Male infertility is a contributing factor in roughly half of all couples who struggle to conceive, and it stems from a wide range of causes, from structural problems and hormonal signals to genetics, infections, and everyday habits. In many cases, multiple factors overlap. Understanding what can go wrong, and where, helps clarify why a semen analysis comes back abnormal and what options exist for addressing it.
Varicoceles: The Most Common Structural Cause
A varicocele is an enlargement of the veins inside the scrotum, similar to a varicose vein in the leg. About 15% of men in the general population have one, but that number jumps to 19 to 41% among men being evaluated for infertility. Even more striking, varicoceles show up in roughly 70% of men with secondary infertility, meaning men who had a child before but now can’t conceive again. This suggests varicoceles cause a progressive decline in fertility over time rather than a single, sudden drop.
The leading explanation is heat. The testes sit outside the body specifically to stay 2 to 8°C cooler than core body temperature, which is critical for healthy sperm production. Swollen veins disrupt the cooling system, raising scrotal temperature. On top of that, increased venous pressure can limit blood flow in and out of the testicle, trapping metabolic waste products and allowing harmful molecules called reactive oxygen species to accumulate. Those molecules damage the fatty outer membrane of sperm cells, reducing their ability to swim and to fuse with an egg.
Genetic Causes
Genetic abnormalities account for about 15 to 20% of severe male infertility cases, specifically men who produce no sperm at all or very few (under 5 million per milliliter, compared to a normal reference of at least 39 million per ejaculate). The two most common genetic culprits are Klinefelter syndrome and Y-chromosome microdeletions.
Klinefelter syndrome is the single most common genetic cause. Men with this condition carry an extra X chromosome (XXY instead of XY), which typically leads to small testes, low testosterone, and absent or severely reduced sperm production.
Y-chromosome microdeletions are the second most common. The Y chromosome contains specific regions, collectively called AZF regions, that carry the genes responsible for making sperm. When chunks of these regions are missing, sperm production can be partially or completely shut down. The most frequent type, AZFc deletions (about 80% of all Y-microdeletions), removes a 3.5 million base-pair stretch containing 21 gene copies. Men with this deletion may produce no sperm or have severely low counts. Deletions in other AZF regions tend to result in complete absence of sperm with almost no exceptions. Genetic testing for these deletions is now a recommended part of the standard workup for men with very low or absent sperm counts.
Hormonal Imbalances
Sperm production depends on a hormone relay that starts in the brain. The hypothalamus releases a signaling hormone that tells the pituitary gland to produce two key hormones: follicle-stimulating hormone (FSH), which drives sperm production in the testes, and luteinizing hormone (LH), which triggers testosterone production. If either the hypothalamus or the pituitary gland malfunctions, this entire chain stalls. The result, called hypogonadotropic hypogonadism, means the testes never receive the signal to make sperm or adequate testosterone.
This can be caused by pituitary tumors, genetic conditions like Kallmann syndrome, head injuries, or certain medications. Elevated prolactin levels (from a benign pituitary growth, for example) can also suppress the relay. Unlike many other causes of male infertility, hormonal problems are often treatable once identified, because restoring the missing hormones can restart sperm production in the testes themselves.
Infections That Damage the Reproductive Tract
Certain infections can cause lasting structural damage. Chlamydia is a major offender: it triggers inflammation throughout the male reproductive tract and is responsible for 40 to 80% of epididymitis, an infection of the coiled tube where sperm mature and are stored. That inflammation can scar and block the ducts that carry sperm, cause the testicle to shrink, and ultimately result in obstructive azoospermia, where sperm are produced but can’t reach the ejaculate.
Mumps orchitis, a complication of mumps infection that inflames one or both testicles, can also permanently damage sperm-producing tissue, particularly when it occurs after puberty. Gonorrhea, untreated urinary tract infections, and prostatitis can contribute in similar ways, either by scarring ducts or directly harming testicular tissue.
