Women Of Advanced Age Research Articles

P0063 Prevalence of sarcopenia in a cohort of patients with inflammatory bowel disease: observational study in a tertiary care centre

Abstract Background Malnutrition is a common condition of patients with inflammatory bowel disease (IBD) and could be associated with sarcopenia i.e. a reduced muscle mass and strength. It is well demonstrated that sarcopenic IBD patients have two to three times higher risk of lost of response to biotechnology drugs than non-sarcopenic patients. Methods A prospective observational study was conducted.Consecutive IBD patients were enrolled. Data were collected on disease characteristics, therapy and disease activity. We collected data about the frequency(none, low,high) and the kind (aerobic or anaerobic) of the physical activity of patients.At the enrolment, nutritional assessments were performed by body mass index(BMI) and the global subjective assessment by the MUST(Malnutrition Universal Screening Tool) index.Moreover, the SARC-F questionnaire, recommended by the scientific consensus EWGSOP 2 to identify individuals at risk for sarcopenia was administrated.A SARC-F value≥4 was significant of sarcopenia. The quality of life was assessed using the inflammatory bowel disease questionnaire (IBDQ). Univariate and multivariate analysis was conducted between BMI, MUST,SARC-F and IBDQ values and patient characteristics(age, current therapy, disease activity and physical activity). Results A total of 353 IBD patients (170 CD, 183 UC),54,55% male, with a mean age of 44.78 years were enrolled. A mean BMI of 24,35 kg/m2, was calculated. Regarding malnutrition, 210 patients (59.66%) were considered at low risk (MUST=0), 88 subjects (25%) at medium risk (MUST=1), 53(15,34%) at high risk (MUST ≥2).A SARC-F value ≥4 was evaluated in 57 patients (16.19%). A reduction in quality of life, understood as IBDQ <209, was found in 124(35.23%) patients. Univariate analysis shows a protective role of male sex(OR vs. female sex: 0.33; p-value:0.018) in the risk of sarcopenia; older subjects had a higher sarcopenic risk (OR 1.04; p.<0.001). The risk was associated with a severe disease activity (OR 9.46,p.<0.001), increasing MUST(OR 1,65, p.<0.001) and with the IBDQ decreases (OR 5.9,p.<0.001). Multivariate analysis confirmed an higher incidence of sarcopenia in women of advanced age with active-stage disease (R2 0.88), furthermore female patients with active-stage disease who did not engage in physical activity had a greater impairment in quality of life (R2: 0.75, p.<0.0001). Physical activity played a protective role in the onset of sarcopenia regardless of sex and age (R2: 0.82, p.<0.0001). Conclusion In our cohort, sarcopenia was present in only 16.19%.Male sex was found to be a protective factor for sarcopenia. Disease status is linked to the risk of sarcopenia. Regular physical activity has been shown to have a protective was related with a lower risk of sarcopenia.

Enhanced Ovarian FKBP51 Expression is Associated with Ovarian Aging: A Molecular Insight for Age-Related Fertility in Women.

