Elective Single Embryo Transfer- An Insight

1. Elective Single
Embryo Transfer-
An Insight
Dr Kaberi Banerjee

2. Ethnic
differences in
ovarian aging
between
Caucasian and
Indian
Women.
• Ovaries from Indian women seem to age at
an earlier stage than Caucasian. Similar
ovarian reserve markers and ovarian
response was observed in women with a 6
year difference in favour of Caucasian, whch
suggest ethnic differences in ovarian aging.
•
Banker et al ,Fert Stert 2013

3. JOINT SOGC–CFAS CLINICAL PRACTICE GUIDELINE
Elective Single Embryo Transfer Following
In Vitro Fertilization
Abstract
Objective: To review the effect of elective single embryo transfer
(eSET) compared with double embryo transfer (DET) following in
vitro fertilization (IVF), and to provide guidelines on the use of
eSET in order to optimize live birth rates and minimize twin
pregnancies.
Options: Rates of live birth, clinical pregnancy, and multiple
pregnancy following eSET and DET are compared.
Outcomes: Live birth, clinical pregnancy, and multiple pregnancy
rates, and cost-effectiveness.
Evidence: Published literature was retrieved through searches of
PubMed, Medline, and The Cochrane Library in 2009, using
appropriate controlled vocabulary (e.g., elective single embryo
transfer) and key words (e.g., embryo transfer, in vitro fertilization,
intracytoplasmic sperm injection, assisted reproductive
technologies, blastocyst, and multiple pregnancy). Results were
restricted to English language systematic reviews, randomized
controlled trials/controlled clinical trials, and observational studies.
There were no date restrictions. Searches were updated on a
regular basis and incorporated in the guideline to November 2009.
Additional references were identified through searches of
bibliographies of identified articles and international medical
specialty societies. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: Available evidence was reviewed by the Joint Society of
Obstetricians and Gynaecologist of Canada–Canadian Fertility
and Andrology Society Clinical Practice Guidelines Committee and
the Reproductive Endocrinology and Infertility Committee of the
Society of Obstetricians and Gynaecologists of Canada, and was
qualified using the evaluation of evidence criteria outlined in the
report of the Canadian Task Force on Preventive Health Care.
Benefits, Harms, and Costs: This guideline is intended to minimize
the occurrence of twin gestations while maintaining acceptable
overall live birth rates following IVF-ET.
JOINT SOGC–CFAS CLINICAL PRACTICE GUIDELINE
No. 241, April 2010
This clinical practice guideline has been prepared by the Joint
Society of Obstetricians and Gynaecologist of Canada–Canadian
Fertility and Andrology Society Clinical Practice Guidelines
Committee, reviewed by the Reproductive Endocrinology and
Infertility Committee of the SOGC and the IVF Directors Special
Interest Group of the CFAS, and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists of
Canada and the Board of the Canadian Fertility and Andrology
Society.
PRINCIPAL AUTHORS
Jason K. Min, MD, Ottawa ON
Ed Hughes, MD, Hamilton ON
David Young, MD, Halifax NS
JOINT SOGC-CFAS
CLINICAL PRACTICE GUIDELINES COMMITTEE
Matt Gysler, MD (Co-Chair), Mississauga ON
Robert Hemmings, MD (Co-Chair), Montreal QC
Anthony P. Cheung, MD, Vancouver BC
Gwendolyn J. Goodrow, MD, Cambridge ON
Ed Hughes, MD, Hamilton ON
Jason Min, MD, Ottawa ON
Vyta Senikas, MD, Ottawa ON
Benjamin Chee-Man Wong, MD, Calgary AB
David Young, MD, Halifax NS
REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY COMMITTEE
Anthony Cheung, MD (Chair), Vancouver BC
Sony Sierra, MD (Co-Chair), Toronto ON
Belina Carranza-Mamane, MD, Sherbrooke QC
Allison Case, MD, Saskatoon SK
Cathy Dwyer, RN, Toronto ON
James Graham, MD, Calgary AB
Jon Havelock, MD, Burnaby BC
Robert Hemmings, MD, Montreal QC
Francis Lee MD, Winnipeg MB
when blastocysts are available for transfer. (II-2A)
8. In oocyte donor–recipient cycles when the donor has good
prognosis and when good quality embryos are available, eSET
should be performed. (II-2B)
9. In women with medical or obstetrical contraindications to twin
pregnancy, eSET should be performed. (III-B)
10. In order to achieve successful uptake of eSET, it is essential to
provide patient and physician education regarding the risks of twin
pregnancy and regarding the similar cumulative live birth rate
following an eSET strategy and DET. (III-C)
11. When considering both direct health care and societal costs, it
should be noted that live birth following eSET is significantly less
expensive than DET in good-prognosis patients. (I-A) Therefore,
from a cost-effectiveness perspective, eSET is indicated in
good-prognosis patients. (III-A)
J Obstet Gynaecol Can 2010;32(4):363–377
in this guideline has bee
evidence criteria outline
Force on Preventative H
THE BURDEN OF MULT
The rate of multiple birth
in the last 3 decades, as it
1995 to 2004, the Canad
from 2.2% to 3.0%, t
multiple births per year
increased by 50% to 60%
of higher order (triplet o
increased by 300% to 70
increase in multiple preg
poraneous increase in m
pregnancies, and at leas
after infertility treatmen
Society of Obstetricians and Gynaecologists of Canada, and was
qualified using the evaluation of evidence criteria outlined in the
report of the Canadian Task Force on Preventive Health Care.
