Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE

The European IVF-monitoring programme, (EIM), for the European Society of Human Reproduction and Embryology (ESHRE),1,,2

1 Report prepared by K.G.Nygren and A.Nyboe Andersen


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
European results of assisted reproductive techniques from treatments initiated during 1997 are presented in this first ESHRE report. Data were collected from 18 European countries, usually from already-existing national registers. A total of 482 clinics from these 18 countries reported 203 893 cycles. In 10 countries with complete registration, 133215 cycles were performed in a population of 174 million, corresponding to 765 cycles per million inhabitants. After IVF and intracytoplasmic sperm injection (ICSI), the distribution of transfer of one, two, three and four or more embryos was 11.5, 35.9, 38.4 and 14.3% respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per transfer was 26.1%, and the delivery rate per embryo transfer 20.9%. For ICSI, the corresponding rates were 26.4% and 21.5%. Singleton, twin, triplet and quadruplet delivery rates for IVF were 70.4, 25.8, 3.6 and 0.2% respectively, giving a total multiple delivery rate for IVF of 29.6%. After ICSI, the corresponding rates were 71.7, 25.2, 2.9 and 0.1%, amounting to a total multiple delivery rate of 28.2%. The range of triplet delivery rates after IVF range from 0.4% to 11.9% among countries.

Key words: ESHRE/Europe/ICSI/IVF/register data


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
Results from IVF treatments have been published in numerous reports from individual clinics, national registers and from regional data collected from Australia-New Zealand (Hurst et al., 1997Go), Latin America (Zegers-Hochshild and Galdames, 1997) and the USA and Canada (SART, 1999Go). Additionally, five World Reports have been presented, the latest containing data from 1996 (World Collaborative Report, 1997).

Until now, Europe has been lacking a reporting system for IVF results, yet the latest World Report indicated that about one-half of all IVF cycles in the world were initiated in Europe.

In 1999, the European Society for Human Reproduction and Embryology (ESHRE) invited representatives from all European national IVF data registers to a joint effort to establish an IVF data collection programme for Europe. In countries where national IVF registers did not exist, other key persons were identified and invited to act as focal points for IVF data collection in their respective country. Representatives from 18 European countries met in June 1999. A Consortium was established, which discussed and adopted an ESHRE proposal for an European IVF Monitoring programme, the EIM programme.

The EIM programme aims at publishing regional data for Europe on clinical results. Later, it is the intention to publish data on side effects, follow-up of children's health and of the availability and structure of assisted reproductive technology (ART) services in the different countries. Such data will be collected, audited and published by ESHRE, possibly on a yearly basis. The reports will allow comparisons between different countries in Europe and other regions of the world.

On its first meeting the Consortium discussed the present situation concerning different IVF data collection systems in the European countries, understanding that the situation is a very dynamic one. Each country has its own data collection system.

The Consortium decided to start data collection of national summary data on direct clinical IVF outcomes for treatments initiated during 1997, including cohort data for the corresponding deliveries.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
National registers
A total of 16 countries already had existing data collection programmes for 1997, and therefore provided data directly from their register. In Greece and Italy, where no such register existed, national data were collected de novo for the purpose of the EIM programme. In western Europe, national data could not be collected from three countries: Austria, Ireland and Luxembourg, while in eastern Europe only the Czech Republic, Hungary and Russia were able to provide data.

All registers in the consortium collect data on the number of ART cycles and pregnancies, as well as deliveries. Apart from this, many differences exist. Among the 18 countries, six have registers with a compulsory reporting system that is administered either by a health authority or by an independent, official body: Denmark, France, the Netherlands, Sweden, Norway and the United Kingdom. Data from those six countries were complete. In Denmark, the data for 1997 were not yet completed in the National Register, and data from the Danish Fertility Society had to be used. In France, data are collected both by FIVNAT and by the French Ministry of Health, through a National Commission (Commission National de Médecine et de Biologie de la Reproduction et du Diagnostic Prénatal). The latter provided the present French data. In Finland, it is voluntary to report to the IVF registry, but there is a compulsory birth registry, where it is recorded whether or not the pregnancy is the result of ART.

The remaining countries have based their registration on a voluntary reporting system administered by a society, typically a National Fertility Society. In some countries a number of clinics do not report their data and the national data are, therefore, incomplete. In some countries, like Belgium, more than 90% of all clinics have joined the register, whereas an unknown fraction of the clinics submit their data in other countries.

