Do alterations in the sex ratio occur at fertilization? A case report using fluorescent in situ hybridization

Abstract

In the clinical application of preimplantation genetic diagnosis (PGD), the efficiency of the fluorescence in-situ hybridization (FISH) technique is high and the sex of an embryo can be unequivocally determined when two X-chromosome signals. Y-chromosome signal or one X-chromosome and one Y-chromosome signal are detected. Furthermore, multicolor FISH with probes for chromosomes X, Y and one or more autosomes has the additional advantage that it can detect simultaneously the sex, ploidy status and numerical abnormalities of the investigated chromosomes. The application of FISH to human embryos has led to the discovery that chromosomal mosaicism is common at the cleavage stage of arrested and/or abnormally developing embryos as well as in normally developing embryos. We report here a case of a couple that wanted to selectively have a male pregnancy. They wished to combine the treatment with PGD so as to have only male embryos implanted. They have two normal female children and no history of clinically documented pregnancy losses. PGD studies on 6–8 cell embryos were done in two different cycles, with the X and Y-specific probes, using standard FISH procedures. In the first round all 3 embryos, resulting from routine insemination exhibited two X-chromosome signals, consistent with a female complement. Thus no implantation was done. In the second cycle, all 4 embryos, resulting from ICSI, were either normal female or showed a triploid XXY complement. Thus no normal male embryo was identified. The sex ratio of sperm from a semen sample is currently in progress. It is well known that there are families with a skewed proportion of male-to-female offspring. The reason for the preponderance of female embryos may be due to such a skewing in the male partner, or a higher incidence of non-disjunction in the Y-bearing sperm. Thus in families with children with only either sons or daughters, it is possible that an alteration in the embryo sex ratio might be explained by the preferential binding of Y-bearing sperm to the oocyte, an oocyte-related “discouragement” of binding of X-bearing sperm, or a postfertilization event like triploidy that is lethal.