ART in Europe, 2014: results generated from European registries by ESHRE^†: The European IVF-monitoring Consortium (EIM)^‡ for the European Society of Human Reproduction and Embryology (ESHRE)

Abstract

STUDY QUESTION

What are the European trends and developments in ART and IUI in 2014 as compared to previous years?

SUMMARY ANSWER

The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries.

WHAT IS KNOWN ALREADY

Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction.

STUDY DESIGN, SIZE, DURATION

Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies.

PARTICIPANTS/MATERIALS, SETTING, METHODS

From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included.

MAIN RESULTS AND THE ROLE OF CHANCE

In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423–2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%).

LIMITATION, REASONS FOR CAUTION

The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution.

WIDER IMPLICATIONS OF THE FINDINGS

The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field.

STUDY FUNDING/COMPETING INTEREST(S)

The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

Introduction

This is the 18th annual report of the European IVF-monitoring Consortium (EIM) under the umbrella of ESHRE containing the data on ART reported by 39 participating European countries in 2014 (Supplementary Data).

Seventeen previous reports, all published in ‘Human Reproduction’ (https://www.eshre.eu/Data-collection-and-research/Consortia/EIM/Publications.aspx), covered treatment cycles from 1997 to 2013. As in previous reports, the printed version contains the five most relevant tables. Nineteen additional Supplementary tables are available online. The settings of the data are consistent with those published in the previous reports, allowing good comparison with earlier trends.

Materials and Methods

Aggregated data on various forms of ART were provided by 39 European countries, covering the following treatment modalities: IVF, ICSI, frozen embryo replacement (FER), egg donation (ED), IVM, and pooled data on preimplantation genetic testing (PGT) and frozen oocyte replacement (FOR). In addition, data on IUI using either husband’s/partner’s semen (IUI-H) or donor semen (IUI-D) were included. The report includes treatments started between 1 January and 31 December in 2014. Data on pregnancies and deliveries are derived from follow-up of the treatments performed in 2014. Each national register is informed about the need to obtain signed informed consent prior to the initiation of infertility treatment from each infertile individual for whom data have to be reported to the national registry.

For the collection of the data, the national representatives of 41 countries were asked to fill out questionnaires and data were transmitted through a software package, specially designed for the requirements of this data collection (Dynamic Solutions, Barcelona, Spain). The same sets of data as in 2013, consisting of six different modules, were requested as in 2014. The software performs all calculations automatically and evaluates the plausibility of all results. If inconsistencies are detected, the administrator of the ESHRE central office (V.G.) contacts the national representative for clarifications.

The data were assembled similarly as in the previous reports making the results comparable. As usual, footnotes to the tables provide additional information on diverging results reported by individual countres, when applicable.

The terminology used was based on the glossary of The International Committee for Monitoring Assisted Reproductive Technology (ICMART) (Zegers-Hochschild et al., 2017).

Results

Participation and data completeness

In Table I the number of institutions or clinics offering ART services and those performing IUI are listed together with all available treatment modalities. In comparison to the 2013 data (Calhaz-Jorge et al., 2017) not only the numbers of reporting clinics has increased (1169 in 2013 to 1279 in 2014, +9.5%), but also the overall number of reported treatments (686 271 in 2013 to 776 556 in 2014, +13.1%). Among the 51 European countries, nine are not members of the EIM Consortium (Supplementary Table SI), most being very small countries not offering ART services. Bosnia-Herzegovina resumed their participation. Armenia became a member of the EIM Consortium but has not yet provided any data to the Consortium, and neither did Turkey and Slovakia. Among the 42 members, 39 have sent in their data (92.9%) and in 14 countries (35.8%) all ART centres have reported complete data sets. Currently, 1280 clinics report their data (87.6% of all known clinics in Europe, 85.4% in 2013). The European countries with the largest treatment numbers in 2014 are Spain (109 275 treatments), Russia (94 985), France (90 434) and Germany (81 177).

Reporting methods and size of the clinics

Among the countries with complete coverage of data reporting there is a clear preponderance of registries to which reporting is compulsory (13 out off 15), although among those countries with incomplete data sets six require compulsory data reporting by the local national health authorities (Supplementary Table SIII). Mainly in countries with incomplete coverage, personal initiatives continue to play a major role (seven countries), as do medical organizations (in 13 countries).

Aggregate data submission by single ART institutions to the respective national registries is still the most commonly used method (8 in 17 countries with full coverage, 16 in 25 countries with incomplete coverage) (Supplementary Table SIII). Individual cycle reporting is being carried out in seven countries with full data coverage and in nine countries with incomplete coverage of the reported cycles.

There is a large variability in the size of reporting institutions, as defined by the number of treatment cycles (Supplementary Table SII). Clinics with cycle numbers between 200 and 499 are the most common (29.6%). When compared to previous EIM reports, there is an ongoing trend towards more large institutions (≥1000 cycles, 18.3% in 2014 versus 17.8% in 2013 and 16.9% in 2012).

Seventeen countries (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Italy, Kazakhstan, Macedonia, Norway, Poland, Portugal, Spain, Sweden, Switzerland and UK) reported some kind of data validation process.

Public access to individual clinic data was available only in nine countries: Albania, Estonia, Ireland, Macedonia, Romania, Slovenia, Spain, Sweden and the UK. Pharmaceutical industries or professional societies provided additional financial support for the national registration in 26 countries. In five countries the centres covered part of the expenses, while in five countries (Albania, Federation of Bosnia and Herzegovina, Poland, Switzerland, The Netherlands) all the expenses were covered by the centres alone. This information is missing in eight countries.

