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OBJECTIVE: To compare the effects of electrical dry needling with a non-invasive multi-component intervention in patients with chronic low back pain. DESIGN: A randomised single-blind clinical trial. SETTING: Outpatient Physiotherapy Clinic; home. PARTICIPANTS: Sixty-four patients with chronic low back pain aged 30-65 years. INTERVENTIONS: Six-week electrical dry needling on myofascial trigger points, and a non-invasive multicomponent intervention (home exercise programme, stretching and ischemic compression). MAIN MEASURES: Pain (Visual Analogue Scale), disability (Roland-Morris Disability Questionnaire and Oswestry Disability Index), kinesiophobia (Tampa Scale of Kinesiophobia), quality of life and sleep (Short Form 36-item Health Survey and Pittsburgh Sleep Quality Index), isometric endurance of trunk flexor muscles (McQuade test), lumbar mobility in flexion (finger-to-floor distance), and pressure pain threshold (algometer) were assessed at baseline, after 6 weeks, and after 2 months. RESULTS: ANOVA showed statistically significant differences in group-by-time interaction for most pain pressure thresholds of myofascial trigger points (P < 0.05), for disability (Roland-Morris Disability Questionnaire: F = 6.14, P = 0.016; and Oswestry Disability Index: F = 7.36, P = 0.009), for trunk anteflexion (F = 10.03, P = 0.002) and for habitual sleep efficacy (F = 6.65, P = 0.012), use of hypnotics (F = 4.77, P = 0.033) and total score of quality of sleep (F = 8.23, P = 0.006). CONCLUSIONS: In comparison to a non-invasive multicomponent intervention, electrical dry needling has more positive effects on disability, pain intensity, kinesiophobia, and reducing patients' sensitivity to myofascial trigger points pressure, at post-treatment and at 2 months. CLINICAL TRIAL REGISTRATION NUMBER: NCT04804228. Registered on May 28th, 2021. Available at https://clinicaltrials.gov/ct2/show/NCT04804228.
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Dolor de la Región Lumbar , Puntos Disparadores , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Inducción Percutánea del Colágeno , Calidad de Vida , Método Simple Ciego , Adulto , Persona de Mediana Edad , AncianoRESUMEN
Capacitation involves tyrosine phosphorylation (TP) as a key marker. Lifestyle-related factors, such as obesity and smoking, are recognized for their adverse effects on semen quality and male fertility, yet the underlying mechanisms, including their potential impact on TP, remain unclear. Moreover, the effect of sperm cryopreservation on TP at the human sperm population level is unexplored. Flow cytometry analysis of global TP was performed on pre-capacitated, post-capacitated and 1- and 3-hours' incubated fresh and frozen-thawed samples from sperm donors (n = 40). Neither being overweight nor smoking (or both) significantly affected the percentage of sperm showing TP. However, elevated BMI and smoking intensity correlated with heightened basal TP levels (r = 0.226, p = 0.003) and heightened increase in TP after 3 h of incubation (r = 0.185, p = 0.017), respectively. Cryopreservation resulted in increased global TP levels after capacitation but not immediately after thawing. Nonetheless, most donors' thawed samples showed increased TP levels before and after capacitation as well as after incubation. Additionally, phosphorylation patterns in fresh and frozen-thawed samples were similar, indicating consistent sample response to capacitation stimuli despite differences in TP levels. Overall, this study sheds light on the potential impacts of lifestyle factors and cryopreservation on the dynamics of global TP levels during capacitation.
