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.

Background: The importance of homocysteine (Hcy) is increasingly recognized in last few decades as an independent risk factor for atherosclerosis and thrombosis, but there is lack of data referring to influence of Hcy on plasma oxidative stress parameters as well as the role of gasotransmitters in these effects. Therefore, this study aim was to assess the role of gasotransmitter inhibitors in Hcy-induced effects on plasma oxidative stress in rats. Material and Methods: Study involved 96 male Wistar albino rats divided into 8 groups: 1) Control group – saline (1ml 0.9 % NaCl i.p.); 2) DL-Hcy (8 mmol/kg i.p. DL homocysteine (DL-Hcy); 3) L-NAME (10 mg/kg i.p. Nω-Nitro-L-arginine methyl ester (L-NAME), inhibitor of NO production); 4) ZnPPR IX (30 mol/kg i.p. protoporphyrin IX zinc (ZnPPR IX), inhibitor of CO production); 5) DL-PAG (50 mg//kg i.p. DL-propargylglycine (DL-PAG), inhibitor of H2S production); 6) DL-Hcy+L-NAME (8 mmol/kg i.p. DL-Hcy + 10 mg/kg i.p. L-NAME); 7) DL-Hcy+ZnPPR IX (8 mmol/kg i.p. DL-Hcy + 30 mol/kg i.p. Zn PPR IX), and 8) DL-Hcy+DL-PAG (8 mmol/kg i.p. DL-Hcy + 50 mg//kg i.p. DL-PAG). In all experimental groups, tested substances were administered in a single dose, intraperitoneally, 60 minutes before animals’ euthanasia. In the collected blood samples malondialdehyde concentration, catalase, glutathione peroxidase and superoxide dismutase activity were measured. Results: Applied substances induced rapid and strong increase of plasma antioxidant enzymatic activity probably as a compensatory response to its pro-oxidant influence. Conclusion: The effects of Hcy on the activity of plasma antioxidant enzymes are in part mediated via interaction with gasotransmitters.

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

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.

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.

A prospective study, which lasted from September 2014 to October 2016, covered the subjects who were examined for various benign tumor changes on the skin. The examinees were divided into 2 groups. The first group A (92 examinees) was composed of the examinees who inhabited a rural area. The second group B (98 examinees) was consisted of examinees who lived in an urban environment. The analyzed examinees gravitate towards rural and urban areas of Banja Luka, Gradiska, Stanari, Prijedor and Teslic in Bosnia and Herzegovina. The aim of this study is to analyze the attitude of examinees from rural and urban areas towards skin tumors. Parameters that were used for comparison of results are: personal attitude to skin tumors and previous skin examinations. There was no statistically significant difference in terms of prejudices among the respondents: that there is no risk of skin cancer, if a person is not exposed to the sun, and/or if changes in the skin are innate, as well as in the number of examinees who said they were not afraid of a skin tumor. In group A the number of examinees that have no opinion about skin tumors is three times higher, while in group B the number of examinees who said that they had a phobia of skin cancer is three times higher. It turned out that regular self-examination of the skin in group A is performed only by 7 (7.6%) examinees, while in group B it is done by 21 (21.5%) examinees, which proved to be statistically significantly different. Occasionally skin examination by a specialist family doctor (and/or a dermatologist) has been performed by 3 (3.3%) examinees of group A and 10 (10.3%) from group B. 4 (4.1%) examinees from group B and no one from group A perform dermoscopic examination occasionally. It was found that regular dermoscopy inspections or skin examinations by a specialist family doctor and/or dermatologist have not been done by any examinees from both analyzed groups. Attitude toward skin tumors of group A is more leisurely (less responsible), so for that group there is a possibility of higher risk degree for late diagnosis of malignant skin tumors.

