Posts Tagged ‘Assisted Reproduction’
Sunday, March 7th, 2010
How about being happy and hopeful as well as healthy?
The couple had been trying to conceive for 5 years unsuccessfully. The tension and anxiety in the relationship was palpable and strained. They had spent well into the 5 digits to have a child with test tube baby technology (IVF) and yet were still not pregnant. His vasectomy reversal had also failed them. And they were going to try one more time, just once, with me, before calling it quits.
When he came to me for care, he was frankly depressed. Out of money and full of debt, close to losing his job in this economy and in a strained relationship hanging on by a thread, he sat across from me. He looked terrible. “Can you help?” he asked me.
Well I did help. I reversed his vasectomy again and it worked. Fast-forward 9 months and a birth announcement arrives in the office from the couple with a long personal note of thanks on the back. But one line really struck me:
”Looking at her, sleeping quietly, I see her future as an astronaut, the President, a doctor, a lawyer or anything else that she wants to be. She can be or do anything!”
Absolutely unbridled hope and enthusiasm was infusing a mind once filled with almost unfathomable despair. All this change, nine months and one baby ago. Wow!
Talk about a biological drive. Reproduction easily ranks up there with breathing and eating. Not for everyone of course, but for many. I am quite sure that if you surveyed infertile couples about their quality of life with infertility, as has been done in patients with cancer, you would find these diagnoses equally impactful. I have no doubt many of my patients would give up five healthy years of their life to have a child. Maybe even 10. Just because it cannot be assessed by a blood pressure cuff, a blood test, or a scar does not make infertility any less important an affliction.
And yet, despite its profound impact, its ability to tear apart relationships, crush self-esteem and slow down an otherwise productive couple to a grinding halt, infertility is not really considered a disease in many societies, including ours.
Want a more productive and healthier society? Cure infertility. And what about something else that this world could use a lot more of, as expressed by my patient: the resurrection of those elemental feelings that lead us to live good lives and to make the world a better place for those who will follow us.
Tags: Assisted Reproduction, azoospermia, conception, fertility restoration, male infertility, men's health, no scalpel vasectomy, reproduction, sexual health, sperm, sperm count, TESE, testicle, vasectomy, vasectomy reversal
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Sunday, February 28th, 2010
The best medicine for man is man...and good government
A couple sees a reproductive specialist for infertility. She gets a complete evaluation and he gets a semen analysis checked. It looks like his semen quality is low and they are recommended to pursue in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to conceive, the highest level of what is termed “assisted reproduction.” They try this at significant expense and it fails. They try again and it fails again. At this point, the man sees a urologist and, after a proper physical examination, he is told that he has a testis mass and is diagnosed with testis cancer.
The point: Male infertility can be a symptom of another medical condition.
The question: What would have happened to this man if they had successfully conceived with IVF-ICSI?
This scenario is not all that uncommon in our field. And it is why I gladly accepted the invitation to go Washington D.C. and consult with the National Institute of Health (NIH) last fall regarding where government research monies should be spent in the future in the field of male reproductive health. At that meeting, I suggested that we start calling infertility a medical disease, just like any other, and get men the medical care that they deserve. I expect several great grant initiatives to stem from this gathering and was honored to have participated in it.
This scenario is also why I am excited to have been more recently invited to join the Medical Advisory Board of the Cooperative Reproductive Medicine Network at the National Institute for Child Health and Diseases (NICHD) at the NIH. The RMN, established in 1989, is a cooperative effort of seven universities and the government and is charged with conducting and publishing high quality clinical research studies in reproductive medicine. Thankfully, one of the areas of focus is on male infertility. So, I will be taking my “infertility as a disease” mantra to Washington quite a bit this year as I believe scenarios like the case outlined above should never happen in modern medicine.
Tags: alternative medicine, Assisted Reproduction, conception, male infertility, men's health, reproduction, sexual health, sperm, sperm count, testicle, testis cancer
Posted in male infertility, men's health | 1 Comment »
Sunday, February 7th, 2010
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.
