Turek On Men's Health » female infertility

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.

The Essential Beginnings of a Vitamin

Paul Turek, MD — Mon, 16 Apr 2012 15:00:57 +0000

Petroglyphs and Paleo: Inspiration for Essential Beginnings

Honestly, my opinion about nutritional supplements has evolved dramatically. Historically, the value of prenatal vitamins for women is well recognized and uncontested. For example, calcium keeps mom’s bones healthy as developing fetuses borrow mom’s calcium for their own bones. And iron prevents the anemia of pregnancy. Folic acid clearly prevents neural disorders and birth defects in children. No doubt, prenatal vitamins for women make sense.

Do Vitamins Treat Cancer?

However, with heart disease or cancer, the story is quite different. In 1998, the government set out to test herbal and other alternative health remedies to find the ones that work for cancer and other diseases. After spending $2.5 billion, the disappointing answer was that none of them help prevent or treat these diseases. As noted here several years ago, vitamins got an “F” for cancer. To top this off, newer data from just last month suggests that excess vitamins supplements may actually lead to an earlier death. Now what’s a guy to do?

Do Vitamins Help Men Conceive?

Thankfully, what is more encouraging is the value of antioxidant supplements for male infertility. In 2011, An august research group in England published a Cochrane Review that analyzed 34 studies of 3876 infertile couples using assisted reproduction to conceive. The meta-analysis found that the partners of men taking antioxidant supplements were 4-fold more likely to get pregnant and 4-fold more likely to give birth than couples in which the male partner was not taking supplements.

The Idea of a Male Prenatal Vitamin

This study changed my worldview to the following:

A large chunk of male infertility (maybe half) is due to what’s called “oxidative stress.”
Antioxidants are a good defense against oxidative stress.
The best antioxidants are found in the diet, and the Paleo diet appears to be the best.
Most men have terrible, antioxidant-poor, diets
If men ate more fruits and vegetables, maybe fertility would improve.
Barring this, men should view antioxidant supplements as prenatal vitamins.

The Essential Beginning

Motivated by this epiphany, I and several trusted colleagues, including fertility physicians and nutritionists, set forth to create a male prenatal supplement that would be better than eating airport food for fertility. We wanted it to be made in California and support the local economy, be certified-organic, and to reflect the latest findings in antioxidant research. It would contain vitamins, minerals and organics with high bioavailability, instead of just putting stuff on a label without regard to whether or not it is absorbed well by the body, like most other supplements. We wanted it to be available online, to avoid the middleman markup, and to be reasonably priced.

After a year of pretty intense work, it has arrived. It is called XY (your chromosomes, get it?). And not only that, we continued our research and developed an entire fertility product line for women all the way from pre-conception through breast-feeding with XX (women’s prenatal), Z (pregnant prenatal) and Z+ (post-natal and breast feeding).

Do all men need a male prenatal? Probably not, because as I said, nothing replaces a healthy antioxidant diet. But if you are like most of us, creatures of habit eating airport food and busting our chops to put food on the table daily, it is to you that I dedicate Essential Beginnings, XY.

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.

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…

Handling The Truth

Paul Turek, MD — Sun, 28 Mar 2010 23:23:24 +0000

Patients can handle the truth…try them.

How would you react to a doctor who, instead of explaining the entirety of your medical options, simply said “trust me, this is the right choice.” Maybe that style of “care” worked a generation or two back, but today’s patients have access to any piece of medical information that their doctors do. Patients want to know as much as they can so they can make the best choices for themselves or their loved ones.

Why do I bring this up? Well, because I got a call the other day from a patient who was seeking for more information about his options for fatherhood after vasectomy. He had an older vasectomy, 25 years or so, and a wife who was 40 years old. He met with two doctors in other cities and asked them about vasectomy reversal and sperm retrieval with assisted reproduction. Both of these are options for vasectomized men. Both urologists said, “forget it!” The patient was stunned. He just wanted information to help him decide how he was going to approach the family building issue. Instead, he received no information, and, without asking, he was told what he should do. Forget it.

Two things are still true after visiting these two doctors:

1. He still wants a family.

2. He knows no more than he did before about how to achieve this goal.

Now what is wrong with this picture? Patients do not necessarily depend on doctors for information; they can get that almost anywhere on the Web. However, they do depend on doctors for wisdom and knowledge–the interpretation of information as it applies to the patient. I believe that life is a journey, one that involves many forks in many roads. Some are chosen and others are not. In the end, there is a story, a memory, of the path that was taken. Making decisions about medical care is also part of the journey that we all take. As doctors, we are obliged to use our experience and wisdom to help patients face decisions and choices that affect their health, their budgets and often their very lives. A patient’s “trust” is earned and is not gifted to doctors. Be their trusted consultant, someone who they can rely on for good solid information and wisdom. Unlike what Col. Nathan R. Jessep says in A Few Good Men, patients can handle the truth.

In my discussion with this patient, I gave him the facts about each choice. Older vasectomies are less successful at being reversed than younger ones, but the results are still very respectable in the right hands. His wife’s age could influence his decision either way, especially if she has limited time left to have children. Pregnancies after reversals of older vasectomies occur later than those after younger vasectomies. Sperm retrieval and assisted reproduction

can be a faster, albeit more expensive, way to conceive. If more than one child is desired, then assisted reproduction can get very expensive compared to vasectomy reversal. No value judgments, just the facts. There are lots of ways to build families and patients armed with good informaton can decide which way is best for them.

It has always been my philosophy as a physician and surgeon to walk the walk with the patient. Even stepping into their shoes and taking the journey with them. This makes good sense in situations in which outcomes cannot be guaranteed. Sure, I will offer an opinion if they ask, “what would you do?” However, in my brief stay on this good earth, I have found that the educated consumer always makes the best choices.