ARTICLE IN PRESS
Preimplantation aneuploid embryos undergo selfcorrection in correlation with their developmental
potential
Shiri Barbash-Hazan, B.Sc.,a,*,# Tsvia Frumkin, M.Sc.,a,* Mira Malcov, Ph.D.,a Yuval Yaron, M.D.,b
Tania Cohen, M.Sc.,a Foad Azem, M.D.,a Ami Amit, M.D.,a and Dalit Ben-Yosef, Ph.D.a
a
Racine IVF Unit and b Prenatal Diagnosis Unit, Genetic Institute, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center,
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To investigate the incidence of embryos’ self-correction during preimplantation development in terms
of mosaicism and in correlation with its developmental stage.
Design: Prospective study to compare the chromosome status of embryos on day 3 with that of day 5, in correlation
with their developmental stage.
Setting: In vitro fertilization unit of a university-affiliated hospital.
Patient(s): Eighty-three aneuploid embryos.
Intervention(s): Fluorescence in situ hybridization (FISH) reanalysis.
Main Outcome Measure(s): Day 3 embryos classified as mosaic or chromosomally abnormal by preimplantation
genetic screening (PGS) were reanalyzed on day 5. The results were evaluated in correlation with the embryos’
developmental stage.
Result(s): Out of 83 day 3 aneuploid embryos, 15 (18.1%) were diagnosed with mosaicism. The FISH reanalysis
on day 5 demonstrated that 27 embryos (32.6%) were partly or entirely normal disomic. Of these 83 aneuploid
embryos, 8 (9.7%) underwent complete self-correction. The PGS results demonstrated that 26.5% of the embryos
were trisomic, of which 41.0% underwent trisomic rescue by day 5. Self-correction was in correlation with the
embryo’s developmental stage, i.e., 38.1% of aneuploid embryos that developed to the blastocyst stage underwent
self-correction compared with only 12.5% of embryos that only cleaved after biopsy.
Conclusion(s): Our results demonstrate that self-correction of aneuploid and mosaic embryos occurs probably
more significantly during development toward the blastocyst stage than in delayed embryos. In addition, trisomic
embryos correct themselves more than other aneuploidies. These findings suggest that PGS results must be interpreted with caution. (Fertil Steril 2008;-:-–-. 2008 by American Society for Reproductive Medicine.)
Key Words: Preimplantation embryos, aneuploidy, mosaicism, self-correction, PGS
Various embryo assessment procedures have been developed
to select top-quality embryos with the best implantation
potential for transfer during in vitro fertilization (IVF).
Most of them are based on the morphologic appearance of
the preimplantation embryo in each developmental stage.
These methodologies include pronuclei scoring and the timing of first mitotic cleavage during the first day after fertilization (1–3), cleavage rate and pattern, compaction, degree of
fragmentation, and mononuclearity of cells in the cleaving
embryo (4). It is not clear, however, how many of these apparently normally developing good-quality embryos are chromosomally normal (euploid).
Received May 19, 2008; revised July 10, 2008; accepted July 15, 2008.
* The first two authors contributed equally to this work.
S.B.-H. has nothing to disclose. T. F. has nothing to disclose. M.M. has
nothing to disclose. Y.Y. has nothing to disclose. T.C. has nothing to
disclose. F.A. has nothing to disclose. A.A. has nothing to disclose.
D.B.-Y. has nothing to disclose.
#
Submitted by S. Barbash-Hazan as M.D. thesis, Faculty of Medicine, Ben
Gurion University, Be’er Sheba, Israel.
Reprint requests: Dalit Ben-Yosef, Racine IVF Unit, Lis Maternity hospital,
Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 6 Weizmann St.,
Tel-Aviv 64239, Israel (FAX: 972-3-6925687; E-mail: dalitb@tasmc.
health.gov.il).
0015-0282/08/$34.00
doi:10.1016/j.fertnstert.2008.07.1761
The most practical technique for analyzing the chromosomal constitution of viable human preimplantation embryos
is fluorescence in situ hybridization (FISH) analysis, which
has been performed on human embryos obtained from infertile couples with repeated IVF failures as well as from fertile
couples who are carriers of genetic diseases and who undergo
preimplantation genetic diagnosis (PGD) (5–10). The results
of these studies demonstrate that only 50% of IVF preimplantation embryos are euploid. The euploidy rate is only
slightly higher in embryos of young fertile patients (55%–
60%). It should be borne in mind that embryos that were
available for FISH analysis had been obtained from individuals who had undergone hormonal stimulation for either
PGD or egg donation for research, including those who
were fertile (3, 11, 12). Selection for only good-quality
embryos, based on morphologic criteria, increased the proportion of euploid embryos to 60%–70% (12). Importantly,
embryos with a normal cleavage rate have the best chance
to be chromosomally normal (13), whereas either lagging
or rapidly cleaving embryos have higher rates of chromosomal aberrations (12).
