Marker Of Reserve Research Articles

Association of frailty with clinical and financial outcomes of allogeneic hematopoietic stem cell transplant.

7046 Background: Considered the only curative therapy for many hematological conditions, allogeneic hematopoietic stem cell transplantation (alloHSCT) is increasingly used in older patients. Yet, chronological age alone has been found to be an inaccurate predictor of posttransplant sequelae. More recently, the concept of frailty has emerged as a better marker of physiologic reserve. While formal frailty instruments have not been widely adopted due to their resource intensive nature, we applied a previously-validated coding-based approach to examine the association of frailty with in-hospital outcomes of alloHSCT. Methods: All adults (≥ 18 years) undergoing alloHSCT for hematological malignancies were identified in the 2010-2019 Nationwide Readmissions Database. The previously-validated binary Johns Hopkins Adjusted Clinical Groups indicator was used to classify patients as frail. In this algorithm, the presence of diagnoses across various domains, including malnutrition, dementia, and decubitus ulcer, constitute frailty. Regression models were developed to evaluate the independent association of frailty with in-hospital mortality, periprocedural complications, length of stay, hospitalization costs, and 30-day non-elective readmissions. Results: Of an estimated 48,161 patients, 9.8% were considered frail. Frail patients were not significantly older (51.8 ± 15.0 vs 51.6 ± 14.2, p = 0.685), but had higher Elixhauser scores (2.8 ± 1.3 vs 2.0 ± 1.3, p < 0.001). After adjustment, frailty was associated with increased odds of in-hospital mortality (AOR 2.22; 95% CI 1.68-2.94; P < 0.001), as well as infectious (AOR 1.44, 95% CI 1.18-1.76; P < 0.001) and respiratory (AOR 1.69, 95% CI 1.41-2.02; P < 0.001) complications. Frailty was also associated with greater risk of acute graft-vs-host disease (AOR 1.39, 95% CI 1.12-1.72; P = 0.003) and CMV (AOR 1.72, 95% CI 1.27-2.33; P < 0.001) or invasive fungal infection (AOR 1.49, 95% CI 1.07-2.06; P = 0.017). Further, frailty was linked to increased likelihood of non-home discharge (AOR 1.29, 95% CI 1.03-1.61; P = 0.026), 30-day non-elective readmissions (AOR 1.29, 95% CI 1.11-1.50; P = 0.001), and significant increases in length of stay (+6.05 days, 95% CI 4.41-7.69; P < 0.001) and costs (+$36,660, 95% CI 27,413-45,907; P < 0.001). Conclusions: Among patients undergoing alloHSCT, frailty, as measured by an administrative tool, was independently associated with increased in-hospital mortality, complications and overall resource use. Inclusion of frailty in risk models may better aid benchmarking efforts and inform shared-decision making. [Table: see text]

MO962: C-Peptide and Epicardial Adipose Tissue in Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Recent studies suggest that C-peptide (CP) may exhibit characteristics of a hormone and show physiological functions in various tissues. Moreover, it has been proposed that CP could be involved in the regulation of lipolysis, adiponectin release and function of mesenchymal stem cells in adipose tissue. However, there is a certain controversy regarding reported effects of the CP. Its beneficial effects have been demonstrated in long-term complication in type 1 diabetes mellitus (T1DM). Substitution of CP in T1DM improves glomerular hyperfiltration, hypertrophy and proteinuria. In contrast to this, CP in T2DM shows proinflammatory and proatherogenic effects. The aim of this study was to find the association between CP, epicardial adipose tissue (EAT) and vascular calcifications in diabetic subjects under insulin treatment on dialysis. METHOD This is a retrospective study of 62 consecutive chronic kidney disease (CKD) stages 5D patients awaiting kidney transplantation referred for risk stratification. Computer tomography (CT) was used to assess quantify coronary artery calcium (CAC) and to measure EAT volume. CAC was considered present if a minimum of three contiguous pixels with an attenuation of ≥130 Hounsfield Units (HU) were detected along the course of a coronary artery. CAC scores were calculated using the method described by Agatston. EAT was identified as a hypodense area surrounding the myocardium and limited by pericardium. The pericardium was traced manually from the mid-left atrium to the left ventricular apex interpolating slices of 10 mm thickness; the application of an attenuation threshold in the range of -250 to -30 HU effectively excluded myocardium, coronary arteries, coronary calcium, aorta and blood pool, leaving in evidence the EAT alone. Demographic and anthropometrics data were collected on all patients through record review. RESULTS Demographic, clinical and laboratorial characteristics of patients enrolled in the study are resume in the Table 1. Young women and smoking were more prevalent; none of the analytical parameters were correlated with CP. Subjects with higher BMI exhibited higher levels of CP (P 0.03). EAT was strongly correlated with higher levels of CP (P 0.03). EAT was significantly correlated with severity of CAC scores (P 0.01). No correlation was found between CP and CAC. CONCLUSION As a marker of insulin reserve, CP can be used to evaluate insulin needs and overdose in dialysis patients and to avoid its lipogenic effects. New and novel hypoglycemic therapies may help in this issue. While EAT was correlated to CP, this was not associated with vascular calcification (CAC); this final observation may be related to the lower levels of vascular damage observed in CKD patients from kidney transplantation waiting list. More studies are needed to explore this association and utility.

