Turek On Men's Health » reproduction

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.

It Takes Two to Tango

Paul Turek, MD — Mon, 30 Apr 2012 15:00:32 +0000

The genetic dance: adding spice to life.

The Case of the Month is an actual patient from The Turek Clinic. It is presented to highlight Infertility Awareness Week.

The Dance Begins

He is a 36-year old who has been trying to conceive with his 35-year old wife for 2 years. After 5 months of trying, the couple achieved a pregnancy she miscarried at 8 weeks. After trying for another 7 months, they conceived again and again lost the baby, this time at 9 weeks. The couple appears disheartened and broken as they tell the story in the office.

“I’m not sure what’s wrong with me…I can’t seem to carry a baby,” says the wife in tears. “My tests look great but for some reason, nothing lasts!” she continues. The husband then pipes in: “We checked on me after the first miscarriage and my sperm count was low. Could I be the problem?” Great question.

The Pregnancy Dance

Normally, the human sperm and egg meet in the fallopian tube soon after sex. Then, over the next several days, a highly orchestrated genetic dance begins. Within 2 days, the sperm molecularly “undresses” for the egg, revealing, in full nakedness, its genetic material. Inspecting the male genome, the egg surveys and corrects its imperfections, making it whole and usable. Based on how this dance goes, usually before day 3, the egg (now an 8 cell embryo) is compelled to make an executive decision: continue developing or stop the dance. This decision is probably the first of many quality control decisions the embryo makes as it develops and is highly dependent upon the acceptability of the sperm genome.

Sperm as Dance Partners

Can sperm contribute to early miscarriages? Yes they can.

And this is despite the fact that you may never see this on any list of presumed causes of pregnancy loss. Here are the ways in which this is thought to happen:

Imbalanced Sperm Chromosomes. The classic example is when chunks of genetic material are misplaced within sperm chromosomes. Termed Robertsonian translocations, imbalanced sperm chromosomes can be found in perfectly healthy men and packaged into perfectly healthy looking (e.g. morphologically normal) sperm. The only clue may be that the sperm concentration in the ejaculate is low (termed oligospermia). When the egg and sperm genomes marry after fertilization, embryonic development is affected by the abnormal chromosomal balance in sperm, and the dance ends when the partners trip over each other’s feet. Fortunately, a blood test termed a karyotype can detect this in a man’s blood and preimplantation genetic diagnosis can be used with assisted reproduction to select for normally balanced embryos that lead to successful pregnancies.

Sperm DNA Breaks. More subtle issues with sperm can also lead to miscarriages. While the genetic payload is being prepared and packed for shipping in each sperm well before ejaculation, there may be subtle alternations in packaging quality that allow for breakages to occur in the sperm DNA ladder. Termed sperm DNA fragmentation, this problem is also found in perfectly normal looking sperm at normal sperm concentrations and motilities. Ultimately, in the first few days of embryonic life, the egg in all of its wisdom may be unable to repair the breaks and fragments of sperm DNA and elects to stop developing. And the dance ends.

Unlike with chromosomal issues, poor DNA integrity can result from acquired rather than genetic causes. Such lifestyle factors include such as smoking, fevers, hot baths, illness, infections, medications (anti-depressants and Propecia), chemotherapy, radiation therapy, oxidant exposure (e.g. air pollution, solvents), older paternal age and the good ole’ varicocele, that bag of veins located above the testicle that overheats the factory through abnormal blood drainage pattern. Sperm DNA damage is also measurable through specialized sperm-based assays that detect DNA strand breaks. And unlike chromosomal issues, they may be correctable by lifestyle changes, improved health or by repairing anatomical issues (varicocele).

So, think of chromosomal imbalances as men with two left feet and fragmented sperm DNA as men with shoes on the wrong feet. Either way, the dance just isn’t as smooth as it should be and it just stops in its tracks.