Another strategy for selecting euploid embryos with the
best implantation potential is based on the embryo’s
Fertility and Sterility Vol. -, No. -, - 2008
Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
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ARTICLE IN PRESS
competence to reach the blastocyst stage at day 5 after fertilization (3, 14, 15). However, although culture to blastocyst
allows self-selection of most viable embryos, still only 65%
of them are chromosomally normal (3). Therefore, although
the selection of top-quality embryos by means of morphologic parameters may increase the ability to choose chromosomally normal embryos, nonetheless 30%–40% of them will
still be aneuploid.
Preimplantation genetic screening (PGS) has been adopted
as a method to select chromosomally normal embryos for
transfer, aimed at increasing the pregnancy rate in repeated
IVF failures with reasonable numbers of good-quality embryos. Preimplantation genetic screening (PGS) is based on
the hypothesis that chromosomal errors could represent an
underlying cause of the infertility, and that transfer of aneuploid embryos may explain some of the IVF failures. Recently however, two randomized controlled trials failed to
show any benefit for performing PGS, using live birth rates
as the measure of success (3, 16, 17). The debate on the usefulness of PGS is ongoing, and the only effective way to resolve this issue is to perform additional well designed and
well executed randomized clinical trials (18).
Aneuploid embryos are a consequence of either fertilization that involves an aneuploid oocyte or sperm which resulted from meiotic errors, or a mitotic error that occurred
de novo after fertilization. Meiotic errors commonly lead to
a uniformly aneuploid embryo, whereas mitotic errors usually lead to mosaicism. Preimplantation genetic screening
identifies meiotic and post-zygotic chromosomal abnormalities. However, because it is based on FISH results obtained
from only one or two biopsied blastomeres, it is not yet clear
whether chromosomal screening of single blastomeres on
day 3 truly represents the chromosomal constitution of the
embryo that will eventually implant 3–4 days later. This uncertainty led the PGD Consortium to recommend that embryos that had been designated as aneuploid by PGS on day
3 undergo FISH reanalysis on day 5 (19). Subsequent studies
that summarized FISH reanalyses of aneuploid embryos on
day 5 demonstrated that the chromosomal constitution of
a preimplantation embryo may change during early cleavages
(20, 21). Indeed, it was suggested that some of them are capable of developing into normal euploid embryos or that
there could be an increase in the normal diploid cells that
comprise the blastocyst. Other reports, however, suggested
that these embryos may accumulate additional chromosomal
anomalies (20–24).
Because all of these studies were based on reanalysis of aneuploid embryos diagnosed by PGS that had been performed
solely on one blastomere, they bear potential limitations of
false negative and false positive results when mosaic embryos are involved. In the present study, we investigated the
incidence of an embryo’s self-correction during preimplantation development in terms of mosaicism and in correlation
with its developmental stage to supplement our current
knowledge on this subject.
2
Barbash-Hazan et al.
TABLE 1
Embryo development profile of the 83 studied
embryos.
Mean ±
SD/cycle
Fertilization
Oocytes
2PN
Fertilization (2PN/MII) (%)
Day 3 embryos
Blastomeres/embryo
High-qualitya embryos
(% of total)
Embryo biopsy
Embryos with 1 cell biopsy
Embryos with 2 cell biopsy
Day 5 embryos
Blastocysts
Compacted morula
Further cleavage
Cleavage arrest
13.5 6.9
9.6 4.7
75.1% 18.3%
7.6 1.8
78.3%
n (% of total)
17 (20%)
66 (80%)
n (% of total)
21 (25.3%)
33 (39.7%)
16 (19.3%)
13 (15.6%)
Note: MII ¼ metaphase II; 2PN ¼ two pronuclei.
a
High-quality embryos indicate the presence of six to
eight cells at grade I–II or compacted morula.
Barbash-Hazan. Self-correction of aneuploid embryos. Fertil Steril 2008.