Number of treatment cycles per technique and availability

In 2014 a total number of 776 556 treatment cycles were reported to EIM (90 285 more than in 2013, +13.1%) (Table I). Since the beginning of its activities EIM has now recorded a total of more than 8 million treatments with ART leading to the birth of nearly 1.5 million infants (Table II). The most common technique is ICSI (362 285 cycles, 46.6%) followed by FER (192 017, 24.7%) and IVF (146 148, 18.8%). Compared to 2013, all treatment modalities numbers have increased, except frozen oocyte replacement (FOR). The steepest increase in treatment numbers since 2013 is observed in PGT (+62.3%) and ED (+40.4%). A number of countries reported fewer treatment cycles (Croatia, Cyprus, Estonia, Germany, Hungary, Iceland, Ireland, Kazakhstan, Moldova, Montenegro, Slovenia, Sweden and the UK). Croatia, Germany, Hungary and Modova had fewer clinics participating. Two countries reported a large increment in treatment numbers (Russia and Spain), both with many more ART institutions participating in the data collection.

Among the total of 508 433 fresh treatments (ICSI+IVF), 71.3% were performed with ICSI, showing a rise of +1.66% compared with 2013. The preponderance of ICSI over conventional IVF has become more pronounced in recent years (Fig. 1).

As in previous years, with 192 017 treatments, FER is rapidly gaining ground (+24.1%) but the relative proportion to fresh treatments was stable (37.8% in 2014 and 38.3% in 2013), Switzerland being the country with the highest proportion of FER (82.1%) and Serbia with the lowest (1.8%).

Availability of ART in any particular country is calculated by dividing the number of treatment cycles by the number of women of reproductive age (15–45 years) (Supplementary Table SIV). Availability can only be calculated in the 14 countries with full coverage. In those 14 countries a huge variability in availabilty was observed, ART being most available in Denmark, and least available in Malta. As a result the proportion of newborns resulting from ART born in Denmark was 6.4% of all newborns in that country and 0.9% in Malta.

Pregnancies and deliveries after treatment

Table III lists pregnancy rates (PR) and delivery rates (DR) after IVF or ICSI and after FER (regardless of the technique). As in previous reports, data on the number of initiated cycles were incomplete. For that reason we calculated outcome data per aspiration. All 39 participating countries were able to provide pregnancy and delivery data after aspiration, but seven countries failed to provide those after FER (completeness rate: 82.5%). Complete coverage data on both pregnancies and deliveries were provided by 14 countries (Supplementary Table SIV). As shown in Table II, the number of infants born after any method was not provided in five countries (completeness rate: 87.5%). As in earlier reports, the PR and DR (all treatment modalities included) varied significantly from one country to another, PR ranging from 17.1 to 53.1%, DR ranging from 7.9 to 37.8% (except Hungary, reporting no deliveries per aspiration for ART). After FER the DR varied between 5.1 and 41.2%.

Taking all data together (Table II), the PR per aspiration were similar in both IVF and ICSI, 29.3 and 27.2%, respectively, as were the DR, 22.3 and 20.1%, respectively. The PR and DR after thawing of embryos were 27.6 and 19.3%, respectively. The total number of ART infants born in 2014 after all techniques amounted to 170 163, a marked increase of 13.8% (total number of children born in 2013: 149 466).

For the first time, information about ‘freeze all’ cycles was collected (Supplementary Table SV). Freeze all was carried out at the oocyte level in eight countries (20.5%), and at the embryonic level in 18 countries (46.1%). The registered data demonstrate that freeze all was the decision in 3080 (0.6%) of all IVF+ICSI cycles (at the oocyte level) and in 23 567 (4.8%) at the embryonic level.

Detailed accounts of cycle numbers, aspirations, transfers, pregnancies, and deliveries in IVF, ICSI and FER (after both IVF and ICSI) are given in the Supplementary Tables SV–SVII.

ED data are given by 22 of 39 participating countries (55%) (Supplementary Table SVIII). In most of the other countries this technology is not being performed for legal reasons. Most donation cycles were carried out in Spain, Russia and the Czech Republic, with 12 632, 3672 and 4924 cycles, respectively. Some of 29 965 ED cycles were carried out with freshly collected oocytes (22, 100%), some with frozen oocytes (FOR). PR were only available per embryo transfer (ET), but were considerably higher with freshly donated oocytes (50.3%) than after thawing of oocytes (37.7%). The differences among countries were considerable, ranging between 15.1 and 66.7%. A total of 17 259 deliveries were counted, which considerably exceeds the 11 861 deliveries counted in 2013 (+45.5%). This increment is due to higher numbers of reported deliveries in Spain (+45.1%) and Russia (+47.4%).

Age distribution

As in previous reports, the age distribution of women treated with IVF and ICSI varied among different countries (Supplementary Tables SIX and SX). Not all countries were able to provide data on the age distribution in ICSI and in IVF, some because no IVF treatments were carried out. The highest percentage of women aged 40 years and older undergoing aspiration for IVF was found in Greece (as in 2013), whereas the highest percentage of women aged <34 years was found in Ukraine and in Poland (as in 2013). Also in ICSI the highest percentage of women aged 40 years and older undergoing aspiration was found in Greece, whereas the highest percentage of women undergoing aspiration aged <34 years was recorded in Albania (as in 2013). Overall the well known age-dependent decline of the reported PR and DR was very similar in IVF and ICSI, but the differences among countries were considerable.

Although the age-related decline was present in FER cycles as well (Supplementary Table SXI), the outcome data of FER were generally higher than in the fresh cycles. In contrast, in ED donation cycles (Supplementary Table SXII) age of the recipient women did not impact on PR or on DR.