Antibodies and Epigenetics. Of course, there may be other ways that sperm contribute to miscarriage. Men are generally “allergic” to their sperm and some may develop antibodies to their sperm as a result. What is not clear is whether these antibodies induce a reaction from the female host to “attack” the embryo containing these same male allergic proteins. Additionally, the way sperm DNA is “fingerprinted,” termed epigenetics, may also influence pregnancy progression although this science is still in its infancy.

Men and Miscarriages: How Can They Help?

So, sperm matter when it comes to miscarriage. Because of this, my advice is:

See a men’s reproductive specialist if you’re having trouble with miscarriages. A good history and a simple physical exam can assess possible risk factors and lead to lifestyle changes.
Take great care of yourself. Stay healthy, avoid tobacco, exposure to smelly solvents, medications (when possible) and hot tubs and eat a diet rich in antioxidants.
If you’re stuck with airport food, consider taking antioxidants vitamins such as that found in a good male pre-natal supplement.
Similar to advice endlessly given to women, it may help to start when you’re young.

And when the tango begins, please be reminded of the power of the female egg: “Remember, Ginger Rogers did everything Fred Astaire did, but backwards and in high heels.” (Faith Whittlesey)

Diabetes Mellitus: The Infertility Triple Threat

Paul Turek, MD — Mon, 26 Mar 2012 15:00:55 +0000

Colors as possibility. Feathers in a kite shop, Beijing, China

Based on the feedback received from doctors reading the blog, we are introducing a new feature: Case of the Month. This Case of the Month is an actual patient from The Turek Clinic. It is presented to recognize American Diabetes Association Alert Day.

The Case of Male Infertility

He is a 31-year old who has been trying to conceive with his 28-year old wife for 2 years. During this time, he has noticed a lower sex drive and has had trouble ejaculating. His medical history is negative except for a 6-year history of diabetes mellitus that is well controlled with insulin injections. Exacerbated, he states “I really don’t know what’s happening to me!”

Upon further questioning, the sex drive issue started even before they were trying to conceive. Regarding ejaculation, the patient states that his erections are not very strong and, although he has the sensation of climax, nothing comes out of the penis with ejaculation. In fact, he is concerned that things might be “backing up” in his body with these symptoms.

A Short Review of Diabetes

First identified as a disease of “sweet urine” in ancient times, diabetes mellitus a metabolic disease characterized by high blood sugar (glucose) levels. It is one of the most common medical diseases in the U.S., affecting 26 million adults and children or about 8% of the population. Among those affected, about 15 million are people of reproductive age.

Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. When the blood glucose rises, say after eating food, insulin is released to decrease the glucose level. In patients with diabetes, there is low or no production of insulin and therefore blood sugar levels are elevated. The sugars spill into the urine, hence the term “sweet urine.” Diabetes is currently a chronic medical condition that is not curable.

Can Diabetes Cause Infertility?

You bet. Diabetes causes male infertility in three ways:

Causes erectile dysfunction-by affecting the health of small blood vessels and lowering testosterone levels
Lowers sex drive-by lowering testosterone levels
Reduces ejaculate volume-by affecting the small nerves that control ejaculation and by lowering testosterone levels

Indeed, this patient had all three issues at the same time along with a low testosterone level. Fortunately, these symptoms are fairly easy to correct with oral medications:

Erectile dysfunction- Viagra, Cialis or Levitra can restore erections
Sex drive and low testosterone-Selective estrogen receptor modulators (i.e. off label use of clomiphene citrate) can correct testosterone deficiency
Ejaculate volume is low because it is emptying backwards into the bladder instead of forward into the penis. This can be treated with over the counter cold medication (alpha agonists) to restore the normal direction of ejaculate flow.

Sure enough, with this combination of pills, the infertility “hat trick” induced by diabetes was overcome and the patient was able to conceive naturally after several months. Another family holiday card on its way to The Turek Clinic this year!

Remember that about 1/3 of infertility is male driven. And diabetes is both a common and quite treatable cause of infertility. So, do yourself and your future family a favor and take the Diabetes Risk Test today.

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.

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.