MATERIALS AND METHODS
Study Material
A total of 83 embryos classified by PGS as chromosomally
abnormal were reanalyzed. Institutional Review Board approval for this study was obtained (295/03, 216/06), and
written consent was provided by each couple. The aneuploid
embryos were the result of 22 PGS cycles (19 women).
Indications for PGS were repeated implantation failure
(16 women), with an average (SD) of 11.0 5.5 previous
failed IVF cycles per subject, and/or recurrent miscarriages
TABLE 2
FISH results of day 3 embryosa.
Chromosomal constitution
No. (%)
Trisomy
Monosomy
Multiple aberration
Mosaic between blastomeres
normal/abnormal
abnormal/abnormal
Haploidy
Polyploidy
Undetermined
22 (26.5%)
23 (27.7%)
14 (16.9%)
15 (18%)
7 (8.4%)
8 (9.6%)
1 (1.2%)
6 (7.3%)
2 (2.4%)
Note: FISH ¼ fluorescent in situ hybridiization.
a
Total of 83 aneuploid embryos.
Barbash-Hazan. Self-correction of aneuploid embryos. Fertil Steril 2008.
Self-correction of aneuploid embryos
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(6 women), with an average of 7.5 2.3 previous pregnancy
losses per subject. The mean maternal age was 38.0 5.1
years (Table 1). The mean number of two-pronuclei (2PN)
zygotes was 9.6 4.7 per cycle (Table 2).
Fertilization and Embryo Culture
Ovarian stimulation, ovulation induction, and oocyte retrieval were performed as described previously (25). Intracytoplasmic sperm injection (ICSI) was performed to avoid
contamination of the biopsied blastomere with sperm DNA
or maternal DNA of cumulus cell origin. Metaphase II oocytes were meticulously denuded of cumulus cells using hyaluronic acid in combination with mechanical pipetting.
Normal fertilization was determined by the presence of
2PN with two distinct polar bodies at 16–19 h after ICSI
using an inverted microscope at 400 magnification (TE;
Nikon, Tokyo, Japan). Each embryo was incubated in a separate drop of medium to allow individual assessment and documentation at different time points during preimplantation
development until the moment of intrauterine transfer. Embryo morphology was assessed on the mornings of days 2
and 3 following oocyte retrieval, and the number of blastomeres, degree of fragmentation cytoplasm uniformity, and
the presence of early compaction were recorded.
Embryo biopsy was performed on day 3 of embryo development at the 6–10-cell stage, as described previously (25).
One blastomere was removed from embryos with <7 cells
and two blastomeres were removed from embryos with R7
cells. Selected blastomeres were subjected to FISH analysis
and classified as either normal or aneuploid. On day 5, chromosomally normal embryos were transfered back to the
uterus and aneuploid embryos underwent FISH reanalysis.
FISH Analysis
The FISH analysis was performed at two time points during
embryo development: 1) on day 3, on individually biopsied
blastomeres as part of the PGS procedure; and 2) on day 5,
when the entire developed embryo, including all blastomeres
comprising it, was spread onto a glass slide and subjected to
FISH analysis. Blastomeres and aneuploid embryos were
spread onto a Superfrost Plus glass slide (Kindler, Freiburg,
Germany) using 0.01 N HCl/0.1% Tween 20 solution (26).
The spreading solution was used to dissolve the zona pellucida
and cytoplasm and to expose the nuclei for FISH analysis. The
slides were left to air dry, washed in phosphate-buffered saline
for 1 min, and dehydrated by transfering through an ethanol
series (70%, 85%, and 100%). All embryonic nuclei were
scanned under a phase-contrast microscope. Fluorescence
in situ hybridization was carried out according to the manufacturer’s recommendations and as described previously
(27). Two rounds of FISH procedures were carried out using
Multivision PB Probe Panel (Vysis, Downers Grove, IL) for
chromosomes 13, 16, 18, 21, and 22 in the first round and X,
Y, and 15 (CEP X a-satellite, Xp11.1-q11.1, CEP Y a-satellite, Yp11.1-q11.1, and CEP 15 satellite III, 15q11.2; Vysis)
Fertility and Sterility
in the second round. The FISH images were captured using
a computerized system (FISHView; Applied Spectral Imaging, Migdal HaEmek, Israel), and the results were interpreted
by two observers. The criterion for signal scoring was that
signals had to be a minimum of a signal’s width apart to be
scored as two separate signals (28). Embryos were classified
as normal when both nuclei of two analyzed blastomeres
showed two signals for each chromosome investigated, aneuploid when both nuclei demonstrated the same chromosomal
abnormality, and mosaic when the two nuclei demonstrated
different results (one normal and the other abnormal, or
two different abnormalities). If only one blastomere was
available for diagnosis, the embryo could be classified as either normal or aneuploid but not mosaic. If a blastomere
showed aneuploidy for two or more chromosomes, it was defined as having multiple aberrations (MAB). A FISH reanalysis on the entire embryos was performed on day 5 using the
same probe panel and the same protocol described for day 3
blastomeres.