Number of embryos transferred and multiple births

The number of embryos transferred after IVF and ICSI together are presented in Table IV. Although the specific number of elective single embryo transfers cannot be identified, the number of transfers of only one embryo per cycle continues to rise, whereas the number of transfers of three or more embryos per cycle decreases (Fig. 2). The number of countries with more than 50% single embryo transfers has risen from six in 2013 to eight in 2014 (Austria, Belgium, Czech Republic, Denmark, Finland, Iceland, Poland and Sweden). The countries with more than 40% of transfers with three embryos were Bosnia-Herzegovina (Republik of Srpska), Lithuania and Serbia. In Greece 7.4% of transfers were carried out with four or more embryos.

Additional details about the pregnancy and delivery data are given in Supplementary Tables SXIII and SXIV. The recorded incidence of pregnancy loss was 15.5% after IVF + ICSI (in 2013: 16.8%) and 18.6% after FER (in 2013: 19.8%). The recorded loss to follow-up was 9.9% after IVF + ICSI (in 2013: 8.3%) and 7.3% after FER (in 2013: 9.7%).

Twin and triplet deliveries were similar after IVF+ICSI treatments and after FER. Those countries with the highest proportion of single embryo transfers also had the lowest twin and triplet DR (the lowest in Sweden, 4.2 and 0.1%, respectively) in fresh cycles. The countries still proceeding with the transfer of three or more embryos in fresh cycles present with DR of twins ranging between 18.2% (Lithuania) and 29.6% (Bosnia-Herzegovina, Republik of Srpska), and with DR of triplets ranging between 1.2% (Greece) and 1.8% (Lithuania). Interestingly, Lithuania with higher numbers of transfers of three and more embryos in fresh cycles did not report any twin or triplet deliveries after FER.

Regarding ED, of 15 749 deliveries with information regarding multiplicity, 3675 were twins (23.3%) and 56 were triplets (0.4%) (data not presented in tables).

Perinatal risks and complications

Data on premature deliveries were availabe from 20 European countries. The incidence of premature delivery is listed according to the number of newborns in Supplementary Table SXV. The prematurity data from fresh IVF and ICSI, of FOR and of ED are listed together. In singleton pregnancies the incidence of extreme preterm birth (gestational weeks 20–27) reached 2.1% (1.3% in 2013), 4.1% in twin pregnancies (2.9% in 2013) and 7.9% in triplet pregnancies (8.3% in 2013). A high incidence of very premature birth rates (gestational weeks 28–32) was found in twin pregnancies: 15.5% (in 2013: 9.2%) and in triplet pregnancies: 32.4% (in 2013: 31.2%). Term delivery (≥37 weeks) was 77.1% delivered in singleton pregnancies, 41.8% in twin pregnancies and 12.7% in triplet pregnancies, all similar to the results achieved in 2013. Interestingly, since the beginning of the recording of this item the premature DR (<37 weeks) of singleton pregnancies calculated per embryo transfer has remained similar to the premature DR of twin pregnancies (Fig. 3).

Complications of various steps of ART, such as ovarian hyperstimulation syndrome (OHSS), haemorrhage, infections and maternal deaths, were reported by 31 countries (Supplementary Table SXVI). With 2040 cases, OHSS was the most common reported complication of ART (incidence rate: 0.3% of all reported cycles). Other complications were much rarer, such as haemorrhage (0.1% of all treatment cycles), infections (0.01%) and maternal death (3 per 700 000 treatment cycles). Two cases of maternal death occurred in the context of pregnancy and delivery (aortic dissection in a pregnant Turner syndrome patient, amniotic fluid embolism). Another patient died of sudden heart failure 1 day before oocyte collection.

Foetal reductions were reported from 16 countries and were performed in 0.07% of all treatment cycles. Most foetal reductions were reported in the UK, Spain and Russia.

PGT/PGT-A

PGT (PGT for monogenic disorders or structural rearrangements) and PGT-A (PGT for aneuploidy) activities were reported from 22 countries (20 in 2013, 19 in 2012). The number of treatment cycles was 15 894 (2.05% of all ART treatments, Table I), which compared to 2013 represents a drastic rise in treatment numbers (+6103). These involved 13 460 fresh cycles and 2434 thawings, resulting in 6269 fresh and 2021 frozen embryo transfers. In total, 2538 pregnancies (42.5% per transfer) and 2024 deliveries (32.3% per transfer) resulted from fresh cycles. Corresponding figures for FER were 801 (41.8% per transfer) and 619 (30.8% per transfer). The main contributor was Spain with 5242 cycles. A more detailed survey of PGT/PGT-A activities can be found in the annual reports of the ESHRE PGT consortium (De Rycke et al., 2017).

IVM

A total of 292 treatments with IVM were reported from eight countries (247 in 2013, 421 in 2012) (Table I). Most IVM cycles were recorded in France and Russia. A total of 124 transfers resulted in 28 pregnancies and 17 deliveries. France accounted for 68.8% of immature oocyte aspirations, but reported only 53 transfers (26.4%) and 10 deliveries after IVM.

FOR

FOR was reported by 16 countries (12 in 2013) and this accounted for 3404 thawing cycles (6611 in 2013) (Table I), 2655 transfers, 790 pregnancies and 548 deliveries. The vast majority was carried out in Italy (1639 treatments) and in Spain (845 treatments).

IUI

Data on IUI with husband semen (IUI-H, Supplementary Table SXVII) and using donated semen (IUI-D, Supplementary Table SXVIII) were collected by 1364 institutions in 25 and 21 countries, respectively. Spain was the most active country in both treatment modalities. All together, 120 789 treatments with IUI-H resulted in 9533 deliveries (7.92%), whereas 49 163 treatments with IUI-D in 5061 deliveries (10.3%), similar to results reported in 2013. In all three age groups most pregnancies led to singleton deliveries (90.3% in IUI-H, 92.2% in IUI-D). The twin and triplet DR were generally low (Table V), depending on the age of the treated patient and were similar to those reported in previous years (twin deliveries: 8.8 and 7.3%, respectively; triplet deliveries: 0.4 and 0.3%, respectively).

