ELECTIVE SINGLE EMBRYO TRANSFER

WHY, WHEN AND HOWDR FESEENA KUNJIMOIDEEN

BDS,MCE(LEEDS,UK)

ARMC IVF Kozhikode

Moulana IVF, Perintalmanna

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)

WHY SET?

• MATERNAL COMPLICATIONS OF MULTIPLE GESTATION• FETAL AND NEONATAL COMPLICATIONS OF MULTIPLE GESTATION.• PSYCHOLOGICAL IMPACT• COST FACTOR

MATERNAL COMPLICATIONS OF MULTIPLE PREGNANCY

MATERNAL MORTALITY• Pulmonary edema in association with parenteral beta-mimetics tocolysis•Eclampsia•Excessive blood loss

MATERNAL COMPLICATIONS(CONTD)

MATERNAL MORBIDITYHypertension (10-20% in twins, 25- 60 % in triplets)ThromboembolismPreterm labour Gestational length inversely related to number of fetusesAnaemia 22 % incidence in multiple when compared to singletonVaginal-Uterine haemorrhageFluid overloadPulmonary edema with parental tocolysis

COMPLICATIONS OF MULTIPLE PREGNANCY

Higher chances for CS when compared to single pregnancy

Complications in CS compared to vaginal delivery InfectionsHaemorrhageThromboembolic diseasesEndometritis.

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)

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%)

CONGENITAL MALFORMATIONS COMMONLY ASSOCIATED WITH MULTIPLE GESTATION

• Cardiac defects• Neural tube and brain defects.• Facial clefts• Gastrointestinal and anterior abdominal wall defects

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

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

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)

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

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.

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 breakdown42-44 post insemination:• Number of blastomeres be equal to or greater than 4• Fragmentation of less than 20%• No multinucleated blastomeres

66-68 hours post insemination:• Number of blastomeres be greater or equal to 8• Fragmentation of less than 20%• No multinucleated blastomeres106-108 hours postinsemination:• The blastocoel cavity be full• Inner cell mass be numerous and tightly packed• Trophectodermal cells be numerous and cohesive .

GRADUATED EMBRYO SCORE (GES) JD FISCH etal

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

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.

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)

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 .

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.