In recent years, preimplantation genetic diagnosis (PGD) has emerged as a potential alternative to and compliments prenatal genetic diagnosis in preventing the birth of children with genetic/chromosomal abnormalities. Apart from congenital chromosomal and genetic abnormalities, PGD is currently used for the screening of late-onset diseases having a genetic predisposition, as well as preimplantation human leukocyte antigen (HLA) typing for the generation of savior siblings. However, certain researchers speculate that the technique is associated with adverse health effects including increased neurological defects in the offspring; probably due to the biopsy conducted in early stage embryos. Now, a recent prospective study published in the journal Human Reproduction rules out the risk for increased birth defects in singletons born after PGD.
Inge Liebaers, Head, Center for Medical Genetics, Brussels University Hospital, Belgium, and coworkers, carried out the prospective cohort study during 1992 to 2005 in order to analyze the effect of PGD on IVF/ICSI-conceived children. Data for 581 post-PGD/PGS and 2,889 ICSI children were collected via questionnaires from physicians and parents during the time of conception and at delivery, and was based on the examination of infants at 2 months of age by clinical genetics experts.
The researchers did not find any statistically significant difference between post-PGD/PGS and ICSI children, with overall 2.13% and 3.38% (OR=0.62) rates for major malformation noted in the corresponding groups.
However, they observed a significantly greater rate of perinatal death among post-PGD/PGS children when compared to the ICSI group (4.64% vs. 1.87%; OR=2.56). Additionally, further stratification based on multiple births showed that the perinatal death rate was more significant in post-PGD/PGS than in ICSI multiple pregnancies (11.73% vs. 2.54%; OR=0.83). The death rates were comparable in PGD/PGS and ICSI singletons (1.03% vs. 1.30%, respectively). Although the study concludes on the safety of blastomere biopsy for PGD, it cautions about an increased risk of perinatal mortality in multiple pregnancies. The researchers mandate long-term follow up to further substantiate the safety of the technique.
In a recent study conducted in mice models, Yu et al (Molecular & Cellular Proteomics, 2009) suggested an elevated risk for neurological disorders in offspring conceived following PGD. The study evaluated the preimplantation development efficiency, postnatal growth, and behavioral and physiological activity of embryos that had undergone blastomere biopsy at the four-cell stage. Mice grown from biopsied embryos demonstrated the occurrence of weight gain and memory decline when compared to the non-biopsied controls. Further analysis of the protein expression profiles of adult brains demonstrated altered expression pattern of proteins in the biopsied group, indicating the increased sensitivity of the nervous system to blastomere biopsy procedures. The study warrants further research to investigate the long-term effect of blastomere biopsy on the future development of offspring, and assess the overall safety of the PGD procedure.
In view of the contradictory findings regarding the benefits and the safety of PGD, extensive and comprehensive counseling is mandatory for the couples opting for the procedure. The recent recommendations put forth by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) ascertains the need for conducting genetic counseling prior to the procedure; the guidelines directed towards conveying the following to the patients:
• Enhanced risk of conceiving a child with genetic abnormality, and the impact of the condition on the future development of the offspring
• Need for performing PGD to reduce the risk of having a child with genetic defects
• Benefits and limitations of all the currently available options for genetic testing
• Chances of false-negative results, and the lack of evidence to substantiate that PGD improves live birth rates.
1. Liebaers I, Desmyttere S, Verpoest W, et al. Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis. Hum Reprod. 2010 Jan;25(1):275-82.
2. Yu Y, Wu J, Fan Y, et al. Evaluation of blastomere biopsy using a mouse model indicates the potential high risk of neurodegenerative disorders in the offspring. Mol Cell Proteomics. 2009 Jul;8(7):1490-500.
3. Wilson RD, Allen V, Audibert F, et al. Preimplantation Genetic Testing. J Obstet Gynaecol Can. 2009;31(8):761–767.