RESULTS
A total of 83 embryos were analyzed on day 3, of which 65
(78.3%) were defined as high-quality embryos, with an average of 7.6 1.8 blastomeres per embryo. Two blastomers
were biopsied from each of 66 embryos (80%) which had
R7 cells and subjected to FISH analysis (Table 1). The
FISH results demonstrated that 22 embryos (26.5%) were trisomic, 23 (27.7%) were monosomic, and 14 (16.9%) had
MAB (aneuploidy of >1 chromosomes) (Table 2). Mosaic
embryos could also be identified, because two blastomeres
were biopsied from most of the embryos studied: 15 embryos
(18%) were found to be mosaic, with seven (8.4%) displaying
mosaicism of both normal and abnormal cells and eight
(9.6%) displaying different aneuploidy between the two analyzed blastomeres. In addition, one embryo was haploid, six
embryos (7.3%) were polyploid, and two (2.4%) were undetermined (Table 2).
For the purpose of FISH reanalysis, aneuploid embryos
were further incubated for another 2 days, and 70 out of 83
(84%) embryos continued to develop following blastomere
biopsy: 21 (25.3%) underwent blastulation, 33 (39.7%) underwent compaction, and 16 (19.3%) further cleaved but
with no signs of compaction (Table 1). The FISH reanalysis
on day 5 was performed on whole embryos, regardless of
the stage of development they had reached. The average number of nuclei analyzed from each day 5 embryo was 8.9 6.4
(1–36 nuclei/embryo, median 7) (Table 3). The FISH results
of day 5 embryos confirmed those of day 3 in 26 embryos
(31.3%), 30 (36.1%) had acquired additional aneuploidies,
and 27 (32.6%) demonstrated normal cells (Table 3) and
presumably had undergone self-correction. Of these 27
corrected embryos, eight (9.7%) underwent complete selfcorrection (presenting 100% normal cells) and were diagnosed as euploid on day 5, eleven (13.2%) had 51%–99%
normal cells, and eight (9.7%) had %50% normal cells.
Ten of the embryos that underwent major self-corrections
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TABLE 3
Day 5 reanalysis of the 83 aneuploid embryos
studied.
Day 5 embryos
No. (%)
Mean no. of cells
analyzed per day 5 embryo
Embryos with confirmation of
day 3 FISH results
Embryos with partly or entirely
normal cells
Embryos that acquired
additional aneuploidies
FISH results
Normal
Trisomy
Monosomy
Mosaic between blastomeres
Normal/abnormal
Abnormal/abnormal
Haploidy
Polyploidy
8.9 6.4
26 (31.3%)
27 (32.6%)
30 (36.1%)
8 (9.6%)
8 (9.6%)
7 (8.4%)
54 (65%)
19 (23%)
35 (42%)
1 (1.2%)
5 (6%)
Barbash-Hazan. Self-correction of aneuploid embryos. Fertil Steril 2008.
(i.e., >50% normal cells) were either trisomic or mosaic on
day 3 (Table 4). We further investigated trisomic rescue as
one of the proposed mechanisms leading to self-correction,
and found that 9 of the 22 trisomic embryos (41.0%) had
>50% normal cells at day 5 (Tables 2 and 4).
Our results demonstrate a linear correlation between preimplantation embryo development and self-correction rate
(Fig 1). The embryos that reached the blastocyst stage by
day 5 of development had the highest self-correction rate,
38.1% (8 out of 21), compared with a rate of 24.2% (8 out
of 33) correction in compacted morula and only 12.5% (2
out of 16) for embryos that further cleaved but showed no
signs of compacting (Fig. 1).