Summary. Ovariectomy is one of the most common ways of inducing experimental osteoporosis, since there are no meaningful differences in bone behavior between surgical and natural menopause. Because ovariectomized rat still represent the “gold standard” in studies of postmenopausal osteoporosis, the present study focuses on an animal model of osteoporosis which we developed for researching the effects of medicament and non-medicament treatment of this bone disease. Experiments were conducted on a total of 18 female Wistar rats aged fourteen weeks, randomly divided into three experimental groups: intact (INT) group and two groups of ovariectomized (OVX) animals (OVX I and OVX II), consisting of 6 animals each. Animals are ovariectomized using a ventral approach, which in our experience is more favorable than the midline dorsal skin incision or double dorsolateral approach, both of which are also commonly used for inducing experimental osteoporosis. The OVX I group consisted of bilateral ovariectomized females sacrificed six weeks after ovariectomy, while OVX II was sacrificed eleven weeks after ovariectomy. The group of intact, un-operated control animals (INT group) was sacrificed after eleven weeks together with animals of the OVX II group. Blood samples for measurement of serum alkaline phosphatase, osteocalcin, calcium and phosphorus level are collected from animals of the INT and OVXI group after six weeks and from animals of INT and OVX II groups after eleven weeks. Histological analyses were done on tibia while biomechanical measurements were done on the femurs of animals from INT, OVXI and OVX II groups. In animals of the OVX I group, levels of alkaline phosphatase, osteocalcin, phosphorus and calcium were statistically significantly increased (p < 0.01) compared to intact female (INT group) controls, indicating an increase in bone degradation. Histological analysis shows that the tibia of ovariectomized females are characterized by the appearance of fine thinned trabecular bone, with enlargement of Haversian channels in cortical bone and with gradual transition of lamellar (cortical) bone to cancellous (trabecular) bone. Biomechanical measurements also confirm significant changes in the quality of the bone after bilateral ovariectomy and show increasing fragility of the femur in the biomechanical bending test. In females that were sacrificed eleven weeks after ovariectomy (OVX II group), biochemical parameters also suggest accelerated bone degradation, but signs of stabilization of resorptive activity were present. Levels of alkaline phosphatase, osteocalcin, phosphorus and calcium were significantly increased in OVXII (p < 0.01) vs. INT, but were very close to those measured in the OVX I group. Histological findings for OVXII also indicate loss of longitudinal trabeculae, extension of the medullary canal and extension of the area with bone marrow 11 weeks after bilateral ovariectomy. This is consistent with the bone becoming more porous and increasingly fragile, resulting in lower and lower bone mass, with increasing holes and spaces. In agreement with this, as the bones become more porous, significantly reduced moment of force and deflection in bending was detected. With this experiment we demonstrated that ovariectomy using a ventral approach is a preferable method which provides 100 percent survival of animals as well as rapid wound healing without complications after the surgical procedure, while results obtained by histological and biomechanical analysis of the bones of ovariectomized animals reliably confirmed the existence of osteoporotic processes that progress over time. Thus, our animal osteoporotic model is suitable for testing the effects of drugs and physical procedures in postmenopausal osteoporosis.

INTRODUCTION Basocellular skin carcinoma (BCC) is the most common cancer in the human population. BCC almost appeared at adult's people, but it can be found at children, too. THE AIM The aim of this study was to determine which the position of BCC on the head skin is the most difficult for the treatment and what the reasons are for it. METHODS With the prospective study, from June 2004 to June 2011, were compared the results of treatment of basocellular carcinomas (BCC) of the head skin. The examinees were divided into 3 groups. The first group, the group A (38 patients) was consisted of examinees treated of BCC on the nose. In the second group, the group B (42 patients) was classified of examinees treated of BCC on the face, temple, eyelids and forehead, while the third group, group C (35 patients) was classified of examinees treated of BCC on the scalp. The parameters for comparison the results of treatment were the method of treatment, number of the relapse, elapsed time from surgery to relapse and consequently defacement. RESULTS There was found a statistical significant difference in terms of choice of methods of operative treatment for the significantly higher number of operations on the scalp operated with cutaneous transplants. It was confirmed that the localization of the tumors on the scalp, and then on the nose are with the highest incidence of the relapse, whereas the postoperative defacement is mostly on the scalp after skin graft placement. Key

UNLABELLED Pancreatic tumor is one with the worst prognosis of all cancers, and the tenth most frequent cancer in Europe, making the 3% of all cancers affecting both sexes. Most patients seek treatment when the disease is in its advanced stage and the level for possible resectability is low. Late presentation of the disease is responsible for the short survival period of 6 months and a five-year survival of 0.4 to 5% of patients. At the Clinic for Surgery in Tuzla during period from January 1st 1996, to January 1st 2011, a total of 127 resection surgeries were performed due to malignant tumors. The goal of this study was to show that adequate assessment of operability, proper surgical strategy and modern techniques of creating anastomoses reduces morbidity and mortality, results in fewer postoperative complications and contributes to better surgical results. In our study sample the most common place of tumor location was the head of pancreas, in 69 (59.7%) patients. Men develop this type of cancer more often than women in the ratio of 2:1, while the median age of patients was 62 years. We faced postoperative complications in 37 (29.1%) patients, pancreatic fistula being the most prevalent complication, occurring in 16 (12.6%) patients. Overall early and late postoperative mortality was observed in 12 (9.8%) patients. CONCLUSION Patients with chronic and hereditary pancreatitis are at a higher risk for developing pancreatic cancer and should be screened for the purpose of early diagnosis. The staging of pancreatic cancer has improved, with the accuracy of 85-90%. Postoperative complications, morbidity, and mortality are significantly reduced (p < 0.05) if the standardized operational procedure is applied and if modern techniques are used to create pancreaticojejunal anastomosis as the anastomosis carrying the highest risk.