Preimplantation genetic screening for abnormal number of

chromosomes (aneuploidies) in in vitro fertilisation or

intracytoplasmic sperm injection (Protocol)

Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 2005, Issue 2
http://www.thecochranelibrary.com

Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic
sperm injection (Protocol)
Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic i
sperm injection (Protocol)
Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Preimplantation genetic screening for abnormal number of

chromosomes (aneuploidies) in in vitro fertilisation or
intracytoplasmic sperm injection

M Twisk, S Mastenbroek, van M Wely, MJ Heineman, Van der F Veen, S Repping

Contact address: Moniek Twisk M.D., Medical Doctor/Researcher, Center for Reproductive Medicine, Academic Medical Center,
Meibergdreef 9 (H4-205), Amsterdam, 1105 AZ, NETHERLANDS. M.Twisk@amc.uva.nl.

Editorial group: Cochrane Menstrual Disorders and Subfertility Group.

Publication status and date: Unchanged, published in Issue 4, 2005.

Citation: Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for
abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection. The Cochrane Database
of Systematic Reviews 2005, Issue 2. Art. No.: CD005291. DOI: 10.1002/14651858.CD005291.

Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

This is the protocol for a review and there is no abstract. The objectives are as follows:

To review the effectiveness of PGS on livebirth rate in women undergoing IVF or ICSI treatment.

