Search

STUDY QUESTION Can chromosomal abnormalities beyond copy-number aneuploidies (i.e. ploidy level and microdeletions (MDs)) be detected using a preimplantation genetic testing (PGT) platform? SUMMARY ANSWER The proposed integrated approach accurately assesses ploidy level and the most common pathogenic microdeletions causative of genomic disorders, expanding the clinical utility of PGT. WHAT IS KNOWN ALREADY Standard methodologies employed in preimplantation genetic testing for aneuploidy (PGT-A) identify chromosomal aneuploidies but cannot determine ploidy level nor the presence of recurrent pathogenic MDs responsible for genomic disorders. Transferring embryos carrying these abnormalities can result in miscarriage, molar pregnancy, and intellectual disabilities and developmental delay in offspring. The development of a testing strategy that integrates their assessment can resolve current limitations and add valuable information regarding the genetic constitution of embryos, which is not evaluated in PGT providing new level of clinical utility and valuable knowledge for further understanding of the genomic causes of implantation failure and early pregnancy loss. To the best of our knowledge, MDs have never been studied in preimplantation human embryos up to date. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort analysis including blastocyst biopsies collected between February 2018 and November 2021 at multiple collaborating IVF clinics from prospective parents of European ancestry below the age of 45, using autologous gametes and undergoing ICSI for all oocytes. Ploidy level determination was validated using 164 embryonic samples of known ploidy status (147 diploids, 9 triploids, and 8 haploids). Detection of nine common MD syndromes (-4p=Wolf-Hirschhorn, -8q=Langer-Giedion, -1p=1p36 deletion, -22q=DiGeorge, -5p=Cri-du-Chat, -15q=Prader-Willi/Angelman, -11q=Jacobsen, -17p=Smith-Magenis) was developed and tested using 28 positive controls and 97 negative controls. Later, the methodology was blindly applied in the analysis of: (i) 100 two pronuclei (2PN)-derived blastocysts that were previously defined as uniformly euploid by standard PGT-A; (ii) 99 euploid embryos whose transfer resulted in pregnancy loss. PARTICIPANTS/MATERIALS, SETTING, METHODS The methodology is based on targeted next-generation sequencing of selected polymorphisms across the genome and enriched within critical regions of included MD syndromes. Sequencing data (i.e. allelic frequencies) were analyzed by a probabilistic model which estimated the likelihood of ploidy level and MD presence, accounting for both sequencing noise and population genetics patterns (i.e. linkage disequilibrium, LD, correlations) observed in 2504 whole-genome sequencing data from the 1000 Genome Project database. Analysis of phased parental haplotypes obtained by single-nucleotide polymorphism (SNP)-array genotyping was performed to confirm the presence of MD. MAIN RESULTS AND THE ROLE OF CHANCE In the analytical validation phase, this strategy showed extremely high accuracy both in ploidy classification (100%, CI: 98.1–100%) and in the identification of six out of eight MDs (99.2%, CI: 98.5–99.8%). To improve MD detection based on loss of heterozygosity (LOH), common haploblocks were analyzed based on haplotype frequency and LOH occurrence in a reference population, thus developing two further mathematical models. As a result, chr1p36 and chr4p16.3 regions were excluded from MD identification due to their poor reliability, whilst a clinical workflow which incorporated parental DNA information was developed to enhance the identification of MDs. During the clinical application phase, one case of triploidy was detected among 2PN-derived blastocysts (i) and one pathogenic MD (-22q11.21) was retrospectively identified among the biopsy specimens of transferred embryos that resulted in miscarriage (ii). For the latter case, family-based analysis revealed the same MD in different sibling embryos (n = 2/5) from non-carrier parents, suggesting the presence of germline mosaicism in the female partner. When embryos are selected for transfer based on their genetic constitution, this strategy can identify embryos with ploidy abnormalities and/or MDs beyond aneuploidies, with an estimated incidence of 1.5% (n = 3/202, 95% CI: 0.5–4.5%) among euploid embryos. LIMITATIONS, REASONS FOR CAUTION Epidemiological studies will be required to accurately assess the incidence of ploidy alterations and MDs in preimplantation embryos and particularly in euploid miscarriages. Despite the high accuracy of the assay developed, the use of parental DNA to support diagnostic calling can further increase the precision of the assay. WIDER IMPLICATIONS OF THE FINDINGS This novel assay significantly expands the clinical utility of PGT-A by integrating the most common pathogenic MDs (both de novo and inherited ones) responsible for genomic disorders, which are usually evaluated at a later stage through invasive prenatal testing. From a basic research standpoint, this approach will help to elucidate fundamental biological and clinical questions related to the genetics of implantation failure and pregnancy loss of otherwise euploid embryos. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. S.C., M.F., F.C., P.Z., I.P., L.G., C.P., M.P., D.B., J.J.-A., D.B.-J., J.M.-V., and C.R. are employees of Igenomix and C.S. is the head of the scientific board of Igenomix. A.C. and L.P. are employees of JUNO GENETICS. Igenomix and JUNO GENETICS are companies providing reproductive genetic services. TRIAL REGISTRATION NUMBER N/A.

