ART in Europe, 2017: results generated from European registries by ESHRE

ART in Europe, 2017: results generated from European registries by ESHRE † The European IVF-Monitoring Consortium (EIM) ‡ for the European Society of Human Reproduction and Embryology (ESHRE), C. Wyns 1, *, Ch De Geyter 2 , C. Calhaz-Jorge 3 , M.S. Kupka 4 , T. Motrenko 5 , J. Smeenk 6 , C. Bergh 7 , A. Tandler-Schneider 8 , I.A. Rugescu 9 , S. Vidakovic 10 , and V. Goossens 11 1 Cliniques Universitaires Saint-Luc, Universite´ Catholique de Louvain, Brussels, Belgium 2 Reproductive Medicine and Gynecological Endocrinology (RME), University Hospital, University of Basel, Basel, Switzerland 3 Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal 4 Fertility Center—Gynaekologicum, Hamburg, Germany 5 Human Reproduction Center Budva, Budva, Montenegro 6 Elisabeth Twee Steden Ziekenhuis, Tilburg, The Netherlands 7 Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Go¨teborg University, Go¨teborg, Sweden 8 Fertility Center Berlin, Berlin, Germany 9 National Transplant Agency, Romania 10 Clinical Center Serbia «GAK», Institute of Obstetrics and Gynecology, Beograd, Serbia 11 ESHRE Central Office, Grimbergen, Belgium *Correspondence address. Cliniques Universitaires Saint Luc, Service FIV-Andrology, Avenue Hippocrate 10, 1200 Brussels, Belgium. Tel: þ3227646576; E-mail: christine.w[email protected] https://orcid.org/0000-0002-6581-5003 Submitted on May 27, 2021; resubmitted on May 27, 2021; editorial decision on June 14, 2021 STUDY QUESTION: What are the data on ART and IUI cycles, and fertility preservation (FP) interventions reported in 2017 as compared to previous years, as well as the main trends over the years? SUMMARY ANSWER: The 21st ESHRE report on ART and IUI shows the continual increase in reported treatment cycle numbers in Europe, with a decrease in the proportion of transfers with more than one embryo causing an additional slight reduction of multiple delivery rates (DR) as well as higher pregnancy rates (PR) and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the number of IUI cycles increased and their outcomes remained stable. WHAT IS KNOWN ALREADY: Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been gathered and analyzed by the European IVF-monitoring Consortium (EIM) and communicated in a total of 20 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION: Data on European medically assisted reproduction (MAR) are collected by EIM for ESHRE on a yearly basis. The data on treatments performed between 1 January and 31 December 2017 in 39 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 1382 clinics offering ART services in 39 countries reported a total of 940 503 treatment cycles, including 165 379 with IVF, 391 379 with ICSI, 271 476 with FER, 37 303 with preimplantation genetic testing (PGT), 69 378 with egg donation (ED), 378 with IVM of oocytes, and 5210 cycles with frozen oocyte replacement (FOR). A total of 1273 institutions reported data on 207 196 IUI cycles using either husband/partner’s semen (IUI-H; n ¼155 794) or donor semen (IUI-D; n¼51 402) in 30 countries and 25 countries, respectively. Thirteen countries reported 18 888 interventions for FP, including oocyte, ovarian tissue, semen and testicular tissue banking in preand postpubertal patients. MAIN RESULTS AND THE ROLE OF CHANCE: In 21 countries (20 in 2016) in which all ART clinics reported to the registry, 473 733 treatment cycles were registered for a total population of approximately 330 million inhabitants, allowing a best-estimate of a mean of 1435 cycles performed per million inhabitants (range: 723–3286). Amongst the 39 reporting countries, the clinical PR per aspiration and per transfer in 2017 were similar to those observed in 2016 (26.8% and 34.6% vs 28.0% and 34.8%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2016 (24% and † ESHRE pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE. ‡ EIM Committee 2019–2021: chairman: C.W.; chairman elect: J.S.; past chairman: C.D.; members: C.B., C.C.-J., M.K., T.M., A.R., A.T.-S. and S.V.; V.G. is a science manager at ESHRE Central Office, Brussels. See also Appendix for contributing centres and contact persons representing the data collection programmes in the participating European countries. V CThe Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Human Reproduction Open, Vol.00, No.0, pp. 1–17, 2021 doi:10.1093/hropen/hoab026 ESHRE PAGES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.5% vs 25% and 33.2% in 2016). When freeze all cycles were removed, the clinical PRs per aspiration were 30.8% and 27.5% for IVF and ICSI, respectively. After FER with embryos originating from own eggs the PR per thawing was 30.2%, which is comparable to 30.9% in 2016, and with embryos originating from donated eggs it was 41.1% (41% in 2016). After ED the PR per fresh embryo transfer was 49.2% (49.4% in 2016) and per FOR 43.3% (43.6% in 2016). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and 4 embryos in 46.0%, 49.2%, 4.5% and in 0.3% of all treatments, respectively (corresponding to 41.5%, 51.9%. 