Assisted Reproductive Technology (ART) in Europe, 2004. Results generated from European registers by ESHRE ESHREs European IVF Monitoring (EIM) A consortium.

Assisted Reproductive Technology (ART) in Europe, 2004. Results generated from European registers by ESHRE

ESHRE’s European IVF Monitoring (EIM)

A consortium of representatives for National Registers

Karl G. Nygren, Chairman

Anders Nyboe Andersen, Co-ordinator

Luca Gianaroli, Ricardo Felberbaum and Jacques de Mouzon, members

Veerle Goossens, ESHRE Central Office

ESHRE’s publication European IVF Monitoring 1997 -

• Assisted Reproductive Technology in Europe, 1997, 1998, 1999, 2000, 2001, 2002.

• Published in Hum. Reprod. 2001 – 2007.

• Last publication.• Assisted reproductive technology in Europe, 2003. Results generated from

European registers by ESHRE (2007) A.Nyboe Andersen, V.Goossens, L.Gianaroli, R.Felberbaum, J.de Mouzon and K.G.Nygren. Hum. Reprod., 22, 1513-1525

The European IVF Monitoring (EIM)

The EIM is basically a summary of data from

already existing National Registers.

Contain data on• Quantity, including ”availability”

• Efficacy

• Quality

• Risks

• Trends

EIM

Why?

Should we summarise data that are so different?

It should be stressed that data should be looked at from individual countries and compared between

countries, rather than concluding that

“In Europe ART ……”

EIM 2004. Basis for data collection

• Data from already existing national registers (n=15)

Austria, Belgium, Denmark, Finland, France, Germany, Hungary, Iceland, Ireland, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom.

• Data collection for the EIM (n=14)

Albania, Bulgaria, Greece, Italy, Latvia, Lithuania, Macedonia,, Poland, Russia, Serbia / Montenegro, Slovenia, Switzerland, Turkey, Ukraine.

Quantity and availability

29 countries in 2004

Albania Iceland Russia

Austria Ireland Serbia / Montenegro

Belgium Italy Slovenia

Bulgaria Latvia Spain

Denmark Lithuania Sweden

Finland Macedonia Switzerland

France Netherlands Turkey

Germany Norway UK

Greece Poland Ukraine

Hungary Portugal

No data from the Czech Republic, Croatia, and Slovakia

New countries 2004: Albania and Turkey

Proportion of clinics reporting to the EIM, 2004

• All Clinics (n=14)

Austria, Belgium, Denmark, Finland, France, Germany, Iceland, Macedonia, Netherlands, Norway, Slovenia, Sweden, Switzerland, United Kingdom

• Proportion of clinics (n=15)

Albania, Bulgaria, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Poland, Portugal, Russia, Serbia / Montenegro, Spain, Turkey, Ukraine,

EIM, 1997 - 2004

Countries Cycles % Increase

1997 18 203 225

1998 18 232 225 + 14

1999 21 249 624 + 10

2000 22 275 187 + 10

2001 23 289 690 + 5

2002 25 324 238 + 12

2003 28 365 103 + 13

2004 29 370 963 + 2

Countries with > 10 000 cycles 2004

2004 2003 2002 2001 2000

France 69746 60 681 59 296 35 598 56 754

Germany 60425 102 426 84 819 71 752 63 005

Spain 40956 17 011 15 030 13 720 14 519

UK 40101 37 348 37 083 35 012 34 634

Italy 26099 25 877 18 948 18 673 19 835

Belgium 20426 15 594 12 827 12 558 11 829

Netherlands 15366 17 649 16 273 15 335 15 062

Russia 14838 10 819 8 667 7 665 6 363

Sweden 12871 11 736 11 081 10 082 9 205

Denmark 11518 10 893 11 321 10 305 9 682

Reduction in oocyte aspirations after change in ART re-imbursements in Germany, 2004

Treatment cycles 2004

IVF 114 512 ↓

ICSI 166 711 ↑

FER 71 997 ↑ (26% of fresh)

