Clinical consequences of an increasing trend of preferential use of cultured villi for molecular diagnosis by CVS.

OBJECTIVE: To compare the use of uncultured versus cultured villus cells for DNA-based prenatal diagnosis. METHODS: A retrospective review of molecular testing of chorionic villus sampling (CVS) cases from 1988-2007. Method of analysis, gestational age (GA) at CVS and at diagnosis, time from procedure to results, results of maternal contamination studies, and the laboratory employed were abstracted from patient charts. Trends in laboratory practices over time were analyzed. RESULTS: Time from CVS to diagnosis was longer when cultured cells were used. Average GA at diagnosis was 14-6/7 weeks with cultured cells vs 13-0/7 weeks with uncultured villi (p < 0.001). Recently, laboratories are more frequently requiring cultured cells, resulting in significantly greater delays in time to diagnosis and GA at results. CONCLUSIONS: 'Direct' DNA extraction saves 2 weeks from CVS to results. More women are afforded the option of an earlier, safer pregnancy termination if uncultured villi are used for molecular diagnosis. Implementation of standardized DNA extraction protocols and sample-size requirements can optimize the use of uncultured villi for molecular prenatal diagnosis. Increased awareness of the importance of rapid results and the advantages of 'direct' DNA extraction from uncultured villi can lead to improvements that are of clinical significance for patients undergoing early prenatal diagnosis.

Association of undetectable unconjugated estriol on multiple marker screening with steroid sulfatase deficiency.

OBJECTIVE: To determine whether all patients with undetectable unconjugated estriol (uE3) on multiple marker screening (MMS) are carriers for steroid sulfatase (STS) deficiency. METHODS: This is a retrospective review of 65 pregnancies with undetectable uE3 on MMS. RESULTS: Of the 65 pregnancies, there were 21 that continued, 40 spontaneous losses, 2 lost to follow-up and 2 elective terminations. Of the 21 continuing pregnancies, 15 were determined to be carriers of the STS deletion. Twenty-seven of the 40 pregnancy losses were associated with elevated alpha-fetoprotein (AFP); about half of the losses were shown to have occurred prior to sampling. CONCLUSION: Patients with undetectable uE3 are likely to be carriers of the STS deletion, except those with associated elevated AFP. Elevated AFP with undetectable uE3 on MMS is a marker of preexisting or impending fetal demise.