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Índice de Masa Corporal , Criopreservación , Capacitación Espermática , Espermatozoides , Tirosina , Humanos , Criopreservación/métodos , Masculino , Fosforilación , Tirosina/metabolismo , Espermatozoides/metabolismo , Adulto , Fumar Cigarrillos/efectos adversos , Preservación de Semen/métodos , Análisis de SemenRESUMEN
The ultimate goal of a preimplantation genetic testing and human leukocyte antigen (PGT-HLA) matching programme is the birth of a healthy, HLA-compatible child for the treatment or cure of a sick sibling. Several authors have published successful cases of the births of children HLA-matched to siblings affected by different conditions and diseases. However, there are many reports of failed attempts. Couples seeking an HLA-matched sibling for their affected child look for positive outcomes in the shortest possible time. Nevertheless, there is no published consensus or guidelines with recommendations for these cases. Here, the authors aimed to analyse different approaches for these programmes, highlighting the most promising strategies for the families and fertility units. Furthermore, the authors mention a successful case of a PGT-HLA matching programme after a previous failed attempt following the strategies proposed. Which is the most cost-effective and time-efficient approach in a PGT-HLA matching programme?
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Diagnóstico Preimplantación , Hermanos , Embarazo , Femenino , Niño , Humanos , Fertilización In Vitro , Pruebas Genéticas , Antígenos HLA/genética , Aneuploidia , BlastocistoRESUMEN
STUDY QUESTION: Does addition of choriogonadotropin beta (recombinant CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? SUMMARY ANSWER: At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and related down-stream parameters including the number of oocytes and blastocysts. WHAT IS KNOWN ALREADY: CG beta is a novel recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6®) and has a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the AUC and the peak serum concentration (Cmax) increased approximately dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than CHO cell-derived rhCG. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial (RAINBOW) was conducted in five European countries to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol. Randomization was stratified by centre and age (30-37 and 38-42 years). The primary endpoint was the number of good-quality blastocysts (Grade 3 BB or higher). Subjects were randomized to receive either placebo or 1, 2, 4, 8 or 12 µg CG beta added to the daily individualized follitropin delta dose during ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 620 women (30-42 years) with anti-Müllerian hormone (AMH) levels between 5 and 35 pmol/l were randomized in equal proportions to the six treatment groups and 619 subjects started treatment. All 619 subjects were treated with an individualized dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering with rhCG was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached. MAIN RESULTS AND THE ROLE OF CHANCE: The demographic characteristics were comparable between the six treatment groups and the overall mean age, body weight and AMH were 35.6 ± 3.3 years, 65.3 ± 10.7 kg and 15.3 ± 7.0 pmol/l, respectively. The incidence of cycle cancellation (range 0-2.9%), total follitropin delta dose (mean 112 µg) and duration of stimulation (mean 10 days) were similar across the groups. At stimulation Day 6, the number and size of follicles was similar between the treatment groups, whereas at the end-of-stimulation dose-related decrease of the intermediate follicles between 12 and 17 mm was observed in comparison to the placebo group. In contrast, the number of follicles ≥17 mm was similar between the CG beta dose groups and the placebo group. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of good-quality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 µg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was 43% per started cycle versus 28-39% in CG beta groups and 49% per transfer versus 38-50% in the CG beta groups. There was no apparent effect of CG beta on the incidence of adverse events, which was 48.1% in the placebo group and 39.6-52.3% in the CG beta dose groups. In line with the number of collected oocytes, the overall ovarian hyperstimulation syndrome incidence remained lower following follitropin delta with CG beta (2.0-10.3%) compared with follitropin delta only treatment (11.5%). Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. LIMITATIONS, REASONS FOR CAUTION: The effect of the unique glycosylation of CG beta and its associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate optimal doses of CG beta for this and/or different indications. WIDER IMPLICATIONS OF THE FINDINGS: The high ongoing pregnancy rate in the follitropin delta group supports the use of individualized follitropin delta dosing in a long GnRH agonist protocol. The addition of CG beta reduced the presence of intermediate follicles with the investigated doses and negatively affected all down-stream parameters. Further clinical research will be needed to assess the optimal dose of CG beta in the optimal ratio to follitropin delta to develop this novel combination product containing both FSH and LH activity for ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Ferring Pharmaceuticals, Copenhagen, Denmark. B.M. and P.L. are employees of Ferring Pharmaceuticals. M.F.S., H.V., C.Y.A., M.F., C.B., A.P. and Y.K. have received institutional clinical trial fees from Ferring Pharmaceuticals. C.B. has received payments for lectures from Organon, Ferring Pharmaceuticals, Merck A/S and Abbott. M.F.S. has received payment for lectures from Ferring Pharmaceuticals. Y.K. has received payment for lectures from Merck and travel support from Gedeon Richter. H.V. has received consulting fees from Oxo and Obseva and travel support from Gedeon Richter, Ferring Pharmaceuticals and Merck. C.Y.A. has received payment for lectures from IBSA, Switzerland. M.F and C.Y.A. were reimbursed as members of the Data Monitoring Board in this trial. M.F. has an issued patent about unitary combination of FSH and hCG (EP1633389). TRIAL REGISTRATION NUMBER: 2017-003810-13 (EudraCT Number). TRIAL REGISTRATION DATE: 21 May 2018. DATE OF FIRST PATIENT'S ENROLMENT: 13 June 2018.