OD 10 334 ↑

PGD 2 051 ↑

2004 IVF / ICSI: 41.0 vs 59.0 %

2003 IVF / ICSI: 45.0 vs 55.0 %

2002 IVF / ICSI: 47.6 vs 52.4 %

2001 IVF / ICSI: 51.8 vs 48.2 %

2000 IVF / ICSI: 55.9 vs 44.1 %

1999 IVF / ICSI: 56,6 vs 43,4 %

Availability. Number of cycles per 1 mill inhabitants

2004 2003 2002 2001 2000 1999 1998 1997

Austria 584 597 - - - - - -

Belgium 1974 1462 1241 1177 - - - -

Denmark 2128 2008 2106 1923 1830 1659 1608 1448

Finland 1747 1421 1463 1538 1446 1407 1528 1538

France 1154 978 993 - 961 882 795 780

Germany 803 1243 - - - - - -

Iceland 1208 1378 1224 1190 1300 1383 1540 1422

Macedonia 252 186 - - - - - -

Netherlands 942 1086 1008 955 946 915 889 897

Norway 1329 1169 921 975 971 915 822 811

Slovenia 1338 1365 1291 1119 - - - -

Sweden 1432 1320 1241 1133 1038 973 947 952

Switzerland 767 769 738 679 644 586 563 472

UK 665 623 625 591 580 - 595 583

Availability. Number of cycles per 1 mill inhabitants (2004)

0

500

1000

1500

2000

Austri

a

Belgiu

m

Denm

ark

Finla

nd

Franc

e

Ger

man

y

Icela

nd

Mac

edon

ia

Nethe

rland

s

Norway

Sloven

ia

Sweden

Switzer

land

UK

Percentage of infants born after ART, 1997 to 2004

2004 2003 2002 2001 2000 1999 1998 1997

Austria 0.4 - - - - - - -Belgium 2.4 1* 2.1 1.5 - - - -Denmark 4.2 3.9 4.2 3.9 3.7 3.2 3.0 2.6Finland 2.9 3.2 2.9 2.4 2.3 2.7 2.8 2.4France 1.7 1.5 1.5 - 1.4 1.4 1.3 1.2Germany 1.6 2.6 - - - - - -Iceland 2.0 2.0 2.9 2.8 3.8 3.6 3.8 3.5 Macedonia 0.3 0.2 - - - - - -Netherlands - - - - - - - -Norway 2.8 2.5 2.4 2.2 2.1 1.8 1.7 1.3 Slovenia 3.4 2.9 3.5 3.2 3.0 - - -Sweden 2.9 2.9 2.8 2.8 2.5 2.6 2.4 2.3Switzerland 1.4 1.5 1.4 1.0 1.0 0.7 0.5 -UK 1.6 1.5 1.4 1.1 1.1 - 1.1 1.0* Belgium: underestimation due to substantial ”loss of follow-up”

Percentage of infants born after ART (2004)

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

5

Austri

a

Belgiu

m

Denm

ark

Finla

nd

Franc

e

Ger

man

y

Icela

nd

Mac

edon

ia

Nethe

rland

s

Norway

Sloven

ia

Sweden

Switzer

land

UK

Efficacy and trends

Pregnancy rate per transfer 1997 - 2004

2004 2003 2002 2001 2000 1999 1998 1997

IVF 30.6 29.6 29.5 29.0 28.4 27.7 27.0 26.1

ICSI 30.4 28.7 29.4 28.3 28.7 27.9 26.8 26.4

FER 19.2 18.6 18.4 16.4 16.6 15.7 14.9 15.2

OD 39.6 37.9 34.9 33.4 32.9 40.0 30.6 27.1

Pregnancy rates per transfer. PGD, 2004

countries 15

transfers 1849

pregnancies 789 (42.7%)

deliveries 331 (17.9%)

