Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

Effects of Different Diets on Biological Characteristics of Predatory Mite Amblyseius Eharai (Acari: Phytoseiidae).

In this study, we investigated the effects of different diets on the development and reproduction of the predatory mite Amblyseius eharai. The results show that feeding on citrus red mite (Panonychus citri) led to the fastest life cycle completion (6.9 ± 0.22 days), the longest oviposition period (26.19 ± 0.46 days), the greatest female longevity (42.03 ± 0.43 days), and the highest total number of eggs per female (45.63 ± 0.94 eggs). Feeding on Artemia fanciscana cysts resulted in the highest oviposition rate (1.98 ± 0.04 eggs), a high total number of eggs per female (33.93 ± 0.36 eggs), and the highest intrinsic rate of increase (rm = 0.242). The hatching rate did not differ significantly among the five types of food, and the proportion of females ranged from 60% to 65% across all diets.

Cumulative live birth rate after oocyte in vitro maturation with a pre-maturation step in women with polycystic ovary syndrome or high antral follicle count.

PURPOSE: This study evaluated the 24-month cumulative live birth rate (CLBR) for women with polycystic ovary syndrome (PCOS) or high antral follicle count (AFC) who underwent oocyte in vitro maturation (IVM) with pre-maturation step (CAPA-IVM). METHODS: This multicenter, retrospective study was performed at IVFMD, My Duc Hospital, and IVFMD Phu Nhuan, My Duc Phu Nhuan Hospital from 1 January 2017 to 31 December 2019. All women with PCOS or high AFC treated with a CAPA-IVM cycle were included. Cumulative live birth was defined as at least one live birth resulting from the initiated CAPA-IVM cycle. Where a woman did not return for embryo transfer, outcomes were followed up until 24 months from the day of oocyte aspiration. Logistic regression was performed to identify factors predicting the CLBR. RESULTS: Data from 374 women were analyzed, 368 of whom had embryos for transfer (98.4%), and six had no embryos for transfer (1.6%). The oocyte maturation rate was 63.2%. The median number of frozen embryos was 4 [quartile 1, 2; quartile 3, 6]. Cumulative clinical pregnancy and ongoing pregnancy rates were 60.4% and 43.6%, respectively. At 24 months after starting CAPA-IVM treatment, the CLBR was 38.5%. Multivariate analysis showed that patient age and number of frozen embryos were significant predictors of cumulative live birth after CAPA-IVM. CONCLUSIONS: CAPA-IVM could be considered as an alternative to in vitro fertilization for the management of infertility in women with PCOS or a high AFC who require assisted reproductive technology.

A spectrum of viral diseases in Odisha state, eastern India: An evidence-based analysis from 2010-2017.

Introduction: Emerging and re-emerging viral diseases are a major threat to public health. Odisha, being one of the coastal states in the country, reports many viral illnesses due to its typical geographical location. This study focuses on the prevalence of different viral diseases in the state of Odisha, India, from 2010-2017. Material and Methods: A total of 43,397 patients with clinical suspicion of viral diseases were screened for different viral etiologies during 2010-2017. The laboratory diagnosis was conducted by serology (ELISA) and RT-PCR for 24 different viruses, i.e., dengue, chikungunya, Japanese encephalitis, hepatitis A virus, hepatitis E virus, hepatitis B virus, hepatitis C virus, rotavirus, herpes simplex virus-1 and herpes simplex virus-2, Epstein-Barr virus, cytomegalovirus, and respiratory viruses. Patients were enrolled from sporadic hospital admissions and outbreaks under different categories as per clinical diagnoses like fever with rash, diarrhoea, encephalitis, jaundice, respiratory illness, and fever of unknown etiology. Results: The majority of patients belonged to exanthematous group, i.e., fever with rash (32.24%). The number of males was more in all categories except fever with rash, where females (53.34%) were more. Children <16 years of age were found to be the predominant age group for suspected viral diarrhoea (85.26%), encephalitis (76.96%), fever of unknown origin (40.16%), and respiratory infections (27.23%). Conclusion: Not only vector-borne diseases pose a threat to the Odisha state, but other viral illnesses have also emerged. This detailed report of different viral diseases in the state of Odisha will support public health management.

The meaning of screening: detection of brain metastasis in the adjuvant setting for stage III melanoma.