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Hormona Folículo Estimulante Humana , Inducción de la Ovulación , Animales , Hormona Antimülleriana , Peso Corporal , Células CHO , Gonadotropina Coriónica , Gonadotropina Coriónica Humana de Subunidad beta , Cricetinae , Cricetulus , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina , Humanos , Inducción de la Ovulación/métodos , Preparaciones Farmacéuticas , Embarazo , Índice de Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas RecombinantesRESUMEN
Current evidence suggests that the hysterosalpingo-foam sonography test (HyFoSy) has emerged as a new option to make Fallopian tube assessment easier. Several published studies have compared the different types of tubal patency test available with the accepted gold standard, laparoscopy and dye, endorsing the advantages of HyFoSy over the other techniques. However, the authors wonder why professionals nowadays do not indicate HyFoSy as a first-choice diagnostic tool, with X-ray hysterosalpingography as still the most recommended procedure in outpatients. The aim of this article is to highlight the latest updates on this topic in order to raise awareness of the benefits of hysterosalpingo-contrast sonography as well as provide some tips for performing HyFoSy to obtain the maximum information in a single consultation.
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Infertilidad Femenina , Laparoscopía , Femenino , Humanos , Histerosalpingografía/métodos , Pruebas de Obstrucción de las Trompas Uterinas/métodos , Trompas Uterinas/diagnóstico por imagen , Ultrasonografía/métodos , Infertilidad Femenina/diagnóstico por imagenRESUMEN
PURPOSE: To assess the exercise intervention focused on high-intensity interval training (HIIT) in lung cancer survivors. DESIGN: We performed a literature search using PubMed, Web of Science, and Science Direct (last search March 2021). Quality assessment and risk of bias were assessed using the Downs and Black scale and the Cochrane tool. PARTICIPANTS: A total of 305 patients of 8 studies were assessed, with their mean age ranging from 61 ± 6.3 to 66 ± 10 years in the exercise group and from 58.5 ± 8.2 to 68 ± 9 years in the control group. METHODS: A systematic review and meta-analysis of randomized controlled trials and pilot randomized controlled trials was performed. We included controlled trials testing the effect of HIIT in lung cancer survivors versus the usual care provided to these patients. The data were pooled and a meta-analysis was completed for cardiorespiratory fitness (VO2peak). RESULTS: We selected 8 studies, which included 305 patients with lung cancer: 6 studies were performed around surgical moment, one study during radiotherapy's treatment, and other during target therapy. After pooling the data, exercise capacity was included in the analysis. Results showed significant differences in favour to HIIT when compared to usual care in cardiorespiratory fitness (standard mean difference = 2.62; 95% confidence interval = 1.55, 3.68; p < 0.00001). CONCLUSIONS AND IMPLICATIONS: The findings indicated a beneficial effect of HIIT for improving cardiorespiratory fitness in lung cancer patients in early stages around oncological treatment moment. Nevertheless, this review has several limitations, the total number of studies was low, and the stage and subtype of lung cancer patients were heterogeneous that means that the conclusions of this review should be taken with caution. Review registration: PROSPERO Identifier: CRD42021231229.