In summary, the majority of European countries have IVF registers already in operation, but the data collection programmes are organized differently.

Data collection
The present report summarizes data from IVF treatments started during 1997. Most of these data were not collected for the purpose of the present study, but come from pre-existing data contained within registers in Europe. Exceptions are Greece and Italy, where data were collected from individual clinics for the purpose of the present study.

The data include treatments from IVF, ICSI, oocyte donation (OD) and frozen embryo replacements (FER) performed between the 1st January 1997 and 31st December 1997. Follow-up data on pregnancies and deliveries are cohort data.

Data quality
The data collection programmes vary considerably from one country to another. Registers from a number of countries have been unable to provide some of the data. Lack of such specific variables will appear in the tables as `not available' (NA).

The reporting principle is either reports of individual cycles (Belgium, Czech Republic, Denmark, Germany, Italy, the Netherlands, United Kingdom and Switzerland) or summaries of treatments performed during the year.

The following countries reported complete data: Czech Republic, Denmark, Finland, France, Iceland, the Netherlands, Norway, Sweden, Switzerland and United Kingdom.

In most countries, reports of pregnancies are based on the presence of one or more gestational sacs at sonography approximately 5 weeks after embryo transfer. In Iceland and Denmark, a pregnancy was defined as a gestational sac with at least one living (fetal heartbeat) fetus, whilst in the Netherlands the definition was that there should be an ongoing pregnancy in the 12th week.

Deliveries were normally reported within the same reporting system as for treatments and pregnancies, but in Sweden and Finland the reports were obtained from separate birth certificates, where it must be stated whether or not the birth was the result of a pregnancy obtained through an ART procedure. The definition of birth has not been standardized, neither in relation to the number of gestational weeks nor in relation to whether both livebirths and stillbirths are included.

Germany, Portugal, Spain and Switzerland had incomplete reporting of the deliveries. This is indicated in the tables.

As the data presented here are incomplete and generated through different principles using different definitions in different countries, they should be interpreted with some caution. Eventually, the quality and conformity of the data will improve in later reports.


    Results
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
Number of treatment cycles
The number of all treatment cycles recorded in each country, the number of clinics in the country (if available) and the number and size of clinics reporting to the register are shown in Table IGo. Cycles includes all initiated cycles (IVF, ICSI, FER and OD). In France and Iceland, the number of aspirations was used, as the number of initiated cycles was not available. In total, 482 clinics from 18 countries reported 203 893 cycles.


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Table I. IVF in European countries, 1997. Total number of clinics, number of clinics reporting to a National Register, total number of cycles recorded and the distribution of the size of the clinics. Cycles include initiated treatment cycles of IVF and ICSI, FER (thawings) and oocyte donations in 1997
 
Data from countries with complete reporting (Czech Republic, Denmark, Finland, France, Iceland, the Netherlands, Norway, Sweden, Switzerland and the United Kingdom) are shown in Table IIGo. The number of cycles is related to the total population in the country. In addition, the number of infants born after ART is expressed as a percentage of the total number of liveborn in that country. Overall, 133 215 cycles were undertaken in a population of 174.22 million, giving a mean of 765 cycles per million. Excluding the Netherlands (where the number of ART deliveries is not available) and Switzerland (where the reporting of deliveries is not complete), the treatments resulted in 18 899 deliveries of 24 283 infants. In countries with a complete reporting system the number of children born after ART constituted 1.33% of the overall number of live births in the countries.


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Table II. IVF in 1997 in those European countries where all clinics have reported to a National Register. Number of reported cycles, deliveries and infants in relation to the population and the national number of liveborn. Cycles include initiated treatment cycles of IVF and ICSI, FER (thawings) and oocyte donations
 
Age distribution
The age distribution of treated women in various countries is shown in Table IIIGo. Among the different countries, the age ranges of women were: <=29 years, 3.2–35.3%; 30–34 years, 31.0–44.7%; 35–39 years, 22.5–38.6%; and >=40 years 6.3–17.9%.


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Table III. Percentage age distribution of women treated with IVF and ICSI (oocyte donation excluded)
 
Number of embryos transferred
Numbers of embryos transferred after IVF and ICSI are shown in Table IVGo. The total number of single embryo transfers was 11 877 (11.5%), dual embryo transfers 37 034 (35.9%), triple embryo transfers 39 521 (38.4%) and four or more embryo transfers 14 693 (14.3%). There were large differences between countries in the number of embryos transferred. The range of triple embryo transfers was 4.9 to 48.7% and the range of transfer of four or more embryos was 0.0 to 56.6%.


