Selection of an embryo from a large number of embryos and then placing it to the uterus is known as selective embryo transfer. This fertility preservation process is usually done after the process of IVF cycle and cancels the risks of spontaneous transfer of multiple embryos. Have a look at the detailed description of elective single embryo transfer in the following ppt.
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Single Embryo Transfer
1. Dr. Laxmi Shrikhande MD; FICOG; FICMU
â˘Director-Shrikhande Fertility Clinic, Nagpur
â˘President Menopause Society, Nagpur
â˘National Corresponding Editor-The Journal of Obstetrics & Gynecology of India
â˘Senior Vice President FOGSI 2012
â˘Vice Chairperson ICOG
â˘Governing Council member ICOG 2012-2017
â˘Governing Council Member ISAR 2014-2019
â˘Governing Council Member IAGE for 3 terms
â˘Patron-Vidarbha Chapter ISOPARB
â˘Chairperson-HIV/AIDS Committee, FOGSI (2007-09)
â˘Received Best Committee Award of FOGSI
â˘Received Bharat excellence Award for womenâs health
â˘President Nagpur OB/GY Society 2005-06
â˘Associate member of RCOG
â˘Member of European Society of Human Reproduction
â˘Visited 96 FOGSI Societies as invited faculty
â˘Delivered 5 orations
â˘Publications-Twenty National & eleven International
â˘Presented Papers in FIGO, AICOG, SAFOG, AICC-RCOG conferences
â˘Conducted adolescent health programme for more than 15,000 adolescent girls
3. Milestones in reproductive medicine
⢠1960 - ovarian stimulation with clomifene and gonadotrophins
- radioimmunoassay
⢠1970 - secretion, synthesis, mechanism gonadotrophins
- in vitro fertilisation
⢠1980 - cryopreservation
⢠1990 - recombinant gonadotrophins
- preimplantation genetic diagnosis
- intracytoplasmatic sperm injection (ICSI)
- GnRH-antagonists and gonadotrophins
⢠2000 - in vitro maturation of oocytes
- embryonic stemcells
- SET (single embryo transfer)
- vitrification
4. Once upon a timeâŚ
07/78 Louise Brown
was born
Birth after reimplantation of a human embryo
Steptoe P.C. / Edwards R.G.
Lancet 2 (1978): 366
5. New Developments in Reproductive Medicine
⢠Ovarian stimulation: GnRH-antagonists and long
acting FSH
⢠Elective single embryotransfer (eSET)
⢠Blastocyst transfer
⢠Preimplantation genetic diagnosis and screening
⢠In-vitro-maturation
⢠Cryopreservation and vitrification
â˘Fertility preservation for women with cancer
6. § 1, Abs. 1, Nr. 5
âa person fertilizing more
oocytes than he or she
intends to tranfer in the
course of one treatment
cycleâ
§ 1, Abs. 1, Nr. 3
âa person transfering more
than
3 embryos to the womb in the
course of one treatment
cycleâ
Prison sentence up to three years or financial penalty
7. Goal in 21st century
⢠To avoid the hazards of multiple
pregnancies
⢠Improve the pregnancy and live
birth rate
Solution: Transfer of one
selected embryo
8. Who will decide-Patient's autonomy
⢠Medical arguments in favour of eSET are often
contrasted with the arguments that support patient
autonomy.
⢠The principle of respect for autonomy entails
âacknowledging the right of an autonomous agent to
hold views, to make choices, and to take actions
based on their values and beliefs.â
Beauchamp TL, Childress J. 7th ed. New York: Oxford University Press; 2013.
Principles of Biomedical Ethics.
9. Patient's autonomy
⢠It has been reported that a significant proportion of
infertile couples in Europe, the United States, and
Africa prefer to transfer more than one embryo in
order to achieve a twin pregnancy.
Okohue JE, Onuh SO, Ikimalo JI, Wada I. Patientsâ preference for number of embryos transferred during IVF/ICSI: A Nigerian
experience. Niger J Clin Pract. 2010;13:294â7.