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Supervivientes de Cáncer , Capacidad Cardiovascular , Entrenamiento de Intervalos de Alta Intensidad , Neoplasias Pulmonares , Anciano , Entrenamiento de Intervalos de Alta Intensidad/métodos , Humanos , Pulmón , Neoplasias Pulmonares/terapia , Persona de Mediana EdadRESUMEN
OBJECTIVES: The aim of this study was to analyze whether differences in the coracohumeral distance (CHD) exist between the symptomatic and the asymptomatic shoulder in patients with subacromial pain syndrome and compare with the shoulder of control participants. METHODS: This was a cross-sectional, observational study. A sample comprising 62 participants with subacromial pain syndrome was recruited from 3 different primary care centers. The CHD was determined from standardized ultrasonography measures performed on both shoulders at 0° and 60° of shoulder abduction, whereas the dominant arm was measured for the control participants. RESULTS: Statistically significant differences in CHD at 0° and 60° were found between the symptomatic and control shoulders (P = .011/P = .002) and between the contralateral asymptomatic shoulder and controls (P = .026/P = .007). CONCLUSION: We found differences in CHD at 0° and 60° of shoulder elevation between both the affected and the nonaffected shoulders when compared with healthy shoulders. These results suggest that CHD may be a contributing factor in chronic shoulder pain.
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Síndrome de Abducción Dolorosa del Hombro , Articulación del Hombro , Humanos , Estudios Transversales , Dolor de Hombro/diagnóstico por imagen , Voluntarios Sanos , Movimiento , Articulación del Hombro/diagnóstico por imagenRESUMEN
INTRODUCTION AND HYPOTHESIS: This study aimed to evaluate the efficacy and safety of ring pessaries under continuous use for > 2 years. Our starting hypothesis was that their use without periodic removal, cleaning or replacement for between 24 to 48 months after insertion is safe and effective. METHODS: This was a prospective observational and descriptive study. One hundred one women who successfully completed the 24 first months of continuous use of a ring pessary were included and monitored for another 24 months. The objectives were to establish the percentage of patients maintaining its use 48 months after insertion, the reasons for discontinuation and the adverse events. Another purpose of this study was to determine the timing of replacement of the vaginal pessary in long-term users. RESULTS: Of the women, 92.1% (93/101) had successful pessary use, and it was discontinued by three patients (2.9%, 3/101); 76.2% (77/101) of the women continued pessary use after the end of the study, and in 16 (15.8%, 16/101) patients, after pessary removal, the prolapse disappeared and did not recur. Forty-five women (48.4%, 45/93) presented some adverse events that required temporary pessary removal. The most common one was an increase in vaginal discharge (73.3%, 33/45). In four women (8.9%, 4/45), the ring pessary was detected embedded in the vaginal epithelium. CONCLUSIONS: Continuous use of a ring pessary can be recommended for 2 years in hysterectomized women and for 4 years in non-hysterectomized women if there are no complications.
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Prolapso de Órgano Pélvico , Pesarios , Femenino , Humanos , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION AND HYPOTHESIS: The study was aimed at evaluating the safety and efficacy of ring pessaries without support under continuous use without periodic removal or replacement for the treatment of advanced pelvic organ prolapse (POP) in women for 2 consecutive years. METHODS: This study was a prospective observational study. A total of 123 women were recruited in a tertiary hospital from January 2013 to January 2016. The primary objective was the percentage of patients maintaining the use of the pessary after 24 months. The secondary objectives were the reasons for discontinuation and the adverse events in patients with successful fittings. RESULTS: A total of 115 patients (93.5%) had a successful fitting. Four patients died of non-pessary-related causes during the study and, one patient dropped out the follow-up so that finally, 110 patients were included in the efficacy analysis. Pessary use was maintained by 91.8% of the women at the end of the study. The adverse events rate was low (27.0%). The two main factors of interruption in the pessary use were: age (OR 0.93; 95% CI 0.87-0.99) and history of urinary urge incontinence (OR 0.33; 95% CI 0.11-0.96]). CONCLUSIONS: A high success rate and low adverse events rate were achieved in patients with advanced-stage POP with continuous pessary use for 24 months, indicating that a ring pessary could also be used without periodic removal for at least the first 2 years. This practice could reduce the number of control visits.
