Male Fertility Mysteries Solved

Medical Contribution By Dr. Melissa Esposito and Michael Tucker,

Thirty percent of couples experience infertility related to a male factor, either alone or in combination with a coexisting female factor. For the affected couple, discovering that they need to seek assistance to get pregnant is often emotionally challenging. Men often react differently than women to the news because of society’s cultural measurements of virility and manhood. The good news is that treatment for male factor infertility is usually successful, often with minor intervention.

Fatherhood, From the Start

A crucial element of successful fertility treatment is that both partners are equally involved in the diagnostic and treatment processes. Proceeding toward treatment without first taking a diagnostic look at both partners’ fertility status will likely result in wasted time, energy, and money.

Though men don’t often want to hear it, the fact is that the semen analysis is one of the first tasks to accomplish in diagnosing the cause of infertility (along with the preliminary testing of the female). It may not be a pleasant test to consider, and it truly is not what any individual has in mind when thinking about making babies, but the semen analysis is the best test in its ability to rapidly and inexpensively detect problems with male infertility.

The often heard phrase “sperm count” is actually only one important component of male fertility. It refers to the concentration of sperm per milliliter (ml). This aspect of a man’s results can impact the type of treatment recommended but, as Shady Grove Fertility’s Dr. Melissa Esposito explains, “There’s no definite count where we’ll say you must use IVF or IUI. It’s really a combination of the multiple semen analysis parameters that we measure.”

The other important parameters besides the number of sperm cells are their shape (morphology) and movement (motility). In fact, even men with zero sperm count (called azoospermia) can often have conception success through various sperm extraction techniques and in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI- a procedure where a sperm can be injected into an egg to try and achieve fertilization), if indeed healthy sperm cells can be found.

As with other health conditions, the definition of “average” plays a part in diagnosis and treatment. The World Health Organization long ago established reference standards for “normal” semen analysis parameters that are widely respected. Dr. Esposito and her colleagues occasionally review the lab results brought in by patients who had their semen analysis done elsewhere. The numbers can be misleading, especially for people without medical training. “Not all labs use WHO criteria and parameters. Some may not even test for morphology, for example. So we encourage patients to use Shady Grove’s andrology lab if at all possible.”

Dr. Esposito discusses the importance of taking all criteria into account. “We look at all of the parameters in relationship with each other — count, motility, morphology, and also, volume. For example, some men can produce four to five milliliters of ejaculate, which is considered more than average (2 mls is the norm). Let’s say they have a count of 10 million sperm per ml. If they have good overall parameters, and would be left with more than 5 million total motile sperm after the sperm wash (the procedure done for IUI), then they may benefit from IUI despite the initial low count. But if they have a good count, but less than 1 ml ejaculate and low motility and morphology, then they may have a low total motile sperm count after the sperm wash and need something more in the way of treatment.”

Some important points to understand about semen analysis:

  • Because the normally functioning male body is constantly producing new sperm cells, a single “negative” test may not be the most reliable indicator of a man’s true fertility status. As with all other health systems, the reproductive system is impacted by lifestyle issues such as stress, nutrition, sleep, and illness.
  • A test that is poorly run — subject to human and lab errors — can render inaccurate findings. Examples of test problems include: too much time passing between the patient procuring the sample and the lab running the test; and labs using more general, non-fertility focused parameters for results.
  • For the above reasons, many patients are asked to undergo subsequent semen analyses for accuracy.

In many cases, the semen sample for analysis or, later, for prescribed fertility treatment can be obtained in privacy at the patient’s home, so long as it can then be transported in relatively warm conditions and within about an hour’s time to the lab. Regarding the use of semen for treatment, cases warranting special attention — such as for men whose jobs require travel that conflicts with scheduled treatment dates — can even make use of previously frozen samples.

Urological Approach to Better Family Health

For some men, finding the answers to their infertility leads serendipitously to better overall health. When the situation warrants it, Shady Grove Fertility’s reproductive specialists refer patients to a team of urologists who specialize in male infertility. An example would be a couple with severe male factor for unknown reasons. Some couples, Dr. Esposito says, simply don’t want to pursue aggressive therapy like IVF and may have a male factor issue that can be corrected by a urologist.

Dr. Esposito details how seeing a urologist can result in more than just assistance with fertility issues. “Virtually any patient with azoospermia or severe male factor infertility will be referred to the urology team. The urology exam can determine, for example in an azoospermic patient, if there’s an absence of the vas deferens (part of the male reproductive tube system), so then we know that we need to test for the cystic fibrosis gene to see if there are any mutations.” Men with congenital absence of vas deferens (CBAVD) often also carry the risk of transmitting cystic fibrosis genetically to their offspring if their wives also carry the gene mutation.