The effect of micronutrient supplementation on serum anti-Mullerian hormone levels: a retrospective pilot study

Background The anti-Müllerian-hormone (AMH) is secreted by the granulosa cells of the oocytes and can be used as a marker of the ovarian reserve; helpful to estimate female fertility or the menopause onset. Although various factors may influence AMH levels, the correlation with nutritional factors needs more research. Objective To evaluate the effect of a micronutrient supplementation on female AMH levels. Methods This retrospective analysis includes a total of 244 women, who attended the Karl Landsteiner Institute, Korneuburg, Austria from January 2013 to June 2019 due to an unfulfilled desire for a child. All women were treated with an oral micronutrient preparation consisting the dosage of one soft capsule and one tablet per day for 3 months. The soft capsule contains omega-3 fatty acids and the tablet is a standardized combination of coenzyme Q10, vitamin E, folic acid, selenium, catechins from green tea extract, and glycyrrhizin from licorice extract. Serum AMH levels before and after 3 months were compared. In addition, available clinical data such as ovulation frequency, endometrium thickness, and luteal phase duration were analyzed. Results The mean age of the women was 37.3 ± 1.8 years, the mean body mass index of 24.3 ± 4.6 k/m2. The mean serum AMH levels and endometrial thickness values were significantly higher after micronutrient supplementation as compared to baseline (1.42 ± 0.86 versus 1.86 ± 0.82 ng/mL and 6.10 ± 1.76 versus 7.29 ± 1.65 mm, respectively). In addition, ovulation frequency and luteal phase duration significantly improved in more than 60%. Conclusion Proposed micronutrient supplementation had a positive effect on serum AMH levels, endometrial thickness, ovulation frequency, and luteal phase duration. It could be a simple, risk-free therapeutic option to improve female fertility. More research is warranted to prove this effect.

Socioeconomic Inequalities and Mild Cognitive Impairment: Evidence From England and Japan

Japan is the world’s fastest ageing population, with a higher prevalence of dementia than in the UK. Less clear is the role of socioeconomic inequalities in neurocognitive disorders between these countries. This study aims to assess comparatively the relationship between education, a marker of cognitive reserve, and income in relation to mild cognitive impairment (MCI) and dementia in England and Japan. We ascertained MCI using a validated algorithm based on one standard deviation below the mean on two standardised cognitive tests. Multinomial logistic regression models were used to study the associations between socioeconomic markers and MCI/dementia. The prevalence of MCI was almost twice as high among English adults compared to Japanese. Results suggest that nations are similar in overall socioeconomic inequalities of MCI/dementia, but this might differ across socioeconomic markers. Considerable variability in the health inequalities could be attributed to the country-specific socio-cultural-political factors, which remains to be further explored.

Медикаментозна корекція діабетичної нефропатії на стадії гіперфільтрації

В статті висвітлена проблема пошуку ранніх доклінічних маркерів діагностики діабетичної хвороби нирок, а саме гіперфільтрації та функціонального ниркового резерву, що відображають початкові структурні та функціональні зміни при діабетичній нефропатії, запропоновані можливості корекції даних порушень з метою запобігання прогресуванню ураження нирок.

P–711 The association between thyroid autoimmunity and serum level of anti-Müllerian hormone in infertile patients with normal ovarian reserve undergoing in vitro fertilisation