Oxidative Stress and Sperm DNA Damage
Oxidative stress is an underlying mechanism in many forms of male infertility, even when the primary trigger is something else like a varicocele or infection. Sperm cells are unusually vulnerable to damage from reactive oxygen species for three reasons: their outer membranes are packed with fragile fatty acids, they carry very little internal fluid to buffer against attack, and they have almost no ability to repair their own DNA once damaged.
When reactive oxygen species overwhelm sperm cells, two things happen. First, the cell membrane breaks down through a chain reaction called lipid peroxidation. This produces toxic byproducts that reduce membrane flexibility and permeability, directly impairing a sperm cell’s motility and its ability to penetrate an egg. Second, the sperm’s DNA fragments. Unlike most cells in the body, mature sperm can’t fix broken DNA strands, so the damage is permanent. High levels of sperm DNA fragmentation are linked not only to difficulty conceiving but also to poorer outcomes with assisted reproduction and potential risks for offspring health.
Heat Exposure and Lifestyle Factors
Because sperm production requires cooler temperatures, anything that consistently heats the scrotum can suppress it. Research on men exposed to 43°C water baths for 30 minutes per session showed significant drops in sperm concentration, motility, and membrane integrity. Interestingly, intermittent heat exposure (once every three days) suppressed sperm production more severely than the same exposure on consecutive days. The effects were reversible, but recovery took weeks to months because a full cycle of sperm production lasts about 74 days.
Practical sources of scrotal heat include hot tubs, saunas, laptops placed directly on the lap for extended periods, prolonged sitting (especially relevant for long-haul drivers), and tight-fitting underwear. Individually, these may seem minor, but combined or repeated regularly, they can meaningfully lower sperm quality.
Other lifestyle factors play a role too. Heavy alcohol use suppresses testosterone and can shrink testicular tissue. Smoking increases oxidative stress in semen. Obesity raises scrotal temperature through insulating fat deposits and disrupts hormone balance by converting testosterone into estrogen in fat tissue. Anabolic steroids, used for bodybuilding, are one of the most potent causes of reversible male infertility: they flood the body with synthetic testosterone, which shuts down the brain’s signal to the testes, often stopping sperm production entirely.
Ejaculatory and Functional Problems
Sometimes sperm production is normal but the sperm never reach the partner. Retrograde ejaculation occurs when semen travels backward into the bladder instead of out through the penis during orgasm. The main sign is a dry orgasm, with little or no fluid expelled. This happens when the muscle at the bladder neck fails to close properly during ejaculation.
Common triggers include diabetes (which can damage the nerves controlling that muscle), multiple sclerosis, spinal cord injuries, and Parkinson’s disease. Certain surgeries, particularly prostate surgery, bladder neck surgery, and retroperitoneal lymph node dissection for testicular cancer, can also cause it. Some medications used for high blood pressure, prostate enlargement, and depression carry retrograde ejaculation as a side effect.
Erectile dysfunction and premature ejaculation can also contribute to infertility by making intercourse difficult or reducing the chance of sperm reaching the cervix, though these are functional issues rather than problems with the sperm themselves.
Age-Related Decline in Sperm Quality
Male fertility doesn’t have a sharp cutoff the way female fertility does, but it does decline with age, and the turning point comes earlier than most men expect. Structural and functional sperm parameters begin a measurable decline around age 40, with semen volume and motility showing more obvious drops by age 50.
The more concerning change is genetic. A study of over 2,100 semen samples found that men 35 and younger had an average sperm DNA damage rate of 14.7%, which rose to 15.9% in men 36 to 44 and 16.2% in men 45 and older. Mitochondrial function in sperm, which powers their movement, also declined: 24.6% of sperm showed abnormal mitochondrial activity in men under 35, compared to 29% in men 45 and older. These changes don’t make conception impossible, but they increase the time to pregnancy, raise miscarriage risk, and are associated with higher rates of certain conditions in offspring.