BACKGROUND In PGS, embryos created in vitro are analysed for aneuploidies

In both in vitro fertilisation (IVF) and intracytoplasmatic sperm
injection (ICSI) selection of the most competent embryo(s) for
transfer is generally based on morphological criteria, such as the
number of pronuclei, the number and regularity of blastomeres
and the percentage of fragmentation. However, many women fail
to achieve a pregnancy after transfer of morphologically good qual-
ity embryos.
One of the presumed causes is that such morphologically normal
embryos show an abnormal number of chromosomes (aneuploi-
dies). Since the early eighties many reports have been published
showing a high number of numerical chromosome abnormalities
in morphologically normal human cleavage stage embryos (Angell
1983). Because most chromosomally abnormal embryos do not
develop to term, preimplantation genetic screening for aneuploi-
dies (PGS), also known as preimplantation genetic diagnosis for
aneuploidy screening (PGD-AS), was designed to improve preg-
nancy rates.
Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic
sperm injection (Protocol)
Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
and only those that show a normal number of chromosomes are
placed into the uterus. There are three approaches to obtain nuclear
material for the genetic analysis. One is the aspiration of the first
and second polar body from fertilized oocytes (Verlinsky 1995).
Another approach is the removal of one or two blastomeres from
embryos at early cleavage stage (Handyside 1989); at the moment
the majority of centres performing PGS use cleavage-stage biopsy (
ESHRE 2002). A third approach is the removal of trophoblast cells
at the blastocyst stage, although this approach is used infrequently.
Removal of polar bodies, blastomeres or trophoblast cells requires
an opening in the zona pellucida. This opening can be created
chemically (with the use of acidic Tyrode’s solution), mechanically
or with the use of a laser. The chromosomes that are analysed in
PGS differ between the different centres. Most centres screen 5 to
10 chromosomes including chromosomes 13, 18, 21, X and Y.
In the literature, PGS and preimplantation genetic diagnosis
(PGD) are often presented as similar treatments. Indeed the tech-
1
nology used by both PGS and PGD is nearly identical. However,
PGS and PGD have completely different indications. As said, PGS
aims to improve pregnancy rates in subfertile couples undergoing
IVF/ICSI treatment. PGD, on the other hand, aims to prevent
the birth of affected children in fertile couples with a high risk of
transmitting genetic disorders. In 1990 the first successful preg-
nancies after PGD were reported (Handyside 1990). The use of
fluorescent in situ hybridisation (FISH) for aneuploidy screening
was first described in 1993 (Munne 1993).
So far, PGS has been suggested and used for the following in-
dications: (i) advanced maternal age (Gianaroli 1999; Kahraman
2000; Munne 1999; Munne 2003; Obasaju 2001) (ii) repeated
IVF failure (Gianaroli 1999; Kahraman 2000; Pehlivan 2003) (iii)
repeated abortions (Pellicer 1999; Rubio 2003) and (iv) testicular
REFERENCES
Additional references
Angell 1983
Angell RR, Aitken RJ, van Look PF, Lumsden MA,
Templeton AA. Chromosome abnormalities in human
embryos after in vitro fertilization. Nature 1983;303(5915):
336–8.
ESHRE 2002
ESHRE PGD Consortium Steering Committee. ESHRE
Preimplantation Genetic Diagnosis Consortium: data
collection III. Human Reproduction 2002;17(1):233–46.
Gianaroli 1999
Gianaroli L, Magli MC, Ferraretti AP, Munne S.
Preimplantation diagnosis for aneuploidies in patients
undergoing in vitro fertilization with a poor prognosis:
identification of the categories for which it should be
proposed. Fertility and Sterility 1999;72(5):837–44.
Handyside 1989
Handyside AH, Pattinson JK, Penketh RJ, Delhanty
JD, Winston RM, Tuddenham EG. Biopsy of human
preimplantation embryos and sexing by DNA amplification.
Lancet 1989;18(8634):347–9.
Handyside 1990
Handyside AH, Kontogianni EH, Hardy K, Winston RM.
Pregnancies from biopsied human preimplantation embryos
sexed by Y-specific DNA amplification. Nature 1990;344
(6268):768–70.
Kahraman 2000
Kahraman S, Bahce M, Samli H, Imirzalioglu N, Yakisn
K, Cengiz G, Donmez E. Healthy births and ongoing
pregnancies obtained by preimplantation genetic diagnosis
in patients with advanced maternal age and recurrent
implantation failure. Human Reproduction 2000;15(9):
2003–7.
Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic
sperm injection (Protocol)
Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
sperm extraction (TESE)-ICSI (Platteau 2004). These indications
were chosen because a relatively large amount of chromosome ab-
normalities have been found in embryos of these women.
Although IVF/ICSI with PGS has been available for over a decade
and is used more and more often (ESHRE 2002) its effectiveness
is still unclear. Therefore we aim to conduct a regularly updated
systematic review to investigate whether PGS is an effective inter-
vention leading to more live births per patient. In order to do so
we will compare IVF/ICSI with PGS to IVF/ICSI without PGS.
OBJECTIVES
To review the effectiveness of PGS on livebirth rate in women
undergoing IVF or ICSI treatment.
Munne 1993
Munne S, Weier HU, Griffo J, Cohen J. A fast and efficient
method for simultaneous X and Y in situ hybridization
of human blastomeres. Journal of Assisted Reproduction &
Genetics 1993;10(1):82–90.
Munne 1999
Munne S, Magli MC, Cohen J, Morton P, Sadowy S,
Gianaroli L, et al. Positive outcome after preimplantation
diagnosis of aneuploidy in human embryos. Human
Reproduction 1999;14(9):2191–9.
Munne 2003
Munne S, Sandalinas M, Escudero T, Velila E, Walmsley
R, Sadowy S, et al. Improved implantation after
preimplantation genetic diagnosis of aneuploidy.
Reproductive Biomedicine Online 2003;7(1):91–7.
Obasaju 2001
Obasaju M, Kadam A, Biancardi T, Sultan K, Fateh M,
Munne S. Pregnancies from single normal embryo transfer
in women older than 40 years. Reproductive Biomedicine
Online 2001;2(2):98–101.
Pehlivan 2003
Pehlivan T, Rubio C, Rodrigo L, Romero J, Remohi
J, Simon C, et al. Impact of preimplantation genetic
diagnosis on IVF outcome in implantation failure patients.
Reproductive Biomedicine Online 2003;6(2):232–7.
Pellicer 1999
Pellicer A, Rubio C, Vidal F, Minguez Y, Gimenez C,
Egozcue J, et al. In vitro fertilization plus preimplantation
genetic diagnosis in patients with recurrent miscarriage:
an analysis of chromosome abnormalities in human
preimplantation embryos. Fertility and Sterility 1999;71(6):
1033–9.
Platteau 2004
Platteau P, Staessen C, Michiels A, Tournaye H, Van
Steirteghem A, Liebaers I, et al. Comparison of the
2
 aneuploidy frequency in embryos derived from testicular
sperm extraction in obstructive azoospermic men. Human
Reproduction 2004;19(7):1570–4.
Rubio 2003
Rubio C, Simon C, Vidal F, Rodrigo L, Pehlivan T, Remohi
J, Pellicer A. Chromosomal abnormalities and embryo
development in recurrent miscarriage couples. Human
Reproduction 2003;18(1):192–8.
Verlinsky 1995
Verlinsky Y, Cieslak J, Freidine M, Ivakhnenko V, Wolf G,
Kovalinskaya L, et al. Pregnancies following pre-conception
diagnosis of common aneuploidies by fluorescent in-situ
hybridization. Human Reproduction 1995;10(7):1923–7.
∗
Indicates the major publication for the study

SOURCES OF SUPPORT

External sources of support

• No sources of support supplied

Internal sources of support

• No sources of support supplied

Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic 3
sperm injection (Protocol)
Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.