Benefits, Harms, and Costs: This guideline is intended to minimize
the occurrence of twin gestations while maintaining acceptable
overall live birth rates following IVF-ET.
Summary Statements
1. Indiscriminate application of eSET in populations with less than
optimal prognosis for live birth will result in a significant reduction
in effectiveness compared with DET. (I)
2. In women aged 38 years and over, eSET may result in a
significant reduction in live birth rate compared with DET. (II-2)
3. Selective application of eSET in a small group of good-prognosis
patients may be effective in reducing the overall multiple rate of an
entire IVF population. (II-3)
4. Given the high costs of treatment, uptake of eSET would be
enhanced by public funding of IVF treatment. (II-2)
Allison Case, MD, Saskatoon SK
Cathy Dwyer, RN, Toronto ON
James Graham, MD, Calgary AB
Jon Havelock, MD, Burnaby BC
Robert Hemmings, MD, Montreal QC
Francis Lee MD, Winnipeg MB
Kim Liu MD, Toronto ON
Tannys Vause, MD, Ottawa ON
Benjamin Chee-Man Wong, MD, Calgary AB
Disclosure statements have been received from all members of
the committees.
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should
not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
Key Words: Embryo transfer, elective single embryo transfer,
in vitro fertilization, intracytoplasmic sperm injection, assisted
reproductive technologies, blastocyst, multiple pregnancy, twins

4. Recommendations
1. Patients should be informed of the reductions in both multiple
pregnancy rate and overall live birth rate after a single fresh eSET
when compared with DET in good-prognosis patients. (I-A)
2. Because the cumulative live birth rate after fresh eSET followed
by transfer of a single frozen-thawed embryo is similar but not
equivalent to the rate after fresh DET in good-prognosis patients,
the eSET strategy should be used in order to avoid multiple
pregnancy. (I-A)
3. Women aged 35 years or less, in their first or second IVF attempt,
with at least 2 good quality embryos available for transfer should
be considered good-prognosis patients. (I-A)
4. In order to maximize cumulative live birth rates following eSET,
effective cryopreservation programs should be in place. (I-A)
5. In order to maintain the reduction in the rate of multiples achieved
INTRODUCTION
In Canada in 200
transfer were a r
of these were tw
transfer was perfo
occurred in 55.8%
of eSET is requir
twin pregnancies.
eSET regardless of
chance of live birth
eSET will be deriv
JOINT SOGC–CFAS CLINICAL PRACTICE GUIDELINE
JOINT SOGC–CFAS CLINICAL PRACTICE GUIDELINE
Elective Single Embryo Transfer Following
In Vitro Fertilization
Abstract
Objective: To review the effect of elective single embryo transfer
(eSET) compared with double embryo transfer (DET) following in
vitro fertilization (IVF), and to provide guidelines on the use of
eSET in order to optimize live birth rates and minimize twin
pregnancies.
Options: Rates of live birth, clinical pregnancy, and multiple
pregnancy following eSET and DET are compared.
Outcomes: Live birth, clinical pregnancy, and multiple pregnancy
rates, and cost-effectiveness.
Evidence: Published literature was retrieved through searches of
PubMed, Medline, and The Cochrane Library in 2009, using
appropriate controlled vocabulary (e.g., elective single embryo
transfer) and key words (e.g., embryo transfer, in vitro fertilization,
intracytoplasmic sperm injection, assisted reproductive
technologies, blastocyst, and multiple pregnancy). Results were
restricted to English language systematic reviews, randomized
controlled trials/controlled clinical trials, and observational studies.
There were no date restrictions. Searches were updated on a
regular basis and incorporated in the guideline to November 2009.
Additional references were identified through searches of
bibliographies of identified articles and international medical
specialty societies. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: Available evidence was reviewed by the Joint Society of
Obstetricians and Gynaecologist of Canada–Canadian Fertility
and Andrology Society Clinical Practice Guidelines Committee and
the Reproductive Endocrinology and Infertility Committee of the
JOINT SOGC–CFAS CLINICAL PRACTICE GUIDELINE
No. 241, April 2010
This clinical practice guideline has been prepared by the Joint
Society of Obstetricians and Gynaecologist of Canada–Canadian
Fertility and Andrology Society Clinical Practice Guidelines
Committee, reviewed by the Reproductive Endocrinology and
Infertility Committee of the SOGC and the IVF Directors Special
Interest Group of the CFAS, and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists of
Canada and the Board of the Canadian Fertility and Andrology
Society.