Abstract Study question Is there a relationship between thyroid autoimmunity and serum level of anti-müllerian hormon (AMH) in infertile women with normal ovarian reserve undergoing in vitro fertilisation (IVF)? Summary answer In infertile women with normal ovarian reserve serum AMH level above 5ng/ml is associated with higher level of thyroid hormones and less frequent thyroid autoimmunity What is known already Previous studies suggest that thyroid autoimmunity is associated with a decreased ovarian reserve. Moreover, it was reported that thyroid hormone administration could improve serum AMH level. However, the relationship between serum AMH level and thyroid autoimmunity and function in infertile women with normal ovarian reserve undergoing IVF is largely unknown. Since in IVF the serum AMH level is an important marker which dictate the management of the couple, the identification of all the factors possibly related to this parameter is very important. Study design, size, duration: We performed a retrospective study in the Department of Reproductive Medicine of a private hospital. The medical records of all consecutive patients who underwent IVF between January 2015 and December 2018 with all causes of infertility were reviewed. Study group included 581patients with a mean age of 34.4±4.1 years, mean AMH of 3.78±2.4 ng/mL, mean serum TSH level of 1.89±1 microUI/ml and mean serum free T4 level of 1.05±0.98 ng/dl. Participants/materials, setting, methods Patients with known thyroid disorders or under thyroid hormone treatment at the moment of evaluation were excluded. Only patients with serum level of thyroid stimulating hormone (TSH), free tyroxine (free T4), anti thyroid peroxidase antibodies (ATPO,) anti thyroglobulin antibodies (ATG), AMH and age available for analysis were included in the study. This parameters are evaluated on a systematic basis in all the patients undergoing IVF in our Department, except very few cases. Main results and the role of chance Patients were divided according to their serum AMH level in two groups: group 1 with AMH level 5 ng/ml and below (n = 450 patients) and group 2 with AMH above 5 ng/ml (n = 131 patients). When the two groups were compared we found that patients in group 2 were younger in comparison with patients in group 1 (32.9±3.8 versus 35±4 years, p < 0.0001). After adjustment for age, patients in group 2 had significantly higher serum free T4 level (1.07±0.12 versus 1.04±0.14 ng/dl, p = 0.015), lower ATG (17.59±41.8 UI/ml versus 39.4±136.16 UI/ml, p < 0.018) and presented less frequently with high ATPO antibodies (35% versus 41.8%, p = 0.047). In a logistic regression model with AMH as a dependent variable, free T4, but not TSH was independently and positively associated with higher AMH levels (above 5 ng/ml) (p = 0.025) after adjustment for anti thyroid antibodies levels. Morever, in this logistic model the presence of high ATPO, but not ATG, were negatively related to higher AMH level (p = 0.037). Limitations, reasons for caution Patients included in this study are infertile patients with indication for IVF treatment. Therefore, the results of this study should be used with caution in other populations Wider implications of the findings: Our study suggest that serum AMH level might be related to thyroid autoimmunity, but also to thyroid hormones levels. If confirmed by further studies, this findings could offer a way to improve serum AMH level and to better understand the markers of ovarian reserve in an IVF setting. Trial registration number NA

P–599 random antral follicle count, performed at any day of the menstrual cycle, demonstrates the same predictive value for ovarian response in in vitro fertilization cycles

Abstract Study question Does antral follicle count (AFC) retains its predictive value for ovarian response to stimulation for in vitro fertilization (IVF) throughout the whole menstrual cycle? Summary answer AFC is strongly correlated to anti-mullerian hormone (AMH) and highly predictive of good ovarian response whatever the day of cycle the ultrasound is performed. What is known already Usually performed in the early follicular phase (at day 2–3 of the menstrual cycle), AFC and AMH are the most accurate markers of ovarian reserve. They are routinely used to predict ovarian response to ovarian stimulation for IVF and eventually to individualize the gonadotropin starting dose. Study design, size, duration Retrospective cohort study performed between January, 2017 and December, 2019. Participants/materials, setting, methods 410 consecutive women aged 20 to 42 years were included. Random AFC (r-AFC) was performed during the fertility workup whatever the day of their menstrual cycle was: early follicular phase i.e. day 1 to day 6 (eFP-AFC), mid follicular phase i.e. day 7 to 12 (mFP-AFC) and luteal phase i.e. day 13 or after (LP-AFC). A second AFC was performed before the start of the stimulation (SD1-AFC). AMH was measured in the early follicular phase. Main results and the role of chance Random AFC (r-AFC) was correlated to AMH (r = 0.692; p < 0.001), SD1-AFC (r = 0.756; p < 0.001) and number of oocytes retrieved (r = 0.491; p < 0.001). When regarding AFC depending on the cycle day group, the correlation with AMH was significantly higher for the LP-AFC, (LP-AFC) (r = 0.853) than for the eFP-AFC (r = 0.657; p < 0.001) and for the mFP-AFC (r = 0.668). The correlation with SD1-AFC was similar regardless of the time of performance of r-AFC (r = 0.739, 0.783, 0.733, respectively for eFP, mFP and LP-AFC). Moreover, the ROC analysis showed the same predictive value for good ovarian response (more than 6 oocytes retrieved) for the eFP-AFC, mFP-AFC and LP-AFC (AUC 0.73, 0.75 and 0.84 respectively) as well as for AMH and SD1-AFC (AUC 0.74 and 0.74, respectively). Limitations, reasons for caution This is a retrospective analysis, however data were prospectively collected and the method for ultrasound acquisition of AFC was standardized. Wider implications of the findings: The absence of significant variation of AFC across the menstrual cycle allows to its random performance. Ultrasound performed besides early follicular phase discloses informations on ovaries, the uterus and the endometrium. It is more comfortable and convenient for women and physicians by limiting targeted appointment during menstruation and reiterated examination. Trial registration number Not applicable