Your Hair or Your Hormones

Paul Turek, MD — Mon, 30 Jan 2012 16:00:25 +0000

Be nice to have Superman's hair…but at what price? (Courtesy; MovieBlog.com)

It’s the perfect drug for 40 million men in America who are going bald. Take it once a day to keep the hair on your head and shrink the prostate, which also commonly bothers men as they age. It’s a pill that has been used by at least 2 million reproductive age men over the last decade. But is it too good to be true?

The Best Hair Pill Yet

This magic pill is finasteride (trade names; Propecia, Proscar, Avodart). It represents a class of drug called the 5-alpha reductase inhibitors. These pills act as enzyme blockers: they prevent the male hormone testosterone from converting to its metabolite dihydrotestosterone (DHT). Although testosterone is responsible for a lot of our “male” features, DHT is more potent than testosterone for scalp hair and our internal reproductive organs (prostate, seminal vesicle). These drugs work by lowering DHT production and protect the gloriously youthful hair on our heads and the enviable ability to write your name in the snow while urinating.

And these drugs work well. More effective than topical or “rub in” medications, finasteride is great for what’s called “male pattern” hair loss which is due to a receding hairline or balding on the top of the head. In essence, it slows the growth phase of hair in these areas. However, it doesn’t treat hair loss on the sides or temple area.

Finasteride, Sex and Male Fertility

Although it may keep you looking like Clark Kent, many male infertility specialists, including myself, have concerns about finasteride. First, there is a 10% chance of sexual side effects that include erectile and ejaculatory dysfunction and lowering of sex drive. These issues can be subtle while on the pill but become very obvious when men stop it; many of my patients have noted a sexual “curtain being lifted” or “coming alive” after discontinuing the pill.

Second, there is an even more profound concern about finasteride among specialists: male infertility. Before it received FDA approval, the drug trials showed that it lowered ejaculate volume but did not change sperm count or motility on semen analysis testing (actual human fertility studies are not routinely required by the FDA). Now that it has been on the market for 10 years, though, impressive declines in semen quality have been observed and published with finasteride by many of us. This effect is not subtle either, as patients with complete sterility (azoospermia) have had recovery of their sperm counts after stopping finasteride!

There are several clues that this effect on fertility was possible. The rabbit studies done for FDA approval of the drug actually showed this effect. At 3 months, there was no effect on rabbit fertility. But, when followed longer, rabbits showed significant decreases in natural fertility. In addition, while I was writing a recent reproductive physiology chapter for Campbell-Walsh Urology, our leading urology textbook, I researched at what levels the 5-alpha reductase enzyme is found in the human testis and epididymis. Lo and behold, there are gobs of this enzyme in these important organs for sperm production and maturation, implying that the blocking agent finasteride would have an effect. So now what do we do?

At this point, controlled clinical trials are needed to prove this effect on fertility. For the time being, current thinking is that finasteride may not dramatically change sperm production in healthy men, but can impair semen quality in infertile men. Typically, the effects of medications on male infertility are reversible. So, to be proactive men should consider stopping the pill at least 6 months prior to trying to conceive. And, have confidence that she loves you just as much for other reasons. As Telly Savalas once said: “We’re all born bald, baby!”

Rise of the Instant Family

Paul Turek, MD — Mon, 09 Jan 2012 16:00:47 +0000

IVF: The elephant in the nursery room

Using sex to conceive, the chance of having twins or higher multiple births is about 1-2%. With assisted reproduction, including intrauterine insemination (IUI) in the office and in vitro fertilization (IVF) in the lab, the chance of twins, triplets or high order births ranges from 30-50%. That’s quite a big difference!

Twins have fascinated us for eons. They run in families but a twin gene has not been found. More twin babies grow up to be left handed than you’d expect, and identical twins built of the exact same genetic blueprint have similar brain wave patterns and may think the same, but have different fingerprints.

Since records have been kept starting in 1915, our multiple birth rate has been stable at 1-2% throughout most of the last century. IVF arrived in 1978 and is now 33 years old and is now performed over 120,000 times annually. One would expect it to affect our birth rate numbers at some point. Well, the data is in and it has.

