Just say no.

Most couples in most countries will conceive within a year of trying. Families in the Ukraine take an average of 2.5 years, according to a new U.S. publication. Why? Radiation discharged from the ill-fated nuclear explosion at nearby Chernobyl in 1986 is the likely culprit. Male infertility is the consequence.

We know that sperm production is exquisitely sensitive to radiation, and we actually know how sensitive it is to this exposure. Believe it or not, this was demonstrated in a series of never-to-be-repeated experiments conducted in the 1960’s right here in America. Recall that this was the time of the Cuban Missile Crisis and extreme Cold War tension. The Walla Walla experiments in Washington state involved irradiation of 64 prisoners with various dose levels at Washington State Penitentiary to find the dose that would sterilize them. A similar, second set of prisoner experiments were also conducted at Oregon State Penitentiary during the same period. These studies on “volunteers” demonstrated two things: 1) prisoners do not have the free will to be considered for scientific experiments and 2) the testis is very sensitive to radiation.

How sensitive? Let’s use a chest X-ray for comparison (0.1 mSV). When 15 mSV (150 chest X-ray equivalents) of radiation was aimed at the testis, sperm counts fell. When 50 mSV (500 chest X-rays) were used, it caused temporary sterility. And after 500 mSV (5000 chest X-rays) of radiation, permanent sterility resulted.

So, it is not surprising that a nuclear explosion in the Ukraine occurring 24 years ago over a fallout area 1/3 as large as Iceland’s recent Eyjafjallajokull volcano (19,000+ square miles) might have an effect on human fertility in the surrounding area. Those exposed to radiation as children are now grown, have survived their thyroid cancers, and are trying to reproduce.

As a scientist and doctor, teacher, humanitarian and ethicist, I find this world an often frightfully complex place, mainly because of a failure to learn and grow from our mistakes. Haven’t we realized that good planets are hard to find? In the case of Chernobyl, and in the words of Alan Eddison:

Modern technology

Owes ecology

An apology

How damaged is your genetic sheet metal?

Imaging parking your car at home after work and all the nicks and scratches are removed while you sleep, before heading to work the next day. All shiny and new, polished even, while you sleep. Believe it or not, this is normally what happens to your genes and chromosomes on a minute-to-minute basis. DNA mismatch repair is a constant and vigilant process, occurring in all cells of the body. Why the biologic vigilance?  Well, It keeps us whole, healthy and cancer free.

About 11 years ago, we published a paper showing for the first time that infertile men can’t repair the errors normally encountered in their DNA as well as normal men. This was startling news in part because it implied that infertile men may be more likely to develop other problems later in life, including cancer. Why cancer? Because the development of cancer has been associated with the inability to normally repair the frequent daily errors that occur to one’s DNA as the body’s cells divide and renew.

Today, however, we know much more. We know that testis cancer is 3-fold more likely to occur in previously infertile men than in fertile men as they age. And our latest research has shown that prostate cancer, thought to be a disease exclusive to older men, occurs more seriously and more commonly in previously infertile men.

So what does this mean? Is male infertility the first sign of a larger problem in our species? It is the ultimate medical problem of a species trying to reproduce?  Well, honestly it isn’t entirely clear. However, to me it indicates that male infertility should certainly be considered an insurable and real medical condition that should be taken as seriously as a heart attack. Even more worrisome is the issue of whether the use of sperm from severely infertile men is putting their offspring at even higher risk of medical issues than that experienced by their fathers.

So do not ignore the infertility issue when it strikes and get that male partner evaluated by a specialist. Teach him to perform testicular self-examination, a simple maneuver performed once monthly in the shower that has far more potential to extend his life than even exercising or weight control. Educate him about prostate cancer so that he does not ignore the powerful screening tools available to find it early. The age of innocence is over. The warning signs are now clear; get men the care that they deserve.

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!

The genetic complexity of sperm and precursor cells when the chromosomes are painted is similar to that of constellations of planets and stars, and look very similar.

So what did we find?

The study showed that men who are infertile have a much higher risk (3 times) of developing testis cancer later in life than the average citizen. And this was based on some serious number crunching. We worked from a huge database of over 51,000 infertile couples who sought care over a 22 year period in California.  The male partners were cross referenced with a California cancer registry to figure out who among them developed testis cancer as they got older. Among infertile couples in whom the male partner was not the reason for infertility, the future risk of testis cancer was the same as in the general population. However, among infertile men who were themselves the cause of the infertility, the risk of future testis cancer was 3 times higher.

So what does this really mean? Well, first of all, it confirms studies from Europe that have suggested the same thing is happening there. This confirmation in a U.S. based study is important, because the rate of testis cancer in many European countries is much higher than it is in the U.S. It also implies that there may be a connection of some kind between male infertility and testis cancer.

But what kind of connection could exist between male infertility and testis cancer? Well, environmental exposures might link these two conditions. However, the kinds of substances that could do this are still unclear. Estrogenic compounds such as bisphenol A, phthalates and pesticides have garnered much press lately as they alter sexual development in animals, but have not been definitively linked either to testis cancer or human infertility.

The connect, I think, may be even more basic: it probably involves genes and gene mutations. About 10 years ago, we and others reported that severely infertile men have more trouble than other men in properly repairing the daily breaks and kinks that occur in everyone’s DNA with daily use. Because faulty DNA repair is clearly associated with cancer in humans, this led us to surmise back then that infertile men with faulty DNA repair might have a higher risk of cancer later in life.  And voila! The results from the recent research appear to support this idea. 

For the time being, the risk holds only for testis cancer, but who know what future research will show? Based on this, I recommend that all infertile men certainly be evaluated by a urologist with a good history and physical examination. They should also be taught testicular self examination as a screening tool to detect testis cancer.

Infertility as a window into men’s health?  As a shift in thinking, it certainly does shine a new light on the problem.