High Responders Research Articles

Individual Postprandial Glycemic Responses to Meal Types by Different Carbohydrate Levels and Their Associations with Glycemic Variability Using Continuous Glucose Monitoring.

This study aimed to investigate individual postprandial glycemic responses (PPGRs) to meal types with varying carbohydrate levels and examine their associations with 14-day glycemic variability using continuous glucose monitoring (CGM) in young adults. In a two-week intervention study with 34 participants connected to CGM, four meal types and glucose 75 g were tested. PPGRs were recorded for up to 2 h with a 15 min interval after meals. Data-driven cluster analysis was used to group individual PPGRs for each meal type, and correlation analysis was performed of 14-day glycemic variability and control with related factors. Participants had a mean age of 22.5 years, with 22.8% being male. Four meal types were chosen according to carbohydrate levels. The mean glucose excursion for all meal types, except the fruit bowl, exhibited a similar curve with attenuation. Individuals classified as high responders for each meal type exhibited sustained peak glucose levels for a longer duration compared to low responders, especially in meals with carbohydrate contents above 50%. A meal with 45% carbohydrate content showed no correlation with either 14-day glycemic variability or control. Understanding the glycemic response to carbohydrate-rich meals and adopting a meal-based approach when planning diets are crucial to improving glycemic variability and control.

Fuzzy Logic System for Classifying Multiple Sclerosis Patients as High, Medium, or Low Responders to Interferon-Beta

Interferon-beta is one of the most widely prescribed disease-modifying therapies for multiple sclerosis patients. However, this treatment is only partially effective, and a significant proportion of patients do not respond to this drug. This paper proposes an alternative fuzzy logic system, based on the opinion of a neurology expert, to classify relapsing–remitting multiple sclerosis patients as high, medium, or low responders to interferon-beta. Also, a pipeline prediction model trained with biomarkers associated with interferon-beta responses is proposed, for predicting whether patients are potential candidates to be treated with this drug, in order to avoid ineffective therapies. The classification results showed that the fuzzy system presented 100% efficiency, compared to an unsupervised hierarchical clustering method (52%). So, the performance of the prediction model was evaluated, and 0.8 testing accuracy was achieved. Hence, a pipeline model, including data standardization, data compression, and a learning algorithm, could be a useful tool for getting reliable predictions about responses to interferon-beta.

Fronto-striatal dynamic connectivity is linked to dopaminergic motor response in Parkinson's disease

IntroductionDifferences in dopaminergic motor response in Parkinson's disease (PD) patients can be related to PD subtypes, and previous fMRI studies associated dopaminergic motor response with corticostriatal functional connectivity. While traditional fMRI analyses have assessed the mean connectivity between regions of interest, an important aspect driving dopaminergic response might lie in the temporal dynamics in corticostriatal connections. MethodsThis study aims to determine if altered resting-state dynamic functional network connectivity (DFC) is associated with dopaminergic motor response. To test this, static and DFC were assessed in 32 PD patients and 18 healthy controls (HC). Patients were grouped as low and high responders using a median split of their dopaminergic motor response. ResultsPatients featuring a high dopaminergic motor response were observed to spend more time in a regionally integrated state compared to HC. Furthermore, DFC between the anterior midcingulate cortex/dorsal anterior cingulate cortex (aMCC/dACC) and putamen was lower in low responders during a more segregated state and correlated with dopaminergic motor response. ConclusionThe findings of this study revealed that temporal dynamics of fronto-striatal connectivity are associated with clinically relevant information, which may be considered when assessing functional connectivity between regions involved in motor initiation.

Reducing Alcohol Use Before and After Surgery: Qualitative Study of Two Treatment Approaches.

High-risk alcohol use is a common preventable risk factor for postoperative complications, admission to intensive care, and longer hospital stays. Short-term abstinence from alcohol use (2 to 4 weeks) prior to surgery is linked to a lower likelihood of postoperative complications. The study aimed to explore the acceptability and feasibility of 2 brief counseling approaches to reduce alcohol use in elective surgical patients with high-risk alcohol use in the perioperative period. A semistructured interview study was conducted with a group of "high responders" (who reduced alcohol use ≥50% postbaseline) and "low responders" (who reduced alcohol use by ≤25% postbaseline) after their completion of a pilot trial to explore the acceptability and perceived impacts on drinking behaviors of the 2 counseling interventions delivered remotely by phone or video call. Interview transcripts were analyzed using thematic analysis. In total, 19 participants (10 high responders and 9 low responders) from the parent trial took part in interviews. Three main themes were identified: (1) the intervention content was novel and impactful, (2) the choice of intervention modality enhanced participant engagement in the intervention, and (3) factors external to the interventions also influenced alcohol use. The findings support the acceptability of both high- and low-intensity brief counseling approaches. Elective surgical patients are interested in receiving alcohol-focused education, and further research is needed to test the effectiveness of these interventions in reducing drinking before and after surgery. ClinicalTrials.gov NCT03929562; https://clinicaltrials.gov/ct2/show/NCT03929562.

Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population.

Vaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination. In total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression. Significant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%). The candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules.

Frequency of B-Cell Subpopulations in Low Responders in Comparison with High Responders to Hepatitis B Vaccine Among Health Care Workers.

Vaccination is the most effective way to prevent Hepatitis B (HB) infection. The goal of vaccination is to induce immunological memory. Hence, determining the frequency of memory B-cell (MBC) subsets is an important indicator of vaccine efficacy. This study aimed to evaluate the frequency of different B-cell subpopulations and the expression of PD-1 on B-cell subsets in low responders (LR) and high responders (HR) to HB vaccine. According to our findings, the expression level of PD-1 was significantly higher on atypical MBC (atMBC) than that of naive B cell and classical MBC (cMBC) in LR and HR groups. Moreover, cMBCs had a significant higher PD-1 expression than naive B cells in LR group. No significant differences were found in the frequency of various B-cell subpopulations and the expression level of PD-1 on B-cell subsets between LR and HR groups. We observed a negative correlation between age and HBsAb titer and a positive correlation between age and PD-1 expression level on cMBC in LR group. It can be concluded that inadequate specific memory B-cell response, rather than total memory B-cell deficiency, may be implicated in low responsive rate to HB vaccine in healthy individuals.

Subacute aphasia recovery is associated with resting-state connectivity within and beyond the language network.

To examine changes to connectivity after aphasia treatment in the first 3 months after stroke. Twenty people experiencing aphasia within the first 3 months of stroke completed MRI before and immediately following 15 hours of language treatment. They were classified based on their response to treatment on a naming test of nouns as either high responders (10% improvement or more), or low responders (<10% improvement). Groups were similar in age, gender distribution, education, days since stroke, stroke volume, and baseline severity. Resting-state functional connectivity analysis was limited to the connectivity of the left fusiform gyrus with the bilateral inferior frontal gyrus, supramarginal gyrus, angular gyrus, and superior, middle, and inferior temporal gyrus, based on previous studies showing the importance of left fusiform gyrus in naming performance. Baseline ipsilateral connectivity between the left fusiform gyrus and the language network was similar between high and low responders to therapy when controlling for stroke volume. Following therapy, change in connectivity was significantly greater among high responders between the left fusiform gyrus and the ipsilateral and contralateral pars triangularis, ipsilateral pars opercularis and superior temporal gyrus, and contralateral angular gyrus when compared with low responders. An account of these findings incorporates primarily proximal connectivity restoration, but also potentially reflects select contralateral compensatory reorganization. The latter is often associated with chronic recovery, reflecting the transitional nature of the subacute period.

RNA-Seq Analysis of Peripheral Whole Blood from Dairy Bulls with High and Low Antibody-Mediated Immune Responses-A Preliminary Study.

Enhancing the immune response through breeding is regarded as an effective strategy for improving animal health, as dairy cattle identified as high immune responders are reported to have a decreased prevalence of economically significant diseases. The identification of differentially expressed genes (DEGs) associated with immune responses might be an effective tool for breeding healthy dairy cattle. In this study, antibody-mediated immune responses (AMIRs) were induced by the immunization of hen egg white lysozyme (HEWL) in six Chinese Holstein dairy bulls divided into high- and low-AMIR groups based on their HEWL antibody level. Then, RNA-seq was applied to explore the transcriptome of peripheral whole blood between the two comparison groups. As a result, several major upregulated and downregulated genes were identified and attributed to the regulation of locomotion, tissue development, immune response, and detoxification. In addition, the result of the KEGG pathway analysis revealed that most DEGs were enriched in pathways related to disease, inflammation, and immune response, including antigen processing and presentation, Staphylococcus aureus infection, intestinal immune network for IgA production, cytokine-cytokine receptor interaction, and complement and coagulation cascades. Moreover, six genes (BOLA-DQA5, C5, CXCL2, HBA, LTF, and COL1A1) were validated using RT-qPCR, which may provide information for genomic selection in breeding programs. These results broaden the knowledge of the immune response mechanism in dairy bulls, which has strong implications for breeding cattle with an enhanced AMIR.

