Developmental History

Special attention should be paid to whether the patient’s testicles descended properly as a child. The presence or history of an undescended testicle has been linked to reduced fertility, with approximately 10% of infertile men having a history of cryptorchidism and subsequent orchiopexy.8-9 Infertility is two times more common in men with a history of unilateral cryptorchidism and six times more common in men with a history of bilateral cryptorchidism.10,11 The reduction in fertility potential has been attributed to a limited number of germ cells as well as defective prepubertal germ cell maturation associated with the abnormal position of the testicle.12 Additional data indicate little fertility potential for testicles that are not descended properly in the scrotum prior to puberty.13 The AUA recommends that orchiopexy be considered in patients who have not had descent of the testicle by 6 months of age because the deleterious effects on the testicle worsen with time.14 It should be noted that although scrotal relocation of the testis may reduce the likelihood of infertility, it will not prevent it entirely.9-14

Absent or delayed puberty is also associated with infertility. Men with these conditions may have an endocrine abnormality such as hypergonadotropic or hypogonadotropic hypogonadism. Klinefelter syndrome, a form of hypergonadotropic hypogonadism, is commonly diagnosed following a developmental delay. Men with Klinefelter syndrome appear to have a decline in the functional capacity of the testicle, and most males become hypogonadal. Histological studies have demonstrated a gradual deterioration of the testes over time with hyperplasia of poorly functioning Leydig cells.15 Although most males with Klinefelter syndrome are azoospermic, approximately 50%-60% of these individuals will have sperm found in their testicles as adults when undergoing microsurgical testicular sperm extraction (m-TESE).16 The timing of this procedure remains controversial as there is some evidence that m-TESE may be more effective in the adolescent population prior to the decline of testicular function, but this concept has not been conclusively proven.17

Kallmann syndrome is a type of hypogonadotropic hypogonadism. It typically presents as absent or delayed puberty and the prevalence is approximately 1:8000 males.18,19 The most common phenotypic manifestation of the disease is anosmia and hypogonadotropic hypogonadism. The most prevalent mechanism resulting in Kallmann syndrome is failure of the neurons responsible for secreting gonadotropinreleasing hormones (GnRHs) that migrate into the hypothalamus.20 These men normally respond to gonadotropic hormonal treatment to stimulate sperm and testosterone production.

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