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Table IV. Number of transferred embryos after IVF and ICSI
 
Pregnancies and deliveries after treatment
The number of pregnancies and deliveries in relation to the number of initiated cycles, aspirations and transfers are shown for IVF (Table VGo), ICSI (Table VIGo) and FER (Table VIIGo). After IVF, the 20 937 pregnancies resulted from 80 209 embryo transfers (Table VGo). Thus, the mean clinical pregnancy rate per embryo transfer was 26.1% (range 17.9–44.7%). If Iceland, where there is only a single clinic, is excluded, the pregnancy rate per embryo transfer showed a range between 17.9 and 32.5%. The delivery rates per embryo transfer after IVF could be calculated in 12 countries. In these countries, a total of 57 794 transfers resulted in 12 062 deliveries, giving a delivery rate per embryo transfer after IVF of 20.9%.


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Table V. Pregnancies and deliveries after IVF in European countries from cycles initiated in 1997
 

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Table VI. Pregnancies and deliveries after ICSI in European countries in 1997
 

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Table VII. Pregnancies and deliveries after FER in European countries from cycles initiated in 1997
 
After ICSI, the 16 462 pregnancies resulted from 62253 embryo transfers (Table VIGo). Thus, the mean clinical pregnancy rate per embryo transfer was 26.4% (range 12.7–34.5%). The delivery rates per embryo transfer after ICSI could be calculated from 12 countries. In these countries, 36 728 transfers resulted in 7904 deliveries, giving a delivery rate per embryo transfer after ICSI of 21.5%.

After FER, 4024 pregnancies resulted from 26 547 embryo transfers (Table VIIGo). Thus, the mean clinical pregnancy rate per embryo transfer after FER was 15.2%. The delivery rates per embryo transfer after FER could be calculated in 11 countries. In these countries, 18 644 transfers resulted in 2112 deliveries, giving a delivery rate per embryo transfer after FER of 11.3%.

In total, 10 registers (Czech Republic, Denmark, Finland, France, Greece, Hungary, Italy, Russia, Spain and the United Kingdom) reported on 3487 oocyte donations (in Finland, these were transfers) resulting in 944 clinical pregnancies, giving a clinical pregnancy rate per donation of 27.1%.

Singleton, twin, triplet and quadruplet deliveries
The deliveries after IVF in relation to singleton, twin, triplet and quadruplet deliveries in 16 countries are shown in Table VIIIGo. The distribution of the deliveries was: singleton 70.4%; twin 25.8%; triplet 3.6%; and quadruplet 0.2%.


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Table VIII. Deliveries in relation to multiple births after IVF treatments initiated in 1997
 
The deliveries after ICSI in relation to singleton, twin, triplet and quadruplet deliveries in 16 countries are shown in Table IXGo. The distribution of the deliveries was: singleton 71.7%; twin 25.2%; triplet 2.9%; and quadruplet 0.1%.


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Table IX. Deliveries in relation to multiple births after ICSI treatments initiated in 1997
 
The deliveries after FER in relation to singleton, twin, triplet and quadruplet deliveries in 13 countries are shown in Table XGo. The distribution of the deliveries was: singleton 82.9%; twin 16.0%; triplet 1.1%; and quadruplet 0.0%.


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Table X. Deliveries in relation to multiple births after FER treatments initiated in 1997
 

    Discussion
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
Data collected in Europe on the results of IVF treatments initiated in 1997 are presented in this first ESHRE report. The data include all information available at the present time from national registers, using different collection systems with different validation systems. Furthermore, a majority of the countries contributing to this report do not yet have complete data registration systems. While recognizing and understanding these shortcomings, the consortium of countries nevertheless decided to publish the present report, and as a consequence the reader should make comparisons with some caution. It is hoped that data collection systems will be refined in the future.

The total number of cycles reported here exceeds 200000 for one year. For comparison, the SART (1999) report from the United States and Canada covered 65 000 cycles in 1996. For the same year, the Latin American Register (Zegers-Hochschild and Galdames, 1997Go) reported 5332 cycles, while the Australian–New Zealand Register (Hurst et al., 1997Go) reported 24124 cycles. Therefore, its seems that Europe provides more IVF treatments than any other region, although specific data for Asia including Japan and for Africa are not available.

Within Europe, three countries dominate by number of cycles, with France, the UK and Germany together reporting >50% of the cycles. The availability of services for the different populations is, on the other hand, dominated by the Nordic countries and the Netherlands.