PRINCIPAL AUTHORS
Jason K. Min, MD, Ottawa ON
Ed Hughes, MD, Hamilton ON
David Young, MD, Halifax NS
JOINT SOGC-CFAS
CLINICAL PRACTICE GUIDELINES COMMITTEE
Matt Gysler, MD (Co-Chair), Mississauga ON
Robert Hemmings, MD (Co-Chair), Montreal QC
Anthony P. Cheung, MD, Vancouver BC
Gwendolyn J. Goodrow, MD, Cambridge ON
Ed Hughes, MD, Hamilton ON
Jason Min, MD, Ottawa ON
Vyta Senikas, MD, Ottawa ON
Benjamin Chee-Man Wong, MD, Calgary AB
David Young, MD, Halifax NS
REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY COMMITTEE
Anthony Cheung, MD (Chair), Vancouver BC
Sony Sierra, MD (Co-Chair), Toronto ON
Belina Carranza-Mamane, MD, Sherbrooke QC

5. 4. In order to maximize cumulative live birth rates following eSET,
effective cryopreservation programs should be in place. (I-A)
5. In order to maintain the reduction in the rate of multiples achieved
by fresh eSET, eSET should be performed in subsequent
frozen-thawed embryo transfer cycles. (II-2A)
6. Because blastocyst stage embryo transfer generally increases
the chance of implantation and live birth compared with cleavage
stage embryo transfer, eSET should be performed in
good-prognosis patients who have good quality blastocysts
available. (I-A)
7. In women aged 36 to 37 years, eSET should be considered in
good-prognosis patients with good quality embryos, particularly
when blastocysts are available for transfer. (II-2A)
8. In oocyte donor–recipient cycles when the donor has good
prognosis and when good quality embryos are available, eSET
should be performed. (II-2B)
9. In women with medical or obstetrical contraindications to twin
pregnancy, eSET should be performed. (III-B)
eSET reg
chance of
eSET will
women w
at risk for
This gui
Recomm
presente
pregnanci
acceptabl
in this gui
evidence c
Force on
THE BURD

6. good-prognosis patients with good quality embryos, particularly
when blastocysts are available for transfer. (II-2A)
8. In oocyte donor–recipient cycles when the donor has good
prognosis and when good quality embryos are available, eSET
should be performed. (II-2B)
9. In women with medical or obstetrical contraindications to twin
pregnancy, eSET should be performed. (III-B)
10. In order to achieve successful uptake of eSET, it is essential to
provide patient and physician education regarding the risks of twin
pregnancy and regarding the similar cumulative live birth rate
following an eSET strategy and DET. (III-C)
11. When considering both direct health care and societal costs, it
should be noted that live birth following eSET is significantly less
expensive than DET in good-prognosis patients. (I-A) Therefore,
from a cost-effectiveness perspective, eSET is indicated in
good-prognosis patients. (III-A)
J Obstet Gynaecol Can 2010;32(4):363–377
in t
evid
For
THE
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in th
199
from
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incr
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7. ...........................................................................................................................
Global variations in the uptake of single
embryo transfer
Abha Maheshwari , Siriol Griffiths , and Siladitya Bhattacharya*
Division of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
*Correspondence address. E-mail: s.bhattacharya@abdn.ac.uk
Submitted on September 8, 2009; resubmitted on May 19, 2010; accepted on June 9, 2010
table of contents
† Background
Human Reproduction Update, Vol.17, No.1 pp. 107–120, 2011
Advanced Access publication on July 15, 2010 doi:10.1093/humupd/dmq028
Downloaded
from
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8. .............................................................................................................................................................................................
Table III Summary table of factors determining variations in the uptake of SET.
Factor Reasons for preferring DET over eSET Reasons for preferring eSET over DET
Clinical Perceived higher success rate of DET by patients Support from the literature—equal success rate of SET when compared with
DET
Perceived higher success rate of DET by clinicians Availability of blastocyst transfer
Need for undergoing more cycles for achieving similar pregnancy
rates
Availability of good cryopreservation facilities
Previous IVF experiences (no success after eSET) Improved awareness of risks associated with twins both by patients and
clinicians
Lack of good cryopreservation facilities
Lack of good prediction models for selection of patients for eSET
Difficulties in accurate assessment of embryo quality
Increasing age of female partner
Efficacy of treatment is considered more important than safety
Awareness of risks associated with twins
Reporting of success rate as per cycle in league tables
Social Desire for twins National guidance
Desire for quick completion of family
Twins not perceived as risky by the society
Intellectual compartmentalization
Respect for patient autonomy—patient having ultimate choice
Lack of national guidance
ban in cryopreservation of embryos
Media propagation of successful multiple pregnancies
Economic Unavailability of insurance coverage/ public funding for ART Availability of insurance coverage/public funding
118 Maheshwari et al.
Downloaded
from
https://academic.oup.com/hum

9. Elective single-embryo transfer
Practice Committee of the Society for Assisted Reproductive Technology and Practice Committee of the American Society
for Reproductive Medicine
American Society for Reproductive Medicine, Birmingham, Alabama
As in vitro fertilization implantation rates have improved, the practice of transfering multiple embryos must be evaluated. The purpose of this document
is to reassess the literature on elective single-embryo transfer, to provide guidance for patient selection, and to discuss barriers to utilization. (Fertil Steril!
2012;97:835–42. "2012 by American Society for Reproductive Medicine.)
Earn CME credit for this document at www.asrm.org/eLearn
N
umerous publications have in-
vestigated the practice of elec-
tive single-embryo transfer
(eSET) (1–27). Single-embryo transfer
after in vitro fertilization (IVF) has
been advocated as the only effective
means to avoid multiple pregnancy in
IVF cycles (28). Elective SET is defined
as the transfer of a single embryo at
either the cleavage or blastocyst stage
of embryo development that is selected
from a larger number of available em-
bryos. It is defined in the Society for
Assisted Reproductive Technologies
(SART) reporting guidelines as ‘‘an em-
bryo transfer in which more than one
must be addressed in order to maximize
the efficacy of eSET and improve its
acceptability and utilization among
clinicians and patients.
APPLICATION OF ESET
In 2000, more than two-thirds of all IVF
transfer procedures in the United States
were of three or more embryos. Practice
guidelines from SART and the Ameri-
can Society for Reproductive Medicine
(ASRM) recommending maximum
numbers of embryos to transfer were
first published in 1998 and have been
periodically revised and adjusted
downward as implantation rates im-
years old in 2009. These trends have
resulted in an increased number of
double-embryo transfers (DETs), lead-
ing to a reduction in number of triplet
gestation but an unchanged rate of
twin gestation (Fig. 2) (32, 34–41).
