Personalized embryo transfer guided by endometrial receptivity analysis: a systematic review with meta-analysis.

STUDY QUESTION: Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures? SUMMARY ANSWER: The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit. WHAT IS KNOWN ALREADY: Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE). MAIN RESULTS AND THE ROLE OF CHANCE: We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42-4.40). LIMITATIONS, REASONS FOR CAUTION: We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies. WIDER IMPLICATIONS OF THE FINDINGS: In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. There are no conflicts of interest to declare. REGISTRATION NUMBER: PROSPERO CRD42022299827.

A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Recuento de folículos antrales como predictor de la respuesta ovárica / Antral follicle counts as a predictor of ovarian response

Objetivo: Evaluar la relación entre el número de folículos antrales en condiciones basales y la cantidad de ovocitos recuperados luego del tratamiento de estimulación ovárica, y establecer el rol del recuento de folículos antrales mediante ecografía como predictor de la respuesta ovárica. Como propósito secundario, se examinó la correlación del recuento de folículos antrales con la edad de las pacientes y el éxito del tratamiento. Materiales y métodos: Entre enero y marzo de 2015 se estudió retrospectivamente a 40 candidatas a punción aspiración folicular, que se habían realizado una ecografía transvaginal con recuento de folículos antrales antes de la estimulación. Se tomaron en cuenta solo los folículos que medían entre 3 y 8 mm. Todas las pacientes recibieron estimulación hormonal y monitoreo ecográfico y hormonal en sangre hasta la punción aspiración de folículos. Resultados: Se observó una importante correlación inversa entre la edad de las pacientes y el recuento de los folículos antrales y una correlación inversa muy marcada entre la edad y la recuperación de ovocitos. También se constató una muy importante correlación positiva entre el recuento de folículos antrales y la cantidad de ovocitos recuperados en la aspiración transvaginal. El número reducido de pacientes limitó el análisis del éxito del tratamiento. Conclusión: El recuento de folículos antrales permite predecir la respuesta ovárica y la cantidad de ovocitos recuperados mediante punción folicular. Debido a su bajo costo, alto rendimiento diagnóstico y fácil acceso y realización, el recuento ovárico folicular mediante ecografía debería ser considerado la prueba de reserva ovárica de primera elección

Objective:To evalúate the relationship between the number of antral follicles under basal conditions and the number of oocytes retrieved after ovarían stimulation treatment, to establish the role of antral count follicles by ultrasonography as a predictor of ovarían response. Secondary objective: to assess the correlation of antral follicle count with the age of patients and the success of treatment. Materials and methods: This is a retrospective cohort study, between January and March 2015, assessing 40 women undergoing transvaginal ultrasonography guided follicular aspiration. Trans-vaginal ultrasonography follicle count was performed prior to antral follicles stimulation, (follicles measuring between 3 and 8 mm were taken into account), they also received hormonal stimulation, ultrasonography and hormonal monitoring blood until the follicle aspiration. Results: A strong inverse correlation between patient age and antral follicle count and a very strong inverse correlation between age and oocyte retrieval was observed. A very strong positive correlation between the antral follicle count and the number of oocytes retrieved in the transvaginal aspiration was also observed. The small number of patients limited the analysis linked to the success of treatment. Conclusion: The antral follicle count had significant associations with ovarían response and the number of oocytes retrieved. The antral follicles count by ultrasonography should be considerad the first choice of test of ovarían reserve because of its low cost, good performance and accessibility

Evaluation of emerging biomarkers in cardiovascular risk stratification of hypertensive patients: a 2-year study.

OBJECTIVE: To evaluate if there is a correlation between some new emerging biomarkers, such as lipoprotein(a) (Lp[a]), apo(a) isoform phenotyping, soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L), serum myeloperoxidase (MPO), and cardiovascular risk stratification. RESEARCH DESIGN AND METHODS: Three hundred patients were enrolled in this open-label, case-control design trial: 156 hypertensive patients and 144 healthy subjects as control group. Hypertensive patients were treated according to the latest ESH/ESC guidelines, until the desirable goal of systolic blood pressure (SBP)<140 mmHg, and diastolic blood pressure (DBP)<90 mmHg was reached. We evaluated at baseline and after 6, 12, 18, and 24 months: SBP, DBP, lipid profile, Lp(a), apo(a) isoform phenotyping, sRAGE, sCD40L, and MPO. RESULTS: Hypertensive patients presented higher levels of blood pressure, Lp(a), sCD40L, and MPO and lower levels of sRAGE compared with controls. We observed a decrease of blood pressure, Lp(a), sCD40L, and MPO and an increase of sRAGE after anti-hypertensive treatment. Moreover we observed moderate, but statistically significant, correlations between blood pressure decrease and Lp(a), MPO, and sCD40L decrease and between blood pressure decrease and sRAGE increase. There was also a modest, positive correlation between low molecular weight apo(a) isoforms and hypertension. A limitation of this study is that we cannot exclude a role for lifestyle measures. Furthermore the studied markers seem to improve with blood pressure lowering treatment, but we do not have enough statistical power to definitely state which drug used has a specific action on the various variables measured. CONCLUSION: Lp(a), sRAGE, MPO, sCD40L, and low molecular weight apo(a) isoforms are associated with hypertension and may represent an increased cardiovascular risk. Longer studies are needed to see if these parameters can be also used to predict specific complications linked to hypertension.

