Prepregnancy genetic testing for age-related aneuploidies by polar body analysis

Abstract

Current practice for prevention of chromosomal aneuploidies involves prenatal screening and termination of pregnancy, a procedure that is not universally acceptable. We introduced prepregnancy genetic testing by sampling and fluorescence in situ hybridization (FISH) analysis of the first and second polar body (PB), to avoid fertilization and transfer of embryos resulting from aneuploid oocytes. In 395 in vitro fertilization (IVF) patients of advanced maternal age, the first and second PBs were removed following their extrusion from oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21, to detect and avoid the transfer of oocytes with common aneuploidies. Overall, 3,651 oocytes obtained from 598 IVF cycles were available for FISH analysis, with 2,952 showing interpretable FISH results (80.9%). The analysis revealed 1,271 (43.1%) oocytes with aneuploidy, which were excluded from transfer and subjected to follow-up FISH analysis to confirm PB diagnosis in the cleavage or blastocyst stage embryos. Only embryos originating from 1,681 aneuploidy-free oocytes were transferred back to patients, resulting in 119 pregnancies overall, from which 78 healthy children have already been born, 35 were spontaneously aborted, and 16 are ongoing, after confirming PB diagnosis by prenatal diagnosis. The results demonstrate that PB-based preimplantation diagnosis may be used for prepregnancy screening in women with age-related risk for common aneuploidies.