Gradual increase in eSET rates over
time is a general worldwide pattern, but
the United States has lagged behind
much of the rest of the world in adop-
tion of eSET (42). Across Europe in
2005, 20% of all transfers were of sin-
gle embryos. Rates vary considerably
within Europe, with the highest re-
ported eSET rates in Sweden (69%),
followed by Finland (50%), Belgium
2012
a substantial reduction in multiple gestations.
! An RCT comparing eSET and DET of blastocyst-stage
embryos demonstrated no statistical difference in PRs
and a reduction in multiple gestation rate from 47% to 0%.
! There is evidence from well controlled nonrandomized tri-
als and clinical reports that if the contribution of cryopre-
served embryo transfers is included, cumulative success
rates per retrieval are similar for eSET and DET.
! Published studies of the cost-effectiveness of eSET versus
DET have included only costs to achieve a pregnancy or
through 4–6 weeks postpartum.
! Elective SET is most appropriate for those with a good prog-
nosis: age <35 years, more than one top-quality embryo
available for transfer, first or second treatment cycle, pre-
vious successful IVF, and recipients of embryos from do-
nated eggs.
! Women aged 35–40 years may be considered for eSET if
they have top-quality blastocyst-stage embryos available
for transfer.
! Decisions regarding eSET of cryopreserved embryos should
take into consideration prognosis, embryo quality, and suc-
cess rates of the individual cryopreservation program.
! Challenges to increased use of eSET exist. These include
provider and patient education, financial considerations,
embryo selection, and successful cryopreservation. Stake-
holders should recognize that the optimal outcome of an
IVF cycle is the birth of a healthy singleton.
ment of this document. All committee members disclosed
commercial and financial relationships with manufacturers
or distributors of goods or services used to treat patients.
Members of the committee who were found to have conflicts
of interest based on the disclosed relationships did not partic-
ipate in the discussion or development of this document.
Samantha Pfeifer, M.D.; Marc Fritz, M.D.; R. Dale
McClure, M.D.; G. David Adamson, M.D.; Kurt Barnhart,
M.D., M.S.C.E.; William Catherino, M.D., Ph.D.; Marcelle Ce-
dars, M.D.; John Collins, M.D.; Owen Davis, M.D.; Jeffery
Goldberg, M.D.; Michael Thomas, M.D.; Catherine Racowsky,
Ph.D.; Eric Widra, M.D.; Mark Licht, M.D.; Clarisa Gracia,
M.D., M.S.C.E.; Robert Rebar, M.D.; Andrew La Barbera, Ph.D.
REFERENCES
1. Tiitinen A, Halttunen M, Harkki P, Vuoristo P, Hyden-Granskog C. Elective
single embryo transfer: the value of cryopreservation. Hum Reprod
2001;16:1140–4.
2. Gerris J, de Neubourg D, Mangelschots K, van Royen E, Vercruyssen M,
Barudy-Vasquez J, et al. Elective single day 3 embryo transfer halves the
twinning rate without decrease in the ongoing pregnancy rate of an
IVF/ICSI programme. Hum Reprod 2002;17:2626–31.
3. de Sutter P, van der Elst J, Coetsier T, Dhont M. Single embryo transfer and
multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal. Reprod Bi-
omed Online 2003;6:464–9.
4. Kovacs G, MacLachlan V, Rombauts L, Healy D, Howlett D. Replacement of
one selected embryo is just as successful as two embryo transfer, without
nated eggs.
! Women aged 35–40 years may be considered for eSET if
they have top-quality blastocyst-stage embryos available
for transfer.
! Decisions regarding eSET of cryopreserved embryos should
take into consideration prognosis, embryo quality, and suc-
cess rates of the individual cryopreservation program.
! Challenges to increased use of eSET exist. These include
provider and patient education, financial considerations,
embryo selection, and successful cryopreservation. Stake-
holders should recognize that the optimal outcome of an
IVF cycle is the birth of a healthy singleton.
! Reduced financial burdens for IVF through insurance cov-
erage or risk-sharing programs have been shown to im-
prove patient acceptance of eSET.
! Selection and successful cryopreservation of the embryos
with the highest IR will facilitate wider use of eSET.
CONCLUSIONS
! Elective SET should be offered to patients with a good prog-
nosis and to recipients of embryos from donated eggs.
! IVF centers should promote eSET when appropriate
through provider and patient education.
REFER
1. Ti
sin
20
2. G
Ba
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VOL. 97 NO. 4 / APRIL 2012
should, in theory, be highest when embryos are transfered
individually.
SUMMARY
! Utilization of eSET has increased over the past decade. Use
of eSET in the United States has lagged behind that of many
other countries. In the United States during this time, the
use of DET has increased and twin pregnancy rates have
remained essentially unchanged.
! RCTs comparing cleavage-stage eSET and subsequent FET
with DET have demonstrated similar PRs and LBRs with
a substantial reduction in multiple gestations.
! An RCT comparing eSET and DET of blastocyst-stage
embryos demonstrated no statistical difference in PRs
and a reduction in multiple gestation rate from 47% to 0%.
! There is evidence from well controlled nonrandomized tri-
als and clinical reports that if the contribution of cryopre-
served embryo transfers is included, cumulative success
rates per retrieval are similar for eSET and DET.
! Published studies of the cost-effectiveness of eSET versus
DET have included only costs to achieve a pregnancy or
through 4–6 weeks postpartum.
! Elective SET is most appropriate for those with a good prog-
nosis: age <35 years, more than one top-quality embryo
available for transfer, first or second treatment cycle, pre-
vious successful IVF, and recipients of embryos from do-
nated eggs.