6.2% and 0.4% in 2016). This resulted in a reduced proportion of twin DRs of 14.2% (14.9% in 2016) and stable triplet DR of 0.3%. Treatments with FER in 2017 resulted in a twin and triplet DR of 11.2% and 0.2%, respectively (vs 11.9% and 0.2% in 2016). After IUI, the DRs remained similar at 8.7% after IUI-H (8.9% in 2016) and at 12.4% after IUI-D (12.4.0% in 2016). Twin and triplet DRs after IUI-H were 8.1% and 0.3%, respectively (in 2016: 8.8% and 0.3%) and 6.9% and 0.2% after IUI-D (in 2016: 7.7% and 0.4%). Amongst 18 888 FP interventions in 13 countries, cryopreservation of ejaculated sperm (n ¼11 112 vs 7877 from 11 countries in 2016) and of oocytes (n ¼6588 vs 4907 from eight countries in 2016) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION: As the methods of data collection and levels of reporting vary amongst European countries, interpretation of results should remain cautious. Some countries were unable to deliver data about the number of initiated cycles and deliveries. WIDER IMPLICATIONS OF THE FINDINGS: The 21st ESHRE report on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, efforts should continue to optimize data collection and reporting with the perspective of improved quality control, transparency and vigilance in the field of reproductive medicine. STUDY FUNDING/COMPETING INTEREST(S): The study has received no external funding and all costs are covered by ESHRE. There are no competing interests. Key words: IVF / ICSI / IUI/ / egg donation / frozen embryo replacement / surveillance / vigilance / registry / data collection/ fertility preservation Introduction This is the 21st annual report of the European IVF-monitoring Consortium (EIM) under the umbrella of ESHRE, assembling the data on ART, IUI and fertility preservation (FP) reported by 39 participating European countries in 2017 (Supplementary Table SI). Eighteen previous annual reports published in Human Reproduction (https://www.eshre.eu/Data-collection-and-research/Consortia/EIM/ Publications.aspx)andtwoinHuman Reproduction Open (De Geyter et al., 2020;Wyns et al.,2020 ) covered treatment cycles from 1997 to 2016. As in previous reports, the printed version contains the five most relevant tables. Twenty additional supplementary tables (Supplementary Tables SI–SXX) are available online on the publisher’s homepage. The presentation of the data is consistent with those published in previous reports to allow easy comparison and assessment of trends. For the second consecutive year, data on FP were collected and added to this report. Material and methods Data collected on an aggregate basis were provided by 39 European countries, covering treatments with IVF, ICSI, frozen embryo replacement (FER), egg donation (ED), IVM, preimplantation genetic testing (PGT; pooled data) and frozen oocyte replacement (FOR). With regards to IUI, data for use of husband’s/partner’s semen (IUI-H) and donor semen (IUI-D) were distinguished. The report includes treatments started between 1 January and 31 December in 2017. Data on pregnancies and deliveries represent the outcomes of treatments performed in 2017. Data on FP, including numbers and types of cryopreserved material and interventions for use of cryostored material between 1 January and 31 December in 2017, were provided and reported as aggregated data of events that occurred during a 1-year period. The national representatives of the 44 countries that are members of the EIM were asked to fill out questionnaires. The same data sets as in 2016 for a total of 10 specific modules were sent using software designed for the requirements of this data collection (Dynamic Solutions, Barcelona, Spain). Any detected inconsistencies were clarified through contacts between the administrator of the ESHRE central office, V.G., and the national representative. The data were analyzed and presented similarly to previous reports, with some additional subgroups of interventions since the report on 2016 data, and footnotes to the tables were added for clarification on diverging results reported by individual countries, when applicable. The terminology used was based on the glossary of The International Committee for Monitoring Assisted Reproductive Technology (Zegers-Hochschild et al., 2017). Results Participation and data completeness Table I shows the number of clinics offering ART services with all available treatment modalities and institutions performing IUI (IUI-H and IUI-D). Compared to 2016, the total number of reporting clinics (1381 in 2017 vs 1347 in 2016) and number of reported treatments (940 503 in 2017 vs 918 159 in 2016, þ2.4%) increased. Amongst the 2Wyns et al. ...................................... .................................................. ........................................... ........................................... .............................................. Table I Treatment frequencies after ART in European countries in 2017. IVF clinics in the country Cycles/million* Country IVF Clinics Included IVF clinics IUI labs Included IUI labs IVF ICSI FER PGD ED IVM FOR All Women 15-45 Population Albania 11 1 11 1 0 105 82 1 24 0 2 214 Armemia 6 5 9 5 513 642 675 0 459 0 15 2304 Austria 29 29 0 0 1702 5298 2801 0 218 0 0 10 019 5870 1137 Belarus 8 7 10 7 1171 1570 663 68 61 0 9 3542 Belgium 