Tags: Assisted Reproduction, azoospermia, babies, fertility preservation, fertility restoration, FNA mapping, male infertility, men's health, reproduction, sexual health, sperm, sperm count, testicle
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Sunday, January 17th, 2010
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.
Tags: Assisted Reproduction, azoospermia, babies, cancer, fertility preservation, fertility restoration, FNA mapping, IVF, male infertility, men's health, reproduction, sexual health, sperm, sperm count, TESE, testicle
Posted in male infertility, men's health, sexual health | 2 Comments »
Saturday, January 2nd, 2010
Heirlooms for the species.
As a living, breathing being on this good earth, we tend to take things for granted. The ability to have offspring can be one of them. That is, until the day that a serious medical condition like cancer rears it ugly head and puts childbearing at risk. In addition to the sterilizing effect of cancer treatments, the mad rush to treat the disease often marginalizes efforts to preserve fertility. Fire all the canons and check for collateral damage later.
Fertility preservation seeks to protect men, adolescents and children from a common, serious and impactful side effect of cancer treatment: infertility. The goal of fertility restoration is to empower patients who are cured and potentially infertile to bear children. These related fields have burgeoned recently because medical care is now shifting from curing cancer to improving the quality of life among survivors. And without a doubt, for many, fertility is a key quality of life issue at some point. Thankfully, exciting new methods of restoring fertility have already been developed and even newer technologies are under study.
Classic techniques for fertility preservation in men include gonadal shielding and sperm banking. Gonadal shielding uses lead-based devices to protect the testicles from being struck directly by sterilizing radiation treatment. Sperm banking is the process of freezing healthy sperm before cancer treatment begins for later use to conceive. But there is more. For patients who are too young to bank sperm, for those who have precious little time to bank sperm, or for those who have no ejaculated sperm to bank, testis sperm retrieval by biopsy (TESE) or needle aspiration (TESA) for banking is now possible before cancer treatment. In fact, in some cases of testis cancer, it is possible to remove only the cancerous nodule instead of the whole testis, or to freeze sperm from the testicle after it is surgically removed. These are now routine ways to preserve fertility in men.
Fertility restoration for men has also seen real advances lately. Sperm “mapping” is an innovation that I developed for men who survive cancer treatment but have no sperm in the ejaculate. It non-invasively and non-surgically deciphers whether there are small numbers of mature sperm in the testis, too few to get into the ejaculate, but usable nonetheless. In men who sustain nerve injury from cancer surgery and who are unable to ejaculate, a special medical instrument can produce an ejaculate for fertility purposes in a process termed electroejaculation. Techniques such as these are valuable tools to help men deemed “sterile” after cancer treatment to become fathers.
One of the most exciting areas of fertility restoration involves stem cell technology. Yes, the “promise” that we have all heard about stem cells curing disease will likely find its way into the fertility field as well. In pre-pubertal boys with cancer, ejaculated sperm is not present. Despite this, it may be possible to freeze the early stem cells from the testicles of boys before sterilizing treatment. After thawing, these “adult” stem cells may later be used to create sperm after further growth in a Petri dish or after transplantation back into the same individual. Also on the horizon is our ability to take skin cells from a sterile man, convert them into an embryonic-like stem cells and then “drive” these cells to become mature sperm in a dish–a true “artificial testicle.” So, with the belief that hope can cure misery, the world of science has taken fertility research from science fiction to reality. Not convinced? Stay tuned!
Tags: Assisted Reproduction, babies, cancer, conception, fertility preservation, fertility restoration, FNA mapping, IVF-ICSI, male infertility, men's health, reproduction, sexual health, sperm, stem cells, TESA, TESE, testicle, testis cancer
Posted in male infertility, men's health, testis cancer | 4 Comments »
Tuesday, September 8th, 2009
Where are you? Green means high and red means low.
When a couple decides to have children, they rarely, if ever, contemplate the effect this has on the nation. But population scientists do. The effect that birth rates have on society is critical—as basic as knowing whether a nation is sustaining their population or not. But, trying to figure out if birth rates are going up or down is also complex, not unlike taking our temperature by feeling our foreheads.
