Report on a Consecutive Series of 581 Children Born After Blastomere Biopsy for Preimplantation Genetic Diagnosis

Abstract

The aim of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) is to prevent the transmission of a genetic condition before pregnancy in couples at high risk. Healthy children have been born following PGD/PGS, but no large prospective studies have investigated the safety of embryo biopsy performed for PGD/PGS in fetuses or newborns. This observational prospective cohort study of children born after embryo biopsy for PGD or PGS was conducted between 1992 and 2005 to determine the possible risk of embryo biopsy at day 3 after intracytoplasmic sperm injection (ICSI) to the health of the fetus or offspring. Data on 581 post-PGD/PGS children were compared with historical data of 2889 children conceived through the use of ICSI technology. Physicians and parents completed questionnaires at conception and at delivery. Two-months after delivery, the babies were examined at an outpatient clinic by trained clinical geneticists. There were no statistically significant differences between the post-PGD/PGS and ICSI children with respect to gestational ages or birth weight. No major differences were found in rates of major malformation between the 2 groups of children (post-PGD/PGS: 2.13% vs. ICSI: 3.38%); the odds ratio (OR) was 0.62, with exact 95% confidence limits (CL) of 0.31–1.15. The overall perinatal death rate, however, was significantly higher in post-PGD/PGS children in comparison to ICSI children (4.64% vs. 1.87%); the OR was 2.56, with a 95% CL of 1.54–4.18. Stratification for multiple births showed that the difference between the 2 groups in perinatal deaths was a reflection of a marked increase in such infant deaths in multiple pregnancies: Although perinatal death rates among PGD/PGS and ICSI singleton children were similar (1.03% vs. 1.30%; OR: 0.83; 95% CL: 0.28–2.44), these rates were significantly higher among post-PGD/PGS multiple pregnancies compared with ICSI multiple pregnancies (11.73% vs. 2.54%; OR: 5.09; 95% CL: 2.80–9.90). The misdiagnosis rate was less than 1%. The investigators conclude from these findings that embryo biopsy is not an additional risk factor in singleton newborn PGD/PGS children and that multiple pregnancies should be avoided because of the increased rate of perinatal deaths.