European IVF-monitoring Consortium Research Articles

O-121 Assisted Reproductive Technology (ART) in Europe 2021 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium

Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2021 as compared to previous years and what are the main trends over the years? Summary answer The 25th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, outcomes for IUI cycles are similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analyzed by the European IVF-monitoring Consortium (EIM) and reported in 23 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31, 2021, in 34 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials, setting, methods In all 1155 clinics offering ART services in 34 countries reported a total of 910 470 treatment cycles, involving 115 567 with IVF, 346 183 with ICSI, 311 487 with frozen embryo replacement (FET), 62 694 with preimplantation genetic testing (PGT), 69 883 with egg donation (ED), 246 with IVM of oocytes and 4410 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1242 institutions offering IUI in 29 and 21 countries, respectively. A total of 139 350 treatments with IUI-H and 45 532 treatments with IUI-D were included. A total of 28 692 fertility preservation (FP) interventions from 15 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and post-pubertal patients were reported. Main results and the role of chance In total, 1155 IVF clinics participated (81.4% of registered clinics in the participating countries). Next to these also 1242 IUI units reported their data. In the 34 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2021 were similar to those observed in 2020 (26.2% and 43.3% versus 25.4% and 40.9%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2020 (23.9% en 45.7% versus 25.2% and 45.3%). Also after FET with own embryos, the PR per thawing is stabilizing, 35.0% in 2020 and 36.2% in 2021. After ED the PR per fresh embryo transfer was slightly increased to 53.1% (51.3% in 2020) and per FOR 45.5% (43.9% in 2020). 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 60.2%, 34.8%, 1.8% and 0.2% of all treatments, respectively (corresponding to 57.9%, 37.5%, 2.1% and 0.2% in 2020). This resulted in a proportion of singleton, twin and triplet DRs of 90.4%, 9.5% and 0.1%, respectively (compared to 88.9%, 10.9% and 0.2%, respectively in 2020). Treatments with FER in 2021 resulted in twin and triplet DR of 7.0% and 0.1%, respectively (versus 7.9% and 0.1% in 2020). After IUI, the DRs remained similar at 9.2% after IUI-H (8.8% in 2020) and at 14.0% after IUI-D (12.5% in 2020). Twin and triplet DRs after IUI-H were 7.4% and 0.2%, respectively (in 2020: 7.9% and 0.4%) and 5.9% and 0.2% after IUI-D (in 2020: 5.7% and 0.1%). The majority of FP interventions included the cryopreservation of oocytes (n= 11 966 from 15 countries) and of ejaculated sperm (n=14 688 from 15 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract, some countries were not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 25th ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived live births in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine.

O-122 ICMART Preliminary World Report 2020

Abstract Abstract title: International Committee for Monitoring Assisted Reproductive Technologies (ICMART) Preliminary World Report on ART, 2020 Study question In 2020 what was the global utilization, effectiveness and safety of ART? Summary answer Globally, ART utilization and data collection continue to increase but with wide variations in utilization, effectiveness and safety. What is known already ICMART has continuously monitored utilization, effectiveness and safety since 1991, with increasing number of cycles, higher pregnancy rates and lower multiple birth rates, the latter due to the transfer of fewer embryos. Frozen embryo transfer (FET), donor egg cycles and preimplantation genetic testing (PGT) continue to increase. Wide variations in practice and outcomes exist globally. At least 12 million ART babies have been born. ICMART has helped develop registries internationally. A new electronic data collection platform has improved validation. Nevertheless, data collection and quality remain challenging. Study design, size, duration Countries and regions annually collect ART data, some prospectively and others retrospectively. ICMART retrospectively requested data from all known global sources for 2020, reviewed them for missing or incorrect data, and obtained additional information when possible. The corrected dataset was validated and analyzed in partnership with University of New South Wales (UNSW). ICMART finalized the results tables. Standardized definitions and previously developed methods were used. Preliminary results are presented. Participants/Materials, setting, methods The European IVF Monitoring Consortium (EIM), Latin American Network of Assisted Reproduction (REDLARA), Australian/ New Zealand Registry and African Network and Registry for ART (ANARA) submitted regional data, and other countries contributed national data, through standardized formats, to ICMART. A few individual clinics with no registry access also contributed. Data received were reviewed, corrected, and validated to the extent possible, analyzed and summarized by ICMART using descriptive statistics. Main results and the role of chance Data collection and analysis are ongoing, so the presented results are preliminary. The number of ART cycles continues to increase, but utilization remains highly variable among countries and regions. While historically Europe has reported the largest number of cycles, China now reports well over 1 million cycles and Japan almost half a million, with Asia overall reporting approximately half of global cycles. Regional and country differences persist in the age of women treated, number of embryos transferred, live birth rates, rate of multiple births, use of ICSI and cryopreservation, and other factors. Covid reduced ART utilization in many countries. The role of chance is minimal. Data are limited to reporting countries and clinics, representing 90 to 95% of global cycles. However, this is a very large sample size from which imputation of total global results is performed. Limitations, reasons for caution Most, but not all, countries report to ICMART. Some countries have limited data and many countries have limited data validation. ICMART can perform only minimal verification of submitted data. Widespread adherence to consensus definitions provided in the Glossary takes time and requires translation into multiple languages. Standardization of validation and reporting is an ongoing process because of missing data and continuing changes in clinical practice. Wider implications of the findings ICMART World Reports standardize data, track trends, enable comparisons, stimulate questions and improve ART quality. Better understanding of ART increases societal acceptance and support for equitable access and ART research.

O-090 The paradox of choice in double (DET) versus single (SET) embryo transfer: more is less!