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Prolapso de Órgano Pélvico , Pesarios , Femenino , Humanos , Prolapso de Órgano Pélvico/terapia , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the effectiveness of supervised physical therapy program versus non-supervised on pain, functionality, fear of movement and quality of life in patients with non-specific chronic low back pain. DESIGN: A randomized double-blind clinical trial. SETTING: Clinical outpatient unit; home. SUBJECTS: A total of 64 participants with non-specific chronic low back pain were randomized into either supervised exercise group (n = 32) or non-supervised home exercise group (n = 32). INTERVENTIONS: The supervised group was treated with therapy exercises (strengthen lumbopelvic musculature), while the non-supervised received an informative session of the exercises, which were performed un-supervised at home. Both groups received three weekly sessions for eight weeks. MAIN MEASURES: Pain, disability, fear of movement, quality of life, trunk muscle endurance and trunk anteflexion motion were assessed at baseline, two, and six months of follow-up. RESULTS: Although analysis of variance (ANOVA) test showed statistically significant differences between groups for pain (P = 0.028; supervised: 2.5 ± 2.1; non-supervised: 3.5 ± 1.5) and disability for Roland-Morris Disability Questionnaire (P = 0.004; supervised: 3.1 ± 2.2; non-supervised: 5.1 ± 3.0) and for Oswestry Disability Index (P = 0.034; supervised: 14.5 ± 7.1; non-supervised: 19.2 ± 10.0) at 8 weeks immediately posttreatment, there were no differences between the groups in patient-rated pain, functionality, fear of movement and quality of life at six months of follow-up. CONCLUSION: Patients with chronic low back pain who received supervised exercise showed more improvement in both the short and long term in all patient-rated outcomes over the non-supervised group, but the differences were small and not clinically significant.
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Terapia por Ejercicio/métodos , Dolor de la Región Lumbar/rehabilitación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Músculo Esquelético , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVE: Our aim was to analyze whether shoulder pain is related to scapular upward rotation (SUR) or to the lengths of the pectoralis minor and levator scapulae muscles. METHODS: This cross-sectional, observational study was carried out in 3 primary-care centers; 54 individuals with chronic shoulder pain participated. Scapular upward rotation and the lengths of the pectoralis minor and levator scapulae muscles were assessed. RESULTS: The level of association was small between shoulder pain and function and (1) the lengths of the pectoralis minor (râ¯=â¯0.08, Pâ¯=â¯.93) and levator scapulae (râ¯=â¯-0.01, Pâ¯=â¯.57) muscles and (2) SUR at 45° (râ¯=â¯0.17, Pâ¯=â¯.21), 90° (râ¯=â¯0.08, Pâ¯=â¯.57), and 135° (râ¯=â¯0.10, Pâ¯=â¯0.45) of shoulder elevation. CONCLUSION: The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account.