Objective: To analyze the perception of students in the 6th year of Medicine and 4th year of Physiotherapy of the Faculty of Medicine and Nursing of the University of Cordoba about the information received and different aspects related to the development of the OSCE test. Methodology: Observational, descriptive and cross-sectional study based on a questionnaire applied, after the OSCE test, to students in their last year of Medicine and Physiotherapy degrees at the University of Cordoba. Results: 95 Medicine degree students and 31 Physiotherapy degree students participated. Medicine students highlight the assessment of the previous information, the organization of the test and the time they had to complete the different stations. On the other hand, Physiotherapy students are more satisfied with the fact that they have seen or performed the clinical skills demanded in the OSCE to a greater extent. The overall assessment given to the test by Medicine and Physiotherapy students was 7.53/10 and 6.13/10, respectively. Conclusion: The perception of students in the 6th year of Medicine and 4th year of Physiotherapy of the Faculty of Medicine and Nursing of the University of Cordoba on different aspects of the OSCE test is different. The opinion of the students, although quite redeemable in general, reveals to be a key piece to generate improvement plans in future editions of this, by working with the teaching and care managers so that the students increase their clinical training during the degree.

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 INTEREST(S) The study has no external funding, and all costs are covered by ESHRE. There are no competing interests declared. TRIAL REGISTRATION NUMBER N/A.

Resumen Introduccion y objetivos La imagineria motora es una tecnica ampliamente utilizada en la rehabilitacion neurologica. Su utilidad y resultados vienen condicionados por la habilidad de imaginar el movimiento, que puede ser evaluada por diversos instrumentos. Este estudio pretende evaluar las propiedades psicometricas de un instrumento de reciente creacion dedicado, en concreto, a la mano/miembro superior: Cuestionario de evocacion mental de imagenes, movimientos y actividades. Materiales y metodos Fueron evaluados 29 sujetos (41% varones y 59% mujeres), con un promedio de 45 anos de edad. A todos ellos se les administro, en un primer encuentro, el «Cuestionario de evocacion mental de imagenes, movimientos y actividades» y el «Movement Imagery Questionnaire-Revised» en su version espanola. En un segundo encuentro se les realizo el retest del Cuestionario de evocacion mental de imagenes, movimientos y actividades. Se calcularon: estadisticos descriptivos, consistencia interna, fiabilidad test-retest, reproducibilidad y validez concurrente entre ambos instrumentos. Resultados Fiabilidad/consistencia interna: se hallaron buenos indices de consistencia interna de la prueba tanto para la escala global como para sus 2 subescalas: evocacion y sensacion. Fiabilidad/test-retest: no se hallaron diferencias significativas en el intervalo de una semana. Reproducibilidad: se hallo un excelente coeficiente de correlacion intraclase. Validez concurrente: el Cuestionario de evocacion mental de imagenes, movimientos y actividades tiene una fuerte correlacion con el Movement Imagery Questionnaire-Revised. Conclusiones El Cuestionario de evocacion mental de imagenes, movimientos y actividades es un instrumento psicometricamente solido que puede ser utilizado para medir la habilidad para formar mentalmente imagenes visuales y cinestesicas de la mano/miembro superior, a la vez que proporciona informacion del proceso de imaginacion por el que pasa la persona que esta siendo evaluada.

