In vitro effects of antidepressants on human sperm function.

Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO2, and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.

Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.

Antimicrobial and anthelmintic effects of copper nanoparticles against Koi carp parasites and their toxicity.

This study investigated the in vitro antimicrobial and anthelmintic effect of copper nanoparticles (CuNPs) against the bacterium Aeromonas hydrophila, the monogeneans Dactylogyrus minutus, Dactylogyrus extensus, Gyrodactylus cyprini, and the cestode Schyzocotyle acheilognathi, as well as their toxicity to Cyprinus carpio Koi. In the antimicrobial in vitro test, the inhibition zone method and minimum inhibitory concentration (MIC) were performed. In order to determine the time and efficacy of monogenean parasite mortality, the parasites were exposed to CuNP concentrations of 20, 50, 100, 150, 200, and 300 mg L-1, and a control group with tank water and one with copper sulphate pentahydrate (CuSO4.5H2O) at a concentration of 0.3 mg L-1, performed in triplicate. The parasites were observed every 10 min for 300 min, and mortality was recorded. For the cestodes, parasites were immersed in CuNP concentrations of 50, 100, 150, and 300 mg L-1. At the end of the in vitro tests, the anthelmintic efficacy of each treatment was calculated. To assess the tolerance and toxicity in fish, they were exposed to CuNP concentrations of 0.6, 1.25, 2.5, 5, 10, 20, and 50 mg L-1 for 12 h. The MIC demonstrated that CuNPs effectively inhibited the growth of A. hydrophila up to a dilution of 12,500 mg L-1 and showed an inhibition zone of 14.0 ± 1.6 mm for CuNPs. The results of anthelmintic activity showed a dose-dependent effect of concentration for both groups of parasites, with the most effective concentration being 300 mg L-1 in 120 min. In the toxicity test, the carps showed tolerance to lower concentrations. The study indicated that CuNPs were effective against the studied pathogens. However, it proved to be toxic to fish at high concentrations. The use of low concentrations is recommended still requires further investigation.

The Low Survivability of Transplanted Gonadal Grafts: The Impact of Cryopreservation and Transplantation Conditions on Mitochondrial Function.

Advances in tissue preservation techniques have allowed reproductive medicine and assisted reproductive technologies (ARTs) to flourish in recent years. Because radio- and chemotherapy procedures are often gonadotoxic, irreversible damage can preclude future gamete production and endocrine support. Accordingly, in recent years, the freezing and storage of gonadal tissue fragments prior to the first oncological treatment appointment and autologous transplantation post-recovery have been considered improved solutions for fertility recovery in cancer survivors. Nevertheless, the cryopreservation and transplantation of thawed tissues is still very limited, and positive outcomes are relatively low. This review aims to discuss the limitations of oncofertility protocols with a focus on the impacts of mitochondrial dysfunction, oxidative stress, and the loss of antioxidant defense in graft integrity.

Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

Measurement properties of patient-reported outcome measures for women with dysmenorrhea: A systematic review.

BACKGROUND: Dysmenorrhea, or menstrual pain, is a subjective experience, and can only be assessed by patient-reported outcomes. These instruments should be reliable, valid and responsive. AIM: To identify and critically appraise the available evidence for the measurement properties of specific patient-reported outcome measures used for dysmenorrhea. METHODS: The PRISMA statement was used to report this systematic review. Databases searched were PubMed, SCOPUS, CINAHL, Web of Science, ScienceDirect and Google Scholar (April 2021; updated on February 2023). Original studies with primary data collection, with no restriction on language and publication date that reported psychometric properties of one or more dysmenorrhea-related patient-reported outcome measure. The literature searches, selection of studies, data extraction and assessment of the risk of bias were performed independently by two reviewers and followed the COSMIN guidelines. RESULTS: Thirty studies were analysed in this review, and 19 patient-reported outcome measures were evaluated. The instruments varied in relation to the measured construct and measurement properties (validity, reliability and responsiveness). The methodological quality of the studies and the quality of evidence of the patient-reported outcome measures were variable. Among the 13 studies that reported the development of patient-reported outcome measures, most had inadequate methodological quality, and the overall rating was insufficient or inconsistent. CONCLUSIONS: The Dysmenorrhea Symptom Interference (DSI) scale was the only identified patient-reported outcome measure that has the potential to be recommended because of its sufficient rating combined with moderate quality of evidence for content validity. Future studies should further evaluate the measurement properties of the existing patient-reported outcome measures, or develop new patient-reported outcome measures following the COSMIN methodology. PATIENT OR PUBLIC CONTRIBUTION: Not applicable as this is a systematic review. TRIAL REGISTRATION: PROSPERO protocol: CRD42021244410. Registration on April 22, 2021.

Assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease: a European perspective.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

INTRODUCTION: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. METHODS: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. RESULTS: Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. CONCLUSION: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Optimization of Platelet-Rich Plasma Preparation for Regenerative Medicine: Comparison of Different Anticoagulants and Resuspension Media.

Platelet-rich plasma (PRP) has emerged as a promising therapy in regenerative medicine. However, the lack of standardization in PRP preparation protocols presents a challenge in achieving reproducible and accurate results. This study aimed to optimize the PRP preparation protocol by investigating the impact of two different anticoagulants, sodium citrate (SC) and ethylenediaminetetraacetic acid (EDTA), and resuspension media, plasma versus sodium chloride (NaCl). Platelet recovery rates were calculated and compared between groups, in addition to platelet activity and vascular endothelial growth factor (VEGF) released into plasma after PRP activation. The platelet recovery rate was higher with EDTA in comparison to SC (51.04% vs. 29.85%, p = 0.005). Platelet activity was also higher, with a higher expression of two platelet antibodies, platelet surface P-Selectin (CD62p) and PAC-1, in the EDTA group. The concentration of VEGF was higher with SC in comparison to EDTA (628.73 vs. 265.44 pg/mL, p = 0.013). Platelet recovery rates and VEGF levels were higher in PRP resuspended in plasma when compared to NaCl (61.60% vs. 48.61%, p = 0.011 and 363.32 vs. 159.83 pg/mL, p = 0.005, respectively). Our study reinforces the superiority of EDTA (as anticoagulant) and plasma (for resuspension) in obtaining a higher platelet recovery and preserving platelet functionality during PRP preparation.

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

Anti-titin antibodies in a cohort of myasthenia gravis patients.

Background: Anti-titin antibodies have been previously associated with thymoma-associated myasthenia gravis (MG) and a more clinically severe form of MG. While currently only serving as a disease biomarker, its possible utility as an indicator of underlying thymus malignancy may be of value in clinical practice. Methods: Data was retrospectively collected and analyzed from 2013 to 2022 using an institutional record of MG patients. Anti-titin antibodies were assessed using Line Blot immunoassay. Results: From 130 MG cases, 32 (24.6%) were anti-titin positive. Anti-titin positive cases were associated with older age of disease onset [median (IQR): 63.0 (44.3-70.8) vs. 35.5 (24.8-60.8) years] (P<0.01). Thymectomy was performed in 46 (35.4%) MG patients, 12 of which anti-titin positive (26.1%). Thymectomy samples from anti-titin positive patients comprised 10 (83.3%) cases of thymoma and 2 (16.7%) cases of thymus hyperplasia. There was a tendency towards anti-titin positive patients having more thymoma while anti-titin negative displayed more hyperplasia (P<0.01). Anti-titin positivity correlated with thymoma in patients with age of onset bellow 50 years (P=0.028). Anti-titin positivity was significantly associated with generalized MG in the late-onset group (P=0.005). Conclusions: The presence of anti-titin antibodies appears to correlate with underlying thymoma in early-onset MG cases and with generalized MG in late-onset cases. Prospective studies are needed to further study this association.

Treatment strategies and treatment-related adverse events in MG according to the age of onset.

Introduction: Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset. Methods: This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records. Results: In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0-64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%). Conclusion: Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.

Pain neuroscience education improves quality of life when added to aquatic exercise therapy for women with fibromyalgia: randomized controlled clinical trial.