To study the relationship between FK506-binding protein 51 (FKBP51) and ovarian aging and/or diminished ovarian reserve (DOR) in human ovaries by comparing FKBP51 levels in granulosa (GC) and cumulus cells (CC), collected during controlled ovarian stimulation (COS) from women of advanced reproductive age and/or with a diagnosis of DOR with that of young women with normal ovarian reserve. To explore the association between increased FKBP51 expression and human ovarian aging further, expression of FKBP51 was compared in ovarian stroma of post-menopausal versus pre-menopausal women. Lastly, this relation was further queried by comparing ovarian expression of several collagen genes as markers of ovarian fibrosis in 14-month-old wild type (Fkbp5+/+) and Fkbp5 knockout (Fkbp5-/-) mice. Laboratory based experimental study. Academic-affiliated assisted reproductive technology unit/laboratory SUBJECTS: (1) Samples collected included follicular fluid (FF), CC, GC and serum from group 1: Young women with normal ovarian reserve (<35 years; n=12); group 2: DOR (anti-Mullerian hormone (AMH) <1 ng/mL; n=10); and group 3: Women of advanced age with normal ovarian reserve (>37 years; n=8). (2) Ovarian stromal tissues obtained from surgical specimen of post-menopausal (50-65 years; n=6) and pre-menopausal (18-30 years; n=6). (3) 14-month-old ovarian tissues from Fkbp5+/+and Fkbp5-/- mice. Comparison of FKBP51 expression in GC and CC from women undergoing COS, ovarian stromal tissue from pre- and post-menopausal women, and ovarian tissue from aged Fkbp5+/+and Fkbp5-/- mice. (1) Level of FKBP51 in human GC and CC, collected during COS by performing RT-quantitative PCR (RT-qPCR). (2) Immunohistochemistry (IHC) to detect FKBP51 levels and Picrosirius Red Staining (PSR) to detect collagen deposition in human ovarian stromal tissue. (3) RT-qPCR to compare expression levels of several collagen genes in Fkbp5+/+ and Fkbp5-/- old mice ovaries. (4) Serum and FF levels of TGF-β1, and soluble Endoglin measured by ELISA. IHC revealed that FKBP51 HSCORE levels in ovarian stromal tissue were significantly higher in post- vs. pre-menopausal women (Mean± SEM; 160.52±17.75 vs. 120.67±14.33, P= 0.002). Stronger Picrosirius Red staining, suggestive of fibrosis, was seen in post- vs. pre-menopausal women (54.06± 6.94 vs. 37.50± 14.29, P=0.02). Analysis of qPCR revelated that 1) Col1a1, Col1a2, Col3a1 levels were significantly lower in ovaries obtained from 14-month-old Fkbp5-/-vs. Fkbp5+/+ mice; 2) FKBP5 levels significantly increased in cumulus cells of advanced age women vs. younger women (1.71± 0.22 vs. 1.11± 0.15, P= 0.03); and 3) FKBP5 levels were ∼3-fold higher in granulosa cells of women with DOR vs. age-matched control (3.22± 1.11 vs. 1.30± 0.54 P= 0.03). This study for the first time demonstrates expression profile of FKBP51 in human ovary and its potential role in ovarian aging. Our results indicate that the upregulation of FKBP51 is associated with ovarian aging. Moreover, in women undergoing IVF treatment, enhanced FKBP51 expression is seen in those with DOR or women of advanced maternal reproductive age, who have poor prognosis. Therefore, drugs targeting inhibition of FKBP51 expression and/or activity may delay ovarian aging or treat premature ovarian aging.

Influencing Factor Analysis and Prediction Model of Emergency Caesarean Delivery for Advanced-Age Nulliparous Women at the Time of Hospitalization

Objective: In Japan, the number of nulliparous pregnant women of advanced age, defined as 35 years or older, has increased, and the age range has lengthened towards older age with the increased use of infertility treatments. Given this trend, adverse labour outcomes, such as emergency caesarean delivery (ECD), are expected to increase. Therefore, by focusing mainly on maternal age and infertility treatment history, we aimed to establish a new prediction model for the likelihood of ECD after identifying the influencing factors related to maternal and labour-related characteristics. Materials and methods: The medical records of 1,521 pregnant women who were nulliparous between 2017/4/1 and 2024/3/31 at our hospital were retrospectively reviewed. First, for the 675 women who were aged 30 years old or more, we calculated the rates of ECD in 8 groups classified according to maternal age, infertility treatment, and other variables. Next, we performed multivariate logistic regression analysis to assess the effect of each representative factor and established a prediction model based on the number of factors that were significant in the multivariate analysis. Results: Simple comparisons classified by maternal age revealed a constant increase in the rate of ECD with increasing maternal age, and multivariate analysis revealed 7 significant factors, namely, advanced maternal age, history of using assisted reproductive techniques (ART), small height, high Body mass index (BMI), low Bishop score, late-term delivery, and large infant. In the prediction model constructed with these 7 factors, the rate of ECD increased as the number of these factors increased. Conclusion: The negative impact of advanced maternal age, namely, 40 years or older, and ART history, on labour outcome is clear. A new prediction model has the potential to identify patients with an extremely high probability of needing an ECD. These results may indicate that the management of the labour process will become more difficult in the future.