BACKGROUND: The incidence of melanoma is increasing and 37% of patients with metastatic melanoma eventually have brain metastasis (BM). Currently, there is no consensus on screening for BM in patients with resected stage III melanoma. However, given the high incidence of BM, routine screening magnetic resonance imaging (MRI) of the brain is considered in patients with completely resected stage III melanoma before the start of adjuvant treatment. The aim of this study was to assess the yield of screening for BM in these patients. MATERIALS AND METHODS: A single-center cohort study was carried out in the Erasmus MC, Rotterdam, The Netherlands, a large tertiary referral center for patients with melanoma. Eligible patients with complete resection of stage III melanoma and a screening MRI of the brain, made within 12 weeks after resection and before adjuvant treatment (programmed cell death protein 1 inhibitors, dabrafenib-trametinib), available between 1 August 2018 and 1 January 2021, were included. RESULTS: A total of 202 patients were included. Eighteen (8.9%) of 202 patients had extracranial metastasis at screening. Two (1.1%) of the remaining 184 patients had BM at screening, resulting in a switch from adjuvant treatment to ipilimumab-nivolumab. At a median follow-up of 21.2 months, BM was detected in another 4 (2.4%) of 166 patients who started with adjuvant treatment. CONCLUSIONS: The yield of screening MRI of the brain is low after complete resection of stage III melanoma, before the start of adjuvant treatment. Therefore, routine screening MRI is not recommended in this setting.

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

Background: Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs. Objective: We sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs. Methods: Genotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model. Results: Polymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17-1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14-2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05-1.63, p = 0.016), but not American RTRs. Conclusions: We report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.

Relationships between resilience and quality of life in parents of children with cancer.

CLINICALTRIALS.GOV ID: NCT03631485.

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients.

STUDY QUESTION: What is the cumulative delivery rate (CDR) per aspiration IVF/ICSI cycle in low-prognosis patients as defined by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER: The CDR of POSEIDON patients was on average ∼50% lower than in normal responders and varied across POSEIDON groups; differences were primarily determined by female age, number of embryos obtained, number of embryo transfer (ET) cycles per patient, number of oocytes retrieved, duration of infertility, and BMI. WHAT IS KNOWN ALREADY: The POSEIDON criteria aim to underline differences related to a poor or suboptimal treatment outcome in terms of oocyte quality and quantity among patients undergoing IVF/ICSI, and thus, create more homogenous groups for the clinical management of infertility and research. POSEIDON patients are presumed to be at a higher risk of failing to achieve a live birth after IVF/ICSI treatment than normal responders with an adequate ovarian reserve. The CDR per initiated/aspiration cycle after the transfer of all fresh and frozen-thawed/warmed embryos has been suggested to be the critical endpoint that sets these groups apart. However, no multicenter study has yet substantiated the validity of the POSEIDON classification in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment using real-world data. STUDY DESIGN, SIZE, DURATION: Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women with infertility between 22 and 42 years old in their first IVF/ICSI cycle of standard ovarian stimulation whose fresh and/or frozen embryos were transferred until delivery of a live born or until all embryos were used. Patients were retrospectively classified according to the POSEIDON criteria into four groups based on female age, antral follicle count (AFC), and the number of oocytes retrieved or into a control group of normal responders (non-POSEIDON). POSEIDON patients encompassed younger (<35 years) and older (35 years or above) women with an AFC ≥5 and an unexpected poor (<4 retrieved oocytes) or suboptimal (4-9 retrieved oocytes) response to stimulation, and respective younger and older counterparts with an impaired ovarian reserve (i.e. expected poor responders; AFC <5). Non-POSEIDON patients were those with AFC ≥5 and >9 oocytes retrieved. CDR was computed per one aspirated cycle. Logistic regression analysis was carried out to examine the association between patient classification and CDR. MAIN RESULTS AND ROLE OF CHANCE: The CDR was lower in the POSEIDON patients than in the non-POSEIDON patients (33.7% vs 50.6%; P < 0.001) and differed across POSEIDON groups (younger unexpected poor responder [Group 1a; n = 212]: 27.8%, younger unexpected suboptimal responder [Group 1b; n = 1785]: 47.8%, older unexpected poor responder [Group 2a; n = 293]: 14.0%, older unexpected suboptimal responder [Group 2b; n = 1275]: 30.5%, younger expected poor responder [Group 3; n = 245]: 29.4%, and older expected poor responder [Group 4; n = 623]: 12.5%. Among unexpected suboptimal/poor responders (POSEIDON Groups 1 and 2), the CDR was twice as high in suboptimal responders (4-9 oocytes retrieved) as in poor responders (<4 oocytes) (P = 0.0004). Logistic regression analysis revealed that the POSEIDON grouping, number of embryos obtained, number of ET cycles per patient, number of oocytes collected, female age, duration of infertility and BMI were relevant predictors for CDR (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Our study relied on the antral follicle count as the biomarker used for patient classification. Ovarian stimulation protocols varied across study centers, potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS: POSEIDON patients exhibit lower CDR per aspirated IVF/ICSI cycle than normal responders; the differences are mainly determined by female age and number of oocytes retrieved, thereby reflecting the importance of oocyte quality and quantity. Our data substantiate the validity of the POSEIDON criteria in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment. Efforts in terms of early diagnosis, prevention, and identification of specific interventions that might benefit POSEIDON patients are warranted. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. J.F.C. declares receipt of statistical services fees from ANDROFERT Clinic. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. P.H. declares receipt of unrestricted research grants from Merck, Ferring, Gedeon Richter and IBSA and lecture fees from Merck, Gedeon Richter and Med.E.A. C.A. declares receipt of unrestricted research grants from Merck and lecture fees from Merck. The remaining authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Low Prognosis by the POSEIDON Criteria in Women Undergoing Assisted Reproductive Technology: A Multicenter and Multinational Prevalence Study of Over 13,000 Patients.