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Movimiento , Músculos Pectorales/fisiopatología , Escápula/fisiopatología , Articulación del Hombro , Dolor de Hombro/fisiopatología , Hombro , Músculos Superficiales de la Espalda/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Rotación , Hombro/patología , Hombro/fisiopatología , Articulación del Hombro/patología , Articulación del Hombro/fisiopatologíaRESUMEN
RESEARCH QUESTION: Is individualization of dosing with follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? DESIGN: A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18-40 years) randomized and treated with follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. RESULTS: Individualized dosing with follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Müllerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus follitropin alfa. CONCLUSION: An individualized follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
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Hormona Folículo Estimulante Humana/administración & dosificación , Síndrome de Hiperestimulación Ovárica/prevención & control , Inducción de la Ovulación , Adolescente , Adulto , Criopreservación , Interpretación Estadística de Datos , Femenino , Fertilización In Vitro , Hormona Folículo Estimulante Humana/uso terapéutico , Humanos , Ovario/efectos de los fármacos , Inducción de la Ovulación/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Riesgo , Inyecciones de Esperma Intracitoplasmáticas , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN: A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). CONCLUSION: Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages.
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Embrión de Mamíferos/metabolismo , Kisspeptinas/metabolismo , MicroARNs/metabolismo , Placenta/metabolismo , Embarazo Ectópico/diagnóstico , Biomarcadores/metabolismo , Estudios de Casos y Controles , Árboles de Decisión , Regulación hacia Abajo , Diagnóstico Precoz , Femenino , Edad Gestacional , Humanos , Kisspeptinas/genética , Embarazo , Embarazo Ectópico/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
PURPOSE: The neurokinin B (NKB)/NK3 receptor (NK3R) and kisspeptin (KISS1)/kisspeptin receptor (KISS1R), two systems essential for reproduction, are present in human granulosa cells (GCs) of healthy women and contribute to the control of fertility, at least partially, by acting on the gonads. However, little is known about the expression of these systems in GCs of women with polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the expression of NKB/NK3R and KISS1/KISS1R in mural granulosa (MGCs) and cumulus cells (CCs) of PCOS women. METHODS: A cross-sectional study was performed in 46 healthy women and 43 PCOS women undergoing controlled ovarian stimulation. MGCs and CCs were collected from pre-ovulatory follicles after transvaginal ultrasound-guided oocyte retrieval and the expression of the genes encoding NKB (TAC3), NK3R (TACR3), KISS1, and its receptor (KISS1R) was analyzed using real-time quantitative RT-PCR. RESULTS: TAC3, TACR3, and KISS1 mRNA levels were decreased in MGCs and CCs of PCOS women. TAC3 positively correlated with KISS1 in MGCs of healthy women and TACR3 was positively associated with KISS1R in CCs from healthy women. These associations were not observed in PCOS women. CONCLUSION: The NKB/NK3R and KISS1/KISS1R systems are dysregulated in MGCs and CCs of PCOS women. The lower expression of these systems in GCs could contribute to the abnormal follicle development and defective ovulation that characterize the pathogenesis of PCOS.
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Células del Cúmulo/metabolismo , Células de la Granulosa/metabolismo , Kisspeptinas/genética , Neuroquinina B/genética , Síndrome del Ovario Poliquístico/genética , Receptores de Kisspeptina-1/genética , Receptores de Neuroquinina-3/genética , Adulto , Estudios de Casos y Controles , Células Cultivadas , Estudios Transversales , Células del Cúmulo/patología , Femenino , Regulación de la Expresión Génica , Células de la Granulosa/patología , Humanos , Kisspeptinas/metabolismo , Neuroquinina B/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Receptores de Kisspeptina-1/metabolismo , Receptores de Neuroquinina-3/metabolismo , Adulto JovenRESUMEN
Leptin is now considered an important signalling molecule of the reproductive system, as it regulates the production of gonadotrophins, the blastocyst formation and implantation, the normal placentation, as well as the foeto-placental communication. Leptin is a peptide hormone secreted mainly by adipose tissue, and the placenta is the second leptin-producing tissue in humans. Placental leptin is an important cytokine which regulates placental functions in an autocrine or paracrine manner. Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes such as proliferation, protein synthesis, invasion and apoptosis in placental cells. Furthermore, deregulation of leptin levels has been correlated with the pathogenesis of various disorders associated with reproduction and gestation, including polycystic ovary syndrome, recurrent miscarriage, gestational diabetes mellitus, pre-eclampsia and intrauterine growth restriction. Due to the relevant incidence of the mentioned diseases and the importance of leptin, we decided to review the latest information available about leptin action in normal and pathological pregnancies to support the idea of leptin as an important factor and/or predictor of diverse disorders associated with reproduction and pregnancy.
