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Various prospective studies have shown a detection rate of 86%–90% for fetal Down syndrome with a positive screening rate of 5% in classic first-trimester screening. A combination of first- and second-trimester markers (integrated screening) allows improvement in the detection rate to 94%–96% if the result is kept until the second-trimester results are available. The early results of first-trimester screening and the better test performance of integrated screening are combined to determine the need for sequential screening, so that additional secondtrimester biochemical testing is only performed in cases of intermediate risk. Patients at high risk after first-trimester screening can be offered invasive diagnostic testing, whereas patients at very low risk do not need further testing. Prospective studies evaluating a definite risk cutoff on which to base recommendation of second-trimester testing have not been published. If further information on the health of the fetus beyond the risk for fetal aneuploidies is requested, extended first-trimester ultrasound is an appropriate alternative. It is currently unclear to what extent screening performance for Down syndrome is improved by additional first-trimester ultrasound markers.

For decades scientists have sought to utilize information obtained for the blood of pregnant women for non-invasive prenatal diagnostic and screening approaches. During the 1990s the enrichment and analysis of fetal cells in maternal blood was the main target of investigations. However, high expectations have not been met and routine application of this approach is not in sight. The finding of fetal DNA and shortly thereafter fetal RNA came at the right time to fill this gap. Meanwhile, the determination of fetal Rhesus D blood group and fetal sex based on non-invasive genotyping of cell-free DNA in the maternal circulation are being introduced into clinical practice throughout Europe. In addition, methods to determine the inheritance of paternal mutations will help to prevent invasive sampling of amniotic fluid or chorionic villi for genetic diagnosis in the near future. Finally, researchers are closing in on the goal to non-invasively diagnose fetal aneuploidies; however, it will take some time until the early investigative successes can be implemented in routine clinical practice.

The techniques used for invasive prenatal diagnostics include methods based on analysis of fetal cells, amniotic fluid or blood samples. The sampling techniques used to collect these cells or fluids are associated with an interventional risk, particularly of abortion or intrauterine fetal death. For this reason, invasive prenatal diagnostics generally requires – in contrast to non-invasive screening methods, some of which are part of the general guidelines for pregnancy care – a medical indication. This indication usually involves an individual disease risk for the fetus.

Preimplantation genetic diagnosis (PID) as the earliest form of prenatal diagnosis (PND) has been available since 1990. Since then, the method has been used for couples at high risk for monogenic disorders to avoid a late termination of pregnancies after PND or to increase pregnancy rates after assisted reproductive techniques. Owing to different laws covering the issues of PND, some countries, including Germany, Austria and Switzerland, as well as Italy since 2005, can only offer a special form of PID consisting of polar body diagnosis (PBD). Although the molecular genetic and cytogenetic methods used for PID and PBD are identical in general, there are differences with regard to medical indications and data interpretation. The present article compares applications and methods of PID and PBD and outlines the procedure for PBD for a monogenic disorder.