Abstract Study question Do couples with two blastocysts opting for DET have a better outcome than those with SET, freezing of the second and eventually subsequent second SET? Summary answer More children are born after 2x SET with the overwhelming majority (96.3%) of these children being singletons, whereas after 1x DET 49.5% are multiples What is known already According to the most recent publication of the European IVF Monitoring Consortium, in 33 European countries reporting data on these topics SET is performed in 55.4% of fresh transfers whereas in the other cycles, two, three and even 4 or more embryos are transferred, often resulting in twin or higher order multiple pregnancies, but there is no information on the duration of culture and number of embryos available in these cycles. The German IVF-Registry (D·I·R) has collected more than 2.4 million datasets from German ART clinics since 1997 and has access to these data and other relevant patient characteristics. Study design, size, duration Retrospective real-world data analysis from 140 German IVF-centers collected by the German IVF-Registry (D·I·R) between 2017 and 2021. Data were collected prospectively, controlled for plausibility, and evaluated anonymously. Treatment cycles from four years between January 1st, 2017 and December 31st, 2020 were evaluated. Pregnancy outcome was monitored until end of 2021. All couples having at least 2 blastocysts available for fresh transfer in their 1st treatment cycle were identified and included in the analysis. Participants/materials, setting, methods 19,702 women with similar characteristics (i.e. first cycle of IVF or ICSI, fresh embryo transfer, two blastocysts available on the day of fresh ET, signed consent to freeze supernumerous 2PN or embryos) were stratified into two groups. Therapy results after 1x DET (fresh) vs. 1x SET (fresh) plus 1x SET (frozen-thawed) were evaluated for clinical pregnancy rates, life birth rates, number and order of multiple pregnancies, multiple deliveries, and total number of children born. Main results and the role of chance From 19,702 women meeting the inclusion criteria, 9,643 (48.9%) had a DET and 10,059 (51.1%) had a SET. The age of patients in both groups was not significantly different (DET: 34.1y vs. SET: 33.7y). As expected, ongoing pregnancy rate (OPR) and life birth rate (LBR) after DET were higher compared to SET (OPR: 49.4% vs. 42.3%; LBR 38.5% vs. 33.1%). Those opting for SET however had the chance of a second SET with the frozen-thawed blastocyst and so far, from 7,207 women who started the frozen embryo transfer cycle (FET), 6,431 had the second blastocyst transferred with a CPR of 29.5% and LBR of 19.4% per started FET. After DET, only 67.4% of deliveries were singletons. Of the 32.6% multiples, 97.4% were twins, 2.5% triplets and 0.1% quadruplets. After fresh (or frozen) SET, 98.4% (97.6%) of deliveries were singletons, the remaining were solely twins (1.6% (2.4%)) and no higher order multiples. Per 1,000 women having a DET, 514 children were born and 49.5% of those were either twins, triplets or quadruplets. Per 1,000 women after 2x SET, more children were born (536), and only 3.7% of those were twins, no triplets or quadruplets. Limitations, reasons for caution In this retrospective analysis, the reasons of the couples for the decision of having SET or DET is not known. One potential bias caused by the additional costs for freezing/thawing (not reimbursable in Germany) can be excluded (only those having opted to freeze supernumerous 2PN or embryos were evaluated). Wider implications of the findings Couples undergoing IVF understandably want to maximize their chances of success, sometimes opting for a DET, underestimating the number of multiples and neglecting the risks. We clearly show that after DET every second child is a twin, triplet or quadruplet, and even more children are born after two successive SETs. Trial registration number not applicable

O-153 Assisted Reproductive Technology (ART) in Europe 2020 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium

Abstract Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2020 as compared to previous years and what are the main trends over the years? Summary answer: author The 24rd ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, outcomes for IUI cycles are similar to previous years. WHAT IS KNOWN ALREADY: Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analyzed by the European IVF-monitoring Consortium (EIM) and reported in 23 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31 2020 in 35 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials, setting, methods In all, 1157 clinics offering ART services in 35 countries reported a total of 713 708 treatment cycles, involving 110 097 with IVF, 253 095 with ICSI, 239 759 with frozen embryo replacement (FET), 46 610 with preimplantation genetic testing (PGT), 59 906 with egg donation (ED), 344 with IVM of oocytes and 3897 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1176 institutions offering IUI in 28 and 18 countries, respectively. A total of 102 702 treatments with IUI-H and 36 476 treatments with IUI-D were included. A total of 18 270 fertility preservation (FP) interventions from 15 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and post-pubertal patients were reported. Main results and the role of chance In total, 1157 IVF clinics participated (88.5% of registered clinics in the participating countries). Next to these also 1176 IUI units reported their data. In the 35 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2020 were similar to those observed in 2019 (27.9% and 32.9% versus 28.5% and 34.6%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2019 (24.3% en 32.2% versus 26.2% and 33.5%). After FET with own embryos, the PR per thawing is stabilizing, 35.1% in 2019 and 34.6% in 2020. After ED the PR per fresh embryo transfer was 50.4% (50.5% in 2019) and per FOR 45.3% (44.8% in 2019). 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 62.1%, 32.3%, 2.2% and 0.3% of all treatments, respectively (corresponding to 55.4%, 39.9%, 2.6% and 0.2% in 2019). This resulted in a proportion of singleton, twin and triplet DRs of 90.5%, 9.3% and 0.2%, respectively (compared to 87.7%, 12.0% and 0.3%, respectively in 2019). Treatments with FER in 2020 resulted in twin and triplet DR of 7.0% and 0.1%, respectively (versus 9.3% and 0.1% in 2019). After IUI, the DRs remained similar at 8.9% after IUI-H (9.2% in 2019) and at 12.4% after IUI-D (12.1% in 2019). Twin and triplet DRs after IUI-H were 8.3% and 0.4%, respectively (in 2019: 8.7% and 0.3%) and 5.8% and 0.2% after IUI-D (in 2019: 6.2% and 0.2%). The majority of FP interventions included the cryopreservation of oocytes (n = 5 365 from 14 countries) and of ejaculated sperm (n = 11 571 from 14 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract, some countries were not able to provide adequate data about the number of centers and initiated cycles and deliveries. WIDER IMPLICATIONS OF THE FINDINGS: The 24rd ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived live births in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine. Trial registration number XXXX

