Tvillinger og Single Embryo Transfer

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THE VANISHING TWIN


Anja Pinborg, MD Fertility Clinic, Copenhagen
University, Rigshospitalet, Denmark
2
CONTENT

• Definition
• Outcome of IVF/ICSI singletons
• Vanishing twins in ART
• Danish cohort study on vanishing ART twins

3
DEFINITION
Disappearance of one of two gestational sacs or
embryos after documented foetal activity is known
as the vanishing twin phenomenon. It occurs in
relation to foeti papyracei, but twin material
can also be reabsorbed without leaving any trace
(Stoeckel 1945 Landy and Keith 1982)
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1955
2005


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Percentage of ART infants 1997 to 2002
2002 2001 2000 1999 1998 1997 Denmark
4.1 3.9 3.7 3.2 3.0 2.6 Slovenia
3.6 3.3 3.0 - - Iceland
3.0 2.7 2.8 3.6 3.8 3.5 Sweden
2.8 2.8 2.5 2.6 2.4 2.3 Finland
2.6 2.4 2.5 2.7 2.8 2.6 Norway
2.3 2.2 1.6 1.8 1.7 1.3 Germany
2.0 Hungary 1.9 1.7 UK
1.3 1.1 1.1 - 1.1 1.0 (Nyboe Andersen et
al., EIM data)


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WHAT ABOUT IVF SINGLETONS ?


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META-ANALYSES
Helmerhorst Jackson RR (95CI) Br Med J,
2004 Am J Obs Gyn, 2004
No 5.361 12.283 lt2500 g 1.7
(1.5-1.9) 1.8 (1.4-2.2) lt1500 g 3.0
(2.1-4.4) 2.7 (2.3-3.1) lt37 weeks 2.0
(1.8-2.3) 2.0 (1.7-2.2) lt32 weeks 3.3
(2.0-5.3) - SGA 1.4 (1.2-1.7) 1.6
(1.3-2.0) Mortality 1.7 (1.1-2.6) 2.2
(1.6-3.0)


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CEREBRAL PALSY Scandinavian registerbased
cohort studies
n period RR Strömberg, Lancet
2002 3183 1982-1995 2.8 (1.3-5.8)Lidegaard,
HR 2005 6052 1995-2001 1.8 (1.2-2.8)


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WHY ?

• IVF/ICSI techniques
• Infertility per se
• Number of gestational sacs

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SPONTANEOUS REDUCTION (SR) IN ART (Dickey RP et
al., AJOG 2002 HR Debate 2004)

• 15 of singleton began as higher order gestations
• After SR (2?1) the average gestational length of
  a singleton birth was shortened by 3 days
• Trend of lower birth weight in SR singletons
• IVF singletons without SR had no increased risk
  of preterm birth compared with spontaneous
  singletons

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THE VANISHING TWIN IN ART

• 6.377 IVF singletons were more likely to have low
  birth weight in pregnancies, if more than one
  foetal heart was present at early UL
• (Schieve, NEJM, 2002, 346, 731-37)
• Increasing no of gestational sacs in early
  pregnancy was associated with a higher risk of
  preterm birth in singleton pregnancies
• (Lancaster, ESHRE, O-245, 2004)

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THE VANISHING TWIN IN ART

• Vanishing embryo syndrome
• Hvidtjørn, Hum Reprod 2005
• 9.444 IVF children and 395.025 non-IVF children
• The risk of cerebral palsy was higher in
  pregnancies, where the number of gestations at
  delivery was less than the number of embryos
  originally transferred
• Cox regression HRR 2.3 (95 CI 1.0-5.3)

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VANISHING TWINS in ART Danish cohort
study Pinborg A, Lidegaard O, la Cour Freiesleben
N, Nyboe Andersen A (HR 2005, 20, 2821-29)


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METHODS

• Retrospective Danish cohort study 1995-2001
• Multi-centre study (11 fertility clinics)
• 72 of all IVF/ICSI cycles in Denmark
• Singleton and twin pregnancies 8.weeks
• The Medical Birth Registry and The National
  Patient Registry

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INCLUSION CRITERIA
Ultrasound 8 weeks gestation A. One viable
foetus one without heart beat/empty gestational
sac B. One viable foetus C. Two viable foetuses


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VANISHING TWINSChildren (n 9557)
Survivors n 642
Singletons n 5237
Twins n 3678
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VANISHING TWIN Survivor cohort

• Early (lt8.weeks) 424 (66)
• Intermediate (gt8.weeks) 187 (29)
• Late (stillborn) 31 (5)
• Total 642 (100)