Sum of fresh and FER (‘cumulative’) DR

Supplementary Table SXIX provides us with an estimate (not a true rate, as the data set presented here is cross-sectional) of a cumulative DR, calculated from the fresh embryo transfers and those carried out after thawing. The data are presented based on the sum of the fresh and FER deliveries and the number of aspirations of the same year as the denominator. As no data on deliveries were available from Hungary, we were able to calculate cumulative DR from the data of 38 countries (35 countries in 2013). Whereas in all data taken together the DR after the fresh cycle amounted to 20.5%, the cumulative DR was 28.1% (a rise of 1.2% compared to 2013). The countries with the highest benefit resulting from FER were Finland (+16.0%), Ukraine (+15.2%), Albania (+14.6%), the Czech Republic (+14.0%), Kazakhstan (+13%) and Sweden (+13.0%). The countries with the lowest benefit resulting from FER were Malta (+0%) and Macedonia (+0.3%).

Cross-border reproductive care

Fifteen countries reported data on cross-border patients: Albania, Belarus, Croatia, Denmark, Finland, Greece, Iceland, Macedonia, Malta, Poland, Portugal, Serbia, Slovenia, Spain and Switzerland. A total of 17 160 cycles were reported, 36.4% of which involved IVF/ICSI with the couple’s own gametes, while 45.6% were ED and 17.4% were IVF or ICSI with semen donation. Additionally, 8021 IUI with sperm donation were registered. Information regarding the countries of origin was very incomplete and not reliable enough to obtain any conclusive information. The main reasons reported by patients were to have access to a technique not legally available in their home countries (53.2%) or to seek a higher quality treatment (17.0%).

Discussion

This is the 18th annual report of the combined activities of the European national registries collecting data on ART. The EIM Consortium, from 1997 to 2014, has reported on more than 8 million treatments (8 010 527) leading to the birth of nearly 1.5 million infants (1 478 452). A comprehensive review of the first 15 years of EIM (from 1997 to 2011) was recently published (Ferraretti et al., 2017).

The present collected data summarizes the totality of the data collections provided by 39 European countries (38 in 2013), as Bosnia-Herzegovina joined the consortium. Data are still not available from Azerbaijan, Georgia and Kosovo. Slovakia and Turkey are members of the EIM Consortium, but were not able to participate. Another group of small European countries never participated in the Consortium, such as Andorra, Armenia, Liechtenstein, Luxemburg, Monaco, San Marino and The Vatican, most of them not offering independent ART services. The level of completeness at the national level has risen to 92.9%, and at the level of the reporting clinics to 87.5%, both a substantial increase as compared to previous years.

Fourteen countries were able to provide data sets for all registered clinics (Supplementary Table SIV), but the quality of data sets varies much from one country to another. A good example are discrepancies on the definition of a treatment: initiated treatment or collection of oocytes. Whereas data on aspirations were available from 34 countries (87.2%), those on initiated cycles were from 33 (or 32) countries (84.6 or 82.0%), both not necessarily the same countries. Only in 27 countries (69.2%) were we able to obtain information about both the number of initiated cycles and the number of oocyte collections. Other countries have failed to report treatment endpoints, most notably delivery outcome data were availabe only in 39 countries after fresh cycles and after FER (97.4%). Underreporting of treatment numbers may lead to overestimation of the efficacy outcome of the offered treatments. Improvements in the quality of the retrieved data sets may still be achieved. This may possibly be achieved through the organization of external audits both in the offices of the national registries and in the local IVF clinics, as exemplified by Switzerland (Van den Bergh et al., 2005) and by the European Liver Transplant register (Karam et al., 2003). However, the introduction of such an external auditing system would require an enormous financial and logistic effort, which can only be performed successfully with support of the national and European authorities.

The steady rise in the observed treatment numbers may be a motivation to improve stringency in the monitoring of the treatments. Whereas in 2013, 686 271 treatments with various forms of ART were reported to EIM (Calhaz-Jorge et al., 2016, 2017), these numbers rose to 776 556 in 2014 (Table II). Close to two-thirds of this increase results from a basic change in the Spanish registry, which now provides nearly complete data sets (78 182 treatments in 2013 to 109 275 treatments in 2014). In addition, the Russian centres contributed with 94 985 treatments in 2014 (in 2013: 67 861). A total of 136 436 deliveries led to the birth of 170 163 infants, representing 2.1% of all children born in Europe (Table III). Due to differences in access to ART, the relative proportion of children born after ART may vary from 0.2% in Serbia to 6.4% in Denmark. These numbers have a significant impact on demography and should therefore be of interest to all stakeholders.

Data collection can only be optimized in the presence of good governance. Compulsory data collection systems have been shown previously to be more effective than voluntary systems, but personal initiative still played a decisive role in seven countries. The countries with the lowest participation of IVF institutions were Serbia (1 of 18), Albania (1 of 8), Bulgaria (4 of 32), Croatia (7 of 13) and Ireland (3 of 7). Except in Croatia, none of these countries benefited from a compulsory data registration. Coherent and systematic data registration and monitoring of all treatment outcomes should become mandatory in ART and be considered as an indicator of excellent quality of care and good governance.

The annual EIM reports have been valuable to detect and monitor ongoing trends in ART. Whereas treatment numbers of IVF, IVM and FOR have appeared to be stable in recent years, those of ICSI, ED, FER and PGT have been on the rise. The predominance of ICSI over IVF has been observed in previous reports (Calhaz-Jorge et al., 2017). The rise in treatment numbers with FER fits well to the current trend towards segmentation of ART (Devroey et al., 2011) including ‘freeze all’ cycles. This is the first report containing data on ‘freeze all’ cycles.