! Women aged 35–40 years may be considered for eSET if
they have top-quality blastocyst-stage embryos available
of reproduct
proved stand
of treatment
taking into
available re
limitations.
tors of the
have approv
The Prac
butions of K
in the prepa
of the ASRM
ment of thi
commercial
or distributo
Members of
of interest ba
ipate in the
Samanth
McClure, M
M.D., M.S.C
dars, M.D.;
Goldberg, M
Ph.D.; Eric
M.D., M.S.C.
REFERENC
1. Tiitinen A
single em

10. REVIEW Open Access
Risks of spontaneously and IVF-conceived
singleton and twin pregnancies differ,
requiring reassessment of statistical
premises favoring elective single embryo
transfer (eSET)
Norbert Gleicher1,2,3*
, Vitally A. Kushnir1,4
and David H. Barad1,2,5
Abstract
Gleicher et al. Reproductive Biology and Endocrinology (2016) 14:25
DOI 10.1186/s12958-016-0160-2

11. in the Canadian province of Québec following introduc-
tion of a provincial eSET mandate [20], would have to
considered poor public health policy, and propagation of
eSET policies by professional societies, insurance compan-
ies and government agencies should be abandoned.
Conclusions
Here presented data raise serious questions about the rap-
idly expanding IVF practice of prolonged embryo culture
to blastocyst stage, followed by eSET. Since it is undis-
puted that eSET reduces clinical pregnancy chances in IVF
when compared to two-embryo transfers [8, 18], propo-
nents of eSET consider such reductions in pregnancy po-
tential appropriately compensated by decreased maternal
and especially neonatal risks from avoided twin pregnan-
cies. In absence of increased risks from twin pregnancies,
patient would, however, be only left with a deficit in preg-
nancy chances, and without compensatory benefits of any
kind. Here presented review, therefore, adds significant
doubts about the medical and economic validity of eSET.
The concept of eSET, therefore, requires serious re-
consideration, unless patients want only one child to
complete their family or have medical contraindications
to twin pregnancies. In all other cases, eSET, as currently
increasingly considered standard of care, actually, likely,
harms pregnancy chances of infertile patients undergo-
ing IVF cycles, therefore unnecessarily prolonging their
3
The Rockefeller University, New York, N.Y., USA. 4
Department of Obstetrics
and Gynecology, Wayne Forrest School of Medicine, Winston Salem, N.C.,
USA. 5
Department of Obstetrics and Gynecology, Albert Einstein College of
Medicine, Bronx, N.Y., USA.
Received: 25 February 2016 Accepted: 25 April 2016
References
1. Templeton A, Morris JK. Reducing the risk of multiple births by transfer of
two embryos after in vitro fertilization. N Engl J Med. 1998;339:573–7.
2. Vilska S, Tiitinen A, Hyden-Granskog C, Hovatta O. Elective transfer of
embryo results in an acceptable pregnancy rate and eliminates the risk of
multiple births. Hum Reprod. 1999;14:2392–5.
3. McLernon DJ, Harrild K, Bergh C, Davies MJ, SeNeubourg D, Dumoulin JCM,
Gerris J, Kremer JAM, Martilainen H, Mol BW, Norman RJ, Thurin-Kjellberg A,
Tiitinen AM, van Montfoort APA, van Peperstraten AM, Van Royen E,
Bhattacharya S. Clinical effectiveness of elective single embryo versus
double embryo transfer: meta analysis of individual patient data from
randomized trials. BMJ. 2010;341:c6945.
4. Roberts SA, McGowan L, Mark Hirst W, Vali A, Rutherford A, Lieberman BA.
Brison DR; Toward SET Collaboration. Hum Reprod. 2011;26:569–75.
5. Gleicher N, Barad DH. Twin pregnancy, contrary to consensus, is a desirable
outcome in infertility. Fertil Steril. 2009;91:2426–31.
6. Gleicher N. The irrational attraction of elective singe-embryo transfer (eSET).
Hum Reprod. 2013;28:294–7.
7. Sazonova A, Källen K, Thurin-Kjellberg A, Wennerhom UB, Bergh C.
Neonatal and maternal outcomes comparing women undergoing two in
vitro fertilization (IVF) singleton pregnancies and women undergoing one
IVF twin pregnancy. Fertil Steril. 2013;99:731–7.
8. La Sala GB, Morini D, Gizzo S, Nicoli A, Palomba S. Two consecutive
singleton pregnancies versus one twin pregnancy as preferred outcome of
in vitro fertilization for mothers and infants: a retrospective case-control
study. Curr Med Res Opin 2016;1–6 [Epub ahead of print
9. Gleicher N. Clinician to Clinician. For some infertility patients, twins are the
puted that eSET reduces clinical pregnancy chances in IVF
when compared to two-embryo transfers [8, 18], propo-
nents of eSET consider such reductions in pregnancy po-
tential appropriately compensated by decreased maternal
and especially neonatal risks from avoided twin pregnan-
cies. In absence of increased risks from twin pregnancies,
patient would, however, be only left with a deficit in preg-
nancy chances, and without compensatory benefits of any
kind. Here presented review, therefore, adds significant
doubts about the medical and economic validity of eSET.
The concept of eSET, therefore, requires serious re-
consideration, unless patients want only one child to
complete their family or have medical contraindications
to twin pregnancies. In all other cases, eSET, as currently
increasingly considered standard of care, actually, likely,
harms pregnancy chances of infertile patients undergo-
ing IVF cycles, therefore unnecessarily prolonging their
time to pregnancy and increasing their medical costs.
