Age In Women Research Articles

Irritable Bowel Syndrome Characterization in a Population from Bihor County Romania

Our aim was to analyse the characteristics of a large cohort of patients with IBS from Bihor County. We retrospectively studied 525 patients with IBS admitted between 2018-2023 in Bihor Emergency Clinical County Hospital. We extracted, interpreted and statistically analysed the following parameters: age, gender, environment, family history, smoking and alcohol status, Bristol scale, results of colonoscopy and treatment. The overall prevalence of IBS was 0.2%. Fifty-six % were women, 61% of patients were from urban environment, average age was 57.74 years, with a significant statistical difference between medium age in women vs men. There was a significant statistical correlation between the medium age, medium height, and weight of our patients and smoking status, alcohol consumption, and positive family history. Colonoscopy was done in 148 patients and conditions found in addition to IBS appeared in 7.6% of the cases. The dominant finding was tumoral (4% of IBS cases), followed by various inflammatory conditions. The mean age for patients with normal results was 55.07 years, 50.84 years for patients with inflammatory lesions and 67.81 years for tumoral lesions, with statistically significant correlations between age and the results of colonoscopy. We did not find statistical correlation between Bristol Scale and the results of colonoscopy. Only 142 patients followed specific treatment, suggesting low compliance. The epidemiological traits of our IBS patients seem to remain constant along the time as our research lines up with other studies. Among these, age, female gender and urban provenance seem to be the most significant factors, whereas habits, body mass index, and family history seem not to be statistically significant. As Rome criteria accurately diagnose IBS, we have to remember that colonoscopy should be recommended to a rather small and well selected cases of patients of older age, as in such cohorts tumoral lesions were most frequent.

P-755 Effect of female age and specific cycle characteristics on success in modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)

Abstract Study question Does the age of woman and specific cycle characteristics impact the success of modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)? Summary answer The success rate of mNC/FET cycles is similar in all age groups. As the LH level increased ( above 23.5ng/dL) the success was significantly increased. What is known already The success of frozen embryo transfer can depend on various factors such as the patient’s age, the number of transferred embryos, the duration of embryo culture, and the method used to prepare the endometrium (Holschbach et al. 2023). However, there is currently insufficient evidence in the literature about the effect of age and cycle characteristics on the effectiveness of mNC/FET cycles in patients who have received single top and good quality euploid embryos. Study design, size, duration This study, conducted at Istanbul Memorial Hospital, ART and Reproductive Genetics Center, is a retrospective, single-centre analysis of 583 cycles of euploid mNC/FET in women aged 22-44 years. The study period was from July 2017 to January 2024. The cycles were divided into two groups based on the age of the women. Group A (n = 408) included women under the age of 38, while Group B (n = 175) included women aged 38 or above. Participants/materials, setting, methods The study investigated success predictors in mNC/FET with top and good-quality embryos. Excluded were women with recurrent pregnancy losses, recurrent implantation failure, high BMI (>35kg/m2), uterine/endometrial problems, severe male infertility, and autoimmune diseases. The mNC/FET success was a pregnancy lasting 12 weeks or more. The analysis included patient demographics and cycle outcomes. Chi-square, t-tests, and Mann-Whitney U tests assessed variables with a p-value < 0.005, indicating statistical significance. Main results and the role of chance No significant demographic differences were observed between the two groups, except for AMH levels. AMH levels were significantly higher in younger group than older group (3.02 ng/ml vs. 1.96 ng/ml, p = 0.000). The mNC/FET success rates were similar, with 76% in the younger group and 73% in the older group. Estradiol levels the day before trigger day were significantly higher in older group (278.02 pg/ml vs. 237.84pg/ml, p = 0.028). Both groups had similar mean LH levels (32.50 IU/L and 32.41 IU/L, respectively), estradiol levels and endometrial thickness on the trigger day. In the younger group, LH rise was observed later, follicular phase was longer, and embryo transfer day was later than the older group (p = 0.001). Univariate regression analysis revealed that increased LH level was an important independent variable in achieving mNC/FET success, with a 1.001-fold increase (p = 0.043). The LH levels of 23.5 IU/L or higher predicted high mNC/FET success with 60% sensitivity and 43% specificity based on the Receiver Operating Characteristic curve. (AUC: 0.606, %95 CI 0.540-0.671, p = 0.002). Prolonged infertility duration and previous ET failures reduced mNC/FET success by 0.889 and 0.544-fold, respectively (p = 0.002, p < 0.001). Higher β-hCG levels on days 14 and 16 increased mNC/FET success by 1.038-fold and 1.008-fold, respectively (p < 0.001). Limitations, reasons for caution Our study has limitations as it was retrospective. Prospective randomized studies are needed to evaluate the differences between the young (age <38) and old patient groups (age ≥38) based on mNC/FET success. The association between LH rise and mNC/FET success needs verification with a larger sample. Wider implications of the findings The mNC/FET success rates are similar in young (age <38) and old patient groups (age ≥38). However, prolonged infertility duration and previous failed ET cycles decreased the success of mNC/FET. Additionally, It is important to schedule trigger time after the optimum LH rise, which is 23.5 IU/L or higher. Trial registration number not applicable