O-173 Decline in anti-Müllerian hormone (AMH) concentrations following radioactive iodine (RAI) treatment in women with differentiated thyroid cancer (DTC): a systematic review and meta-analysis

Abstract Study question Does radioactive iodine (RAI) treatment in premenopausal women with differentiated thyroid cancer (DTC) affects ovarian reserve, as evaluated by anti-Müllerian hormone (AMH), antral follicle count (AFC) and follicle-stimulating hormone (FSH)? Summary answer AMH concentrations decreased at three, six and 12 months following RAI treatment in women with DTC, whereas no difference was observed regarding FSH. What is known already Thyroid cancer is the third most common type of female malignancy and DTC is the most common histopathological type. Thyroidectomy constitutes the mainstay of treatment for DTC, followed by administration of RAI, which acts as an adjuvant therapy to destroy residual cancerous thyroid tissue. However, the effect of RAI on ovarian reserve of these women, as assessed by AMH, AFC and FSH, remains controversial. Study design, size, duration A systematic review and meta-analysis was performed aiming to identify studies evaluating the effect of RAI treatment on ovarian reserve in women with DTC. For this purpose, a literature search in the electronic databases PubMed, Scopus and CENTRAL was carried out until 06/12/2020. The primary outcome measure was the effect of RAI on ovarian reserve, as evaluated by AMH, AFC and FSH. Participants/materials, setting, methods Studies were eligible if they included premenopausal women with DTC, treated with a single RAI dose and assessed for at least one marker of ovarian reserve repeatedly within 12 months post-RAI.Meta-analysis of weighted data was performed using random effects model. Results were reported as weighted mean difference (WMD) with 95% confidence interval (CI). Main results and the role of chance Four prospective eligible studies, published between 2005 and 2020, were eligible for the meta-analysis, evaluating a total of 154 women. The number of participants ranged from 24 to 50. The single dose of RAI used to treat DTC ranged from 50 to 150 mCi. AMH concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p < 0.0001; I2 0%), six (WMD -1.58 ng/ml, 95% CI -2.63 to -0.52, p = 0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p < 0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n = 104). With respect to FSH concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to + 7.70, p = 0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to + 1.32, p = 0.83; I2 55.2%) post-RAI compared with baseline (two studies; n = 83). No data on AFC was available. Limitations, reasons for caution The small number of studies and patients included, as well as the lack of data on AFC may have compromised the validity of the conclusions drawn. Moreover, subgroup analysis according to female age was not feasible, due to the lack of relevant data. Wider implications of the findings The negative effect of RAI on ovarian reserve in premenopausal women with DTC, as indicated by the decreased AMH, should be confirmed by data on AFC, which are currently not available. These findings necessitate close monitoring of ovarian reserve in such women, counselling them regarding the need for fertility preservation. Trial registration number N/A

P–617 Idiopathic early ovarian aging: Do biomarkers of ageing indicate premenopausal accelerated biological ageing in young women with diminished response to ART?

Abstract Study question Do young women with idiopathic early ovarian ageing have changes in telomere length and epigenetic age indicating accelerated biological aging? Summary answer The telomere length and epigenetic age were comparable to those in young women with normal ovarian ageing. What is known already Increased risk of several health events usually considered to be age-related such as cardiovascular disease, osteoporosis, over-all morbidity and mortality have been associated with premature and early menopause when compared to the risk in women with normal menopausal age suggesting an accelerated general ageing process associated to early ovarian ageing. It is unclear whether the onset of this process may start before menopause. Study design, size, duration A prospective cohort study. Young women (≤ 37 years) having ART at two Danish Public fertility clinics during the period 2016 to 2018 were divided into two groups dependent on their ovarian reserve status: early ovarian ageing (EOA) (N = 55) and normal ovarian ageing (NOA)( N = 52). Number of oocytes harvested in first and subsequent cycles was used as a marker of ovarian reserve. Blood samples was drawn at time of oocyte retrieval to assess biological age. Participants/materials, setting, methods EOA was defined as ≥ 2 IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with FSH and NOA as ≥ 8 oocytes harvested in minimum 1 cycle. Known causes influencing the ovarian reserve (endometriosis, ovarian surgery, etc.) was reason for exclusion. Relative telomere length (qPCR) and epigenetic age acceleration (DNA methylation levels) were measured in white blood cells as markers of accelerated biological ageing. Main results and the role of chance Relative telomere length was comparable with a mean of 0.46 (± sd 0.12) in the EOA group and 0.47 (0.14) in the normal ovarian ageing group (p = 0.64). The difference of predicted mean epigenetic age and mean chronological age (i.e. epigenetic age acceleration) was, insignificantly, 0.5 years older in the EOA group when compared to the NOA group( (–1.02 years (2.62) and –1.57 years (2.56), respectively, p = 0.27)), but this difference disappeared when adjusting for chronological age. Limitations, reasons for caution Discrete changes in epigenetic age acceleration may not have been captured as the study only had power to detect an age acceleration of ≥ 2 years. Wider implications of the findings: By analysis of biomarkers for ageing in whole blood, we did not find any indications of a premenopausal accelerated aging in young women with idiopathic EOA. Further investigations in a similar cohort of premenopausal women is needed to fully elucidate the potential relationship between premenopausal accelerated biological ageing and EOA. Trial registration number The study was approved by the Danish Data protection Agency (nr 1–16–02–320–14) and the Regional committee on health research ethics of Central Region Denmark (jr.no 1–10–72–142–14).

