Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Cytogenetic research has had a major impact on the field of reproductive medicine, providing an insight into the frequency of chromosomal abnormalities that occur during gametogenesis, embryonic development and pregnancy. In humans, aneuploidy has been found to be relatively common during fetal life, necessitating prenatal screening of high-risk pregnancies. Aneuploidy rates are higher still during the preimplantation stage of development. An increasing number of IVF laboratories have attempted to improve pregnancy rates by using preimplantation genetic diagnosis (PGD) to ensure that the embryos transferred to the mother are chromosomally normal. This paper reviews some of the techniques that are key to the detection of aneuploidy in reproductive samples including comparative genomic hybridization (CGH). CGH has provided an unparalleled insight into the nature of chromosome imbalance in human embryos and polar bodies. Methods for chromosomal analysis have become increasingly powerful, benefiting enormously from the fusion of traditional cytogenetic techniques and molecular genetics. Fluorescence in situ hybridization and comparative genomic hybridization have been amongst the most significant methodological advances. CGH has overcome many of the technical limitations that beset earlier cytogenetic methods, allowing detailed chromosomal data to be obtained from a variety of tissues that were previously considered problematic. In the field of reproductive medicine, as in other fields, CGH has been employed for the ascertainment of chromosomal duplications, amplifications and deletions that contribute to neoplastic transformation. This has revealed the chromosomal location of tumor suppressor genes and oncogenes that play a role in neoplasia affecting tissues of the reproductive system. The application of CGH to prenatal and pediatric samples has also proven extremely beneficial, allowing the delineation of complex or cryptic chromosomal rearrangements that could not be defined using classical cytogenetic techniques. CGH has also been applied to the analysis of mitotically inactive cells derived from products of conception, shedding light on the spectrum of chromosomal abnormalities causing miscarriage. Finally, the use of CGH to analyze human preimplantation embryos has provided unique scientific data concerning the variety and rate of aneuploidy at this early developmental stage. Most recently, this has led to methods for screening IVF embryos, assisting in the identification of those with the greatest potential for further development. In the future, CGH or related techniques such as M-CGH, will allow IVF clinics to screen embryos for any form of aneuploidy. It is hoped that this will enable the preferential transfer of the embryos most likely to form a viable pregnancy and thus lead to improvements in the outcome of assisted reproductive procedures.

Source References:

http://www.ncbi.nlm.nih.gov/pubmed?term=Cytogenetics%20in%20reproductive%20medicine%3A%20the%20contribution%20of%20comparative%20genomic%20hybridization%20(CGH)