ANEUPLOIDY-16 IN HUMAN EMBRYOS INCREASES SIGNIFICANTLY WITH MATERNAL AGE

Objectives: To determine aneuploidy for chromosome 16 by recycling nuc lei of cells already analyzed for chromosomes X, Y, 18, 13, and 21 usi ng multiple-probe fluorescence in situ hybridization in preimplantatio n human embryos in a time frame compatible with clinical NF and to ass ess the incidence of chromosome 16 aneuploidy in embryos related to ma ternal age, Design: Prospective experimental study. Setting: In vitro fertilization program in a tertiary center. Patients: One hundred four consenting patients undergoing IVF. Main Outcome Measures: Chromosome 16 ploidy was analyzed in a total of 195 embryos. In 89 embryos, a st andard multiple-probe fluorescence in situ hybridization was used for chromosomes X, Y, 18, and 16 (series 1). The remaining 106 embryos (se ries 2) were reanalyzed with a new procedure for chromosome 16, which involves rehybridization with a digoxigenin-labeled cr satellite probe after the standard analysis for chromosomes X, Y, 18, 13, and 21 was completed. The embryos were assigned to one of three groups according to the women's age; group 1: less than or equal to 34 years (n = 34), group 2: 35 to 39 years (n = 47); group 3: greater than or equal to 40 years (n = 23). Results: Successful analysis, including biopsy, fixat ion, and fluorescence in situ hybridization was achieved in 86% of the blastomeres within approximately 10 hours. a significant relationship was found between the rate of aneuploidy for chromosome 16 and increa sing maternal age: group 1: 0%, group 2: 6.3%, and group 3: 11.7%. Mon osomy for chromosome 16 was found in 72.7% of the II embryos carrying chromosome 16 anomalies, with the remaining three embryos having two t risomies and one tetrasomy. This new protocol was applied clinically t o five patients undergoing reimplantation aneuploidy assessment. Aneup loidy for chromosome 16 was found in five embryos from three of those patients. Conclusions: This study demonstrates that preimplantation ge netic diagnosis of the major human aneuploidies is achievable within a time frame compatible with IVF. In addition, this study confirms, for embryos, the existing data from spontaneous abortions suggesting that chromosome 16 aneuploidy increases with maternal age. The high preval ence of embryonic monosomy, which is rarely found in spontaneous abort ions, suggests that monosomy 16 could be a factor-associated with fail ure of implantation, as well as pointing to a different mechanism invo lved in the generation of chromosome 16 aneuploidy.