This document discusses elective single embryo transfer (eSET), which is defined as transferring one embryo when at least two top quality embryos are available to avoid complications of multiple pregnancies. eSET is recommended for patients under 38 with at least one high-quality embryo to reduce maternal and fetal risks of multiple pregnancies while maintaining pregnancy rates. The document outlines maternal and fetal risks of multiple pregnancies and strategies for selecting the highest quality embryo for transfer based on developmental benchmarks.
2. DEFINITION
Elective Single Embryo Transfer is defined as the transfer of only one
embryo when atleast 2 top quality embryos are available ,to avoid the
complications of multiple pregnancy.
(Norian etal,2009)
3. WHY SET?
• MATERNAL COMPLICATIONS OF MULTIPLE GESTATION
• FETAL AND NEONATAL COMPLICATIONS OF MULTIPLE GESTATION.
• PSYCHOLOGICAL IMPACT
• COST FACTOR
4. MATERNAL COMPLICATIONS OF MULTIPLE
PREGNANCY
MATERNAL MORTALITY
• Pulmonary edema in association with parenteral beta-mimetics
tocolysis
•Eclampsia
•Excessive blood loss
5. MATERNAL COMPLICATIONS(CONTD)
MATERNAL MORBIDITY
Hypertension
(10-20% in twins, 25- 60 % in triplets)
Thromboembolism
Preterm labour
Gestational length inversely related to number of fetuses
Anaemia
22 % incidence in multiple when compared to singleton
Vaginal-Uterine haemorrhage
Fluid overload
Pulmonary edema with parental tocolysis
6. COMPLICATIONS OF MULTIPLE PREGNANCY
Higher chances for CS when compared to single pregnancy
Complications in CS compared to vaginal delivery
Infections
Haemorrhage
Thromboembolic diseases
Endometritis.
7. FETAL AND NEONATAL COMPLICATIONS IN
MULTIPLE BIRTHS
• Stillbirths, early and late neonatal mortality, infant mortality higher in
multiple pregnancies.(~ 5times for twins and 10 times for triplets )
• Preterm delivery (54% of twins preterm compared to 9.6 % for
singletons).Generally, gestational age 3 weeks less for every additional
fetus.
• Low birth weight(Average triplet weighed about half of the average
singleton at birth).
Infants born as multiples comprise only 3 % of all live births but they
comprise 13 % of the preterm babies,15 % of the early preterm babies,
21% of the LBW babies and 25% of the VLBW babies (Martin etal)
8. NEONATAL MORBIDITY ASSOCIATED WITH LBW
• Birth Asphyxia
• Intraventricular haemorrhage (11.4 % more in twins)
• Sepsis (7.6 %)
• Necrotising enterocollitis (9.9%)
• Respiratory distress syndrome(13.8%)
9. CONGENITAL MALFORMATIONS COMMONLY
ASSOCIATED WITH MULTIPLE GESTATION
• Cardiac defects
• Neural tube and brain defects.
• Facial clefts
• Gastrointestinal and anterior abdominal wall defects
10. FOETOFOETAL TRANSFUSION SYNDROME
• Occurs in multifoetal pregnancy in which vascular anastomosis
between 2 monochorionic foetuses allow shunting of blood from one
(donor) to the other foetus(recipient), resulting in severe
oligohydramniosis in the donor and polyhydramniosis in the recipient.
• Discordance in size with larger twin in polyhydromniotic sac.
• Mortality is high even with treatment (40-60%)
• High chance of neurologic impact in surviving foetus
11. PROBLEMS ASSOCIATED WITH MULTIPLE
PREGNANCY(CONTD)
• Handicap incidence rates increased
3.7 % increase in twins and 8.7 % in triplets
• Cerebral Paresis(CP) increases with plurality of the foetus
• Mental retardation
• Neurologic and visual impairment
• Psychological impacts on children themselves,siblings and parents
12. EVIDENCES
Titinen etal 2003,
• e-SET done if on day 2,atleast 2 top quality embryos were available
• Concluded that if applying SET to about 1/3 of total patients ,possible
to half the multiple pregnancy without reducing ongoing pregnancy
rate.