O-154 ICMART preliminary world report 2019

Abstract Abstract title International Committee for Monitoring Assisted Reproductive Technologies (ICMART) Preliminary World Report on ART, 2019 Study question In 2019 what was the global utilization, effectiveness and safety of ART? Summary answer Globally, ART utilization and data collection continue to increase but with wide variations in utilization, effectiveness and safety. What is known already ICMART began ART global data collection in 1991. Utilization, effectiveness and safety have continuously improved with more cycles, higher pregnancy rates and lower multiple birth rates, the latter due to the transfer of fewer embryos. Frozen embryo transfer (FET) and donor egg cycles continue to increase. However, wide variations in practice and outcomes exist globally. Approximately 10 million ART babies have been born. ICMART has helped develop registries internationally. A new electronic data collection platform has been developed with the University of New South Wales (UNSW) in Sydney, Australia; nevertheless, data collection and quality remain challenging. Study design, size, duration Countries and regions annually collect ART data, some prospectively and others retrospectively. ICMART retrospectively requested data from all known global sources for 2019 and reviewed them for missing or incorrect data. The dataset was reviewed and corrected by ICMART, in partnership with UNSW for validation and analysis, then ICMART finalized the results tables. Standardized definitions from The International Glossary on Infertility and Fertility Care, 2017, and previously developed methods were used. Preliminary results are presented. Participants/materials, setting, methods The European IVF Monitoring Consortium (EIM), Latin American Network of Assisted Reproduction (REDLARA), Australian/ New Zealand Registry and African Network and Registry for ART (ANARA) submitted regional data, and other countries contributed national data, through standardized formats, to ICMART. A few individual clinics with no registry access also contributed. Data received were reviewed, corrected, and validated to the extent possible, analyzed and summarized by ICMART using descriptive statistics. Main results and the role of chance Data collection and analysis are ongoing, so the presented results are preliminary. The number of ART cycles continues to increase, but utilization is still highly variable among countries and regions. Regional and country differences persist in the age of women treated, number of embryos transferred, live birth rates, rate of multiple births, use of ICSI, cryopreservation cycles and other factors. The role of chance is minimal. Actual global ART results are limited to reporting countries and clinics representing 90 to 95% of global cycles. However, this is a very large sample size from which imputation of total global results is performed. Limitations, reasons for caution Most, but not all, countries report to ICMART. Some countries have limited data and many countries have limited data validation. ICMART can perform only minimal verification of submitted data. Widespread adherence to consensus definitions provided in the Glossary takes time and requires translation into multiple languages. Standardization of validation and reporting is an ongoing process because of missing data and continuing changes in clinical practice. Wider implications of the findings ICMART World Reports standardize data, track trends, enable comparisons, stimulate questions and improve ART quality. Better understanding of ART increases societal acceptance and support for equitable access and ART research.

The time has come for harmonized international ART registration

For more than two decades, the European IVF-Monitoring Consortium has collected data on IVF in Europe with the aim of monitoring the quality and safety of assisted reproductive technology (ART) treatments, to ensure the highest performance with the lowest risk for patients and their offspring. Likewise, the Society for Assisted Reproductive Technology in the USA and the Australia/New Zealand Assisted Reproduction Database collect, process and publish data in their regions. The better the legal framework for ART surveillance, the more complete and reliable are the datasets. Worldwide, the landscape of ART regulation is fragmented, and until there is a legal obligation to report ART data in all countries, with an appropriate quality control of the data collected, the reported outcomes should be interpreted with caution. Once uniform and harmonized data are achieved, consensus reports based on collective findings can begin to address key topics such as cycle segmentation and complications. Improved registration systems and datasets allowing optimized surveillance should be developed in collaboration with patient representatives to consider patients’ needs, especially aiming to provide higher transparency around ART services. Support from national and international reproductive medicine societies will also be essential to the future evolution of ART registries.

Comparison of clinical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection on sibling oocytes

Background and Aim: The first indication of ICSI procedure is severe male infertility. Nevertheless, it is also used in case of normal sperm parameters. The latest report from the European IVF-monitoring Consortium (2014) showed how ICSI was applied in 71.3% of fresh treatments. The aim of the present study was to compare reproductive outcomes in sibling human oocytes after split insemination.

O-150 Assisted reproductive technology (ART) in Europe 2019 and development of a strategy of vigilance Preliminary results generated from European registers by the ESHRE EIM consortium

Abstract Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2019 as compared to previous years, as well as the main trends over the years? Summary answer The 23rd ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, outcomes for IUI cycles are similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analyzed by the European IVF-monitoring Consortium (EIM) and reported in 22 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31 2019 in 32 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials, setting, methods In all, 1133 clinics offering ART services in 32 countries reported a total of 784 192 treatment cycles, involving 116 615 with IVF, 285 481 with ICSI, 250 997 with frozen embryo replacement (FER), 55 121 with preimplantation genetic testing (PGT), 71 413 with egg donation (ED), 473 with IVM of oocytes and 4092 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1033 institutions offering IUI in 25 and 20 countries, respectively. A total of 123 106 treatments with IUI-H and 43 798 treatments with IUI-D were included. A total of 20 400 fertility preservation (FP) interventions from 12 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and post-pubertal patients were reported. Main results and the role of chance In total, 1133 IVF clinics participated (90.0% of registered clinics in the participating countries). Next to these also 1033 IUI units reported their data. In the 32 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2019 were similar to those observed in 2018 (28.5% and 34.7% versus 28.8% and 34.1%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2018 (25.3% en 33.1% versus 27.3% and 32.1%). After FER with own embryos the PR per thawing is still on the rise, from 33.4% in 2018 to 35.0% in 2019. After ED the PR per fresh embryo transfer was 50.1% (49.6% in 2018) and per FOR 44.1% (44.9% in 2018). 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 61.1%, 36.2%, 2.6% and 0.2% of all treatments, respectively (corresponding to 50.7%, 45.1%, 3.9% and 0.3% in 2018). This resulted in a proportion of singleton, twin and triplet DRs of 89.7%, 10.1% and 0.2%, respectively (compared to 87.4%, 12.4% and 0.2%, respectively in 2018). Treatments with FER in 2019 resulted in twin and triplet DR of 8.3% and 0.1%, respectively (versus 9.4% and 0.1% in 2018). After IUI, the DRs remained similar at 9.5% after IUI-H (8.9% in 2018) and at 12.0% after IUI-D (12.6% in 2018). Twin and triplet DRs after IUI-H were 8.8% and 0.4%, respectively (in 2018: 8.4% and 0.3%) and 6.4% and 0.2% after IUI-D (in 2018: 6.4% and 0.2%). The majority of FP interventions included the cryopreservation of oocytes (n = 9 813 from 10 countries) and of ejaculated sperm (n = 9 521 from 12 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract some countries were not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 23rd ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine. Trial registration number