The steady rise in the demand for PGT may well be attributed to the availability of arays for genetic testing, with PGT-A numbers increasing from 4% in 2010 to 20% in 2013 (De Rycke et al., 2017), and now replacing less effective forms of chromosome analysis, such as fluorescent in situ hybridization (Mastenbroek et al., 2007). The report of the PGD consortium of ESHRE has demonstrated that the bulk of PGD consists of aneuploidy screening (De Rycke et al., 2017) and the demand/offer for that sort of treatment seems to be rising constantly, despite the current lack of prospective randomized clinical trials substantiating the benefits and specific indications for this technology (Sermon et al., 2016; Harper et al., 2018).

Another trend visible from the annual EIM reports is the lower numbers of embryos transferred per treatment cycle resulting in fewer multiple deliveries. The number of embryo transfers with only one embryo continues to rise (Fig. 2) and, in parallel, the numbers of twin and triplet deliveries decline. Interestingly, whereas the proportion of premature deliveries of twins and triplets remains similar to previous years, the proportion of premature deliveries (<37 weeks) of singletons per embryo transfer has risen from 0.96% in 2006 to 1.79% in 2014 (Fig. 3). The reason for this steady increase in premature singleton deliveries remains speculative, but all these findings point towards the need for continuous and prospective follow-up of all activities in ART.

Other severe adverse events, such as infection and haemorrhage complicating oocyte retrieval, but also maternal death, continue to occur. Three cases of maternal death were reported in 2014, all within the context of ongoing pregnancies (incidence rate: 1.59/100 000 pregnancies). The latter seem to be underreported, as an earlier Dutch survey has demonstrated a much higher incidence of maternal death within the context of ART. Indeed, an incidence of maternal mortality of 6/100 000 directly related to IVF and of 42.5/100 000 pregnancies resulting from ART, mainly in twin pregnancies (Braat et al. 2010) was reported. Underreporting of adverse events leads to an overestimation of the safety of the treatment. Although the number of reported foetal reductions has risen from 416 to 526 in 2014 (reported to be performed in 16 countries), these numbers most likely are also drastically underreported. Without this intervention, the number of high order multiple deliveries would be higher, but with current technology developments in ART (including elective single embryo transfer and cryostorage of remaining oocytes or embryos) multiple pregnancies and related complications should be avoidable today.

The practice of freezing oocytes and embryos is on the rise and that can be clearly seen in the steep rise of the number of recorded FER treatments, which in 2014 for the first time exceeded that of conventional IVF (i.e. 192 017 versus 146 148, Table I). Earlier studies have shown that singleton newborns born from fresh treatments have lower birthweights than those born after a thawing cycle (De Geyter et al., 2006; Henningsen et al., 2011). Recently, the incidence of neonates born large for gestational age has been shown to be significantly more prevalent in FER cycles (Pinborg et al., 2010, 2014; Luke et al., 2017). Although the EIM data set cannot provide data on this particular potential adverse effect of ART, the EIM datasets will continue to monitor the relative importance of FER within the context of ART.

The EIM data sets also reveal large differences in access to infertility treatment in the various participating European countries. The World Health Organization (WHO) has defined ‘infertility’ as a ‘disease of the reproductive system’ and as a ‘disability’ and access to medical treatment has been issued as a human right. In contrast to those basic principles, the number of treatments with either form of ART varies greatly between European countries. This is best exemplified in those countries with complete coverage (Supplementary Table SIV). Not only the number of cycles per million inhabitants varies between 423 in Malta and 2978 in Iceland, but also the relative number of infants born from ART treatments. The ESHRE Capri Group has estimated that ~1500 couples with infertility per million inhabitants should be treated with ART per year (ESHRE Capri Group, 2001). Even among the 14 countries with complete coverage five countries did not fulfil that requirement in 2014 (35.7%) and these countries might be thought to belong to the more advanced ones. Transparency in data both at the national level but also, for comparison purposes, at the international level may be particularly helpful in convincing politicians and health care authorities to undertake measures in improving access to treatment.

Until today the data collection handled by the EIM Consortium has been cross-sectional and based on annual data reporting. Cumulative data analysis has only been possible within the frame of 1 year. The EIM Consortium has come far to push the completeness of the European data collection beyond 90%, as first demonstrated in the 2014 data sets, described here. Increasingly, infertility treatments are being fragmented into small treatment units that may easily cross the time frame of cross-sectional data collections, which points to the need for developing new surveillance tools. A concept for prospective follow-up of infertility treatment has therefore been elaborated earlier (De Geyter et al., 2016).

So far the annual reports published by the EIM consortium, including the present 18th report, have been limited to being purely descriptive. The organization of the data collection, as carried out by the EIM Consortium, may be further developed towards medical surveillance and vigilance. Surveillance is defined by the continuous and systematic collection of health data (here related to ART and its outcome) needed for the analysis and interpretation of trends in medical care with a special focus on safety. Surveillance in medical care goes far beyond considering the results of prospective randomized trials, in which very selected cohorts of patients are recruited and treated under well-controlled conditions. Register-based data have their value by being less biased by predefined selection criteria. They reflect to a much larger extent real-life conditions and for that reason have the capacity to give a more realistic picture of the outcome results. However, real surveillance can only be achieved with more or less complete data sets, in which underreporting is avoided. That goal can best be achieved if data submission to the national registries is made compulsory.