Investigating Aging-Related Endometrial Dysfunction Using Endometrial Organoids.

Ageing of the endometrium is a critical factor that affects reproductive health, yet its intricate mechanisms remain poorly explored. In this study, we performed transcriptome profiling and experimental verification of endometrium and endometrial organoids from young and advanced age females, to elucidate the underlying mechanisms and to explore novel treatment strategies for endometrial ageing. First, we found that age-associated decline in endometrial functions including fibrosis and diminished receptivity, already exists in reproductive age. Subsequently, based on RNA-seq analysis, we identified several changes in molecular processes affected by age, including fibrosis, imbalanced inflammatory status including Th1 bias in secretory phase, cellular senescence and abnormal signalling transduction in key pathways, with all processes been further validated by molecular experiments. Finally, we uncovered for the first time that PI3K-AKT-FOXO1 signalling pathway is overactivated in ageing endometrium and is closely correlated with fibrosis and impaired receptivity characteristics of ageing endometrium. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of ageing or accelerate dysfunction of endometrial organoids. This discovery is expected to bring new breakthroughs for understanding the pathophysiological processes associated with endometrial ageing, as well as treatment strategies to improve reproductive outcomes in women of advanced reproductive age.

Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes.

To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) benefits women of advanced reproductive age (≥38 years old) with a diminished ovarian reserve (DOR; not more than three retrieved oocytes). A retrospective analysis comparing two groups: (a) PGT-A group: women who chose PGT-A and subsequent single re-warmed embryo transfers (ETs) and (b) non-PGT-A group: women who chose not to genetically test their embryos and underwent subsequent fresh or re-warmed ETs of one to two embryos on days 3 or 5. Two hundred and thirty patients underwent PGT-A therapy, with 49 of these individuals undergoing more than one PGT-A cycle. Meanwhile, 309 patients received non-PGT-A treatment, among whom 89 underwent more than one cycle of this type. Collectively, this study encompassed a total of 298 PGT-A cycles and 429 non-PGT-A cycles from a single center (April 2019-June 2023). All women had a DOR and advanced reproductive age. The exposure variable was the use of PGT-A. The primary outcome was live birth rates (per cycle and retrieval). Secondary outcomes were clinical pregnancy rates (per cycle and retrieval), miscarriage rates (per pregnancy and retrieval). While PGT-A cycles had lower transfer rates (14.1% vs. 73.2%), they achieved significantly higher pregnancy (66.7% vs. 12.4%) (adjusted odds ratio [aOR] = 11.474; 95% confidence interval [95% CI], 5.462, 24.102; p < 0.001) and live birth rates (57.1% vs. 7.5%) per transfer (aOR = 13.065; 95% CI, 5.987, 28.510; p < 0.001). The PGT-A group also had lower miscarriage rates (14.3% vs. 40.0%) (aOR = 0.142; 95% CI, 0.030, 0.661; p = 0.013). However, overall pregnancy and live birth rates were similar, and the PGT-A group required fewer cycles for live birth (p = 0.023). While PGT-A improved clinical pregnancy and live birth rates per transfer cycle in women of advanced reproductive age with a low oocyte yield, it did not impact these rates per retrieval.