Singleton survivors 10.4 (611/5848)
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VANISHING TWINSObstetric outcome


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VANISHING TWINS Results
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Singletons vs. survivors
Outcome OR (95CI) BW lt2500g 1.7 (1.2
2.2) BW lt1500g 2.1 (1.3 3.6) GAlt37 weeks 1.3
(1.0 1.7) GAlt32 weeks 2.3 (1.4 4.0) Neu.
sequelae 0.8 (0.4 1.6) Cerebral palsy 1.9 (0.7
5.2)
(OR adjusted for age, parity and treatment
method)
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VANISHING TWINSTime of vanish
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VANISHING TWINSNeurological sequelae


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Neurological sequelae

Early
Intermediate Late (lt8 wks) (gt8
wks) (stillborn Spearman co-twin) correlatio
n (N424) (N187) (N31) (r)
P No. (per 1000) Cerebral palsy 3 (7.1)
2 (10.7) 0 -0.008 0.85 Neurological sequelae 4
(9.4) 5 (26.7) 2 (64.5) -0.09
0.022 All neurological diagnoses 14 (33.0) 15
(80.2) 3 (96.8) -0.109 0.006  Spearman
correlation coefficient (r) for ordinal data
 
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SUMMARY

• 10.4 prevalence among IVF/ICSI singletons
• Poorer perinatal outcome
• Poor perinatal outcome was inversely correlated
  to gestational age at onset of spontaneous
  reduction
• The risk of cerebral palsy was 2-fold increased

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VANISHING TWINS- another argument for eSET
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Number of embryos transferred - IVF and ICSI ()

• 2002 2001 2000 1999 1998 1997
• 1 13.4 11.9 12.1 12.0 11.5 11.5
• 2 56.4 51.6 46.8 40.1 37.2 35.7
• 3 26.9 30.9 33.2 39.0 42.0 38.4
• 3.3 5.6 6.7 8.9 9.4 14.2
• (Nyboe Andersen et al., EIM data)

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CONCLUSIONEIM data 2002

• The first sign of eSET detectable in 2002
• One or two embryos in 70 of all transfers
• Maintaining overall pregnancy rates

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PERSPECTIVE

• The goal is one healthy child
• Strict eSET selection criteria
• Twin birth rate ?10

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FINE
30


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Availability EIM 2002No. of cycles per 106
inhabitants
2002 2001 2000 1999 1998 1997
Denmark 2106 1923 1826 1659 1608 1448 Finland 14
63 1486 1440 1407 1528 1538 Slovenia 1291 1122 11
99 - - - Iceland 1243 1410 1020 1383 1540 1422 Sw
eden 1241 1133 1034 973 747 952 Netherlands 1007
963 966 915 889 897 Norway 921 983 986 915 822 81
1 Switzerland 753 - - - - - Hungary 671 578 - - -
- UK 625 593 585 - 595 583 Croatia 589 - - - -
-


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THE VANISHING TWIN IN ART

• Dickey RP, AJOG 2002
• Pregnancy duration and birth weight was
  inversely related to the initial number of
  gestational sacs in 5962 ART singletons and 709
  ART twins irrespective of the final birth number
• Dickey RP, HR debate 2004
• 15 of IVF singleton births began as higher
  order gestations and to a large part this could
  explain the increased risk of preterm birth

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DEATH OF A CO-TWIN

• Petterson B, BMJ 1993
• Survivors 1 year 96.2/1000
• Live born twins 6.4/1000
• Live born singletons 1.6/1000
• Intrauterine death of a co-twin is associated
  with a 10 greater risk of cerebral palsy
• Pharoah and Adi, Lancet 2000
• The risk of cerebral impairment of the live-born
  co-twin of a fetus that died in utero 20 (95
  CI 16-25)
• Pharoah and Cooke, Dev Med Child Neu 1997
• A hypothesis for the aetiology of cerebral
  palsy the vanishing twin

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Scandinavian multicentre randomized controlled
trialThurin et al., 2005, NEJM, 351, 2392-2402

• eSET DET P-value
• No. of patients 330 331
• OPR 38.8 42.9 0.3
• Twin birth rate 0.8 33.1 lt0.001
• Female age lt36 years
• 1. or 2. IVF/ICSI cycle
• gt2 high quality embryos

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ResultsCopenhagen University Hospital,
Rigshospitalet 2005

• 48 of SET cycles (30 eSET)
• OPR per started cycle 28.1
• Positive HCG per transfer 50
• Twin birth rate lt10