Dose Nomogram of Individualization of the Initial Follicle-Stimulating Hormone Dosage for Patients with Polycystic Ovary Syndrome Undergoing IVF/ICSI with the GnRH-Ant Protocol: A Retrospective Cohort Study.

For high responders with polycystic ovary syndrome (PCOS), there is no clear recommendation for the initial follicle-stimulating hormone (FSH) dosage to ensure an optimal number of retrieved oocytes and avoid ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine the ideal initial FSH dosage of in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) using the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol to obtain the optimal number of retrieved oocytes and minimize the risk of OHSS. The data of 1898 patients with PCOS aged 20-40years from January 2017 to December 2020 were retrospectively analyzed to explore the factors related to the number of retrieved oocytes. Statistically significant variables were used to construct a dose nomogram and it was then validated using an independent cohort of patients with PCOS from January 2021 to December 2021. Multivariate analyses demonstrated that body mass index (BMI) was the most significant factor to predict the number of retrieved oocytes compared to body weight (BW) and body surface area (BSA). Among patients with PCOS aged 20-40years undergoing their first IVF cycles with the GnRH-ant protocol, age was not a significant predictor of the initial FSH dosage. We developed a nomogram based on BMI, basal FSH, basal luteinizing hormone (bLH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) to calculate the ideal initial FSH dosage for patients with PCOS undergoing IVF/ICSI using the GnRH-ant protocol. In addition, low BMI and high bLH and AMH levels and AFC appear to be risk factors for OHSS. We clearly demonstrated that the initial FSH dosage for patients with PCOS undergoing IVF/ICSI with the GnRH-ant protocol may be calculated on the basis of the woman's BMI and ovarian reserve markers. The nomogram will help guide clinicians in the selection of the most appropriate initial FSH dose in the future.

Experiential Learning and Self-Efficacy in Physical Education of the Senior High School Students

This study aimed to determine the level of involvement of senior high school students in experiential learning and also to determine of their described self-efficacy in physical education. This employed the research and descriptive correlation design of quantitative method as participated by three hundred fifty (350) senior high school respondents in San Isidro National High School who were chosen using purposive sampling procedures. The data were gathered using survey questionnaires which are validated with the help of the experts. Data communication was established before data gathering procedures and was analyzed using weighted mean, standard deviation, and Pearson’s r. &#x0D; Findings revealed that senior high school students agreed that they were involved in experiential learning. Students enhanced and boosted their self-efficacy through the use of mastery experiences, social modeling, social persuasions, and psychological responses. It was concluded that there’s a significant and strong positive correlation between experiential learning and students’ self-efficacy. It implied that as the students engage more in experiential learning, the higher the chance the students’ self-efficacy developed. Otherwise, the lesser engagement in experiential learning, the lower of chance developing self-efficacy. Based on the conclusion, it was recommended that the teachers are also recommended to motivate their students in involving experiential for them to mold and described their self-efficacy in engaging in physical activities.

P-205 comparison of GnRH antagonist protocol versus progestin-primed protocol in high ovarian responders: a propensity score-matched study