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Leptina/metabolismo , Complicaciones del Embarazo/metabolismo , Tejido Adiposo/metabolismo , Femenino , Humanos , Factores Inmunológicos/metabolismo , Placenta/embriología , Placenta/metabolismo , Embarazo , ReproducciónRESUMEN
The neurokinin B/NK3 receptor (NK3R) and kisspeptin/kisspeptin receptor (KISS1R), two systems which are essential for reproduction, are coexpressed in human mural granulosa (MGC) and cumulus cells (CCs). However, little is known about the presence of other members of the tachykinin family in the human ovary. In the present study, we analyzed the expression of substance P (SP), hemokinin-1 (HK-1), NK1 receptor (NK1R), and NK2 receptor (NK2R) in MGCs and CCs collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. RT-PCR, quantitative RT-PCR, immunocytochemistry, and Western blotting were used to investigate the patterns of expression of tachykinin and tachykinin receptor mRNAs and proteins and the possible interaction between the tachykinin family and kisspeptin. Intracellular free Ca(2+) levels ([Ca(2+)]i) in MGCs after exposure to SP or kisspeptin in the presence of SP were also measured. We found that SP, HK-1, the truncated NK1R isoform NK1R-Tr, and NK2R were all expressed in MGCs and CCs. NK1R-Tr mRNA and NK2R mRNA and protein levels were higher in MGCs than in CCs from the same patients. Treatment of cells with kisspeptin modulated the expression of HK-1, NK3R, and KISS1R mRNAs, whereas treatment with SP regulated kisspeptin mRNA levels and reduced the [Ca(2+)]i response produced by kisspeptin. These data demonstrate that the whole tachykinin system is expressed and acts in coordination with kisspeptin to regulate granulosa cell function in the human ovary.
Asunto(s)
Células del Cúmulo/metabolismo , Células de la Granulosa/metabolismo , Kisspeptinas/metabolismo , Receptores de Taquicininas/metabolismo , Taquicininas/metabolismo , Calcio/metabolismo , Células Cultivadas , Femenino , HumanosRESUMEN
BACKGROUND: The Shoulder Pain and Disability Index (SPADI) is a tool designed to evaluate the impact of shoulder pathology. The aim of this study was to cross culturally adapt a Spanish version of the SPADI for Spanish population with a musculoskeletal shoulder pain, and to determine the psychometric properties of this instrument using confirmatory factor analysis (CFA). METHODS: Cross-cultural adaptation was performed according to the international guidelines. To assess factor structure, a confirmatory factor analysis was done. Internal consistency was measured using Cronbach's alpha. Item-total and inter-item correlations were assessed. Pearson and Spearman correlations were calculated to assess the convergent validity between SPADI and quick-DASH. RESULTS: A new Spanish version of SPADI was achieved. The original SPADI factor structure was tested by CFA, obtaining a poor fit: relative chi-square (χ2/df) 3.16, CFI 0.89, NFI 0.92, and RMSEA 0.10 (90 % CI 0.08 to 0.12). An additional model was tested, after deleting items which have had a poor adjustment in the model (1, 11, and 12), obtaining the best fit: relative chi-square (χ2/df) of 1.94, CFI 0.98, NFI 0.95, GFI 0,95, and RMSEA 0.06 (90 % CI 0.04 to 0.09). The analysis confirmed the bidimensional structure (pain and disability subscales). A correlation Spearman's Rho coefficient of 0.752 (p < 0.0001) and a Cronbach's alpha of 0.90 were obtained. CONCLUSIONS: This study validated a new 10-items version of SPADI for Spanish population with musculoskeletal shoulder pain providing a patient reported outcome measure that could be used in both clinical practice and research.
