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RESEARCH QUESTION : Is the efficacy of imported vitrified oocytes donation affected by the cryobank of origin? DESIGN : Longitudinal cohort study including 249 completed oocyte warming cycles from 200 recipients (January 2016-July 2020). No severe male factor was included. Vitrified oocytes were provided by three Spanish cryobanks. The primary outcome was the cumulative live birth-delivery rate (cLBR) per completed oocyte warming cycle. RESULTS : After warming 1535 oocytes, 1244 survived (81.0%) and 945 fertilized (76.0%) with an embryo utilization rate of 65.3%. The overall cLBR per completed cycle was 47.0%, but it was lower in cryobank 1 (31.2%) in comparison to cryobank 2 (56.0%, p=0.0010) and 3 (50.8%, p=0.0241). The multivariate logistic regression analysis identified the survival of ≥4 oocytes as the strongest predictor for delivery (p=0.0282). Only 202 of the 249 oocyte warming cycles had ≥4 survived oocytes in a proportion that was significantly lower in cryobank 1 versus cryobank 2 (70.1% vs. 89.0%, p=0.0020), whereas the comparison with cryobank 3 (81.0%) was not significant. In the 202 oocyte warming cycles, the cLBR in cryobank 1 (37.0%) was lower in comparison to cryobank 2 (58.8%, p=0.0115) and cryobank 3 (60.8%, p=0.0019) suggesting a reduced viability also in oocytes from cryobank 1 that survived warming. CONCLUSIONS : There are differences in the efficacy of the imported vitrified oocytes in relation to the cryobank of origin. Each center needs to evaluate the results internally when starting a collaboration with an oocyte cryobank to put in place the necessary measures to maximize treatments’ efficacy.

Study question Do RIF patients have the preimplantation genetic testing for aneuploidy (PGT-A) overcome their infertility condition? Summary answer PGT-A positively impact on implantation rate in RIF patients What is known already The most common definition of RIF is failure to achieve a pregnancy after three consecutive transfers of good quality embryos. This term possibly represents a heterogeneous category of infertile couples as the causes of repeated failures can be diverse. Especially intriguing is the case of patients with an age lower than 39 years for which the oocyte quality is expected not to be compromised by the well known age effect on female fertility. The chromosome analysis of the resulting embryos has been proposed as a valid method to improve implantation in the great majority of RIF patients Study design, size, duration This retrospective study included 49 patients with at least three previous consecutive implantation failures, which underwent PGT-A from January 2016 to April 2020. Both partners had a normal karyotype. Only patients with a female age below 39 years were included, who presented with a normal uterine cavity. Couples with a severe male factor were excluded. Single frozen blastocysts were transferred according to chromosomal results Participants/materials, setting, methods Maternal age was 35.5 ± 3.1 years. All blastocysts were vitrified after trophectoderm biopsy. Whole genome amplification and array comparative genomic hybridization were performed on biopsies. Only euploid embryos were transferred. The primary outcome was the live-birth delivery rate after the first transfer Main results and the role of chance Before starting a PGT-A cycle, these patients underwent 213 embryo transfers with 251 embryos replaced. A total of 264 blastocysts were analyzed, 140 of which were aneuploid (53%). Monosomy or trisomy was reported in 67 of the diagnosed samples (67/140, 48%) whereas the remaining 73 carried complex aneuploidies (73/140, 52%). The remaining 124 blastocysts (47%) were diagnosed as euploid. All patients performed an embryo transfer resulting in 28 clinical pregnancies (57%). There were 5 spontaneous abortions and the live-birth delivery rate per patient was 47% Limitations, reasons for caution This study suffers from the weakness related to retrospectivity. In addition, as euploid embryos are still cryopreserved, the delivery rate could change at completion of the cycles Wider implications of the findings: A RIF condition can be attributed, at least in a good proportion of cases, to the generation of high percentages of aneuploid embryos. In this case, the transfer of euploid blastocysts has high chances to classify this category of RIF patients has having an embryonic cause of infertilit. Trial registration number Not applicable