18 18 28 28 2819 13 133 12 881 1145 1334 149 76 31 537 14 411 2778 Bosnia-Herzegovina 6 2 6 2 82 80 0 0 0 0 162 Bulgaria 36 36 37 37 311 4644 1365 124 714 0 0 7158 4719 1015 Croatia 15 15 16 16 1607 2727 1389 1436 0 0 62 7221 8864 1682 Czech Republic 44 44 0 0 15 557 13 907 0 5328 0 0 34 792 16 547 3286 Denmark 23 23 51 50 7262 6394 2726 345 798 0 19 17 544 15 783 3045 Estonia 6 6 6 6 637 1203 890 13 216 0 0 2959 11 705 2249 Finland 16 16 21 21 2471 1790 3584 97 645 0 0 8587 7519 1558 France 103 103 183 183 23 538 44 165 37 469 1452 1459 120 617 108 820 8528 1620 Germany 134 127 0 0 18 679 53 290 27 234 0 0 0 263 99 466 Greece 37 29 37 29 2166 13 588 5192 1534 5008 9 50 27 547 Hungary 14 13 0 0 1386 4022 0 0 23 0 0 5431 Iceland 1 1 1 1 259 221 267 0 65 0 0 812 11 498 2400 Italy 204 204 366 366 8049 44 965 17 281 3133 4864 0 1391 79 683 7335 1316 Kazakhstan 15 8 0 0 1664 3497 2416 1422 1103 0 0 10 102 Latvia 6 3 6 3 265 581 549 2 159 0 15 1571 Lithuania 6 5 6 5 395 187 2 0 0 0 584 Luxembourg 1 1 0 0 260 457 429 0 0 0 0 1146 9482 1904 Malta 2 2 3 0 17 214 0 0 0 0 155 386 3893 811 Moldova 4 3 5 0 960 346 0 0 0 0 1306 Montenegro 5 4 5 4 0 582 84 0 0 0 0 666 North-Macedonia 7 5 2 0 421 2100 277 0 142 0 0 2940 Norway 11 11 10 10 3963 2997 4476 0 0 0 0 11 436 11 566 2175 Poland 42 42 0 39 465 14 100 10 390 1242 1257 18 335 27 807 4712 723 Portugal 24 24 26 26 2646 3681 2317 275 1292 5 48 10 264 5387 997 Romania 19 10 19 10 1168 1732 1452 14 29 0 2 4397 Russia 220 159 0 0 38 874 48 739 35 979 5228 7777 20 594 137 211 Serbia 18 1 18 1 147 75 34 0 0 0 1 257 Slovenia 3 3 2 2 1054 2092 1422 62 5 0 4 4639 8986 2245 Spain 247 239 366 301 6473 43 790 27 690 15 373 31 441 27 798 125 592 Sweden 17 17 0 0 6187 5906 7006 504 267 0 0 19 870 Switzerland 27 27 0 0 986 5013 4944 76 0 0 0 11 019 6595 1299 The Netherlands 13 13 0 0 6417 7574 13 469 497 0 0 0 27 957 8936 1637 Ukraine 48 40 17 17 849 10 904 9080 1634 1134 0 7 23 608 UK 85 85 103 103 20 953 22 594 20 443 1624 3556 30 747 69 947 5392 1080 All 1531 1381 1370 1273 165 379 391 379 271 476 37 303 69 378 378 5210 940 503 7662 1435 Treatment cycles in IVF and ICSI refer to initiated cycles. For Austria, Belgium and Iceland treatment cycles refer to aspirations. For Austria, Belgium and Lithuania the total number of initiated cycles was only available for IVF and ICSI together, being 10 216, 18 681 and 395, respectively. For the Czech Republic and Lithuania, no distinction between IVF and ICSI is made. All cycles are counted as ICSI. Treatment cycles in frozen embryo replacement (FER) refer to thawings. For Croatia, Finland, Sweden and the Netherlands, treatment cycles refer to transfers. Treatment cycles in PGD contain both fresh and frozen cycles and refer to initiated cycles in the fresh cycles and aspirations in the frozen cycles. Treatment cycles in egg donation (ED) refer to donation cycles and contain fresh and frozen cycles. ED fresh: For Bulgaria, France and Iceland treatment cycles refer to aspirations. Treatment cycles in IVM refer to aspirations. Treatment cycles in frozen oocyte replacement (FOR) refer to thawings, for Finland it refers to transfers. ART in Europe, 2017 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 European countries, 44 are EIM members including 28 that are members of the European Union and 39 (40 in 2016) provided data (Supplementary Table SI). Non-EIM members are mainly small countries not offering ART services. Cyprus, Georgia, Ireland, Slovakia and Turkey failed to deliver data (11.3% of EIM members, as in 2016). In 21 countries (53.8% of reporting countries, 45% in 2016) all of the ART clinics within the country reported data sets. Amongst 1531 known IVF clinics in Europe, 1381 clinics reported their data (90.1%; 91.8% in 2016). Similar to 2016, the four European countries with the largest treatment numbers in 2017 were Spain (125 592; 140 909 in 2016), Russia (137 211; 121 232 in 2016), France (108 820; 104 773 in 2016) and Germany (99 466; 99 226 in 2016). Size of the clinics and reporting methods The size of reporting clinics between and inside countries, defined by the number of treatment cycles, remains highly variable (Supplementary Table SII). In 2017, clinics with cycle numbers between 200–499 and 500–999 were the most common (25.9% and 26.3%, respectively vs 29.5% and 26%). The proportion of clinics performing more than 1000 treatment cycles per year is comparable to 2016 (18.9% vs 19.4% in 2016). Small clinics providing less than 100 treatments cycles per year were present in 24 countries (57% of the countries). Registry requirements and reporting methods for each country are presented in Supplementary Table SIII. Data collection was either voluntary (15 out of 39 countries) or compulsory. Nineteen countries had only a partial reporting and provided the data mainly on a voluntary basis (15/19 countries) to medical organizations (9 countries), to the national health authority (2 countries) or as a single person who took the initiative (3 countries). One country reported as personal initiative and to the National Health Authority and one country to a medical organization and the National Health Authority. By contrast, complete reporting