Non-invasive Prenatal Diagnosis Using Cell-Free Fetal DNA in Maternal Plasma From PGD Pregnancies

Reprod Biomed Online. 2009 Nov;19(5):714-20. doi: 10.1016/j.rbmo.2009.09.005.


Preimplantation genetic diagnosis (PGD) is usually used to establish a non-affected pregnancy for those couples facing a genetic risk of having an affected child. However, an invasive test is still recommended to all PGD patients due to the risk of misdiagnosis. The discovery of cell-free fetal DNA in maternal plasma provides the possibility for noninvasive prenatal diagnosis. Studies have shown that fetal single-gene disorders can be detected in cell-free fetal DNA by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single-allele base extension reaction (SABER) approach or by the size-fractionation approach, whereby cell-free fetal DNA is enriched on the basis of its smaller size compared with maternal DNA fragments. Recent studies have indicated that a combination of the two approaches increases the accuracy of detection. This study combined the two methods and examined fetal paternally inherited gene mutations in maternal plasma obtained from four PGD-conducted pregnancies. The presence or absence of mutations was correctly detected in all cases. This combined method could be used for risk-free prenatal diagnosis of diseases caused by single-gene mutations, and in particular for couples who undergo PGD who opt not to perform invasive prenatal confirmation due to the risk of abortion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / blood*
  • Female
  • Genotype
  • Gestational Age
  • Humans
  • Male
  • Maternal-Fetal Exchange / genetics
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Preimplantation Diagnosis
  • Prenatal Diagnosis / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • DNA