide in my job forever.

I turned the corner at rock bottom when I realized that if I did not start controlling my emotions and start being honest with myself, my life as I knew it would change dramatically. It was on that day, a very cold one in December, that I realized that I was just too exhausted to continue to fight with myself and others. I couldn’t bear to face another year continuing on the same as the last. So, I stopped lying to myself and began to face the reality of my emotions.”

The second and final part of this guest series will be available Monday, March 19th.

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.

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

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.

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…

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….

The Ultimate “Green” Book

Paul Turek, MD — Sun, 06 Mar 2011 06:52:06 +0000

If I could only draw like this surgeon could…

It’s the age of “green” no doubt about it. Houses, cars, and even lifestyles with small carbon footprints are part of a larger deeper, planetary respect. You may know of green pencils (from recycled newspapers), sugar cane paper and, of course, green books. But, did you know that the ultimate green book is one that has been around for 54 years and has a huge worldwide following in medicine?

The Netter Green Books are a veritable medical bible that has now been revised for the first time in five and half decades. I am honored to be one of its new editors. Giddy as I write this, Volume One, The Reproductive System, was just sent to me and it is absolutely glorious. Have a look on Amazon and you’ll see.

Who is Frank Netter?

Arguably the finest medical illustrator of the human body since Da Vinci, Dr. Frank Netter’s career as a medical illustrator began in the 1930′s. As a surgeon in training at NYU, he learned by cramming his notebooks with pictures, not words. His professors discovered this talent and offered to pay him for his art and helped to fund his medical education. Near the end of his career, his incredibly detailed, lifelike renderings of the human body in watercolor led the New York Times to hail him as “The Medical Michelangelo.”

How to Update a Masterpiece

Physicians old and young have looked at these images time and again for five decades, seeing in them comfortable sources of clear and clinically succinct information. The privilege of editing this monumental tomb has been both daunting and revealing. Dr. Netter’s art is utterly timeless, highly exact and informed to the point of being prescient. How do you improve on a masterpiece? On the other hand, medicine has change dramatically over the past half century and really demands that entirely new knowledge be revealed. Similar to restoring a Michelangelo painting or translating a Nabokov novel, editing this volume highlighted to me both the vast changes in medicine and the timelessness of Dr. Netter’s art. I chose to let the art do the talking and wrote text to frame it with context, clarification and modern clinical relevance.

Medicine as Art

I come from a family of painters and, as a surgeon, rather fancy myself a craftsman of sorts. This may be why I so enjoyed working with great artists such as Carlos Machado and Tiffany deVanzo who illustrated this volume. As a team, we were able to tackle such complex concepts as ejaculatory duct obstruction, microsurgery and the genetics of sex determination and convey them as medical art. Indeed, some of the figures we proposed for the new Netters took several months to get just right.

Just as challenging for me was my duty to examine the authority of current scientific knowledge. Although I have written and published 60 or more textbook chapters to date, for the first time and for this book, I would constantly ask myself whether what I had written is true not only now, but would be for the next 50 years, until the next edition is written. Trying to tell the difference between what we really know and what we really don’t is a daunting but intensely fulfilling task. My admiration and respect for the wondrously rich and intricate, baffling yet logical, and powerful but delicate workings of the human body have grown in unimaginable ways from this effort. Such are he “soft whisperings” of beauty of which Kahlil Gibran speaks.

That Azoospermic Feeling

Paul Turek, MD — Tue, 08 Feb 2011 06:09:48 +0000

Was Van Gogh Azoospermic?

At the beginning of the office visit, I like to ask men with no sperm in the ejaculate who are unable to conceive a simple question: “What crossed your mind when you first heard that you were azoospermic?” The answers varying greatly but are very telling:

“It must be a mistake.”
“I shouldn’t have joined that fraternity in college…”
“It wasn’t the best sample I’ve ever done.”
“I was simply and utterly devastated.”
“I was in shock and then got really depressed.”
“It changed my life…I always thought that I would be a father.”

The Meaning of Azoospermia

Azoospermia is the lack of sperm in the ejaculate. It can be due to a blockage in the system (obstruction) or failure of the testicles to make sperm (nonobstructive). The most common reason for blockage is a vasectomy. Other causes include infections, prior surgery, injury or congenital absence of certain reproductive tract organs. Failure to make sperm can be due to exposures (hot tubs), medications, varicocele, a history of undescended testicles, cancer and cancer treatment. However the largest chunk of men with poor sperm production have none of these issues. Instead, they have a subtle genetic cause: either they are missing genes on the Y chromosome or have other chromosomes harboring subtle alterations that do not otherwise affect their health or lives.

So, like Captain Renault in the movie Casablanca, most men with azoospermia are “shocked, shocked!” because they feel so normal in every other way. And the vast majority are normal (as normal as men can get) in every other way. Most of the things they worry about, like college indiscretions, are exposures that are entirely reversible with time. My response is usually to allay fear and guilt by saying: “This is not something that you have done to yourself; let’s see if we can do something about it at this point.”

Treating Azoospermia

In fact there is a whole lot that we can do with azoospermia. Men with blockages can often be unblocked with microsurgery, one of my favorite things to do. This gives them the chance to conceive naturally again. And most men with poor production as a cause of azoospermia will have pockets of sperm in the testicles that can be identified by techniques like sperm mapping and that can be used for high-technology pregnancies.