STUDY QUESTION Is de novo segmental aneuploidy (SA) a biological event or an artifact that is erroneously interpreted as partial chromosome imbalance? SUMMARY ANSWER The detection of de novo SA in sequential biopsies of preimplantation embryos supports the biological nature of SA. WHAT IS KNOWN ALREADY Although some SAs are detected in oocytes and in blastocysts, the highest incidence is observed in cleavage-stage embryos. Based on these findings, we can postulate that the majority of cells affected by SAs are eliminated by apoptosis or that affected embryos mainly undergo developmental arrest. STUDY DESIGN, SIZE, DURATION This retrospective study includes 342 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed between January 2014 and December 2018. Chromosome analysis was performed on 331 oocytes, 886 cleavage-stage embryos and 570 blastocysts (n = 1787). From 268 expanded blastocysts, the blastocoelic fluid (BF) was also analyzed (resulting in 2025 samples in total). In cases of SAs involving loss or gain in excess of 15 Mb, embryos were not considered for transfer and sequential biopsies were performed at following stages. This resulted in 66 sets where the initial diagnosis of SAs (4 made in polar bodies, 25 in blastomeres and 37 in trophectoderm (TE) cells) was followed up. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 2082 samples (2025 + 27 whole embryos) were processed by whole genome amplification followed by array comparative genomic hybridization. MAIN RESULTS AND THE ROLE OF CHANCE The incidence of SAs was 6.3% in oocytes, increased to 16.6% in cleavage-stage embryos (P LIMITATIONS, REASONS FOR CAUTION Chromosome analyses were performed on biopsies that might not be representative of the true constitution of the embryo itself due to the occurrence of mosaicism. WIDER IMPLICATIONS OF THE FINDINGS The permanence of SAs throughout the following stages of embryo development in more than half of the analyzed sets suggests for this dataset a very early origin of this type of chromosome imbalance, either at meiosis or at the first mitotic divisions. Since SAs remained in full concordance with the initial diagnosis until the blastocyst stage, a corrective mechanism seems not to be in place. In the remaining cases, it is likely that, as for full chromosome aneuploidy, mosaicism derived from mitotic errors could have occurred. In following cell divisions, euploid cell lines could prevail preserving the embryo chances of implantation. Due to the scarcity of data available, the transfer of embryos with SAs should be strictly followed up to establish possible clinical consequences related to this condition. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained. There are no conflicts of interest.

BackgroundThe success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation.MethodsWe did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078.FindingsBetween Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79–1·25; p=0·96). No hysteroscopy-related adverse events were reported.InterpretationOutpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted.FundingEuropean Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

Objective To investigate blastocysts, defined as euploid and aneuploid by trophectoderm (TE) cell analysis, for the presence of DNA in the blastocoelic fluid (BF) detected by whole-genomic amplification (WGA); and to correlate the presence of DNA in BF with the clinical outcome after the transfer of TE-euploid blastocysts. Design Retrospective study. Setting In vitro fertilization unit. Patient(s) This study included 91 patients performing preimplantation genetic testing for aneuploidy on TE cells from January 2015 to December 2017. In the case of ET, only single blastocyst transfers were performed. Intervention(s) Blastocoelic fluids and TE cells were retrieved from 256 blastocysts before vitrification. All blastocysts were diagnosed by array-comparative genomic hybridization (a-CGH) on TE cells. Amplification and a-CGH of DNA from BFs was performed at a later time after TE biopsy and ET. Main Outcome Measure(s) Whole-genomic amplification of BFs, evaluation of the chromosome condition in BFs and TE cells, and correlation of BF results with the clinical outcome of TE-euploid transferred blastocysts. Result(s) The incidence of amplification after WGA was significantly lower in BFs from TE-euploid blastocysts (n = 32, 45%) when compared with the aneuploid ones (n = 150, 81%), resulting in 182 BFs with successful DNA amplification. When submitted to a-CGH, informative results were obtained from 172 BFs. Comparison of these results with those from the corresponding TE cells gave a ploidy concordance of 93.6% and a mean number of aneuploid events per sample that was higher in BFs than in TE cells (2.0 vs. 1.4, respectively). After the transfer of 53 TE-euploid blastocysts, the clinical pregnancy rate was 77% in the group with BF-failed amplification, and 37% after BF-successful amplification. The same trend was found for the ongoing pregnancy rate (68% vs. 31.5%, respectively). Conclusion(s) The presence of DNA in BFs detected by WGA is correlated with the blastocyst ploidy condition defined by TE cell biopsy and with the implantation potential of TE-euploid blastocysts. These findings could have a clinical implication for the selection of the most viable embryo for transfer because, after submitting BFs to WGA, priority would be given to TE-euploid blastocysts with BF-failed amplification. Similarly, BF-failed amplification could be an additional selection criterion to prioritize embryos for transfer even in conventional IVF cycles with blastocysts that were vitrified after BF aspiration.

