Why an Evaluation in the Male is Necessary

The World Health Organization defines infertility as “the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.” Using this definition approximately 15% of couples will experience infertility in their reproductive lifetime. This definition is appropriate because couples that have failed to achieve pregnancy after the first year have a 50% probability of success when trying a second year.

From the above table we can conclude that while couples that fail to achieve pregnancy in 12 months as defined by the WHO are classified as “infertile” a more accurate term would be “subfertile”. Importantly, among these “subfertile” couples, in 50% a contributing male factor abnormality is found.

How necessary is it to identify these men? The Male Fertility Center at Premier has four specific goals in identifying and treating these men:

1. Identify correctable conditions and treat these conditions to improve fertility; this includes couples committed to pursuing a spontaneous pregnancy or assisted reproductive techniques (ART).
2. Identify conditions associated with male fertility that can have an influence on overall health.
3. Identify irreversible conditions that are best managed with assisted reproductive techniques (ART).
4. Because both time and finances are not limitless, proceed with an evaluation that is not only state-of-the-art but efficient and sensitive to the limited resources couples have at their disposal in a highly specialized multidisciplinary arena that protects the man and his partner’s privacy.

Your Ejaculated Sperm: The Two Day Journey

Semen, the bodily fluid secreted by the male reproductive organs, usually contain on average 200-300 million spermatozoa. After semen is deposited in the vagina (on day one) motile sperm attach themselves to the woman’s cervical mucus (the first physical barrier to reaching the egg). These attached sperm then (on day two, but up to day five) swim through the cervical canal into the uterus where they encounter the small oviducts (the second barrier) before ultimately reaching, attaching, and fertilizing the egg. Because only a fraction of the original ejaculated sperm survives this 2-day journey, the monthly fecundity rate (MFR), the monthly probability of conception among couples having regular, unprotected intercourse is only approximately 20%. Therefore, it is not surprising that the total number of sperm and the movement of sperm is potentially an important metric in determining a man’s potential fertility.

The Cornerstone to a Male Evaluation: The Semen Analysis

By testing the quality and quantity of the semen, urologists can successfully identify factors that are affecting the man’s fertilization capacity. A semen analysis is a sophisticated review of an ejaculated specimen that analyzes:

1. The volume of semen
2. The concentration or number of sperm
3. The percentage of sperm in movement and the quality of that movement
4. The microscopic appearance of the sperm
5. And additional factors

How Semen Analysis Testing is Conducted at the Male Fertility Center at Premier

What the Semen Analysis Tells Us—and What it Doesn’t

What we now know about semen analysis testing is that its clinical interpretation can be rather complicated. Guzick et al. published a landmark study in the New England Journal of Medicine that shed some light on what a semen analysis tells us—and what it doesn’t:

Before analyzing the above table let us think of a test that we have more familiarity with like the SAT, which high school students take before entering college. The SAT is designed to assess students’ potential for success in college. But what would it mean if large proportions of poorly performing college students had excellent SAT scores? It would mean the SAT lacks “sensitivity” or the ability to forecast a poor performing college student. Semen analysis testing works in this fashion. Although sperm concentrations less than 13.5 x 10⁶ are abnormal and highly predictive of infertility, approximately 85% of infertile men have semen analysis greater than 13.5 x 10⁶. In fact, there is large overlap between fertile and subfertile men— men who fall into an indeterminate range between 13.5 x 10⁶ and 48 x 10⁶. Inside this indeterminate range there is roughly an equal proportion of fertile and infertile men.

Now what if we looked only at well performing college students? What percentage of them have good SAT scores? This is really asking: what is the likelihood of the SAT excluding from college a student that actually does well in college but performed poorly on the SAT? This is the test’s “specificity”. Semen analysis performs well under this standard as 95% of fertile couples have concentrations > 13.5 x 10⁶.