Even if the number of embryos transferred is restricted to 2, twinning
rate can exceed 40 % of pregnancy(Catt J etal)
13. WHEN
Strandell etal
1.Female patient younger than 35-37 years
2.In 1st
and 2nd
IVF/ICSI cycles
3.Number of top quality embryos available should be 2 or more .
4.Absence of tubal factor infertility
14.
15. A STRATEGY FOR SELECTING THE BEST EMBRYO
18-19 hours post ICSI:
The pronuclei are examined for
• Symmetry, greater blastocyst development and implantation when
the numbers and alignment of NPB are symmetrical.
• Presence of even number of nucleolar precursor bodies(NPB)
• Number of NPBs in both pronuclei never differ by more than three
• NPBs polarized or nonpolarized in both pronuclei but never polarized
in one pronucleus and not in the other
• The angle from the axis of the pronuclei and the furthest polar body
be less than 50 degree.
16. STRATEGY (CONTD)
25-26 hours postinsemination or post ICSI:
• Embryos that have already cleaved to the 2 cell stage
• Zygotes that have progressed to nuclear membrane breakdown
42-44 post insemination:
• Number of blastomeres be equal to or greater than 4
• Fragmentation of less than 20%
• No multinucleated blastomeres
17. 66-68 hours post insemination:
• Number of blastomeres be greater or equal to 8
• Fragmentation of less than 20%
• No multinucleated blastomeres
106-108 hours postinsemination:
• The blastocoel cavity be full
• Inner cell mass be numerous and tightly packed
• Trophectodermal cells be numerous and cohesive .
20. BLASTOCYST TRANSFER
• Facilitates the natural selection of the best embryo.
• Increase implantation rate and reduces multiple birth
• Require good culture conditions in the lab.
• May end up in no ETs
21. STUDIES ON SINGLE BLASTOCYST
TRANSFER
• Gardner etal conducted a prospective study on a group of 48 selected
patients and concluded that the transfer of a single blastocyst
resulted in an implantation and ongoing pregnancy rate of 60.9 %
with no twins while transfer of 2 blastocysts resulted in implantation
rate of 56%, ongoing pregnancy rate of 76% but with a 47.4 %
incidence of twins.
22. NONINVASIVE ASSESSMENT OF EMBRYOS
• Microfluorimetry uses conventional biochemical assays.
Blastocysts with high glucose uptake and reduced lactate production
are found to have more viability and implantation potential
(Vanderbergh etal, lane and gardner)
• Measuring preimplantation embryo physiology using self-referencing
probe to measure the movement of ions and molecules between cell
and the surrounding media.(Trimarchi JR etal)
23. GLOBAL VARIATION IN THE UPTAKE OF SET
• Most countries show a gradual increase in SET cycles
• Sweden is the country performing maximum SET cycles(69.4%)
followed by Finland(49.7%), Belgium (48%), Denmark (32.6%).
• Reasons favouring SET uptake globally
Access to public funding
Legislation .
24.
25. CONCLUSION
• In patients younger than 38 years with atleast 1 top quality embryo, e SET can be
the transfer policy of choice in at least 3 treatment cycles, since the pregnancy
rates obtained in each treatment cycle are comparable to those after DET.( Land
JA etal).
• Fresh SET and a subsequent transfer of a single frozen thawed embryo in failed
cases clearly improves the cumulative pregnancy rate (per oocyte retrieval)
(Martikainen etal)
• Utilization of technological improvements like Time lapse monitoring allows
continuous ,non-invasive embryo monitoring without removing them from
optimal culture conditions.
• Degree of SET performed at a centre is the best indicator of the performance of
that centre
• In the future,SET is going to be more acceptable as both patients and society
realize the risk of multiple pregnancy.