Medical surveillance may also be used for the establishment of vigilance. Vigilance aims at detecting serious or less serious adverse events resulting from medical activities. Through the increasing trend towards replacing fewer embryos per treatment cycle, present-day ART has been successful in reducing the incidence of multiple delivery and the EIM annual reports have been able to make this trend visible and this increases the awareness on the usefulness of such practice. In addition, a more novel development is the adoption of the principle of ‘freeze all’ and the delayed thawing and transfer of frozen embryos, which has already resulted in an upsurge of the number of FER cycles. All these trends are expected to lower the incidence of other common complications, such as OHSS and foetal reduction. Other adverse events may still occur and need to be registered, because vigilance does not only consist of merely recording adverse events, but also the assessment of underlying causes and proper understanding of the mechanisms leading to the adverse events, which ultimately may lead to the formulation of preventive measures as part of an ongoing quality management development.

As shown here, one in 50 children born in Europe are the result of ART treatments. Practitioners, professional bodies, and national and European political bodies have a duty to realize that such therapies require appropriate logistic and financial support in order to set up compulsory national reporting electronic databases, ideally a pan-European centralized data collection, to monitor both the efficiency and safety of therapy and also the long-term health of children born after treatment. The creation of a unique individual patient European coding system will ensure all aspects of an ever increasing spectrum of ART care can be measured and analysed thus ensuring full surveillance and vigilance. The time is now. The concept of evolving the current cross-sectional register towards prospective surveillance and vigilance of care in ART will take years to become real and will require top down support from national and supranational health care authorities. Such a concept can only be supported by all stakeholders of ART, including the patients, and should be motivated to provide care with excellence.

Authors’ roles

V.G. performed the calculations. CDG wrote the article. All other co-authors reviewed the final article and made appropriate corrections and suggestions to improve it. In all, this document represents a fully collaborative work.

Funding

The study did not receive any external funding. All costs were covered by ESHRE.

Conflict of interest

There are no competing interests.

Appendix

Contact persons who are collaborators and represent the data collection programmes in participating European countries, 2014.

Albania

Prof. Orion Gliozheni, University Hospital for Obst&Gynecology, Departement of Obstetrics & Gynecology, Bul.B.Curri, Tirana, Albania. Tel: +355-4-222-3632; Fax: +355-4-225-7688; Mobile: +355-682029313. E-mail: [email protected]

Austria

Prof. Dr Heinz Strohmer, Dr Obruca and Dr Strohmer Partnerschaft Goldenes Kreuz-Kinderwunschzentrum, Lazarettgasse 16-18, 1090 Wien, Austria. Tel: +43-40-111-1400; Fax: +43-40-111-1401. E-mail: [email protected]

Belarus

Dr Elena Petrovskaya, ART centre ‘Embryo’, Filimonova 53, 220053 Minsk, Belarus. E-mail: [email protected]

Dr Oleg Tishkevich, Centre For Assisted Reproduction ‘Embryo’ Belivpul, Filimonova Str. 53, 220114 Minsk, Belarus. Tel: +375-29-622-2722; Fax: +375-17-237-6404; Mobile: +375-296222722; E-mail: [email protected]

Belgium

Prof. Christine Wyns, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Av. Hippocrate, 10, 1200 Brussels, Belgium. Tel. +32-27-64-6576; Fax: +32-27-64-9050; E-mail: [email protected]

Prof. Kris Bogaerts, I-Biostat, Kapucijnenvoer 35 bus 7001, 3000 Leuven, Belgium. Tel: +32-016-33-6890; Fax: +32-016-33-7015. E-mail: [email protected]

Bosnia

Prof. Dr Devleta Balic, Zavod za humanu reprodukciju ‘Dr Balic’, Kojsino 25, 75000 Tuzla, Bosnia—Herzegovina. Tel: +387-35-26-0650; Mobile: +387-61140222; E-mail: [email protected]

Prof. Dr Sanja Sibincic, Health Centre Medico-S, Jevrejska 58/A, 78000 Banja Luka, Bosnia—Herzegovina. Tel: +387-51-232-100; Mobile: +387-65515942; E-mail: [email protected]

Bulgaria

Irena Antonova, ESHRE certified clinical embryologist (2011), Ob/Gyn Hospital Dr Shechterev, 25-31, Hristo Blagoev Strasse, 1330 Sofia, Bulgaria. Tel: +359-88-712-7651; E-mail: [email protected]

Croatia

Prof. Dr Hrvoje Vrcic, Zagreb University Medical School, Obstetrics and Gynecology, Petrova 13, 10000 Zagreb, Croatia. Tel: +385-14-60-4646; Fax: +385-14-63-3512; E-mail: [email protected]

Dr Dejan Ljiljak, Clinical Hospital Centre ‘Sestre milosrd’, Department for Biology of Human Reproduction, Ob/Gyn Clinic, Vinogradska c. 29, 10000 Zagreb, Croatia. Tel: +385-378-7597; Fax: +385-13-76-8272; Mobile: +385-378-7125; E-mail: [email protected]

Cyprus

Dr Michael Pelekanos, Fertility Centre Aceso, 1, Pavlou Nirvana str., 3021 Limassol, Cyprus. Tel: +357-99-64-5333; Fax: +357-25-82-4477; Mobile +30-6944248433; E-mail: [email protected]

Czech Republic

Dr Karel Rezabek, Medical Faculty, University Hopsital, CAR-Assisited Reproduction Centre, Gyn/Ob departement, Apolinarska 18, 12000 Prague, Czech Republic. Tel: +420-22-496-7479; Fax: +420-22-492-2545; Mobile: +420-724685276; E-mail: [email protected]

Mgr. Jitka Markova, Institute of Health Information and Statistics of the Czech Republic, Palackeho namesti 4, 12801 Prague, Czech Republic. Tel: +420-22-497-2832; Mobile: +420-72-182-7532; E-mail: [email protected]

Denmark

Dr Josephine Lemmen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: +45-35-450-934; Fax: +45-35-454-945; Mobile: +45-30285712; E-mail: [email protected]