The highest availability of services is reported from Finland, with little more than 1500 cycles per million inhabitants. As a consequence, 2.4% of all children born in Finland were from different types of IVF treatment. The mean percentage of children born after ART was 1.3% of all newborn.

The number of embryos transferred has changed over time—in some countries quite dramatically. During the 1980s, most clinics transferred several embryos, but many countries now use only two or three embryos. This situation differs considerably, however. In the Nordic countries, dual embryo replacements were the dominant procedure in 1997, and for Sweden the proportion of triple embryo transfers was as low as 5%. Several countries report the transfer of higher numbers of embryos, with transfer of four or more embryos being a frequent occurrence in Russia (57%), Greece (42%), the Czech Republic (40%), Hungary (38%) and Spain (35%).

Clinical results are presently reported as pregnancies and deliveries. The numbers are related to initiated cycles, oocyte aspirations and transfers. All three ratios contain different information, but no single rate contains all the information needed. Internationally, the proportion of deliveries per embryo transfer is often highlighted. In the present report, the delivery rate per transfer was 20.9% after IVF and 21.5% after ICSI. This compares with values between 20 and 25% in most countries.

The rate of multiple births—which is a major concern in relation to IVF treatments—varied greatly in Europe. The overall rate of multiple births was 29.6%, with twins at 25.8%, triplets at 3.6% and quadruplets at 0.2%. By comparison, values for 1996 in the United States and Canada were 31% twins, 5.8% triplets and 0.5% quadruplets, giving a total of approximately 37% multiple deliveries (SART, 1999Go).

Several countries in Europe—especially the Nordic countries—have reduced their triplet rates considerably. For example, Denmark and Sweden report here only 0.4% triplets compared with 3.3% in the United Kingdom and 11.9% in Spain.

In this report, data on spontaneous abortions and ectopic pregnancy are not presented separately but may be deduced as the difference between pregnancy and delivery rates.

Fetal reduction is being used to a very different degree in different European countries. No definite data exist on the occurrence of this procedure.

In conclusion, this first ESHRE report on IVF results in Europe shows that, during 1997, more than half of all IVF cycles world-wide were performed in Europe, although the number of cycles reported (slightly more than 200000) is an underestimation as the report is incomplete. The availability of services is highest in the Nordic countries, while deliveries per embryo transfer lie between 20% and 25% for most countries, there being no differences between standard IVF and ICSI procedures. Mean multiple delivery rates were reported as 25.8% for twins, 3.6% for triplets and 0.2% for quadruplets after standard IVF, with similar corresponding rates after ICSI. Thus, the total multiple delivery rate was 29%.


    Appendix
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
Contact persons representing data collection programmes in participating European countries:

Belgium
Josiane Van Der Elst, Infertility Centre, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium. Tel: +32 9 240 37 74; Fax: +32 9 240 49 72; E-mail: josiane.vanderelst{at}rug.ac.be

Czech Republic
Pavel Ventruba, 1st Dept. of Obstetrics and Gynaecology, Masarik University of Brno, Obilni trh 11, 656 77 Brno, Czech Republic. Tel: +42 0 5 4252 2236; Fax: +420 5 4121 3364; E-mail: ventruba{at}fp-brno.cz

Denmark
Karin Erb, The Fertility Clinic, Odense University Hospital, DK-5000 Odense, Denmark. Tel: +45 65 41 23 24; Fax: +45 65 90 69 82; E-mail: karin.erb{at}ouh.fyns-amt.dk

Finland
Aila Tiitinen, Department of Obstetrics and Gynaecology, Helsinki University - Central Hospital, P.O. Box 140, FIN - 00029 Hus Finland. Tel: +358 9 471 61 271; Fax: +358 9 471 74 801; E-mail: aila.tiitinen{at}hus.fi

France
Jacques De Mouzon, Inserm U. 292, Hôpital de Bicêtre, 78 rue du Général Leclerc, F-75252, Kremlin Bicêtre, France. Tel: +33-1-4521 2338; Fax: +33-1-4521 2075; E-mail: demouzon{at}vjf.inserm.fr

Germany
Ricardo Felderbaum, Schildstraze 13, D-23552 Lübeck, Germany. Tel: +49 451 70029; Fax: +49 451 70049; E-mail: Rfelderbaum{at}aol.com