Objective: To estimate the prevalence of low-prognosis patients according to the POSEIDON criteria using real-world data. Design: Multicenter population-based cohort study. Settings: Fertility clinics in Brazil, Turkey, and Vietnam. Patients: Infertile women undergoing assisted reproductive technology using standard ovarian stimulation with exogenous gonadotropins. Interventions: None. Main outcome measures: Per-period prevalence rates of POSEIDON patients (overall, stratified by POSEIDON groups and by study center) and the effect of covariates on the probability that a patient be classified as "POSEIDON". Results: A total of 13,146 patients were included. POSEIDON patients represented 43.0% (95% confidence interval [CI] 42.0-43.7) of the studied population, and the prevalence rates varied across study centers (range: 38.6-55.7%). The overall prevalence rates by POSEIDON groups were 44.2% (group 1; 95% CI 42.6-45.9), 36.1% (group 2; 95% CI 34.6-37.7), 5.2% (group 3; 95% CI 4.5-6.0), and 14.4% (group 4; 95% CI: 13.3-15.6). In general, POSEIDON patients were older, had a higher body mass index (BMI), lower ovarian reserve markers, and a higher frequency of female factor as the primary treatment indication than non-POSEIDON patients. The former required larger doses of gonadotropin for ovarian stimulation, despite achieving a 2.5 times lower number of retrieved oocytes than non-POSEIDON patients. Logistic regression analyses revealed that female age, BMI, ovarian reserve, and a female infertility factor were relevant predictors of the POSEIDON condition. Conclusions: The estimated prevalence of POSEIDON patients in the general population undergoing ART is significant. These patients differ in clinical characteristics compared with non-POSEIDON patients. The POSEIDON condition is associated with female age, ovarian reserve, BMI, and female infertility. Efforts in terms of diagnosis, counseling, and treatment are needed to reduce the prevalence of low-prognosis patients.

Antral follicle count and anti-Müllerian hormone to classify low-prognosis women under the POSEIDON criteria: a classification agreement study of over 9000 patients.