Estonia

Dr Deniss Sõritsa, Tartu University Hospital and Elitre Clinic, Tartu, Estonia. Tel: +372-740-9930; Fax: +372-740-9931; E-mail: [email protected]

Finland

Prof. Mika Gissler, THL National Institute for Health and Welfare, PO Box 30, 00271 Helsinki, Finland. Tel: +385-29-524-7279; E-mail: [email protected]

Dr Aila Tiitinen, Helsinki University Central Hospital, Dept. of Ob/Gyn, Haartmaninkatu, 2, PO Box 140, 00029 HUS—Helsinki, Finland. Tel: + 358-50-427-1217; E-mail: [email protected]

France

Prof. Dominique Royere, Agence de la Biomédecine, 1 Av du stade de France, 93212 Saint-Denis La Plaine Cedex, France.Tel.: +33-15-593-6555; Fax: +33-15-593-6561; E-mail: [email protected]

Germany

Dr Andreas Tandler—Schneider; Fertility Centre Berlin; Spandauer damm 130; 14050 Berlin; Germany. Tel: +49-30-23-320-8110; Fax: +49-30-23-320-8119; E-mail: [email protected]

Dr Markus Kimmel, D.I.R. Geschäftsstelle, Torstrasse 140, D-10119 Berlin, Germany. Tel: +49-303-980-0743; E-mail: [email protected]

Greece

Prof. Aris J. Antsaklis; Professor of Obstetrics and Gynecology, University of Athens, President Hellenic Authority of Assisted Human Reproduction. Tel: +30-694-429-9699; E-mail: [email protected]

Dr Dimitris Loutradis, Athens Medical School, 1st Department of OB/GYN, 62, Sirinon Street, 17561 P. Faliro, Athens, Greece. Tel: +30-19-83-3576; Fax: +30-19-88-3834; Mobile: +30-693-242-1747; E-mail: [email protected]

Hungary

Prof. Janos Urbancsek, Semmelweis University, 1st Dept. of Ob/Gyn, Baross utca 27, 1088 Budapest, Hungary. Tel: +36-12-66-0115; Fax: +36-12-66-0115; E-mail: [email protected]

Prof. G. Kosztolanyi, University of Pecs, Dept. of Medical Genetics and Child Development, Jozsef A.u.7., 7623 Pecs, Hungary. Tel: +36-72-53-5977; Fax: +36-72-53-5972; E-mail: [email protected]

Iceland

Mr Hilmar Bjorgvinsson, Art Medica, Baejarlind 12, 201 Kopavogur, Iceland. Tel: +354-515-8100; Fax: +354-515-8103; E-mail: [email protected]

Ireland

Dr Edgar Mocanu, Human Assisted Reproduction Ireland Rotunda Hospital, HARI Unit, Master’s House, Parnell Square, 1 Dublin, Ireland. Tel: +353-18-07-2732; Mobile: +353-86-81-8839; Fax: +353-18-72-7831; E-mail: [email protected]

Italy

Dr Giulia Scaravelli, Istituto Superiore di Sanità, Registro Nazionale della Procreazione Medicalmente Assistita, CNESPS, Viale Regina Elena, 299, 00161 Roma. Tel: +39-49-90-4050; Fax: +39-49-90-4324; E-mail: [email protected]

Dr Roberto de Luca, Istituto Superiore di Sanità, Registro Nazionale della Procreazione Medicalmente Assistita, CNESPS, Viale Regina Elena, 299, 00161 Roma. Tel: +39-064-990-4320; E-mail: [email protected]

Kazachtstan

Prof. Dr Vyacheslav Lokshin, The Urban Centre of Human Reproduction, Tole Be Street 99, 50012 Almaty, Kazakhstan. Tel: +7-727-234-3434; Fax: +7-727-264-6615; Mobile: +7-7017558209; E-mail: [email protected]

Dr Valiyev Ravil, The Scientific Centre for Obstetrics, Gynecology and Perinatology, Dostyk street 125, 050020 Almaty, Kazakhstan. Tel: +7-727-300-4530; Fax: +7-727-300-4529; Mobile: +7-7772258189; E-mail: [email protected]

Latvia

Dr Valeria Magomedova, Jusu Arsti Private Clinic, Apuzes 14, 1046 Riga, Latvia. Tel: +371-67-87-0029; E-mail: [email protected]

Lithuania

Dr Zivile Gudleviciene, Baltic American Clinic, IVF Laboratory, Nemencines rd 54 A, 10103 Vilnius, Lithuania. Tel: + 370-52-34-2020; Mobile: +370-68682417; E-mail: [email protected]

Dr Giedre Belo lopes, Northway Medical Centre, S. Žukausko g. 19, Vilnius 08234, Lithuania. Tel: + 370-529-8290; E-mail: [email protected]

Macedonia

Prof. Zoranco Petanovski, Re-medika Hospital; Jane dandaniski 87/1/4, 1000 Skopje, Macedonia. Tel: +389-23-07-3335; Mobile: +389-72443114; E-mail: [email protected]

Malta

Dr Jean Calleja-Agius, University of Malta, 12, Mon Nid, Gianni Faure Street, TXN2421 Tarxien, Malta. Tel: +356-21-69-3041; Mobile: +356-99-55-3653; E-mail: [email protected]

Ms Josephine Xuereb, Mater Dei Hospital Malta, Apt 1 Hampton Place, BKR 104 B’Kara, Malta. Tel: +356-99-99-2382; E-mail: [email protected]

Moldova

Prof. Dr Veaceslav Moshin, Medical Director at Repromed Moldova, Centre of Mother @ Child protection, State Medical and Pharmaceutical University ‘N.Testemitanu’, Bd. Cuza Voda 29/1, Chisinau, Republic of Moldova. Tel: +373-22-26-3855; Mobile: +373-69724433; E-mail: [email protected]