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Maternal attachment levels of advanced age mothers and relation factors

Being mother at advanced age is associated with physical, emotional and social problems during pregnancy. The purpose of study to finding out the maternal attachment of pregnant women of advanced age and the associated factors. The methodology used was a descriptive and cross-sectional research. The minimum sample size was calculated as 323 in a confidence interval of 95%, with a margin of error of 5%. Total 278 pregnant women were included in this study. Data were collected through Personel Information Form and the Maternal Attachment Inventory. Non-parametric tests (Kruskal-Wallis,Mann-Whitney U), logistic regression analysis was performed for evaluating statistically significant data. The mean of Maternal Attachment Inventory scores is 97.22 ± 17.38 points. The maternal attachment level was higher in cases in which the mother did not work (O.R:0.944), the epidural anesthesia was used (O.R:2.937), the mother had low number of stillbirths (O.R:0.868), the mother gave birth to male infant (O.R:1.022), the newborn had high birth weight (O.R:1.038), the newborn had congenital anomaly (O.R: 0.795) and the mother had no skin-to-skin contact (O.R:0.933). we conclude that though it was discerned that mothers of advanced age had high levels of MA, it was identified that the MA level was affected by certain demographic variables.

Progestin-primed ovarian stimulation outcomes in in-vitro fertilization (IVF) – A systematic review of the literature

Background: Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: ‘progestin-primed ovarian stimulation’, ‘PPOS’, ‘micronized progesterone’, ‘medroxyprogesterone’, and/or ‘dydrogesterone’. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

Preimplantation Genetic Testing for Aneuploidy (PGT-A) in In-Vitro Fertilisation (IVF) Treatment: Study Protocol for Pilot Phase of a Randomised Controlled Trial.

Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on morphological evaluation alone. This leads to patients requiring numerous embryo transfers and, consequently, a prolonged time interval before live birth. Embryo selection following preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) has been suggested as an intervention to shorten time to pregnancy in women undergoing in vitro fertilisation (IVF). Past studies assessing the clinical efficacy of PGT-A in improving clinical outcomes have been conflicting and the associated clinical pregnancy rates and live birth rates following the transfer of a mosaic embryos have yet to be determined. None of the existing studies solely included women of advanced reproductive age (ARA). The pilot study and proposed RCT will determine if, compared to morphological evaluation alone, the use of PGT-A through NGS is a more clinically effective, safer, and more cost-effective way to provide IVF treatment in women of advanced reproductive age. Method and Analysis: The proposed pilot study will aim to randomise 100 patients within a single-centre study to evaluate recruitment, randomisation, and adherence to study protocol and allocated trail arms by participating patients. The results of the pilot study will enable us to determine the sample size for a larger study to establish the effectiveness of PGT-A in ARA women. Ethics and Dissemination: The study (Integrated Research Application System Number 236067) received approval from the Health Research Authority and Health and Care Research Wales (HCRW) and the East Midlands-Leicester South Research Ethics Committee (20/EM/0290). The results will be made available to patients, the funders, the Reproductive Medicine societies, and other researchers. Trial registration: ClinicalTrials.gov Identifier: NCT05009745, n.

Identification of metabolomic changes and potential therapeutic targets during ovarian aging.

To reveal the metabolic differences of follicle fluid (FF) and granulosa cell (GC) between younger women and advanced age women in ART cycles, and then find potential therapeutic targets of ovarian aging. Forty-five patients were included in the study and they were divided into three groups according to their age (Group A: 20-30 years old; Group B: 30-35 years old; Group C: 35-45 years old). All patients underwent controlled ovarian stimulation using the follicular phase long-acting protocol, FF and GC were obtained 36-38 hours after HCG administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for metabolomics analysis and metabolic pathway analysis (MetPA) was utilized to find related pathways. Between group A and group C, there were 72 and 21 differential metabolites in FF and GC, respectively. KEGG enrichment analysis showed six pathways were co-enriched by the differential metabolites of FF and GC. Among them, we noticed that in the pathway GABAergic synapse, GABA (gamma-aminobutyric acid) was down-regulated in GC, while its downstream metabolite succinic acid was down-regulated in FF. Further ROC curve analysis was performed on these two metabolites, and the results showed that they all had a favorable predictive value. This study indicated that GABA and succinic acid could be potential therapeutic targets for ovarian aging, GABA may delay ovarian aging and improve ovarian function through its antioxidant properties, which may be a future direction of clinical treatment.

