The impact of inflammatory and metabolic markers on depression, anxiety, and cognition after COVID-19: A narrative review.

INTRODUCTION: There has been growing concern about the long-term effects of COVID-19 on mental health. The biological factors common to psychiatric conditions and COVID-19 are not yet fully understood. METHODOLOGY: We narratively reviewed prospective longitudinal studies that measured metabolic or inflammatory markers and assessed psychiatric sequalae and cognitive impairment in individuals with COVID-19 at least 3 months after the infection. A literature search identified three relevant cohort studies. RESULTS: Overall, depressive symptomatology and cognitive deficits persisted for up to one year after COVID-19; depression and cognitive changes were predicted by acute inflammatory markers, and changes in these markers correlated with changes in depressive symptomatology; female sex, obesity, and the presence of inflammatory markers were associated with more severe clusters of physical and mental health status in patients' self-perceived recovery; and plasma metabolic profiles of patients continued to differ from those of healthy controls three months after hospital discharge, which were associated with widespread alterations in neuroimaging, reflecting issues with white matter integrity. This is a non-systematic review and cautions should be made while interpreting the conclusions. CONCLUSION: In individuals affected by the COVID-19, prolonged exposure to stress and alterations in metabolic and inflammatory markers plays a central role in psychiatric sequalae and cognitive deficits in the long term.

One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients / Um mais um é melhor que dois: Uma abordagem pela prática da transferência de embrião único para todos os pacientes de FIV

Abstract Objective It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. Methods This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. Results After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p =0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET +SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). Conclusion Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozenthawed DET, while drastically reducing the rate of multiple pregnancies.

Resumo Objetivo Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. Métodos Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. Resultados Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p <0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). Conclusão Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients.

OBJECTIVE: It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. METHODS: This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. RESULTS: After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p = 0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET + SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). CONCLUSION: Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozen-thawed DET, while drastically reducing the rate of multiple pregnancies.

OBJETIVO: Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. MéTODOS: Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. RESULTADOS: Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p < 0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). CONCLUSãO: Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

Increasing rate of anti-SARS-CoV-2 antibodies between the first and second waves of COVID-19 in Sao Paulo, Brazil: A cross-sectional blood donors-based study

ABSTRACT Background: SARS-CoV-2 infections rapidly spread along with Brazilian territory with heterogeneous transmission and mortality rates, mostly depending on region and period. Investigation of SARS-CoV-2 antibodies is an important tool to understand virus circulation. Given that blood donors are a representative casuistic of a healthy population, the authors evaluated the seroprevalence of IgG and IgM COVID-19 antibodies in 2,806 blood donors from a blood bank located in São Paulo, Brazil. Methods: Aiming to evaluate viral behavior over time, the authors selected samples from blood donors who donated in June and October 2020, and February 2021. To determine whether socio-demographic features affected the seroprevalence, the authors analyzed samples from three different regions from São Paulo (capital, metropolitan and countryside regions) and evaluated predictors as gender, age, educational level, race, and use of public transportation. Results: As expected, the authors observed that seroprevalence increased over time. Seroprevalence was greater in São Paulo city compared to metropolitan and countryside regions, being smallest in the countryside. Characteristics associated with a lower percentage of antibodies were age above 50 years, higher educational level, self-declared Caucasian, and use of individual transportation. Conclusion: In conclusion, blood donors' samples proved to accurately reflect virus circulation in the healthy population.

Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.

Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.

Criteria for evaluating studies at scientific medical events

Medical journals value the quality of studies. Scientific events are spaces for discussion in the face of scientific advances, innovation and consensus. In them, space is opened for the presentation of clinical studies, translational studies, experience reports and videos, with the best-designed studies being selected and awarded. The lack of clear criteria allows for differences in assessments, making it difficult to place value on situations associated with research. In order to improve quality, it is necessary to evaluate ethics, the hierarchy of scientific evidence (methodology), the study design, the originality, the relevance, and the linearity of the material presented. The present study aims to discuss these points, presenting proposals to be used in the evaluation of clinical studies, translational studies, case reports and videos in scientific medical events.

The developmental competence of oocytes retrieved from the leading follicle in controlled ovarian stimulated cycles.

BACKGROUND: This study compares the developmental capacity of gametes retrieved from the largest follicle with small follicles of a cohort in controlled ovarian stimulated cycles. MATERIALS AND METHODS: This prospective study performed in a private assisted fertilization center included 1016 follicles collected from 96 patients who underwent intra cytoplasmic sperm injection (ICSI). After follicular aspiration, oocytes were assigned to two groups according to the diameter of the derived follicle. The large follicle group (n=96) comprised oocytes derived from the leading follicle of the cohort and the small follicle group (n=920) consisted oocytes derived from the smaller follicles of the cohort. The fertilization and percentage of topquality embryos were compared between groups by Chi-square or Fisher's exact test, where appropriate. The effect of the follicular diameter on oocyte dimorphism was assessed by binary logistic regression. RESULTS: A significantly higher percentage of oocytes derived from the leading follicle were in the metaphase II (MII) stage (100 vs. 70.0%, p<0.001). However we observed no significant differences regarding the percentage of degenerated oocytes between the large (6.25%) and small follicle (5.0%) groups (p=0.550). Regression analysis demonstrated a nearly two-fold increase in the incidence of vacuoles in oocytes derived from the largest follicle of the cohort (OR: 1.81, p=0.046). The fertilization rate (50.0 vs. 38.8%, p=0.038) and the percentage of top quality embryos (84.7 vs. 76.4%, p=0.040) were significantly higher for oocytes derived from the largest follicle. However, the percentage of abnormal fertilized oocytes was equally distributed between the large follicle (15.0%) and small follicle (12. 8%) groups (p=0.550). CONCLUSION: Our data suggest that intrafollicular mechanisms within the larger follicle of the cohort may allow for these follicles to amplify the responsiveness to exogenous gonadotropin, which leads to the formation of more competent oocytes with higher fertilization and developmental capacities.

