Survey on ART and IUI: legislation, regulation, funding, and registries in European countries-an update.

STUDY QUESTION: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018? SUMMARY ANSWER: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups. WHAT IS KNOWN ALREADY: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field. STUDY DESIGN, SIZE, DURATION: A survey was designed using the SurveyMonkey tool consisting of 90 questions covering several domains (legal, funding, and registry) and considering specific details on the situation of third-party donations. New questions widened the scope of the previous survey. Answers refer to the situation of countries on 31 December 2022. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: All members of the EIM were invited to participate. The received answers were checked and initial responders were asked to address unclear answers and to provide any additional information considered relevant. Tables resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, requesting a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE: Information was received from 43 out of the 45 European countries where ART and IUI are performed. There were 39 countries with specific legislation on ART, and artificial insemination was considered an ART technique in 33 of them. Accessibility is limited to infertile couples only in 8 of the 43 countries. In 5 countries, ART and IUI are permitted also for treatments of single women and all same sex couples, while a total of 33 offer treatment to single women and 19 offer treatment to female couples. Use of donated sperm is allowed in all except 2 countries, oocyte donation is allowed in 38, simultaneous donation of sperm and oocyte is allowed in 32, and embryo donation is allowed in 29 countries. Preimplantation genetic testing (PGT)-M/SR (for monogenetic disorders, structural rearrangements) is not allowed in 3 countries and PGT-A (for aneuploidy) is not allowed in 10; surrogacy is accepted in 15 countries. Except for marital/sexual situation, female age is the most frequently reported limiting criterion for legal access to ART: minimal age is usually set at 18 years and the maximum ranges from 42 to 54 with some countries not using numeric definition. Male maximum age is set in very few countries. Where third-party donors are permitted, age is frequently a limiting criterion (male maximum age ranging from 35 to 50; female maximum age from 30 to 37). Other legal restrictions in third-party donation are the number of children born from the same donor (or, in some countries, the number of families with children from the same donor) and, in 12 countries, there is a maximum number of oocyte donations. How countries deal with the anonymity is diverse: strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), a mixed system (anonymous and non-anonymous donations), and strict non-anonymity. Inquiring about donors' genetic screening showed that most countries have enforced either mandatory or scientific recommendations that exclude the most prevalent genetic diseases, although, again, diversity is evident. Reimbursement/compensation systems exist in more than 30 European countries, with around 10 describing clearly defined maximum amounts considered acceptable. Public funding systems are extremely variable. One country provides no financial assistance to ART/IUI patients and three offer only minimal support. Limits to the provision of funding are defined in the others i.e. age (female maximum age is the most used), existence of previous children, BMI, maximum number of treatments publicly supported, and techniques not entitled for funding. In a few countries reimbursement is linked to a clinical policy. The definitions of the type of expenses covered within an IVF/ICSI cycle, up to which limit, and the proportion of out-of-pocket costs for patients are also extremely dissimilar. National registries of ART are in place in 33 out of the 43 countries contributing to the survey and a registry of donors exists in 19 of them. When comparing with the results of the previous survey, the main changes are: (i) an extension of the beneficiaries of ART techniques (and IUI), evident in nine countries; (ii) public financial support exists now in Albania and Armenia; (iii) in Luxembourg, the only ART centre expanded its on-site activities; (iv) donor-conceived children are entitled to know the donor identity in six countries more than in 2018; and (v) four more countries have set a maximum number of oocyte donations. LIMITATIONS, REASONS FOR CAUTION: Although the responses were provided by well-informed and committed individuals and submitted to double checking, no formal validation by official bodies was in place. Therefore, possible inaccuracies cannot be excluded. The results presented are a cross-section in time, and ART and IUI frameworks within European countries undergo continuous modification. Finally, some domains of ART activity were deliberately left out of the scope of this survey. WIDER IMPLICATIONS OF THE FINDINGS: Our results offer a detailed updated view of the ART and IUI situation in European countries. It provides extensive answers to many relevant questions related to ART usage at the national level and could be used by institutions and policymakers 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.

Aneuploidy in oocytes from women of advanced maternal age: analysis of the causal meiotic errors and impact on embryo development.

