Assisted reproductive technology in Europe, 1998. Results generated from European registers by ESHRE

The European IVF-monitoring programme (EIM)*for the European Society of Human Reproduction Embryology (ESHRE)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 1998 are presented in this second ESHRE report. Data was collected from 18 European countries usually from pre-existing national registers. A total of 521 clinics from these 18 countries reported 232 443 cycles: IVF 103 919 intracytoplasmic sperm injection (ICSI) 89 192 unclassified fertilization method 667 frozen embryo replacement (FER) 34 03 oocyte donations (OD) 4629. In nine countries where all clinics reported to the register a total of 128 801 cycles were performed in a population of 165 million corresponding to 781 cycles per millioin habitants 3.2 cycles per 1000 women aged 15–49 years. After IVF ICSI the distribution of transfer of 1, 2, 3 4 embryos was 11.5, 37.2, 42.0 and 9.4% respectively. Huge differences existed between countries. For IVF the clinical pregnancy rate per aspiration per transfer was 23.2% 27.0% respectively. For ICSI the corresponding rates were 24.8% 26.8%. The distribution of singleton, twin, triplet, quadruplet deliveries for IVF and ICSI combined was 73.7, 23.9, 2.3 and 0.1%. This gives a total multiple delivery rate of 26.3%. The range of triplet deliveries after IVF and ICSI differed from 0.2-5.3% between countries. Compared with 1997, the number of reported cycles has increased by 14% and the number of reporting clinics by 8%. The clinical pregnancy rate per transfer increased from 26.1 to 27.0% after IVF and from 26.4 to 26.8% after ICSI. Multiple deliveries after IVF and ICSI decreased from 29.6 to 26.3%.

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


    Introduction
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Appendix
 References
 
This report is the second publication (ESHRE, 2001Go) on European data on assisted reproduction technology (ART). Data has been collected from 18 European countries and covers IVF, intracytoplasmatic sperm injections (ICSI), frozen embryo replacements (FER) and oocyte donations (OD) initiated during 1998.

A Consortium meeting was held at the ESHRE Central Office in April 2001 with representatives from participating countries, where present and future reporting systems were discussed. It was noted that Germany reported an increased coverage in their register. Belgium, Hungary and Switzerland were planning to advance their registration systems from voluntary, non-governmental registers to mandatory registers run by the authorities. Additionally, contacts were made to countries that have not yet participated in the European IVF-monitoring (EIM) programme, such as Austria, Ireland and Ukraine. For the present report it was decided to add a list of participating centres in each country in order to give credit to all contributors.

One of the difficulties in the present reporting system is the different definitions used in each country. It was decided to have an inventory done and to list the various definitions used. Although difficult, it would be highly recommendable for the future to try and harmonize the definitions used. The Consortium noticed that efforts are being made to that effect by the International Federation of Fertility Societies (IFFS) Taskforce for IVF World Data and by the World Health Organization (WHO).

The Consortium again noted that the quality of data needs to be improved in the future. European countries have different data collection systems with a variable degree of coverage, loss of follow-up and with different definitions. The Consortium decided to continue to present annual reports and to try to improve the quality of the reports.


    Material and Methods
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Appendix
 References
 
National registers
A total of 16 countries had pre-existing data collection programmes for 1998, and provided data directly from these sources. In Greece and Italy, where no such register existed, national data was collected de novo for the purpose of the EIM programme. National data have not been available from two Western European countries: Austria and Ireland. From Eastern Europe only the Czech Republic, Hungary and Russia were able to provide data. Details regarding the registers has been described earlier (ESHRE, 2001Go). Regarding the Czech Republic, the 1997 report covered all clinics in the country, whereas one clinic did not wish to participate in the data collection for 1998.

Data collection
The present report summarizes data from IVF treatments started during 1998. The data include treatments from IVF, ICSI, OD and FER performed from January 1–December 31, 1998. Follow-up data on pregnancies and deliveries are cohort data.

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 used for 1998 data is basically similar to the preceding year (ESHRE, 2001Go). The following nine countries reported data from all clinics in the country: Denmark, Finland, France, Iceland, the Netherlands, Norway, Sweden, Switzerland and the UK. In most countries reports of pregnancies are based on the presence of one or more intrauterine gestational sacs at sonography ~5 weeks after embryo transfer. Deliveries were normally reported within the same reporting system as for treatments and pregnancies. For the present report neither the definitions of pregnancies nor births have been standardized.

As the data presented here is incomplete and generated through different methods using different definitions in different countries, interpretation of the data must be done 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
Table IGo shows 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. The cycles are subdivided into IVF, ICSI, FER and OD. In Germany, France, Iceland and Spain the number of aspirations were used, as the number of initiated cycles were not available. In total 521 clinics from 18 countries reported 232 443 cycles.


