Preimplantation diagnosis of common aneuploidies in infertile couples of advanced maternal age

Because age-related aneuploidies are mainly due to nondisjunction occurring in maternal meiosis, preimplantation genetic diagnosis (PGD) of aneuploidies may have considerable impact on the effectiveness of assisted reproduction technology (ART) for patients of advanced maternal age. Two different approaches have recently become available for PGD of chromosomal disorders, involving fluorescent in-situ hybridization (FISH) technique, which makes it possible to detect chromosome specific signals in interphase nuclei. One of these approaches is based on the cleavage stage biopsy and FISH analysis of one or two blastomeres, the other involving FISH analysis of polar bodies removed from the oocytes (Verlinsky et al. 1996). While both of these approaches have a great potential for preimplantation detection of common aneuploidies, each of them has its own limitations: the cleavage stage PGD may not reflect the chromosomal constitution of the embryo due to a high frequency of mosaicism in cleaving embryos (Delhanty et al, 1993; Munn6 et al, 1993; 1994; Harper et al., 1995), while PGD by polar body FISH analysis does not pick up paternally derived aneuploidies (Verlinsky et al, 1995; 1996a). However, because paternal contribution to the aneuploidy rates is minor compared to that originating in the maternal first and second meiotic divisions (Antonarakis et al, 1992; Hassold et al., 1993), and there is no evidence for the paternal age-related risk, the polar body diagnosis may allow detection and elimination from transfer of the majority of aneuploid embryos. Therefore, the polar body approach should make it possible to detect aneuploid oocytes in in-vitro fertilization (IVF) patients of advanced maternal age to prevent the transfer of embryos resulting from aneuploid oocytes (Verlinsky et al., 1995; 1996a; Munn6 et al., 1995). Accordingly, this should not only reduce the chances of an IVF couple of having a child with Down's syndrome and other common aneuploidies, but may also improve the efficiency of FVF as most aneuploid embryos are lost before or during implantation. The available experience on PGD of chromosomal aneuploidies reviewed by 5th Annual Meeting of International Working Group on Preimplantation Genetics has already demonstrated feasibility of both approaches (Verlinsky, 19%). The majority of the cases have been performed by polar body approach and involved 193 IVF patients of advanced maternal age (Verlinsky et al, 1996b). In these patients 1293 oocytes were biopsied and subjected to FISH analysis, with results of the first and/or second polar bodies available in 993 oocytes. Abnormal FISH patterns were observed in 328 (33%) oocytes based on the analysis of the first and/or second polar bodies. Of