Montenegro

Dr Tatjana Motrenko Simic, Medical Centre Cetinje, Human Reproduction Departement, Vuka Micunovica 4, 81310 Cetinje, Montenegro. Tel: +382-41-23-2690; Fax: +382-41-23-1212; Mobile: +382-69-05-2331; E-mail: [email protected]

Dragana Vukicevic, Hospital ‘Danilo I’, Humana reprodukcija, Vuka Micunovica bb, 86000 Cetinje, Montenegro. Tel: +382-67-55-1371; E-mail: [email protected]

Norway

Dr Liv Bente Romundstad, St. Olavs Hospital, Postboks 3250 Sluppen, Olav Kyrres gt.17, 7006 Trondheim, Norway. Tel: +47-73-86-8000; Fax: +47-73-86-7602; Mobile: +47-90-55-0207; E-mail: [email protected], [email protected]

Poland

Dr Anna Janicka, VitroLive, Kasprzaka 2 A, 71-074 Szczecin, Poland. Tel: +48-69-167-6305; E-mail: [email protected]

Portugal

Prof. Dr Carlos Calhaz-Jorge, CNPMA, assembleia da Republica, Palacio de Sao Bento, 1249-068 Lisboa, Portugal. Tel: +351-21-391-9303; Fax: +351-21-391-7502; E-mail: [email protected]

Ms Ana Rita Laranjeira, CNPMA, Assembleia da Republica, Palaio de Sao Bento 1249-068 Lisboa, Portugal. Tel: +351-21-391-9303; Fax: +351-21-391-7502; E-mail: [email protected]

Romania

Mrs Ioana Rugescu, Gen Secretary of AER Embryologist association and Representative for Human Reproduction Romanian Society. Tel: +40-74-450-0267; E-mail: [email protected]

Dr Bogdan Doroftei; Univ. of Medicine and Pharmacy Iasi; Teaching Hospital Obgyn ‘Cuza Voda’; Cuza Voda Str. 34; 700038 Iasi; Romania. Tel: + 40-23-221-3000/int. 176; Mobile: +40-744515297; E-mail: [email protected]; [email protected]

Russia

Dr Vladislav Korsak, International Centre for Reproductive Medicine, General Director, Liniya 11, Building 18B, Vasilievsky Island, 199034 St-Petersburg, Russia C.I.S. Tel: +7-812-328-2251; Fax: +7-812-327-1950; Mobile: +7-921-965-1977; E-mail: [email protected]

Serbia

Prof. Nebosja Radunovic, Institute for Obstetrics and Gynecology, Visegradska 26, 11000 Belgrade, Serbia. Tel: +38-111-361-5592; Fax: +38-111-361-5603; Mobile: +381-63200204; E-mail: [email protected]

Dr Sci. Nada Tabs, Klinika za ginekologiju i akuserstvo, Klinicki centar Vojvodine, Branimira Cosica 37, 21000 Novi Sad, Serbia. Mobile: +381-63508185; E-mail: [email protected]

Slovenia

Dr Irma Virant-Klun, University Medical Centre Ljubljana, Departement of Obstetrics and Gynecology, Slajmerjeva 3, 1000 Ljubljana, Slovenia. Tel: +386-1-522-6013; Fax: +386-1-431-4355; Mobile:+386-31625774; E-mail: [email protected]

Spain

Mrs Irene Cuevas Saiz, Hospital General de Alicante, Infertility Dept., Av Pintor Baeza, 12, 03010 Valencia, Spain;. Tel: +34-96-197-2000; Fax: +34-91-799-4407; Mobile +34-677245650; E-mail: [email protected]

Dr Fernando Prados Mondéjar, Hospital de Madrid-Montepríncipe, HM Fertility Centre Monteprincipe, C/Montepríncipe 25, 28660 Boadilla del Monte, Spain. Tel: +34-91-708-9931; Mobile +34-646737237; E-mail: [email protected]

Sweden

Prof. Christina Bergh, Sahlgrenska University Hospital, Department of Obstetrics and Gynaecology, Bla Straket 6, 413 45 Göteborg, Sweden. Tel: +46-31-342-1000, +46-73-688-9325; Fax: +46-31-41-8717; Mobile +46-736889325; E-mail: [email protected]

Switzerland

Ms Maya Weder, Administration FIVNAT, Postfach 754, 3076 Worb, Switzerland. Tel: +41-031-819-7602; Fax + 41-031-819-8920; E-mail: [email protected]

Prof. Christian De Geyter, University Women’s Hospital of Basel, Abteilungsleiter gyn. Endokrinologie und Reproduktionsmedizin, Spitalstrasse 21, 4031 Basel, Switzerland. Tel: +41-61-265-9315; Fax: + 41-61-265-9194; E-mail: [email protected]

The Netherlands

Dr Jesper M.J. Smeenk, St Elisabeth Hospital Tilburg, Dept. of obstetrics and Gynaecology, Hilv, The Netherlands. Tel: +31-13-539-3108; Mobile: +31-622753853; E-mail: [email protected]

Ukraine

Prof. Dr Mykola Gryshchenko, IVF Clinic Implant Ltd, Academician V.I.Gryshchenko Clinic for Reproductive Medicine, 25 Karl Marx Str., 61000 Kharkiv, Ukraine. Tel: +380-57-12-4522; Fax: +380-57-70-507-0703; Mobile +380-57705070703; E-mail: [email protected]

UK

Mr Richard Baranowski, Deputy Information Manager, Human Fertilization and Embryology Authority (HFEA), Finsbury Tower, 103-105 Bunhill Row, London EC1 Y 8HF, UK. Tel: +44-020-7539-3329; Fax: +44-020-7377-1871; E-mail: [email protected]

References

Author notes