P-625 Association between advanced maternal age in women with polycystic ovary syndrome and adverse obstetric outcomes

Abstract Study question What is the effect of advanced maternal on the likelihood of experiencing adverse pregnancy, delivery, and neonatal outcomes in pregnant women with PCOS? Summary answer Advanced maternal age in women with polycystic ovary syndrome confers an additional risk of pregnancy induced hypertension, preeclampsia, preterm delivery, c-section, and placenta previa. What is known already Women with PCOS have an increased risk of obstetric complications, including preterm delivery, PROM, hypertensive disorders, gestational diabetes, cesarean section, and placental abruption. Similarly, the impact of advanced maternal age on pregnancy outcomes has been widely studied. Studies have highlighted the association between advanced maternal age and increased risks of preeclampsia, gestational diabetes mellitus, preterm labor, cesarean section, stillbirth, and fetal growth restriction. The role of advanced maternal age on pregnancy complications in PCOS in a population database has not been thoroughly evaluated. Study design, size, duration A retrospective population-based study using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database was performed. All deliveries between 2004 to 2014, inclusively, were studied using ICD-9 codes. Within the study period, 14,846 women had a diagnosis of PCOS, of which 943 (6.35%) were of significant advanced maternal age (38-43 years/old). The study could not be extended since in 2015 ICD-10 codes were used which are not compatible with ICD-9 codes. Participants/materials, setting, methods Chi-squared tests were used for comparison of demographics. Multivariate logistic regression analysis was performed to calculate unadjusted and adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI), controlling for confounding effects. According to Tri-Council Policy statement (2018), IRB approval was not required, given data was anonymous and publicly available Main results and the role of chance Women with PCOS and advanced maternal age were more likely to develop pregnancy complications, including pregnancy induced hypertension (aOR 1.32; 95% CI: 1.09-1.59; p = 0.004), preeclampsia (aOR 1.51; 95% CI: 1.16-1.98; p = 0.003), and gestational diabetes mellitus (aOR 1.66; 95% CI: 1.40-1.97; p < 0.001), after controlling for confounding demographics. Women with PCOS of advanced maternal age were also at increased risk of delivery by cesarean section (aOR 1.20 95% CI: 1.10-1.43; p < 0.001). Women with PCOS and advanced maternal age were not at an increased risk of preterm delivery, PPROM, placental abruption, chorioamnionitis, operative vaginal delivery, post-partum hemorrhage, wound complications, transfusion, maternal infection, deep vein thrombosis, pulmonary embolism, venous thromboembolism, disseminated intravascular coagulation and eclampsia (p > 0.05 in all cases). Results demonstrated no difference in the rate of women who gave birth to SGA infants, the rate of IUFDs, and the rate of infants with congenital anomalies between the two groups. Limitations, reasons for caution The limitations of our study are its retrospective nature and use of an administrative database which relies on the accuracy and consistency of the individuals coding the data. There are known limitations in how accurately hospital coding is able to capture perinatal conditions and complications. Wider implications of the findings The impact of advanced maternal age on the relationship between PCOS and pregnancy outcomes should be considered when counseling and planning care for pregnant women affected by these conditions. This emphasizes the importance of optimal perinatal care in older women with PCOS as they have higher risks of obstetric complications. Trial registration number NA