Details of ethics approval
As a review article of the literature no ethics approval
was required.
Competing interests
All authors have in the past received research support, travel funds and speaker
honoraria from various Pharma and medical device companies, none related to
here- presented data. N.G. and D.H.B. have been awarded various U.S. patents,
none related to here-presented manuscript. Both of these authors also receive
royalties from some of these patents. N.G. is shareholder in a number of
multipl
3. McLern
Gerris J
Tiitinen
Bhattac
double
random
4. Roberts
Brison D
5. Gleiche
outcom
6. Gleiche
Hum Re
7. Sazono
Neonat
vitro fe
IVF twi
8. La Sala
singleto
in vitro
study. C
9. Gleiche
best Ou
10. Helmer
singelto
control
11. Källén B
neonat
BJOG. 2
12. Anbazh
Higgns
FD. Com
reprodu
13. Dar S, L
births a
review

13. Cochrane
Library
Cochrane Database of Systematic Reviews
Number of embryos for transfer following in vitro fertilisation or
intra-cytoplasmic sperm injection (Review)
Kamath MS, Mascarenhas M, Kirubakaran R, Bhattacharya S
Cochrane
Library
Trusted evidence.
Informed decisions.
Better health.
Cochrane Database of Systematic Reviews
the chance following repeated single embryo transfer would be between 34% and 46%. Moderate-quality evidence suggests that the risk
of multiple birth is much lower in the SET group (between 0% and 3%) compared to a 13% chance of multiple pregnancy following a single
cycle of DET. The chance of miscarriage rate is similar between the two groups.
Single versus multiple embryo transfer in a single cycle
We found low-quality evidence that the rates of live birth and clinical pregnancy (CPR) were lower after one cycle of fresh SET compared
with the outcome of one cycle of fresh DET. For a woman with a 46% chance of live birth following one cycle of DET, the chance following
one cycle of SET was between 27% and 35%. However, the risk of multiple pregnancy was higher after DET. There was no difference in the
chance of miscarriage between the two groups.
Conclusion
While live birth and clinical pregnancy was lower following SET compared to DET after single fresh cycle, there was no difference between
overall live birth rate and CPR following consecutive SET versus a single cycle of DET. However, the multiple pregnancy rate is much lower
following SET compared to DET. Most of the evidence currently available concerns younger women with a good prognosis.
Quality of evidence
The quality of evidence was low to moderate primarily due to inadequate reporting of study methods and absence of masking those
delivering, as well as receiving the interventions.
2020
Please note
Young
Good prognosis

14. Ma et al.
Reproductive Biology and Endocrinology (2022) 20:20
https://doi.org/10.1186/s12958-022-00899-1
REVIEW
Comparisons of benefits and risks of single
embryo transfer versus double embryo transfer:
a systematic review and meta-analysis
Shujuan Ma1†
, Yangqin Peng1†
, Liang Hu1
, Xiaojuan Wang1
, Yiquan Xiong2
, Yi Tang1
, Jing Tan2*
and Fei Gong1*
Abstract
Background: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET)
versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those
women with a defined embryo quality or advanced age.
Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE,
Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through
February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds
ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0.
Results: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared
with DET, SET decreased the probability of a live birth (OR=0.78, 95% CI: 0.71–0.85, P< 0.001, n=62), and lowered the
rate of multiple pregnancy (0.05, 0.04–0.06, P< 0.001, n=45). In the sub-analyses of age stratification, both the differ-
ences of LBR (0.87, 0.54–1.40, P=0.565, n=4) and MPR (0.34, 0.06–2.03, P=0.236, n=3) between SET and DET groups
became insignificant in patients aged ≥40years. No significant difference in LBR for single GQE versus two embryos
of mixed quality [GQE+PQE (non-good quality embryo)] (0.99, 0.77–1.27, P= 0.915, n=8), nor any difference of MPR
in single PQE versus two PQEs (0.23, 0.04–1.49, P= 0.123, n=6). Moreover, women who conceived through SET were
associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage
(0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1<7 rate (0.12, 0.02-0.93) or
neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET.
Open Access
• Better pregnancy rate with DET
• Preferable in < 40 Caucasians/ < 35 Indian
• Older SET worse results
Background: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET)
versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those
women with a defined embryo quality or advanced age.
Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE,
Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through
February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds
ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0.
Results: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared
with DET, SET decreased the probability of a live birth (OR=0.78, 95% CI: 0.71–0.85, P< 0.001, n=62), and lowered the
rate of multiple pregnancy (0.05, 0.04–0.06, P< 0.001, n=45). In the sub-analyses of age stratification, both the differ-
ences of LBR (0.87, 0.54–1.40, P=0.565, n=4) and MPR (0.34, 0.06–2.03, P=0.236, n=3) between SET and DET groups
became insignificant in patients aged ≥40years. No significant difference in LBR for single GQE versus two embryos
of mixed quality [GQE+PQE (non-good quality embryo)] (0.99, 0.77–1.27, P= 0.915, n=8), nor any difference of MPR
in single PQE versus two PQEs (0.23, 0.04–1.49, P= 0.123, n=6). Moreover, women who conceived through SET were
associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage
(0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1<7 rate (0.12, 0.02-0.93) or
neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET.
Conclusions: In women aged <40years or if any GQE is available, SET should be incorporated into clinical practice.
While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40years, current evidence
is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed.