O-151 ICMART preliminary world report 2018

Abstract Abstract title International Committee for Monitoring Assisted Reproductive Technologies (ICMART) Preliminary World Report on ART, 2018 Study question In 2018 what was global utilization, effectiveness and safety of ART? Summary answer Globally, ART utilization and data collection continue to increase but with wide variations in utilization, effectiveness and safety. What is known already ICMART began ART global data collection in 1991. Utilization, effectiveness and safety have continuously improved with more cycles, higher pregnancy rates and lower multiple birth rates, the latter as a result of transfer of fewer embryos. Frozen embryo transfer (FET) and donor egg cycles continue to increase. However, wide variations in practice and outcomes exist globally. Approximately 9 million ART babies have been born. ICMART has helped develop registries internationally. A new electronic data collection platform has been developed in conjunction with the University of New South Wales in Sydney, Australia; nevertheless, data collection and quality remain challenging. Study design, size, duration Countries and regions annually collect ART data, some prospectively and others retrospectively. ICMART retrospectively requested these data from all known global sources for 2018 and reviewed them for missing or incorrect data. The dataset was corrected and then analyzed utilizing standardized definitions from The ICMART/WHO Revised Glossary on ART Terminology, 2009 which was current at the time but is now replaced by The International Glossary on Infertility and Fertility Care, 2017, and previously developed methods. Preliminary results are presented. Participants/materials, setting, methods The European IVF Monitoring Consortium (EIM), Latin American Network of Assisted Reproduction (REDLARA), Australian/ New Zealand Registry and African Network and Registry for ART (ANARA) submitted regional data, and other countries contributed national data, through standardized formats to ICMART. A few individual clinics with no registry access also contributed. Data were reviewed, corrected, validated to the extent possible, analyzed and summarized by ICMART using descriptive statistics. Main results and the role of chance Data collection and analysis are ongoing, so presented results are preliminary. The number of ART cycles continues to increase, but utilization is still highly variable among countries and regions. Regional and country differences persist in the age of women treated, number of embryos transferred, live birth rates, rate of multiple births, use of ICSI, cryopreservation cycles and other factors. The role of chance is minimal. Actual global ART results are limited to reporting countries and clinics representing approximately 3/4 of global cycles. However, this is a very large sample size from which imputation of total global results is performed. Limitations, reasons for caution Some countries have limited data and many countries have limited data validation. ICMART can perform only minimal verification of submitted data. Widespread adherence to consensus definitions provided in the Glossary takes time and requires translation into multiple languages. Wider implications of the findings ICMART World Reports standardize data, track trends, enable comparisons, stimulate questions and improve ART quality. Better understanding of ART increases societal acceptance and support for equitable access and ART research.

ART in Europe, 2018: results generated from European registries by ESHRE.

What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2018 as compared to previous years? The 22nd ESHRE report shows a continued increase in reported numbers of ART treatment cycles and children born in Europe, a decrease in transfers with more than one embryo with a further reduction of twin delivery rates (DRs) as compared to 2017, higher DRs per transfer after fresh IVF or ICSI cycles (without considering freeze-all cycles) than after frozen embryo transfer (FET) with higher pregnancy rates (PRs) after FET and the number of reported IUI cycles decreased while their PR and DR remained stable. ART aggregated data generated by national registries, clinics or professional societies have been gathered and analysed by the European IVF-monitoring Consortium (EIM) since 1997 and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE on a yearly basis. The data on treatment cycles performed between 1 January and 31 December 2018 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons of 39 countries. Overall, 1422 clinics offering ART services in 39 countries reported a total of more than 1 million (1 007 598) treatment cycles for the first time, including 162 837 with IVF, 400 375 with ICSI, 309 475 with FET, 48 294 with preimplantation genetic testing, 80 641 with egg donation (ED), 532 with IVM of oocytes and 5444 cycles with frozen oocyte replacement (FOR). A total of 1271 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 148 143) or donor semen (IUI-D; n = 50 609) in 31 countries and 25 countries, respectively. Sixteen countries reported 20 994 interventions in pre- and post-pubertal patients for FP including oocyte, ovarian tissue, semen and testicular tissue banking. In 21 countries (21 in 2017) in which all ART clinics reported to the registry, 410 190 treatment cycles were registered for a total population of ∼ 300 million inhabitants, allowing a best estimate of a mean of 1433 cycles performed per million inhabitants (range: 641-3549). Among the 39 reporting countries, for IVF, the clinical PR per aspiration slightly decreased while the PR per transfer remained similar compared to 2017 (25.5% and 34.1% in 2018 versus 26.8% and 34.3% in 2017). In ICSI, the corresponding rates showed similar evolutions in 2018 compared to 2017 (22.5% and 32.1% in 2018 versus 24.0% and 33.5% in 2017). When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.8% (29.4% in 2017) and 27.3% (27.3% in 2017) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was 33.4% (versus 30.2% in 2017), and with embryos originating from donated eggs 41.8% (41.1% in 2017). After ED, the PR per fresh embryo transfer was 49.6% (49.2% in 2017) and per FOR 44.9% (43.3% in 2017). 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 50.7%, 45.1%, 3.9% and 0.3% of all treatments, respectively (corresponding to 46.0%, 49.2%. 4.5% and 0.3% in 2017). This resulted in a reduced proportion of twin DRs of 12.4% (14.2% in 2017) and similar triplet DR of 0.2%. Treatments with FET in 2018 resulted in twin and triplet DRs of 9.4% and 0.1%, respectively (versus 11.2% and 0.2%, respectively in 2017). After IUI, the DRs remained similar at 8.8% after IUI-H (8.7% in 2017) and at 12.6% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%), and 6.4% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). Among 20 994 FP interventions in 16 countries (18 888 in 13 countries in 2017), cryopreservation of ejaculated sperm (n = 10 503, versus 11 112 in 2017) and of oocytes (n = 9123 versus 6588 in 2017) were the most frequently reported. The results should be interpreted with caution as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. The 22nd ESHRE data collection on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts towards optimization of both the collection and reporting, with the aim of improving surveillance and vigilance in the field of reproductive medicine, are awaited. The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