DISCUSSION
Not all morphologically normal IVF embryos are also chromosomally normal. Although day 3 embryo morphology
has been recently shown to be a selection marker of euploidy
among advanced–maternal age subjects, it had a poor predictive value for euploidy in younger women who may have
other factors responsible for embryo dysmorphism (4). Indeed, a high rate of aneuploidy and mosaicism is revealed
even when only top-quality IVF embryos are analyzed by
FISH. For obvious ethical reasons, comparative studies on
chromosome abnormalities in in vivo–derived and in vitro–
produced human embryos are not available. Studies on other
mammalian species (mouse, cow, sheep), however, have
demonstrated a higher rate of aneuploidy in IVF embryos
compared with their in vivo counterparts (29). Collectively,
these data indicate that human IVF embryos probably have
a higher degree of aneuploidy compared with the naturally
developed embryos which are not accessible for research.
Aneuploid pregnancies may result in miscarriage, stillbirth,
or ultimately the birth of a child with an abnormality, such
as trisomy 21 or monosomy X (Turner syndrome) (30). The
incidence of chromosomal abnormalities in early spontaneous abortions (<7 weeks) is more than 60% compared with
5% in induced abortions at 10 weeks (31–33). This is probably an underestimation of the true rate of chromosome abnormalities in preimplantation embryos and early fetuses, owing
to early natural selection of chromosomal aberrations. These
data suggest that the incidence of chromosome abnormality
at conception is high and that natural selection occurs before
and after implantation.
The FISH results of human IVF embryos demonstrated
that around 70% of the best-quality embryos are chromosomally normal. This estimation, however, is based on the extrapolation of values to the entire embryo from single
TABLE 4
Correction rate of embryos through day 5.
Chromosomal constitution
at day 3
% Correction
within 5 days
100%
<100% and >50%
%50%
Total embryos
with corrected cells
No. of embryos (% of total)
8 (9.7%)
11 (13.2%)
8 (9.7%)
27 (32.6%)
Trisomy or mosaic
5T
2 T þ 1 T*, 2 N/M
1 T*,1 M
Other aberrations
1 M, 1 tetra, 1 mab
3 M,1 haploid, 2 mab
4 mab, 1 poly, 1 haploid
Note: haploid ¼ haploidy; M ¼ monosomy; mab ¼ multiabnormal; N/M ¼ mosaic for normal and monosomy; poly ¼ polyploidy; T ¼ trisomy; T* ¼ mosaic of two different trisomies; tetra ¼ tetraploidy.
Barbash-Hazan. Self-correction of aneuploid embryos. Fertil Steril 2008.
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Barbash-Hazan et al.
Self-correction of aneuploid embryos
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FIGURE 1
Correction rate in relation to developmental
stage at day 5.
50
Correction rate * (%)
40
38.1
30
24.2
20
12.5
10
7.6
0
Blastocyst
Compacted
Morula
Further
Cleavage
Arrest
*Correction rate ¼ embryos with >50% of normal
cells in relation to developmental stage.
Barbash-Hazan. Self-correction of aneuploid embryos. Fertil Steril 2008.
blastomeres sampled for PGS application (12, 34). Some of
the aneuploid embryos, however, subsequently acquire chromosomal abberations at a later stage (21). Conversely, some
of the aneuploid embryos undergo self-correction during
cleavage and propagation toward the blastocyst stage (22–
24). Munne et al. (24) compared PGS results with the chromosomal status of the derived blastocysts 2 days later and
found that 65% of them comprised normal cells. Li et al.
(23) examined whole blastocysts and classified 44% of the
embryos as euploid. It was previously demonstrated that
the process of culturing to the blastocyst itself allows self-selection of euploid embryos (3, 35). In addition, euploid day 3
embryos develop more blastocysts than aneuploid ones (35,
36). Indeed, when embryos from all developmental stages,
including delayed embryos, were reanalyzed by FISH, only
20% of the aneuploid ones had undergone self-correction
(20, 22).
We present new data on self-correction of aneuploid and
mosaic embryos, and demonstrate its correlation to embryo
development. For the analysis of self-correction, we combined both the >50% corrected embryos (i.e., partially corrected) and the completely corrected embryos. The
rationale for doing this was based on the observation that
when at least two-thirds of the cells comprising the mosaic
preimplantation embryo are normal, it can develop into a normal blastocyst and even to a normal live birth (23). Therefore,
although mosaicism seems to be a frequently occurring pheFertility and Sterility
nomenon during the preimplantation period, it can be naturally eliminated during further development. The present
results are based on FISH analysis of an average of nine cells
per day 5 embryo, thereby enabling us to illustrate a more accurate and representative picture of the embryos’ chromosomal status at this stage. Peura et al. (37) recently showed
that embryonic stem cells derived from PGS-aneuploid embryos were mostly euploid, suggesting that not all aneuploidies diagnosed in IVF embryos are ‘‘permanent.’’