O-038 Impact of maternal aging on the DNA repair landscape in mouse oocytes

Abstract Study question How does maternal aging impact DNA damage accumulation and DNA repair capacity in mammalian oocytes? Summary answer Age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in DNA repair capacity. What is known already Oocyte loss occurs progressively from birth and accelerates as women approach their mid-30s, posing a significant challenge to female reproductive health. Recent studies have highlighted the role of the DNA repair response in driving ovarian ageing and oocyte loss. Aged oocytes accumulate elevated levels of DNA damage. Unless repaired, persistent DNA damage activates DNA repair checkpoints, causing the elimination of defective oocytes. Although we know DNA double-strand breaks (DSBs) in oocytes increase with maternal age, surprisingly, little is known about why this damage is not repaired efficiently. Study design, size, duration Oocytes were isolated from ovaries of 8 weeks or 68-86-week-old CD1 mice, which correspond to reproductively young and old females respectively. Over 600 and 1000 oocytes from aged any young females were used to analyse DNA damage levels, DNA repair effciency, DNA repair compartments and for other live assays. Participants/materials, setting, methods DNA damage was induced in CD1 oocytes from young and aged mice using neocarzinostatin. Levels of DNA damage and DNA repair proteins were quantified using immunofluoresnce confocal/STED microscopy. High-resolution light sheet microscopy was used to perform live imaging of dynamics of DNA damage foci and chromosome segregation during meiosis. Main results and the role of chance Our work demonstrates that aged oocytes have a lower DNA repair capacity and reduced mobility of DNA damage sites compared to young oocytes. We further show that incomplete DNA repair results in defective chromosome integrity and partitioning, thereby compromising oocyte quality. To investigate the causes of the age-related decline in DNA repair, we systematically studied the localization and abundance of several DNA repair proteins in oocytes from young and aged mice. We found that DNA repair proteins localized in spatially distinct DNA repair compartments in oocyte nuclei, that form during the late stages of oocyte growth, accompanied by changes in the activity of DNA repair pathways. Several DNA repair proteins, their corresponding compartments, and their response to DNA damage were altered in aged oocytes. Lastly, we demonstrate that age-related cohesin loss increases DNA damage levels and reduces DNA repair capacity. We hypothesize that cohesin dissociation with maternal ageing may make chromosomes prone to accumulate DNA damage without proper DNA repair. Thus, age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in reproductive potential. Limitations, reasons for caution Neocarzinostatin, a radiomimetic drug used to induce DNA DSBs in mouse oocytes in vitro, may not fully represent sources of DNA damage during aging. The CD1 mouse model and ages were selected to recapitulate equivalent advanced maternal age in women. Further investigation is needed to confirm these findings in humans. Wider implications of the findings Overall, we propose that altered DNA repair machinery and cohesin loss contribute to persistent DNA damage and reduced DNA repair capacity in aged oocytes, which can cause chromosome defects and fragmentation, and eventually trigger oocyte death, thereby accelerating the loss of female fertility. Trial registration number Not Applicable

P-688 Fertility and age at childbirth in polycystic ovary syndrome: results from a longitudinal population-based cohort study