Terapias emergentes en artritis reumatoide / Emergent therapies for rheumatoid arthritis

The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h study.

The influence of acute sleep deprivation during the first part of the night on 24-h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to moderate hypertensive patients. According to a crossover design, they were randomized to have either sleep deprivation or a full night's sleep 1 week apart, during which they were monitored with ABPM. Urine samples for analysis of nocturnal urinary excretion of norepinephrine were collected. During the sleep-deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were higher in comparison with those recorded during the routine workday, the difference being more pronounced during the nighttime (P < .01). Urinary excretion of norepinephrine showed a significant increase at night during sleep deprivation (P < .05). Blood pressure and heart rate significantly increased in the morning after a sleep-insufficient night (P < .05). These data suggest that lack of sleep in hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased blood pressure and heart rate. This situation might represent an increased risk for both target organ damage and acute cardiovascular diseases.

Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.

[Atrioventricular node catheter ablation with condenser discharge and radiofrequency]. / Ablación del nódulo atrioventricular con descarga de condensadores y radiofrecuencia.

The AV junction ablation was useful to treat patients with drug-refractory supraventricular arrhythmias. The purpose of this study was to determine short and long-term success and complications of the atrioventricular nodal catheter ablation and to compare direct current and radiofrequency energy. Forty patients underwent AV nodal ablation with direct current energy (Group I) and forty patients with radiofrequency (Group II). They were followed up for a mean of 76 +/- 49 and 28 +/- 20 months, respectively. Persistent complete AV block was successfully induced during the first ablation session in 45% of 40 patients who underwent DC energy, while in 50% it was modulated. All patients in the radiofrequency group had complete AV block. The rate of recurrence of AV conduction was 7.5% and 2.5% respectively. Immediate complications did not occur after either procedure. One patient died suddenly in each group during follow-up. AV nodal ablation with radiofrequency energy appears to be as efficacious and safe as direct current energy.

Pulmonary artery catheterization in exacerbations of COPD requiring mechanical ventilation: a cost-effectiveness analysis.

UNLABELLED: The cost-effectiveness of pulmonary artery catheterization (PAC) has been questioned in many clinical situations. We sought to assess the cost-effectiveness of PAC in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. METHODS: We constructed a decision analysis model and calculated the incremental cost/quality-adjusted life-year (QALY) saved for hypothetical patients, comparing a PAC strategy to one of no PAC. Sensitivity analyses were performed to test the stability of conclusions over wide ranges of values. RESULTS: The incremental cost/QALY saved in the cost-effectiveness analysis using baseline data is $77,407 when catheterization-driven therapeutic changes result in a 5% improvement in survival. Cost-effectiveness is sensitive to variations in post-hospital life expectancy, quality of life, and the probability of favorable therapeutic changes resulting from the use of catheterization data. CONCLUSIONS: Pulmonary artery catheterization in COPD exacerbation requiring mechanical ventilation is expensive compared to accepted medical interventions for other conditions, unless changes in therapy prompted by catheterization increase hospital survival to a level 8.7% above baseline. Randomized, controlled trials are needed to investigate the economic impact of PAC and its effect on morbidity and mortality of critically ill patients.

Adult respiratory distress syndrome as a complication of postanginal sepsis.

Adult respiratory distress syndrome (ARDS) was described in 1971 by Petty and Ashbaugh. Since that time it has been reported in association with many disease entities. We report a case in which a patient with postanginal sepsis, also known as Lemierre's syndrome, had development of ARDS.

Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule.

A case of Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule is described. This case is unusual because the patient was female, did not have underlying pulmonary disease, was not immunocompromised, had no evidence of dissemination, and had no history of aspiration or diabetes mellitus. The patient underwent thoractomy for resection of the pulmonary nodule, which led to the diagnosis. She recovered fully and is doing well without chemotherapy.

