What Causes Male Infertility?

If you’ve made it to this blog, I’m assuming that you or someone you’re close with is experiencing male factor infertility, and you want to know more about the common causes of male infertility.

So, I’m going to pretend like we’re sitting across from each other at a coffee shop, and I’m going to tell you everything I know about male factor infertility and what can cause it.

Common Causes of Male Infertility

The most common categories of male infertility include:

• Primary spermatogenic failure, or non-obstructive causes

• Varicocele

• Endocrine or hormonal disorders, such as hypogonadism

• Obstructive causes, such as obstructive azoospermia

• Genetic abnormalities

• Infection or inflammation

• Sexual or ejaculatory dysfunction

• Idiopathic oligoasthenoteratozoospermia, which means abnormal semen parameters without an identifiable cause

The proportion of male infertility that falls into the “idiopathic” category shrinks substantially with a thorough evaluation.

Sperm Production and Quality

Sperm production and quality is the most prevalent category of male infertility and the most common cause of non-obstructive azoospermia. This is characterized by impaired sperm production with elevated FSH, small or atrophic testes, and normal or low testosterone.

When a semen analysis is performed, several different aspects of sperm production and quality are evaluated, including sperm concentration and count, motility, morphology, and DNA integrity.

Here are the lower reference limits.

These represent the fifth percentile of recent fertile fathers whose partners conceived within 12 months:

Semen Parameter/Lower Reference Limit

Semen volume/1.5 mL

Sperm concentration/15 million/mL

Total sperm count/39 million per ejaculate

Total motility/40%

Normal morphology/4%

One important thing to understand is that the number of abnormal parameters is more informative than any single value. Infertility risk rises steeply as the number of abnormal parameters increases.

For example, a man with three abnormal parameters carried an odds ratio for infertility of about 15, compared with about 2.5 for an isolated abnormal morphology.

Basically, multiple abnormalities occurring together are more clinically significant than looking at one abnormal semen parameter in isolation.

Hormonal and Medical Factors

Hormonal and medical factors can cause male infertility by disrupting the HPG axis, or hypothalamic-pituitary-gonadal axis, or through systemic disease processes that impair spermatogenesis.

Secondary Hypogonadotropic Hypogonadism

Secondary hypogonadotropic hypogonadism occurs when there is deficient or inadequate gonadotropin drive as a result of hypothalamic or pituitary pathology.

This can include congenital forms, such as Kallmann syndrome, as well as acquired organic causes, including:

• Pituitary adenomas

• Craniopharyngiomas

• Hyperprolactinemia

• Traumatic brain injury, or TBI

• Cranial irradiation

• Surgery

• Infiltrative diseases, such as hemochromatosis and sarcoidosis

• Pituitary apoplexy

This category is actually one of the most treatable causes of male infertility.

Functional Secondary Hypogonadism

Functional secondary hypogonadism is potentially reversible. Contributing factors can include:

• Obesity

• Type 2 diabetes

• Opioids

• Glucocorticoids

• Exogenous androgens

• Anabolic steroids

• Severe caloric restriction

• GnRH agonists or antagonists

• Excessive exercise

• Systemic illness that suppresses the HPG axis

This is most often correctable by treating the underlying condition or stopping whatever may be contributing to suppression of the axis.

Exogenous Testosterone and Steroids

Exogenous testosterone and steroids suppress LH and FSH as well as intratesticular testosterone, which can produce oligospermia or azoospermia.

Any man seeking fertility should not be using exogenous testosterone.

Primary Hypergonadotropic Hypogonadism

Primary hypergonadotropic hypogonadism is characterized by low testosterone with elevated LH and FSH. This represents testicular-level failure.

Contributing factors can include:

• Klinefelter syndrome

• Cryptorchidism

• Prior orchitis

• Testicular torsion

• Trauma

• Testicular radiation

• Alkylating chemotherapy

Other Hormonal Causes

Hyperprolactinemia can be a cause of secondary hypogonadism.

Androgen resistance is characterized by high testosterone with elevated LH due to androgen receptor mutations.

Lifestyle and Environmental Factors

There are also several modifiable lifestyle factors that can negatively affect male fertility.

Obesity and Metabolic Disease

Obesity and metabolic diseases, including type 2 diabetes and metabolic syndrome, negatively affect semen quality, sperm DNA integrity, and both natural and assisted reproductive technology, or ART, live birth rates.

A waist circumference greater than 102 centimeters is inversely associated with sperm concentration and total motile sperm count.

Smoking, Alcohol, and Recreational Drugs

Smoking has a dose-dependent adverse effect on male fertility through oxidative DNA damage.

Alcohol appears to be more dependent on the amount consumed. Low to moderate alcohol intake does not appear to reduce semen quality, but high alcohol consumption can adversely affect it.

Recreational drugs, including marijuana, can reduce semen quality. Opioids and cannabis are also associated with higher sperm DNA fragmentation. High sperm DNA fragmentation reduces fertility.

Caffeine

Moderate caffeine intake does not appear to have a significant effect on fecundability. However, high caffeine and cola consumption have been linked to increased sperm abnormalities and reduced semen volume.

Sleep, Diet, and Exercise

Sleep disorders are associated with decreased semen quality.

On the other hand, adherence to a healthy dietary pattern, nut consumption, and regular physical exercise may partially reverse impairment.

Testicular Heat Exposure

Spermatogenesis is temperature dependent. The testicles need to remain approximately 2 to 4°C below core body temperature.

Heat exposure can increase germ cell apoptosis, oxidative stress, and DNA damage.

Environmental Exposures

Other environmental factors that can adversely affect male fertility include:

• Endocrine-disrupting chemicals

• Heavy metals

• Air pollution

• Occupational hazards

• Radiation

Taken together, these lifestyle and environmental factors are likely to help explain the reported 50 to 60% global decline in sperm concentration since the 1970s.

When to Seek Professional Help

Per the guidelines, it is recommended to seek professional help after six months of unsuccessful trying when the female partner is over the age of 35, or after 12 months of unsuccessful trying when the female partner is 35 or younger.

However, I want to make something really clear:

“Just keep trying for 12 months” does not mean doing nothing for 12 months.

I often find that couples will try for six to 12 months without success, and then they have to wait another three months to get in to see a doctor. Then they may be referred to another doctor, which means more waiting. Before you know it, the timeline just continues to extend.

You don’t have to spend that entire six or 12 months doing nothing.

During that time, you can begin implementing lifestyle changes and have medications reviewed, if applicable. There are things you can be looking into and changes you can be making while you are trying, rather than simply waiting until you hit that six- or 12-month mark to start taking action.

What’s next?

If you have known or suspected male factor infertility, Jordan and I would love to work with you.

You can find more information about how to work with us on this page here. We would be happy to help you on your journey to a baby.