Borkenhagen A, Brähler E, Kentenich H. Attitudes of German infertile couples towards multiple births and elective embryo transfer.
Hum Reprod. 2007;22:2883â7.
Højgaard A, Ottosen LD, Kesmodel U, Ingerslev HJ. Patient attitudes towards twin pregnancies and single embryo transfer - A
questionnaire study. Hum Reprod. 2007;22:2673â8.
Gleicher N, Barad D. Twin pregnancy, contrary to consensus, is a desirable outcome in infertility. Fertil Steril. 2009;91:2426â31-35.
Ryan GL, Zhang SH, Dokras A, Syrop CH, Van Voorhis BJ. The desire of infertile patients for multiple births. Fertil Steril.
2004;81:500â4
10. Coupleâs desire
⢠Couples with infertility often express a desire for
delivering twins instead of a single child. They may
think; "we want kids, and all this treatment is
expensive and unpleasant, so let's just have 2 kids
and get it over with".
⢠The psychological, social, and economic stresses
involved with caring for twins is substantial, but
patients often say they would welcome facing those
stresses if they were so blessed.
11. In my experience
⢠In my experience, if a couple has high-quality embryos available for
transfer on day 5 and they are offered the options of transferring one
embryo with a 50% expectation for pregnancy (almost all singles) or two
embryos with an 75% expectation for pregnancy (about 50% twins, 50%
single, and about 3% triplets), very few patients choose to transfer only
one.
They want the higher chance for pregnancy and are accepting (even
welcoming) the risks of a multiple pregnancy.
⢠The few who do choose to have a single embryo transferred almost
always have excellent high order socio economic status and often have at
least one child already.
12. Ethical issues:pt autonomy vs obs complications
⢠Where does patient autonomy over treatment end
and national regulation begin?
⢠The management of obstetric complications and the
long-term sequelae of premature birth should be
factored in when considering treatment costs.
14. Risk to baby
⢠Compared to a singleton, a twin is about five times more
likely to die in the first year of life.
⢠For a triplet, this risk is about 13 times that of a singleton.
⢠The risk of having a lifelong handicap (e.g., cerebral palsy,
mental retardation) is increased about 10 times for twins
compared to singles, and these risks are substantially higher
for triplets.
⢠Quadruplet and other high-order pregnancies are much
riskier.
⢠Fortunately, with current embryo transfer policies,
pregnancies beyond triplets are rare with IVF.
15. Why donât we perform elective single embryo transfer? A
qualitative study among IVF patients and professionals
Domain 1 Domain 2 Domain 3 Domain 4
Characteristics of eSET itself Characteristics of the professional Characteristics of the patient Characteristics of the context
Uncertainty about eSET technique Negative attitude towards eSET
Lack of knowledge of
patients Impeding reimbursement system
Complexity: complex situations that
Bad quality of doctorâpatient
relationship about essential eSET aspects Lack of legislation about eSET
impede eSET use Lack of knowledge and motivation Bad financial situation/social Impeding mentality of the society
No possibility to observe others that Doubts about consequences of full economic status Competition between hospitals
perform eSET implementation of eSET Strict religion Lack of continuity of care
Lack of objective results Lack of negative experience with twins Lack of responsibility for the
Media coverage about IVF and
twins
Lack of scientific fundament for
eSET Lack of sufficient communicating skills consequences of the choice Peer standards
Low cost-effectiveness Lack of responsibility eSET/DET Variation between hospitals
Technical barriers For the couple
Lack of willingness to
change Lack of leadership
Lack of prognostic models for
eSET For the unborn child Liberty of choice for couples Absence of protocol
Inferior cryopreservation success Difficulties to change routines Desire for twins
Bad performance publicly
available
rates Lack of time Level of profession
Type of practice: university
versus
Age general hospital
Gender
Place of education
Factors related to eSET use according to IVF professionals.