So there are several important conclusions to be made about semen analysis testing:

1. Sperm Concentrations <13.5 x 10⁶ are highly predictive of infertility and sperm concentrations >48x 10⁶ are highly predictive of successful conception at one year but there represents a broad “indeterminate” range between these two levels that is poorly predictive of fertile or subfertile couples.
2. Knowing what we know about a sperm’s arduous two to five-day journey to reach and fertilize an egg, sperm concentrations that are “indeterminate” while technically “normal” (greater than 13.5 x 10⁶) could be associated with lower monthly fecundity rates (MFR) than sperm concentrations >48 x 10⁶ and therefore explain why some couples take an extended period of time to conceive. Their difficulty may represent a lower likelihood of conception (MFRs <20%), not necessarily an absolute inability to conceive (MFR=0%).
3. If men have more than one abnormality on semen analysis, say a low count and a low motility, the odds of subfertility would be compounded. We see this, too, from the following data from Guzeck, et al:
   

   Concentration	Motility	Number of Abnormal Semen Parameters	Odds Ratio for Subfertility
   >48 x 106	>63%	0	1.0
   <13.5 x 106	>63%	1	2.2
   >48 x 106	<32%	1	2.5
   <13.5 x 106	<32%	2	5.5

4. With such a broad indeterminate range among evaluated fertile and infertile couples, there may be other explanations for male infertility that are beyond the precision or accuracy of semen analysis testing.

Spermatogenesis: How Sperm Are Produced

Imagine a car factory that uses a moving assembly line to produce a new car. As the car moves through the assembly line, it begins to slowly take the form of a mature car, eventually set to be released by the factory. Now, imagine that the factory is shaped like a doughnut, like the Apple Headquarters in Cupertino. And imagine there are several assembly lines inside this doughnut-shaped factory with the assembly lines oriented radially from the outside of the doughnut to towards the inside. And when a car gets produced, it drops into the hole of the doughnut. The above process is very similar to spermatogenesis, the formation of sperm that occurs not in a doughnut-shaped factory but inside the doughnut-shaped seminiferous tubules of the testicle.

The process begins with a spermatogonia , a germ cell, which rests on the outside of the doughnut and then differentiates into a primary spermatocyte. It then enters the assembly-line-like seminiferous tubule and initiates a process called meiosis dividing the cell into two secondary spermatocytes (meiosis I) followed by another division creating four spermatids (meiosis II). Like the car, as this process moves forward the cells begin to take the appearance of a sperm.

Each spermatid is further transformed by a process called spermiogenesis—loss of its cytoplasm, formation of its tail, nuclear changes that compress its DNA—into a fully mature sperm, or spermatozoa. It is released into the lumen of the tubule, the hole in the doughnut, where it joins other sperm that have undergone the same metamorphosis and then travel towards the epididymis for storage.

Ejaculation: How Sperm Are Transported

Ejaculation is a neurologically-controlled mechanism that involves the transport of sperm. It occurs in two phases: emission and expulsion. Emission is transport of sperm from the tail of the epididymis to the urethra, while expulsion is the propulsion of sperm outside the urethra.

Other Tests at The Male Fertility Center at Premier

The Male Fertility Center at Premier offers other tests to identify the broad range of causes of male infertility, identify their clinical meaningfulness, and correct the condition.

History and Physical Examination: There is no test more important than a careful history and physical examination. As we see with semen analysis testing, the result is often not binary and needs to be interpreted and placed into context among a range of other clinical, biochemical and radiographic findings.

Blood Hormone Testing: By simple blood testing, our team can check for genetic or hormone problems that can directly contribute to problems with spermatogenesis. Treatment options are then recommended based on the results.

Testes Biopsy: If the hormone testing is not helpful, a testes biopsy under anesthesia, a minimally invasive procedure, may be performed to allow us to look at the seminiferous tubules and look for visible signs of spermatogenesis.

Male Fertility Imaging: Scrotal ultrasound is a safe, non-invasive option for accessing a male’s reproductive health. Ultrasound enables urologists to detect abnormalities in the veins within the scrotum that can lead to testicular damage, accurately measure the volume of the testicles, and rule-out testes cancers.

Post Ejaculatory Urine: This is the examination of urine under the microscope for sperm. If sperm are found in high numbers, it suggests there exists some form of ejaculatory dysfunction.