Keywords: Single embryo transfer, Double embryo transfer, Live birth rate, Multiple pregnancy rate, Perinatal
complication

15. Guidance on the limits to the number
of embryos to transfer: a
committee opinion
Practice Committee of the American Society for Reproductive Medicine and the Practice Committee for the
Society for Assisted Reproductive Technologies
American Society for Reproductive Medicine and Society for Assisted Reproductive Technologies, Birmingham, Alabama
On the basis of American Society for Reproductive Medicine and Society for Assisted Reproductive Technology data, the American So-
ciety for Reproductive Medicine's guidelines for the limits on the number of embryos to be transferred during in vitro fertilization cycles
have been further refined in continuing efforts to promote singleton gestation and reduce the number of multiple pregnancies. This
version replaces the document titled ‘‘Criteria for number of embryos to transfer: a committee opinion’’ that was published most recently
in August of 2017 (Fertil Steril 2017;107:901–3). (Fertil Steril! 2021;116:651-54. "2021 by American Society for Reproductive Med-
icine.)
El resumen está disponible en Español al final del artículo.
Key Words: Assisted reproduction, transfer, blastocyst, euploid, IVF
Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/33359
BACKGROUND
The American Society for Reproductive
Medicine’s (formerly The American
Fertility Society) guidance for the limits
to the number of embryos to be trans-
ferred during in vitro fertilization
(IVF) cycles aims to promote singleton
gestation and reduce the number of
multiple pregnancies while maxi-
mizing the cumulative live birth rates.
Although the incidence of high-
order multiple pregnancies (three or
more fetuses in one pregnancy) have
diminished in recent years, twin gesta-
tions are still a relatively common
occurrence with assisted reproductive
technology (ART). Multiple gestation
leads to an increased risk of complica-
cycles reported to the Society for
Assisted Reproductive Technology
(SART) in 2017, 12.4% of women <38
years of age who had a successful IVF
cycle had a twin gestation (7), down
from 23% in 2014 but still
significantly more than baseline.
Almost half of all ART multiple
gestations in the United States
occurred in women <35 years old
when 2 fresh or frozen blastocysts
were transferred (8).
Respect for a patient's autonomy to
consider placement of more than one
embryo requires a full discussion of
the ethical and medical considerations,
ensuring that a patient is able to make a
fully informed decision. Elective place-
ment of multiple embryos is often
favor of multiple embryo transfer. In
contrast, if patients are informed of
the risks inherent in twin or high-
order pregnancy and these financial
pressures are removed or at least allevi-
ated, most patients would opt to maxi-
mize their chance of a singleton, safe
pregnancy and birth (10).
Although multifetal pregnancy
reduction can be performed to reduce
the fetal number, the procedure may
result in the loss of all fetuses, it does
not completely eliminate the risks asso-
ciated with multiple pregnancies, and it
may have adverse psychological conse-
quences (11). Moreover, multifetal
pregnancy reduction is not an accept-
able option for many women.
reflects appropriate management of a problem encountered in
the practice of reproductive medicine, it is not intended to be
multicountry survey on maternal and newborn health. Obstet Gynecol
2016;127:631–41.
TABLE 1
Recommendations for the limit to the number of embryos to transfer
Prognosis
Age
<35 35-37 38-40 41-42
Cleavage stage embryos
Euploida
1 1 1 1
Other Favorableb
1 1 %3 %4
Embryos not Euploda
or Favorableb
%2 %3 %4 %5
Blastocysts
Euploida
1 1 1 1
Other Favorableb
1 1 %2 %3
Embryos not Euploida
or Favorableb
%2 %2 %3 %3
a
Demonstrated euploid embryos, best prognosis
b
Other Favorable ¼ Any ONE of these criteria: Fresh cycle: expectation of 1 or more high-quality embryos available for cryopreservation or previous live birth after a prior transfer with sibling em-
bryo(s); FET cycle: availability of vitrified day-5 or day-6 blastocysts, euploid embryos, 1st
FET cycle, or previous live birth after an IVF cycle.
Practice Committee of the American Society for Reproductive Medicine and the Practice Committee for the Society for Assisted Reproductive Technologies*ASRM@asrm.org. Fertil Steril 2021.
Fertility and Sterility®

16. Introduction
There is a general consensus in the medical commu-
steady decrease in multiple pregnancies (EHRE,
2010).
Belgium was one of the first countries to imple-
Does transferring three or more embryos make sense for a well-
defined population of infertility patients undergoing IVF/ICSI?
T. MASSCHAELE, J. GERRIS, F. VANDEKERCKHOVE, P. DE SUTTER
Centre for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Correspondence at: jan.gerris@uzgent.be
FVV IN OBGYN, 2012, 4 (1): 51-58 Original paper
Abstract
Recently, there has been a marked increase in the use of Single Embryo Transfer (SET) subsequent to In Vitro
Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI), with the aim of reducing the risk of multiple
gestations. However, critics have stated that by reducing the number of embryos transferred, a group of women
with an a priori reduced chance of pregnancy are at particular greater risk of undertreatment. This group includes
women who are of a certain age (≥ 40 years) or have already received a number of – failed –IVF attempts. We
wanted to study whether the practice of three or more embryos being transferred would be of added value to these
patients and whether the strategy of Heavy Load Transfer (HLT) is likely to boost the pregnancy rates to an
acceptable level. We performed both a literature study and a retrospective cohort analysis of 7,850 IVF/ICSI cycles
of early cleavage stage embryo transfer.
Notwithstanding the limitations associated with this approach, we contend that HLT in the group of patients with
poor prognosis should be recommended. This article outlines a suggested protocol within the legal framework
relevant to Belgium.
