Purpose: An attempt to make a rational strategy for treatment of cryptorchidism. Materials and Methods: 1,335 cryptorchid boys with biopsy at surgery (1,638 specimens). We studied: frequency of no germ cells in biopsies from 698 patients <12 years at surgery; fertility potential of 140 patients who were now adults, and apperance of testicular neoplasia in all biopsies. Results: Lack of germ cells appeared from 18 months. The frequency increased with increasing age. It appeared in 30% (61/202) bilateral, and 18% (88/496) unilateral cases. In men who had undergone bilateral or unilateral orchiopexy, respectively, there was normal sperm count in 19% (14/75) and 83% (54/65), and infertility was suspected in 56% (42/75) and 8% (5/65) (FE, p < 0.00005, p < 0.00005), respectively. The lowest, the mean, and the highest age-matched spermatogonia count per tubule at orchiopexy was associated with sperm count (Spearman test, p < 0.0001, p < 0.005, p < 0.05). Isolated, this was demonstrated for the 75 formerly bilateral (Spearman, p < 0.0001, p < 0.0001, p < 0.0001), but not the 65 formerly unilateral cases (Spearman, p = 1.0). No germ cells at orchiopexy was associated with suspected infertility. Risk was 78–100% in bilateral (dependent on one or both testes affected), and 33% in unilateral cryptorchidism. There was one invasive germ cell tumor, six cases of carcinoma in situ testis, and one Sertoli cell tumor. Three neoplasms were diagnosed in intra-abdominal testes, four in boys with abnormal external genitalia, and two in boys with known abnormal karyotype. Risk of neoplasia was 5% (7/150) in patients with intra-abdominal testis, abnormal external genitalia or diagnosed abnormal karyotype, versus 0% (0/1,185) in patients without these characteristics (FE, p < 0.00005). Conclusion: We recommend surgery for cryptorchidism before 15–18 months of age because: (a) lack of germ cells is very rare before, and (b) lack of germ cells is associated with subsequent risk of infertility. At primary surgery for cryptorchidism, we recommend examination for testicular neoplasia in cases of intra-abdominal testis, abnormal external genitalia or known abnormal karyotype.

spermatogenesis, spermatogenic arrest and Sertoli-cell only status was assessed. RESULTSInfertility was suspected in 38 of 70 (54%) of formerly bilateral and six of 65 (9%) formerly unilateral cryptorchid patients. High FSH values were expected in these suspected infertile patients, but 15 of 38 (59%) formerly bilateral and five of six formerly unilateral cryptorchid patients had normal FSH values. These patients were identified in childhood at orchidopexy; those with bilateral cryptorchidism generally presented with germ cells, but the mean number of spermatogonia per tubule was <30% of the lowest normal value, and the germ cells were seldom normally differentiated, whereas those with unilateral cryptorchidism generally lacked germ cells in the biopsies. No patients had a decreased FSH value. CONCLUSIONDespite surgery for cryptorchidism, infertility was probable in a third (44 of 135) of the patients. We expected high FSH values in these patients, but in 45% (20/44) the FSH values were normal. These patients may have relative FSH deficiency. At orchidopexy these patients were identified to be bilaterally cryptorchid with few germ cells and those unilaterally cryptorchid had none in the biopsy. After orchidopexy in childhood, additional hormonal treatment, e.g. recombinant FSH or buserelin, may be indicated in these patients.

An hypothesis is proposed that the abnormal development of the diaphragmatic ligaments of the testes may lead to lack of their involution, with consequent cryptorchidism. In the case of splenogonadal fusion, the abnormal ligaments are colonized by splenic cells, possibly because of an abnormal proximity to the splenic anlage, with the resulting abnormal ligament persisting as the splenic cord and thus resulting in cryptorchidism. The basic abnormality may be in the connections of the diaphragmatic ligaments, caused by abnormal midline development in the third to fourth week of gestation.

In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.