Centrifuged Semen Analysis: For patients that have no sperm identified on semen analysis, a semen specimen is centrifuged and reevaluated under a microscope looking for rare sperm.

Vasogram: A vasogram is a test done in the operating room with the aide of an operating microscope. In cases of suspected obstruction, generally situations where there is no sperm but spermatogenesis appears to be intact, contrast is infused in the vas deferens and x-rays are taken delineating the precise location of the obstruction.

DNA fragmentation: Very much like the airlines that put restrictions on the size of luggage you can carry on a flight, insisting you compress your clothes into smaller and smaller bags, the DNA inside sperm are packed much more tightly than other cells’ DNA. The body does this by winding the sperm DNA tightly around a protein inside the nucleus in the same way a thread is wrapped around a spool. Like a piece of luggage, this highly compressed DNA is protected from outside or even inside molecules that can potentially damage it. As a result, the integrity of the DNA—the clothes inside the luggage—shouldn’t be damaged as it is about to embark on its 2-5 day journey.

Now let’s go back to high school biology and revisit the Kreb’s Cycle, the physiologic explanation for foods’ conversion into energy inside the body. Spermatozoa need a lot of energy because they require movement. The Krebs Cycle is simply the conversion of the chemical energy contained inside glucose (what you find in food) to a form of energy that can be utilized by the sperm— like converting an English pound into an American dollar. The English pound is of no use in the United States but when it is converted to US dollars it becomes useful as a form of currency. Like a currency kiosk stand at an airport, oxygen helps with this transformation of glucose into usable energy— the Kreb’s Cycle.

But consequently, metabolites of oxygen—reactive oxygen species (ROS)— may be created that can fragment the sperm’s highly protected DNA and damage the sperm. Potential causes of ROS include smoking, alcohol abuse, radiation, environmental toxins, infection, aging, diabetes, and varicoceles. DNA fragmentation testing may be useful in certain situations where the semen analysis is otherwise normal.

Male Infertility Causes

Whether sperms are blocked or there are hormonal or environmental factors affecting the quality or quantity of a patient’s sperm, our fertility specialists provide the care and support to help address the root causes of male infertility. Four common causes of male infertility include the following:

1. Varicocele. One of the most common causes of infertility in males, varicocele occurs when the veins in a male’s scrotum are enlarged due to a malfunction of the veins’ valves. This leads to blood pooling into the scrotum. The blood, which would otherwise flow from the scrotum to the rest of the body, enlarges the veins. Increased temperature in the testicles results and other associated factors lead to lower quantity and quality of sperm in the semen.
2. Azoospermia. This occurs when there is no measurable amount of sperm in the semen. It can result due to a blockage in the reproductive tract, for instance, due to a vasectomy. In this case, the condition is called obstructive azoospermia. It can also occur when the body produces low quality sperm or no sperm at all. This is called non-obstructive azoospermia.
3. Hormonal imbalances. A male’s ability to produce sperm can be affected by hormonal factors such as those related to the hypothalamus or pituitary glands. Damage to these glands can result in low or abnormal sperm production. The use of testosterone can also have a negative impact on male fertility.
4. Genetic disorders. Genes can carry mutations that affect fertility. These genetic mutations occur in individuals with myotonic dystrophy, Klinefelter’s syndrome and Y-chromosome microdeletion.

Treatment Options

We offer comprehensive treatment for male infertility which may involve medicine, surgery, or assisted reproductive technology. Factors that often influence the treatment options recommended by our fertility specialists at Premier include the following:

• The factors influencing infertility or diagnosis
• The duration of infertility
• The age and general health of the male patient and his partner
• The patient’s preferences for treatment after receiving advice on the recommended treatment option(s)

In all cases we encourage our patients to prioritize their health and refrain from any activities that may adversely impact their fertility treatment. This often includes refraining from smoking or excessive drinking of alcohol. Learn more about the male fertility treatment options provided by our team at Premier today or contact a fertility specialist at The Male Fertility Center at Premier.