Intraovarian platelet-rich plasma injection and IVF outcomes in patients with poor ovarian response: a double-blind randomized controlled trial.

STUDY QUESTION: Does platelet-rich plasma (PRP) intraovarian injection increase the number of retrieved oocytes in successive ovarian punctions among patients with poor ovarian reserve (POR)? SUMMARY ANSWER: The injection of PRP increases the number of retrieved oocytes without increasing the quality of developed blastocysts. WHAT IS KNOWN ALREADY: Management of women with reduced ovarian response to stimulation is one of the significant challenges in reproductive medicine. Recently, PRP treatment has been proposed as an adjunct in assisted reproduction technology, with controversial results. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial included 60 patients with POR stratified according to the POSEIDON classification groups 3 and 4. It was conducted to explore the efficacy and safety of intraovarian PRP injection. Patients were proposed to undergo three consecutive ovarian stimulations to accumulate oocytes and were randomized to receive either PRP or placebo during their first oocyte retrieval. Randomization was performed using computer-generated randomization codes. Double blinding was ensured so that neither the participant nor the investigators knew of the treatment allotted. All patients underwent three ovarian stimulations and egg retrieval procedures. ICSI was performed after a third ovarian puncture. The primary endpoint was the number of mature oocytes retrieved after PRP or placebo injection in successive ovarian punctures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty women (30-42 years) fulfilling inclusion criteria were randomized in equal proportions to the treatment or control groups. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline demographic and clinical characteristics [age, BMI, anti-Müllerian hormone (AMH) levels] were comparable between the groups. Regarding the primary endpoint, the cumulative number (mean ± SEM) of retrieved mature oocytes was slightly higher in the treatment group: 10.45 ± 0.41 versus 8.91 ± 0.39 in the control group, respectively (95% CI of the difference 0.42-2.66; P = 0,008). The number of mature oocytes obtained among all patients increased in successive egg retrievals: 2.61 ± 0.33 (mean ± SEM) in punction 1 (P1), 3.85 ± 0.42 in P2, and 4.73 ± 0.44 in P3. However, the increase was higher among patients receiving the assessed PRP treatment. In P2, the number of retrieved mature oocytes was 4.18 ± 0.58 versus 3.27 ± 0.61 in controls (95% CI of the difference: -0.30 to 2.12; P = 0.138) and in P3, 5.27 ± 0.73 versus 4.15 ± 0.45 (95% CI of the difference: 0.12-2.12; P = 0.029). The mean ± SEM number of developed and biopsied blastocysts was 2.43 ± 0.60 in the control group and 1.90 ± 0.32 in the treatment group, respectively (P = 0.449). The mean number of euploid blastocysts was 0.81 ± 0.24 and 0.81 ± 0.25 in the control and treatment groups, respectively (P = 1.000). The percentages of patients with euploid blastocysts were 53.33% (16 out of 30) and 43.33% (13 out of 30) for patients in the control and treatment groups, respectively (Fisher's exact test P = 0.606). The overall pregnancy rate per ITT was 43% (26 out of 60 patients). However, the percentage of clinical pregnancies was higher in the control group (18 out of 30, 60%) than in the treatment group (8 out of 30, 27%) (P = 0.018). There was also a trend toward poorer outcomes in the treatment group when considering full-term pregnancies (P = 0.170). There were no differences between control and treatment groups regarding type of delivery, and sex of newborns. LIMITATIONS, REASONS FOR CAUTION: The mechanism of the potential beneficial effect of PRP injection on the number of retrieved oocytes is unknown. Either delivered platelet factors or a mechanical effect could be implicated. Further studies will be needed to confirm or refute the data presented in this trial and to specify the exact mechanism of action, if any, of PRP preparations. WIDER IMPLICATIONS OF THE FINDINGS: The increasing number of women with a poor response to ovarian stimulation supports the exploration of new areas of research to know the potential benefits of therapies capable of increasing the number of oocytes available for fertilization and improving the quality of developed blastocysts. An increase in the retrieved oocytes in both arms of the trial suggests that, beyond the release of growth factor from platelets, a mechanical effect can play a role. However, neither improvement in euploid blastocyst development nor pregnancy rates have been demonstrated. STUDY FUNDING/COMPETING INTEREST(S): This trial was supported by Basque Government and included in HAZITEK program, framed in the new Euskadi 2030 Science and Technology Plan (PCTI 2030). These aids are co-financed by the European Regional Development Fund (FEDER). The study funders had no role in the study design, implementation, analysis, manuscript preparation, or decision to submit this article for publication. No competing interests are declared by all the authors. TRIAL REGISTRATION NUMBER: Clinical Trial Number EudraCT 2020-000247-32. TRIAL REGISTRATION DATE: 3 November 2020. DATE OF FIRST PATIENT'S ENROLLMENT: 16 January 2021.

