PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders

Reproduction. 2020 Nov;160(5):A1-A11. doi: 10.1530/REP-19-0591.


The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has enabled a paradigm shift in prenatal testing, allowing for safer, earlier detection of genetic conditions of the fetus. Non-invasive prenatal testing (NIPT) for fetal aneuploidies has provided an alternative, highly efficient approach to first-trimester aneuploidy screening, and since its inception has been rapidly adopted worldwide. Due to the genome-wide nature of some NIPT protocols, the commercial sector has widened the scope of cell-free DNA (cfDNA) screening to include sex chromosome aneuploidies, rare autosomal trisomies and sub-microscopic copy-number variants. These developments may be marketed as 'expanded NIPT' or 'NIPT Plus' and bring with them a plethora of ethical and practical considerations. Concurrently, cfDNA tests for single-gene disorders, termed non-invasive prenatal diagnosis (NIPD), have been developed for an increasing array of conditions but are less widely available. Despite the fact that all these tests utilise the same biomarker, cfDNA, there is considerable variation in key parameters such as sensitivity, specificity and positive predictive value depending on what the test is for. The distinction between diagnostics and screening has become blurred, and there is a clear need for the education of physicians and patients regarding the technical capabilities and limitations of these different forms of testing. Furthermore, there is a requirement for consistent guidelines that apply across health sectors, both public and commercial, to ensure that tests are validated and robust and that careful and appropriate pre-test and post-test counselling is provided by professionals who understand the tests offered.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy*
  • Cell-Free Nucleic Acids / analysis
  • Cell-Free Nucleic Acids / genetics
  • DNA Copy Number Variations*
  • Female
  • Fetal Diseases / diagnosis*
  • Fetal Diseases / genetics
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / embryology
  • Genetic Diseases, Inborn / genetics
  • Genetic Testing / methods*
  • Humans
  • Pregnancy
  • Preimplantation Diagnosis / methods*


  • Cell-Free Nucleic Acids