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Table I. ART in European countries in 1998. Number of clinics in the country, number of clinics reporting to the national register and number of initiated1 cycles of IVF, ICSI, frozen embryo replacement [FER (thawings)] and oocyte donation (OD) in 1998
 
Table II Goshows data from those nine countries where all clinics have reported to the register. The number of cycles are related to the total population in the country and to the female populations aged 15–49 years. Overall there were 3.2 cycles per 1000 women in the fertile age. In addition, the number of infants born after ART are expressed in percentage of the total number of live-born in the country. Overall, 128 801 cycles were undertaken in a population of 164.9 million, giving a mean of 781 cycles per million. The percentage of infants born after ART was 1.14 in the UK, 1.29 in France and from 1.70–3.79 in the Nordic countries.


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Table II. IVF in 1998 in those European countries where all clinics have reported to a national register. Number of reported initiated1 cycles, deliveries and infants in relation to the population and the national number of live born. Cycles include initiated treatment cycles of IVF and ICSI, frozen embryo replacement [FER (thawings)] and oocyte donation (OD)
 
Size of the clinics
Table IIIGo shows the size distribution of the 521 reporting clinics. The size of a clinic (or unit) is based on all cycles performed per year.


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Table III. Size of IVF clinics in Europe, 1998
 
Age distribution
Table IVGo shows the age distribution of the treated women in various countries.


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Table IV. Percentage age distribution in women treated with IVF and ICSI (oocyte donation excluded)
 
Number of embryos transferred
Table VGo shows the number of embryos transferred after IVF and ICSI combined. As indicated in the table, wide differences were seen between countries. The range of triple embryo transfers was 4.4–58.8% and the range of transfer of >=4 embryos was 0.0–54.7%.


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Table V. Number of transferred embryos after IVF and ICSI (fresh cycles)
 
Pregnancies and deliveries after treatment
Tables VI–IX show the number of pregnancies and deliveries in relation to number of initiated cycles, aspirations and transfers for IVF (Table VIGoGoGoGoGo), ICSI (Table VIIGo), FER (Table VIIIGo) and OD (Table IXGo).


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Table VI. Pregnancies and deliveries after IVF in European countries in 1998
 

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Table VII. Pregnancies and deliveries after ICSI in European countries in 1998
 

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Table VIII. Pregnancies and deliveries after frozen embryo replacment in European countries in 1998
 

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Table IX. Pregnancies and deliveries after oocyte donation in European countries in 1998
 

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Table X. Deliveries in relation to multiple births after IVF and ICSI treatments initiated in 1998 (frozen embryo replacment excluded)
 
Table VIGo shows that after IVF, 22 683 pregnancies resulted from 84 066 embryo transfers. The mean clinical pregnancy rate per embryo transfer was 27.0%, with a range from 21.0–44.6%. If Iceland, with only a single clinic, is excluded, the pregnancy rate per embryo transfer ranges between 21.0–35.1%. The delivery rate per embryo transfer after IVF has not been summarized due to incomplete follow-up of pregnancies in many countries.

Table VIIGo shows that after ICSI, 21 665 pregnancies resulted from 80 785 embryo transfers. The mean clinical pregnancy rate per embryo transfer was 26.8%, with a range from 18.2–46.4%. If Iceland, with only a single clinic, is excluded, the pregnancy rate per embryo transfer ranges between 18.2–33.8%. The delivery rate per embryo transfer after ICSI has not been summarized due to incomplete follow-up of pregnancies in many countries.

Table VIIIGo shows that after FER, 4620 pregnancies resulted from 31 121 transfers. The mean clinical pregnancy rate per embryo transfer after FER was 14.9%. The delivery rates per embryo transfer after FER has not been summarized due to incomplete follow-up of pregnancies in many countries.

Table IXGo shows that after OD, 4264 transfers resulted in 1306 clinical pregnancies, giving a pregnancy rate per transfer of 30.6%.

Singleton, twin, triplet and quadruplet deliveries
Table XGo shows the deliveries after IVF and ICSI in relation to singleton, twin, triplet and quadruplet deliveries in 16 countries. It is seen that the distribution of the deliveries was: singleton 73.7%, twin 23.9%, triplet 2.3% and quadruplet 0.1%.

Table XIGo shows the deliveries after FER in relation to singleton, twin, triplet and quadruplet deliveries in 16 countries. It is seen that the distribution of the deliveries was: singleton 84.5%, twin 13.9%, triplet 1.5% and quadruplet 0.0%.


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Table XI. Deliveries in relation to multiple births after frozen embryo replacement treatments initiated in 1998
 
Table XIIGo shows the proportion of infants born as singletons, twins, triplets and quadruplets. It is seen that 57.3% are born as singletons, 37.1% as twins, 5.4% as triplets and 0.2% as quadruplets.


