The increased mortality after

ART: the egg or the hen?

Arne Sunde, PhD

Head, Fertility Clinic St.Olav’s University Hospital

Professor, Norwegian Institute for Science and Technology
 Nordic ART registries
• Similar structure:
Governmental
Profession Mandatory report
Body(ies)

ART registry
 Nordic registries
• Similar structure:
Governmental
Profession Mandatory report
Body (ies)

Coupling trough a unique

ART registry Birth registry
personal number
given at birth

Hospital
Infant Cancer Malformations
discharge
registry registry registry
Registry
Number of IVF/ICSI and FER cycles
per year in the Nordic countries
45 000
40 000
35 000
30 000
25 000 FER
20 000 IVF/ICSI
15 000
10 000
5 000
0
1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2003

2004

2005

2006
2002

~ 40 000 cycles, ~25 million inhabitants: ~1600 cycles per million annually
 Children after ART
• The major cause of:

– increased premature births,

– increased mortality rate,
– increased malformation rate

• is the high multiple pregnancy rate

 Twins after IVF and ICSI
Nordic countries 1997 -2005
35

30

25 Denmark
20 Finland
Iceland
15 Norway
10 Sweden

0
1997 2001 2002 2003 2004 2005
 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
 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
 Proportion of single embryo transfers
Fresh embryos
St. Olav’s University hospital in Trondheim
100
90 84 84 87
80 75
70
60 54
%

50
40
30
20 11
9 10
10
0
2001 2002 2003 2004 2005 2006 2007 2008
 Multiple pregnancy rate all transfers
(FER/IVF/ICSI)
St-Olav’s University hospital in Trondheim
40
36
35 32
30
30
25
20 17
15
10 8
5 4
5 2
0
2001 2002 2003 2004 2005 2006 2007 2008

IVF/ICSI
 Question
• Concerning the neonatal mortality rate of
twins:

– 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

 ART - Children

• Outcome can be compiled form various

registries
 Question
• Concerning the neonatal mortality rate of
singletons born after ART:

– 1) it is the same as spontaneously conceived

singletons

– 2) it is higher than spontaneously conceived

singletons

– 3) it is lower than spontaneously conceived

singletons

– 4) I don’t know
Swedish ART children, deaths
Källén et al. Fertil Steril 84:605 2005
 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)

 The Norwegian Birth registry

• All ART cycles reported (mandatory)

• All ART pregnancies registered at week 16

(mandatory)

• The ART registry coupled to the general birth

registry

• Information on outcome of pregnancies and

births can be extracted and compared
 1st Trondheim study
births in the period 1988-2002
• Two singletons from
the same mother

• One spontaneous
conception
• One IVF/ICSI

• 1349 women
• 2698 children/births
Romundstad et al. Human Reproduction, 21, No.9, 2353–2358, 2006
1st Trondheim study births
in 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 (1.4–6.1)

• i.e. ART itself seems to increase the risk of

placenta praevia. It’s not the mother

Romundstad et al. Human Reproduction, 21, No.9, 2353–2358, 2006

 2nd study births in the period
1984-2006
• Singletons

• 1 200 922 spontaneous conceptions in

the general population

• 8 229 following IVF/ICSI

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

 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

 2nd study births in the period
1984-2006
• Two singletons from
the same mother

• One spontaneous
conception
• One IVF/ICSI

• 2204 women
• 4408 children/births
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

 Conclusion
• The hen or the egg?

• Concerning placenta praevia:

– The egg (ART)

• Concerning, SGA and premature birth,

perinatal death :
– The hen (mother/infertility)
•Thank you