STUDY QUESTION: What is the agreement between antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels when used to patient classification according to the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER: Our study indicates a strong agreement between the AFC and the AMH levels in classifying POSEIDON patients; thus, either can be used for this purpose, although one in four women will have discordant values when both biomarkers are used. WHAT IS KNOWN ALREADY: According to the POSEIDON criteria, both AFC and AMH may be used to classify low-prognosis patients. Proposed AFC and AMH thresholds of 5 and 1.2 ng/ml, respectively, have their basis in published literature; however, no study has yet determined the reproducibility of patient classification in comparing one biomarker with the other, nor have their thresholds ever been validated within this patient population. STUDY DESIGN, SIZE, DURATION: A population-based cohort study involving 9484 consecutive patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were infertile women between 22 and 46 years old in their first in vitro fertilization/intracytoplasmic sperm injection cycle of standard ovarian stimulation with exogenous gonadotropins whose baseline ovarian reserves had been assessed by both AFC and AMH. Details of pre- and post-treatment findings were input into a coded research file. Two indicators of interest were created to classify patients according to the POSEIDON criteria based upon AFC and AMH values. Patients who did not fit any of the four POSEIDON groups were classified as non-POSEIDON. AFC was determined in the early follicular phase using two-dimensional (2D) transvaginal ultrasonography, whereas AMH values were based on the modified Beckman Coulter generation II enzyme-linked immunosorbent assay. Agreement rates were computed between AFC and AMH to classify patients using Cohen's kappa statistics. Logistic regression analyzes were carried out to examine the association between ovarian markers and low (<4) and suboptimal (4-9) oocyte yield. MAIN RESULTS AND THE ROLE OF CHANCE: The degree of agreement in classifying patients according to POSEIDON groups was strong overall (kappa = 0.802; 95% CI: 0.792-0.811). A total of 73.8% of individuals were classified under the same group using both biomarkers. The disagreement rates were ∼26% and did not diverge when AFC or AMH was used as the primary biomarker criterion. Significant regression equations were found between ovarian markers and oocyte yield (P < 0.0001). For low oocyte yield, the optimal AFC and AMH cutoff values were 5 and 1.27 ng/ml with sensitivities of 0.61 and 0.66, specificities of 0.81 and 0.72, and AUC receiver operating characteristics of 0.791 and 0.751, respectively. For suboptimal oocyte yield respective AFC and AMH cutoffs were 12 and 2.97 ng/ml with sensitivities of 0.74 and 0.69, specificities of 0.76 and 0.66 and AUCs of 0.81 and 0.80. LIMITATIONS, REASONS FOR CAUTION: Our study relied on 2D transvaginal sonography to quantify the AFC and manual Gen II assay for AMH determination and classification of patients. AMH data must be interpreted in an assay-specific manner. Treatment protocols varied across centers potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS: Three of four patients will be classified the same using either AFC or AMH values. Both biomarkers provide acceptable and equivalent accuracy in predicting oocyte yield further supporting their use and proposed thresholds in daily clinical practice for patient classification according to the POSEIDON criteria. However, the sensitivity of POSEIDON thresholds in predicting low oocyte yield is low. Clinicians should adopt the biomarker that may best reflect their clinical setting. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. The remaining authors have nothing to disclose. TRIAL REGISTRATION NUMBER: not applicable.

Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study.

STUDY QUESTION: Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? SUMMARY ANSWER: Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone. WHAT IS KNOWN ALREADY: Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. STUDY DESIGN, SIZE, DURATION: Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks' gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints. MAIN RESULTS AND THE ROLE OF CHANCE: The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99-1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01-1.68), P = 0.042), with a statistically significant lower rate of miscarriage at <12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32-0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group. LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability. WIDER IMPLICATIONS OF THE FINDINGS: Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant. TRIAL REGISTRATION NUMBER: NCT0399876.

Fresh embryo transfer versus freeze-only after in vitro maturation with a pre-maturation step in women with high antral follicle count: a randomized controlled pilot study.