A good barometer of birth rate assesses the average number of births per woman, and is generally noted by country. For a country to sustain its population in the future, the replacement rate is 2.1, or 2.1 births to every woman. What has occupied the minds of population scientists over the past 20 years is the fact that birth rates have dropped around the world, especially in Europe, but also in China and Japan. Interestingly, many countries in Africa do not have this problem, with birth rates well above 4.
Also notable is the fact that in the past 20 years, the population of the world has dropped, falling an average of 1% per year. You can imagine how much this issue has occupied the minds of population scientists who seek to explain the phenomenon. Contributing factors include changing attitudes about family size, the cost of raising a child and the wider availability of contraceptives. The birth rate may also be dropping because child mortality on the whole has dropped. Or, because women who choose to have children later create a temporary lull in the birth rate. One concern with population drops is that countries whose populations become too small may not be able to afford to support its infrastructure, causing economic decline. So, on the one hand, it’s expensive to raise a child. On the other, it’s also expensive not to.
A recent study however, does show a change in these trends. Fertility rates now show a recent increase in developed nations. For years it has been thought that for some reason, developed nations, including most of Europe, have steadily dwindling populations. But this may not actually be the case. For example, in the 1970s, the US fertility rate was at a low of 1.74; lately it’s been relatively stable at 2.05. It appears that children are still wanted in a modernized world.
It’s quite hard to see these trends in my daily medical practice, as I perform as many vasectomies as I do vasectomy reversals. It’s even harder to render an opinion when the information is so diffuse and generational. So, to population scientist, I am a professionally “neutral contributor” to fertility rates. Like to think I do more good than that though…
Tags: Assisted Reproduction, birth rates, contraception, male pill, men's health, reproduction, vasectomy, vasectomy reversal
Posted in sexual health | 4 Comments »
Wednesday, August 19th, 2009
The most fun he ever had without laughing
You might have “practiced” the art of baby making for quite a while. But have you actually tried to make a real baby? What does it mean when a couple says they’re “trying”, besides jettisoning the condoms, scheduling free time, and practicing your “sore throat” voice for calling in sick to work. No one teaches you the nitty gritty of baby making in sixth grade sex ed classes. So, here are some of the finer points.
First of all, your chances of conceiving decrease if the two of you are under stress. Frequent travelling, major life changes, a long sickness, being vetted for the Supreme Court, running a start up with a gazillion hours weekly, are terrible for getting one “in the mood.” If the body is under stress, it’s in the primitive “fight or flight” response, and it’s not exactly in the mood to reproduce. So to improve your chances, decrease your stress level by eating well, sleeping well, staying healthy and relaxed, and treating your body right. If you are chronically overworked, you may consider decreasing or delegating your responsibilities. If this isn’t possible, force your body to relax with exercise, yoga, massage or acupuncture. Also, quit smoking, drink no more than two glasses of alcohol daily and avoid hot tubs and hot baths (showers are fine).
Like many things in life, timing is everything. Eighty percent of pregnancies occur when sex takes place before or during ovulation, which is the time when a woman’s ovary releases an egg for fertilization. But how to tell when ovulation is occurring? The most accurate way would be with an “ovulation predictor kit” purchased at any drugstore. Like a pregnancy test, it uses urine to determine if ovulation is about to occur. The old-fashioned method, which also works well, would be to pay attention to her basal body temperature. To do this, she should take her temperature first thing in the morning, for a string of consecutive days during the middle of her monthly cycle. There should be a dip in her temperature, followed by a rise. This indicates ovulation.
Once you know that the egg is on its way, intercourse is best performed every other day. Men need time between ejaculations to “reload”, and daily intercourse may not give a man enough time to do so (sorry guys). As for the act itself, studies have shown that no particular position is best. Research is suggesting that the two of you can bend yourselves into pretzels, if desired, with no effect on your chances of conceiving or on the gender of the child.
Baby making is a special experience. And, it’s fun! As Woody Allen said in the movie Annie Hall, ”…sex is the most fun I ever had without laughing.” If you think about it, what I am suggesting is that you and your partner make it a habit to take the best care of yourselves, just as you are going to take the best care of your child. Set the example for the new family and enjoy the ride!
