F. Spinella1, E. Greco2, A. Victor3, M.G. Minasi2, F. Barnes3, C. Zouves3, J.
Grifo4, E.H. Cheng5, S. Munnè6, A. Biricik1, M. Surdo1, M. Baldi1, A. Ruberti2,
F. Fiorentino1, M. Viotti3.
1Genoma Group srl, Molecular Genetics
Laboratories, Rome, Italy.
2European Hospital, Centre For Reproductive
Medicine, Rome, Italy.
3Zouves Fertility Center, Fertility Center, Foster
4New York University, Langone Fertility Center, New York,
5Lee Women’s Hospital, Lee Women’s Hospital, Taichung, Taiwan R.O.C..
6Cooper Genomics, Cooper Genomics, Livingston, U.S.A..
Is the clinical outcome of mosaic embryos influenced by
of mosaic embryos is affected by the complexity of and the number of aneuploidy
cells present in trophectoderm (TE) biopsy.
What is known already:
Chromosomal mosaic embryos are characterized by the presence of chromosomally
different cell lines within the same embryo. While the transfer of these embryos
is now offered as an option for women who undergo in vitro fertilization (IVF),
several concerns remain. For instance, the limited data on pregnancy outcome and
the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the
ploidy status of the ICM. Therefore, some argue that mosaicism should be not
reported until a clear classification of such embryos in relation with their
reproductive potential has been defined.
Study design, size, duration:
We collected the clinical outcomes of 822 mosaic embryos transferred in women
underwent IVF between May 2016-May 2019. All embryos were cultured to blastocyst
stage; trophectoderm (TE) biopsy was performed on Day-5 of development or Day6/7
for slow growing embryos. The clinical outcome obtained after transfer of mosaic
embryos with different chromosomal constitution was compared with each other and
with that obtained from a control group of 3781 euploid blastocysts.
Participants/materials, setting, methods:
genetic testing (PGT) was performed using high resolution next generation
sequencing (NGS) methodology. TE biopsies were classified as mosaic if they had
20%-80% abnormal cells. For statistical analysis mosaic embryos were divided in
groups based on mosaic levels and chromosomal constitution detected in TE:
single mosaic aneuploidy (monosomy/trisomy; SM), double mosaic chromosomes
(monosomy/trisomy or combination, DM), complex mosaic aneuploidy (>2 different
aneuploidies; CM) and mosaic segmental aneuploidy (single and double
deletion/insertion >5Mb, MS).
Main results and the role of chance:
The embryos were
plotted in 10% increments, representing a progressive increase in the proportion
of aneuploid cells in the TE, and linear regression showed a statistically
significant decline in rates of implantation and ongoing pregnancy/birth
(regression function with respective slopes -0.42 and -0.55, P=0.0381 and
0.0099). Regarding chromosomal constitution, MS had the best outcomes, followed
by the group with one affected chromosome, followed by the group with two
affected chromosomes, followed by the complex group (implantation P<0.0001,
ongoing pregnancy/birth P<0.0001). MS showed a significantly poorer clinical
outcomes compared to the euploid control group (implantation 51.3% vs 61.1%,
P=0.0004; ongoing pregnancy/birth 42.6% vs 52.7%, P=0.0003).
Additional clinical data must be obtained to evaluate
the contribution of each different chromosome before this approach can be
evaluated as an additional tool to choose mosaic embryos for transfer.
Wider implications of the findings:
The study provides the largest
dataset of transferred mosaic embryo outcomes reported to date. This compiled
analysis conclusively shows that embryos with different pattern of chromosomal
mosaicism have a distinct set of clinical outcomes. This findings should be
considered for genetic counseling.
genetic testing for aneuploidy
Next generation Sequencing