P–657 Prostaglandin D2 is correlated with follicles development and a reliable marker of ovarian reserve of poor ovarian responder patients

Abstract Study question Is the prostaglandin D2 (PGD2) associated with growing follicles and ovarian reserve of poor ovarian responders? Summary answer PGD2 is correlated with ovarian stimulation activity and follicle growth. Especially, poor ovarian responders show a significant decrease in the level of follicular fluid. What is known already Prostaglandins (PGs) are involved in the female reproductive process, mainly ovulation, fertilization, and implantation. Study design, size, duration We investigated the PGD2 level in the follicular fluid of poor ovarian responders. The collection of human follicular fluid was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. Follicular fluid was collected from patients with normal ovarian response and patients with POR. Participants/materials, setting, methods We studied whether prostaglandin has related to POR in the clinical key factor by measuring human follicular fluid. Follicular fluid was collected from patients with normal ovarian response and patients with POR. The concentration of PGD2 in follicular fluid was determined with ELISA kits following the manufacturer’s protocol. Main results and the role of chance We analyzed the level of PGD2 in the follicular fluid of patients with normal ovarian response and patients with POR using an ELISA. The PGD2 concentration was significantly lower in the follicular fluid of patients with POR than in the follicular fluid of young and old patients with normal ovarian response. Limitations, reasons for caution This study has an identification of biomarker of the clinical samples as POR criteria patients. Therefore, further investigations aimed at specific recovery of low PGD2 metabolic activity in the CCs during control ovarian stimulation. Wider implications of the findings: Until now there is no specific biomarker of POR. AMH is just an ovary reserve marker for an indication of ovary function. PGD2 is one of the metabolites in steroid metabolism in the ovary. Therefore, we can find some cure through further study for improved PGD2 production to POR patients. Trial registration number none

P–636 Anti-Müllerian-Hormone levels are not correlated to the probability of obtaining an ongoing pregnancy and time to pregnancy in women undergoing intra-uterine inseminations with donor sperm

Abstract Study question Is Anti-Müllerian hormone (AMH) level associated with the probability of obtaining an ongoing pregnancy (OP) and with time to pregnancy (TTP) in women undergoing d-IUI? Summary answer AMH is neither associated with the probability of obtaining an OP nor with time to pregnancy (TTP) in women undergoing d-IUI What is known already Anti-Müllerian hormone (AMH) is a glycoprotein produced by the granulosa cells of preantral and antral follicles. While AMH has been widely recognized as a quantitative marker of ovarian reserve used to predict ovarian responsiveness to ovarian stimulation in IVF, its relationship with fecundability in spontaneous conceptions is still a matter of debate. There is currently no consensus on the role of AMH on time to pregnancy in unassisted conceptions. The question of whether AMH is a qualitative marker of oocyte quality is therefore still unanswered. Study design, size, duration This prospective cohort study was carried out between 9/1/2017 and 12/30/2020 on 592 women aged 19 to 44, who underwent d-IUI in a natural cycle (n = 1788) the day after LH peak. Patients were single, homosexual, or heterosexual with an infertile partner and underwent 1 to maximum 6 d-IUI. All patients had regular ovulatory cycles and bilateral tubal patency confirmed before starting d-IUI. AMH evaluation was performed within the previous 3 months of the first d-IUI. Participants/materials, setting, methods The primary outcomes were the likelihood of obtaining an OP (>14 weeks) and TTP calculated as the number of d-IIU up to an OP. Multivariate logistic regression was used to compare the probability of obtaining an OP according to age and AMH levels. Kaplan-Meier curves with log-rank test were used to assess the TTP stratified by age groups (≤35, >35 to ≤ 39, and > 39 years old) and AMH groups (< 1ng/mL and ≥ 1ng/mL). Main results and the role of chance AMH levels were negatively correlated with age (p < 0.001). OP were significantly lower with increasing age (OR 0.92 (0.89–0.95) p < 0.001) but did not differ according to AMH levels (OR 1.07 (0.97–1.18) p = 0.18). When adjusting for AMH, the association between age and OP remained significant (OR 0.91 (0.88–0.95)). TTP was significantly different between age groups: ≤35 years old (n = 338), >35 to ≤ 39 years old (n = 136) and > 39 years old (n = 118) (p < 0.001), but did not differ significantly according to AMH levels < 1ng/mL (n = 130) and ≥1ng/mL (n = 462)(p = 0.55). Limitations, reasons for caution Our results concern d-IUI and can therefore not be extrapolated to natural conception. However, the study model is close to natural fecundity as there was no history of female infertility and as all IUI were performed on the day of ovulation with donor sperm proven to be fertile. Wider implications of the findings: While measuring AMH seems necessary for gonadotropin dose adjustment in ART, our data suggest that it cannot qualitatively assess fertility outcome and should therefore not be used routinely for preconception counseling in the absence of infertility history. Trial registration number P2017/396