Key words: advanced maternal age, subfertility, Heavy Load Transfer, embryo transfer, multiple gestations, never
pregnant prone.
The combination of reduced fertility and deliber-
ately postponing pregnancy has resulted in a large
group of women aged more than 35 failing to con-
ceive within twelve months. A growing number of
these couples are forced to rely on ART to compen-
sate for the effects of their diminished fertility
(Leridon, 2004). Unfortunately, IVF in itself cannot
compensate for reduced natural fecundity (Klipstein
et al., 2005; Spandorfer et al., 2007). The chances of
a spontaneous conception occurring in women aged
35 and older are still significant, but in case of
failure, ART will never recover the lost years
(Leridon, 2004).
Several factors determine IVF/ICSI success rates.
Ageing in women has been shown to correlate with
follows that lower implantation rates (which is com-
mon in older women) (Tarlatzis et al., 2003; Rowe,
2006) demand a higher number of embryos to be
transferred in order to achieve a higher pregnancy
rate (Martin and Welch, 1998) (Fig. 1). However,
when transferring multiple embryos, consideration
should be given to the risk of multiple births. Multi-
ple pregnancies typically worsen the prognosis for
the mother and babies, inducing high costs for
society (Wennerholm, 2009).
On the other side of the clinical spectrum of the
earlier discussed twin prone group, there is a never-
pregnant group that tends to be undertreated when
only eSET is used. Mostly, they are women aged
40 years or older with a low ovarian response to
Table 1. — The Belgian policy for financing IVF (Dhont et al., 2009; Gerris et al., 2009).
< 36 years
First attempt Single Embryo Transfer (SET)
2nd
attempt
– Single Embryo Transfer (SET), if one or more good-quality embryos
are available.
– Transfer of two embryos, if no good embryos are available.
3th
to 6th
attempt Maximum of two embryos
≥ 36 and ≤ 39 years
1th
and 2nd
attempt Maximum of two embryos
3th
to 6th
attempt Maximum of three embryos
> 39 and ≤ 42 years No limit to the maximum number of embryos
haele-_Opmaak 1 19/03/12 14:48 Pagina 52
52 FVV IN OBGYN
ESHRE, 2005; Van Blerkom et al., 2000). Women
of older reproductive age are therefore considered as
patients with a poor prognosis (Klipstein et al., 2005;
Lass et al., 1998, Schieve et al., 1999; Tarlatzis et al.,
2003; Templeton et al., 1996). The number of em-
bryos obtained after stimulation and transferred also
matters. Indeed, the number of live births in each age
group increases with each additional embryo transfer
carried out (Elsner et al., 1997; Klipstein et al.,2005;
Opsahl et al., 2001; Roest et al., 1996; Widra et al.,
1996). A number of previous failed IVF attempts,
typically associated with poor embryo quality, also
correlates with a poor IVF prognosis (Elsner et al.,
1997; Templeton et al., 1998).
The only rationale for improving IVF/ICSI out-
come in these patients (older age and multiple fail-
ures) is to increase the number of available embryos
transferred. Martin and Welch (1998) examined the
theoretical pregnancy rates after completion of a sin-
gle IVF cycle: increasing the number of embryos
transferred improves the probability of pregnancy. It
treatment strategy. In the never-pregnant group, HLT
implies that multiple embryos are transferred –
Fig. 1. — The effect of increasing the number of embryos trans-
ferred on the probability of pregnancy outcome (assuming an
implantation rate of 30%). IR = Implantation Rate; Pmult =
probability of multiple births; Pone = probability of a singleton
birth; Pnone = probability of no birth. (adapted from Martin et
al., 1998).
the NPP group: one must of course have five em-
bryos. Study starts from the first treatment cycle,
which is a different starting point than we use for the
HLT concept. The study of Stern et al. (2009) in-
cluded only women with their first ART-treatment
therefore the effect on the outcome of previous failed
IVF-cycles could not be determined. They reported
themselves that the analysis misses embryo quality
and previous cycle failure.
Both the studies discussed and our own data are
retrospective and of a purely descriptive character.
Only a large randomized trial can prove the useful-
ness of transferring many versus just one or two
We suggest that HLT can be considered for the
poor prognosis group of women. Limiting the
number of embryos to transfer to a maximum of two
in all cases probably leads to undertreatment of this
subpopulation. It will be difficult to prove this,
nevertheless further studies are needed to strengthen
this finding.
Acknowledgements
Petra De Sutter is holder of a fundamental clinical re-
search mandate of the Flemish Foundation of Scientific
Researchh (FWO-Vlaanderen).
Table 5. — Suggested clinical protocol. For whom would heavy load transfer (HLT) be a good option (within Belgium's legal
framework)?
< 36 years From the 7th
attempt: HLT
[36-39] years • From the 3rd
to the 6th
attempt: 3ET
• From the 7th
attempt: HLT
[40-42] years • First attempt: 2ET
• 2nd
attempt: 3ET
• 3rd
– before last attempt: HLT (5ET)
• Last attempt: transfer of all embryos
≥ 43 years • HLT
• Last attempt: transfer of all embryos
> 44 years Alternatives: egg donation, adoption, abandoning the desire to have children, …

17. • eSET needs to be implemented very
judiciously in India ,where IVF is not
state/privately insured…
• One needs to know that there is loss
of embryos in blastulation, often lower
pregnancy rate/transfer and increase
number of attempts when eSET is
adopted
• Each lab must study its blastulation
rate, implantation rate for cleavage and
blastocysts separately, cryopreservation
rates and pregnancy rates before
deciding its policy…