Pregnancy rates per transfer IVF - 2004

Serbia/Montenegro 100.0 Hungary 33.0 Switzerland 27.9

Turkey 52.4 Macedonia 32.8 Ukraine 27.6

Latvia 40.8 Norway 32.4 France 26.9

Spain 40.0 Portugal 32.2 Finland 26.7

Poland 36.8 Iceland 31.5 Italy 26.0

Greece 36.1 Slovenia 31.1 Albania 24.4

Russia 34.3 Ireland 30.4 Bulgaria 24.4

Netherlands 33.8 UK 29.3 Belgium 23.5

Sweden 33.5 Germany 28.7

Denmark 33.1 Lithuania 28.2

Austria: no data availableSerbia/Montenegro: overestimated, only 2 transfers

Pregnancy rates per transfer ICSI - 2004

Latvia 45.5 Denmark 32.6 Norway 27.0

Turkey 44.4 Iceland 31.8 Lithuania 27.0

Spain 36.7 Slovenia 31.2 France 26.5

Greece 36.5 Sweden 29.6 Switzerland 26.2

Bulgaria 35.9 UK 29.2 Italy 26.1

Serbia/Montenegro 35.5 Ireland 29.1 Albania 24.6

Poland 35.3 Ukraine 29.1 Belgium 21.5

Netherlands 34.5 Germany 28.4 Macedonia 14.6

Hungary 34.4 Finland 27.8

Russia 33.0 Portugal 27.2

Austria: no data available

Conclusion. Efficacy – pregnancies/ transfer

During the 7 year period 1997 – 2004

Despite the transfer of less and less embryos a gradual increase:

26 to 30%, IVF/ICSI

15 to 19%, FER

27 to 40%, ED

The “optimal end-points”. The cumulative delivery rates after fresh and FER. Deliveries/ initiated cycle

Initiated

cycles IVF

and ICSI

Deliveries,

“fresh”

cycles IVF

and ICSI

Multiple

Deliveries

fresh

FER cycles

(thawings)

Deliveries

FER

Multiple

deliveries

FER

Deliveries

fresh

Cumulative

Deliveries,

Fresh and

FER

All

multiples

Finland 4761 886 118 3434 518 55 18.6% 29.5% 12.3%

Sweden 9593 2027 115 3205 498 48 21.1% 26.3% 6.45%

UK 30495 6747 1635 7349 1072 172 22.2% 25.6% 23.1%

”Quality” and trends

Percentage 3 or 4 embryo transfers. IVF and ICSI, 2004

HIGH > 50% % LOW < 20% %

Turkey 72.5 Ireland 14.1

Lithuania 71.1 Iceland 12.6

Albania 68.7 Slovenia 12.2

Hungary 64.6 Belgium 9.1

Bulgaria 64.4 UK 5.5

Serbia/Montenegro 62.7 Denmark 5.2

Greece 62.0 Finland 0.3

Ukraine 61.5 Sweden 0.1

Italy 52.4

Number of embryos transferred after IVF and ICSI, 2004The largest countries

0

10

20

30

40

50

60

70

80

90

1 emb 2 emb 3 emb 4 emb

GermanyFranceUK

Number of embryos transferred after IVF and ICSI, 2004The Nordic countries

0

10

20

30

40

50

60

70

80

1 emb 2 emb 3 emb 4 emb

FinlandSwedenDenmarkNorway

Number of embryos transferred after IVF and ICSI, 2004Southern Europe

0

510

1520

2530

354045

50

1 emb 2 emb 3 emb 4 emb

SpainItalyGreeceTurkey

Number of embryos transferred after IVF and ICSI, 2004Eastern Europe

0

510

1520

2530

3540

4550

1 emb 2 emb 3 emb 4 emb

RussiaBulgariaHungaryUkraine

Number of embryos transferred after IVF and ICSI, 2004Central Europe

0

10

20

30

40

50

60

70

1 emb 2 emb 3 emb 4 emb

BelgiumSwitzerland

Number of embryos transferred. IVF and ICSI, 2004 (%)