The effect of laser shock peening (LSP) on the fatigue crack initiation of 2205 duplex stainless steel curved specimens was studied. The aim of this research work was to examine the effectiveness of LSP on curved beams when bending stress is dominant. Two curved specimen types were considered, one with smooth surfaces and another similar but with a small blind hole on the inner surface to investigate the effect of the stress concentrator. The technology implemented to perform the surface treatment consisted of a Nd: YAG pulsed laser 1064 nm, with frequency 10 Hz, releasing an energy of 1 J/pulse and with pulse density 2500 pulses/cm2. The confining medium was water and no protective coating was used. The residual stress in the specimens were determined using the contour method. Curved samples were prepared and treated with LSP only on the inner surface. Fatigue tests were conducted using a load ratio R = 0.1 and the results were compared to estimates obtained with a finite element software and fatigue analysis. LSP simulation by the finite element method followed by a fatigue analysis provided a satisfactory prediction of the onset of failure in curved samples. LSP simulation predicts a detrimental effect of LSP on smooth curved specimens where bending stress dominates over membrane stress. In the case of curved specimens with a stress concentrator on the inner surface, it was observed that LSP enhanced fatigue life by about 82%. SEM analysis of fracture surfaces provided findings coherent with the numerical predictions.

Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5–1 Gy on every other day up to a total dose of 3–6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. With a median follow-up of 10.5 months (range 7.55–12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p

Lactate dehydrogenase (LDH) catalyzes the reversible conversion of L-lactate to pyruvate. LDH-A deficiency is an autosomal recessive disorder (glycogenosis type XI, OMIM#612933) caused by mutations in the LDHA gene. We present two young adult female patients presenting with intolerance to anaerobic exercise, episodes of rhabdomyolysis, and, in one of the patients, psoriasis-like dermatitis. We identified in the LDHA gene a homozygous c.410C>A substitution that predicts a p.Ser137Ter nonsense mutation in Patient One and a compound heterozygous c.410C>A (p.Ser137Ter) and c.750G>A (p.Trp250Ter) nonsense mutation in Patient Two. The pathogenicity of the variants was demonstrated by electrophoretic separation of LDH isoenzymes. Moreover, a flat lactate curve on the forearm exercise test, along with the clinical combination of myopathy and psoriatic-like dermatitis, can also lead to the diagnosis.

Under ballast mats (UBM) have demonstrated their capacity to reduce section stiffness and ballast degradation. However, UBM can cause ballast destabilisation under some circumstances due to excessive vertical track deflections, requiring the installation of geogrids over the mat which increases costs and time. As alternative to this solution, this paper shows the design of GridMat: a sustainable technology for ballasted railways that combines the concepts of geogrids and under ballast mats (UBM) manufactured from recycled crumb rubber. This aims to provide damping capacity while limiting the oscillations and settlement of ballast layer. To obtain the optimal GridMat design, five different configurations varying the aperture size and void areas were assessed through laboratory box tests reproducing the track section including the GridMat. Results showed that the optimal Gridmat was of 55 mm aperture seize and 25% void area. To evaluate the sustainability of this design, the expected number of conservation and renewal operations were calculated from full-scale laboratory tests and a life-cycle assessment and life-cycle cost analysis were undertaken. GridMat showed long-term reduction in ballast degradation and track settlement, reducing need for maintenance and renewal operations in comparison with standard mats., Spanish Government RTI2018-102124-J-IOO

To explore the feasibility of image-guided and respiratory-gated Stereotactic Body Radiation Therapy (SBRT) for Accelerated Partial Breast Irradiation (APBI) in patients with very early breast cancer. Selected patients with early breast carcinoma after breast-conserving surgery were enrolled in this phase II trial. A fiducial marker was percutaneously placed close to surgical bed and five external fiducials were set on the skin. A CT scan for planning was acquired at free breathing. The treatment was planned and DVH were assessed according to international recommendations. Prescription dose was 30 Gy in five consecutive fractions of 6 Gy. A 6MV monoenergetic LINAC (linear accelerator) that combines stereoscopic X-ray imaging system and ExacTrac Adaptive Gating technique was used. PTV (planning target volume) intrafraction motion was controlled and PTV was irradiated in a selected gated area of the respiratory cycle. Shifts for a correct, gated set-up were calculated and automatically applied. Between April 2013 and October 2015, a total of 23 patients were included. The median tumor size was 12 mm. The mean PTV volume was 114 cc. The mean ipsilateral lung V9 Gy was 2.2% and for left-sided breast cancers, the volume of the heart receiving 1.5 Gy was 11.5%. Maximum skin dose was 30.8 Gy. Acute toxicity was grade1 in all the patients and 100% experienced excellent/good breast cosmesis outcomes. With a median follow-up of 66 months (range 8–99 months) local-relapse-free-survival reaches 100%. One patient developed a second breast cancer outside the treated quadrant after 25.1 months. APBI with SBRT and ExacTrac Adaptive Gating System was feasible. The acute and late toxicities were almost null and cosmesis was excellent. We also found that the margins of 5 mm applied from CTV to PTV were sufficient to compensate for geometric uncertainties.

Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are essential tools in radiation oncology. In Spain, the use of these techniques continues to grow as older linear accelerators (linacs) are replaced with modern equipment. However, little is known about inter-centre variability in prescription and dose heterogeneity limits. Consequently, the SBRT-Spanish Task Group (SBRT-SG) of the Spanish Society of Radiation Oncology (SEOR) has undertaken an initiative to assess prescription and homogeneity in SRS/SBRT treatment. In the present study, we surveyed radiation oncology (RO) departments to obtain a realistic overview of prescription methods used for SBRT and SRS treatment in Spain. A brief survey was developed and sent to 34 RO departments in Spain, mostly those who are members of the SEOR SBRT-SG. The survey contained seven questions about the specific prescription mode, dose distribution heterogeneity limits, prescription strategies according to SRS/SBRT type, and the use of IMRT–VMAT (Intensity Modulated Radiation Therapy–Volumetric Modulated Arc Therapy). Responses were received from 29 centres. Most centres (59%) used the prescription criteria D95% ≥ 100%. Accepted dose heterogeneity was wide, ranging from 107 to 200%. Most centres used IMRT–VMAT (93%). This survey about SRS/SBRT prescription and dose heterogeneity has evidenced substantial inter-centre variability in prescription criteria, particularly for intended and accepted dose heterogeneity. These differences could potentially influence the mean planning target volume dose and its correlation with treatment outcomes. The findings presented here will be used by the SEOR SBRT-SG to develop recommendations for SRS/SBRT dose prescription and heterogeneity.

This paper describes an experimental investigation performed to evaluate the low-velocity impact behavior of prepreg-based carbon fiber reinforced polymers (CFRPs) and fiber metal laminates (FMLs) with and without open holes subjected to different impact energies. The laminates were made of carbon fiber/epoxy prepregs and aluminum layers and manufactured by using autoclave. The impact responses of these laminates were experimentally obtained using a drop-weight tower at impact energies of 15, 20 and 30 J. After testing, the impact damage area of tested specimens was quantified from C-scan ultrasonic technique. In addition, an X-ray tomography analysis was performed to assess the through-thickness distribution of damage in FMLs with and without open holes. The results showed that the woven FMLs exhibit the highest impact peak force compared to that of CFRP plates due to the presence of aluminum layers, which induce a higher deformation capability to the laminates. The presence of open holes in laminates tends to augment their damage extension and decreases their impact peak force due to the local stress concentration effect. Nevertheless, it was observed by C-scan ultrasonic images that the aluminum layers reduce the extent of delamination of laminates during the impact event. Postimpact evaluation using X-ray computed tomography showed that impact causes a severe damage to the laminates around their impact point and confirmed that matrix cracking and delamination are the principal damage mechanisms induced on the through-thickness direction of the FML plates. In specific, the results confirm that the aluminum layers provide good impact properties and damage resistance when they are added to the CFRPs.