Drought conditions, aridity and forest structure control the responses of Iberian holm oak woodlands to extreme droughts: A large-scale remote-sensing exploration in eastern Spain.

Understanding how Mediterranean forests respond to the increasing frequency of extreme droughts and forest densification is crucial for effective land management in the present context of climate change and land abandonment. We study the responses of Iberian holm oak (Quercus ilex L.) woodlands to recent extreme droughts during 2000-2019 along broad gradients of climate aridity and forest structure. To this purpose, we apply large-scale remote-sensing using MODIS EVI as a primary production proxy in 5274 Q. ilex sites distributed within a 100,000 km2 region in eastern Spain. These woodlands were extensively affected by two extreme drought events in 2005 and 2012. Resistance, assessed as the capacity of the ecosystems to maintain primary production during drought, was significantly lower for semi-arid than for sub-humid and dry-transition conditions. Holm oak woodlands located in semi-arid areas of the region showed also poorer resilience to drought, characterized by low capacity to fully recover to their pre-drought production levels. Further, drought intensity and both pre- and post-drought hydric conditions controlled the variations of resistance, recovery and resilience between the two analyzed extreme drought events. Drought effects were particularly negative for dense Q. ilex stands under semi-arid climate conditions, where strong competition for scarce water resources reduced drought resistance. The observed drought vulnerability of semi-arid holm oak woodlands may affect the long-term stability of these dry forests. Adaptive management strategies, such as selective forest thinning, may be useful for improving drought responses in these more vulnerable semi-arid woodlands. Conversely, natural rewilding may more appropriately guide management actions for more humid areas, where densely developed Q. ilex woodlands show in general a high ability to maintain ecosystem primary production during drought.

Association Between the Seed Storage Proteins 2S Albumin and 11S Globulin and Severe Allergic Reaction After Flaxseed Intake.

BACKGROUND: Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about the allergens implicated in hypersensitivity reactions to flaxseed. The present study aimed to identify the allergens involved in IgE-mediated reactions in 5 patients with a clinical history of severe systemic symptoms after flaxseed consumption. METHODS: Proteins that were potential allergens with IgE-binding capacity were purified from flaxseed extract using chromatography and identified via MALDI-TOF mass spectrometry. Immunoassays were performed using the 5 allergic patients' sera tested individually and as a pool. RESULTS: Immunoblotting of the flaxseed extract revealed a low-molecular-mass protein (around 13 kDa) in 4 of the 5 patients, while a protein of approximately 55 kDa was detected in 2 patients. The proteins were identified by mass spectrometry as flaxseed 2S albumin, which is included in the WHO/IUIS allergen nomenclature as Lin u 1, and 11S globulin. Inhibition assays revealed in vitro IgE-mediated cross-reactivity between Lin u 1 and peanut and cashew nut proteins, while IgE-mediated recognition of 11S globulin by patients' sera was partially inhibited by several plant-derived sources. CONCLUSIONS: Seed storage proteins from flaxseed were involved in the development of severe symptoms in the 5 patients studied and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, this is the first time that 11S globulin has been identified as a potential allergen. Taking these data into account should ensure a more accurate diagnosis.

Allergen Profile of London Plane Tree Pollen: Clinical and Molecular Pattern in Central Spain.

