Prenatal diagnosis after assisted reproductive technology

Over the last three decades, prenatal screening for Down’s syndrome (DS) has become an integrated part of antenatal care in most developed countries. In the second trimester, the most common markers are maternal serum human chorionic gonadotrophin (hCG) or its free ß–subunit (Fß–hCG), alpha–fetoprotein (AFP), and unconjugated estriol (uE3). Large studies using combinations of hCG or Fß–hCG and either or both of the other markers have confirmed model predictions that about two thirds of DS-affected pregnancies can be detected with a false positive rate (FPR) of about 5% [1,2]. The most recent addition to the second–trimester serum markers has been inhibin–A, which is found at higher levels in affected pregnancies [3,4]. This combination of markers (the “quadruple test”) allows the detection of about 75% of DS–affected pregnancies with a FPR of approximately 5% if gestational age is based on an ultrasound scan [5]. It is presently accepted that ultrasound can identify and measure subcutaneous fluid collections between the soft tissue covering the fetal spine and the overlying skin during the late first trimester [6–8]. The thickness of this hypoechoic ultrasonographic feature, defined as nuchal translucency (NT), is associated with chromosomal abnormalities [6–8], cardiac and other structural defects [9], as well as an increased risk of spontaneous abortion [10]. In the first trimester, the combination of maternal serum pregnancy–associated placental protein–A (PAPP–A) and Fß-hCG can achieve a detection rate of approximately 60% with a FPR of about 5% [11].