P–698 Antimüllerian Hormone (AMH) value as a predictive marker of cycle ploidy outcome

Abstract Study question Do woman with diminished ovarian reserve exhibit poor blastocyst formation and ploidy outcomes, irrespective of age? Summary answer Patients with extreme diminished ovarian reserve (AMH≤0.65ng/ml) have a lower chance to have at least one euploid blastocyst compared to their age-related reference population (AMH=1.3–6.25ng/ml). What is known already AMH is an established marker of the ovarian reserve for predicting ovarian response to ovarian stimulation and it is strongly correlated with female age. However, it has been suggested that AMH is not only a quantitative, but also a qualitative biomarker of oocyte/embryo competence. Previous studies show conflicting outcomes as to whether reduced ovarian reserve per se is associated with decreased oocyte developmental competence, leading to increased aneuploidy rates in embryos independent of the patient’s age. Study design, size, duration A retrospective analysis was performed between March 2017 and July 2020 at ART Fertility Clinics (Abu Dhabi) including all couples that were triggered for final oocyte maturation and planned for Preimplantation Genetic Testing for Aneuploidies (PGT-A). Patients were stratified into four age categories [≤30, 31–35, 36–40, >40 years]. For each age category patients were further divided into three AMH groups: ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml (reference group). Participants/materials, setting, methods Trophectoderm biopsy samples were subjected to Next Generation Sequencing. AMH serum levels (ng/ml) were determined using the commercial fully automated Elecsys® (Roche) assay. Patients with a Progesterone rise of > 1.5ng/ml on the day of final oocyte maturation and patients with AMH values >6.25ng/ml were excluded from the analysis. Per patient that was triggered, the chance to have at least one euploid blastocyst in that cycle, was calculated. Main results and the role of chance A total of 1.300 couples were included with an mean maternal age of 35.6±6.2 years, AMH of 2.1 ±1.5ng/ml and body mass index of 27.5±5.0 kg/m2. The chance to have at least one blastocyst biopsied per cycle was affected in all patients with extreme low AMH (≤0.65ng/ml), irrespective of age; ≤30 years: 58.33%–100.00%–94.84% (p < 0.001); 31–35 years: 50.00%–74.55%–95.32% (p < 0.001); 36–40 years: 56.52%–81.93%–92.56% (p < 0.001) and ≥40 years: 38.06%–73.02%–88.24% (p < 0.001), for AMH ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml, respectively. In all age categories, patients with AMH values ≤0.65ng/ml had a significantly reduced probability of having a euploid blastocyst compared to the reference group (1.31–6.25ng/ml). For women ≤30 years the chances of getting a euploid blastocyst decreased from 88.89% (n = 252) to 41.67% (n = 12) (OR 0.01 [0.03–0.30], p < 0.001), for 31–35 years from 88.09% (n = 235) to 43.75% (n = 32) (OR 0.10 [0.05–0.23], p < 0.001), for 36–40 years from 77.67% (n = 215) to 21.74% (n = 69) (OR 0.08 [0.04–0.15], p < 0.001) and among women >40 years from 29.42% (n = 102) to 6.45% (n = 155) (OR 0.16 [0.08–0–36], p < 0.001). Woman within AMH range of 0.65–1.3ng/ml presented the same decreased probability of having a euploid blastocyst only when 31–35 (52.73%, n = 55) or 36–40 years old (56.63%, n = 83) (OR 0.15 [0.08–0.29], p < 0.001 and OR 0.37 [0.22–0.64], p < 0.001, respectively). Limitations, reasons for caution The main limitation of this study is its retrospective design. Wider implications of the findings: AMH is a clear biomarker of oocyte-embryo competence. Incorporation of AMH-specific counseling recommendations into clinical practice guidelines, could lead to a more informed guidance on cycle ploidy outcomes, rather than age alone. Trial registration number Not applicable

Prediction of short-term prognosis in elderly patients with spontaneous intracerebral hemorrhage.