Greece
Basil C.Tarlatzis, Infertility & IVF Centre, Geniki Kliniki, 2 Gravias Street,GR-54645, Thessaloniki, Greece. Tel: +30-31 866 477/821 681; Fax: +30-31 821 420; E-mail: tarlatzis{at}hol.gr

Hungary
Janos Urbancsek, 1st Dept of Obstetrics and Gynaecology, SOTE, Baross utca 27, H-1088, Budapest, Hungary. Tel: +36 1 2660 115; Fax: +36 1 266 01 15; E-mail: UrbJan{at}Noil.sote.hu

Iceland
Thordur Oskarsson, Kvennadeild-IVF Unit, Landspitalinn 101, Reykjavik, Iceland. Tel: +354-1-601000; Fax: +354-1-601519; E-mail: Thorduro{at}rsp.is

Italy
Anna Pia Ferraretti, S.I.S.M.E.R. s.r.l., Via Mazzini 12, I-40137 Bologna, Italy. Tel: +39 51 307 307; Fax: +39 51 302 933; E-mail: sismer{at}iol.it

The Netherlands
Jan A.M.Kremer, Department of Obstetrics and Gynaecology, A.Z. Nijmegen (St Radboud), Geert Grooteplein 10, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands. Tel: +31 24 361 47 48; Fax: +31 24 354 11 95; E-mail: j.kremer{at}obgyn.azn.nl

Norway
Arne Sunde, Department of Obstetrics and Gynaecology, University of Trondheim, N-7006 Trondheim, Norway. Tel: +47 73868852; Fax: +47 73 86 77 89; E-mail: arne.sunde{at}medisin.ntnu.no

Portugal
Angelina Correia Tavares, Praceta Teixeira Lopez, 18-2 DT, P-4405-082 Arcozelo VNG, Portugal. Tel: +351 2 753 41 62; Fax: +351 2 379 60 60; E-mail: joaoramalho{at}mail.telepac.pt

Russia
V.S.Korsak, IVF Centre, Ott Institute, Mendeleyevskay linia 3, 199034 St-Petersburg, Russia, C.I.S. Tel: 07 812 328 2251; Tel/Fax: 07 812 327 1952; E-mail: Korsak{at}bk3298.spb.edu

Spain
Pedro Viscasillas, Argensola, 7-1. °Dcha., E-28004 Madrid, Spain. Tel: +34-91-3080280; Fax: +34-91-3080280; E-mail: 7369pvm{at}comb.es

Sweden
Anders Ericson, National Board of Health & Welfare, S-10630 Stockholm, Sweden. Tel: +46 8 5555 30 00; Fax: +46 8 5555 33 27; E-mail: anders.ericson{at}sos.se

Switzerland
Martin H.Birkhäuser, Abteilung für gyn. Endokrinologie, Universitäts-Frauenklinik, Schanzeneckstrasse 1, CH-3012 Bern, Switzerland. Tel: +41 31 23 03 33; Fax: +41 31 300 14 17

United Kingdom
Suzanne McCarthy, Human Fertilisation and Embryology Authority, Paxton House, 30 Artillery Lane, E1 7LS London, United Kingdom. Tel: +44-171 377 5077; Fax: +44-171 377 1871; E-mail: Suzanne.mccarthy{at}hfea.gov.uk


    Notes
 
* EIM subcommittee: Chairman, K.G.Nygren; co-ordinator, A.Nyboe Andersen; members, M.J.Heineman, L.Gianaroli, D.Royère. See Appendix for contact persons representing the data collection programmes in the participating European countries. Back

2 Address for correspondence: ESHRE Central Office, Van Aakenstraat 41, B-1850 Grimbergen, Belgium. E-mail: ESHRE{at}popost.eunet.be Back


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 Appendix
 References
 
Hurst, T., Shafir, E. and Lancaster, P. (1997) Assisted Conception, Australia and New Zealand, 1996. AIHW National Perinatal Statistics Unit, Sydney.

SART (Society for Assisted Reproductive Technology) (1999) The American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 1996 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil. Steril., 71, 798–807.[ISI][Medline]

World Collaborative Report on IVF for 1995 (1997) International Working Group for Registers on Assisted Reproduction. J. Assist. Reprod. Genet., 14 (No. 5, Suppl.).

Zegers-Hochschild, F. and Galdames, I.V. (1997) Registro Latinoamericano de Reproduccion Asistida 1997. Red Latinoamericana de Reproduccion Asistida.

Submitted on September 7, 2000; accepted on November 1, 2000.