Electrophysiologic-structural correlations in chagasic aneurysms causing malignant arrhythmias.

We studied the structure and ultrastructure of three chagasic aneurysms, the excision of which abolished malignant arrhythmias. Chronic recurrent ventricular tachycardia often occurs in patients with chagasic aneurysms, and ventricular mapping indicates that these arrhythmias originate in regions adjacent to those aneurysms. In our patients, ventricular tachycardia had been refractory to medical treatment. During surgery, epicardial and endocardial mapping showed abnormal potentials. Sutures were placed in the areas of resection, their sizes approximating those of earliest activation so that these sites could be identified. The myocardium showed chronic inflammatory reaction, myocytolysis and fibrosis. The presence of "islets" was common (normal, "early" damaged or "established" necrotic myocytes surrounded by fibrous tissue). The "early" lesions were predominant at the previously identified areas of arrhythmogenic activity. The ultrastructural studies showed hypertrophy of myocytes and partial or complete loss of myofibrils, swelling of mitochondria and disruption of mitochondrial cristae, accumulation of lipofuscin granules, and intracellular oedema. A most striking alteration was the thickening of the basement membranes of myocytes and vascular endothelial and smooth muscle cells. The interlaced fronts of respectively healthy (fast conducting) and "early" damaged (slow conducting) myocytes seen in serial sectioning produced an ideal configuration for reentry circuits. The final proof that the arrhythmias originated in these endocardial regions was their abolition by resection of the aneurysm.

[A case of polymyositis in autoimmune thyroiditis with hyperthyroidism]. / Su un caso di polimiosite in corso di tiroidite autoimmune con ipertiroidismo.

A young woman, during an autoimmune thyroiditis with hyperthyroidism, suffered from progressive proximal weakness at her four limbs. The diagnosis of a concomitant polymyositis was indicated by a marked increase of plasma CPK, myopathic findings at EMG and a clearcut picture of inflammatory alterations at muscle biopsy. Steroid therapy brought a full recovery of both thyroid and muscular symptoms. In the following months, the patient suffered from a second episode of thyroiditis and subsequently from another poussée of polymyositis. The possible pathogenesis underlying the unusual association of an autoimmune thyroiditis with a polymyositis is discussed.

[Histologic findings in laser radiation of myocardial pericrater in dogs]. / Hallazgos histológicos en la irradiación por laser sobre el miocardio canino pericrater.

Laser beam constitutes a potential therapy in modern cardiology. Although its myocardial effects are known, they have been insufficiently evaluated at the surviving myocytes zone surrounding the evaporated crater. In order to assess myocyte cellular and organelar damage, we studied 8 isolated canine hearts radiated with different intensities by a CO2He laser beam 2.4, 3.5, 5, 15, 25, 30 and 40 Watts, varying the exposition time from 1 to 6 sec. Color photographs from the post-radiated lesions on front and depth were obtained. Their volumes were measured applying the cylinder and the cut out-conus formulas according to the shape of the lesions and then the involved tissues were embedded in paraffin for histological studies. Previously, samples of the lesions were fixed in glutaraldehyde for ultrastructural studies. Volumes of the craters were from 0.0004 to 19.57 mm3. Three layers were observed: a) a carbonized internal lining which measured x 15 microns in thickness; b) a coagulation necrotic zone ("gruyere cheese-like"), 70 microns thickness; c) finally more peripherally, a layer consisting of myocytes with patchy homogeneous cytoplasm, and scare positivity for the Barbeito López Trichome Stain (a positive technique in cases of myocardial damage). Ultrastructurally, crater peripherical cells showed cytosol and mitochondrial edema without membrane disruptions. These findings suggest that myocytes surrounding the laser beam crater, show reversible lesions. Therefore laser beam apperrs a safe procedure to be used in myocardium.

Tracheal obstruction presenting as new-onset wheezing.

Two cases of recent-onset dyspnea and wheezing initially treated with bronchodilator therapy for presumed reactive airway disease are presented. Plain-film chest radiographs subsequently demonstrated mediastinal masses causing extrinsic tracheal compression. The first patient had inoperable poorly differentiated squamous cell carcinoma resistant to radiotherapy. The second patient underwent resection of a substernal multinodular goiter with complete resolution of symptoms. The physician should always entertain the diagnosis of upper airway obstruction in all adult patients with new-onset wheezing. New-onset adult wheezing of uncertain etiology should prompt the physician to refer the patient for pulmonary function testing with flow-volume loops.