PURPOSE: In vitro maturation (IVM) is an alternative to in vitro fertilization (IVF) for women at high risk of developing ovarian hyperstimulation syndrome (OHSS). This study determined the effectiveness and safety of a freeze-only strategy versus fresh embryo transfer (ET) after IVM with a pre-maturation step (CAPA-IVM) in women with a high antral follicle count (AFC). METHODS: This randomized, controlled pilot study (NCT04297553) was conducted between March and November 2020. Forty women aged 18-37 years with a high AFC (≥24 follicles in both ovaries) undergoing one cycle of CAPA-IVM were randomized to a freeze-only strategy with subsequent frozen ET (n = 20) or to fresh ET (n = 20). The primary endpoint was ongoing pregnancy resulting in live birth after the first ET of the started treatment cycle. RESULTS: The ongoing pregnancy rate in the freeze-only group (65%) was significantly higher than that in the fresh ET group (25%; p = 0.03), as was the live birth rate (60% versus 20%; p = 0.02). Clinical pregnancy rate was numerically, but not significantly, higher after frozen versus fresh ET (70% versus 35%; p = 0.06), while the number of day 3 or good quality embryos, endometrial thickness on the day of oocyte pick-up, implantation rate, and positive pregnancy test rate did not differ significantly between groups. No cases of OHSS were observed, and miscarriage and multiple pregnancy rates were similar in the two groups. CONCLUSIONS: These findings suggest that the effectiveness of CAPA-IVM could be improved considerably by using a freeze-only strategy followed by frozen ET in subsequent cycles. TRIAL REGISTRATION NUMBER: NCT04297553 ( www.clinicaltrials.gov ).

Epidemiology of viral disease outbreaks in Odisha, India (2010-2019).

Despite consistent public health efforts, the burden of viral disease in India remains high. The present study was undertaken to understand the aetiology, frequency and distribution of viral disease outbreaks in the state of Odisha between 2010 and 2019. This was a prospective study conducted at the Virology Research and Diagnostic Laboratory located at ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, wherein all the outbreaks of viral aetiologies were investigated and analysed to provide a comprehensive picture of the state of viral disease outbreaks in the region. A total of 191 suspected viral outbreaks were investigated by the team from VRDL during September 2010 and September 2019 reported from all the 30 districts of Odisha. Annual number of suspected cases ranged from 185 to 1002. The most commonly suspected outbreaks were of viral hepatitis (55 outbreaks; 1223 cases) followed by dengue (45 outbreaks; 1185 cases), chickenpox (30 outbreaks; 421 cases), viral encephalitis (27 outbreaks; 930 cases), measles (23 outbreaks; 464 cases), chikungunya (10 outbreaks; 593 cases) and rubella (1 outbreak; 60). The outbreaks peaked in frequency and intensity during the months of July and September. The epidemiology of viral disease outbreaks in the region is presented in the study. Health system preparedness based on evidence is essential for early detection and adequate response to such viral outbreaks.

A systematic review of nudge theories and strategies used to influence adult health behaviour and outcome in diabetes management.

BACKGROUND: Diabetes is a chronic disease associated with a variety of complications, and nudging may be a potential solution to improve diabetes control. Since nudging is a new concept, no review of literature on nudging diabetic patients into improving their health behaviour has been done. Therefore, we aim to collate a list of nudge intervention and determine the context in which nudging is successful. METHODS: We adopted a two-arm search strategy comprising the search of literature databases and snowballing using relevant search terms. We summarized patient characteristics, the nudge intervention, according to nudging strategies, delivery mode and their outcomes. The conditions present in effective nudge interventions were assessed and reported. RESULTS: We retrieved 11,494 studies from our searches and included 33. An additional five studies were added through snowballing. Studies included utilized framing (n=5), reminders (n=10), gamification (n=2), social modelling (n=5) and social influence (n=16). Studies on reminders and gamification were more likely to have a statistically significant outcome. The targeted health behaviours identified were medication adherence, physical activity, diet, blood glucose monitoring, foot care, self-efficacy, HbA1c and quality of life. Of these, studies with adherence to medication, foot care practice and quality of life as targeted health behaviours were more likely to show a statistically significant outcome. CONCLUSION: Nudging has shown potential in changing health behaviour of patients with diabetes in specific context. We identified two possible factors (delivery mode and patient characteristics) that may affect the effectiveness of nudge intervention.

Molecular and phylogenetic analysis of the dengue strains circulating in Odisha, India.

