NIPT interpretation requires tailored algorithms for donor-oocyte pregnancies
The study examines circulating cell-free DNA screening in pregnancies conceived with donor oocytes, where fetal chromosomal risk is donor-derived but cfDNA interpretability depends on the recipient and placental biology. Investigators note that recipient factors such as advanced maternal age, obesity, placental dysfunction and multiple gestation frequently destabilize the cfDNA signal, making fetal fraction a biological indicator of placental health rather than merely a technical quality metric. Counting-based and SNP-based NIPT platforms also diverge in performance, particularly for sex chromosome analysis and when maternal genetic confounding is present. For laboratory directors and prenatal screening programs, the findings underscore that no-call results carry clinical meaning and that generic NIPT algorithms require explicit fetal-fraction reporting, targeted pre-test counseling and ultrasound correlation to ensure accurate interpretation.
The original study
Non-Invasive Prenatal Testing in Donor-Oocyte Pregnancies: Biological Determinants, Algorithmic Limitations and Clinical Implications.
- Authors
- Miscia M, Pesaresi I, Dini B, Morano D, Cavoretto PI, Farina A
- Journal
- Molecular diagnosis & therapy
- Type
- Journal Article
- PMID
- 42570189
Original abstract
Non-invasive prenatal testing (NIPT) based on circulating cell-free DNA (cfDNA) has transformed prenatal screening for common aneuploidies, but its interpretation is less straightforward in pregnancies conceived with donor oocytes. In this setting, fetal chromosomal risk is largely donor-driven, whereas cfDNA interpretability is shaped mainly by the recipient and the placenta. Donor-oocyte pregnancies are enriched for advanced maternal age, obesity, hypertensive and immunologic complications, low-molecular-weight heparin exposure, multiple gestation, vanishing twin, and placental dysfunction - all factors that can destabilize the cfDNA signal. Fetal fraction should therefore be read not only as a technical quality metric but also as a biological marker of placental performance. Analytical platform behavior also matters; counting-based and single-nucleotide polymorphism-based approaches may behave differently in biologically complex samples, particularly for sex chromosome findings and in the setting of maternal confounding. In donor-oocyte pregnancies, a no-call result may be clinically informative rather than neutral. Pre-test counseling, explicit communication with the laboratory, availability of fetal-fraction reporting, and integration with first-trimester ultrasound are essential. Donor-oocyte pregnancy should be regarded as a biologically distinct model for cfDNA screening, one that exposes the limits of generic NIPT algorithms and argues for more tailored interpretation.