Human Reproduction Vol.23, No.9 pp. 2036â2042, 2008
16. Why donât we perform elective single embryo transfer? A qualitative
study among IVF patients and professionals
Domain 1 Domain 2 Domain 3 Domain 4
Characteristics of eSET itself Characteristics of the Characteristics of the patient Characteristics of the context
professional
Uncertainty about eSET technique
Negative attitude towards
eSET
Lack of knowledge of patients about
essential
Impeding reimbursement
system
Complexity: complex situations
that Bad quality of doctorâpatient eSET aspects
Lack of legislation about
eSET
impede eSET use relationship
Bad financial situation/social economic
status
Impeding mentality of the
society
Possibility to attempt eSET
without Lack of knowledge and Previous positive experiences with twins Logistic organisation of IVF
obligation to do it again motivation Health condition that impede eSET use treatment
Too much time investment
Lack of responsibility: for the
consequences
System of information
provision
necessary to perform eSET of the choice eSET/DET Results of clinic
Resistance to change Practice in foreign countries
Liberty of choice
Desire for twins
Focus only on chance for pregnancy
Losing track of personal boundaries
Anxiety for experiences of the first
treatment
cycle
Prognostic characteristics
Human Reproduction Vol.23, No.9 pp. 2036â2042, 2008
Factors related to eSET use according to patients.
18. ASRM
⢠The ASRM identifies the following characteristics as
being associated with a "more favorable prognosis":
⢠First cycle of IVF
⢠Good embryo quality by morphology grading criteria
⢠Excess embryos available for freezing
⢠Having a previous successful IVF cycle
19. Society for Assisted Reproductive Technology (SART) &
CDC data 2014
⢠These annual reports show the trend in the United States toward
transferring fewer embryos.
⢠In 1997, the average number of embryos transferred to women under 35
was 3.7 By 2000, it was down to 2.9
⢠Over the same time period, there was a significant increase in the overall
live birth rates for IVF procedures
⢠At the same time, the percentage of births that were triplets or more
dropped from about 14% to about 9%
⢠However, over the same period of time, no progress was made with
regard to reducing the rate of twin pregnancies, which remained at about
32% of births.
⢠Over that 4-year period, US IVF centers transferred less embryos,
resulting in higher success rates, a lower percentage of triplets, but no
change in the percentage of twins.
20. Cycles with single embryo transfer. Trends in the percentage of cycles
using elective single embryo transfer, United States from 2005 to 2013.
Society for Assisted Reproductive Technology (SART) &(CORS) database
21. USA vs european policy
⢠In general, European infertility clinics are transferring fewer
embryos as compared to American IVF centers. On average,
they have lower pregnancy rates and a lower percentage of
multiple births than clinics in the United States.
There are several factors involved in this difference. In some
European countries, physicians are restricted by law so that
they cannot transfer more than two embryos. Also, IVF is
more commonly paid for by insurance or socialized medical
systems in Europe.
22. Canadian fertility society-2010
⢠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)
23. Summary-canadian guidelines
⢠Although the Canadian ART higher order multiple
delivery rate has declined significantly in recent years
to 1.5% in 2006, the incidence of twins has remained
unchanged at approximately 30%.
⢠The evidence supports successful reduction in the
twin rate with eSETin appropriate patients with a
minimal reduction in the live birth rate.
⢠In order to promote the uptake of eSET, public
funding of IVF should therefore be provided.
24. Elective single embryo transfer (eSET) policy in
the ďŹrst three IVF/ICSI treatment cycles
⢠CONCLUSIONS: In patients younger than 38 years
with at least one top quality embryo, eSET can be
the transfer policy of choice in at least the ďŹrst three
treatment cycles, since the pregnancy rates obtained
in each treatment cycle are comparable to those
after DET
Human Reproduction Vol.20, No.2 pp.433â436, 2005
25. Economic evaluations of single- versus double-
embryo transfer in IVF
⢠Several databases were searched .A total of 496 titles were identified
through the searches and resulted in the selection of one observational
study and three randomized studies.
