Results of preimplantation genetic diagnosis in patients with Klinefelter's syndrome.

With the application of preimplantation genetic diagnosis (PGD), a possible genetic contribution of spermatozoa obtained from 47,XXY non-mosaic Klinefelter patients on preimplantation embryos was analysed in eight couples. Interpretable fluorescence in-situ hybridization results were obtained for 28 out of 33 embryos biopsied (84.8%) and 23 blastomeres were analysed for chromosomes 13, 18, 21, X and Y. Nine out of 23 embryos were diagnosed as abnormal (39.1%). Five out of nine contained sex chromosome abnormalities (55.5%). Two were diagnosed as 47,XXY and three were found to have monosomy X. Besides sex chromosomal abnormalities, other abnormalities detected were haploidy, triploidy, monosomy 13, monosomy 18 and trisomy 13. Five blastomeres were analysed for sex chromosomes only and all of them were found to be normal. Overall, the rate of sex chromosome abnormality in biopsied embryos was found to be 17.8% (5/28). Moreover, among 33 embryos biopsied, five of the eight zygotes, which were classified as a poor prognosis group according to pronuclear morphology scoring, showed an impaired growth profile after biopsy and were found to be chromosomally abnormal. Elimination of abnormal embyos and transfer of normal ones resulted in four pregnancies in eight cycles (50%). Two pregnancies, one singleton and one twins resulted in healthy births. Two pregnancies, one singleton and one twins are continuing beyond the second trimester. These results show that there is in fact elevated chromosomal abnormality for both sex chromosomes and autosomes in embryos developed from Klinefelter males. Furthermore together with PGD, embryo scoring according to pronuclear morphology can give additional benefit for selecting chromosomally abnormal embryos. Therefore, PGD should be recommended in cases with Klinefelter's syndrome and this information should be discussed with the couple when genetic counselling is given.