Genetic risk of Klinefelter's syndrome in assisted reproductive technology

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.

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.

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.

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