Dengue has emerged as a major public health challenge in terms of both changing clinical pattern and epidemiological features. The state of Odisha reported first dengue epidemic in the year 2010 and this continued each year in epidemic form during post monsoon period gradually becoming an endemic phenomenon. Present study depicts the changing epidemiological and clinical pattern of dengue with reference to its serotypes and genotypes. The study included 5320 suspected dengue cases from different health facilities of the state during 2010-2017. Dengue NS1 antigen and IgM antibody was done through ELISA. Serotyping was done through RTPCR by amplifying a part of core-pre-membrane gene (CprM) followed by sequencing and phylogenetic analysis. Dengue IgM antibody in 17.7% cases and NS1 antigen in 53.20% cases was detected. Dengue serotype 2 (DEN-2) was the only serotype detected in 2010 and 2011 where as all four serotypes 1, 2, 3, 4 were detected in 2012-2017, DEN-2 being dominant but in 2017 DEN-3 was found to be dominant. Phylogenetic analysis revealed genotype IV of DEN-2 and genotype III of DEN-1 and DEN-3 circulating in this region. In 6 cases involvement of DEN-2 in clinically evident encephalitis cases is an important observation in this region and needs public health attention. High prevalence of dengue was observed without any previous reported outbreaks in the state with increased number of cases from 2010 to 2012 affecting both urban and rural areas. High incidence in 2012 was due to co-circulation of more than one serotype which continued in the following years. Severity in some cases was associated with mixed infection but in most cases it was mild indicating the endemic nature of the virus in most parts of Odisha.

Epidemiological and clinical profile of Influenza A(H1N1) pdm09 in Odisha, eastern India.

Epidemic of flu is highly contagious and it spreads through air. In 2009 H1N1 influenza virus emerged after reassortment of North American TRIG and Eurasia Avian like virus of swine and started epidemic in Mexico. The first cases were reported from Hyderabad city on 16th May 2009 in India that spread rapidly within a short span of time. During this period large population of Odisha situated at the eastern side of India was also affected and incidences of H1N1 cases were recorded through state Government surveillance system. In this study real time RT-PCR based diagnosis was conducted for the throat swabs collected from suspected H1N1 cases in Odisha during 2009-2017. A total of 2872 throat swabs were received from 23 different Government and private hospitals and 21.1% positivity was confirmed. The disease affected mostly 46-60 years age group, males (50.6%) being more affected. The clinical features had shown that fever with cough (89.6%) was the most common symptom followed by shortness of breath (72.7%). Post monsoon was the peak season in which most of the cases were reported. Neurological signs, pregnancy, diabetes and hypertension were found to be risk factors for H1N1. The case fatality rate (CFR) was 15%.

The association between platelet dysfunction and adverse outcomes in cardiac surgical patients.

Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point-of-care-assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass-associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non-functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in-hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two-fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (IQR [range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8-28% [1-99%]) vs. 19% (11-45% [2-98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95%CI 1.006-1.018). This exploratory study suggests that cardiopulmonary bypass-associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Adventure-based training to promote physical activity and reduce fatigue among childhood cancer survivors: A randomized controlled trial.

BACKGROUND: Cancer-related fatigue is one of the most distressing symptoms reported by childhood cancer survivors. Despite the body of evidence that regular physical activity helps alleviate cancer-related fatigue, insufficient participation in physical activity is frequently observed among childhood cancer survivors. OBJECTIVES: This study examined the effectiveness of an adventure-based training programme in promoting physical activity, reducing fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. DESIGN: A prospective randomised controlled trial. SETTINGS: A paediatric oncology outpatient clinic, a non-governmental organisation, and a non-profit voluntary organisation. PARTICIPANTS: Hong Kong Chinese childhood cancer survivors aged 9-16 years who reported symptoms of fatigue and had not engaged in regular physical exercise in the past 6 months. METHODS: The experimental group underwent a 4-day adventure-based training programme. The control group received a placebo intervention. The primary outcome was fatigue at 12 months. Secondary outcomes were physical activity levels, self-efficacy and quality of life at 12 months. Data collection was conducted at baseline, and 6 and 12 months after the intervention began. We performed intention-to-treat analyses. RESULTS: From 6 January, 2014 to 8 June, 2015, we randomly assigned 222 eligible childhood cancer survivors to either an experimental (n = 117) or a control group (n = 105). The experimental group showed statistically significantly lower levels of cancer-related fatigue (P < 0.001), higher levels of self-efficacy (P < 0.001) and physical activity (P < 0.001), and better quality of life (P < 0.01) than the control group at 12 months. CONCLUSIONS: This study provides evidence that adventure-based training is effective in promoting physical activity, reducing cancer-related fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. These results may help inform parents and healthcare professionals that regular physical activity is crucial for the physical and psychological wellbeing and quality of life of childhood cancer survivors.