12460 Bilateral Parietal Thinning: A Rare Condition Of Unclear Etiology

Abstract Disclosure: T.L. Madsen-Barbosa: None. M. Cheikh: None. I. Marcano: None. Background: Bilateral parietal bone thinning (BPT) is an infrequent and often underdiagnosed condition characterized by the external thinning of the skull's parietal bone. The pathophysiology is unclear, but some studies suggest a link to osteoporosis. We present a case of osteoporosis diagnosed on evaluation of BPT. Case Description: A 77-year-old woman with a history of chronic kidney disease (CKD stage IV) and type 2 diabetes was referred to the Bone Health Clinic for evaluation of low bone density. She initially presented to Neurosurgery clinic for evaluation of head indentations. A dual energy x-ray absorptiometry (DEXA) scan showed values in osteopenia range (left total hip bone mineral density (BMD) 0.678 and T-score of -2.2, left femoral neck BMD 0.272 and T-score of -1.6, and left 33% radius BMD 0.577 and T-score of -2.0), leading to the referral. The patient reported painless indentations in the parietal bones that had been progressing for four years, with no history of head trauma, inflammatory disease, or prolonged steroid use. A head computed tomography (CT) scan showed symmetric thinning of the skull’s parietal bones, with an average thickness of 2.34 mm (compared to 5.1 mm four years earlier). Review of prior images also revealed a T11 compression fracture on spine X-ray from 2019. Laboratory tests showed elevated parathyroid hormone (PTH) 155 pg/mL (reference range 15-65 pg/mL), low vitamin D 25-OH 10.6 ng/mL (reference range 30-100 ng/mL), elevated alkaline phosphatase 142 units/L (reference range 46-116 units/L), and high creatinine level 2.7 mg/dL (reference range 0.5-0.8 mg/dL), other laboratory tests were normal. After discussion with the patient and Nephrology, Denosumab therapy along with Calcium and Vitamin D supplementation were started in November 2023. The patient continues the treatment with antiresorptive medication every 6 months and head CT scan to monitor the skull thinning changes. Discussion: BPT is rare, with only approximately 150 cases reported. Crucial aspects such as its etiology, pathophysiology, treatment, and prognosis remain unknown. It can result from various conditions like trauma, systemic mastocytosis, diabetes mellitus, hereditary diseases, or idiopathic causes and mainly affects women of advanced age. Osteoporosis is suggested as a possible cause based on histological findings on prior studies that propose BPT may result from osteoporosis-induced decreased bone formation rather than increased bone destruction. The reason for excessive bone resorption in the skull of osteoporotic patients remains unclear. Our case highlights progressive and symmetric BPT possibly related to systemic conditions like osteoporosis, with a focus on treatment options. Conclusion: This case sheds light on the clinical presentation, imaging findings, pathogenesis, and treatment options for the rare condition of bilateral parietal bone thinning. Presentation: 6/3/2024

Gender Differences in Outcomes of Ambulatory and Hospitalized Patients With Obesity Hypoventilation Syndrome