What I have learned after caring for hundreds of azoospermic men over two decades is that they really don’t care what their sperm counts are as long as they can be fathers. And once they are fathers, it is clear that that “azoospermic feeling” goes away, as it should.

Bringing It Home

Paul Turek, MD — Sun, 07 Nov 2010 05:46:28 +0000

It's the age of William Carlos Williams all over again.

The workday was winding down. I made a cup of tea and pulled up the dashboard on my computer to review the progress of my patients after surgery. Everyone was progressing beautifully…but one. He reported that his pain had increased over the last 2 days. So I called him on his cell phone:

“John, it’s Dr. Turek. You seem to be having more pain than before after your surgery. Is everything OK?”
“Dr. Turek?? Wow! Yes, everything is fine. I stopped my pain pills yesterday and also went back to work. I guess I pushed it a bit.”
“No problem, John. Just making sure.”

That, my friends, is the new face of great medical care. Taking care of patients in the moment, where they live. Your doctor watching over you when you need it the most.

It’s called Healthloop.com and what a great asset it is to my practice. Why? Because men simply don’t call. However, they will tell you what’s happening on a secure website when asked about how they are doing after surgery. In fact, they will even take the opportunity to “tweet” me on Healthloop when they might not know exactly how they should be doing.

The brainchild of a physician-colleague named Dr. Jordan Schlain, Healthloop is a medical work of art at the vanguard of a whole new field of medicine called “home-based care.” What’s revolutionary about this concept is that it helps patients stay at home, obviates travel to the doctor’s office, opens up new lines of communication and empowers patients. It is also a practical and inexpensive alternative to the vaunted “house call” of generations past. I offer it to every patient under my knife.

The time is now for remote monitoring—taking care of patients from afar. Aged patients are less mobile and harbor more chronic conditions that may just as well be watched from home. In addition, technology is now more widespread (Healthloop is web-based), miniaturized and portable than ever. Finally, there is a constant push to reduce healthcare costs and what better way to do that than by helping patients avoid doctor’s visits or even emergency room visits.

What I like most about home-based care is that it engages patients in self-care as never before. And with young men, the added communication with a provider is empowering. As John said: “Thanks, Dr. Turek…it’s nice to know that my body is healing normally after surgery.” The house call is back. William Carlos Williams would be proud.

Babies…Naturally

Paul Turek, MD — Sat, 14 Aug 2010 15:35:08 +0000

The magic bullet? You decide.

In my daily fertility practice, while trying to help couples to conceive, I’ve noticed a trend lately. Patients are less interested in using high levels of “assisted reproduction” to have children. In particular, they would like to avoid in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the Cadillac of all techniques. Even before they meet me, they have decided against it. Not all couples, mind you, but certainly more than before.

Briefly, IVF-ICSI is a busy month for women. It involves stimulating them with daily, injectable hormones during the first half of the menstrual cycle to generate more eggs than normal within the ovary. Ovulation of eggs is induced by injection of a second hormone, which is closely followed by egg retrieval using needle aspiration under anesthesia. Retrieved eggs are then stripped of their cell coats in a dish and a single sperm is individually injected into each egg by an embryologist. The criteria for choosing sperm are: good looking and hopefully moving. Eggs then become embryos in a Petri dish and are transferred back to the female reproductive tract three to five days later, depending on how they develop. Extra embryos can be frozen for future use. A pregnancy test is obtained two weeks later.

As a male fertility specialist whose practice mantra has been “treat the male, cure the disease,” I find this trend very interesting. Assisted reproduction is almost always an option for couples, but I have spent a good deal of time publishing research showing that classic male infertility treatments such as varicocele repair and vasectomy reversal are very cost-effective ways to conceive compared to more expensive techniques like IVF-ICSI. On the other hand, these techniques are the only option for many men with azoospermia, or the absence of ejaculated sperm, and I am glad that it exists for this.

I wrote down what patients said when I asked them why IVF-ICSI is not an option on the table for them and here are some of the responses:

“It seems pretty invasive and unnatural.”
“Isn’t it relatively new?” (IVF is 32 years old, ICSI is 18 years old)
“Who selects the sperm?” (Since it is not God or Darwin)
“Wasn’t ICSI developed as an experimental mistake?” (Yes)
“How do we know that those are our eggs and our sperm? (Rare)
“It’s only a single try at having children.” (Maybe two)
“Isn’t there an issue with higher birth defects and syndromes in babies” (Very likely)
“Are our children going to be infertile?” (Unknown)
“We’d prefer to have the hope of trying every month at home.”
“IVF-ICSI is too expensive”

What I think is happening is that as IVF-ICSI is being offered to consumers more often than ever (currently 1-2% of U.S. babies are born from these techniques), patients are becoming better educated about the technology and are making more informed, personal choices. My gut also says that good, old-fashioned sex has a strong following among infertile couples as a way to conceive. In the words of Woody Allen in Annie, “that was the most fun I’ve ever had without laughing.”

Metabolomics: The Picture of Fatherhood

Paul Turek, MD — Sun, 07 Feb 2010 18:05:14 +0000

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.

The Quiet After the The Storm of Cancer

Paul Turek, MD — Sun, 17 Jan 2010 23:38:36 +0000

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.