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Table XII. Percentage of infants born as singletons, twins, triplets and quadruplets after IVF and ICSI (frozen embryo replacement and oocyte donation excluded)
 
Table XIIIGo presents calculations on the number of clinical pregnancies per embryo replaced. The same parameter can also be expressed as the number of embryos replaced in order to achieve one clinical pregnancy. It is seen that on average the number of pregnancies per embryo was 0.13 and the number of embryos used to achieve one pregnancy was 7.7.


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Table XIII. The number of clinical pregnancies for each embryo transferred and the number of embryos transferred per pregnancy. Data on IVF and ICSI with fresh embryos
 

    Discussion
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Appendix
 References
 
The first report on European ART treatments was published in Human Reproduction in February this year (ESHRE, 2001Go) and included a total of 203 893 cycles from 18 European countries during 1997. The present report covers the same countries and includes data from 232 443 (+14%) initiated cycles from 521 clinics (+8%) initiated in 1998. For comparison the report from the USA from 1997 covered a total of 73 069 cycles (ASRM/SART Registry, 2000)Go

The largest number of cycles again comes from France and Germany, with ~46 000 cycles each, and the UK with ~35 000 cycles. Altogether these countries contribute to >50% of all cycles.

Germany reported a large increase in treatment cycles from ~28 000 in 1997 to ~46 000 cycles in 1998. According to the German register there will be a further marked increase in the number of reported cycles in the following years, primarily due to a better coverage of the reporting system in Germany. A similar increase was observed in Italy and Belgium, whereas the number of reported treatment cycles declined in Spain. In other countries the number of reported cycles remained relatively stable. During 2001 contacts have been made with Austria, Ireland and Ukraine, in order to achieve data for future reports.

IVF treatments with standard fertilization techniques still predominate over ICSI (103 919, 53.8% versus 89 192, 46.2%), but the difference is less than in 1997. In several countries such as Belgium, Germany, Hungary, Italy, Portugal, Spain, and Switzerland, ICSI is now the most frequently performed treatment.

The mean availability of treatment cycles, expressed as the number of cycles per million inhabitants was defined in those countries where all clinics reported to the register. A small increase was observed from 765 cycles per million in 1997 to 781 cycles per million in 1998.

The highest availability is found in the Nordic countries and the Netherlands. Denmark reported the highest number of treatments with 1608 cycles per million, whereas 595 cycles per million were performed in the UK.

The proportion of children born after ART can be compared with the total number of live-births in the same countries. It is seen that in the Nordic countries 1.70–3.45% of all infants are born after ART, whereas the corresponding figure is 1.14 for the UK and 1.29 for France.

The proportion of single embryo transfers remain relatively constant at ~10–15%. Finland has the highest rate of 16.4 followed by France with 14.5%. The proportion of dual embryo transfers varies. Sweden has the highest proportion with 85.1%, followed by Finland with 74.1% and Iceland with 63.0%. From 1997–1998 a substantial increase in the proportion of dual embryo transfers was reported from Belgium (41–48%), France (31–37%), Switzerland (50–58%) and the UK (42–47%).

Regarding triple embryo transfers the reported percentage has gone down in some countries, notably Belgium from 41.1–33.8%, but it remained high and actually increased in several countries. Two countries reported very low rates of triple embryo transfers. In Sweden and Finland three embryos were replaced in 4.4 and 9.4% of all transfers respectively.

Transfers of >=4 embryos are still performed in many countries. Three Eastern European countries reported a high proportion of replacements of >=4 embryos: Russia 54.7%, the Czech Republic 33.3% and Hungary 24.0%. From Southern Europe: Greece 37.8%, Spain 31.9% and Portugal 25.8%. In a number of countries four embryos are never replaced.

The pregnancy rate per transfer was 27.0% after IVF and 26.8% after ICSI. This is a small increase compared with 26.1% after IVF and 26.4% after ICSI in 1997 (ESHRE, 2001Go).

For comparison, the clinical pregnancy rate per transfer was 36.5% (IVF) and 35.2% (ICSI) in 1997 in the USA (ASRM/SART Registry, 2000)Go). The delivery rates should not be summarized due to incomplete follow-up of pregnancies in several countries. For IVF the highest pregnancy rates were reported from Iceland (44.6%), Norway (36.3%) and Sweden (35.1%).

The mean proportion of singleton deliveries after IVF and ICSI has increased from 71.0% in 1997 to 73.7% in 1998. The proportion of twin and triplet deliveries decreased to 23.9 and 2.3%, respectively. For comparison, the data after IVF from the USA from 1997 gives the following distribution of deliveries: 60.9% singletons, 32.2% twins, 6.3% triplets and 0.5% quadruplets (ASRM/SART Registry, 2000)Go). Major differences exist between European countries, where the rate of twin deliveries is as high as 35.5% in the Czech Republic and 37.1% in Greece. Triplets deliveries occurred at ~1% in the Nordic countries but up to 5.1% in Russia and 5.3% in Portugal. Spain reported a major decline in the rate of triplets which was reduced from 11.9% in 1997 to 3.9% in 1998. However, the total number of cycles reported from Spain was reduced in 1998 compared with 1997, so there may be a reporting bias in this marked reduction.