Introduction Preimplantation genetic testing for monogenic diseases (PGT-M) is a clinical method developed to prevent the transmission of monogenic inherited disorders to the future offspring. The reproductive risk of carriers of single gene disorders depends on the typology of the disorder, with the probability of affected conceptions ranging from 25% in recessive or X-linked diseases to 50% in dominant diseases. Therefore, the possibility of having embryos suitable for transfer and the consequent chances of ongoing pregnancy are strictly related to the number of embryos available for the genetic analysis. The aim of this study was to evaluate how many embryos need to be analyzed for having one or more genetically transferrable embryos. Material and Methods 86 carriers of genetic disorders performed 99 cycles of genetic analysis between January 2010 and September 2018. They were divided into two groups according to the typology of the disorder transmission. Group 1 included recessive and X-linked diseases (58 patients, 70 cycles of analysis), while with dominant disorders were in Group 2 (28 patients, 29 cycles of analysis). Maternal age was comparable in the two groups. Following blastocyst biopsy, embryos were vitrified to complete the genetic analysis. Results Clinical results were the following. For both groups, the mean number of analyzed embryos to have genetically transferrable embryos are reported in the following table: Conclusions Based on the reported data, we define for each case the minimum number of analyzable embryos needed to have one or more transferrable embryo depending on the typology of genetic disorder. Therefore, we eventually advise patients to undergo further oocyte retrievals for the best clinical outcome.

Introduction. Poor response to ovarian stimulation is still a major problem in IVF. The study presents a new stimulation protocol evaluated in a suppopulation of very difficult young poor ovarian responders.Material and Methods. The study consists in two sections. The first includes data from a randomized controlled study involving forty-three young patients with a poor ovarian response in at least two previous cycles (intended as cycle cancellation or with ≤3 collected oocytes). Patients were randomized in two groups: group A (control) received FSH (400 IU/day), while group B received the new stimulation protocol consisting in a sequential association of 150 IU r-LH for 4 days followed by 400 IU r-FSH/after downregulation with daily GnRh agonist. The second includes data from the overall results in 65 patients treated with the new protocol compared to their previous performance with conventional cycles (historical control).Results. Both in the RCT and in the historical control study, LH pretreatment was able to decrease the cancellation rate, to improve thein vitroperformance, and to significantly increase the live birth rates.Conclusions. LH pretreatment improved oocyte quantity and quality in young repeated poor responders selected in accordance with the Bologna criteria.

La valutazione dei fattori che incidono sullo stress lavoro-correlato: l'accordo tra osservatori di uno strumento osservativo - Most of the research on work-related stress has been focused on self-rated assessment of stressors. The self-reported perceptions may be influenced by workers’ interpretations and the problem is particularly prominent when both psychosocial conditions and health are collected by means of self-report at the same time (common method variance). It is important to adopt instrument based on objective measures (i.e. independent from the assessor). According to this premises, the aim of this work is to show an observational structured checklist for the psychosocial risk factors assessment. In a pilot study 10 workers have been observed by two independent judgers. The data showed a good withingroup interrater reliability between observers.

Background Stress evaluation is a field of strong interest and challenging due to several methodological aspects in the evaluation process. The aim of this study is to propose a study protocol to test a new method (i.e., the Stress Assessment and Research Toolkit) to assess psychosocial risk factors at work. Design This method addresses several methodological issues (e.g., subjective vs. objective, qualitative vs quantitative data) by assessing work-related stressors using different kinds of data: i) organisational archival data (organisational indicators sheet); ii) qualitative data (focus group); iii) worker perception (questionnaire); and iv) observational data (observational checklist) using mixed methods research. In addition, it allows positive and negative aspects of work to be considered conjointly, using an approach that considers at the same time job demands and job resources. Discussion The integration of these sources of data can reduce the theoretical and methodological bias related to stress research in the work setting, allows researchers and professionals to obtain a reliable description of workers’ stress, providing a more articulate vision of psychosocial risks, and allows a large amount of data to be collected. Finally, the implementation of the method ensures in the long term a primary prevention for psychosocial risk management in that it aims to reduce or modify the intensity, frequency or duration of organisational demands.

