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Cell-free fetal DNA testing in singleton IVF conceptions.

Timothy J Lee1,2, Daniel L Rolnik2, Melody A Menezes3

  • 1Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria 3800, Australia.

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Summary
This summary is machine-generated.

Cell-free fetal DNA (cffDNA) testing shows lower fetal fraction, higher test failure rates, and poorer positive predictive value in pregnancies conceived via in vitro fertilization (IVF) compared to spontaneous conceptions. These findings highlight important differences for patient counseling.

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Area of Science:

  • Reproductive Medicine and Genetics
  • Prenatal Diagnostics
  • Genomic Analysis

Background:

  • Cell-free fetal DNA (cffDNA) testing offers high accuracy for detecting trisomies in the general obstetric population.
  • Limited evidence exists on the specific performance of cffDNA testing in pregnancies conceived through in vitro fertilization (IVF).

Purpose of the Study:

  • To compare key performance metrics of cffDNA testing between singleton pregnancies conceived via IVF and those conceived spontaneously.
  • To investigate differences in fetal fraction, test failure rate, and positive predictive value (PPV) between these two conception groups.

Main Methods:

  • Retrospective cohort study including 4633 spontaneously conceived and 992 IVF-conceived singleton pregnancies.
  • cffDNA testing performed after 10 weeks' gestation for screening of trisomies 21, 18, 13, and sex chromosome aneuploidies (SCA).
  • Multivariate regression analyses used to identify predictors of fetal fraction and test failure.

Main Results:

  • IVF pregnancies had significantly lower median fetal fraction (10.3% vs. 11.9%) and higher test failure rates (5.2% vs. 2.2%) compared to spontaneous conceptions.
  • Positive predictive value (PPV) for trisomies 18, 13, and SCA was poorer in the IVF group, although PPV for trisomy 21 remained high (100.0%).
  • IVF conception, increased BMI, earlier gestational age, and certain ethnicities were independent predictors of lower fetal fraction.

Conclusions:

  • cffDNA testing performance differs between IVF and spontaneously conceived pregnancies, with lower fetal fraction and higher failure rates in the IVF group.
  • The findings necessitate consideration of these differences during pre-test counseling for pregnant women who conceived via IVF.
  • While PPV for trisomy 21 is high, caution is advised for other aneuploidies in IVF conceptions due to poorer PPV.