The Instant Family

The Centers for Disease Control and Prevention (i.e., CDC) just published the information on twin births over the last 3 decades (1980-2009). Here are the key findings:

The twin birth rate rose 76% over this time, from 19/1000 births to 33/1000 births.
In 2009, 1/30 U.S. births was a twin compared to 1/53 babies 30 years ago. Among multiple births reported in 2009, 96% were twins.
Twin birth rates increased by 100% in women ages 35-39 years and by over 200% in women ages 40 years and older.
If the twinning rate had not changed, almost 1 million fewer babies would have been born over the last 30 years.

Since only about 1/3 of the rising twin rate can be ascribed to older moms in the study, this leaves the rise of IVF and fertility treatments as the only elephant left in the room.

An Epidemic of Multiples

Although convenient for many couples as the entire family is complete with a single birth event, the twinning epidemic has other implications. Here are some of them that concern the CDC:

Higher risk to moms health (eclampsia, gestational diabetes)
Higher rate of premature births
Less healthy, smaller sized babies (about half of twins)

When I see those twin strollers while walking down the street, I think “chock it up to technology changing the face of humanity yet again.” For the couple pushing those strollers, you will never seen bigger, or more tired, smiles. In the words of Josh Billings: “There are two things in life for which we are never truly prepared: twins.” But there is something to be said for getting the family built in one fell swoop.

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).

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Wi-Fi, Sperm Counts and Fertility

Paul Turek, MD — Mon, 05 Dec 2011 16:00:03 +0000

Does the radiation danger icon apply to Wi-Fi?

Maybe it’s time to rename the “laptop” computer something else and keep if off our laps (how about mobile computers or “mobees”?). First we hear that they generate heat that elevates scrotal temperature, and now the Wi-Fi radiation itself may be a problem.

The Effect of Wi-Fi on Sperm

The Wi-Fi issue was published last week and has my patients all worked up. In this Argentinean study, researchers placed one half of the semen samples from 29 healthy men under a laptop connected to the Internet via Wi-Fi. They put the other half far away from a Wi-Fi equipped computer. A better control group would have been to keep the control sperm under the computer like the exposed sperm but with the computer turned on but disconnected to Wi-Fi. The temperature of the sperm dishes was kept constant, so any effect would not be thermal in nature. After four hours, 25% of the sperm exposed to Wi-Fi stopped moving forward, and 9% showed DNA damage. In contrast, only 14% of the sperm placed some distance from the Wi-Fi equipped computer stopped moving forward and 3% showed DNA damage.

Importantly, the proportion of sperm that was dead was exactly the same in each case, so the exposure did not actually kill the sperm. The biggest difference they found was that sperm exposed to Wi-Fi lost the ability to move forward purposefully. It would have been a better study if these sperm were then followed for 4 more hours without exposure to Wi-Fi to see if there was a recovery of motility. The authors “speculated” that Wi-Fi could affect male fertility.

An Alternate View of Wi-Fi and Sperm

Does this bench top test accurately reflect real life biology? Hardly. Is this the natural environment of sperm, bare-naked in a half ounce of fluid spilled onto a computer with Wi-Fi all around? No, but I guess it depends what kinds of websites the computer’s owner is perusing and what kind of personal activity that it generates. So, it’s really impossible to infer that a man using a laptop with Wi-Fi on his lap for more than four hours will be less fertile.

A lesson in electromagnetic fields (EMFs) might better convince you of this belief. The strength of Wi-Fi (wireless fidelity) and W-LAN (wireless local area network) electromagnetic fields is considered weak. Although Wi-Fi moves data quickly, it emits very weak signals that do not travel very far. Typically only 30 to 200 mW of power is emitted from Wi-Fi devices. For a comparison, below is a list of power levels associated with devises that we normally hold near our heads:

Blue tooth headset 100 mW
Cell phone 200-600 mW
CB radio 4000 mW

In addition, Wi-Fi operates at far lower power densities (2.4 to 5 GHz) than cell phones (900MHz to 1.9 GHz). Lastly, the power density, and therefore any effect, from Wi-Fi (as with any other form of energy) rapidly decreases with distance away from the Wi-Fi antenna, following the “inverse-square law.” Thus overall, the exposure from Wi-Fi is 10-fold less than cell phone exposure, as one normally does not hold the Wi-Fi antennae that close to the body – as is done with cell phones.