PURPOSE: The aim of the present study was to investigate the effects of adding Pain Neuroscience Education (PNE) to an aquatic therapy protocol on pain, fibromyalgia (FMS) impact, quality of life and sleep. MATERIALS AND METHODS: Seventy-five women were randomly allocated into two groups: aquatic exercises (AEG, n = 36) and aquatic exercises + PNE (PNG, n = 39). The primary outcome was pain, and the secondary outcomes were FMS impact, quality of life, sleep and pain sensitivity (pressure pain thresholds - PPTs). Participants performed 45-min sessions of aquatic exercises, twice a week, for 12 weeks. PNG also received 4 PNE sessions during this period. Participants were assessed four times: initial (before treatment), after 6 weeks (intermediate) and 12 weeks (final) of treatment and after 12 weeks after the end of treatment (follow-up). RESULTS: Both groups improved pain after treatment, with no difference between them (p > 0.05, partial ƞ2 0.10). FMS impact and PPTs improved after treatment with no difference between groups, and sleep did not change. Quality of life improved several domains for both groups, with slightly better results for the PNG, with low effect sizes between groups. CONCLUSIONS: The present results show that the addition of PNE to an aquatic exercise intervention did not provide larger effects than aquatic exercises alone for people with FMS concerning pain intensity, but provided benefit for health-related quality of life for this population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03073642, version 2, April 1st, 2019). PERSPECTIVE: The addition of 4 Pain Neuroscience Education sessions to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome on pain, fibromyalgia impact, and sleep, but improved quality of life and pain sensitivity.IMPLICATIONS FOR REHABILITATIONAquatic exercises are commonly prescribed, but patient education is crucial for the treatment.The addition of Pain Neuroscience Education to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome.The positive changes on quality of life and pain sensitivity that this combination led to had small effect sizes and did not achieve minimal important clinical difference.

Towards standardized human platelet lysate production in Europe: An initiative of the European Blood Alliance.

Human platelet lysate (hPL) is a supplement for cell culture media that can be derived from platelet concentrates. As not-for-profit blood establishments, we endorse the evolution of maximally exploiting the potential of donated blood and its derived components, including platelets. The decision to use platelet concentrates to supply hPL as a cell culture supplement should align with the principles and values that blood establishments hold towards the use of donated blood components in transfusion. As a consequence, questions on ethics, practical standardization of hPL production and logistics as well as on assuring hPL quality and safety need careful consideration. We therefore propose an opinion on some of these matters based on available literature and on discussions within the proceedings of the Working Group on Innovation and New Products of the European Blood Alliance. In addition, we propose collaboration among European blood establishments to streamline efforts of hPL supply to maximize the potential of hPL and its application in the wider field of medicine.

New Insights on Sperm Function in Male Infertility of Unknown Origin: A Multimodal Approach.

The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universitário de Coimbra (CHUC), from July 2018-July 2022. Based on the couples' clinical data, seminal/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Do the instruments used to assess fibromyalgia symptoms according to American College of Rheumatology criteria generate similar scores in other chronic musculoskeletal pain?

BACKGROUND: As with fibromyalgia, several musculoskeletal disorders are characterized by chronic pain, raising a clinical question - do the instruments used to assess fibromyalgia symptoms according to ACR criteria (ACR criteria) generate similar scores in other chronic musculoskeletal pain? OBJECTIVE: To compare the symptoms among fibromyalgia and other chronic musculoskeletal pain. Additionally, we also compared the most researched outcomes in fibromyalgia (i.e., present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptom). METHODS: A cross-sectional study. Participants over 18 years old were included if they presented report of chronic musculoskeletal pain (≥ 3 months) and after that, they were divided into two groups (fibromyalgia and chronic pain). They answered the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), Brief Pain Inventory (BPI), Numerical Pain Rating Scale (NPRS) for pain and fatigue, WPI, and SSS. RESULTS: A total of 166 participants were included in this study into two independent groups (chronic pain, n = 83; fibromyalgia, n = 83). We observed significant differences (p < 0.05) and large effect sizes (Cohen's d, ≥ 0.7) in clinical outcomes comparisons between groups (i.e., widespread pain; symptom severity; present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptoms). CONCLUSION: Fibromyalgia patients (2016 ACR criteria) compared to other chronic musculoskeletal pain patients have higher levels of pain (at rest or after movement) and fatigue, greater impairment in both functionality and global impact, and worse symptoms. Therefore, the WPI and SSS instruments should be used exclusively to assess fibromyalgia symptoms.