The aim of this study was to evaluate the clinical impact of preimplantation genetic diagnosis (PGD) for aneuploidy on 193 patients who subsequently achieved 208 clinical pregnancies, in relation to their reproductive history. The 208 clinical pregnancies included in the study resulted from 1029 assisted conception cycles in combination with PGD for aneuploidy in 740 couples with a history of poor reproductive performance. According to the reproductive history of the 193 patients, 61 had previously experienced 112 pregnancies with 105 abortions and seven deliveries, corresponding to 3.6% take-home baby rate and 10.9% implantation rate. During the PGD cycle, preimplantation embryos were analysed for 5-9 chromosomes. The transfer of euploid embryos was performed in 699 cycles (68% of oocyte retrievals), generating 171 term pregnancies with 210 infants born, whereas 34 aborted spontaneously and three were ectopic, giving a take-home baby rate per pregnant patient of 88.6% and an ongoing implantation rate per pregnant patient of 53.2%. According to these data, selection made in preimplantation embryos against chromosomal abnormalities is associated with a significantly higher (P < 0.001) take-home baby rate when compared with the previous reproductive history of the parents.

BACKGROUND: Robbery in workplaces represents a potentially traumatic experience for workers. OBJECTIVES: This article describes the set up and evaluation of a comprehensive psychological intervention designed to help to reduce the adverse consequences of bank robberies. PARTICIPANTS: The study population was selected among the employees of two Italian banks. METHODS: The psychological protocol was designed according to the results of a comprehensive non-systematic review of the scientific literature and it was evaluated at work site. RESULTS: The protocol consists of a "pre-event" formative intervention and "post-event" psychological support. The qualitative data collected allowed us to understand that the reactions after a robbery can differ depending on the phase during which the workers were exposed to the robbery. We noted that the main consequences can be classified in emotional/sentimental reactions, behavioral reactions, physiological reactions and experiences during the event; emotions/feelings following the robbery and psycho/physical state and emotions/feelings in the following days. CONCLUSIONS: In a working environment, the chance to take advantage of a specific protocol for the traumatic event of a bank robbery offers both the company and the workers important tools for well-being, including post-robbery psychological support and classroom instructions.

OBJECTIVE: The present study investigates the role of boredom within the Job Demands-Resources model. Although empirical evidence suggests that the incidence of boredom at work is widespread, the study of job boredom remains neglected today. PARTICIPANTS: Data were collected from 269 mass-retail workers, by means of structured face-to-face interviews. METHODS: Results of multiple mediation analyses partially supported our hypotheses. RESULTS: Boredom mediates the relationship between transformational leadership, low learning opportunities and general dysphoria, while work engagement mediates the relationship between transformational leadership, low learning opportunities and job satisfaction as well as general dysphoria. CONCLUSIONS: Taken together, our results confirm the suitability of conceptualizing boredom within the JD-R model and contribute to the ongoing conceptualization of both the boredom literature and the JD-R literature. © 2013 - IOS Press and the authors. All rights reserved.

Objective. To provide an overview of the spectrum of available for measurement and evaluation of work-related psychosocial factors. Methods. We systematically searched the literature/internet to identify and describe the main available questionnaires and observational instruments for assessment of work-related psychosocial factors (with/without other job stressors). Results. A total of 33 instruments were identified (26 questionnaires, 7 observational), many (11 questionnaires, 5 observational) linked to national institutions/intiatives. Accessibility of relevant information (on the internet or elsewhere) regarding the instruments varied widely. Conclusions. This summary of the range of instruments currently available for evaluation of multiple work stressors at individual, group and/or organizational levels may provide a useful tool for operators and researchers.