Tags: Assisted Reproduction, babies, conception, male infertility, men's health, reproduction, sexual health, sperm, sperm count, testosterone, vitamins
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Monday, July 13th, 2009
It's true...it hurts to be infertile. Like any other disease.
Recently, sitting face to face with an
infertile patient, I asked him what the first thing was that came to his mind after being told that he had no sperm count. After a short silence in which his eyes gazed downward and then back again toward me, he stated, quietly “I thought it might be the end of my family lineage.”
Facing a diagnosis of infertility is one of the loneliest experiences a man can have, as evidenced by a study I recently co-authored with Drs. James Smith and Patty Katz at UCSF. Published in The Journal of Sexual Medicine this week, it found that men with a diagnosis of male infertility suffer intense negative sexual, personal and social strains that might be considered typical for other medical illnesses, including cancer. It affects not only their self esteem, but their sexual confidence and sexual function. Think about it. Men find the inability to sire children a real and palpable blow to their manhood and self-identity. The impact of this diagnosis is easily comparable to the mortal challenge associated with a cancer diagnosis. Infertility causes an immense strain to their relationships both with their partners and socially. Adding to the strain, this diagnosis is as taboo as syphilis or AIDS. The ramifications for the rest of his life are significant, especially if his lifelong assumption was that having kids is normal, expected, eventually, would not be a problem. Infertility is often one big secret that is kept from the rest of the world, making the patient, and his partner, feel isolated and desperate.
I have seen this distress in my practice, day in and day out, for years. Finally, through this study, some proof has surfaced that male infertility is one of the toughest challenges a man can face in life. The funny thing is, male infertility is not as uncommon as one might think. It affects 10% to 15% of reproductive aged couples worldwide. About half as common as diabetes. But far more silent a disease than diabetes. The bright side is that it is treatable in many cases.
So what should men do if they have a diagnosis of infertility? First, get information so that you can make decisions and get control of the situation. You need to “own” it, and this is a great start. Learn through websites such as ASRM.org and SSMR.org, or TheTurekClinic.com and see a urologist or specialist. Also, talk openly with your partner and people you trust, and get the support that you need. Decide with your partner who needs to know about this and who doesn’t. Keep the lines of communication open with your partner, as this can be the most significant threat your relationship will ever see. Keep doing the things that you do best, as these are not likely the cause of infertility and can keep the balance in your life. Importantly, take time to “blow off” stress through exercise, sports, yoga, massage or whatever works for you. Maintain that critical balance as you tackle this issue like you have tackled others, and as you will tackle future issues.
Tags: Assisted Reproduction, male infertility, men's health, reproduction, sexual health, sperm count, testicle
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Thursday, July 9th, 2009
Does this look like a real sperm? Do you believe in UFO's?
We saw it coming. We created stem cells from testis tissue and
published it earlier this year and I mentioned previously that it should be possible to do the opposite and create
sperm from stem cells. Well, as announced yesterday from a research group in Britain, that possibility is closer to becoming a reality. Sperm created in a Petri dish. Artificial sperm.
Published yesterday in the journal Stem Cells and Development, this is being hailed by the press as “breakthrough” research. Now call me cautious, or call me a stem cell biologist, but I get suspicious when that term is used to describe medical research. More on that later. The technique, discovered by a team of biologists at the University of Newcastle in England and led by Dr. Karim Nayernia, purports to have created actual moving sperm from human embryonic stem cells. Not in a testicle, but in a laboratory dish. This group has some amount of “street cred” as they had previously published a paper in which mouse embryonic stem cells were used to produce in a dish. In fact, these sperm were injected into mouse eggs, formed mouse embryos and baby mice. However, a close look at the small print reveals the mouse pups all had “growth abnormalities” and died after birth.
Now back to being Mr. Cautious. If you look closely at the figures and video in the human paper, you might not be convinced that these are actual sperm. Pictures are a little too fuzzy. Kind of UFO-like. Could they really be neurons instead of sperm? Also, the sperm neither look nor move quite like what we would expect with normal sperm. Finally, some of the “reporter” genes that are used to classify the genetic origin of the cells are not working all that perfectly. Why didn’t the researchers provide more convincing evidence of the universally recognized elements of a sperm including the acrosome, midpiece with mitochondria and characteristic axonemal structure? Oh, and where are the controls?