STUDY QUESTION: In oocytes of advanced maternal age (AMA) women, what are the mechanisms leading to aneuploidy and what is the association of aneuploidy with embryo development? SUMMARY ANSWER: Known chromosome segregation errors such as precocious separation of sister chromatids explained 90.4% of abnormal chromosome copy numbers in polar bodies (PBs), underlying impaired embryo development. WHAT IS KNOWN ALREADY: Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years) and can affect over half of oocytes in this age group. This underlies the rationale for PB biopsy as a form of early preimplantation genetic testing for aneuploidy (PGT-A), as performed in the 'ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis' (ESTEEM) randomized controlled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), Meiosis II (MII) non-disjunction (ND), and reverse segregation (RS) are the main mechanisms leading to aneuploidy in oocytes. STUDY DESIGN, SIZE, DURATION: Data were sourced from the ESTEEM study, a multicentre RCT from seven European centres to assess the clinical utility of PGT-A on PBs using array comparative genomic hybridization (aCGH) in patients of AMA (36-40 years). This included data on the chromosome complement in PB pairs (PGT-A group), and on embryo morphology in a subset of embryos, up to Day 6 post-insemination, from both the intervention (PB biopsy and PGT-A) and control groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 461/693 PB pairs showed abnormal segregation in 1162/10 810 chromosomes. The main observed abnormal segregations were compatible with PSSC in Meiosis I (MI) (n = 568/1162; 48.9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%), and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9.6%), we observed a chromosome copy number in the first PB (PB1) and second PB (PB2) that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between 2 and 6 days post-insemination compared to the control group, indicating that PB biopsy did not affect embryo quality. Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day, aneuploidy was associated with a decrease in embryo quality on Day 3 (adjusted odds ratio (aOR) 0.62, 95% CI 0.43-0.90), Day 4 (aOR 0.15, 95% CI 0.06-0.39), and Day 5 (aOR 0.28, 95% CI 0.14-0.58). LIMITATIONS, REASON FOR CAUTION: RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer. WIDER IMPLICATIONS OF THE FINDINGS: Our finding of frequent unexplained chromosome copy numbers in PBs indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by mis-segregation of chromosomes during MI and MII. STUDY FUNDING/COMPETING INTEREST(S): Data were mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of PBs. None of the authors have competing interests. TRIAL REGISTRATION NUMBER: Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284).

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

STUDY QUESTION: How 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 ANSWER: It 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 ALREADY: European 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, DURATION: We 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, METHODS: We 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 CHANCE: During 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 CAUTION: The 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 FINDINGS: The 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 NUMBER: N/A.

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age.

OBJECTIVE: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age? DESIGN: Decision tree model. POPULATION: A randomised clinical trial on PGT-A (ESTEEM study). METHODS: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. RESULTS: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. CONCLUSIONS: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. TWEETABLE ABSTRACT: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

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).

STUDY QUESTION: What are the European trends and developments in ART and IUI in 2014 as compared to previous years? SUMMARY ANSWER: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. WHAT IS KNOWN ALREADY: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). LIMITATION, REASONS FOR CAUTION: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

ESHRE PGD Consortium data collection XIV-XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013.

STUDY QUESTION: How does the data collection XIV-XV of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium compare with the cumulative data for data collections I-XIII? SUMMARY ANSWER: The 14th and 15th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the increased application of array technology at the cost of FISH testing in PGS cycles and in PGD cycles for chromosomal abnormalities. WHAT IS KNOWN ALREADY: Since 1999, the PGD Consortium has collected, analysed and published 13 previous data sets and an overview of the first 10 years of data collections. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a FileMaker Pro database (versions 5-12). Separate predesigned FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar years 2011 and 2012 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2013). PARTICIPANTS/MATERIALS, SETTINGS, METHOD: Data were submitted by 71 centres (full PGD Consortium members). Records with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XIV-XV, 71 centres reported data for 11 637 cycles with oocyte retrieval (OR), along with details of the follow-up on 2147 pregnancies and 1755 babies born. A total of 1953 cycles to OR were reported for chromosomal abnormalities, 144 cycles to OR for sexing for X-linked diseases, 3445 cycles to OR for monogenic diseases, 6095 cycles to OR for PGS and 38 cycles to OR for social sexing. From 2010 until 2012, the use of arrays for genetic testing increased from 4% to 20% in PGS and from 6% to 13% in PGD cycles for chromosomal abnormalities; the uptake of biopsy at the blastocyst stage (from <1% up to 7%) was only observed in cycles for structural chromosomal abnormalities, alongside the application of array comparative genomic hybridization. LIMITATIONS, REASONS FOR CAUTION: The findings apply to the 71 participating centres and may not represent worldwide trends in PGD. WIDER IMPLICATIONS OF THE FINDINGS: The annual data collections provide an important resource for data mining and for following trends in PGD/PGS practice. STUDY FUNDING/COMPETING INTEREST(S): None.

Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE.

STUDY QUESTION: Are there any changes in the treatments involving ART and IUI initiated in Europe during 2013 compared with previous years? SUMMARY ANSWER: An increase in the overall number of ART cycles resulting from a higher number of countries reporting data was evident, the pregnancy rates (PRs) in 2013 remained stable compared with those reported in 2012, the number of transfers with multiple embryos (3+) was lower than ever before yet the multiple delivery rates (DRs) remained unchanged, and IUI activity and success rates were similar to those of last years. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 16 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the European IVF-monitoring Consortium for ESHRE. Data for cycles between 1 January and 31 December 2013 were collected from National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: From 38 countries (+4 compared with 2012), 1169 clinics reported 686 271 treatment cycles including 144 299 of IVF, 330 367 of ICSI, 154 712 of frozen embryo replacement (FER), 40 244 of egg donation (ED), 247 of IVM, 9791 of PGD/PGS and 6611 of frozen oocyte replacements. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1095 IUI labs in 22 countries. A total of 175 467 IUI-H and 43 785 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 17 countries where all clinics reported to their ART register, a total of 374 177 ART cycles were performed in a population of around 310 million inhabitants, corresponding to 1175 cycles per million inhabitants (range, 235-2703 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.6% (29.4% in 2012) and 34.5% (33.8% in 2012), respectively. For ICSI, the corresponding rates also were stable with 27.8% (27.8% in 2012) and 32.9% (32.3% in 2012). In FER-cycles, the PR per thawing/warming increased to 27.0% (23.1% in 2012). In ED cycles, the PR per fresh transfer increased to 49.8% (48.4% in 2012), to 38.5% (35.9% in 2012) per thawed transfer, and to 46.4% for transfers after FOR (45.1% in 2012). The DRs after IUI remained stable at 8.6% (8.5% in 2012) after IUI-H and was slightly lower after IUI-D (11.1% versus 12.0% in 2012). In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 31.4, 56.3, 11.5, and 1.0% of the cycles, respectively (corresponding numbers were 30.2, 55.4, 13.3 and 1.1% in 2012). The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82., 17.5 and 0.5%, respectively, resulting in a total multiple DR of 18.0% compared to 17.9% in 2012. In FER-cycles, the multiple DR was 12.8% (12.5% twins and 0.3% triplets), nearly the same as in 2012 (12.5, 12.2 and 0.3% respectively). Twin and triplet DRs associated with IUI cycles were 9.5%/0.6% and 7.5%/0.3%, following treatment with husband/donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, the results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 17th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 685 000 cycles reported in 2013 and an increasing contribution to birth rate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies, remains manifest. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE.

