In vitro fertilization does not increase chromosomal rearrangements in fetal and placental cells

A recently published international study indicates that, unlike what has been suspected based on animal studies, IVF treatments do not increase chromosomal alterations in placental or fetal cell lineages compared to the naturally conceived.

Researchers in University of Helsinki and University Hospital have participated in international collaboration where chromosomal rearrangements associated with IVF treatments have been examined.

Earlier studies have shown significant amount of chromosomal mosaicism in IVF derived embryos: altered number of chromosomes and duplications or deletions of chromosomal regions. Unstable chromosomes can significantly affect the success rate of embryo transfers and IVF treatments. Furthermore, chromosomal rearrangements have raised concern about the effect of suboptimal in vitro environment on genetic integrity and health of IVF derived children.

This study concerns a significant and constantly growing portion of the population. Assisted reproductive treatments have resulted in more than seven million children since 1978. According to the Finnish institute for health and welfare 5.4 % of the children born in Finland in 2016 were derived from IVF treatments.

The amount of chromosomal rearrangements was examined by comparing 49 IVF derived and 62 naturally conceived newborns’ DNA collected from blood and placental tissue. To discern new mutations from inherited ones, also DNA from the parents was collected. Importantly, the IVF embryos selected for intrauterine transfer were not screened for potential chromosomal rearrangements prior to the transfer.

Altogether, chromosomal alterations which were not inherited from the parents, were found in twelve placentas of 111 (10.8%). There were 15 alterations in total, of which four were observed in the newborns’ blood and  11 merely in the placenta.

In the IVF group there were chromosomal alterations only in three placentas and in two cases they were detected also in the newborn’s blood samples. Indications of any effects of the specific methods used in the treatments – microinjection and fresh or frozen embryo – were not observed in this study.

Nine chromosomal alterations were observed in the naturally conceived placentas. Two of those alterations were detected also in the newborns’ blood.

When only newborns with appropriate birth weight were included to the examination, the number of chromosomal alterations in the IVF derived samples was 3/48 (6.3%, all the IVF associated alterations were in this group) and 6/50 (12%) in the naturally conceived samples.

“According to this study, IVF does not increase the number of chromosomal rearrangements in placental or newborns’ cells. The increased chromosomal mosaicism observed in early blastocyst stage will disappear during the following developmental periods before the birth. Also, it is known that the development in part of the embryos is interrupted in the very early stage”, tells Docent Nina Kaminen-Ahola from the University of Helsinki.

The chromosomal alterations were scattered randomly across the genome, without any observed functional consequence on placental biology or fetal health.

Finnish samples collected in epiART and epiFASD projects were involved in this study.

The study has been published in Nature Medicine.

For more information, please contact:

Prof. Andres Salumets, University of Tartu, Estonia, and University of Helsinki,

Dr. Nina Kaminen-Ahola, PhD, University of Helsinki
(epiART and epiFASD research projects)
Tel. +358 50 4482768
Research Group of Environmental Epigenetics

Viite: Zamani Esteki M, Viltrop T, Tšuiko O, Tiirats A, Koel M, Nõukas M, Žilina O, Teearu K, Marjonen H, Kahila H, Meekels J, Söderström-Anttila V, Suikkari AM, Tiitinen A, Mägi R, Kõks S, Kaminen-Ahola N, Kurg A, Voet T, Vermeesch JR, Salumets A. In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages. Nat Med. 2019, 25(11):1699-1705.