Serial first- and second-trimester Down's syndrome screening tests among IVF- versus naturally-conceived singletons

Background: It has been reported that second-trimester serum markers may be affected by assisted reproduction, leading to a higher false-positive rate. Methods: A total of 285 naturally and 71 IVF-conceived singletons which underwent a serial disclosure Down's syndrome screening programme were compared. The study protocol included first-trimester combined [nuchal translucency (NT), free beta-HCG and pregnancy-associated plasma protein-A (PAPP-A)] testing. The second-trimester triple serum screening included alpha-fetoprotein (AFP), intact HCG and unconjugated estriol (uE(3)). After excluding aneuploidies, miscarriages, anatomical anomalies and cases with incomplete follow-up, the serum samples of normal cases were assessed and correlated. Results: NT measurement was not significantly changed in either group. However, the IVF group had lower PAPP-A [0.96 versus 1.05 multiples of normal median (MoM)] and higher AFP (1.13 versus 1.07 median MoM). Both groups had similar rates of first-trimester false-positive results (FPR; 7 and 9% respectively), but the IVF group had a significantly higher mid-gestation FPR rate (10 versus 5%; Pearson chi(2), p=0.029). This has contributed to amniocentesis uptake rates of 15 and 13% for the IVF and natural conception pregnancies respectively. Conclusions: The IVF group tended to have a significantly higher second-trimester FPR rate. To counterbalance this phenomenon, integrated first- and second-trimester screening tests or the use of NT alone might be a reasonable option that deserves further investigation.