So if you want to, worry about cell phones and blue tooth headsets rather than Wi-Fi networks in terms of exposure and health. Honestly, there is no real evidence yet that exposure to radio signals from Wi-Fi adversely affects any health issue in the general population. Maybe if we wore computers like hats or kept them in our underwear we might be at risk…maybe. For now, put a pillow between your privates and your laptop.

Why is Awake the New Sleep?

Paul Turek, MD — Mon, 28 Nov 2011 16:00:01 +0000

Sleeping Beauty definitely gets enough sleep (Source: Disney)

It was no surprise to me to read a recent study that showed that when Stanford men’s basketball players got more than 10 hours of sleep nightly, their on-court performance improved dramatically. They ran faster sprints, took more accurate shots and were less fatigued. Another example of more sleep translating into improved awake performance.

Facts About Sleep Deprivation

According to a recent national survey and the American Academy of Sleep Medicine, here are the current facts about sleep:

Adults should get 7-9 hours of sleep nightly.
Short sleep is defined as less than 6 hours of sleep.
Almost half (48%) of Americans say that they are not great sleepers.
More than 35% of Americans get less than 7 hours of sleep.
On average, “good” sleepers get 1-hour more sleep every night than poor sleepers.
13% say that they never get a good night’s sleep.
1 in 20 Americans have fallen asleep at the wheel while driving in the past month.
1 in 5 Americans have sex less often or have lost interest in sex because they are too sleepy.
In general, we sleep one hour less every night with each passing generation.

Sleep as Oxygen

During sleep, body temperature falls, muscles relax, the heart beats more slowly, blood pressure and pulse rate fall, and breathing slows. Clearly, sleep is more than simply rest and relaxation. It is a time of growth, recuperation and repair. Losing sleep may not physically kill you like being oxygen-deprived, but short sleep patterns are linked to depression, obesity, heart disease, loss of sex drive, attention disorders and a higher likelihood of developing a work-related disability. One Swedish study even showed that sleep deprived people look tired and less healthy and therefore less attractive to others.

Not only that, it’s not that easy to bounce back after losing sleep. The impairments caused by sleep-deprivation remain even after sleeping in for a day. Full recovery after sleep deprivation may take several nights of extended sleep.

So why does our society applaud those who stay up working all night rather than sleeping? Sleep deprivation is no badge of honor; it’s a threat to your health. Maybe this is why the Guinness Book of World Records refuses to recognize any record claims for lack of slumber. In my view, sleep ranks up there with nutrition and exercise as important pillars for a healthy, long and fulfilling life.

Are Fathers Better Citizens?

Paul Turek, MD — Mon, 21 Nov 2011 16:00:01 +0000

What wouldn't you give to help one of these? (Source: Leonardo Da Vinci, 1468)

As a surfer, I remember charging pretty big walls of cold, wintery Northern California water with the goal of getting a fast, albeit short, adrenaline-stoked ride. Years ago on Thanksgiving, I was pummeled by a big swell to the point that I wondered whether I would make it out of the water alive. But once I married and had kids, the risk element of waves larger than a single story high became less attractive to me. It wasn’t worth it. Too much at stake. Does fatherhood also reduce other types of risky behavior?

Fatherhood is Transforming

It apparently does. It is well known that fatherhood can be “transformative” or “tempering” for men. But what shape that transformation takes has not been studied very much, despite the fact that unattached men are considered by some to be a source of society’s ““suffering” or “instability.” Loose cannons so to speak.