Low responders may benefit from undergoing ovarian stimulation with a long GnRH agonist protocol with corifollitropin alfa followed by hMG.

OBJECTIVE: To evaluate the outcomes of a long GnRH agonist protocol with corifollitropin alfa followed by hMG in low responders. METHODS: Retrospective cohort study. Patients with a suboptimal previous ovarian response (<9 oocytes) and a normal ovarian reserve (Poseidon groups 1 and 2) were classified in 1) Group 1 (n=88), submitted to a second cycle with a GnRH antagonist protocol using rFSH/hMG; 2) Group 2 (n=66), submitted to a long GnRH agonist protocol with corifollitropin alfa followed by hMG (named as simplified long protocol). Clinical outcomes were compared between groups and between the first/second cycle of each group. RESULTS: Clinical outcomes were similar between groups. There were no differences in the number of oocytes [7(5-11.75) versus 7(5-10), p=0.802], clinical pregnancy (19.3% versus 18.2%, p=0.858) and live birth rates (18.2% versus 15.2%, p=0.619). However, baseline characteristics were different, decoding a poor prognosis among women in group 2. Both groups (1 and 2) had significantly higher number of oocytes, pregnancy, and live birth rates in the second cycle. In group 2, there was a higher rate of embryo transfer (56.1% versus 27.3%, p<0.001). In group 1, despite the similar rate of embryo transfer, there was a higher positive hCG (23.9% versus 8.0%, p=0.004). CONCLUSIONS: Both simplified long protocol and GnRH antagonist protocol are suitable for low responders. The best second cycle clinical outcomes experienced in a population with worse prognosis (group 2) suggests that the simplified long protocol may be a better option, although prospective well-conducted studies must explore this hypothesis.

Aging and oocyte competence: A molecular cell perspective.

Follicular microenvironment is paramount in the acquisition of oocyte competence, which is dependent on two interconnected and interdependent processes: nuclear and cytoplasmic maturation. Extensive research conducted in human and model systems has provided evidence that those processes are disturbed with female aging. In fact, advanced maternal age (AMA) is associated with a lower chance of pregnancy and live birth, explained by the age-related decline in oocyte quality/competence. This decline has largely been attributed to mitochondria, essential for oocyte maturation, fertilization, and embryo development; with mitochondrial dysfunction leading to oxidative stress, responsible for nuclear and mitochondrial damage, suboptimal intracellular energy levels, calcium disturbance, and meiotic spindle alterations, that may result in oocyte aneuploidy. Nuclear-related mechanisms that justify increased oocyte aneuploidy include deoxyribonucleic acid (DNA) damage, loss of chromosomal cohesion, spindle assembly checkpoint dysfunction, meiotic recombination errors, and telomere attrition. On the other hand, age-dependent cytoplasmic maturation failure is related to mitochondrial dysfunction, altered mitochondrial biogenesis, altered mitochondrial morphology, distribution, activity, and dynamics, dysmorphic smooth endoplasmic reticulum and calcium disturbance, and alterations in the cytoskeleton. Furthermore, reproductive somatic cells also experience the effects of aging, including mitochondrial dysfunction and DNA damage, compromising the crosstalk between granulosa/cumulus cells and oocytes, also affected by a loss of gap junctions. Old oocytes seem therefore to mature in an altered microenvironment, with changes in metabolites, ribonucleic acid (RNA), proteins, and lipids. Overall, understanding the mechanisms implicated in the loss of oocyte quality will allow the establishment of emerging biomarkers and potential therapeutic anti-aging strategies. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology.