The document discusses preimplantation genetic testing for aneuploidy (PGT-A), which screens embryos for chromosomal abnormalities during in vitro fertilization (IVF) treatment. It notes that while PGT-A is purported to improve live birth rates and reduce miscarriage risks, two recent large randomized controlled trials found no significant benefits. A study analyzed in the document found PGT-A to be not cost-effective due to the high costs associated with preventing one miscarriage. Overall, the document concludes that the current evidence is insufficient to support the routine use of PGT-A in clinical practice.

1. Pitfalls of
PGTa
Dr Kaberi Banerjee

2. WHAT IS PGS WHAT IS PGTA PROBLEMS
WITH PGTA
VARIOUS
STUDIES

3. The Earlier
names of
Genetic Tests
on Embryos

4. Current names of Genetic Tests on the
Embryo

5. PGTa claims to reduce
implantation failure in IVF and
reduce the risk of miscarriages.
It is a very expensive test!
Is it true?

7. Some Facts of
PGTa
• All cells in any embryo doesn’t
demonstrate aneuploidies i.e
chromosomal abnormalities.
There are only small number of
cells which shows abnormalities.
If embryo biopsy shows abnormal
DNA, it is not the whole cell will
be abnormal.

8. Some Facts of
PGTa
• It is also observed that abnormal cells
often self-destruct and some cells self-
correct by themselves. This self-correction
happens more in cells which makes baby
than the cells which makes placenta
(trophectoderm). For PGT-a, embryo
biopsy is taken from trophectoderm. This
shows that there is no benefit of doing
blastocyst stage embryo biopsy as cells
which are tested are of outer layer not the
inner layer which forms the baby.

9. The STAR Study
• A total of 661 women (average age 33.7 ± 3.6
years) were randomized to PGT-A (n = 330) or
morphology alone (n = 331).
• PGT-A did not improve overall pregnancy
outcomes in all women, as analyzed per embryo
transfer or per ITT. There was a significant
increase in OPR per embryo transfer with the
use of PGT-A in the subgroup of women aged
35-40 years who had two or more embryos that
could be biopsied, but this was not significant
when analyzed by ITT.

10. SHORT COMMUNICATION Open Access
Preimplantation genetic screening- the
required RCT that has not yet been carried
out
Raoul Orvieto1,2
Abstract
The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for
embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. The
ongoing discussion on the unrestricted clinical adoption of preimplantation genetic screening (PGS) has called for a
proper randomized controlled trial (RCT), aiming to further evaluate the cumulative live birth rates (LBRs) following
Orvieto Reproductive Biology and Endocrinology (2016) 14:35
DOI 10.1186/s12958-016-0171-z
• The utilization of trophectoderm biopsy combined
with comprehensive chromosome screening (CCS) tests
for embryonic aneuploidy was recently suggested to
improve IVF outcome, however, not without criticisms.
The ongoing discussion on the unrestricted clinical
adoption of preimplantation genetic screening (PGS) has
called for a proper randomized controlled trial (RCT),
aiming to further evaluate the cumulative live birth rates
(LBRs) following a single oocyte retrieval, utilizing all
fresh and frozen embryos. Since this study seems not to
appear for various reasons, we present herewith, the
hypothetical required RCT based on the hitherto
published literature.
• After implementing data from the hitherto published
literature on blastulation and aneuploidy rates, the rate
of mosaicism and technical errors and implantation
rates/LBRs of non-PGS day-3 and blastocyst and PGS
blastocyst, we could clearly demonstrate the superiority
of non-PGS embryo (day-3 and blastocyst) transfer over
PGS blastocyst transfer, in terms of cumulative LBR
(18.2–50 % vs 7.6–12.6 %, respectively).
• We therefore believe that until the proper, non-
hypothetical RCT on the efficacy of this procedure will
appear, PGS should be offered only under study
conditions, and with appropriate informed consents.

11. Overall same , but can show as 50% and 100%
Depends which data you want to show!
Non PGS-50%?
10
8
6
4
2+2
-ve/+ve
PGS-100%?
10
8
6
4
2
+ve
Extra Cost
Freezing
Transfer Time
Extra Cost
PGS
Personnel
Laboratory
WaitingTime

12. Assumptions
• Blastulation Rate- 47%
• Aneuploidy Rate- 59%
• IR-D3 21-50%, Non PGS D5
38-47%, PGS D5 39-65%
• Mosaicism and Technical
Errors reduce LBR
SHORT COMMUNICATION Open Access
Preimplantation genetic screening- the
required RCT that has not yet been carried
out
Raoul Orvieto1,2
Abstract
The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for
embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. The
ongoing discussion on the unrestricted clinical adoption of preimplantation genetic screening (PGS) has called for a
proper randomized controlled trial (RCT), aiming to further evaluate the cumulative live birth rates (LBRs) following
a single oocyte retrieval, utilizing all fresh and frozen embryos. Since this study seems not to appear for various
reasons, we present herewith, the hypothetical required RCT based on the hitherto published literature.
After implementing data from the hitherto published literature on blastulation and aneuploidy rates, the rate of
mosaicism and technical errors and implantation rates/LBRs of non-PGS day-3 and blastocyst and PGS blastocyst,
we could clearly demonstrate the superiority of non-PGS embryo (day-3 and blastocyst) transfer over PGS blastocyst
transfer, in terms of cumulative LBR (18.2–50 % vs 7.6–12.6 %, respectively).
Orvieto Reproductive Biology and Endocrinology (2016) 14:35
DOI 10.1186/s12958-016-0171-z

13. For the propose of the analysis, we will assume that
each group yielded 100 day-3 embryos and that all
In a recent study [12] evaluating the accuracy of troph-
ectoderm multiple biopsies using next-generation
Fig. 1 The required hypothetical RCT

14. • Presented reanalysis here of the recently
published STAR study [8], which already has
been affecting IVF practice worldwide,
reveals significant shortcomings in the study’s
statistical analyses. Those, however, do not
change the principal conclusion of the STAR
study that PGT-A does not favorably affect IVF
outcomes by increasing pregnancy chances or
reducing miscarriage risks.
• The STAR study thus reveals that PGT-A
does not beneficially affect IVF outcomes in
confirmation of another relatively recent
study in women 37 years and older by Kang
et al. Like the STAR study, Kang et al. reported
seemingly improved live birth rates following
PGT-A but this outcome advantage, actually,
reversed itself after correct intent-to-treat
analysis of outcomes with reference cycle
start: Pregnancy as well as live birth rates,
indeed, ended up to be significantly higher in
control non-PGT-A patients (49.5 vs 21.5%
and 39.8 vs 19.9%).
• Considering all presented evidence here, it
is difficult to understand what further
argument can be made for the continuous
routine clinical utilization of PGT-A to improve
IVF outcomes.
•
COMMENTARY
Preimplantation genetic testing for aneuploidy (PGT-A)
—finally revealed
Raoul Orvieto1,2
& Norbert Gleicher3,4,5,6
Received: 10 December 2019 /Accepted: 27 January 2020 /Published online: 2 February 2020
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Keywords PGT-A . PGS . Live-birth rate . Intention to treat . RCT
Introduction
Natural fecundity of women decreases gradually and more
rapidly after age 37 years. This decrease is accompanied by
aneuploidies. The procedure was, ther
formed biopsying 1–2 blastomeres of d
embryos, often given the acronym PGS
This form of embryo testing has, sinc
Journal of Assisted Reproduction and Genetics (2020) 37:669–672
https://doi.org/10.1007/s10815-020-01705-w

15. 4/5/2021 Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation - Cornelisse, S - 2020 | Cochrane Library
Authors' conclusions
There is insu icient good‐quality evidence of a di erence in cumulative live birth rate, live birth rate a er the first embryo transfer, or miscarriage rate
between IVF with and IVF without PGT‐A as currently performed. No data were available on ongoing pregnancy rates. The e ect of PGT‐A on clinical
pregnancy rate is uncertain.
Women need to be aware that it is uncertain whether PGT‐A with the use of genome‐wide analyses is an e ective addition to IVF, especially in view of the
invasiveness and costs involved in PGT‐A. PGT‐A using FISH for the genetic analysis is probably harmful.
The currently available evidence is insu icient to support PGT‐A in routine clinical practice.
Plain language summary
Available in English Español ‫ر‬ Français 한국어 Bahasa Malaysia
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005291.pub3/full 1/6
Cochrane Database of Systematic Reviews Review - Intervention New search
Abstract
Available in English Español ‫ر‬ Français 한국어
Background
In in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is based on
morphological criteria. However, many women do not achieve a pregnancy even a er 'good quality' embryo transfer. One of the presumed causes is that
such morphologically normal embryos have an abnormal number of chromosomes (aneuploidies). Preimplantation genetic testing for aneuploidies (PGT‐
Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro
fertilisation
,
Simone Cornelisse ,
Miriam Zagers ,
Elena Kostova ,
Kathrin Fleischer ,
Madelon Wely Sebastiaan Mastenbroek Authors' declarations of interest
Version published: 08 September 2020 Version history
https://doi.org/10.1002/14651858.CD005291.pub3

16. Preimplantation genetic
screening: what is the
clinical efficiency?
In the current practice of in vitro fertilization (IVF), preim-
plantation genetic screening (PGS) is increasingly used to
select embryos for transfer. This strategy is designed to maxi-
mize the probability of embryo implantation by eliminating
embryos with low implantation potential from the cohort.
However, PGS is inherently imperfect. Errors may occur dur-
ing the genetic analysis of the small amount of DNA collected.
More importantly, mitotic mosaicism, whose precise inci-
dence in the preimplantation embryo is not known, may
lead to sampling errors due to the intentionally limited collec-
tion of cells in the trophectoderm biopsy. In this manner,
abnormal cells may be collected in an otherwise euploid em-
bryo and vice versa. Therefore, it is inevitable that some
normal embryos will be discarded, leading to an overall
EI(idealized). The efficiency of the screening process can then
be expressed as:
Efficiency ¼
EIðscreenedÞ
EIðidealizedÞ
The percentage of embryos lost in the process can then be
calculated as:
% embryos lost ¼ 1 $ Efficiency
The depiction of this analysis is most easily demonstrated
in a graphic fashion. For this example, let us consider a hypo-
thetical cohort of embryos from ‘‘good-prognosis’’ patients
(2), under the age of 35 years, with multiple blastocysts in
the 4AA or 4BB category, an unscreened implantation rate
of 50%, and an ‘‘aneuploidy’’ rate of 40%. In the parlance
of this calculation:
EIðunscreenedÞ ¼ 0:50
INKLINGS
• Errors may occur during the genetic analysis of the small
amount of DNA collected.
• Mitotic mosaicism may lead to sampling errors
• Some normal embryos will be discarded, leading to an
overall decrease in the cumulative pregnancy rate
achievable by the eventual transfer of all embryos in the
cohort.
• Real possibility of damage to the blastocyst as result of the
trophectoderm biopsy.
• No studies have addressed the impact of trophectoderm
biopsy in embryos with less than ideal morphologic
characteristics, in older patients, or after an intervening
cryopreservation procedure.

17. Preimplantation genetic
screening: what is the
clinical efficiency?
In the current practice of in vitro fertilization (IVF), preim-
plantation genetic screening (PGS) is increasingly used to
select embryos for transfer. This strategy is designed to maxi-
mize the probability of embryo implantation by eliminating
embryos with low implantation potential from the cohort.
However, PGS is inherently imperfect. Errors may occur dur-
ing the genetic analysis of the small amount of DNA collected.
EI(idealized). The efficiency of the
be expressed as:
Efficiency ¼
EIðscreenedÞ
EIðidealizedÞ
The percentage of embryos lo
calculated as:
% embryos lost ¼ 1 $ Efficienc
The depiction of this analysis
in a graphic fashion. For this exam
INKLINGS

18. Clinical application of PGT‐A: is the price too high?
T El‐Toukhy
Guys and St. Thomas Hospital NHS Trust, London, UK
Linked article: This is a mini commentary on K Neumann et al., pp. 710–718 in this issue. To view this article visit
https://doi.org/10.1111/1471-0528.16089
Published Online 8 March 2020.
Pre‐implantation genetic testing for
aneuploidy (PGT‐A) continues to pro-
voke interest, discussion and debate in
the field of reproductive medicine.
The two touted benefits of compre-
hensive screening of pre‐implantation
embryos for chromosomal aneuploidies
in in vitro fertilisation (IVF) treat-
ment are improvement in the live
birth rate per cycle and reduction in
miscarriage risk.
Two recent large randomised trials
employing two different techniques
for PGT‐A (ESTEEM Trial – Verpoest
et al. Hum Reprod 2018;33:1767–76
et al., Reprod Biomed Online 2019;
39:617–23).
In this issue of our journal, the
study of Neumann et al. (BJOG
2020;127:710–8) focused on the
cost‐effectiveness of PGT‐A, using
data from the ESTEEM trial. The
study demonstrated the high cost
of preventing one miscarriage
through the application of PGT‐A,
in both high‐cost and low‐cost
healthcare settings. This result is con-
sistent with the conclusion of a ‘theo-
retical’ cost‐effectiveness study in a UK
setting (Scriven, Reprod Biol Endocrinol
cycles to achieve a live birth, it
would seem more reasonable to use
the limited resources for funding
more standard IVF cycles to achieve
more live births rather than chasing
the possibility of fewer miscarriages
and end up with fewer babies.
Although the initial PGT‐A results
involving day‐3 embryo biopsy and
fluorescence in situ hybridisation
were disappointing, it was expected
that improvement in blastocyst cul-
ture, embryo cryopreservation and
molecular genetic testing technolo-
gies would enable PGT‐A to achieve
Economic analysis of preimplantation genetic testing for aneuploidy
Pre‐implantation genetic testing for
aneuploidy (PGT‐A) continues to pro-
voke interest, discussion and debate in
the field of reproductive medicine.
The two touted benefits of compre-
hensive screening of pre‐implantation
embryos for chromosomal aneuploidies
in in vitro fertilisation (IVF) treat-
ment are improvement in the live
birth rate per cycle and reduction in
miscarriage risk.
Two recent large randomised trials
employing two different techniques
for PGT‐A (ESTEEM Trial – Verpoest
et al. Hum Reprod 2018;33:1767–76
and STAR Study – Munne et al. Fertil
Steril 2019;112:1071–9) have shown
no improvement in the live birth rate
per IVF cycle started in screened
cycles compared with no screening.
The ESTEEM trial did not show a
shorter time to pregnancy and the
STAR study did not show a reduc-
tion in the miscarriage rate associated
et al., Reprod Biomed Online 2019;
39:617–23).
In this issue of our journal, the
study of Neumann et al. (BJOG
2020;127:710–8) focused on the
cost‐effectiveness of PGT‐A, using
data from the ESTEEM trial. The
study demonstrated the high cost
of preventing one miscarriage
through the application of PGT‐A,
in both high‐cost and low‐cost
healthcare settings. This result is con-
sistent with the conclusion of a ‘theo-
retical’ cost‐effectiveness study in a UK
setting (Scriven, Reprod Biol Endocrinol
2017;15:49). Both studies highlighted
the financial burden of PGT‐A and
emphasised that applying PGT‐A to all
IVF cycles in women below the age of
40 years would be a very expensive
approach to reduce the risk of
miscarriage.
Although it is important not to
underestimate the emotional and
cycles to ach
would seem m
the limited r
more standard
more live birt
the possibility
and end up wi
Although th
involving day‐
fluorescence
were disappoi
that improvem
ture, embryo
molecular gen
gies would en
its potential
IVF outcome
Reprod 2014;2
recent publica
those improved
the study of N
2020;127:710–8
reminder of th
ased objective

19. • Any Intervention that claims to
increase the pregnancy rate in IVF
must stand the test of time…till
then must be clearly offered as an
experimental test and at least
should not financially drain the
patient.