The secret of age—maternal age and embryo aneuploidy
11/08/2016 05:05:00 PM
The chromosomal abnormality (aneuploidy)
rate increases with maternal age.
By analyzing with next-generation sequencing, more precise information can be obtained.
Preimplantation genetic screening (PGS) is an examination to screen the embryos with abnormal dosage of
chromosomes (aneuploid) in the IVF realm, and it is strongly recommended to the
women with advanced maternal age or undergoing recurrent miscarriage. By
excluding the aneuploid embryo transfer, the success rate of IVF can be
significantly improved.
The newly released platform of comprehensive chromosome screening
(CCS) in 2014 is next-generation sequencing (NGS).
The PGS/NGS have better resolution to detect the
low-rate aneuploiy in the embryo biopsy, and the low-rate aneuploidy is known as the pure mosaicism (diploid and aneuploid mixture). By
using high-resolution Next-generation sequencing (NGS) to analyze the
relationship between maternal age and blastocysts as different ploidies in
preimplantation genetic screening (PGS) in 1736 embryos, the result was shown
as below,
(The involved embryos were from women aged 21 to 46 years
and biopsied on Day 5 and 6: 363 embryos from egg donors (20.9%), and 1373 from
non-donors (80.1%). The PGS/NGS includes whole-genome amplification and
following sequencing (Miseq®). The copy number variation was analyzed by
BlueFuse Multi® software. Absolutely aneuploid was defined as over 50% of
aneuploidy, and low-rate aneuploid as between 20% to 50%, and absolutely
euploid as under 20%.)
Every woman can always keep one secret—the secret of her age.
However, the women can choose not to speak out her age, but can't choose to
hide her age. The human body can release one's age by many ways, including the ovarian reserve, hormone levels, and the aneuploid rate of her embryos. The aneuploid rate of
each age was shown as below,
Of absolutely aneuploid rate, the percentage continuously increased
with the maternal age. The embryo aneuploidy showed lowest in women aged 26 to
29 years and dramatically increased in women over 34 years by non-linear (R2=0.815)
and linear regression analyses (R2=0.849), respectively.
The aneuploid rate of embryo increases with maternal age. It is
because that the incidence of meiotic errors during the oogenesis is significantly
higher in older women, and the main causes to the anomalies are
nondisjunction and anaphase lagging. Intriguingly, the mosaicism rate (combining
the abnormal mosaic and pure mosaic) remains constant among each age span
(around 25%).
The actual mechanism of mosaicism has not been validated, and it is believed
to relate with the mitotic errors during the first three cell divisions. The
main causes of these errors might be the culture condition (varied dramatically
in the different labs) or male factors (post-zygotic errors).
Conclusively, the
aneuploid rate significantly increases with the maternal age in women over 34
years and is lowest at age spanning 26 to 29 years; the mosaicism rate stays
constant at each age span (around 25%). The results reflects that the embryo
aneuploidy are mainly due to meiotic errors affecting by maternal age, but the
embryo mosaicism are mostly caused by mitotic errors, which occur during the
post-zygotic stage and do not relate to the maternal age.
References:
Munné
S, Grifo J, Wells D. Mosaicism: "survival of the fittest" versus
"no embryo left behind". Fertil Steril. 2016;105:1146-1149.
Data were
analyzed from the Stork Fertility Center and released in the annual meeting of 2016 Taiwan Society of Reproductive Medicine.
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