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Evaluación de la Discapacidad , Dolor Musculoesquelético/diagnóstico , Dolor de Hombro/diagnóstico , Encuestas y Cuestionarios/normas , Adulto , Análisis Factorial , Femenino , Humanos , Masculino , Dimensión del Dolor , Psicometría , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Dolor de Hombro/clasificación , EspañaRESUMEN
OBJECTIVE: To study the association between serum anti-Müllerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5·2-12·1 µg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. DESIGN: Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5·0-14·9 pmol/l; higher stratum: 15·0-44·9 pmol/l). PATIENTS: Infertile women of good prognosis (n = 265). MEASUREMENTS: Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. RESULTS: Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P < 0·001) positive dose responses were observed for the number of follicles ≥ 12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. CONCLUSIONS: Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS.
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Hormona Antimülleriana/sangre , Hormona Folículo Estimulante/uso terapéutico , Adolescente , Adulto , Femenino , Fertilización In Vitro , Hormona Folículo Estimulante/sangre , Humanos , Inducción de la Ovulación/métodos , Embarazo , Adulto JovenRESUMEN
The purpose of this study was to determine which strategy of embryo transfer has a better trade-off in live birth delivery rate versus multiple pregnancy considering patient acceptance: elective single embryo transfer (eSET) or elective double embryo transfer (eDET). In all, 199 women <38 years of age undergoing their first IVF treatment in a private centre were included in a prospective open-label randomised controlled trial. Patients were randomised into four groups: (1) eSET on Day 3; (2) eSET on Day 5; (3) eDET on Day 3; and (4) eDET on Day 5. Per patient, main analysis included acceptance of assigned group, as well as multiple and live birth delivery rates of the fresh cycle. Secondary analysis included the rates of subsequent cryotransfers and the theoretical cumulative success rate. Of 98 patients selected for eSET, 40% refused and preferred eDET. The live birth delivery rate after eDET was significantly higher after eDET versus eSET (65% vs 42%, respectively; odds ratio=1.6, 95% confidence interval 1.1-2.1). No multiple births were observed after eSET, compared with 35% after eDET. Although live birth delivery is higher with eDET, the increased risk of multiple births is avoided with eSET. Nearly half the patients refused eSET even after having been well informed about its benefits.
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Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Aceptación de la Atención de Salud , Transferencia de un Solo Embrión , Adulto , Tasa de Natalidad , Femenino , Humanos , Nacimiento Vivo , Edad Materna , Embarazo , Resultado del Embarazo , Índice de Embarazo , Embarazo Múltiple , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Alterations in the spinal column and obesity are on the rise, causing great concern in health and educational strata. This paper aims to take a step further and study in detail the relationship of the presence of scoliotic hump in obese schoolchildren. OBJECTIVE: was to determine the relationship between prevalence of types of variables hump and sociodemographic, anthropometric, and functional-side dominance. METHODS: The sample consisted of 2,822 schoolchildren in Spain, analyzed in 2010 with an average age of 8.5 years (SD: 1.792). Analyzed for Adams test, BMI, Edinburgh inventory, deep flexion test, and demographic questionnaire, we used the SPSS 20.0 (descriptive and test multivariate binary logistic regression). RESULTS: The number of subjects who had scoliosis was 1,023 (36.3%), obesity occurred in 359 (12.7%) cases, and after regression including associations regarding gender, (adjusted OR: 2.044; 1.731-2.413), age (adjusted OR: 1.121; 1.070-1.174), presence of obesity (adjusted OR: 0.676; 0.518-0.882), and flexibility (adjusted OR: 1.015; 1.001-1.029). CONCLUSIONS: The female participants were twice as likely to have hump. The prevalence with respect to age indicates that any schoolchild with a year of chronological age has 1.12 times higher risk of developing hump and subjects carrying the school supplies backpack have less risk of hump.