Evaluation of single nucleotide polymorphisms in microRNAs (hsa-miR-196a2 rs11614913 C/T) from Brazilian women with breast cancer.

BACKGROUND: Emerging evidence has shown that miRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in pre-miRNAs may affect the processing and therefore, influence the expression of mature miRNAs. Previous studies generated conflicting results when reporting association between the hsa-miR-196a2 rs11614913 common polymorphism and breast cancer. METHODS: This study evaluated the hsa-miR-196a2 rs11614913 SNP in 388 breast cancer cases and 388 controls in Brazilian women. Polymorphism was determined by real-time PCR; control and experimental groups were compared through statistical analysis using the X2 or Fisher's exact tests. RESULTS: The analysis of the SNPs frequencies showed a significant difference between the groups (BC and CT) in regards to genotype distribution (χ2: p = 0.024); the homozygous variant (CC) was more frequent in the CT than in the BC group (p = 0.009). The presence of the hsa-miR-196a2 rs11614913 C/T polymorphism was not associated with histological grades (p = 0.522), axillary lymph node positive status (p = 0.805), or clinical stage (p = 0.670) among the breast cancer patients. CONCLUSIONS: The results of this study indicated that the CC polymorphic genotype is associated with a decreased risk of BC and the presence of the T allele was significantly associated with an increased risk of BC.

Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients.

OBJECTIVE: To evaluate the effect of male age on clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles, according to sperm concentration. DESIGN: Retrospective, observational study. SETTING: Assisted reproduction center. PATIENT(S): The study included 1,024 couples undergoing ICSI cycles with fresh spermatozoa. INTERVENTION(S): The influence of paternal age on ICSI outcomes of oligozoospermic and normozoospermic patients was evaluated. MAIN OUTCOME MEASURE(S): Rates of high-quality embryos, pregnancy, implantation, and miscarriage were evaluated through linear logistic regression analyses. RESULT(S): When the sperm concentration was abnormal, paternal age influenced implantation (regression coefficient value = -0.7009) and pregnancy rates (odds ratio = 0.95, 95% confidence interval 0.91-0.99). However, in normozoospermic patients, no influence of paternal age was observed on implantation (regression coefficient value = 0.0566) or pregnancy rates (odds ratio = 1.00, 95% confidence interval 0.97-1.03). CONCLUSION(S): For couples in which the men are oligozoospermic, the implantation rate could be impaired by increased paternal age. In these couples, the chance of pregnancy decreased 5% for each year of paternal age. When men are normozoospermic, this effect is not observed.

Use of pig oocytes for training new professionals in human assisted reproduction laboratories.

OBJECTIVE: To evaluate whether swine oocytes are useful for training new technicians in a human reproduction laboratory. DESIGN: Prospective study. SETTING: Graduate school in assisted reproductive techniques (ART) in Brazil. PATIENT(S): Students in a human reproduction laboratory. INTERVENTION(S): Medium-sized follicles were aspirated from prepubertal gilts' ovaries and collected at a slaughterhouse. Oocytes were retrieved from the follicular fluid. Twenty-one students trained during four periods of 20 hours each were evaluated as to their ability to perform micromanipulation and were compared with a group of well-trained professionals (control group). MAIN OUTCOME MEASURE(S): Students' ability in oocyte retrieval, oocyte manipulation, and intracytoplasmic sperm injection during and after the 80 hours of training. RESULT(S): Students were able to retrieve, on average, 23.8 oocytes per ovary. Their micromanipulation skills substantially increased, reaching an oocyte retrieval rate of 77.2%, compared with 84.9% in the control group after the training period. Although the oocyte damage rate gradually decreased, from 52.0% after 20 hours of training to 5.4% after 80 hours, these figures were still above the control group oocyte damage rate by 0.3%, which was a statistically significant level. Regarding intracytoplasmic sperm injection, within 40 hours, no students were able to perform a single injection; and by the end of 80 hours, they achieved an average of 4.0 oocytes per hour, whereas the control group injected 20.6 oocytes per hour, a statistically significant difference. CONCLUSION(S): Swine ovaries may be a useful tool in the spectrum of training techniques for unskilled assisted reproductive techniques laboratory professionals.