Chromosomal analysis of pre-implantation embryos was carried out in patients with a poor prognosis of full term pregnancy, which underwent induction of multiple follicular growth. In all, 1034 embryos generated from 191 stimulated cycles were screened for nine chromosome aneuploidy by using the multicolour fluorescence in situ hybridisation technique. Thirty-five percent of the diagnosed embryos were chromosomally normal, whereas the remaining presented with numerical abnormalities, which made them not suitable for transfer. The results obtained confirmed that the incidence of abnormalities is mostly dependent on age; however, monosomy and trisomy are more frequent in poor responders. Accordingly, the pregnancy rate per started cycle was significantly higher in women with a normal response to gonadotropic stimulation (33% vs. 8%, P

Background The aim of this work was to introduce a new combined method of subjective and objective measures to assess psychosocial risk factors at work and improve workers’ health and well-being. In the literature most of the research on work-related stress focuses on self-report measures and this work represents the first methodology capable of integrating different sources of data. Method An integrated method entitled St.A.R.T. (STress Assessment and Research Toolkit) was used in order to assess psychosocial risk factors and two health outcomes. In particular, a self-report questionnaire combined with an observational structured checklist was administered to 113 workers from an Italian retail company. Results The data showed a correlation between subjective data and the rating data of the observational checklist for the psychosocial risk factors related to work contexts such as customer relationship management and customer queue. Conversely, the factors related to work content (workload and boredom) measured with different methods (subjective vs. objective) showed a discrepancy. Furthermore, subjective measures of psychosocial risk factors were more predictive of workers’ psychological health and exhaustion than rating data. The different objective measures played different roles, however, in terms of their influence on the two health outcomes considered. Conclusions It is important to integrate self-related assessment of stressors with objective measures for a better understanding of workers’ conditions in the workplace. The method presented could be considered a useful methodology for combining the two measures and differentiating the impact of different psychological risk factors related to work content and context on workers’ health.

In a prospective, controlled, randomized study where two different agonists were used, we compared three different long desensitization protocols for induction of multiple follicular growth in medically assisted conception cycles. In protocol A, 30 patients were injected with buserelin twice a day for 15 days prior to ovarian stimulation until human chorionic gonadotrophin (HCG) administration. In protocol B, 30 patients were injected with a single dose of long acting Triptorelin (3.75 mg) 15 days before the ovarian stimulation onset. In protocol C, 30 patients were injected with the long acting Triptorelin 4 weeks before ovarian stimulation followed by daily administration of 0.1 mg of the same agonist until HCG injection. There was no difference in the ovarian response to exogenous gonadotrophin stimulation, except for the presence of premature luteinization in two patients in group B. A significantly higher number of mature oocytes was collected from patients with protocol A; however, the fertilization and cleavage rate demonstrated no significant difference among the three groups of patients. The ongoing pregnancy rate and the implantation rate per treatment cycle were very similar in the three study groups. When the convenience, cost and side-effects for the patient are being considered, protocol B should be selected as the first choice when the agonist is utilized for the purpose of inducing pituitary desensitization before and during ovarian stimulation.

The clinical application of preimplantation genetic diagnosis (PGD) for aneuploidy has confirmed the hypothesis that implantation failure and spontaneous abortions are frequently due to aneuploidy. Following PGD, a higher implantation rate and a lower incidence of spontaneous abortions are obtained in patient categories where aneuploidy is the main cause of reproductive failure: women in advanced reproductive age, patients with an altered karyotype due to translocations or gonosomal mosaicism, and patients with recurrent spontaneous abortions. In these cases, the transfer of euploid embryos overcomes the poor prognosis condition in these couples. As expected, aneuploidy increases proportionally with female age; however, not all the chromosomes studied show this trend, suggesting that segregation errors could occur at different rates for each chromosome in relation to maternal age. Furthermore, the retrospective analysis of the results obtained in patients who repeated at least twice a PGD cycle permitted to estimate their chances of reproducing the same pattern of chromosomal abnormalities and consequently evaluating their possibility of a pregnancy: when no euploid embryos are detected at the first attempt, the chance of on-term pregnancy is below 10%; however, this chance is approximately 30% for couples with at least two euploid embryos in the first cycle.