⢠It can be concluded that DET is the most expensive strategy.DET is also
most effective if performed in one fresh cycle.
⢠eSET is only preferred from a cost-effectiveness point of view when
performed in good prognosis patients and when frozen/thawed cycles are
included.
⢠If frozen/thawed cycles are excluded, the choice between eSET and DET
depends on how much society is willing to pay for one extra successful
pregnancy
Human Reproduction Update, Vol.13, No.1 pp. 5â13, 2007
26. Ryan GL, Sparks AE, Sipe CS, Syrop CH, Dokras A, Van Voorhis BJ.
A mandatory single blastocyst transfer policy with educational campaign
in a United States IVF program reduces multiple gestation rates without
sacrificing pregnancy rates. Fertil Steril. 2007;88(2):354â60.
Desired treatment outcome before and after education
27. Debating Elective Single Embryo Transfer after
IVF : A Plea for a Context-Sensitive Approach
⢠What a physician should do when confronted with a
patient's request which conflicts with medical
recommendations depends on the specificities of the
context in which patients and physicians are
implicated.
⢠The arguments brought forward in this article
pointed out that shared decision making is the
appropriate approach, which does justice to the
responsibilities that both patients and physicians have
in assisted reproduction.
Ann Med Health Sci Res. 2015 Jan-Feb; 5(1): 1â7.
28. Risks of spontaneously and IVF-conceived singleton and twin pregnancies
differ, requiring reassessment of statistical premises favoring elective single
embryo transfer (eSET)-review
Gleicher et al. Reproductive Biology and Endocrinology (2016) 14:25
29. Risks of spontaneously and IVF-conceived singleton and twin
pregnancies differ, requiring reassessment of statistical premises
favoring elective single embryo transfer (eSET)-review
Authors Year Study format Singletons Twins Comments
KällÊn et al [11] 2010 National X Significant increase in IVF of PTB (<32 weeks); No difference
in LBW
Pinborg et al [15] 2013 Review AOR 1.27, (95 % CI Even in same mother an IVF offspring has more PTB
1.08, 1,49) than non-IVF
Offspring
Sazonova et al [7] 2013 This study is only indirectly relevant to here reviewed subject but is listed because it is the only study, which correctly
compared in a large national population outcomes of twin pregnancies in comparison to two consecutive singleton
pregnancies. Unfortunately, as previously in detail reviewed by us, the authors misrepresented their data in discussing
their conclusions [9]. A correct analysis of their data demonstrated no clinically significant outcome differences in either
maternal or neonatal outcomes, with AORs listed in the reference. The study, however, did not comment on
differences between spontaneously- and IVF-conceived pregnancies.
Anbazahagan et al [12] 2014 MCPT no significant X No difference between IVF and spont. twins but small
difference size and prospective study
Henningsen et al [16] 2014 Scandinavian AOR 1.54 (95 % CI X IVF singletons had increased neonatal death risk. IVF
population study 1.28, 1.85) twins had lower risk, which was lost when restricted to
opposite-sex twins
Dar et al [13] 2014 Review and meta-analysis; Study does not comment on differences In outcomes between spontaneously and IVF-conceived
singletons and twins but demonstrates significantly increased PTB risk for blastocyststage embryo transfer in comparison to
cleavage-stage embryo transfer, a finding with relevance to here discussed topic since blastocyst-stage embryo transfer is a
prerequisite for eSET.
Declercq et al [17] 2015 Cohort AOR for PTB 1.23 Both AORs are in comparison to a subfertile patient
AOR for LBW 1.26 group: Risks of singletons among IVF patients and in a
sub-fertile patient group were, both, higher than in
normally fertile population.
