A Molecular Perspective on Procedures and Outcomes with Assisted Reproductive Technologies

The emerging association of assisted reproductive technologies with adverse perinatal outcomes has prompted the in-depth examination of clinical and laboratory protocols and procedures and their possible effects on epigenetic regulatory mechanism(s). The application of various approaches to study epigenetic regulation to problems in reproductive medicine has the potential to identify relative risk indicators for particular conditions, diagnostic biomarkers of disease state, and prognostic indicators of outcome. Moreover, when applied genome-wide, these techniques are likely to find novel pathways of disease pathogenesis and identify new targets for intervention. The analysis of DNA methylation, histone modifications, transcription factors, enhancer binding and other chromatin proteins, DNase-hypersensitivity and, micro- and other noncoding RNAs all provide overlapping and often complementary snapshots of chromatin structure and resultant "gene activity." In terms of clinical application, the predictive power and utility of epigenetic information will depend on the power of individual techniques to discriminate normal levels of interindividual variation from variation linked to a disease state. At present, quantitative analysis of DNA methylation at multiple loci seems likely to hold the greatest promise for achieving the level of precision, reproducibility, and throughput demanded in a clinical setting.