Study question Does the embryonic cell-free DNA (cfDNA) in the culture medium represent the chromosomal content of the inner cell mass (ICM)? Which factors impact concordance rates? Summary answer There is high ploidy concordance between ICM biopsies and embryonic cfDNA. This value is independent of female age, insemination technique and embryo quality. What is known already The existence of embryonic cfDNA in spent blastocyst medium (SBM) has been confirmed in recent studies, opening a new era of possibilities for non-invasive preimplantation genetic testing for aneuploidy (niPGT-A). High concordance rates of cfDNA with trophectoderm (TE) biopsies and with whole blastocysts have been reported. However, the compartment(s) from where this DNA originates remain unclear. Both TE and ICM are potential sources, but, at the moment, the origin of this cfDNA is unknown as well as the mechanisms underlying its secretion into the medium. Study design, size, duration We carried out a prospective study to investigate the concordance of cfDNA with the corresponding TE and ICM biopsies. 141 day-6/7 blastocysts were donated for research after written informed consent signature for the project approved by the Ethics Committee. Embryos underwent TE biopsy and SBM collection in the same PGT-A cycle. ICM biopsy in thawed blastocysts was performed after TE biopsy diagnosis. cfDNA, TE and ICM biopsies were analyzed from January 2019 to November 2021. Participants/materials, setting, methods Embryos were cultured in routine conditions up to day 4. They were then washed and transferred to a new 10μl culture medium droplet. On day 6, SBM was collected and frozen at -20 °C; and blastocyst biopsy and vitrification were performed. Subsequently, blastocysts were thawed and ICM biopsy was conducted. All samples were analyzed by NGS (Ion ReproSeq PGS kit, ThermoFisher Scientific) and the results were analyzed with customized algorithms for TE, ICM and cfDNA. Main results and the role of chance In combination, the three sample types (cfDNA, ICM and TE) were informative in 81.6% of the blastocysts (115/141). Considering the ICM as the reference, ploidy concordance (i.e. being both euploid or aneuploid) for cfDNA was 86.1% (99/115) and for TE was 89.6% (103/115), without statistical difference. False positive rates were similar for cfDNA and for TE biopsies (6.1% and 9.6%, respectively), and false negative rates were not significantly different, but higher in cfDNA (7.8%) than in TE (0.9%), due to potential contamination with maternal DNA. Ploidy concordance between embryo cfDNA and TE biopsies was 89.6% (103/115). When the results were stratified by female age (≤37 or > 37 years), insemination technique (ICSI or IVF), blastocyst expansion degree (expanded, hatching or fully hatched), and ICM/TE quality (A or B), the informativity of the cfDNA was very similar between the different groups and ranged from 83.7% to 100%. Nevertheless, there were subtle differences for ICM-cfDNA ploidy concordance. It was slightly increased for the older female age group (88.3% vs 83.6% female age ≤37) as well as for ICSI (89.7% vs 82.5% in IVF) and for ICM quality B (88.4% vs 80.0% for ICM A). None of those differences reached statistical significance. Limitations, reasons for caution When stratifying according to the different criteria, the sample size analyzed was too small to draw strong conclusions. Therefore, more studies, with bigger sample size, are needed to replicate the results. Wider implications of the findings The embryonic cfDNA released to the culture medium provides information of the overall blastocyst chromosomal constitution, as suggested by the high ploidy concordance rates reported between ICM and cfDNA. This supports the use of niPGT-A as an alternative to other invasive aneuploidy detection methods that require a biopsy. Trial registration number ClinicalTrials.gov. ID NCT03520933

Study question Which are the trends shown in data collection XXII of the European Society of Human Reproduction and Embryology (ESHRE) PGT Consortium compared with previous years? Summary answer Data collection XXII, year 2020, represents valuable data on PGT activity in (mainly) Europe and reports on the main trends observed, being the further expansion of comprehensive testing technology in PGT-SR and PGT-A. What is known already The ESHRE PGT Consortium was set up in 1997 and from that time has been collecting data on PGT and PGT-A. The PGT database comprises the world’s largest collection of PGT / PGT-A data providing a valuable resource for data mining and for following trends in PGT practice. So far, up to the year 2015, data collections were carried out in a retrospective data way, from 2016 onwards a prospective cycle-by-cycle data collection was in place. Study design, size, duration As the nature of PGT/ PGT-A treatments has changed significantly over the last years and IVF cycle management and genetic analysis techniques are getting more complex, ESHRE uses an online data collection system in which data are collected prospectively from oocyte retrieval to analysis, embryo transfer and pregnancy / live birth. Data are collected cycle by cycle on a voluntary basis. Participants/materials, settings, method For the 2020 data, individual centres (37) from 20 countries directly entered the data into the PGT database through software developed by ESHRE. Data were analysed at ESHRE headquarters and include all aspects of PGT/PGT-A cycles. Main results and the role of chance The Consortium has analysed the PGT analyses (n = 2809) performed in 2020. The indications for PGT included inherited chromosomal abnormalities (n = 331 analyses), monogenic disorders (n = 987 analyses), aneuploidy testing for infertility (n = 1417 analyses) or combinations of the above (n = 74 analyses). In addition, 704 clinical pregnancies and 335 deliveries have been analysed in detail. The methods used for biopsy were polar body (2%), cleavage stage biopsy (20%) and blastocyst biopsy (78%), showing a further increase of blastocyst biopsy compared to 2019. The methodology used for diagnosis is what is evolving most over the last years, with data set XXII (2020) showing around 4% of FISH, 28% of PCR and 68% of WGA. Within WGA 95% of the analysis were done using NGS, in 4% of the cases SNP arrays were used and in 1% array-CGH was used. The overall clinical pregnancy rate is about 25% per analysis. The baby data show that it is difficult for most centres to have a detailed follow-up. Limitations, reasons for caution The findings apply to the 37 participating centres and may not represent worldwide trends in PGT. Data were collected prospectively, but details of the follow-up on PGT pregnancies and babies born were limited. Wider implications of the findings The ESHRE PGD Consortium continues its activities as an important forum for PGT practitioners to share data and exchange experiences. The information extracted from the data collections helps to monitor quality issues in PGT and survey the introduction and effectiveness of new PGT technologies and methods. Trial registration number