Gleicher et al. Reproductive Biology and Endocrinology (2016) 14:25
30. Risks of spontaneously and IVF-conceived singleton and twin
pregnancies differ, requiring reassessment of statistical premises
favoring elective single embryo transfer (eSET)-review
⢠Conclusions
⢠Here presented data raise serious questions about the rapidly expanding
IVF practice of prolonged embryo culture to blastocyst stage, followed by
eSET. Since it is undisputed that eSET reduces clinical pregnancy chances
in IVF when compared to two-embryo transfers . proponents of eSET
consider such reductions in pregnancy potential appropriately
compensated by decreased maternal and especially neonatal risks from
avoided twin pregnancies. 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.
⢠Â
Gleicher et al. Reproductive Biology and Endocrinology (2016) 14:25
31. Risks of spontaneously and IVF-conceived singleton and twin
pregnancies differ, requiring reassessment of statistical premises
favoring elective single embryo transfer (eSET)-review
⢠ConclusionsÂ
⢠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.
Gleicher et al. Reproductive Biology and Endocrinology (2016) 14:25
32. Elective single embryo transfer- the power of one
Contraception and Reproductive Medicine 2016 1:11
⢠Advancement in embryo cryopreservation, extended embryo culture with
blastocyst selection, and preimplantation genetic screening has facilitated
the expansion of elective single embryo without compromising outcomes.
⢠Mandated infertility coverage in Europe, Canada and selected states have
resulted in increased eSET utilization and decreased costs associated with
ART.
⢠Moving forward, reproductive medicine should aim for the gold standard
IVF outcome to be a singleton term live birth pregnancy with eSET.
⢠When the goal is to minimize IVF complications, multiple embryo transfer
does not necessarily translate to a superior outcome.
⢠The future success of ART lies in elective single transfer, the power of
one.
33. Summary
⢠Elective single embryo transfer should be encouraged to
decrease the incidence of twin pregnancy and the associated
complications.
⢠The extra cost associated with achieving an equal number of
pregnancies through elective single embryo transfer needs to
be considered in the context of any additional neonatal care
expenses associated with double embryo transfer.
⢠Maternal age, previous attempts, day of embryo transfer and
cost should be taken into account.
34. Take Home Message
All IVF centres must try to reduce the numbers of
multiple births without compromising on the success
rate for that individual couple
These annual reports show the trend in the United States toward transferring fewer embryos.
In 1997, the average number of embryos transferred to women under 35 was 3.7
By 2000, it was down to 2.9
Over the same time period, there was a significant increase in the overall live birth rates for IVF procedures
At the same time, the percentage of births that were triplets or more dropped from about 14% to about 9%
However, over the same period of time, no progress was made with regard to reducing the rate of twin pregnancies, which remained at about 32% of births.
Over that 4-year period, US IVF centers transferred less embryos, resulting in higher success rates, a lower percentage of triplets, but no change in the percentage of twins.
What a physician should do when confronted with a patient&apos;s request which conflicts with medical recommendations depends on the specificities of the context in which patients and physicians are implicated. The arguments brought forward in this article pointed out that shared decision making is the appropriate approach, which does justice to the responsibilities that both patients and physicians have in assisted reproduction. But shared decision-making is just a procedural approach, and the quality of the eventual decision that is reached may be very different from context to context.
The past three decades have seen the emergence of IVF as the gold standard treatment for infertility. The era of low live birth rates and the routine practice of multiple embryo transfer are a thing of the past. Advancement in embryo cryopreservation, extended embryo culture with blastocyst selection, and preimplantation genetic screening has facilitated the expansion of elective single embryo without compromising outcomes. Mandated infertility coverage in Europe, Canada and selected states have resulted in increased eSET utilization and decreased costs associated with ART. Moving forward, reproductive medicine should aim for the gold standard IVF outcome to be a singleton term live birth pregnancy with eSET. When the goal is to minimize IVF complications, multiple embryo transfer does not necessarily translate to a superior outcome. The future success of ART lies in elective single transfer, the power of one.