was mostly achieved when data collection was compulsory (20/21 countries) with subsequent data communication to the national health authority (all but four countries). Transfer of data was mostly done on an aggregate basis (24 countries/39). Number of treatment cycles per technique and availability In 2017, 940 503 treatment cycles were reported to EIM (22 344 more than in 2016, þ2.4%). Since 1997, increasing numbers of clinics reported to EIM to reach a total 10 713 407 treatments cycles and the birth of more than 2 059 975 infants (Table II). As seen in Table I, 10 countries reported fewer treatment cycles and, compared to 2016, Croatia was now able to provide data, whereas Ireland and Cyprus not. Furthermore, the largest increments in reported treatment numbers were observed for Kazakhstan (þ5642, þ3 clinics) and Russia (þ15 976, þ8 clinics). Table I shows the numbers of treatment cycles per technique in 2017: ICSI remains the most used (391 379, 41.6% of all treatment cycles versus 407 222, 44.4% in 2016). Cycles of IVF, FER, ED, FOR, PGT and IVM represented 17.6%, 28.9%, 7.4%, 0.5%, 4% and 0.0004% of all cycles, respectively. While the distribution of the available techniques remained similar to 2016 (respectively, 17%, 27%, 8.1%, 0.5%, 2.9% and 0.0007%), reported cycle numbers increased for IVF, FER, FOR and PGT and decreased for ICSI, ED and IVM. The steepest rise in treatment numbers was observed for PGT (þ37.8%, þ27.4% in 2016) and FER (þ8.2%, þ13.9% in 2016). However, while in 2016, ED and IVM cycle numbers increased (þ14.7% and þ246.8%, respectively), a decrease of 6.1% and 42.2% was observed in 2017. The proportion of FER relative to fresh treatments (IVFþICSI) is still on the rise (48.9%, versus 44.1% in 2016, 40.3% in 2015 and 37.8% in 2014). Denmark, Hungary and Malta did not report FER in 2017. The highest proportions of FER treatments (calculated as FER/(FERþICSIþIVF)) were reached in BosniaHerzegovina (49.4%), The Netherlands (49%), Czech Republic (47.2%), Finland (45.7%), Switzerland (45.2%), Belgium (44.7%), Albania (43.9%) and Ukraine (43.6%), with an overall proportion of 32.6% (Fig. 1). Figure 1 shows the evolution and continuing preponderance of ICSI over conventional IVF. Amongst a total of 556 758 fresh treatments (ICSIþIVF), 70.3% (72.3% in 2016) were performed with ICSI. The number of cycles per million women of reproductive age and per million inhabitants is shown in Table I and Supplementary Table SIV. Availability of ART was calculated for the 21 countries with full coverage (Supplementary Table SIV). While there is a huge ............ .......... ........ .......... ............ .......... ........ .......... ........ .............. Table II Number of institutions offering ART services, treatment cycles and infants born after ART in Europe, 1997–2017. Year Countries Clinics Cycles Cycle increase (%) Infants born 1997 18 482 203 225 35 314 1998 18 521 232 225 þ14.3 21 433 1999 21 537 249 624 þ7.5 26 212 2000 22 569 275 187 þ10.2 17 887 2001 23 579 289 690 þ5.3 24 963 2002 25 631 324 238 þ11.9 24 283 2003 28 725 365 103 þ12.6 68 931 2004 29 785 367 056 þ0.5 67 973 2005 30 923 419 037 þ14.2 72 184 2006 32 998 458 759 þ9.5 87 705 2007 33 1029 493 420 þ7.7 96 690 2008 36 1051 532 260 þ7.9 107 383 2009 34 1005 537 463 þ1.0 109 239 2010 31 991 550 296 þ2.4 120 676 2011 33 1314 609 973 þ11.3 134 106 2012 34 1354 640 144 þ4.9 143 844 2013 38 1169 686 271 þ7.2 149 466 2014 39 1279 776 556 þ13.1 170 163 2015 38 1343 849 811 þ10.2 187 542 2016 40 1347 918 159 þ8.0 195 766 2017 39 1382 940 503 þ2.4 198 215 Total 10 713 407 2 059 975 4Wyns et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . variability in availability when all techniques are considered (range: 3893–16 547 per million women aged 15–45 years), ART was most available in Czech Republic and least available in Malta. Hence, corresponding proportions of newborns resulting from ART were 5.4% and 1.1% of all newborns in these countries. Other countries that reported high proportions were Denmark (5.6%), Iceland (5.6%), Estonia (5.3%) and Slovenia (5.3%). Pregnancies and deliveries after treatment Table III shows pregnancy and delivery rates (DR) after IVF or ICSI and after FER (after both IVF and ICSI). As numbers of initiated cycles have constantly been incompletely reported, outcome data were calculated per aspiration. Amongst the 39 reporting countries, 35 were able to provide both pregnancy and delivery data per aspiration after IVF (n ¼30) and/or ICSI (n ¼35). For FER when considering thawing cycles, 29 and 28 countries were able to report pregnancy and delivery rates, respectively. Supplementary Table SIV shows the numbers of deliveries for the 21 countries with full coverage of the reporting. Pregnancy and delivery rates (for all types of treatment cycles) varied significantly from one country to another, as in previous years. Per aspiration, pregnancy rates (PR) ranged from 18.4% to 42.3% and DR from 10.4% to 40.9% in fresh cycles after IVF or ICSI (when considering data from countries able to provide data excluding the freeze-all cycles). Pregnancy and delivery rates per thawing for FER varied between 22% and 49.1% and between 3.2% and 