Abstract Study question To compare the clinical outcomes and cost-efficiency between gonadotropin-releasing hormone (GnRH) antagonist and progestin-primed ovarian stimulation (PPOS) protocol in high ovarian responders. Summary answer Comparing with PPOS protocol, GnRH antagonist protocol was associated with shorter time to live birth, higher OHSS rate and less cost in high responders. What is known already For high ovarian responders prone to develop ovarian hyperstimulation syndrome (OHSS), the best option should be the GnRH antagonist, as it has been shown to significantly reduce the incidence of OHSS. By applying ovarian stimulation using the combination of antagonist with agonist trigger and embryos freezing, OHSS can be erased. PPOS protocol in combination with a freeze-all strategy has proved to be a valid alternative to the conventional stimulation protocols. Recent studies showed that comparing with antagonist protocol, a lower cumulative live birth rate (CLBR) was associated with PPOS in general population, with no data available in high responders. Study design, size, duration This was a propensity score-matched retrospective cohort study. From Jan. 2016 to Jan. 2023, 5810 patients with AMH &amp;gt; 3.67ng/ml undergoing IVF treatment with antagonist or PPOS protocol at the Sixth Affiliated Hospital of Sun Yat-sen University were screened. Participants/materials, setting, methods Two-to-one propensity score matching was performed with a caliper of 0.2. After matching, 540 patients in GnRH antagonist group and 270 patients in PPOS group were included. Generalized estimated equation regression was applied to evaluate the impact of independent variables on the CLBR. Main results and the role of chance No significant difference in baseline characteristics was found in two groups. The OHSS (moderate to severe) rate was significantly higher in the GnRH antagonist group than in the PPOS group (7% vs. 3%). The clinical pregnancy rate and live birth rate per transfer were comparable between the two groups. After excluding patients who didn't achieve live birth but had surplus embryos, the CLBR was comparable between the antagonist and PPOS group (67.4% vs. 61.0%; Risk ratio = 1.106; 95% confidence interval [CI], 0.973-1.256, P = 0.109), and the generalized estimated equation regression analysis also showed that protocol selection had no significant impact on CLBR. The average time to live birth (TTLB) in the antagonist group was significantly shorter than the PPOS group (11.45 months vs. 12.13 months, P &amp;lt; 0.05). Besides, the average cost in the antagonist group was about $4933, while it was about $5465 in the PPOS group. Limitations, reasons for caution Although we recruited a large sample size and the sophisticate statistical analysis method, this was a retrospective study with an intrinsic limitation, besides more patients in the PPOS group had surplus embryos than in the antagonist group (24.1% vs. 19.8%). Further prospective RCTs are required to confirm our findings. Wider implications of the findings For infertile patients with high ovarian reserve, the clinical outcomes were comparable between GnRH antagonist and PPOS group. The antagonist group was associated with a shorter TTLB and more cost-effective, while the PPOS was associated with a lower OHSS rate. Trial registration number Not Applicable

P-680 Oocyte maturation triggering protocols in in vitro fertilisation treatment: a systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of final oocyte maturation trigger protocols in women undergoing in vitro fertilisation (IVF) treatment? Summary answer OHSS rate was lowest with GnRH agonist trigger and no difference in LBR was observed comparing various trigger protocols in normal, high and poor responders. What is known already Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation(OS). Pituitary suppression is an important component of OS in IVF, involving the use of GnRH analogues. Currently, the GnRH antagonist regimen is predominantly used given its comparable efficacy and lower risk of OHSS compared with GnRH agonist (GnRHa) regimens. Whilst only hCG trigger can be used with GnRH agonist regimens, GnRH antagonist regimen enables use of hCG trigger, GnRH agonist trigger or combinations of both as dual or double trigger. However, there is no consensus on how these trigger protocols compare in their effectiveness and safety. Study design, size, duration The following databases were searched until August 2022: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger (hCG and GnRH agonist administered at the same time) and double trigger (GnRH agonist followed by hCG after a time interval) with the antagonist regimen were included. Primary outcome was live birth (LBR) per participant. Secondary outcomes included number of oocytes and OHSS rates. Participants/materials, setting, methods Two reviewers independently screened, selected studies and extracted data. Pairwise and network meta-analyses (NMA) were conducted according to ovarian response groups (normal, high and poor response). Effect estimates were presented as weighted means difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) for continuous and dichotomous outcomes respectively. Quality assessment was performed using GRADE Main results and the role of chance Initial searches identified 4225 studies, of which 54 RCTs involving 5838 women met the inclusion criteria to be included in the analysis. In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, direct comparison(DC)),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;indirect comparison(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2 = 44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2 = 37%, low-certainty evidence, DC), double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49,95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence,DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women,low-certainty evidence,DC). OHSS rates were lowest with the use of GnRHa in high responders (RR:0.39,95%CI:0.04-3.78;9 studies;960 women;I2 =43%, low-certainty evidence,DC) and normal responders (RR:0.88, 95%CI:0.78 to 0.99;7 studies; 2246 women; I2=0%, low-certainty evidence,DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. Limitations, reasons for caution Stratifying results by predicted ovarian response resulted in disconnected networks, limiting our ability to perform NMA for certain groups and outcomes. The certainty of the evidence was limited by high risk of bias. Wider implications of the findings Our results suggest that the use of short GnRH agonist trigger results in reduced OHSS rates in women with predicted normal or high ovarian response. There is no difference in LBR and number of oocytes comparing the different trigger protocols in all response groups (normal, high, poor responders) Trial registration number Not applicable

P-645 standard- and low-dose dual trigger compared with human chorionic gonadotropin trigger in preimplantation genetic testing cycles

