Male infertility is defined as the inability to achieve conception after one year of regular, unprotected intercourse. This condition affects an estimated 15% of couples attempting to conceive, with male factors contributing to roughly half of all infertility cases. Understanding the specific cause often relies on classifying the problem based on where the reproductive system failure occurs. These classifications help determine the most appropriate diagnostic and treatment pathways for the couple.
Systemic and Hormonal Causes
This category, often termed pre-testicular, involves issues originating outside the testicles that disrupt the hormonal signals required for sperm production. The hypothalamic-pituitary-gonadal axis is a delicate feedback loop that regulates reproductive function, and a failure here can lead to hypogonadotropic hypogonadism. The hypothalamus and pituitary gland must release Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), and Follicle-stimulating hormone (FSH) in precise amounts to stimulate the testicles.
If the pituitary gland is compromised by a tumor or other condition, it may not produce sufficient FSH and LH, leading to very low sperm counts (azoospermia or severe oligospermia). Conditions like Kallmann syndrome are a genetic cause of this signaling failure, combining hypogonadism with an inability to smell. External factors can also disrupt this axis, with the use of exogenous testosterone or anabolic steroids being a common cause. The body senses the high hormone level and shuts down its own production of FSH and LH, effectively acting as a male contraceptive.
Issues with Sperm Production
The majority of male infertility cases are classified as testicular, meaning the problem lies directly within the testicles, the primary sites of sperm creation (spermatogenesis). This failure results in low sperm count (oligospermia), poor sperm movement (asthenozoospermia), or abnormal shape (teratozoospermia). A varicocele, an enlargement of the veins within the scrotum, is the most common correctable cause, found in up to 40% of men presenting with infertility. This condition is theorized to negatively impact sperm by increasing scrotal temperature, which is detrimental to sperm development and leads to increased oxidative stress and DNA damage.
Genetic factors represent another significant issue, where defects in chromosomes or genes prevent proper sperm development. Klinefelter syndrome, characterized by an extra X chromosome (47,XXY), is the most frequent chromosomal cause of male infertility, often resulting in primary testicular failure and azoospermia. Y-chromosome microdeletions, which involve missing segments on the Y chromosome, directly affect genes responsible for spermatogenesis, leading to a spectrum of outcomes from severe oligospermia to complete absence of sperm.
Acquired factors also contribute to production issues by damaging the sperm-producing tissue within the testicles. Exposure to gonadotoxic treatments like chemotherapy or radiation can permanently impair or destroy sperm stem cells. Infections such as mumps, if they occur after puberty, can cause inflammation of the testicles (orchitis) resulting in damage to the seminiferous tubules. Environmental exposures to heavy metals, pesticides, and certain industrial chemicals are known to interfere with sperm function and production.
Problems with Sperm Transport and Delivery
Post-testicular infertility occurs when sperm is produced normally within the testicles but cannot successfully exit the body due to blockages or functional issues. This is distinct from production problems because the initial “factory” is functioning, but the “plumbing” is faulty. Blockages can occur anywhere along the reproductive tract, including the epididymis or the vas deferens.
Obstructions are sometimes caused by prior infections, previous surgeries like hernia repair, or intentional sterilization through a vasectomy. Congenital conditions, such as mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, can lead to the bilateral absence of the vas deferens, meaning the transport tubes never fully developed.
Issues with ejaculation can also prevent effective sperm delivery, even without a physical blockage. Retrograde ejaculation causes semen to travel backward into the bladder instead of moving forward out of the urethra, often resulting from neurological damage due to conditions like diabetes or certain surgeries. Immunological factors, such as the body producing anti-sperm antibodies, can impair sperm movement and fertilization capacity by attaching to the sperm surface.
Cases Where No Cause is Identified
In approximately 10% to 30% of men undergoing a standard infertility workup, results appear normal, yet conception still does not occur. This is referred to as idiopathic or unexplained male infertility, where the underlying cause is not detectable with conventional testing methods.
The difficulty in conception may be due to subtle defects in sperm function, such as elevated levels of sperm DNA fragmentation, which is a measure of genetic damage within the sperm head. High levels of oxidative stress, an imbalance between free radicals and antioxidants in the semen, are also implicated in many of these unexplained cases. Advanced genetic or epigenetic issues, which involve changes in gene expression rather than the DNA sequence itself, can also affect sperm quality in ways that standard tests cannot detect.