37.8%, respectively. Overall, pregnancy and delivery rates were higher for FER cycles (per thawing) than for both fresh IVF and ICSI cycles (per aspiration) (Table III). When considering the stage of replaced embryos, data showed PR for blastocyst transfers to be higher (38.5% vs 27.2% for cleavage stage embryos for FER and 41.7% vs 29.4% for cleavage stage embryos, for fresh IVF and ICSI cycles, respectively). For the fourth time, «freeze all» cycles were collected (Supplementary Tables SV and SVI) including either freezing of all oocytes reported by 10 countries for IVF (10 in 2016 and 6 in 2015) and 17 countries for ICSI (15 in 2016 and 14 in 2015), or of all embryos by 22 countries for IVF (22 in 2016 and 21 in 2015) and 27 countries for ICSI (22 in 2016 and 24 in 2015). The highest proportions of freeze all cycles per aspiration for oocytes and for embryos together were 5.4% (IVF) (5.1% in 2016) and 49.1% (ICSI) (28.9% in 2016), respectively. Cycle numbers, aspirations, transfers, pregnancies, deliveries in IVF, ICSI and FER (after both IVF and ICSI) by country are presented in the Supplementary Tables SV–SVII. ED cycle numbers were available for 21 countries (26 in 2016) although 26 (29 in 2016) provided outcome data (Supplementary Table SVIII). Most ED cycles were reported from Spain, the Czech Republic and Russia. The number of aspirations of donated oocytes was 34 443 (33 406 in 2016) that led to 26 447 fresh transfers (28 451 in 2016), while the replacements of frozen oocytes (FOR) were 14 129 (11 757 in 2016). The PR per embryo transfer were 49.2% (49.4% in 2016) for freshly donated oocytes and 41.1% (41% in 2016) for thawed oocytes although a high variability was seen between countries, ranging from 0% (2 cycles) to 61.6% for fresh oocytes and from 23.1% to 62.2% for thawed oocytes. Overall, 21 137 deliveries were reported (22 497 in 2016 and 19 849 in 2015) and pregnancy and delivery rates per transfer were higher than in cycles with own gametes (partner donation) both for fresh (IVF and ICSI) and FER cycles. Age distribution As seen in Supplementary Tables SIX and SX, age distributions of women treated with IVF and ICSI varied between countries. Some countries were not able to provide age categories (10 for IVF and six for ICSI). The highest percentage of women aged 40 years and older undergoing aspiration for IVF was found in Greece (as in 2016), Figure 1. Proportion of IVF versus ICSI and frozen embryo replacement (FER) in Europe, 1997–2017. ART in Europe, 2017 5 ...................................................................................... ....................................................... ....................................................................................................... ............................................... Table III Results after ART in 2017. IVF ICSI FER Country Initiated Cycles IVF 1ICSI Aspirations Pregnancies per aspiration (%) Deliveries per aspiration (%) Aspirations Pregnancies per aspiration (%) Deliveries per aspiration (%) Thawings FER Pregnancies per thawing (%) Deliveries per thawing (%) ART infants ART infants per national births (%) Albania 105 0 105 37.1 29.5 82 28.0 20.7 65 Armenia 1155 492 42.3 40.9 636 38.2 36.8 675 36.7 33.0 884 2.2 Austria 10 216 1702 31.6 28.0 5298 28.5 24.4 2801 32.9 28.4 2824 3.2 Belarus 2741 1117 36.5 27.6 1511 35.3 25.8 663 39.1 24.7 1066 1.0 Belgium 18 681 2819 24.1 18.0 13 133 22.2 15.8 12 881 27.1 18.8 5711 4.8 Bosnia-Herzegovina, Federation part 82 72 25.0 23.6 80 38.7 20.0 172 Bulgaria 4955 311 30.9 21.9 4644 20.3 14.9 1365 28.4 21.1 Croatia 4334 Czech Republic 15 557 15 122 22.4 14.0 13 907 29.7 17.7 6191 5.4 Denmark 13 656 6525 22.6 13.1 5659 23.5 16.9 3411 5.6 Estonia 1840 620 28.1 21.6 1199 29.6 21.9 890 27.9 18.8 725 5.3 Finland 4261 2341 22.9 17.5 1679 21.0 16.6 France 67 703 20 768 21.0 17.7 41 412 21.2 18.3 37 469 22.9 19.2 20 966 2.7 Germany 71 969 17 771 25.1 17.8 50 863 26.6 19.0 27 234 26.5 17.7 21 292 Greece 15 754 2166 24.9 18.1 13 588 18.4 12.7 5192 43.4 24.2 6276 Hungary 5408 1326 4003 Iceland 259 28.2 25.5 221 26.7 21.7 267 41.9 32.2 229 5.6 Italy 53 014 7201 21.8 14.8 40 710 19.0 12.2 17 281 29.3 20.2 12 638 2.8 Kazakhstan 5161 1285 24.3 14.1 3497 23.7 13.1 2416 49.1 26.5 1700 5.7 Latvia 846 265 28.7 20.8 581 25.3 18.2 549 43.0 29.5 401 Lithuania 395 187 36.4 3.2 125 0.4 Luxembourg 717 234 28.6 20.5 419 27.9 21.2 429 29.1 17.2 243 3.9 Malta 231 17 204 48 1.1 Moldova 960 891 33.8 24.7 346 38.7 21.4 Montenegro 582 575 24.3 19.0 84 26.2 23.8 170 2.3 North-Macedonia 2521 385 34.0 10.4 1885 32.9 27.5 277 41.9 31.0 747 4.7 Norway 6960 3759 24.6 20.8 2856 23.7 20.5 4476 22.0 17.8 Poland 14 565 465 27.7 22.2 13 923 26.6 16.3 10 390 35.8 22.0 5680 1.4 Portugal 6327 2521 27.4 20.5 3490 21.7 16.1 2317 33.7 24.8 2436 2.8 Romania 2900 1138 26.9 20.3 1631 25.6 20.4 1452 33.5 26.4 1105 0.6 Russia 87 613 37 275 29.2 21.2 47 500 25.1 17.4 35 979 40.2 27.7 34 173 2.0 Serbia 222 146 31.5 26.0 74 29.7 24.3 34 41.2 74 (continued) 6Wyns et al. ...................................................................................... ....................................................... ....................................................................................................... ............................................... Table