The experience of in vitro fertilization data collection in Turkey

Collecting and reporting data is a crucial aspect of in vitro fertilization (IVF) practice. During the following two decades after the first report of the European IVF-monitoring Consortium (EIM) on IVF data, the number of contributing countries increased gradually reaching nearly forty. For the first seven years of publication, between 2001 and 2007, Turkey did not provide IVF data to the European registry. Turkey first took part in the European registry in 2008 and thus also in the World registry. The addition of Turkish data to EIM was an important milestone, since Turkey appeared as the country with the sixth highest number of cycles, performing nearly eight percent of all European assisted reproductive technology (ART) cycles. Turkey continued contributing to the European registry for the following four years consecutively but after 2012 the input of Turkish IVF data stopped. Strikingly, between 2008-2012 Turkey became one of the main contributors to the registry with an ability to give a full report. So far, we do not have a complete European set of data and the number of cycles reported by European Society for Human Reproduction and Embryology (ESHRE) EIM can easily be said to be an underestimation of the actual number of cycles. IVF data from Turkey - a country having the 17th highest population in the World and appearing among the first six countries in Europe in terms of the number of ART cycles per year- will definitely contribute very much to ESHRE EIM database. It is now time to turn the tide and restart submitting Turkish data to European registry, but this time regularly and in a systematic method. Such an achievement will greatly contribute to the aim of EIM of achieving a complete data set.

P–731 Correlation between fertility rate, utilisation of ART and gross domestic product across Europe

Abstract Study question Are there any correlations between a country’s wealth determined by GDP per capita and its total fertility rate (TFR) and utilisation of ART in Europe? Summary answer There is strong correlation across Europe between GDP and utilisation of ART. This correlation does not exist when only investigating the European Economic Area (EEA) What is known already The number of documented ART cycles has increased significantly from 203,893 cycles in 1997 (first European report) to 918,159 in 2016. During the same period, growth was observed in European GDP and, to a lesser extent, TFR following a significant and prolonged decline. Global data suggest that utilisation rate is higher in developed countries, speculated to be due to either generous reimbursement systems or higher affordability for patients paying out of pocket. This study analysed for the first time the relationships between national GDP, TFR and utilisation in Europe both as a whole, and specifically the more affluent EEA Study design, size, duration This study was an analysis of publicly available primary international reports: total cycles in the European IVF-monitoring Consortium (EIM) and TFR, GDP and population size from the World Bank indicators (https://data.worldbank.org/indicator). The period studied ranged from the first EIM report for 1997 (published in 1999) to the 20th report for 2016 (published in 2020). Participants/materials, setting, methods TFR was described as births per women (BPW) and country wealth was presented as GDP per capita in US Dollars. Utilisation rate was defined as the total national number of cycles (fresh IVF and ICSI, and frozen embryo transfer) divided per population, and presented as cycles per million (CPM). When utilisation was not reported, total cycles were projected by proportional calculation. Pearson Correlations were calculated using Sigmaplot for utilisation, GDP and TFR in 2016 Main results and the role of chance Forty countries were included in the EIM report for 2016, of which 18 reported in full. The median utilisation rate was 1280 CPM (range 162 - 3,156) and median TFR was 1.6 BPW (range 1.26 - 2.73); only one country, Kazakhstan, had a TFR above the natural fertility replacement level of 2.1 BPW. Mean GDP was $31604 per capita (range $10,610 - $110,650). There was no correlation between TFR and utilisation or between TFR and GDP, however there was a significant positive correlation between GDP and CPM (correlation coefficient = 0.428; P = 0.00661). Compared to Europe as a whole, analysis of only the EEA countries – EU member states plus Norway, Iceland, and Switzerland – revealed a similar median TFR (1.59), but a 27% increase in the utilisation rate to 1629 CPM (range: 317 – 3157) and 24% rise in GDP per capita to $39,300 (range: $19,885- $110,650). For the EEA, no significant correlations were observed, including between GDP and utilisation (correlation coefficient = 0.131; P = 0.507). Additionally, there was no significant correlation between TFR and GDP in the EU for the period of 1997 – 2016. Limitations, reasons for caution The data is a snapshot of a single year, but we observed similar outcomes in previous years. Projection calculation of utilisation in partially reporting countries may cause bias, however, with a reporting level of 92% (1347 of 1467 clinics), this bias is probably very limited. Wider implications of the findings: Findings of this study confirm that there are strong disparities in the availability of ART even in Europe. This difference does not exist in the more affluent countries in Europe suggesting that the reason for lower utilisation in lower-income countries being reduced affordability. Trial registration number NA

O-042 Assisted Reproductive Technology (ART) in Europe 2018 and development of a strategy of vigilance. preliminary results generated from european registers by ESHRE