Even prior to urology referral, though, Shady Grove’s doctors will test all men with azoospermia and some cases of oligospermia (very low sperm count) for genetic conditions that can not only stand in the way of fertility but can also impact the health of their children.

High-Tech Conception Help

Depending on the diagnosis, there are a variety of techniques to treat male factor infertility. Problem areas can be roughly grouped thus:

  • barriers to sperm cell transport and delivery
  • barriers to sperm production

Treatment can either focus on the individual problematic condition, such as repairing a varicocele to promote higher quality of future sperm cells produced, or treatment can be used to bypass the condition, which is essentially the effect of ICSI with IVF. Patients will likely hear their condition referred to as either obstructive or non-obstructive or, in fewer cases, neurogenic. Neurogenic reasons for infertility would be related to nerve damage, such as for men with spinal cord injury or complications of diabetes.

In addition to ICSI with IVF, other treatment options that may be considered are:

  • Vasectomy reversal
  • Varicocele ligation
  • Microsurgical repair of obstructions
  • Electroejaculation
  • Several methods of sperm retrieval, both surgical and needle-aspiration
  • Intrauterine insemination (IUI)

Male reproductive surgery can be used to clear the path, which is made up of several different sections of tiny tubing, for sperm cells. In cases of severe oligospermia (low sperm count) or azoospermia (no sperm in ejaculate), cells can be retrieved through a variety of sperm aspiration techniques.

Medical treatment is sometimes recommended for less severe cases of sperm quantity and quality issues. Therapeutic level hormones and antioxidants may be prescribed, or antibiotics if infection is found to be a factor.

Cellular Level Experts

The laboratory is an important component in the treatment of male factor infertility, particularly since treatment has successfully been narrowed down to the cellular level.

Michael Tucker, PhD, Director of Shady Grove Fertility’s IVF and Embryology Laboratory, pioneered ICSI over fifteen years ago. The cell-by-cell conception technique remains the predominant successful treatment for male factor infertility resulting from myriad causes.

“ICSI is the standard for enabling us to take a small number of sperm and be able to fertilize however many eggs the patient has available,” says Tucker, “but there’s been a change in thinking about it as we’ve learned more about male infertility. Early on, we thought all we needed was one sperm, just any one cell, to make ICSI work. You can, in fact, have pregnancy success with technically dead sperm cells in mice, but no one’s ventured to attempt it in humans routinely. So now, we know more about how much sperm quality really counts.”

The result is that Shady Grove’s lab staff and clinicians work together more to try and find those healthy sperm cells. Sometimes that means going to the point of cell production — the testicle. Sperm removed directly from the testes are often healthier than those that have traveled all the way through the male reproductive tubing and urethra.

Highly sophisticated equipment now allows increased magnification and a better perspective of individual cells by lab scientists. “More than just whether or not a sperm is moving,” Tucker details, “we can really focus now on apparent qualities of them. Defects in the head morphology, in particular, can indicate potential problems. For example, very generally, smaller sperm heads are often lacking DNA, whereas unusually large ones are often diploid and have too many chromosomes. We also assume that misshapen heads may be a manifestation of underlying poor quality.”

A key area that is now being analyzed beyond what lab staff can see with their state-of-the-art optical equipment is actually measuring the DNA integrity. “That’s a sort of catch-all term for the amount of fragmentation of the DNA in cells,” Tucker explains. “For example, if a man is taking chemo-toxic or recreational drugs, or is a frequent user of hot tubs, we’re finding a deleterious effect on the production of sperm itself. That often registers in terms of the health of the sperm’s DNA.”

Semen samples can be tested for DNA integrity at specific laboratories, and Tucker believes there may even be home-testing for the fertility indicator in the future.

Today’s high tech fertility labs might resemble a computer gamer’s dream. The Lab Director describes the equipment of his profession. “We use joysticks, micro-manipulators, tiny glass micro-tools, hollow needles.”

“We’re talking about holding an egg that’s only about 120 microns across. The tool that holds it measures about 100 microns across, about a tenth of a millimeter. The sperm head is about 3 to 3.5 microns across, the length of the head is about five microns, while the tail is a good 20 to 30 microns long. The tool used to pick up the sperm and push it into the egg cell is about seven to eight microns across.”

Tucker says that his technical field that demands the highest level of skill has done nothing but improve over the years. “Not only our fertilization rate, which has crept up, but the overall level of damage [to cells manipulated in the lab] seen annually has dropped off.” He believes that one factor in the improved quality of embryo quality resulting from ICSI-fertilized eggs is testament to the increase in skill. “We’ve honed the process over the past decade, not unlike any surgeon whose skills get better with time and experience.”

The diagnosis and treatment of male fertility problems has improved significantly over the past couple of decades, to the point that pregnancy success is the most usual result. The scientific and technological advances have interacted in tandem to develop a wide array of answers to the perplexing questions of what stands in the way of reproduction for many men.