An appropriate hormonal milieu must exist for the reproductive organs to produce, mature and transport the highly specialized male gamete to the ejaculatory duct.

The entire system of hormone balance is initiated by the pulsatile hypothalamic release of GnRH (gonadotropin-releasing hormone). Pituitary LH (luteinizing hormone) secretion is determined by GnRH pulses from the hypothalamus that occur approximately every two hours and are carried via a venous portal network to the pituitary.

This hypothalamohypophyseal portal connection allows an exact synchrony of GnRH and LH pulse secretion.

FSH (follicle-stimulating hormone) secretion is also stimulated by GnRH, but FSH and LH are differentially regulated by hormonal and other factors that are poorly understood.

The factors influencing FSH secretion are produced by Sertoli cells and other components of the testis that probably includes peptides of the inhibin and activin families. Within the testis, LH stimulates Leydig cell synthesis of testosterone. Testosterone production by the Leydig cell provides locally high intratesticular concentrations of this hormone that stimulates spermatogenesis.

Testosterone concentrations in peripheral blood of men change dramatically during the life cycle.

Testosterone reaches a maximum concentration during the second or third decade of life, then reaches a plateau, and declines thereafter.

Additionally, annual and daily rhythms in testosterone concentration occur, typically with a testosterone peak in the early morning.

Other, irregular fluctuations in testosterone concentration may also be detectable in peripheral blood.

Testosterone is normally aromatized in peripheral tissue to estrogens.

Excessive testosterone levels, associated with gonadotropin, clomiphene citrate or flutamide treatment, may paradoxically result in increased feminization from conversion of androgens to estrogens by aromatase. Similarly, increased aromatase activity is associated with alcoholism and chronic liver disease, as well as testis tumors.

Accurate clinical assessment of the pituitary gonadotropins LH and FSH must take into account their pulsatile release.

During clinical research studies, three serum samples are obtained, one every 30 minutes, and the sera pooled for accurate determination of mean gonadotropin levels.

This process is usually not necessary in clinical practice, but the clinician should be aware of the potential for LH and FSH peaks to be measured in a single gonadotropin determination, and perform repeat evaluation if LH and FSH hormone levels are both elevated.

Testosterone levels may be decreased in the late afternoon or evening. Interpretation of serum testosterone levels should take the diurnal secretion of this hormone into account.

Prolactin, another pituitary hormone, may affect fertility by decreasing LH production, resulting in a decrease in testosterone and subsequently, decreased libido.

The release of prolactin is mediated by dopamine, and the dopamine antagonist bromocriptine will ameliorate the antifertility effects of hyperprolactinemia.

Testosterone is converted intracellularly within most androgen-sensitive organs to dihydrotestosterone.

Function of the prostate, seminal vesicles, vas deferens, and other sex accessory organs are all androgen-dependent. The degree to which partial androgen deprivation in the hypogonadal man affects the function of these organs is unknown.

Furthermore, the effects of "low-normal" serum testosterone levels on these organs and a man's fertility potential are unknown.

Abnormally elevated serum testosterone levels are peripherally converted by the aromatase enzyme to estrogens. In addition, chromosomal abnormalities such as Klinefelter's syndrome (xxy), and some testicular tumors have elevated aromatase levels.

Some obese patients may also have increased aromatase activity, since aromatase levels are high in adipose tissue, as well as fat.

Therefore, hormonal evaluation of the infertile man should include determination of serum LH, FSH, testosterone and prolactin. For men with clinical gynecomastia, serum estradiol should be measured.

The human testis is an ovoid mass that lies within the scrotum. The average testicular volume is 20 cc in healthy young men and decreases in elderly men. In Asian men, testes tend to be smaller. Normal longitudinal length of the testis is approximately 4.5 to 5.1 cm.

The testicular parenchyma is surrounded by a capsule containing blood vessels, smooth muscle fibers and nerve fibers sensitive to pressure.

The functional role of the testicular capsule is unknown, but may relate to movement of fluid out through the rete testis or control of blood flow to the testis.

The testis contains seminiferous tubules and interstitial cells.

The tubules are segregated into regions by connective tissue septa.

The seminiferous tubules are long V-shaped tubules, both ends of which usually terminate in the rete testis.

Measurement of testicular size is critical in the evaluation of the infertile man, since seminiferous tubules (the spermatogenetic region of the testis) occupy approximately 80% of testicular volume.

So, a rough estimate of spermatogenic cell capacity is provided by assessment of testicular size.

Testicular consistency is also of value in determining fertility capacity.

A soft testis is likely to reflect degenerating or shrunken spermatogenic components within the seminiferous tubules. The seminiferous tubules drain toward the central superior and posterior regions of the testis,

The rete testis, that has a flat cuboidal epithelium. The rete coalesces in the superior portion of the testis,

Just anterior to the testicular vessels, to form 5-10 efferent ductules.

These efferent ducts leave the testis and travel a short distance to enter the head, or caput region of the epididymis.

The efferent ducts coalesce in a somewhat variable pattern within the caput epididymis to form a single epididymal tubule.

The artery to the testis is specialized in that it is highly coiled and intimately associated with a network of anastomotic veins that form the pampiniform plexus. The counterflowing vessels are separated only by the thickness of their vascular wall in some areas.

This vascular arrangement facilitates the exchange of heat and small molecules, including testosterone. The transport of testosterone is a concentration-limited, passive diffusion process in men.

The counter-current exchange of heat in the spermatic cord provides blood to the testis that is 2 to 4 °C lower than rectal temperature in the normal individual. A loss of the temperature differential is associated with testicular dysfunction in humans with idiopathic infertility, as well as men with varicocele or cryptorchidism.

Whether elevated testicular temperature causes or is simply a reflection of testicular dysfunction is unknown.

Only the association between elevated testicular temperature and seminiferous failure has been demonstrated.

In the distal inguinal canal, 50% of men will have a single testicular artery identifiable under l0 x power magnification dissection of the cord, with 30% of men having two arteries and 20% with three arteries.

The venous system is somewhat unique because the spermatic veins are thin-walled, poorly muscularized, and lack effective valves except at the inflow points into the inferior vena cava or the renal vein.

The right spermatic vein usually drains into the vena cava. The left spermatic vein drains into the left renal vein. The renal vein on the left side is thought to have a higher intraluminal pressure because the vein is compressed as it passes between the superior mesenteric artery and the aorta.

This "nutcracker effect" may impair flow through the left renal and spermatic veins, especially in young men with limited retroperitoneal fat.

The differential anatomy of the left and right spermatic veins is thought to explain, at least in part, the higher prevalence of varicoceles on the left side.

The exact mechanism by which varicoceles cause infertility is unknown.

In animal models, varicoceles are associated with increased blood flow to the testis and increased interstitial fluid in the testis.

These two findings may impair regulation of testicular temperature and decrease intratesticular concentrations of testosterone or other local factors important for spermatogenesis.