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IVF Doesn't Increase Chromosomal Instability in Newborns, Study Finds

NEW YORK –In vitro fertilization (IVF) does not appear to lead to a rise in copy number changes in newborns, compared with children conceived without reproductive assistance, a new genomic analysis suggests, despite the fact that chromosomal instability has been documented in IVF embryos.

"Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages," University of Tartu researcher Andres Salumets, along with Joris Vermeesch and Thierry Voet of University Hospital Leuven, the study's co-senior authors, and their colleagues wrote.

For their analyses, the researchers performed array-based SNP profiling on placental and cord blood cell samples from more than 100 successful IVF pregnancies, along with samples collected from mothers and fathers — data that made it possible to distinguish between de novo and maternally inherited copy number variants in the fetal and placental samples. Their findings, published online today in Nature Medicine, showed that new chromosomal abnormalities had similar frequencies in IVF and non-IVF pregnancies.

"We demonstrate that [chromosomal instability] is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived, live-born neonates," the authors wrote.

Past studies have demonstrated that chromosomal instability is more likely to occur in cleavage-stage embryos after IVF, leading to mosaicism in later stages of embryo development, the team explained. That has prompted speculation that chromosomal mosaicism might contribute to the implantation problems after IVF transfer, though its potential consequences at later stages of prenatal development have not been as clearly characterized.

"Despite the high prevalence of human IVF embryos with aberrant chromosomal configurations, its clinical implications are poorly understood," the authors wrote.

In an effort to understand if, and how, chromosomal changes might manifest themselves after birth, the researchers compared genome-wide, SNP array-based CNV patterns in post-partum samples from 111 pregnancies, including 49 IVF and 62 natural conception pregnancies.

Using CNV profiles in each quartet — made up of mothers, fathers, placenta samples, and umbilical cord blood — the team determined that de novo copy number changes are found at similar rates in post-IVF fetal and placental samples. Likewise, examples of mosaic trisomies turned up in placenta samples from both naturally conceived and IVF pregnancies, the group reported, and the type of fertilization method used for IVF did not seem to impact CNV rates.

"Although we found a low-level mosaic trisomy in one IVF placental genome," the authors noted, "it was not present in the fetal lineage of the same pregnancy, suggesting a proliferative defect of trisomic cells."

Along with analyses focused on IVF and infant birth weight subgroups, the researchers considered the source of new CNVs. They also used placental transcriptome sequencing to look at the gene expression consequences of de novo CNVs in a dozen of the families. In those cases, the copy number changes seemed to impact only a small proportion of highly expressed genes, they reported, and did not fall in pathways with known ties to placenta-specific processes. 

"The sporadic de novo genomic aberrations found in approximately 10.8 percent of pregnancies were scattered across the genome," they reported, "and represented random and rare events of embryonic [chromosomal instability], without any observed functional consequence on placental biology or fetal health."

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