Obesity hypoventilation syndrome (OHS) is associated with high morbidity and mortality. There are few data on whether there are gender differences in outcomes. Is female gender associated with worse outcomes in ambulatory and hospitalized patients with OHS? Post hoc analyses were performed on 2 separate OHS cohorts: (1) stable ambulatory patients from the 2 Pickwick randomized controlled trials; and (2) hospitalized patients with acute-on-chronic hypercapnic respiratory failure from a retrospective international cohort. We first conducted bivariate analyses of baseline characteristics and therapeutics between genders. Variables of interest from these analyses were then grouped into linear mixed effects models, Cox proportional hazards models, or logistic regression models to assess the association of gender on various clinical outcomes. The ambulatory prospective cohort included 300 patients (64%female), and the hospitalized retrospective cohort included 1,162 patients (58%female). For both cohorts, women were significantly older and more obese than men. Compared with men, baseline Paco2 was similar in ambulatory patients but higher in hospitalized women. In the ambulatory cohort, in unadjusted analysis, women had increased risk of emergency department visits. However, gender was not associated with the composite outcome of emergency department visit, hospitalization, or all-cause mortality in the fully adjusted model. In the hospitalized cohort, prescription of positive airway pressure was less prevalent in women at discharge. In unadjusted analysis, hospitalized women had a higher mortality at 3, 6, and 12months following hospital discharge compared with men. However, after adjusting for age, gender was not associated with mortality. Although the diagnosis of OHS is established at a more advanced age in women, gender is not independently associated with worse clinical outcomes after adjusting for age. Future studies are needed to examine gender-related health disparities in diagnosis and treatment of OHS.

Childbirth at advanced reproductive age: the impact of biopsychosocial factors on the mode of delivery

Introduction Contemporary society reflects a clear trend towards delayed motherhood, raising significant concerns in the management of pregnancy and childbirth in women of advanced reproductive age. In this context, the mode of delivery and associated risks for this age category require increased attention. Birth methods have been thoroughly examined to identify risks and influencing factors within this specific cohort. Material and methods A descriptive cross-sectional study was conducted on a sample of 528 women. Data were collected using a pre-tested semi-structured questionnaire, and respondents were divided into three groups based on the mode of delivery: vaginal delivery, planned cesarean section, and emergency cesarean section. Sociodemographic, anthropometric, medical, and obstetric characteristics were analyzed using linear regression. Statistical analyses included descriptive and inferential statistics (Chi-square), with a 95.0% confidence interval. Results The analysis revealed statistically significant variations in the mode of delivery based on maternal age (p=0.013) and paternal age (p=0.001), with an increased rate of cesarean sections at more advanced ages. Significant variations were also found in relation to area of residence (p=0.003), education level (p=0.001), nature of work (p=0.028), GP appointments (p=0.020), number of GP appointments(p&lt;0.001), number of obstetrician appointments (p=0.032), time of informing on risk factors (p=0.005), parity (p&lt;0.001), multiple pregnancies (p=0.016), mode of first delivery (p&lt;0.001), pregnancy complications (p=0.003), delivery complications (p&lt;0.001), gestational age at birth (p=0.017), Apgar scores at 1 and 5 minutes (p&lt;0.001). Conclusions Advanced reproductive age has been associated with a higher risk of cesarean section compared to vaginal delivery. The influence of age is modulated by various sociodemographic, medical, and obstetric characteristics, including area of residence, education level, history of cesarean section, parity, pregnancy and delivery complications, pre-existing chronic conditions, antenatal care and provision of information on risk factors.

Autoimmune Metaplastic Atrophic Gastritis (AMAG): Regional Demographics and Their Effect on Prevalence.

Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic immune-mediated form of gastritis characterized by damage to oxyntic cells, ultimately resulting in both iron deficiency with or without anemia and pernicious anemia. The current dogma is that AMAG is a disease of White Northern European women of advanced age. We, therefore, sought to examine the prevalence of AMAG in biopsies obtained from populations enriched for self-identified Hispanics for cross-comparison against data from previously reported populations enriched for self-identified White, non-Hispanic patients. To that end, we prospectively collected 1708 sequential gastric biopsies performed at the University of Miami Hospitals/Jackson Health Systems clinics from 1692 patients over a 1-year period as well as pertinent clinical parameters. These Florida data were then compared against data previously collected from the Baltimore population, which has far lower numbers of Hispanic patients. Self-identified race and/or ethnicity were used. From these 1692 patients, we identified 79 patients (4.6%) with AMAG. These included 60 women (76%) and 19 men (24%), with a F:M ratio of 3.1:1. Patients had a median age of 60 years (range: 15-83). Self-identified race and/or ethnicity were: 60 (76.0%) Hispanic, 9 (11.4%) Black, 9 (11.4%) White, and 1 Asian (1.2%). The median age at initial presentation was: 51 years (range: 15-83) in Hispanics, 77.2 years (range: 46-74) in Blacks, 59 years (range: 49-79) in Whites, and 58 years in the only Asian patient. The overall demographics of AMAG largely mirrored the Florida population, with an over-representation of Hispanics (Florida inhabitants self-report as 70% Hispanic). The overall 4.6% prevalence of AMAG in the Florida population differed significantly from the 1.1% in Baltimore (p < .00001), a finding that presumably reflects the large Hispanic population. In fact, the prevalence of AMAG is far higher in Hispanic patients. Awareness of these data should increase recognition of AMAG in this population.