Abstract Study question Standard-dose dual trigger (SDT) and low-dose dual trigger (LDT) could improve the number of oocytes, blastocysts and euploid blastocysts or not compared with hCG trigger. Summary answer LDT increased the number of oocytes and blastocysts but not euploid blastocysts among high ovarian responders, while SDT cannot help poor to normal ovarian responders. What is known already For low and normal responders, hCG trigger was recommended by the ESHRE guidelines for ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) in 2020. For high responders, this guideline recommended gonadotropin-releasing hormone agonist (GnRH-a) as the first-choice treatment. While recent studies showed that SDT could increase the number of oocytes and blastocysts to achieve equivalent or better pregnancy outcomes among poor and normal ovarian responders. And LDT was designed to prevent severe ovarian hyperstimulation syndrome (OHSS) while guaranteeing embryo quality among high responders by previous studies. Study design, size, duration This retrospective cohort study was performed at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from July 2018 to December 2021. A total of 2,649 IVF-PGT cycles involving 2,275 patients were analyzed, of which 2,270 cycles had complete baseline data. A total of 1,131, 715, and 424 cycles were included in the hCG trigger, SDT, and LDT groups, respectively. Participants/materials, setting, methods Patients who were triggered by SDT(triptorelin acetate 0.2 mg and rhCG 250 µg), LDT(triptorelin acetate 0.2 mg and rhCG 125 µg or hCG 2,000 IU), and hCG (rhCG 250 µg) with GnRH-antagonist stimulation protocol in IVF-PGT cycles were enrolled. The number of oocytes retrieved, blastocysts, and euploid blastocysts were compared as primary endpoints. Propensity score matching (PSM) was used to control for confounding factors of retrospective study. Main results and the role of chance The SDT and hCG groups had a comparable number of oocytes retrieved (11.0 [7.0, 16.0] vs. 11.0 [7.0, 15.0], p = 0.580), blastocysts (2.0 [1.0, 3.0] vs. 2.0 [1.0, 3.0], p = 0.517), and euploid blastocysts (1.0 [0.0, 2.0] vs. 1.0 [0.0, 2.0], p = 0.383) after PSM. LDT increased the number of oocytes retrieved (19.0 [14.0, 25.0] vs. 16.0 [12.0, 21.0], p &amp;lt; 0.001) and blastocysts (3.0 [2.0, 6.0] vs. 3.0 [2.0, 5.0], p = 0.001), but not euploid blastocysts (2.0 [1.0, 3.0] vs. 1.0 [1.0, 3.0], p = 0.111), compared with the hCG trigger after PSM. Limitations, reasons for caution This was a single-center retrospective cohort study. The baseline characteristics of SDT and LDT differed from those of the hCG group because of clinical decision preferences. PSM was used to control for these effects and generate a balanced cohort. Pregnancy outcomes after embryo transfer has not been assessed yet. Wider implications of the findings The hormone change curve induced by LDT is more similar to the natural cycle. Probably LDT could also benefit poor to normal ovarian responders in IVF/ICSI cycles. And LDT might help in fresh embryo transfer cycles because of its advantage on endometrial receptivity. Trial registration number the National Natural Science Foundation of China (Grant No.82171626)

P-592 Follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger in oocyte cryopreservation cycles

Abstract Study question Can follicular GnRH agonist administration predict suboptimal response to GnRH agonist trigger assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program? Summary answer Follicular agonist challenge test (FACT) can serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist trigger. What is known already Suboptimal response to GnRH agonist ovulation trigger refers to failure to retrieve the expected number of oocytes. It was demonstrated in up to 5.5% of cycles based on relatively low number of studies with heterogenous suboptimal response definitions and prevalence, no clear cut-offs and mainly post - stimulation tools to predict unsuccessful cycle. The most studied variable associated with suboptimal response was LH levels 10-12 hours after ovulation trigger below 12-15IU. Study design, size, duration We prospectively recruited all women that underwent non-medical fertility preservation in our tertiary university affiliated medical center between October 2020 and February 2022 and agreed to participate in the study. The study included 91 women. Participants/materials, setting, methods On day 2 to menstrual cycle, blood tests were drawn (basal Estradiol/E2, basal FSH/FSH2, basal LH/LH2, Progesterone/P2) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist and arrive for repeated blood workup 10-12 hours later at the next morning, followed by a flexible antagonist protocol. On the morning after ovulation trigger blood tests were again taken and LH levels were compared to FACT LH levels. Main results and the role of chance LH levels following agonist ovulation trigger below 15IU occurred in 1.09 % of cycles and were predicted by FACT, r = 0.57, p &amp;lt; 0.001. ROC analysis demonstrated that FACT LH &amp;gt; 42.70 IU would predict LH post trigger of more than 30 IU with 75% sensitivity and 70% specificity, AUC= 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p &amp;lt; 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the total number of retrieved oocytes and mature oocytes was progesterone level post ovulation trigger (r = 0.74, p &amp;lt; 0.001). Limitations, reasons for caution Limitation of our study include the relatively small sample size designed to detect 5% suboptimal proportion and might have been insufficient to allow identification of very rare suboptimal responses Wider implications of the findings Suboptimal response to agonist trigger, as assessed with post trigger LH levels is a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders. Trial registration number 0304-20-ASF

