Non-invasive first-trimester aneuploidy screening using cell-free DNA in a fertility practice: acceptability and outcomes

Abstract

First-trimester noninvasive prenatal screening (NIPS) for aneuploidy using cell-free DNA (cfDNA) in maternal blood, a relatively new screening approach, has improved validity over conventional methods.1 While general OB-GYNs have been slow to adopt cfDNA, fertility practices may easily incorporate this screening. We describe the first report of acceptance and outcomes of cfDNA NIPS among patients in a single fertility practice. Retrospective chart review. Beginning 1 June 2014, all non-oocyte-recipient women presenting with first-trimester singleton pregnancies in our practice were offered NIPS using cfDNA. Charts were extracted for demographics, genetic and pregnancy histories, diagnosis, treatment, and index pregnancy details. Descriptive and comparative statistics were used to analyze NIPS acceptance and outcomes. NIPS using cfDNA was offered to 233 women, of whom 81.5% presented for infertility and 18.5% for recurrent spontaneous abortion (RSA). cfDNA screening was accepted by 188 (80.7%). Demographic, historical, and diagnostic parameters were not associated with acceptance; 79.5% with infertility and 86.0% with RSA accepted cfDNA NIPS. NIPS was done at a mean 74.4±6.4 (SD) days’ gestational age (GA; median 73, IQR 70-76, range 64-111), and showed low probability of aneuploidy (LO) in 91.4%, high probability in 1.6% [trisomy 21 (2); trisomy 18 (1)], and no result (NR) in 7.0%. NR trended toward a negative association with GA (OR 0.94/day, 95% CI 0.879-1.008, p=0.058). Six of the 10 women with NR advised to repeat testing did so; 4 were again NR and 2 LO, giving a definitive result in 174/185 (94.1%) overall. cfDNA fetal fraction (FF) was >4%, as needed for validity, in 91.3%, and was negatively correlated with maternal weight (r=-0.53, p<0.0001). A NIPS result was not returned in 2.6% of 152 women weighing <200 lb, but in 27.3% of 33 women >200 lb (p<0.0001). At first, all tests were sent to a single lab (Lab1), which used single nucleotide polymorphism (SNP)-based sequencing. For the heavier women, we switched to a second lab using massively parallel sequencing; it returned a result in 10/10, while Lab1 did so in only 13/22 (p=0.03). Fetal sex information was requested by 94.1% of couples; 47.2% were reported as female, 46.6% as male, and 6.2% gave no result. Of the 188 screened women, all 99 livebirths to date have confirmed the screen findings, including one trisomy 21, while 76 pregnancies are ongoing; outcomes were unavailable for 13. The predicted trisomy 18 is ongoing with multiple anatomic anomalies. First-trimester aneuploidy screening, recommended to be offered in all pregnancies,2 can be successfully implemented in a fertility practice using cfDNA, with 81% acceptance, a definitive result in 94%, and a low-probability-of-abnormal result in 91%, providing reassurance to most couples.1 Massively parallel sequencing is superior to SNP-based sequencing for heavier women.