Vulvar Paget’s Disease with Inguinal Lymph Node Metastasis: A Case Report

Vulvar Paget's disease is a clinical condition with an invariable course affecting women of advanced age, and is associated with a significant rate of recurrence and dissemination, especially in its invasive form, which has a high metastatic potential. Here we present details of a unique case involving a 77-year-old woman with a history of disease progression over more than a decade. She initially presented with an erythematous lesion in the vulvar region, which was later diagnosed as adenocarcinoma in situ. During follow-up, the affected area extended to the perineal and gluteal regions, indicating an invasive aspect of the tumor. Due to surgical oncology recommendations, tissue resection was not feasible. The pacient experienced a significant worsening of symptoms, including local peeling of the affected region, and a biopsy confirmed Paget's disease in the vulvar region. Subsequently, imaging tests indicated changes in the volume of the inguinal lymph nodes. The patient underwent lymphadenectomy for histological analysis and to prevent systemic dissemination. Indicators of lymph node metastasis, suggestive of a gynecological primary site, were observed. Our case provides valuable insights for pathologists to consider the differential diagnosis of vulvar lesions.

Assessing Visceral Fat Percentage with Advancing Age in Women using Bioelectric Impedance Analysis

Obesity and related morbidities are rising globally. This study aims to evaluate the relationship between visceral fat percentage (VF%) and advancing age in 126 female participants aged 20-70 years. These participants underwent anthropometric measurements and Bioelectric Impedance Analysis (BIA). The correlation between VF% and advancing age was 0.42 (P&lt;0.001). BIA is a simple and effective measurement technique for estimating VF%, which can be performed by trained health professionals. This study demonstrated a strong correlation between VF% and advancing age in females.

Effect of LH level on HCG trigger day on clinical outcomes in patients with diminished ovarian reserve undergoing GnRH-antagonist protocol

Research questionDoes luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol?MethodsRetrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups.ResultsIn patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379–10.643, P < 0.05).ConclusionsLHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.

Aging promotes accumulation of senescent and multiciliated cells in human endometrial epithelium.