STUDY QUESTION: The 15th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2011: are there any changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting data, while the overall number of ART cycles has continued to increase year by year, the pregnancy rates in 2011 decreased slightly to those reported in 2010, and the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 14 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1 January and 31 December 2011 are collected on a yearly basis. The data are collected by National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS SETTING, METHODS: From 33 countries (+2 compared with 2010), 1064 clinics reported 609 973 treatment cycles including: IVF 138 592, ICSI 298 918, frozen embryo replacement (FER) 129 693, egg donation (ED) 30 198, in vitro maturation 511, preimplantation genetic diagnosis/screening 6824 and frozen oocyte replacements 5237. European data on intrauterine insemination (IUI) using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 861 IUI laboratories in 24 countries. A total of 174 390 IUI-H and 41 151 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 17 countries where all clinics reported to the ART register, a total of 361 972 ART cycles were performed in a population of 285 million inhabitants, corresponding to 1269 cycles per million inhabitants. For all IVF cycles, the clinical pregnancy rates per aspiration and per transfer were stable with 29.1 and 33.2%, respectively, and for ICSI, the corresponding rates also were stable with 27.9 and 31.8%, respectively. In FER cycles, the pregnancy rate per thawing increased to 21.3% if compared with previous years. In ED cycles, the pregnancy rate per fresh transfer decreased to 45.8% (47.4% in 2010) and increased to 33.6% (33.3% in 2010) per thawed transfer. The delivery rate after IUI-H decreased to 8.3 (8.9 in 2010), and to 12.2% (13.8% in 2010) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 27.5, 56.7, 14.5 and 1.3% of cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 80.8, 18.6 and 0.6%, respectively, resulting in a total multiple delivery rate of 19.2% compared with 20.6% in 2010, 20.2% in 2009, 21.7% in 2008, 22.3% in 2007 and 20.8% in 2006. In FER cycles, the multiple delivery rate was 13.2% (12.8% twins and 0.4% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.7/0.6% and 7.3/0.3%, following IUI-H and IUI-D treatment, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 15th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 600 000 cycles reported in 2011. Since 2006, the proportion of IVF to ICSI cycles has reached a plateau after a small decrease in 2009. Pregnancy and delivery rates after IVF remained relatively stable compared with 2010 and 2009. The pregnancy rate per aspiration in ICSI cycles declined for the first time by 0.9%. The multiple delivery rate is lower than ever before. STUDY FUNDING/COMPETING INTERESTS: The study had no external funding; all costs are covered by ESHRE. There are no competing interests.

Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE.

STUDY QUESTION: The 16th European IVF-monitoring (EIM) report presents the data of the treatments involving assisted reproductive technology (ART) and intrauterine insemination (IUI) initiated in Europe during 2012: are there any changes compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year, the pregnancy rates (PRs) in 2012 remained stable compared with those reported in 2011, and the number of transfers with multiple embryos (3+) and the multiple delivery rates were lower than ever before. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and re-ported in 15 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Data for cycles between 1 January and 31 December 2012 were collected from National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 34 countries (+1 compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139 978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605 of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic diagnosis/preimplantation genetic screening and 5549 of frozen oocyte replacements (FOR). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1126 IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 18 countries where all clinics reported to their ART register, a total of 369 081 ART cycles were performed in a population of around 295 million inhabitants, corresponding to 1252 cycles per million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.4 (29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8% in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in 2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011) and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3% in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of the cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%, respectively, resulting in a total multiple delivery rate of 17.9% compared with 19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was 12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 16th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 640 000 cycles reported in 2012 with an increasing contribution to birthrate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies remains manifest. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

ESHRE PGD Consortium data collection XIII: cycles from January to December 2010 with pregnancy follow-up to October 2011.

STUDY QUESTION: How do data in the 13th annual data collection (Data XIII) of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium compare with the cumulative data for collections I-XII? SUMMARY ANSWER: The 13th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the decrease in the routine implementation of PGS. WHAT IS KNOWN ALREADY: Since 1999, the PGD Consortium has collected, analysed and published 12 data sets and an overview of the first 10 years of data collections. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a FileMaker Pro database (versions 5-11). Separate predesigned FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2010 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2011). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were submitted by 62 centres (full PGD Consortium members). The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XIII, 62 centres reported data for 5780 cycles with oocyte retrieval (OR), along with details of the follow-up on 1503 pregnancies and 1152 babies born. A total of 1071 OR were reported for chromosomal abnormalities, 108 OR for sexing for X-linked diseases, 1574 OR for monogenic diseases, 2979 OR for preimplantation genetic screening and 48 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION: The findings apply to the 62 participating centres and may not represent worldwide trends in PGD. WIDER IMPLICATIONS OF THE FINDINGS: The annual data collections provide an important resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTERESTS: None.

Socio-demographic and fertility-related characteristics and motivations of oocyte donors in eleven European countries.