Two mechanisms have been suggested to explain self-correction: the high incidence of mosaicism within preimplantation embryos, and trisomic rescue. The most common
mechanisms leading to aneuploidy mosaicism are postzygotic chromosome loss, chromosome gain, and mitotic nondisjunction (38). The incidence of mosaicism can be as high
as 50% of the preimplantation embryos (39, 40). This high
rate of mitotic errors is likely due to the deregulation of the
mitotic processes and/or temporary relaxation of the centromere function during the several cell divisions that take place
after fertilization (38). Additionally, it was speculated that in
vitro culture conditions may increase the occurrence of mitotic errors in IVF embryos (41). Mosaicism is detected in
about 1%–2% of chorionic villous samples (CVS) during
the first trimester of pregnancy (42). A systematic DNA polymorphism analysis of CVS, however, demonstrated that some
cases of the confined placental mosaicism will undergo postzygotic aneuploid correction (42). With pregnancy progression through the second trimester, generalized mosaicism of
both the placenta and the fetus is observed in only 0.1%–
0.4% of viable pregnancies, as detected in amniotic fluid
cell cultures (43). It was suggested that there is a preferential
allocation of euploid cells to the inner cell mass during early
cleavage stage, when the aneuploid cells are directed toward
the extra-embryonic compartments (trophectoderm). Thus,
a mosaic morula can develop within a chromosomal dichotomy between the inner cell mass and the trophectoderm
(29, 40). Conversely, others have shown that the chromosomal abnormalities observed in human blastocysts are
equally present in both compartments of the blastocyst (44).
The second mechanism suggested for explaining self-correction is trisomic rescue, whose exact mechanism is not
known: anaphase lagging or nondisjunction in early postzygotic cell divisions have been proposed (24). We report
a 26.5% trisomy rate in day 3 embryos, with 41% of them
(9 out of 22) having undergone significant self-correction
(>50% of normal cells within a day 5 embryo), probably
by a mechanism of trisomic rescue. In accordance, Rubio
et al. (35) demonstrated that the trisomic embryos develop
more blastocysts than other aneuploid ones.
Mosaicism can be identified by PGS only when at least two
blastomeres are biopsied, as was done in the current study.
Earlier reports have debated between the need to sample
two blastomeres for efficient and accurate FISH results and
the potential damage incurred to the embryo. Goossens
et al. (45) recently reported, in a prospective randomized
study, on the diagnostic efficiency and clinical outcome after
5
ARTICLE IN PRESS
the biopsy of either one or two blastomeres for PGD, demonstrating that live birth rates were not significantly different in
embryos from which two blastomeres were biopsied.
When discussing discrepancy between day 3 FISH analysis and day 5 reanalysis, one also needs to bear in mind the
possibility of an error in FISH analysis stemming from technical limitations of the procedure. The false-negative and
false-positive rates are estimated to be 7%–15 % (28, 46), although the error rate is only 5%, when using probes for two
different loci on the same chromosome (38).
In conclusion, our current investigation’s contribution is
threefold. First, because two blastomeres were FISH analyzed in day 3 embryos, mosaicism and its correlation to
self-correction prevalence by day 5 could be studied. Second,
our study demonstrated that self-correction of aneuploid and
mosaic embryos is more likely to occur during development
toward the blastocyst stage than in delayed embryos. The fact
that whole embryos were reanalyzed on day 5 of development—independent of their developmental status or morphologic quality—enables the evaluation of self-correction in
correlation with the embryo’s developmental stage. The results demonstrate that viable embryos developing with a normal cleavage rate and pattern are more capable of correcting
their aneuploidy. Moreover, embryos with higher correction
capability may catch up and reach normal cleavage and developmental rates. Finally, we showed that trisomic embryos
correct themselves more than other aneuploidies, probably
owing to self-correction governed by the mechanism of trisomic rescue.
Our results further strengthen the accumulating data indicating that PGS on day 3 of embryo development is not always representative of the chromosomal constitution of the
implanting embryo. However, PGS may have an important
prognostic value in couples with normal karyotype who produce morphologically normal embryos but still experience
recurrent IVF failures. In these cases, two blastomeres should
be aspirated to increase the accuracy of the PGS results and
take into account mosaicism where possible. Nevertheless,
the presence of a high aneuploidy rate among IVF embryos
as detected by PGS may guide the couple and their physician
to choose another route of parenthood.
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