Abstract Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2018 as compared to previous years, as well as the main trends over the years? Summary answer AUTHOR: The 22th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, higher pregnancy and delivery rates after FER compared to fresh IVF and ICSI cycles, and outcomes for IUI cycles similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analysed by the European IVF-monitoring Consortium (EIM) and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31 2018 in 34 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organisations. Participants/materials, setting, methods In all, 1004 clinics offering ART services in 34 countries reported a total of 827 545 treatment cycles, involving 132 332 with IVF, 342 589 with ICSI, 260 013 with frozen embryo replacement (FER), 44 854 with preimplantation genetic testing (PGT), 42 869 with egg donation (ED), 406 with IVM of oocytes and 4482 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 783 institutions offering IUI in 24 and 20 countries, respectively. A total of 132 624 treatments with IUI-H and 43 140 treatments with IUI-D were included. A total of 12 609 fertility preservation (FP) interventions from 13 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and postpubertal patients were reported. Main results and the role of chance In total, 1004 IVF clinics participated (93.4% of registered clinics in the participating countries). Next to these also 783 IUI units reported their data. In the 34 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2018 were similar to those observed in 2017 (28.7% and 41.6% versus 29.4% and 39.0%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2017 (26.3% en 40.9% versus 27.3% and 40.2%). After FER with own embryos the PR per thawing is still on the rise, from 30.2% in 2017 to 33.0% in 2018. After ED the PR per fresh embryo transfer was 49.8% (49.2% in 2017) and per FOR 39.6% (43.3% in 2017). 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 51.1%, 45.4%, 3.4% and 0.1% of all treatments, respectively (corresponding to 46.0%, 49.2%, 4.5% and 0.3% in 2017). This resulted in a proportion of singleton, twin and triplet DRs of 86.9%, 12.8% and 0.3%, respectively (compared to 85.5%, 14.2% and 0.3%, respectively in 2017). Treatments with FER in 2017 resulted in twin and triplet DR of 9.3% and 0.1%, respectively (versus 11.2% and 0.2% in 2017). After IUI, the DRs remained similar at 9.1% after IUI-H (8.9% in 2017) and at 12.3% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%) and 6.7% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). The majority of FP interventions included the cryopreservation of ejaculated sperm (n = 8 257 from 13 countries) and of oocytes (n = 3230 from 13 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract a number of countries was not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 22nd ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine. Trial registration number: Study funding: Funding source:

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

STUDY QUESTIONWhat 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 ANSWERThe 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 ALREADYSince 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, DURATIONData 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, METHODSOverall, 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 = 155 794) or donor semen (IUI-D; n = 51 402) 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 pre- and postpubertal patients.MAIN RESULTS AND THE ROLE OF CHANCEIn 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 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 = 11 112 vs 7877 from 11 countries in 2016) and of oocytes (n = 6588 vs 4907 from eight countries in 2016) were the most frequently reported.LIMITATIONS, REASONS FOR CAUTIONAs 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 FINDINGSThe 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.

20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions.

STUDY QUESTIONHow has the performance of the European regional register of the European IVF-monitoring Consortium (EIM)/European Society of Human Reproduction and Embryology (ESHRE) evolved from 1997 to 2016, as compared to the register of the Centres for Disease Control and Prevention (CDC) of the USA and the Australia and New Zealand Assisted Reproduction Database (ANZARD)?SUMMARY ANSWERIt was found that coherent and analogous changes are recorded in the three regional registers over time, with a different intensity and pace, that new technologies are taken up with considerable delay and that incidental complications and adverse events are only recorded sporadically.WHAT IS KNOWN ALREADYEuropean data on ART have been collected since 1997 by EIM. Data collection on ART in Europe is particularly difficult due to its fragmented political and legal landscape. In 1997, approximately 78.1% of all known institutions offering ART services in 23 European countries submitted data and in 2016 this number rose to 91.8% in 40 countries.STUDY DESIGN, SIZE, DURATIONWe compared the changes in European ART data as published in the EIM reports (2001–2020) with those of the USA, as published by CDC, and with those of Australia and New Zealand, as published by ANZARD.PARTICIPANTS/MATERIALS, SETTING, METHODSWe performed a retrospective analysis of the published EIM data sets spanning the 20 years observance period from 1997 to 2016, together with the published data sets of the USA as well as of Australia and New Zealand. By comparing the data sets in these three large registers, we analysed differences in the completeness of the recordings together with differences in the time intervals on the occurrence of important trends in each of them. Effects of suspected over- and under-reporting were also compared between the three registers. X2 log-rank analysis was used to assess differences in the data sets.MAIN RESULTS AND THE ROLE OF CHANCEDuring the period 1997–2016, the numbers of recorded ART treatments increased considerably (5.3-fold in Europe, 4.6-fold in the USA, 3.0-fold in Australia and New Zealand), while the number of registered treatment modalities rose from 3 to 7 in Europe, from 4 to 10 in the USA and from 5 to 8 in Australia and New Zealand, as published by EIM, CDC and ANZARD, respectively. The uptake of new treatment modalities over time has been very different in the three registers. There is a considerable degree of underreporting of the number of initiated treatment cycles in Europe. The relationship between IVF and ICSI and between fresh and thawing cycles evolved similarly in the three geographical areas. The freeze-all strategy is increasingly being adopted by all areas, but in Europe with much delay. Fewer cycles with the transfer of two or more embryos were reported in all three geographical areas. The delivery rate per embryo transfer in thawing cycles bypassed that in fresh cycles in the USA in 2012, in Australia and New Zealand in 2013, but not yet in Europe. As a result of these changing approaches, fewer multiple deliveries have been reported. Since 2012, the most documented adverse event of ART in all three registers has been premature birth (<37 weeks). Some adverse events, such as maternal death, ovarian hyperstimulation syndrome, haemorrhage and infections, were only recorded by EIM and ANZARD.LIMITATIONS, REASONS FOR CAUTIONThe methods of data collection and reporting were very different among European countries, but also among the three registers. The better the legal background on ART surveillance, the more complete are the data sets. Until the legal obligation to report is installed in all European countries together with an appropriate quality control of the submitted data the reported numbers and incidences should be interpreted with caution.WIDER IMPLICATIONS OF THE FINDINGSThe growing number of reported treatments in ART, the higher variability in treatment modalities and the rising contribution to the birth rates over the last 20 years point towards the increasing impact of ART. High levels of completeness in data reporting have been reached, but inconsistencies and inaccuracies still remain and need to be identified and quantified. The current trend towards a higher diversity in treatment modalities and the rising impact of cryostorage, resulting in improved safety during and after ART treatment, require changes in the organization of surveillance in ART. The present comparison must stimulate all stakeholders in ART to optimize surveillance and data quality assurance in ART.STUDY FUNDING/COMPETING INTEREST(S)This study has no external funding and all costs are covered by ESHRE. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

ART in Europe, 2016: results generated from European registries by ESHRE.

