Enrichment of fetal trophoblast cells from the maternal peripheral blood followed by detection of fetal deoxyribonucleic acid with a nested X/Y polymerase chain reaction.

OBJECTIVE: Fetal cells circulate in the maternal blood during early pregnancy. Because these cells are rare, noninvasive prenatal diagnosis from fetal cells can be achieved only after efficient enrichment procedures. Our aim was to develop a two-step enrichment procedure to isolate trophoblast cells from 20 ml of peripheral blood. STUDY DESIGN: Blood was obtained from pregnant women between 6 and 15 weeks of gestation, before invasive procedures were performed. After enrichment, the success of isolating fetal cells was determined by amplification of Y chromosome sequences. RESULTS: A highly specific X/Y polymerase chain reaction was established, sensitive enough to detect X and Y chromosome-specific sequences in one single cell and in one male among 100,000 female cells. Sex determination by polymerase chain reaction was compared with results from conventional karyotyping. The success rate was 91.7%. CONCLUSION: Enrichment of trophoblast cells from maternal blood as described here might be useful for early noninvasive prenatal diagnosis.