BACKGROUND AND OBJECTIVES: Platanus acerifolia (London plane tree) is a deciduous tree of the Platanaceae family. Sensitization to this plant varies with geography. Madrid, located in central Spain, has one of the highest London plane tree pollen concentration levels on the Iberian Peninsula. We evaluated both the clinical characteristics and the molecular sensitization pattern of patients with allergy to London plane tree pollen in the region of Madrid. METHODS: Thirty-eight patients allergic to London plane tree pollen were selected according to their clinical symptoms and positive results in skin prick testing and/or specific IgE determination. Serum was collected, and allergen components were evaluated using immunodetection techniques as well as ImmunoCAP. The IgE-binding proteins detected were identified and characterized using mass spectrometry. RESULTS: Analysis of serum samples from allergic patients revealed 9 IgE-binding bands in London plane tree pollen extract. Among these, the 45-kDa protein, which corresponded to Pla a 2, was detected in 76.3% of patients. However, the 18-kDa (Pla a 1) and 9-kDa (Pla a 3) bands were detected in 44.7% and 23.7% of sera, respectively. These results were confirmed using purified proteins. Characterization of the allergen revealed the 27-kDa protein to be glutathione-S-transferase. CONCLUSIONS: The molecular profile of patients sensitized to London plane tree pollen differs from that reported in studies from other locations. In the population we studied, the prevalence of Pla a 2 was higher than that of Pla a 1 and Pla a 3. In addition, the minor allergen previously referred to as Pla a 4 was characterized as glutathione-S-transferase.

Functioning in adult patients with idiopathic inflammatory myopathy: Exploring the role of environmental factors using focus groups.

OBJECTIVE: Health-related quality of life is impaired in idiopathic inflammatory myopathies. This study aimed to identify the main areas of the health-related quality of life environment domain that are affected in patients with myositis. METHODS: A qualitative study was performed using focus groups and applying the International Classification of Functioning, Disability, and Health. Participants were recruited from a cohort of 323 adult inflammatory myopathy patients consulting at a reference center for idiopathic inflammatory myopathy in Spain, selected by the maximum variation strategy, and placed in focus groups with 5 to 7 patients per group. The number of focus groups required was determined by data saturation. RESULTS: Twenty-five patients distributed in 4 focus groups were interviewed. The verbatim provided 54 categories directly related with environmental factors. Those associated with products or substances for personal consumption (e110), health professionals (e355), health services, systems and policies (e580), products and technology for personal use in daily living (e115), and immediate family (e310) were the ones most frequently reported. CONCLUSION: The results of this study led to identification of several environmental factors that affect the health-related quality of life of patients with myositis. Remedial interventions should be designed to address some of these factors.

Ensayo clínico aleatorizado para evaluar la escala mPADSS en la recuperación y alta domiciliaria tras endoscopia / No disponible

ANTECEDENTES: las guías de práctica clínica vigentes recomiendan el empleo de escalas objetivas como criterio de alta postendoscopia con sedación. OBJETIVO: valorar el tiempo de recuperación, las complicaciones y el grado de satisfacción del paciente empleando la escala mPADSS. MATERIAL Y MÉTODOS: se recogieron datos demográficos y antecedentes médicos. Se midieron constantes vitales, ansiedad y dolor abdominal preendoscopia. Se aleatorizó a los pacientes, que fueron divididos en grupo control, el cual recibió el alta según la práctica habitual, y grupo intervención, al cual se le pasó la escala mPADSS cada diez minutos, hasta alcanzar una puntuación objetivo. RESULTADOS: fueron aleatorizados 118 pacientes (78 colonoscopias, 32 gastroscopias, tres gastro + colonoscopia y 15 colangiopancreatografía retrógrada endoscópica/ultrasonografía endoscópica [CPRE/USE]). Como antecedentes médicos, 36 pacientes presentaron hipertensión arterial (HTA) y 19, diabetes mellitus (DM); 15 tenían medicación anticoagulante/antiagregante y 21, hipnótica/ansiolítica. Se requirió una media de 160 mg de propofol por paciente y se emplearon también flumazenilo y midazolam en 49 pacientes. Se registraron dos episodios de vómitos y tres de desaturación leves, todos ellos en grupo control. Incluimos 60 pacientes en grupo control y 58 en grupo mPADSS, los cuales recibieron el alta en 15 y 10 minutos de media respectivamente (p < 0,005). Se dispone de datos de seguimiento telefónico las 24-48 h de 105 sujetos. Se registraron cuatro reingresos (tres control y uno mPADSS). No hubo diferencias en cuanto a dolor y síntomas postsedación. El grado de satisfacción en cuanto a la atención y al tiempo de estancia fue similar en ambos grupos. CONCLUSIONES: este trabajo muestra la eficiencia, seguridad y satisfacción del paciente ante el empleo de la escala mPADSS, por lo que puede recomendarse su empleo

No disponible

Randomized clinical trial to assess the mPADSS scale in recovery and home discharge after endoscopy.