Fatherhood and High Risk Behavior

A newly published study has tackled this issue. It addressed the changing patterns of crime and substance abuse in new fathers, as these behaviors can threaten both health and society. Specifically, the study asked whether men are less likely to drink, use tobacco or commit crimes after they become fathers. In other words, do tough guys straighten out after having kids?

The authors followed over 200 men ages 12 to 31 who demonstrated high rates of juvenile delinquency in a metropolitan area. They were assessed annually for self-reported acts of crime and court records were reviewed for arrests. Self-reported rates of beer, wine, hard liquor, tobacco and marijuana use were documented, as were co-habitation, marital status and age at first fatherhood. And remarkably, this study was conducted over 19 years!

It has been previous shown that marriage itself and getting older can reduce men’s negative behavior, but this study clearly demonstrated a real association between fatherhood by itself and reduced crime and substance abuse patterns. And, the effects were large and long lasting. Of note, these changes were greater amongst the older men in the group (late 20’s and 30s) and were distinct from those changes expected as men age. Lastly, unlike marriage, cohabitation alone was not shown to reduce risky behavior in young men.

A Golden Opportunity to Help Men Help Themselves

Why is this important? One reason is because it suggests that first fatherhood may present a real opportunity to improve the health and behavior of young men. God knows that there are not many opportunities to do this with those who consider themselves otherwise immortal. New fathers might be more willing to hear messages and make life style changes when they are holding what might be their noblest work in their arms. And these changes in behavior could affect the health of the individual, his children and his family. After all, and I am not sure who said this, “A baby will make love stronger, days shorter, nights longer, bankroll smaller, home happier, clothes shabbier, the past forgotten, and the future worth living for.”

Guide to Surviving the Holiday Season

Paul Turek, MD — Mon, 14 Nov 2011 16:00:30 +0000

Cleaning a set of these every week is one way to "busy your hands."

Two patients told me that they were getting divorced this week. They came to the office and thanked me for all that I have done for them. They wished that the assisted reproductive technology had worked and given them children, but it didn’t. The relationships simply couldn’t tolerate the strain and gave way. Unfortunately this is not uncommon.

The Stress of Infertility

Don’t doubt for a minute that being infertile doesn’t have the same impact as having cancer. Very little can tear holes in the fabric of a relationship like infertility can. Add to this the romance of the holiday season and you have a recipe for potential disaster. Gathered families encircled by the howling laughter of children; smartly dressed kids at parties just learning to be polite; parents reveling in the enchantment written on the faces of children hearing holiday stories. To the infertile, its like having walking pneumonia—it just never seems to get better or go away.

Eight Ways to Reduce Your Holiday Stress

Maybe it’s not that bad. Maybe the holiday season is just more stressful. What can you do about it? Here are some tips for men as the holidays approach:

Take smaller steps. Stress and depression are like the flu: give them some time to run their course and pass through. You will make it, and you will be stronger because of it.
Make a plan. Spinning out of control without a plan for the problem can cause great anxiety. Simply agreeing to take the next month off and start again in the New Year can make all the difference in the world.
Enjoy each other. After all, you have found a soul mate that is going through the same experience. Give and get that big hug that can make all the difference in the world
Express yourself. Cry on her shoulder and not in a closet. Vent about that wicked day by journaling. A belly laugh or a primal scream is even better. Empathy is a very rich and particularly human experience with immense healing power.
Relieve your stress. Exercise, yoga, massage and acupuncture are fabulous ways for men to “vent” and relax. There is something about those endorphins that waft through the body after a long run…
Be mindful. Take your eyes off the Ipad and lose circular thoughts that lead to nowhere. Take note of the present. Quietly observe life. Breathe to relax. You are an organism, not a machine.
Try fasting. From emails, texts, news, stock quotes. Do you really think that you can keep up with the web growing at a rate of 7.3 million pages per day?
Busy your hands. There is enormous therapy to be found by working with your hands. In the words of Michael Crawford, author of Shop Class as Soulcraft: “Fixing things feels good.”

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