Noninvasive First-Trimester Aneuploidy Screening Is Feasible in Routine Fertility Practice

A new, noninvasive approach to prenatal aneuploidy screening in the first trimester using cell-free DNA (cfDNA) obtained from maternal plasma is highly feasibly in routine fertility practice, according to findings from a new study. 

Karen R. Hammond, DNP, CRNP, from the Alabama Fertility Specialists in Birmingham, AL, presented results from a real-world retrospective analysis at the Scientific Congress & Expo of the American Society for Reproductive Medicine held October 15 to 19, 2016, in Salt Lake City, UT.

Historically, a diagnosis of aneuploidy required invasive procedures, such as amniocentesis or chorionic villus sampling, offered to high-risk women alone. Results were not typically available until the second trimester, and false-positive rates of approximately 5% were tolerated to permit high specificity for aneuploidy detection.

With the availability of noninvasive screening tools, the American Congress of Obstetricians and Gynecologists now recommends prenatal screening for genetic disorders for all women in early pregnancy. One emerging option for noninvasive prenatal screening involves the detection of cell-free fetoplacental DNA derived from placental cell apoptosis. The half-life of cfDNA fragments in maternal blood is less than 20 minutes, and cfDNA is undetectable by 2 hours postpartum, meaning that prior pregnancies do not influence cfDNA results.

Advantages of noninvasive prenatal screening with cfDNA include high sensitivity rates (eg, 99% for trisomy 21) and low false-positive rates (0.5%), leading to fewer unnecessary invasive procedures for confirmatory testing. Screening can be performed at 9 to 10 weeks, and the results are available in 5 to 14 days. Compared with amniocentesis or chorionic villus sampling, there is no procedure-related risk of miscarriage. In the present study, Hammond and her colleagues analyzed the feasibility of cfDNA screening for aneuploidy in a routine fertility practice.

The research team evaluated the medical records of women in the fertility practice with non–donor-egg singleton gestations that reached 9 weeks of gestational age. Between June 2014 and June 2016, all women meeting these criteria (N = 233) were offered noninvasive prenatal screening using cfDNA. The mean age of the patients was 31.7 years; 23% of patients were 35 years of age or older. Medical histories included infertility (78.5%), prior spontaneous pregnancy loss (47.2%), and recurrent spontaneous abortion (RSA; 18.5%).

Patient acceptance of noninvasive prenatal screening with cfDNA was high: 188 women (81%) agreed to undergo screening. Acceptance rates were similar for patients presenting with infertility (80%) or a history of RSA (86%). However, patients with a history of RSA were less likely to request fetal sex determination when compared with those who presented with infertility (86% vs 97%; P = .06). No other factors correlated with testing for noninvasive prenatal screening, including patient age, race/ethnicity, body weight, prior live birth, history of genetic disease, or use of ovulation induction, assisted reproductive technology, or donor sperm.

Noninvasive prenatal screening with cfDNA was performed at a mean of 74.4 days of gestational age. Screening results showed a low probability of aneuploidy in 172 patients (91.5%) and a high probability of aneuploidy in 3 patients (1.6%). All live births to date have confirmed the results of noninvasive prenatal screening, with 2 cases of trisomy 21 and 1 case of trisomy 18.

For 13 patients (7%), the fraction of fetal DNA detected was too low to provide screening results. In this group, higher body weight significantly predicted a lower fraction of fetal cells and an increased risk of test failure (Table). Each 10-lb increase in maternal body weight was associated with a 0.5% decrease in mean fetal fraction (P < .0001). However, next-generation sequencing techniques, such as massively parallel sequencing, may improve the detection of fetal cfDNA regardless of maternal body weight.

Table. Maternal Body Weight and Test Failure Due to Low Fetal Fraction

Body Weight < 200 lb (n = 155) Body Weight > 200 lb (n = 33) P Value
Test failure, n (%) 4 (3) 9 (27) < .0001
Mean fetal fraction, % 9.1 4.6 < .0001

Overall, these findings support the use of noninvasive prenatal screening with cfDNA for fetal aneuploidy screening within fertility practices. “Better adoption of first-trimester noninvasive prenatal screening within reproductive endocrinology practices should keep women with their provider longer, delaying the separation anxiety that women feel when they must go elsewhere for testing,” Hammond said.

Source: Hammond KR, Cataldo NA, Malizia BA, et al. Non-invasive first-trimester aneuploidy screening using cell-free DNA in a fertility practice: acceptability and outcomes. Presented at: American Society for Reproductive Medicine 2016 Scientific Congress & Expo; October 15-19, 2016; Salt Lake City, UT. Abstract O-49.