Abstract 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 INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Abstract STUDY QUESTION What are the data on ART and IUI cycles, and fertility preservation (FP) interventions reported in 2017 as compared to previous years, as well as the main trends over the years? SUMMARY ANSWER The 21st ESHRE report on ART and IUI shows the continual increase in reported treatment cycle numbers in Europe, with a decrease in the proportion of transfers with more than one embryo causing an additional slight reduction of multiple delivery rates (DR) as well as higher pregnancy rates (PR) and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the number of IUI cycles increased and their outcomes remained stable. WHAT IS KNOWN ALREADY Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been gathered and analyzed by the European IVF-monitoring Consortium (EIM) and communicated in a total of 20 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on European medically assisted reproduction (MAR) are collected by EIM for ESHRE on a yearly basis. The data on treatments performed between 1 January and 31 December 2017 in 39 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1382 clinics offering ART services in 39 countries reported a total of 940 503 treatment cycles, including 165 379 with IVF, 391 379 with ICSI, 271 476 with FER, 37 303 with preimplantation genetic testing (PGT), 69 378 with egg donation (ED), 378 with IVM of oocytes, and 5210 cycles with frozen oocyte replacement (FOR). A total of 1273 institutions reported data on 207 196 IUI cycles using either husband/partner’s semen (IUI-H; n = 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 CHANCE In 21 countries (20 in 2016) in which all ART clinics reported to the registry, 473 733 treatment cycles were registered for a total population of approximately 330 million inhabitants, allowing a best-estimate of a mean of 1435 cycles performed per million inhabitants (range: 723–3286). Amongst the 39 reporting countries, the clinical PR per aspiration and per transfer in 2017 were similar to those observed in 2016 (26.8% and 34.6% vs 28.0% and 34.8%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2016 (24% and 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 CAUTION As the methods of data collection and levels of reporting vary amongst European countries, interpretation of results should remain cautious. Some countries were unable to deliver data about the number of initiated cycles and deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 21st ESHRE report on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, efforts should continue to optimize data collection and reporting with the perspective of improved quality control, transparency and vigilance in the field of reproductive medicine. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Introduction: Thanks to ever-growing advances in medical science, couples who are in the in vitro fertilisation (IVF) now have more options than ever to encase their chances at a successful pregnancy. One of the options is the use of EmbryoGlue (EG), that creates a bridge between the embryo and the uterus and provides protection to the embryo itself during the transfer process. Aim of this study was to determine whether EG medium is of greater importance for embryo implantation than conventional medium in assisted reproductive technology and compare the rate of embryo implantation with EG and conventional medium in relation to the quality of the embryo, the age of the patients and tobacco smoking. Methods: The retrospective study included 50 patients who used EG medium in embryo transfer (ET) and 50 patients in the control group using conventional medium. All patients underwent ET after stimulation of the cycle according to a short protocol. ETs were done on Day 2, 3, or 5 in the blastocyst stage. Age and smoking status were recorded. Results: Out of a total of 100 patients, 42 patients had successful implantation and positive β-hCG 15 days after ET. In a control group 38 % had positive β-hCG and in the group of patients who used EG 46 %. A higher rate of embryo implantation success was observed on the second day of transfer in the group of patients using EG. In the EG group a significant increase in the embryo implantation rate was observed in patients older than 35. In tobacco smokers the implantation rate was higher if they used EG during ET. Conclusion: EG medium had a positive effect on the second day of ET, patients above the age of 35 and patients who were tobacco smokers.

Abstract STUDY QUESTION What are the European trends and developments in ART and IUI in 2015 as compared to previous years? SUMMARY ANSWER The 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 ALREADY Since 1997, the ART data generated by national registries have been collected, analysed and reported in 18 manuscripts published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Collection 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, METHODS From 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 CHANCE In 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 CAUTION The 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 FINDINGS The 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.

Abstract STUDY QUESTION What are the European trends and developments in ART and IUI in 2015 as compared to previous years? SUMMARY ANSWER The 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 ALREADY Since 1997, the ART data generated by national registries have been collected, analysed and reported in 18 manuscripts published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Collection 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, METHODS From 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 CHANCE In 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 CAUTION The 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 FINDINGS The 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.

both in the prenatal and postnatal period2. The syndrome is like a big puzzle whose parts need to be carefully assembled to get a whole picture.2 Good multidisciplinary approach, proper communication and collaboration with parents and all physician’s involved are required in the diagnostic process. All available resources and tools are needed to increase diagnostic precision in the prenatal diagnosis of fetal syndromes.4

Objective: The aim of this work is to show the importance of the depth of myometrium invasion, tumour size and lymphovascular invasion as prognostic factors in dissemination of lymphatic nodes at endometrial carcinoma (CE). Materials and methods: In the period from 2010 to 2015 at the University Clinic for Gynecology and Obstetrics in Banja Luka, 221 endometrial cancer surgeries were done (laparatomy 184-83%, laparascopy 37-16,74%). Patients who had uterus bleeding in peri/postmenopause or those whose endometrium thickness was bigger than 5 mm which was established by ultrasound, or those who had in their cavum uteri pathological (PH) diagnosis, underwent fractional curettage (FC) or hysteroscopy in order to obtain pathohistological endometrium diagnosis. Substances which were removed by fractional curettage, biopsy or by surgery were sent to patohystological analysis. We analysed the following factors: age (5 groups), histological grade (G) of tumour, depth of myometrial invasion (DIM), whether it is more or less than 50%, the size of the tumour (if it is bigger or smaller than 2 cm), positive or negative lymphovascular invasion (LVI), positive or negative pelvic lymph nodes (PLN). Results: Within histological type the endometrioid type CE 166 (75,11%) was most dominant. Adenocarcinoma of endometrium was present 25 (11,31%), serous CE 11 (4,97%) and clear cell KE 2 (0,90%). Dominant population with CE was over 60 years old 127 (57,46) of female patients. At G3 where DIM was <50% positive PLN were present 2 (3.92%), whereas if DIM was>50%, 6 (26,73%) patients with positive PLN were registred. Tumour size < 2 cm was found with 57 (25,79%) female patients with positive PLN 8 (14,03%), while 164 (74,20%) patients had tumours > 2 cm who had 21 (12,80) PLN metastases. At G1 when tumour was <2 cm, positive PLN had 3 patients (5,88), while when tumour was >2 cm, positive PLN were found at 6 patients (9,69%). At G3 whose size was <2 cm, positive PLN were found at 2 patients (16,66%), but when tumour was >2 cm, PLN metastases were more frequent, 6 (25,00%). Negative LVI was found with 168 patients (76,01%) whose PLN were positive 16 (9,52%), while positive LIV was with 53 patients (23,99%) of whom 14 had PLN metastases (26,41%). At G1 two patients had positive PLN (2,32%) with negative LVI, while with positive LVI, positive PLN were found at 3 patients (11,11%). At G3 having negative LVI positive PLN were found with 6 patients (24,00%), while if LIV was positive, the number of positive PLN were 6 (54,54%). Conclusions: With low risk for lymphatic spread (DIM less than 50%, tumour size smaller than 2 cm and lack of LVI at G1 CE) we also encounter low metastasis rate of PLN. Diagnoses of this kind have an aim to lower the number of pelvic lymphadenectomies. With patients who have a high risk of lymphatic spread (myometrium invasion >50%, tumour size > 2cm, LVI present at G2 and G3) metastasis rate of PLN is high, therefore it is necessary to perform pelvic and paraaortic lymphadenectomy which lowers the mortality rate for more than 50% and at the same time patients get an absolute chance of 5-year survival period.