Genetic risk of Klinefelter's syndrome in assisted reproductive technology.

Aim: The main cause of Klinefelter's syndrome (KS) has been believed to be XY sperm. Accordingly, in the intracytoplasmic sperm injection treatment of patients with KS, hereditary KS has been a concern. Therefore, this study attempted to estimate the risk before and after the assisted reproductive technology.

Methods: First, in order to validate the safety of the gametes of the patients with KS, a fluorescent in situ hybridization (FISH) analysis, following an original cell identification method using 1052 testicular gametes of 30 patients, was conducted. Second, in the resultant 45 babies, cytogenetic and physical-cognitive screening data were analyzed. In addition, a first attempt was conducted to investigate the origin of the extra X chromosome in 11 patients with KS by using 12 X-chromosome short tandem repeat (STR) analysis in order to estimate the paternal contribution to KS.

Results: No sex chromosomally abnormal gamete was found in the FISH analysis and the babies were normal genetically, physically, and cognitively. In the STR, it was confirmed that most (7/11) of the patients with KS resulted from the fertilization of the XX oocytes, suggesting that a baby with KS that had been reported previously might not have resulted from XY sperm.

Conclusion: These results indicate that the risk of assisted reproductive technology for patients with KS is not as high as previously expected.