What changes occur in the endometrium during aging, and do they impact fertility? Both the transcriptome and cellular composition of endometrial samples from women of advanced maternal age (AMA) are significantly different from that of samples from young women, suggesting specific changes in epithelial cells that may affect endometrial receptivity. Aging is associated with the accumulation of senescent cells in aging tissues. Reproductive aging is mostly attributed to the decline in ovarian reserve and oocyte quality, whereas the endometrium is a unique complex tissue that is monthly renewed under hormonal regulation. Several clinical studies have reported lower implantation and pregnancy rates in oocyte recipients of AMA during IVF. Molecular studies have indicated the presence of specific mutations within the epithelial cells of AMA endometrium, along with altered gene expression of bulk endometrial tissue. Endometrial transcriptome profiling was performed for 44 women undergoing HRT during the assessment of endometrial receptivity before IVF. Patients younger than 28 years were considered as the young maternal age (YMA) group (age 23-27 years) and women older than 45 years were considered as the AMA group (age 47-50 years). Endometrial biopsies were obtained on Day 5 of progesterone treatment and RNA was extracted. All endometrial samples were evaluated as being receptive based on the expression of 68 common endometrial receptivity markers. Endometrial samples from another 24 women classified into four age groups (YMA, intermediate age group 1 (IMA1, age 29-35), intermediate age group 2 (IMA2, age 36-44), and AMA) were obtained in the mid-secretory stage of a natural cycle (NC) and used for validation studies across the reproductive lifespan. A total of 24 HRT samples (12 YMA and 12 AMA) were subject to RNA sequencing (RNA-seq) and differential gene expression analysis, 20 samples (10 YMA and 10 AMA) were used for qPCR validation, and 24 NC samples (6 YMA, 6 IMA1, 6 IMA2 and 6AMA) were used for RNA-seq validation of AMA genes across the woman's reproductive lifespan. Immunohistochemistry (IHC) was used to confirm some expression changes at the protein level. Computational deconvolution using six endometrial cell type-specific transcriptomic profiles was conducted to compare the cellular composition between the groups. Comparisons between YMA and AMA samples identified a lower proportion of receptive endometria in the AMA group (P = 0.007). Gene expression profiling identified 491 differentially expressed age-sensitive genes (P adj < 0.05) that revealed the effects of age on endometrial epithelial growth and receptivity, likely contributing to decreased reproductive performance. Our results indicate that changes in the expression of the cellular senescence marker p16INK4a and genes associated with metabolism, inflammation, and hormone response are involved in endometrial aging. Importantly, we demonstrate that the proportion of multi-ciliated cells, as discovered based on RNA-seq data deconvolution and tissue IHC results, is affected by endometrial aging, and propose a putative onset of age-related changes. Furthermore, we propose that aging has an impact on the transcriptomic profile of endometrial tissue in the context of endometrial receptivity. The raw sequencing data reported in this article are deposited at the Gene Expression Omnibus under accession code GSE236128. This retrospective study identified changes in the endometrium of patients undergoing hormonal replacement and validated these changes using samples obtained during a NC. However, future studies must clarify the importance of these findings on the clinical outcomes of assisted reproduction. The findings reported in this study have important implications for devising future strategies aimed at improving fertility management in women of advanced reproductive age. This research was funded by the Estonian Research Council (grant no. PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193), EU 874867 project HUTER, the Horizon Europe NESTOR grant (grant no. 101120075) of the European Commission, the EVA specialty program (grant no. KP111513) of the Maastricht University Medical Center (MUMC+), MICIU/AEI/10.13039/501100011033 and FEDER, EU projects Endo-Map (grant no. PID2021-12728OB-100), ROSY (grant no. CNS2022-135999), and the National Science Fund of Bulgaria (grant no. KII-06 H31/2). The authors declare no competing interests.

Zygotic spindle orientation defines cleavage pattern and nuclear status of human embryos

The first embryonic division represents a starting point for the development of a new individual. In many species, tight control over the first embryonic division ensures its accuracy. However, the first division in humans is often erroneous and can impair embryo development. To delineate the spatiotemporal organization of the first mitotic division typical for normal human embryo development, we systematically analyzed a unique timelapse dataset of 300 IVF embryos that developed into healthy newborns. The zygotic division pattern of these best-quality embryos was compared to their siblings that failed to implant or arrested during cleavage stage. We show that division at the right angle to the juxtaposed pronuclei is preferential and supports faithful zygotic division. Alternative configurations of the first mitosis are associated with reduced clustering of nucleoli and multinucleation at the 2-cell stage, which are more common in women of advanced age. Collectively, these data imply that orientation of the first division predisposes human embryos to genetic (in)stability and may contribute to aneuploidy and age-related infertility.

Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women stimulated with corifollitropin alfa: a non-inferiority randomized controlled trial.

Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women stimulated with corifollitropin alfa: a non-inferiority randomized controlled trial.