There is no doubt that Dr Nayernia will face scrutiny for this work, as he has before. And this is all good. Because if the scientific world believes that it is true, then this is an amazing feat of science with enormous potential. For such acceptance to occur, a confirmatory study by another group will likely be necessary. Maybe ours, as we are investigating the same concept but in a radically different and much more feasible way—by trying to create an entire artificial testicle instead.
There are other meaty issues surrounding this research. Is it safe? Is it practical? Remember how inefficient it was to clone Dolly the lamb? Inefficiency runs rampant in any reproductive process. As an example, say that you discovered that humans can reproduce through sex and tried to license the process. With a 20% efficiency rate, you would probably be denied the license. On the other hand, if it is really true, this work has demonstrated the enormous potential of embryonic stem cells, as making a sperm is about as complex a process of cellular transformation that you will find in the body. Making bone, cartilage or heart cells should be much easier. Will it ever get to the point in which a healthy child might be conceived in this way? If that happens, then I might start thinking more about the real role of man in mankind. But not sooner. After all, if men become redundant in the reproductive process, who will replace men’s uncanny knack for opening jars?
Tags: Add new tag, Assisted Reproduction, male infertility, men's health, reproduction, sperm, sperm count, stem cells, testicle
Posted in male infertility | 24 Comments »
Wednesday, May 27th, 2009
Stem cells, like wine grapes, need tender nuturing to reach their potential.
Silicon Valley started in a small garage across the way from Stanford University by one man named Hewlett and another named Packard. There’s an historic plaque on that garage now, and a worldwide industry surrounds it. Stem cell research has just as much potential.
Last week, I mentioned that I was a believer, that I have seen things happen in stem cell research that others haven’t. Collaborating with Renee Reijo Pera, PhD at Stanford, we have been developing adult stem cells that would not involve embryos, or viruses, and that would not be rejected from the body. It all started when we put our heads together and thought hard about how sperm are made and how stem cells are grown. From this line of thinking, we concluded that the adult human testicle would be a great place to create a stem cell. Why? Because the first thing a developing embryo does as it begins to grow is to set aside cells and designate them as “germ” or reproductive cells. Much later on in fetal life, other tissues develop. So, germ cells are special and very closely related to embryonic stem cells; that is, they are very “stem like.”
The next problem, and a big one at that, was how to take adult stem cells and “reprogram” them to become embryonic-like stem cells. This took the better part of four years to figure out. And, like your grandmother’s great apple pie, the secret is in the recipe. Indeed, we found that just the right combination of feeder layers (a layer of cells in a petri dish which help the stem cells to develop) and bathing solutions were instrumental in nurturing these rare testis stem cells to become embryonic-like in a laboratory dish. I developed a lot of respect and a certain fondness for these rare and special cells through this process of discovery. The care lavished on them reminds me of winemakers and their finicky pinot noir vines, which require the right conditions and care to produce their transcendent fruit. Both require a delicate touch.
So, slowly, with persistence, we were able to generate a very “stem like” adult germ cell in a dish starting from a testicle. We showed that, like a real embryonic stem cell, this cell could begin to form the different layers of the body, including nerve, in a dish. What is still not clear from all of this work is exactly what kinds of body tissues can be made from this cell. Can we make an entire heart? How about a clavicle? Or can we just make sperm? This is what the next four years of research are for. In any case, this discovery may help to bypass the whole moral debate surrounding embryonic stem cells. There would also be no viruses to worry about, nor tissue rejection issues to dodge, because your body would simply be rebuilding itself.
Understand that this research is still in its infancy, but it’s a whole new world of medicine, where whole organs may be regrown, and sight and fertility restored. With more time, this kind of research may be as earthshaking as the discovery of antibiotics a century ago. Stem cell research is likely to be even more transformative than this. May the wonder and awe from scientific discovery never end.
Tags: Assisted Reproduction, male infertility, men's health, reproduction, sexual health, stem cells, testis cancer
Posted in Uncategorized | 8 Comments »