P-616 Evaluation of salivary ELISA for Oestradiol and Progesterone monitoring in IVF patients

Abstract Study question How do salivary E2 and P correlate with serum determinations across ovarian stimulation (OS) for IVF and artificial endometrial preparation cycles for embryo transfer? Summary answer Saliva-blood correlations were higher for E2 than for P. E2 saliva-blood ratios were patient-dependent. High serum P cases on trigger day could be identified. What is known already Steroid hormone concentrations in saliva are lower than in serum, even if the hormone is predominantly free. Therefore, quantitative assays need to be as sensitive as possible. Saliva-based assessments are a reliable and proven method for quantifying female hormone levels in premenopausal women during the natural cycle while being very precise and painless for patients. However, the cumulative experience in ovarian stimulation is relatively low. A recent study including 652 pairs of saliva-serum E2 samples reported correlations between 0.68 and 0.91, while 237 pairs of samples for P showed correlations ranging from -0.02 to 0.22 (Sakkas et al, 2020). Study design, size, duration Prospective cohort study including 300 saliva-blood pair samples from 120 patients undergoing OS for IVF (n = 90) or artificial endometrial preparation for embryo transfer (n = 30) between February and October 2022. Data were collected at each of 3 points of OS: early (days 1-5), mid (days 6-9), and trigger. Patients following endometrial preparation collected just one sample on the day of embryo transfer Participants/materials, setting, methods Thirty expected poor responders, 30 normal, and 30 expected high responders according to ovarian reserve evaluation were included. Two saliva samples per blood sample were collected: immediately after waking up, and at the clinic just before or after the blood sample was taken. Saliva samples were stored at -20ºC and shipped to Mint Diagnostics (Kent, UK) for analysis of salivary E2 and P4 Main results and the role of chance Saliva-blood E2 correlations (Spearman) were 0.68 (fasting) and 0.69 (clinic). 72% of individuals showed saliva-serum correlations &amp;gt; 0.8. Correlations improved when controlling for subgroup (low, normal, high responders). P4 saliva-blood correlations (Spearman) were 0.44 (fasting) and 0.29 (clinic). 41% of individuals showed correlations &amp;gt;0.8 on fasting samples, and 33% on clinic samples. There was a high variance of individual correlations (0-1), which were dependent on ovarian response subgroups (p &amp;lt; 0.05). A multivariable approach was developed to identify patients with a serum P4&amp;gt;1.5 ng/mL the day of trigger (n = 11) with clinic samples showing 81% sensitivity and 91% specificity and fasting samples showing 83% and 91% respectively demonstrating the possibility of shifting hormone analysis to the home rather than the clinic. Eighteen of 30 (60%) saliva samples collected on the day of ET on patients under hormonal replacement therapy showed values out of the assay range (&amp;gt;5000 pg/mL). Therefore, no correlations could be estimated. Limitations, reasons for caution Detection of patients with high P4 on the day of trigger was limited due to a short number of cases. No conclusions could be drawn in HRT patients for embryo transfer due to high salivary P4 values. Wider implications of the findings The current study shows that salivary monitoring of E2 and P4 is feasible. This more friendly non-invasive method could allow frequent hormone monitoring without the need for appointments at the clinic and for phlebotomy, thus resulting in more convenience for both the clinics and the patients. Trial registration number NCT05184777

P-666 High embryo yield (and not oocyte yield) despite low ovarian stimulation dose correlates with cumulative livebirth rate in normal-high responders undergoing IVF/ICSI