The incidence of spontaneous intracerebral hemorrhage (SICH) increases with age. Data on SICH mortality in the very old are sparse. We aimed to describe the predictors of 30-day SICH mortality in the very elderly in southern Portugal. A total of 256 community representative SICH patients aged ≥ 75years (2009-2016) were included. Multiple logistic regression was used to identify predictors of 30-day mortality. Mean age was 82.1years; 57.4% males. The 30-day case fatality was 38.7%. The frequency of patients taking anticoagulants (29.3% vs. 11.5%); comatose (46.9% vs. 2.5%); with hematoma volume ≥ 30mL (64.6% vs. 13.4%); intraventricular dissection (78.8% vs. 27.4%) was higher in deceased patients (p < 0.05). Survivors were more often admitted to stroke unit (SU) (68.2 vs. 31.3%) and had lower mean admission glycaemia values (p < 0.05). The likelihood of death was increased in patients with higher admission hematoma volume (≥ 30mL) (OR: 8.817, CI 1.753-44.340, p = 0.008) and with prior to SICH history of ≥ 2 hospitalizations OR = 1.022, CI 1.009-1.069, p = 0.031). Having higher Glasgow coma scale score, OR: 0.522, CI 0.394-0.692, p < 0.001, per unit was associated with reduced risk of death. Age was not an independent risk factor of short-term death. The short-term mortality is high in very elderly SICH. Prior to SICH history of hospitalization, an indirect and gross marker of coexistent functional reserve, not age per se, increases the risk of short-term death. Other predictors of short-term death are potentially manageable reinforcing the message against any defeatist attitude toward elderly patients with SICH.

Urinary vitamin D-binding protein as a marker of ovarian reserve

BackgroundOvarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve.MethodsUrine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis.ResultsWhen Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS.ConclusionsUrinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.

Anti-Müllerian hormone (AMH) as a marker of ovarian reserve and premature ovarian insufficiency (POI) in children and women with cancer: A systematic review.

e24057 Background: Female patients undergoing anticancer treatment are at elevated risk of ovarian damage including development of POI. AMH is a key serum biomarker of ovarian reserve. However, its role to identify risk of POI in cancer patients prior to and after treatment is less well understood. Methods: A systematic literature search for AMH in women with cancer was conducted up to 30 August 2020, with formal bias assessment. We aimed at evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment. Exploratory subgroups were based on age, cancer type and length of follow-up. Results: : Eighty publications (including 7,708 patients) were included in this analysis. All papers reporting AMH before and after treatment reported a large reduction in AMH following treatment, in both adult and paediatric populations. Effect sizes varied depending on the treatment and diagnosis, but ranged from 42% to below the limit of detection, and many reported declines of ≥90%. A majority (25/34, 74%) of studies also reported at least partial recovery of AMH at follow-up. Pre-treatment AMH correlated with post-treatment levels in all studies and younger patient age with higher post-treatment AMH in 21/29 (72%) studies. In 18/32 (58%) publications, oligo/amenorrhea correlated with lower post-treatment AMH. No studies reported correlations between post-treatment AMH and pregnancy, although pregnancy was reported in some patients with low or undetectable AMH. 70% of publications found that within-study variations in treatment (estimated by chemotherapy or radiotherapy type, dosage, duration and/or number of cycles) correlated with AMH reductions and degree of recovery, indicating its potential value as a marker of gonadotoxicity. In women with breast cancer, recovery of AMH was reported in some patients in 10/18 publications; however, AMH levels showed no recovery in many patients receiving alkylating agents or cyclophosphamide-based chemotherapies. In lymphoma, patients receiving ABVD-based regimens had at least partial post-treatment recovery of AMH at follow-up compared with those receiving cyclophosphamide-containing regimens. 16/20 (80%) publications in pediatric cancer patients showed significant reductions in AMH compared with pre-treatment levels or controls. The diagnostic value of post-treatment AMH for POI was supported in 5/5 (100%) studies. AMH levels measured 1–2 years after treatment appeared to be equally reliable at indicating longer-term menstrual outcomes as studies with longer followup. Conclusions: AMH levels were strongly impacted by anticancer treatment, with recovery in some women determined by treatment regimen, age, and pretreatment AMH level. There was evidence for its role in diagnosis of POI, nut further studies are required to clarify its value to assist in patient management.