STUDY QUESTIONWhat are the reported data on cycles in ART, IUI and fertility preservation (FP) interventions in 2016 as compared to previous years, as well as the main trends over the years?SUMMARY ANSWERThe 20th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, with a decrease in the number of transfers with more than one embryo causing a reduction of multiple delivery rates (DR), as well as higher pregnancy rates and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the outcomes for IUI cycles remained stable.WHAT IS KNOWN ALREADYSince 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analysed by the European IVF-monitoring Consortium (EIM) and reported in 19 manuscripts published in Human Reproduction and Human Reproduction Open.STUDY DESIGN, SIZE, DURATIONYearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between 1 January and 31 December 2016 in 40 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations.PARTICIPANTS/MATERIALS, SETTING, METHODSIn all, 1347 clinics offering ART services in 40 countries reported a total of 918 159 treatment cycles, involving 156 002 with IVF, 407 222 with ICSI, 248 407 with FER, 27 069 with preimplantation genetic testing, 73 927 with egg donation (ED), 654 with IVM of oocytes and 4878 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1197 institutions offering IUI in 29 and 24 countries, respectively. A total of 162 948 treatments with IUI-H and 50 467 treatments with IUI-D were included. A total of 13 689 FP interventions from 11 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and postpubertal patients were reported.MAIN RESULTS AND THE ROLE OF CHANCEIn 20 countries (18 in 2015) with a total population of approximately 325 million inhabitants, in which all ART clinics reported to the registry, a total of 461 401 treatment cycles were performed, corresponding to a mean of 1410 cycles per million inhabitants (range 82–3088 per million inhabitants). In the 40 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2016 were similar to those observed in 2015 (28.0% and 34.8% vs 28.5% and 34.6%, respectively). After ICSI, the corresponding rates were also similar to those achieved in 2015 (25% and 33.2% vs 26.2% and 33.2%). After FER with own embryos, the PR per thawing is still on the rise, from 29.2% in 2015 to 30.9% in 2016. After ED, the PR per fresh embryo transfer was 49.4% (49.6% in 2015) and per FOR 43.6% (43.4% in 2015). 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 41.5%, 51.9%, 6.2% and 0.4% of all treatments, respectively (corresponding to 37.7%, 53.9%, 7.9% and 0.5% in 2015). This resulted in a proportion of singleton, twin and triplet DRs of 84.8%, 14.9% and 0.3%, respectively (compared to 83.1%, 16.5% and 0.4%, respectively in 2015). Treatments with FER in 2016 resulted in twin and triplet DR of 11.9% and 0.2%, respectively (vs 12.3% and 0.3% in 2015). After IUI, the DRs remained similar at 8.9% after IUI-H (7.8% in 2015) and at 12.4% after IUI-D (12.0% in 2015). Twin and triplet DRs after IUI-H were 8.8% and 0.3%, respectively (in 2015: 8.9% and 0.5%) and 7.7% and 0.4% after IUI-D (in 2015: 7.3% and 0.6%). The majority of FP interventions included the cryopreservation of ejaculated sperm (n = 7877 from 11 countries) and of oocytes (n = 4907 from eight countries).LIMITATIONS, REASONS FOR CAUTIONAs the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. A number of countries failed to provide adequate data about the number of initiated cycles and deliveries.WIDER IMPLICATIONS OF THE FINDINGSThe 20th ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control of the data, transparency and vigilance in the field of reproductive medicine.STUDY FUNDING/COMPETING INTEREST(S)The study has no external funding and all costs were covered by ESHRE. There are no competing interests.

Survey on ART and IUI: legislation, regulation, funding and registries in European countries: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE).