STUDY QUESTION: Do the socio-demographic and fertility-related characteristics and motivations of oocyte donors differ in European countries? SUMMARY ANSWER: The socio-demographic and fertility-related characteristics and motivations of oocyte donors differ considerably across countries. WHAT IS KNOWN ALREADY: There have been no other international studies comparing the characteristics of oocyte donors. Regarding their motivations, most studies indicate mixed motives. STUDY DESIGN, SIZE, DURATION: The proposed study was a transversal epidemiological study. Data were collected from 63 voluntarily participating assisted reproduction technology centres practising oocyte donation in 11 European countries (Belgium, Czech Republic, Finland, France, Greece, Poland, Portugal, Russia, Spain, UK and Ukraine). The survey was conducted between September 2011 and June 2012 and ran for 1-6 calendar months depending on the number of cycles of oocyte donation performed at the centre. The sample size was computed in order to allow an estimate of the percentage of a relatively rare characteristic (∼2%) with a precision (95% confidence interval) of 1%. The calculation gave 1118 donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1423 forms were obtained from oocyte donors. All consecutive donors in these centres filled out an anonymous questionnaire when they started their hormonal stimulation, asking for their socio-demographic and fertility-related characteristics, their motivations and compensation. Population characteristics were described and compared by country of donation. Motives for donation and mean amount of money were compared between countries and according to the donors characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: The socio-demographic and fertility-related characteristics and motivations of oocyte donors varied enormously across European countries. The number of received forms corresponded with a participation rate of 61.9% of the cycles performed by the participating centres. Mean age was 27.4 years. About 49% of donors were fully employed, 16% unemployed and 15% student. The motivation in the total group of donors was 47.8% pure altruism, 33.9% altruism and financial, 10.8% pure financial, 5.9% altruism and own treatment and finally 2% own treatment only. About 15% of the donors were egg sharers (patient donors), mainly from the UK and Poland. Women were donating for the first time in 55.4% of cases, for the second time in 20.3% and for the third time in 12.8%. The motivation to donate was significantly related to being of foreign origin (P < 0.01), age (P < 0.001), living in couple or not (P < 0.01), level of education (P < 0.001) and number of donations (P < 0.001). The amount of compensation differed considerably between centres and/or countries. The general donor profile in this study was a well-educated, 27-year-old woman living with her partner and child who mainly donated to help others. LIMITATIONS, REASONS FOR CAUTION: The selection of clinics in some countries and the limited participation rate may have led to a bias in donor characteristics. A possible effect of social desirability in the answers by the donors should be taken into account. WIDER IMPLICATIONS OF THE FINDINGS: The diversity of the donor population reflects the differences in European legislation (for example, on anonymity and payment) and economic circumstances. The differences in systems of reimbursement/payment demonstrate the need to have a thorough discussion on the specific meaning of these terms. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the European Society for Human Reproduction and Embryology. The authors declare no conflicting interests.

ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010.

STUDY QUESTION: How do data in the 12th annual data collection (Data XII) of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis (PGD) Consortium compare with the cumulative data for collections I-XI? SUMMARY ANSWER: Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. WHAT IS KNOWN ALREADY: The PGD Consortium has collected, analysed and published 11 previous data sets since 1997. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a pre-designed FileMaker Pro database (versions 5-10). Separate FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2009 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2010). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were submitted by 60 centres (full PGD Consortium members), and the blank files were distributed to each PGD Consortium member centre at the end of 2008. The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete data were excluded from the calculations. Corrections, tables and calculations were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XII, 60 centres reported data for 6160 cycles with oocyte retrieval (OR), along with details of the follow-up on 1607 pregnancies and 1238 babies born. A total of 870 OR were reported for chromosomal abnormalities, 113 OR for sexing for X-linked diseases, 1597 OR for monogenic diseases, 3551 OR for preimplantation genetic screening and 29 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION: These data cannot include every PGD cycle performed annually, and only indicate the trends in PGD worldwide. WIDER IMPLICATION OF THE FINDINGS: The annual data collections provide an extremely valuable resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTEREST(S): None.

Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†.