BACKGROUND: current clinical practice guidelines recommend the use of objective scales as a criterion for post-endoscopy sedation discharge. OBJECTIVE: to assess the recovery time, complications and patient satisfaction level using the mPADSS scale. MATERIAL AND METHODS: demographic data and medical history were collected. Vital signs, anxiety and abdominal pain were measured pre-endoscopy. Patients were randomized into a control group, discharged according to the usual practice, and the intervention group, who underwent the mPADSS scale every ten minutes, until an objective score was reached. RESULTS: one hundred and eighteen patients were randomized (78 colonoscopies, 32 gastroscopies, three gastro + colonoscopies and 15 endoscopic retrograde cholangiopancreatographies/endoscopic ultrasound [ERCP/USE]). With regard to medical history, there were 36 cases of elevated blood pressure and 19 diabetes cases, 15 with anticoagulant/antiplatelet and 21 with hypnotic/anxiolytic medication. An average of 160 mg of propofol was required per patient, with additional flumazenil and midazolam in 49. There were two episodes of vomiting and three of mild desaturation, all of them in the control group. Sixty patients were included in the control group and 58 in the mPADSS group, who were discharged in 15 and 10 minutes on average respectively (p < 0.005); 24-48h telephone call follow-up data were available for 105 subjects. There were four readmissions (three control and one mPADSS). There were no differences in pain and post-sedation symptoms and the level of satisfaction in terms of attention and duration of stay was similar in both groups. CONCLUSIONS: this study shows the efficiency, safety and patient satisfaction using the mPADSS scale. Thus, its use is recommend.

Prevalence of dental and mandibular disorders in culled sheep in Spain.

At the slaughterhouse, 1465 culled sheep heads were studied in order to identify disorders of the mandibular cheek teeth. Of these, 227 (15.5%) had evidence of osteomyelitis. The lesional profile showed that the mandible was affected in a similar proportion on both sides (46.7% on the right side vs 50.7% on the left side), mainly in the middle region (55.3%) and with most of the lesions closed without fistulisation (89.4%). In addition, swelling was palpable, with an increase in thickness in the area of the affected body (2.65 ± 0.065 cm vs 1.74 ± 0.030 cm). In 78.6% of the animals, the regional lymph nodes were enlarged. Concerning the mandibular cheek teeth, more than half of the animals lacked at least one tooth (57.0%), with the first premolar being the most frequently missing tooth (34.8%) and the third molar the least (8.2%). The impaction of food around the teeth was very common with the posterior molars being more frequently affected. In the knowledge of the authors, this is the first study that analyses the prevalence of mandibular molar and premolar disorders in sheep, and these are revealed as an important condition affecting culled sheep.

Contributions of throughfall, forest and soil characteristics to near-surface soil water-content variability at the plot scale in a mountainous Mediterranean area.

Soil water-content (SWC) variability in forest ecosystems is affected by complex interactions between climate, topography, forest structure and soil factors. However, detailed studies taking into account the combined effects of these factors are scarce. This study's main aims were to examine the control that throughfall exerts on local spatial variation of near-surface soil water-content and to combine this information with forest structure and soil characteristics, in order to analyze all their effects together. Two stands located in the Vallcebre Research Catchments (NE Spain) were studied: one dominated by Quercus pubescens and the other by Pinus sylvestris. Throughfall and the related shallow SWC were monitored in each plot in 20 selected locations. The main characteristics of the nearest tree and soil parameters were also measured. The results indicated that mean SWC increment at the rainfall event scale showed a strong linear relationship with mean throughfall amount in both forest plots. The % of locations with SWC increments increased in a similar way to throughfall amount in both forest plots. The analyses considering all the effects together indicated again that throughfall had a significant positive effect in both forest plots, while soil litter depth showed a significant negative effect for the oak plot but lower statistical significance for the pine plot, showing a comparable -although more erratic- influence of the organic forest floor for this plot. These results, together with lower responses of SWC to throughfall than expected in rainfall events characterized by low preceding soil water-condition and high rainfall intensity, suggest that litter layer is playing an important role in controlling the soil water-content dynamics. The biometric characteristics of the nearest trees showed significant but very weak relationships with soil water-content increment, suggesting that stemflow and throughfall may act at lower distances from tree trunk than those presented in our study.