Cryptorchidism is a major, but poorly studied, cause of male infertility. From studies of a large cohort of men treated at the Children's Hospital of Pittsburgh, we have determined that attempted paternity is decreased in both formerly bilateral and unilateral cryptorchid men compared with controls. We now propose to use this cohort to further assess risk factors and indicators of infertility after cryptorchidism (specifically sperm and hormone indicators) to determine the effect of this condition, its treatment and age of treatment. Infertility associated with cryptorchidism may result from progressive, irreversible damage to germ cells of the undescended testis during childhood prior to treatment, from effects of operative correction, or from various combinations of these. Because not all study subjects have attempted paternity, we propose to study parameters that can be quantified which are associated with paternity that will be potentially available for the entire cohort. We will test hypotheses that (1) sperm quality and quantity are diminished after cryptorchidism as reflected by decreased sperm density, total count, motility and morphology; (2) serum follicle-stimulating hormone (FSH) levels are elevated in cryptorchid men, a reflection of damage to testicular sperm producing elements; (3) plasma testosterone, total and free, is diminished in formerly cryptorchid men because of testicular injury; and (4) the independent variables of age of correction of cryptorchidism, type of surgery, location and size of the pretreatment undescended testes are associated with poorer sperm parameters, more elevated FSH and lower testosterone and free testosterone. This study will identify predictors of male infertility (potential predictors-sperm parameters, FSH, testosterone, free testosterone) and assess the benefit of treatment and age of treatment of cryptorchidism. We present data to verify that the parameters we propose to measure can be determined to address our hypotheses. We will use hormone assays with which we have experience and can sufficiently detect differences between individuals. Sperm analyses will be done in collaboration with the Reproductive Health Network including videotaping of sperm motility for computer analysis. The results will provide a definition of fertility after cryptorchidism, provide a basis for guidelines not only for treatment of cryptorchidism, but for treatment and counseling of formerly cryptorchid men concerning fertility.