STUDY QUESTION: The 14th European IVF--monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting, the overall number of ART cycles has continued to increase year by year, and while pregnancy rates in 2010 remained similar to those reported in 2009, the number of transfers with multiple embryos (three or more) further declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 13 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective collection of European ART data by the EIM Consortium for ESHRE; data were collected from cycles started between 1st January and 31st December 2010 by the National Registries of individual European countries, or on a voluntary basis by personal information for European countries without a national registry. PARTICIPANTS/MATERIALS SETTING, METHODS: Out of 31 countries, 991 clinics reported 550 296 ART treatment cycles: IVF (125 994), ICSI (272 771), frozen embryo replacement (FER, 114 593), egg donation (ED, 25 187), in vitro maturation (493), preimplantation genetic diagnosis/preimplantation genetic screening (6399) and frozen oocyte replacements (4859). European data on IUI using husband/partner's semen (IUI-H) or donor semen (IUI-D) were reported from 22 and 19 countries, respectively. A total of 176 512 IUI-H (+8.4% compared with 2009) and 38 124 IUI-D (+30.4% compared with 2009) cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 16 countries where all clinics reported to the national ART registry, a total of 267 120 ART cycles were performed in a population of 219 million inhabitants, corresponding to 1221 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer increased to 29.2 and 33.2%, respectively, and for ICSI, the corresponding rates also increased to 28.8 and 32.0%, when compared with the rates of 2009. In FER cycles, the pregnancy rate per thawing was 20.3%; in ED cycles the pregnancy rate per fresh transfer was 47.4% and per thawed transfer 33.3%. The delivery rate after IUI-H was 8.9 and 13.8% after IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 25.7, 56.7, 16.1 and 1.5%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.4, 19.6 and 1.0%, respectively, resulting in a total multiple delivery rate of 20.6% compared with 20.2% in 2009, 21.7% in 2008, 22.3% in 2007, 20.8% in 2006. In FER cycles, the multiple delivery rate was 12.8% (12.5% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.6/0.5 and 8.5/0.2%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting is not standardized in Europe but varies among countries. Furthermore registries from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. Therefore, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 14th ESHRE report on ART and IUI treatments shows a continuing expansion of the number of ART treatment cycles in Europe, with more than half a million of cycles reported in 2010. The use of ICSI may have reached a plateau. When compared with 2009/2008, pregnancy and (multiple) delivery rates after IVF and ICSI remained relatively stable. The number of multiple embryo transfers (three or more embryos) has shown a decline. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE.

STUDY QUESTION: The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. PARTICIPANTS/MATERIALS SETTING, METHODS: From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. MAIN RESULTS AND THE ROLE OF CHANCE: In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

ESHRE PGT Consortium data collection XXI: PGT analyses in 2018.

STUDY QUESTION: What are the trends and developments in preimplantation genetic testing (PGT) in 2018 as compared to previous years? SUMMARY ANSWER: The main trends observed in this 21st dataset on PGT are that the implementation of trophectoderm biopsy with comprehensive whole-genome testing is most often applied for PGT-A and concurrent PGT-M/SR/A, while for PGT-M and PGT-SR, single-cell testing with PCR and FISH still prevail. WHAT IS KNOWN ALREADY: Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 20 datasets and an overview of the first 10 years of data collections have been published. STUDY DESIGN SIZE DURATION: The data for PGT analyses performed between 1 January 2018 and 31 December 2018 with a 2-year follow-up after analysis were provided by participating centres on a voluntary basis. Data were collected using an online platform, which is based on genetic analysis and has been in use since 2016. PARTICIPANTS/MATERIALS SETTING METHODS: Data on biopsy method, diagnostic technology, and clinical outcome were submitted by 44 centres. Records with analyses for more than one PGT for monogenic disorders (PGT-M) and/or PGT for chromosomal structural rearrangements (PGT-SR), or with inconsistent data regarding the PGT modality, were excluded. All transfers performed within 2 years after the analysis were included, enabling the calculation of cumulative pregnancy rates. Data analysis, calculations, and preparation of figures and tables were carried out by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: The current data collection from 2018 covers a total of 1388 analyses for PGT-M, 462 analyses for PGT-SR, 3003 analyses for PGT for aneuploidies (PGT-A), and 338 analyses for concurrent PGT-M/SR with PGT-A.The application of blastocyst biopsy is gradually rising for PGT-M (from 19% in 2016-2017 to 33% in 2018), is status quo for PGT-SR (from 30% in 2016-2017 to 33% in 2018) and has become the most used biopsy stage for PGT-A (from 87% in 2016-2017 to 98% in 2018) and for concurrent PGT-M/SR with PGT-A (96%). The use of comprehensive, whole-genome amplification (WGA)-based diagnostic technology showed a small decrease for PGT-M (from 15% in 2016-2017 to 12% in 2018) and for PGT-SR (from 50% in 2016-2017 to 44% in 2018). Comprehensive testing was, however, the main technology for PGT-A (from 93% in 2016-2017 to 98% in 2018). WGA-based testing was also widely used for concurrent PGT-M/SR with PGT-A, as a standalone technique (74%) or in combination with PCR or FISH (24%). Trophectoderm biopsy and comprehensive testing strategies are linked with higher diagnostic efficiencies and improved clinical outcomes per embryo transfer. LIMITATIONS REASONS FOR CAUTION: The findings apply to the data submitted by 44 participating centres and do not represent worldwide trends in PGT. Details on the health of babies born were not provided in this manuscript. WIDER IMPLICATIONS OF THE FINDINGS: The Consortium datasets provide a valuable resource for following trends in PGT practice. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding, and all costs are covered by ESHRE. There are no competing interests declared. TRIAL REGISTRATION NUMBER: N/A.

Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE.

BACKGROUND: This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. METHODS: From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%). RESULTS: In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6 million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%. CONCLUSIONS: In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.

ESHRE PGD Consortium data collection XI: cycles from January to December 2008 with pregnancy follow-up to October 2009.

The 11th report of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis Consortium is presented, documenting cycles collected for the calendar year 2008 and follow-up of the pregnancies and babies born until October 2009 which resulted from these cycles. Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection XI, 53 centres have participated, reporting on 5641 cycles to oocyte retrieval (OR), along with details of the follow-up on 1418 pregnancies and 1169 babies born. A total of 774 OR were reported for chromosomal abnormalities, 96 OR for sexing for X-linked diseases, 1363 OR for monogenic diseases, 3401 OR for preimplantation genetic screening and 5 OR for social sexing. Data XI is compared with the cumulative data for data collections I-X.

Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE.

BACKGROUND: This 12th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2008. METHODS: From 36 countries (3 more compared with 2007), 1051 clinics reported 532 260 treatment cycles including: IVF (124 539), ICSI (280 552), frozen embryo replacements (FER, 97 120), egg donation (ED, 13 609), in vitro maturation (IVM, 562), preimplantation genetic diagnosis/screening (PGD/PGS, 2875) and frozen oocyte replacements (FOR, 4080). Overall, this represents a 7.9% increase in the activity since 2007, which is mainly related to an increase in cycles from almost all registers and only partially to the new countries entering EIM (Estonia, Kazakhstan, Moldova and Romania, 5480 cycles in total). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 27 and 21 countries, respectively. A total of 144 509 IUI-H (+1.5%) and 24 960 IUI-D (-4.3%) cycles were included. RESULTS: In 19 countries where all clinics reported to the ART register, a total of 350 143 ART cycles were performed in a population of 369.8 million, corresponding to 947 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.5 and 32.5%, respectively, and for ICSI the corresponding rates were 28.7 and 31.9%. In FER cycles, the pregnancy rate per thawing was 19.3%. The delivery rate after IUI was 9.1% for IUI-H and 13.8% for IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 22.4, 53.2, 22.3 and 2.1%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 78.3, 20.7 and 1.0%, respectively, resulting in a total multiple delivery rate of 21.7%, compared with 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.7% (13.4% twins and 0.3% triplets). In women undergoing IUI, twin and triplet deliveries occurred in 10.6% and 0.7% with IUI-H and in 9.4 and 0.3% with IUI-D, respectively. CONCLUSIONS: In comparison with previous years, there was an increase in the reported number of ART cycles in Europe. For the first time in 5 years, the pregnancy rates failed to show a year-on-year increase. Compared with 2007, the number of transfers of multiple embryos (3+) and a multiple delivery rate showed a marginal decline.

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

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN SIZE DURATION: 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. PARTICIPANTS/MATERIALS SETTING METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

ESHRE's good practice guide for cross-border reproductive care for centers and practitioners.

This paper outlines ESHRE's guidance for centers and physicians providing fertility treatment to foreign patients. This guide aims to ensure high-quality and safe assisted reproduction treatment, taking into account the patients, their future child and the interests of third-party collaborators such as gametes donors and surrogates. This is achieved by including considerations of equity, safety, efficiency, effectiveness (including evidence-based care), timeliness and patient centeredness.