Abstract Study question Does a good response i.e., high oocyte or embryo yield with low ovarian stimulation correlate with cumulative live birth outcome in IVF/ ICSI treatment? Summary answer High ovarian sensitivity to stimulation (embryos to gonadotropin dose ratio) positively predicts cumulative live birth in IVF, while oocytes to stimulation dose ratio does not. What is known already The conventional belief that the higher the number of eggs retrieved, the better for IVF outcome has been challenged. Oocyte yield fails to predict fresh-cycle live birth in presence of high ovarian response. Ovarian sensitivity index (OSI) which is an expression of inherent ovarian responsiveness to stimulation remained overlooked as a predictor of success in IVF. We explore whether attention should be on the oocyte or embryo yield as a function of ovarian stimulation (OSI) can predictor of positive outcomes in IVF. Study design, size, duration Retrospective analysis of 750 patients who underwent IVF/ ICSI treatment with ≤150 IU of gonadotropin in an antagonist protocol due to predicted normal or high response. This is a further analysis of a previously published study covering a period between 1 January 2016 to 31 Dec 2018. Participants/materials, setting, methods Multi-centre study within a group company using the same treatment protocols. Participants were normal or high responders of IVF/ ICSI, predicted poor responders (according to Bologna criteria) were excluded. All patients received ≤150 IU daily dose of gonadotropin (FSH) in an antagonist cycle. Cumulative LBR calculated. Univariate and multivariate (regression) analysis, adjusting for all significant variables were done to find the predictors of cumulative livebirth. Main results and the role of chance When the women who achieved a livebirth were compared with those who did not, there was no difference in the mean BMI (23.7 vs 23.6, p = 0.81), antral follicle counts (p = 0.33), Anti-mullerian hormone levels (p = 0,89), mean starting (149.5 vs 140.5 IU/ day, p = 0.16), and total gonadotropin doses (1360.7 vs 1342.8 IU, p = 0.62). Women’s age (33.5 vs 35.3 years, p &amp;lt; 0.0001) and the number of embryos transferred (p &amp;lt; 0.0001) had significantly correlation with LBRs. There was no difference in the mean number of oocyte (9.1 vs 8,6, p = 0.21) or oocyte yield per unit of gonadotropin (7.4 vs 6.7, p = 0.32).. The mean number of embryos (5.4 vs 4.1, p &amp;lt; 0.0001), transferable embryos (2.5 vs 1.9, p = 0.0006) and embryo yield per unit of gonadotropin (4.1 vs 3.2, p &amp;lt; 0.0001) were significantly higher in the livebirth group. After adjusting for woman’s age and the number of embryos transferred, the embryo yield (both total (p &amp;lt; 0.0001) and transferable (p = 0.01) embryos and embryo yield per gonadotropin unit (p = 0.0007) were predictors of cumulative livebirth whereas oocyte yield and oocyte number per unit of gonadotropin were not. The above findings remained the same when only IVF cycles excluding male infertility or only the cycles with a fixed 150 IU/d gonadotropin dose were analysed. Limitations, reasons for caution A moderate-sized study population. The poor responders have been excluded to minimise variations in the protocol and stimulation dose. Wider implications of the findings Our study is a proof of concept of ‘ovarian sensitivity index’ indicating the inherent ovarian responsiveness rather than the strength of stimulation determines the IVF/ICSI outcome. Embryo yield appeared to be a predictor of cumulative livebirth while oocyte yield is not, in normal and high responders of IVF. Trial registration number Not applicable

Qualitative Analysis of Barriers and Facilitators to Glaucoma Medication Adherence in a Randomized Controlled Trial Intervention

In the Medication Adherence In Glaucoma To Improve Care trial, 200 veterans with medically-treated glaucoma were randomized to an intervention designed to improve glaucoma medication adherence or to usual care. In the 6 months after intervention, the mean proportion of doses taken on schedule was higher for participants in the intervention group compared with controls (0.85 vs. 0.62, P < 0.001). The purpose of this study was to use a mixed-methods approach to compare barriers and facilitators with adherence among participants through qualitative analysis of structured interviews. This is an analysis of interviews conducted from patients participating in a clinical trial. Participants from the intervention arm were separated into quartiles based on medication adherence according to the electronic monitor to sample from high and low responders to the intervention. We interviewed 23 participants; 11 participants with low adherence and 12 with high adherence. Interviews were conducted over telephone and transcribed. Staff members used grounded theory to conduct content analysis and code the transcribed interviews. The iterative process produced categories of common barriers and facilitators for medication adherence. The frequency of responses addressing common barriers and facilitators were compared between participants with high and low adherence. In the lowest- and highest-adherence groups, a difficult schedule was the most cited barrier for regular drop usage (63.6% and 58.3%, respectively). In the lowest and highest-adherence groups, the most cited facilitator for adherence was use of the smart bottle (100% and 91.7%, respectively). In the lowest-adherence group, 72.7% of participants cited that improved ability to administer drops was a benefit from the intervention. In the highest-adherence group, 75% of participants cited increased disease knowledge and formation of habits as facilitators from the intervention. Of the 22 of 23 participants who mentioned the smart bottle, 100% cited that they had increased adherence and would continue using the smart bottle. Using dosing reminders and personalized patient education may be important avenues for addressing difficulties with adhering to an eye drop schedule to improve glaucoma self-management. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Heterogeneous circulating tumor cells correlate with responses to neoadjuvant chemotherapy and prognosis in patients with locally advanced breast cancer.

Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The predictive value of heterogeneous circulating tumor cells (CTCs) in NCT response has not been determined. All patients were staged as LABC, and blood samples were collected at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i·FISH strategy was applied to detect CTCs. Heterogeneities were successfully analyzed in patients undergoing NCT. Total CTCs increased continuously and were higher in Low-R group, while in High-R group, CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 increased in Low-R but not High-R group. The number of small CTCs in Low-R group increased significantly until the last sample, however, remained constant in High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the eighth course of NCT. Total CTCs following NCT could predict patients' responses. More detailed characterizations of CTC blood profiles may improve predictive capacity and treatments of LABC.

Skin conductance responses to oral stimuli: The role of taste quality and intensity, and personality traits

Measuring emotional responses to tastes and foods, using both self-reports and also implicit and physiological measurements is gaining attention. Among physiological measurements, skin conductance response (SCR) is one the most commonly used indicators of emotional activation but it has been rarely applied to taste and other oral stimuli and its interpretation is not yet clear. Furthermore, the effect of individual differences in SCR to tastes has been rarely taken into account. To address these issues, SCR to bitter, astringent, and sweet samples presented both at weak/moderate and moderate/strong intensity was recorded while eighty Italians, selected based on PROP (6-n-propylthiouracil) status (only Medium-Tasters), performed an implicit affective test. Samples were presented blind in aqueous solutions monadically in triplicate. Subjects (Ss) were asked to taste a sample, then a neutral face was briefly presented on a screen, and Ss were asked to indicate if they trusted the face (yes/no) and how much (on a 9-point Scale). Data on Ss’ psychological traits (anxiety, sensation seeking, food neophobia, emotional stability) was also collected. Two clusters were identified based individual SCR. These clusters differed in their SCR mainly to strong bitterness, and partially to astringency, while they did not differ for their response to the sweet samples. The High bitter responders were more anxious and neurotic than Low bitter responders. For this cluster higher intensities induced higher SCR, but this was not found in the Low bitter responders cluster that tended to have higher SCR to the least intense samples. No differences in the implicit affective responses to samples were found between clusters. These results indicate that SCR to tastes reflect mainly different sources of arousal, such as novelty/surprisingness, quality and intensity of the stimuli, and this may change at an individual level. This suggests that measurement of SC can contribute to a better understanding of individual differences in taste and oral experience and could provide a link between taste responsiveness and sympathetic nervous system activity.

Significance of effective cardiac resynchronization therapy pacing for clinical responses: An analysis based on the effective cardiac resynchronization therapy algorithm

High percent ventricular pacing maximizes cardiac resynchronization therapy (CRT) response. An effective CRT algorithm classifies each left ventricular (LV) pace as effective or ineffective on the basis of the detection of QS or QS-r morphology on the electrogram; however, the relationship between percent effective CRT pacing (%e-CRT) and responses is unclear. We aimed to clarify the association between %e-CRT and clinical outcomes. Of the 136 consecutive CRT patients, 49 using the adaptive and effective CRT algorithm with percent ventricular pacing > 90% were evaluated. The primary and secondary outcomes were heart failure (HF) hospitalization and prevalence of CRT responders, defined as patients with an improvement in LV ejection fraction of ≥10% or a reduction in LV end-systolic volume of ≥15% after CRT device implantation, respectively. We divided the patients into the effective group (n = 25) and the less effective group (n = 24) by the median value of %e-CRT (97.4%). During the median follow-up period of 507 days (interquartile range 335-730 days), the effective group had a significantly lower risk of HF hospitalization than did the less effective group as revealed by Kaplan-Meier analysis (log-rank, P = .016). Univariate analysis revealed %e-CRT ≥ 97.4% (hazard ratio 0.12; 95% confidence interval 0.01-0.95; P = .045) as a predictor of HF hospitalization. The effective group had a higher prevalence of CRT responders than did the less effective group (23 [92%] vs 9 [38%]; P < .001). Univariate analysis revealed that %e-CRT ≥ 97.4% (odds ratio 19.20; 95% confidence interval 3.63-101.00; P < .001) was a predictor of CRT response. High %e-CRT is associated with high CRT responder prevalence and low HF hospitalization risk.