Assessment of different markers of ovarian reserve in women with differentiated thyroid cancer treated with radioactive iodine

Assessment of different markers of ovarian reserve in women with differentiated thyroid cancer treated with radioactive iodine

Anti-Mullerian hormone and its predictive value for assessing oocyte quality

The article systematizes information on the diagnostic capabilities of modern clinical and laboratory markers of ovarian reserve. The diagnostic capabilities of anti-Mllerian hormone (AMH) as a marker of ovarian reserve are discussed, which make it possible to adjust the dose of hormonal drugs and predict the response of the ovary to stimulation in programs of assisted reproductive technologies. This paper discusses for the first time the role of AMH in assessing the quality of oocytes and subsequent embryos. Despite insufficient literature data, further study of AMH, as well as full-scale research in this direction, seems to be extremely promising.

Pathway Analysis of Leisure Activity and Cognitive Function in the Long Life Family Study

Familial longevity and greater involvement in activities purported to build cognitive reserve (e.g. education, cognitively stimulating leisure activity) have both been associated with better cognitive function in later life, yet little is known about how these protective factors relate with one another. In this work, we modeled the associations among familial longevity, proxies of cognitive reserve, and cognitive function in the Long Life Family Study (LLFS). We assessed cognitive function using a comprehensive battery of neuropsychological tests (i.e. Digit-Spans, California Verbal Learning Test, Rey-Osterrieth Complex Figure, phonemic fluency, category fluency, Word Generation, DKEFS Sorting Test, and logical memory) in a subset of LLFS family members and a referent cohort (N=314, mean age 75.7±14.6 years). To model these associations, we used a series of Bayesian hierarchical regression pathways that incorporate a random effect for family relatedness, adjusted by age and sex. All continuous variables were rescaled and bounded to be approximately between (0,1) in order to standardize regression coefficients and to allow for an asymmetrical beta-distribution. Controlling for education level, age, and sex, referents had greater engagement in late-life cognitive activities compared to LLFS family members, β=0.38 (95% CI: 0.18 to 0.57). In turn, those with higher markers of cognitive reserve exhibited better neuropsychological performance. Despite LLFS family members having lower participation in cognitively stimulating leisure activities, there were no differences between LLFS family members and referents on cognitive test performance. These results suggest long-lived family members may have more unique pathways (i.e. genetic/environmental) that preserve cognition later in life.

The Role of Leisure Activities as Markers of Cognitive Reserve on Dementia Risk in English Older Adults

We examined the frequency of participation in cognitive and social type of leisure activities in association with dementia risk over 15 years of follow-up in 12,280 participants aged 50+ from the English Longitudinal Study of Ageing. Cox proportional hazards regression models were used to estimate the hazard of dementia in relation to the cognitive and social type of leisure activities as well as their interactions with sex and marital status. Medium and higher levels of engagement in cognitive leisure activities were associated with a lower risk of dementia. An analysis of the social type of leisure activities showed a similar pattern with protection for higher levels of engagement in a model adjusted for sex and marital status but further explained by wealth. This study shows a reduced risk of dementia for individuals with higher levels of engagement in cognitively stimulating activities, that may preserve cognitive reserve until later in life.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to ovarian reserve parameters, namely AFC and AMH (study 2).

This is the second of five studies undertaken on women preparing for assisted reproduction, to sequentially examine the relevance of the insulin-like growth factor (IGF) profile (IGF-1, IGFBP-3 and the IGFBP-3/ IGF-1 ratio) which, in children, provides the essential criteria to identify the GH-deficient individual. Whilst our first, published study, focussed on clinical parameters, this study examines its relevance to the two parameters which define the ovarian reserve. The first, that of the antral follicle count (AFC), shows highly significant, sequential changes across 4 age groups ranging from high counts in the younger women &lt;35 years and low counts in the older women, namely those aged 35-39 years, those aged 40-44 years and those aged ≥45 years (p&lt;0.0001). Similarly, the serum levels of anti-Mullerian hormone (AMH), a later introduced marker of ovarian reserve, also showed highly significant sequential changes across the 4 age groups with high levels recorded in the young women and low counts in the older women (p&lt;0.0001). At the higher AFC range, concordance between AFC groups and AMH groups was high at r=0.79 for precise matching and r=0.95 when neighbouring groups were included. The correlation was also clear with inter-quartile AMH levels ranging 27 pmol/L to 50 pmol/L across the higher AFC groups and 8 pmol/L to 10 pmol/L in the lowest groupings. However, IGF profiles showed no significant variations across the entire range, neither for the AFC nor for the AMH groups. Our next study will report on the relevance of the IGF profile to clinical outcomes.