III Continued IVF ICSI FER Country Initiated Cycles IVF 1ICSI Aspirations Pregnancies per aspiration (%) Deliveries per aspiration (%) Aspirations Pregnancies per aspiration (%) Deliveries per aspiration (%) Thawings FER Pregnancies per thawing (%) Deliveries per thawing (%) ART infants ART infants per national births (%) Slovenia 3146 1010 30.5 25.0 2047 23.4 18.8 1422 33.1 24.3 1063 5.3 Spain 50 263 5831 25.3 18.8 38 607 21.3 15.6 27 690 34.9 24.6 30 898 7.9 Sweden 12 093 5823 29.3 25.0 5540 26.2 21.7 5284 4.5 Switzerland 5999 907 23.7 18.2 4629 23.9 18.2 4944 25.3 17.8 2195 2.5 The Netherlands 13 991 5536 29.6 21.7 6500 33.5 25.8 Ukraine 11 753 826 35.4 28.1 10 690 22.6 17.9 9080 48.4 37.8 7728 1.9 UK 43 547 18 409 32.0 28.0 22 402 33.3 29.2 20 443 35.9 31.2 22 047 2.9 All 562 223 151 250 26.8 20.5 367 796 24.0 17.7 243 302 32.2 23.1 198 567 3.1 Total rates refer to these countries where all data were reported for the given technique:. † ART infants also include ED. For IVF and ICSI there were for Belarus, Czech Republic, Denmark, Finland, France, Greece, Latvia, Lithuania, Poland, Portugal, Russia and Sweden respectively 35, 18,3 688, 16, 8, 10, 9, 220, 6, 1303 and 14 deliveries with unknown outcome. These were accepted as singletons to calculate the ART infants. For FER there were for Austria, Czech Republic, Finland, France, Greece, Kazakhstan, Latvia, Poland, Portugal, Russia and Sweden respectively 796, 16, 849, 9, 7, 2, 31, 167, 4, 1100 and1 deliveries with unknown outcome. These were accepted as singletons to calculate the ART infants. For ED there were for Belarus, Czech Republic, Finland, Greece, Kazakhstan, Latvia, Portugal, Russia and Spain respectively 3, 27, 147, 2, 2, 8, 1, 153 and 1221 deliveries with unknown outcome. These were accepted as singletons to calculate the ART infants. For PGD there were for Finland, France, Portugal and Russia respectively 37, 2, 1 and 26 deliveries with unknown outcome. These were was accepted as singleton to calculate the ART infants. In the Czech Republic, IVF and ICSI were reported together under ICSI. In Lithuania, IVF and ICSI were reported together, no details on pregnancies and deliveries. ART in Europe, 2017 7 ...................................................................................... ....................................................... ....................................................................................................... ............................................... Table IV Number of embryos transferred after ART and deliveries in 2017. IVF 1ICSI FER Country Transfers Fresh Transfers cleavage stage Fresh Transfers blastocyst stage Fresh Transfers Unkown stage % Fresh transfers cleavage stage** % Fresh transfers blastocyst stage** 1 embryo (%) 2 embryos (%) 3 embryos (%) 41embryos (%) Deliveries Twin (%) Triplet (%) Deliveries Twin (%) Triplet (%) Albania 90 90 0 0 100.0 0.0 12.2 85.6 2.2 0.0 31 25.8 0.0 17 0.0 0.0 Armemia 1109 501 608 0 45.2 54.8 32.9 61.1 6.0 0.0 435 9.7 0.0 223 0.9 0.0 Austria 8646 2499 6147 0 28.9 71.1 69.6 30.2 0.2 0.0 2565 9.6 0.2 796 Belarus 2325 1374 951 0 59.1 40.9 20.7 71.1 8.2 0.0 698 21.1 0.8 164 9.8 0.6 Belgium 12 328 8389 3939 0 68.0 32.0 67.9 28.1 3.4 0.5 2587 7.5 0.0 2422 6.4 0.1 Bosnia-Herzegovina 494 393 101 0 79.6 20.4 15.4 43.7 39.9 1.0 115 27.0 2.6 16 25.0 0.0 Bulgaria 2986 2986 Croatia 3930 3930 45.8 49.6 4.6 0.0 Czech Republic 10 887 10 887 73.7 25.9 0.5 0.0 2119 6.3 0.1 2460 6.8 0.2 Denmark 9253 6648 2596 9 71.9 28.1 75.8 24.0 0.2 0.0 1812 4.3 0.0 1307 2.4 0.0 Estonia 1493 855 638 0 51.8 43.6 4.6 0.0 397 12.6 0.3 167 15.6 0.0 Finland 2881 2881 91.3 8.7 0.0 0.0 688 849 France 44 318 30 250 14 068 0 68.3 31.7 50.8 45.2 3.7 0.3 11 268 11.6 0.2 7189 7.2 0.0 Germany 54 255 34 789 19 466 0 64.1 35.9 25.1 69.5 5.4 0.0 12 813 21.3 0.7 4808 15.0 0.4 Greece 7985 4971 3014 0 21.3 61.8 12.9 4.0 2122 19.7 0.2 1257 22.6 0.2 Hungary 4854 4854 Iceland 363 363 93.4 6.6 0.0 0.0 114 3.5 0.0 86 1.2 0.0 Italy 33 832 33 832 34.1 48.9 16.0 1.1 6029 15.2 0.4 3486 6.6 0.1 Kazakhstan 3184 2974 210 100.0 0.0 640 16.3 0.5 640 16.0 1.3 Latvia 601 350 251 0 58.2 41.8 59.4 39.6 1.0 0.0 161 10.6 0.0 162 7.6 0.0 Lithuania 857 192 68 597 73.8 26.2 12.6 56.6 30.9 0.0 88 26.6 3.8 6 16.7 0.0 Luxembourg 487 483 4 0 99.2 0.8 43.9 56.1 0.0 0.0 137 19.0 0.0 74 8.1 0.0 Malta 197 197 0 0 100.0 0.0 47 2.1 Moldova 701 701 Montenegro 454 362 92 0 79.7 20.3 27.1 38.8 33.5 0.7 109 27.5 1.8 20 35.0 0.0 North-Macedonia 1889 1440 449 0 31.3 61.8 6.9 0.0 559 8.8 0.0 86 18.6 0.0 Norway 5085 5085 Poland 9431 5489 3888 54 58.5 41.5 55.9 43.4 0.7 0.0 2368 11.5 0.2 2288 6.6 0.2 Portugal 4252 3032 1220 0 71.3 28.7 38.0 61.1 0.8 0.0 1080 18.6 0.2 575 14.0 0.2 Romania 1792 630 1162 0 35.2 64.8 42.2 48.9 8.3 0.6 563 14.9 0.4 384 14.6 0.3 Russia 62 891 14 732 35 018 13 141 29.6 70.4 43.4 55.1 1.5 0.0 16 163 16.8 0.4 9973 15.1 0.2 Serbia 176 176 0 0 100.0 0.0 20.5 30.1 49.4 0.0 56 28.6 1.8 (continued) 8Wyns et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .whereas the highest percentage of women aged <34 years was found