Study question In recent decades there has been an increase in environmental contaminants than can affect assisted reproduction techniques. We analyze the influence of vanadium (V) and lead (Pb) on these results. Summary answer Higher seminal fluid V levels affect fertilization rate (FR). Higher Pb and V levels decrease embryo cleavage rate (CR). What is known already Some animal studies have shown that V produces toxicity in the male reproductive system through oxidative stress, and this leads to decreases sperm count and motility, as well increased concentration of abnormal sperm. Pb is one of the main pollutants and, it accumulates in the male reproductive organs, deteriorates the quality of semen, increases the frequency of spontaneous abortion and male infertility. And it has also been seen that it inhibits sperm functions in vitro, although its mechanism of action is still unknown. Study design, size, duration A prospective study was conducted in 102 males, with a mean age of 38.0 ± 5.7, attended successively for initial evaluation, in the Human Reproduction Unit of the Hospital Universitario de Canarias, between february and april 2018, who underwent a semen analysis and metal detection and, subsequently, an IVF/ICSI treatment during years 2019 and 2020 (n = 92). The relationship between the presence of metals and the results of ART has been established. Participants/materials, setting, methods We included two groups based on semen parameters: 41 patients with pathological spermiograms (40.2%), while the remaining 61 (59.8%) had a normal semen analysis and constituted the control group.The study of seminal parameters was performed according to the WHO guidelines. The metals analysis was carried out in the Toxicology Area of the Universidad de La Laguna, using the digestion for microwave method. Metal measurement was performed using inductively coupled plasma optical emission spectrometry (ICP-OES). Main results and the role of chance In our study we have observed 79.4% of patients have V in semen. Significant differences have been found in the concentration of V in semen (t100=1.988, p = 0.05), is higher in patients who drink alcohol (0.51± 0.40 mg/Kg) than in abstinent patients (0.35± 0.30 mg/Kg). The group with FR above 75% presented lower V values compared to those with rates below 75% (p = 0.039). Within this last group, 33.3% present V values higher than 0.7 mg / kg compared to 15.8% who present it in the group with FR greater than 75% (OR = 2.67 CI95% 1.01, 7.52; p = 0.048). A statistical relationship was found between CR and Pb and V. Those who did not reach 100% CR presented higher Pb values (p = 0.052). Of them, 63.6% presented Pb compared to 38.5% in the group reaching 100% division. This same relationship was observed for V, with higher values in the group that did not reach 100% (p = 0.032), and V being present in 90.9% of the samples compared to 79.5% in the group reaching 100%. Limitations, reasons for caution The limitation of this study was the volume of semen that could be obtained for the metal detection, only 0.5 ml. This was because the semen sample was used at the same time to make a diagnosis of infertility though a spermiogram Wider implications of the findings The determination of metals in semen opens a new field in the study of infertility, and many cases of unknown infertility could due to metal presence or absence in seminal fluid, with the option of performing several treatments to correct these possible anomalies. Trial registration number not applicable

The implementation of high-resolution genome-wide methods, usually next-generation sequencing-based, in preimplantation genetic testing (PGT), has led to the frequent detection of embryos with chromosomal mosaicism (whole chromosome and/or segmental aberrations). Despite a growing series of papers showing the birth of healthy babies following the transfer of embryos indicating mosaicism on PGT-A analysis - albeit with lower implantation rates and higher miscarriage rates in comparison with euploid embryo transfer - many questions remain, making it difficult to decide on how to handle chromosomally mosaic embryos in the clinic. A dedicated ESHRE working group developed good practice recommendations on how to manage chromosomal mosaicism in clinical practice. The recommendations were formulated based on the expert opinion of the working group while taking into consideration the published data and outcomes of a survey on current practices in 239 PGT laboratories and ART clinics, mostly within Europe, Asia and America. The recommendations with regards to detection and management of chromosomal mosaicism were developed following the manual for development of ESHRE good practice recommendations with a stakeholder review of the paper on the ESHRE website. In addition to the recommendations, the working group identified missing information and scientific questions, which should guide further research in PGT, with relevance to the occurrence, detection and impact of chromosomal mosaicism. Trial registration number

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: “In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient’s clinical course.” Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists—radiation oncologists (RO), medical physicists (MP), and related staff —involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process.