This year data have also been calculated on the percentage of infants born as singletons, twins, triplets and quadruplets. In this perspective 57.3% of the children are born as singletons, 37.1% as twins, 5.4% as triplets and 0.2% as quadruplets.

Table XIIIGo gives a presentation of the number of clinical pregnancies per embryo replaced, and the number of embryos used for one clinical pregnancy. This will be different from the implantation rates, and it will focus on achievement of singleton pregnancies and deliveries and replacement of few embryos with a high implantation rate. It is seen that around 7.7 embryos have to be replaced to give one clinical pregnancy.

The coverage of data collection has increased since the first report, the definitions are still different and the loss of follow-up of deliveries remains high in several countries. Therefore the data in this report should be interpreted cautiously.

In summary, the report from 1998 shows that the number of reported treatment cycles has increased and the pregnancy rate per treatment has increased slightly simultaneously with a reduction in the rate of multiple deliveries.


    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. 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. E-mail: ventruba{at}fp-brno.cz

Denmark: Karin Erb, The Fertility Clinic, Odense University Hospital, DK–5000 Odense, Denmark. 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. 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. E-mail: demouzon{at}vjf.inserm.fr

Germany: Ricardo Felberbaum, Schildstraze 13, D – 23552 Lübeck, Germany. E-mail: rfelberbau{at}aol.com

Greece: Basil C. Tarlatzis, Infertility & IVF Centre, Geniki Kliniki, 2 Gravias Street,GR – 54645 Thessaloniki, Greece. E-mail: tarlatzis{at}hol.gr

Hungary: Janos Urbancsek, 1st Dept. of Obstetrics and Gynaecology, SOTE, Baross utca 27, H – 1088 Budapest, Hungary. E-mail: UrbJan{at}Noi1.sote.hu

Iceland: Hilmar Bjorgvinsson. IVF Unit, Depart. Obstet Gynecol, Natiaonal University Hospital. Landspitalinn, Reykjavik 101, Iceland. E-Mail: Hilmar{at}rsp.is

Italy: Anna Pia Ferraretti, S.I.S.M.E.R. s.r.l., Via Mazzini 12, I – 40137 Bologna, Italy. 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. E-mail: j.kremer{at}obgyn.azn.nl

Norway: Johan T Hazehamp, Dept. of Reproductive Medicine, Volvat Medical Center, Postboks 5280, Majorstuea, Oslo 303, Norway. E-mail: Hazekamp{at}online.no

Portugal: Carlos Calhaz-Jorge. Human Reproduction Unit, Dept. Obstet Gynecol, Hopital de Santa Maria, Av. Prof. Equs Monitz, 1649–028 Lisboa, Portugal. E-mail: Calhazjorge{at}mail.telepac.pt

Russia: V. S. Korsak, IVF Centre, Ott Institute, Mendeleyevskay linia 3, 199034 St-Petersburg, Russia C.I.S. E-mail: Korsak{at}bk3298.spb.edu

Spain: Jose Luis Ballesca, Unidad de Repoduction, Hospital Clinic, E-08036 Barcelona, Spain. E-mail: 8658jlb{at}comb.es

Sweden: Clas Hedberg, Center for Epidemiology, National Board of Health & Welfare, S – 10630 Stockholm, Sweden. E-mail: Clas.hedberg{at}sos.se

Switzerland: Professor Michael K. Hohl, Dept. Obstet Gynecol, Kantonspital, 5404 Baden, Switzerland. E-mail:administration.sgfsf{at}bluewinch

UK: Richard Baranowski, Human Fertilisation and Embryology Authority, Paxton House, 30 Artillery Lane, E1 7LS London, UK. E-mail: richard.baranowski{at}hfea.uk


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

* EIM subcommittee: Chairman, K.G. Nygren; Co-ordinator, A.Nyboe Andersen; Members, M.J.Heineman, L.Gianaroli, D.Royere. See Appendix for contact persons and contributing centres representing the data collection programmes in the participating European countries.Human Reproduction Vol.16, No.11 pp. 2459–2471, 2001 Back


    References
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Appendix
 References
 
ESHRE (2001) The European IVF-monitoring programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE. Hum. Reprod., 16, 384–391.[Abstract/Free Full Text]

ASRM/SART Registry. (2000) Assisted reproductive technology in the United States: Results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil. Steril., 72, 641–654.