in Ukraine (Montenegro in 2016). For ICSI the highest percentage of women aged 40years and older undergoing aspiration was found in Greece (as in 2016), whereas the highest percentage of women undergoing aspiration aged <34 years was recorded in Albania (in Kazakhstan in 2016 and Albania in 2015). An age-dependent decrease of pregnancy and delivery rates for IVF and ICSI cycles was reported as expected, with pregnancy and delivery rates in women aged 40 years and older ranging between 5.9% and 32.5%, and 0% and 20%, respectively. Concerning FER (Supplementary Table SXI), the age related decline was still visible and DR recorded amongst women aged 40 years and older were between 0 and 36.4%. In ED cycles (Supplementary Table SXII), the age of the recipient women had no influence on outcomes. Numbers of embryos transferred and multiple births Subgroups defined by the number of embryos replaced per transfer procedure after IVF and ICSI together as well as multiple birth rates are presented in Table IV. Six countries did not report on the number of replaced embryos or on multiplicity. While overall most transfers involved the replacement of two embryos (49.2%, 51.9% of the transfer cycles in 2016), the proportion of transfers of only one embryo per cycle is still on the rise (46% vs 41.5% in 2016), and the number of transfers of three or more embryos continued to decrease (Fig. 2A). Thirteen countries reported more than 50% of single embryo transfers (elective or not) (10 in 2016) (same 10 as in 2016 plus Estonia, France and Latvia). For the first time, none of the reporting countries carried out more than 50% of their transfers with three embryos (in 2016 only Serbia did). The highest proportion of transfers of four or more embryos was recorded in Greece (4% vs 4.2% in 2016). For the second consecutive year, the embryo stage at transfer was collected. Taking into account that the embryo stage at transfer was unknown for 23.2% of the fresh (IVFþICSI) cycles, 44.1% (41.9% in 2016) of the transfers were performed at the blastocyst stage. The corresponding figure for FER was 64.1% (62.2% in 2016). Such information was not available for each of the subgroups for numbers of embryos replaced. As a result of decreasing numbers of embryos replaced per transfer, the proportion of both twin and triplet deliveries continued to decrease (Fig. 2B). In 2017, twin and triplet rates for fresh IVF and ICSI cycles together were 14.2% (range 2.1–28.6) and 0.3% (range: 0–1.8), respectively. Corresponding results for FER were 11.2% and 0.2%. In the three countries with rates of single embryo replacement above 80% in fresh cycles (93.4% for Iceland, 91.3% for Finland and 84.2% for Sweden), twin rates were as low as 3.5% (for Iceland and Sweden, not available for Finland). Additional information on pregnancies and deliveries is provided in Supplementary Tables SXIII and SXIV. The reported incidence of pregnancy loss was 16.6% (16.4% in 2016) after IVFþICSI and 18.3% (18.6% in 2016) after FER. The proportion of recorded lost to followup was 7.5% (7.8% in 2016) after IVFþICSI and 8.1% (7.5% in 2016) after FER. ...................................................................................... ....................................................... ....................................................................................................... ............................................... Table IV Continued IVF 1ICSI FER Country Transfers Fresh Transfers cleavage stage Fresh Transfers blastocyst stage Fresh Transfers Unkown stage % Fresh transfers cleavage stage** % Fresh transfers blastocyst stage** 1 embryo (%) 2 embryos (%) 3 embryos (%) 41embryos (%) Deliveries Twin (%) Triplet (%) Deliveries Twin (%) Triplet (%) Slovenia 2449 1339 1110 0 54.7 45.3 57.1 42.8 0.1 0.0 637 7.8 0.0 345 7.5 0.0 Spain 27 351 21 884 5467 0 80.0 20.0 37.2 60.3 2.5 0.0 7122 15.7 0.1 6805 13.0 0.2 Sweden 8956 6226 2730 0 69.5 30.5 84.2 15.8 0.0 0.0 2656 3.5 0.0 2301 2.2 0.0 Switzerland 3945 2425 1520 0 61.5 38.5 44.4 50.7 4.9 0.0 1007 17.6 0.2 881 13.4 0.5 The Netherlands 10 715 10 715 Ukraine 5993 1464 4529 0 24.4 75.6 36.6 54.9 8.4 0.0 2143 16.9 0.0 3428 20.8 0.2 UK 35 999 13 060 22 939 0 36.3 63.7 58.6 38.7 2.7 0.0 11 695 10.5 0.1 6373 10.2 0.2 All* 389 434 167 214 131 975 90 245 55.9 44.1 46.0 49.2 4.5 0.3 91 024 14.2 0.3 59 588 11.2 0.2 *Totals refer only to these countries where data on number of transferred embryos and on multiplicity were reported. ART in Europe, 2017 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vilnius, Lithuania. Tel: þ370 620 86826; E-mail: raminta.bausyte@ gmail.com Ieva Masliukaite, Academic Medical Center, Cener for Reproductive Medicine, Ijburglaan 1086ZJ Amsterdam, The Netherlands. Tel: þ31 653 688 815; E-mail: [email protected] Luxembourg Dr Caroline Schilling, Centre Hospitalier de Luxembourg, Centre de Ste´rilite´etdeMe´decine de Reproduction, Rue Fiederspiel 2, 1512 Luxembourg, Luxembourg. Tel: þ35244113230;Mobile:þ352 66 13 13 912; E-mail: [email protected] Malta Dr Jean Calleja-Agius, University of Malta, 12, Mon Nid, Gianni Faure Street, TXN2421 Tarxien, Malta. Tel: þ356 216 930 41; Mobile: þ356 995 536 53; E-mail: [email protected] Moldova Prof. Dr Veaceslav Moshin, Medical Director at Repromed Moldova, Center of Mother @Child Protection, State Medical and Pharmaceutical University ‘N.Testemitanu’, Bd. Cuza Voda 29/1, Chisinau, Republic of Moldova. Tel: þ37322 263855; Mobile: þ37369724433; E-mail: [email protected]; veaceslavmoshin@ yahoo.com Montenegro Dr Tatjana Motrenko Simic, Human Reproduction Center Budva, Prvomajska 4, 85310 Budva, Montenegro. Tel: þ382 33402432; Mobile: þ382 69 052 331; E-mail: [email protected] Dragana Vukicevic, Hospital ‘Danilo I’, Humana reprodukcija, Vuka Micunovica bb, 86000 Cetinje, Montenegro. Tel: þ382 675 513 71; E-mail: [email protected] The Netherlands Dr Jesper M.J. Smeenk, Department of Obstetrics and Gynaecology, St. Elisabeth Hospital Tilburg, Hilv, The Netherlands. Tel: þ31 13 539 31 08; Mobile þ31 622 753 853; E-mail: [email protected] North Macedonia Mr Zoranco Petanovski, Hospital ReMedika, Nas. Zelezara, 1000 Skopje, Macedonia. Tel: þ389 224 475 45, Fax: þ389 226 031 00; E-mail: [email protected] Norway Dr Liv Bente Romundstad, Spiren Fertility Clinic, Nardoskrenten 11, 7032 Trondheim, Norway. Tel: þ47 73523000; Mobile þ47 90550207; E-mail [email protected] Poland Dr Anna Janicka, VitroLive, Wojska Polskiego 103, 70-483 Szczecin, Poland. Tel: þ48 91 88 69 260; E-mail [email protected] Portugal Prof. Dr Carlos Calhaz—Jorge, CNPMA, assembleia da Republica, Palacio de Sao Bento, 1249-068 Lisboa, Portugal. Tel: þ351 21 391 93 03; Fax: þ351 21 391 75 02; E-mail: [email protected] Ms Joana Maria Mesquita Guimaraes. Hospital Geral Santo Antonio, Largo Professor Abel Salazar, 4050-011 Porto, Portugal. Tel: þ351 96 616 02 37; E-mail: [email protected] Ms Ana Rita Laranjeira, CNPMA, Assembleia da Republica, Palaio de Sao Bento 1249-068 Lisboa, Portugal. Tel þ351 21 391 93 03; Fax þ351 21 391 75 02; E-mail [email protected] Romania Mrs Ioana Rugescu, Gen Secretary of AER Embryologist Association and Representative for Human Reproduction Romanian Society. Tel: þ40744500267; E-mail: [email protected] Dr Bogdan Doroftei, University of Medicine and Pharmacy Iasi; Teaching Hospital Obgyn ‘Cuza Voda’; Cuza Voda Str. 34, 700038 Iasi, Romania. Tel: þ40 232 213 000/int. 176; Mobile: þ40 744 515 297; E-mail [email protected]; [email protected] Russia Dr Vladislav Korsak, International Center for Reproductive Medicine, General Director, Liniya 11, Building 18B, Vasilievsky Island, 199034 St-Petersburg, Russia C.I.S. Tel: þ7 812 328 2251; Fax: þ7 812 327 19 50; Mobile: þ7 921 9651977; E-mail: [email protected] Serbia Prof. Snezana Vidakovic, Institute for Obstetrics and Gynecology, Clinical Centre ’GAK’, Visegradska 26, 11000 Belgrade, Serbia. Tel: þ381 63 24 23 80; E-mail: [email protected] Slovenia Prof. Irma Virant-Klun, University Medical Centre Ljubljana, Department of Obstetrics and Gynecology, Slajmerjeva 3, 1000 Ljubljana, Slovenia. Tel: þ386 1 522 60 13; Fax: þ38614314355; Mobile: þ38631625774; E-mail: [email protected] Spain Mrs Irene Cuevas Saiz, Hospital General de Alicante, Department of Infertility, Av Pintor Baeza, 12, 03010 Valencia, Spain. Tel: þ34 961972000; Fax: þ34 91 799 4407; Mobile: þ0034677245650; E-mail [email protected] Dr Fernando Prados Monde´jar, Hospital de Madrid-Monteprı´ncipe, HM Fertility Center Monteprincipe, C/Monteprı´ncipe 25, 28660 Boadilla del Monte, Spain. Tel: þ34 917 089 931; Mobile þ34 646 737 237; E-mail [email protected] Sweden Prof. Christina Bergh, Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Bla Straket 6, 413 45 Go¨teborg, Sweden. Tel: þ4631 3421000, þ46736 889325; Fax: þ4631 418717; Mobile: þ46 736 889325; E-mail [email protected] Switzerland Ms Maya Weder, Administration FIVNAT, Postfach 754, 3076 Worb, Switzerland. Tel: þ41 (0)31 819 76 02; E-mail: [email protected] Dr med. Marco Buttarelli, Centro Cantonale di Fertilita`, Ospedale Regionale di Locarno ‘La Carita`’, Via all’Ospedale 1, 6600 Locarno, Switzerland. Tel: þ41 91 811 45 38; E-mail: [email protected] Dr Marie-Pierre Primi, Laboratoire Andrologie et Biologie de la Reproduction (LABR), Unite´deMe´decine de la Reproduction, Maternite´ 07, CHUV, 1011 Lausanne, Switzerland. Tel: þ41 21 314 34 26; E-mail: [email protected] Turkey Dr Basak Balaban, Amerikan Hastanesi—American Hospital, Assisted Reproduction Unit, Gu¨zelbahc¸e Sok N20 Nisantesi, 34365 Istanbul, Turkey. Tel: þ90 212 444 3 777; Fax: þ90 212 311 2190; Mobile: þ90 532 253 27 92; E-mail [email protected] Prof. Dr Timur Gu¨rgan, Gurgan Clinic, Infertility, Cankaya caddesi, 20/3, 06680 Cankaya-Ankara, Turkey. Tel: þ90 312 4427404; Fax: þ90 312 4427407; Mobile: þ90 532 231 7706; E-mail: [email protected] UK Mr Richard Baranowski, Deputy Information Manager, Human Fertilization and Embryology Authority (HFEA), Finsbury Tower, 103105 Bunhill Row, London EC1 Y 8HF, UK. Tel: þ44 (0) 20 7539 16 Wyns et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3329; Fax: þ44 (0) 20 7377 1871; E-mail: Richard.baranowski@hfea. gov.uk Ukraine Prof. Dr Mykola Gryshchenko, IVF Clinic Implant Ltd, Academician V.I. Gryshchenko Clinic for Reproductive Medicine, 25 Karl Marx Str., 61000 Kharkiv, Ukraine. 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