2004 2003 2002 2001 2000 1999 1998 1997

1 19.2 15.7 13.7 12.0 12.1 11.9 11.5 11.5

2 55.4 55.9 54.8 51.7 46.7 39.2 37.2 35.7

3 22.1 24.9 26.9 30.8 33.3 39.6 42.0 38.4

4 3.3 3.5 4.7 5.5 6.8 9.3 9.4 14.2

Triplet deliveries, IVF and ICSI, 2004

High, > 2,5% % Low, < 1,0% %

Lithuania 10.0 Slovenia 0.7

Iceland 3.8 Ireland 0.5

Macedonia 3.4 France 0.5

Bulgaria 3.3 Finland 0.5

Hungary 3.1 Denmark 0.4

Turkey 3.0 Norway 0.3

UK 0.3

Belgium 0.2

Albania 0.0

Latvia 0.0

Sweden 0.0

Percentage singleton, twin, triplet and quadruplet deliveries. IVF and ICSI, 2004

2004 2003 2002 2001 2000 1999 1998 1997

Singleton 77.2 76.7 75.5 74.5 73.6 73.7 73.7 70.4

Twin 21.7 22.0 23.2 24.0 24.4 24.0 23.9 25.8

Triplet 1.0 1.1 1.3 1.5 2.0 2.2 2.3 3.6

Quadruplet 0.01 0.08 0.04 0.02 0.04 0.1 0.1 0.15

Conclusion. Multiple deliveries

During the 7 year period 1997 – 2004

• Decline off the overall muliple delivery rates from 29.5 to 22.7%

• A 3-fold reduction in triplet delivery rates from 3.6 to 1.0%

Safety and risks

OHSS, 2004

• Data from 25 of the 29 contributing countries

• 326 351 stimulation cycles resulted in

2 858 cases of OHSS

• The incidence was 0.9%

Fetal reduction (FR), 2004

In 21 countries, 748 fetal reductions were reported

Deliveries FR % Deliveries FR %

Albania 10 0 0.0 Poland 970 0 0.0

Bulgaria 218 2 0.9 Russia 2 518 47 1.9

France 10 387 106 1.0 Serbia/Montenegro 0 3 0.0

Finland 1 410 0 0.0 Slovenia 522 2 0.2

Germany 8 458 222 2.6 Spain 5 668 83 1.5

Greece 1 514 84 5.5 Sweden 2 545 0 0.0

Hungary 671 15 2.2 Switzerland 845 0 0.0

Iceland 64 0 0.0 Turkey 575 77 13.4

Latvia 27 0 0.0 UK 8 338 92 1.1

Lithuania 10 0 0.0 Ukraine 354 9 2.5

Macedonia 59 6 10.2

Fetal Reduction: A major cause of the low triplet rates

• The 748 FR should be related to the 45.148 reported deliveries after ”fresh transfer”

• This correspond to 1.7% of deliveries after ”fresh transfer”, so the 1.0% triplet rates after IVF/ICSI is lower than it would be without FR.

Intrauterine inseminations IUI-H and IUI-D, 2004

Countries with data on IUI-H (n=19)

Albania Macedonia

Bulgaria Norway

Denmark Poland

France Portugal

Greece Serbia / Montenegro

Hungary Slovenia

Ireland Spain

Italy Turkey

Latvia Ukraine

Lithuania

IUI-H and IUI-D, 2004

CyclesPregnant %

IUI-H < 40 94 100 11 866 12.6

IUI-H > 40 4 288 350 8.2

IUI-D < 40 15 882 2 965 18.7

IUI-D > 40 1 710 143 8.2

All 115 980 15 324 13.2

Multiple gestations IUI-H and IUI-D, 2004

All Single % Twin % Triplet %

IUI-H < 40 11 911 87.0 11.7 1.3

IUI-H > 40 347 89.3 10.4 0.3

IUI-D < 40 2 906 88.0 11.1 0.8

IUI-D > 40 140 91.4 7.7 1.4

All 15 304 87.3 11.5 1.1

Conclusions Multiple gestations and IUI

• The number of twin pregnancies after IUI-H in women < 40 (11.7%) is half the rates than the twin delivery rates after IVF and ICSI (21.6%)

• The triplet pregnancy rates after IUI-H were similar to IVF/ICSI

Future developments

• New cycle based statutory registers being established around Europe

• Better coverage – complete coverage

• Gradual evolution of a common European consensus on core-data-sets

• An infant follow-up database based on selected countries.