STUDY QUESTIONHow are ART and IUI regulated, funded and registered in European countries?SUMMARY ANSWEROf the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding (also available in the 39 countries) varies across and sometimes within countries and national registries are in place in 31 countries.WHAT IS KNOWN ALREADYSome information devoted to particular aspects of accessibility to ART and IUI is available, but most is fragmentary or out-dated. Annual reports from the European IVF-Monitoring (EIM) Consortium for ESHRE clearly mirror different approaches in European countries regarding accessibility to and efficacy of those techniques.STUDY DESIGN, SIZE, DURATIONA survey was designed using the online SurveyMonkey tool consisting of 55 questions concerning three domains—legal, funding and registry. Answers refer to the countries’ situation on 31 December 2018.PARTICIPANTS/MATERIALS, SETTINGS, METHODSAll members of EIM plus representatives of countries not yet members of the Consortium were invited to participate. Answers received were checked, and initial responders were asked to address unclear answers and to provide any additional information they considered important. Tables of individual countries resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, asking for a second check. Conflicting information was clarified by direct contact.MAIN RESULTS AND THE ROLE OF CHANCEInformation was received from 43 out of the 44 European countries where ART and IUI are performed. Thirty-nine countries reported specific legislation on ART, and artificial insemination was considered an ART technique in 35 of them. Accessibility is limited to infertile couples in 11 of the 43 countries. A total of 30 countries offer treatments to single women and 18 to female couples. In five countries ART and IUI are permitted for treatment of all patient groups, being infertile couples, single women and same sex couples, male and female. Use of donated sperm is allowed in 41 countries, egg donation in 38, the simultaneous donation of sperm and egg in 32 and embryo donation in 29. Preimplantation genetic testing (PGT) for monogenic disorders or structural rearrangements is not allowed in two countries, and PGT for aneuploidy is not allowed in 11; surrogacy is accepted in 16 countries. With the exception of marital/sexual situation, female age is the most frequently reported limiting criteria for legal access to ART—minimal age is usually set at18 years and maximum ranging from 45 to 51 years with some countries not using numeric definition. Male maximum age is set in very few countries. Where permitted, age is frequently a limiting criterion for third-party donors (male maximum age 35 to 55 years; female maximum age 34 to 38 years). Other legal constraints in third-party donation are the number of children born from the same donor (in some countries, number of families with children from the same donor) and, in 10 countries, a maximum number of egg donations. How countries deal with the anonymity is diverse—strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), mixed system (anonymous and non-anonymous donations) and strict non-anonymity.Public funding systems are extremely variable. Four countries provide no financial assistance to patients. Limits to the provision of funding are defined in all the others i.e. age (female maximum age is the most used), existence of previous children, maximum number of treatments publicly supported and techniques not entitled for funding. In a few countries, reimbursement is linked to a clinical policy. The definition of the type of expenses covered within an IVF/ICSI cycle, up to what limit and the proportion of out-of-pocket costs for patients is also extremely dissimilar.National registries of ART and IUI are in place in 31 out of the 43 countries contributing to the survey, and a registry of donors exists in 18 of them.LIMITATIONS, REASONS FOR CAUTIONThe responses were provided by well-informed and committed individuals and submitted to double checking. Since no formal validation was in place, possible inaccuracies cannot be excluded. Also, results are a cross section in time and ART and IUI legislations within European countries undergo continuous evolution. Finally, several domains of ART activity were deliberately left out of the scope of this ESHRE survey.WIDER IMPLICATIONS OF THE FINDINGSResults of this survey offer a detailed view of the ART and IUI situation in European countries. It provides updated and extensive answers to many relevant questions related to ART usage at national level and could be used by institutions and policymakers in planning services at both national and European levels.Study funding/competing interest(s)The study has no external funding, and all costs were covered by ESHRE. There were no competing interests.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

ART in Europe, 2015: results generated from European registries by ESHRE.

STUDY QUESTIONWhat are the European trends and developments in ART and IUI in 2015 as compared to previous years?SUMMARY ANSWERThe 19th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe, and this increase, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries all point towards the increasing impact of ART on European society.WHAT IS KNOWN ALREADYSince 1997, the ART data generated by national registries have been collected, analysed and reported in 18 manuscripts published in Human Reproduction.STUDY DESIGN, SIZE, DURATIONCollection of European data by the European IVF-Monitoring Consortium (EIM) for ESHRE. The data for treatments performed between 1 January and 31 December 2015 in 38 European countries were provided by national registries or on a voluntary basis by clinics or professional societies.PARTICIPANTS/MATERIALS, SETTINGS, METHODSFrom 1343 institutions in 38 countries offering ART services a total of 849 811 treatment cycles, involving 155 960 with IVF, 385676 with ICSI, 218098 with frozen embryo replacement (FER), 21 041 with preimplantation genetic testing (PGT), 64 477 with egg donation (ED), 265 with IVM and 4294 with FOR were recorded. European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1352 institutions offering IUI in 25 countries and 21 countries, respectively. A total of 139 050 treatments with IUI-H and 49 001 treatments with IUI-D were included.MAIN RESULTS AND THE ROLE OF CHANCEIn 18 countries (14 in 2014) with a population of approximately 286 million inhabitants, in which all institutions contributed to their respective national registers, a total of 409 771 treatment cycles were performed, corresponding to 1432 cycles per million inhabitants (range: 727–3068 per million). After IVF the clinical pregnancy rates (PRs) per aspiration and per transfer were slightly lower in 2015 as compared to 2014, at 28.5 and 34.6% versus 29.9 and 35.8%, respectively. After ICSI, the corresponding PR achieved per aspiration and per transfer in 2015 were also slightly lower than those achieved in 2014 (26.2 and 33.2% versus 28.4 and 35.0%, respectively). On the other hand, after FER with own embryos the PR per thawing continued to rise from 27.6% in 2014 to 29.2% in 2015. After ED a slightly lower PR per embryo transfer was achieved: 49.6% per fresh transfer (50.3% in 2014) and 43.4% for FOR (48.7% in 2014). The delivery rates (DRs) after IUI remained stable at 7.8% after IUI-H (8.5% in 2014) and at 12.0% after IUI-D (11.6% in 2014). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 37.7, 53.9, 7.9 and in 0.5% of all treatments, respectively (corresponding to 34.9, 54.5, 9.9 and in 0.7% in 2014). This evolution towards the transfer of fewer embryos in both IVF and ICSI resulted in a proportion of singleton, twin and triplet DR of 83.1, 16.5 and 0.4%, respectively (compared to 82.5, 17.0 and 0.5%, respectively, in 2014). Treatments with FER in 2015 resulted in twin and triplet DR of 12.3 and 0.3%, respectively (versus 12.4 and 0.3% in 2014). Twin and triplet delivery rates after IUI-H were 8.9 and 0.5%, respectively (in 2014: 9.5 and 0.3%), and 7.3 and 0.6% after IUI-D (in 2014: 7.7 and 0.3%).LIMITATIONS, REASONS FOR CAUTIONThe methods of data collection and reporting vary 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 FINDINGSThe 19th EIM 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 worldwide, detailed information about ongoing developments in the field is provided.STUDY FUNDING/COMPETING INTEREST(S)The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

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).

What are the European trends and developments in ART and IUI in 2014 as compared to previous years? 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. 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. 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. 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. 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%). 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. 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. The study has no external funding and all costs are covered by ESHRE. There are no competing interests.