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The increased mortality after

ART: the egg or the hen?

Arne Sunde, PhD

Head, Fertility Clinic St.Olavs University HospitalProfessor, Norwegian Institute for Science and Technology

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Nordic ART registries

Similar structure:

ProfessionGovernmental

Body(ies)

ART registry

Mandatory report

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Nordic registries

Similar structure:

ProfessionGovernmental

Body (ies)

ART registry Birth registry

Cancer

registry

Hospital

discharge

Registry

Infant

registry

Mandatory report

Malformations

registry

Coupling trough a unique

personal number

given at birth

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Number of IVF/ICSI and FER cycles

per year in the Nordic countries

0

5 000

10 000

15 000

20 000

25 000

30 000

35 000

40 000

45 000

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

FER

IVF/ICSI

~ 40 000 cycles, ~25 million inhabitants: ~1600 cycles per million annually

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Children after ART

The major cause of:

increased premature births, increased mortality rate,

increased malformation rate

is the high multiple pregnancy rate

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Twins after IVF and ICSI

Nordic countries 1997 -2005

0

5

10

15

20

25

30

35

1997 2001 2002 2003 2004 2005

Denmark

Finland

Iceland

Norway

Sweden

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Question

The total cost of pregnancy care,delivery and neonatal care (1st week)for twins is approximately:

1 Similar to that of singletons

2) Twice as much as that of singletons

3) Four times as much as that of singletons 4) Six times as much as that of singletons

5) Ten times as much as that of singletons

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Question

The total cost of pregnancy care, delivery and

neonatal care (1st week) for triplets is

approximately:

1 Twice as much as that of singletons

2) Four times as much as that of singletons

3) Similar to that of twins

4) Ten times as much as that of singletons

5) Twenty times as much as that of singletons

5) Thirty times as much as that of singletons

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Proportion of single embryo transfers

Fresh embryos

St. Olavs University hospital in Trondheim

9 1011

54

75

84 8487

0

10

20

30

40

50

60

70

80

90

100

2001 2002 2003 2004 2005 2006 2007 2008

%

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Multiple pregnancy rate all transfers

(FER/IVF/ICSI)

St-Olavs University hospital in Trondheim

3032

36

17

85 4

2

0

5

10

15

20

25

30

35

40

2001 2002 2003 2004 2005 2006 2007 2008

IVF/ICSI

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Question

Concerning the neonatal mortality rate oftwins:

1) it is the same as that of singletons

2) it is two times as high as that of singletons

3) it is three times as high as that of singletons

4) I it is four times as high as that of singletons

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ART - Children

Outcome can be compiled form variousregistries

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Question

Concerning the neonatal mortality rate ofsingletons born after ART:

1) it is the same as spontaneously conceived

singletons

2) it is higher than spontaneously conceivedsingletons

3) it is lower than spontaneously conceivedsingletons

4) I dont know

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Swedish ART children, deaths

Klln et al. Fertil Steril 84:605 2005

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ART-singletons

Seems to be doing worse than spontaneously

conceived singletons

We initiated a line of research trying to find

out whether this was due to

The ART-Technology (The egg)

Maternal factors (The hen)

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The Norwegian Birth registry

All ART cycles reported (mandatory)

All ART pregnancies registered at week 16(mandatory)

The ART registry coupled to the general birthregistry

Information on outcome of pregnancies andbirths can be extracted and compared

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1st Trondheim study

births in the period 1988-2002

Two singletons from

the same mother

One spontaneousconception

One IVF/ICSI

1349 women

2698 children/births

Romundstad et al. Human Reproduction, 21, No.9, 23532358, 2006

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1st Trondheim study birthsin the period 1988-2002

Two singletons from the same mother Adjusted Odds ratio for placenta preavia:

Spontaneous conception ART OR OR (95% CI) 1.0 2,9 (1.46.1)

i.e. ART itself seems to increase the risk ofplacenta praevia. Its not the mother

Romundstad et al. Human Reproduction, 21, No.9, 23532358, 2006

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2nd study births in the period

1984-2006

Singletons

1 200 922 spontaneous conceptions inthe general population

8 229 following IVF/ICSI

Romundstad et al. The Lancet, online July 31, 2008

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2nd study births in the period

1984-2006

Singletons: Spontaneous conception in the general population

versus

conceptions after ART

Spontaneous ART

OR OR (95% CI)

SGA 1 1,3 (1.1-1,4)

Birth < 37 weeks 1 1,7 (1.6-1.9)

Perinatal death 1 1.3 (1.1-1.7)

Romundstad et al. The Lancet, online July 31, 2008

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2nd study births in the period

1984-2006

Two singletons from

the same mother

One spontaneousconception

One IVF/ICSI

2204 women

4408 children/births

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2. Trondheim study 1984-2006

Singletons Same mother,

one ART versus

one Spontaneous

Spontaneous ART

OR OR (95% CI)

SGA 1 1,0 (0,6-1,6)

Birth < 37 weeks 1 1,2 (0,9-1,6) Perinatal death 1 0,4 (0,2-0,7)

Romundstad et al. The Lancet, on line July 31, 2008

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Conclusion

The hen or the egg?

Concerning placenta praevia: The egg (ART)

Concerning, SGA and premature birth,perinatal death :

The hen (mother/infertility)

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Thank you