Abstract Study question How does fertility differ between women with and without polycystic ovary syndrome (PCOS), and which factors are associated with advanced maternal age? Summary answer Women with PCOS have less births. PCOS was associated with advanced maternal age, with later diagnosis associated with double the rate of advanced maternal age. What is known already PCOS affects 12% or 140 million women globally. Women with PCOS have broad features including ovulatory disturbances and increased infertility; however, few studies have explored reproductive outcomes in PCOS at the end of reproductive age. In the general population advanced maternal age, defined as giving birth after age 35 years, is associated with increased risk of pregnancy complications and reduced fertility. A recent register-based study found increased risk of advanced maternal age in women with PCOS, yet PCOS prevalence was underreported, and the study did not adjust for important confounders. Study design, size, duration Prospective cohort study. Women with (n = 981) and without (n = 13 266) self-reported PCOS diagnosis were compared during a 25-year follow-up. Participants/materials, setting, methods Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women’s Health were assessed with surveys every third year from 1996 (age 18-23 years) to 2021 (age 43-48 years). Main results and the role of chance Overall 9.9% of women reported having PCOS and by 43-48 years, those with PCOS had less births (1.7 ±1.3 vs. 1.9 ±1.2, p < 0.001), and more were nulliparous, 23% vs. 18%, p = 0.003. They were older than women without PCOS at their first, and second childbirth (29.5 ±5.49 vs. 28.8 ±5.48 years and 32.1 ±5.16 vs. 31.1 ±5.00 years, p < 0.001 for both). PCOS was associated with increased odds of advanced maternal age at first childbirth, adjusted odds ratio (aOR) 1.34 (95% confidence interval 1.04-1.75), whereas type 2 diabetes (aOR 0.68 (0.61-1.10)) or hypertension (aOR 0.82 (0.61-1.10)) were not associated with advanced maternal age. Within the PCOS group, a late PCOS diagnosis was associated with increased odds of advanced maternal age, aOR 2.05 (1.24-3.40). Limitations, reasons for caution All outcomes were self-reported. Wider implications of the findings Women with PCOS have lower parity. Later diagnosis is associated with increased odds of advanced maternal age at first childbirth. Given poor reproductive outcomes with increased maternal age, we highlight the importance of earlier diagnosis, patient education and implementation of a reproductive life-plan to optimize attainment of aspirational family size. Trial registration number not applicable

O-085 Oocyte cryopreservation: a comprehensive analysis of live birth rate by age and indication of treatment provides reassurance for young cancer patients

Abstract Study question Does the outcome of oocyte cryopreservation vary across different age groups and treatment indications, i.e. cancer diagnosis, other medical conditions or non medical fertility preservation? Summary answer Live birth rate (LBR) is significantly influenced by a woman's age, although not by indication of treatment. What is known already OC is increasingly applied in assisted reproduction, although little is about the outcomes, including livebirth according to indication. Study design, size, duration Retrospective cohort study analyzing all OC and subsequent warmed oocyte cycles in two fertility centers - Melbourne IVF and the Royal Women’s Hospital, Melbourne, Australia, between the years 2014 to 2022. Participants/materials, setting, methods Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Outcome of stimulation cycles and warmed oocyte cycles were assessed according to women’s age at OCP (≤ 35 years, 35-40 years and ≥ 40 years) and treatment indication- cancer diagnosis, other medical conditions and non medical. Main results and the role of chance 2689 women underwent a total of 3801 cycles of OC, comprising 702 cycles for cancer diagnosis (18.6%), 1146 cycles for other medical (30.5%), and 1953 cycles for non-medical (50.9%). Regardless of indication, younger age groups exhibited a higher median number of mature oocytes: <35 (11, 8-17), 35-40 (9, 6-11), and >40 (6, 3-9) (H(2)=15.1, p < 0.05). Among 582 warmed oocytes cycles, the >40 group demonstrated lower rate cycles with at least one good-quality blastocyst (76.7%) compared to 35-40 (87.1%) and <35 (87.2%), p < 0.05. Cumulative live birth rates (cLBR) were also lower in the >40 age group (14.9%) compared to 35-40 (34.9%) and <35 (46.5%), p < 0.01. When analyzing cycles by indication, patients with cancer had lower oocyte survival rate (80.8% vs 84.8% in other medical and 82.1% in non medical, p < 0.01). Nonetheless, no differences in rate of cycles with at least one good quality embryo rates (cancer diagnosis 87.2%, other medical 82.1% and non medical 89.3%, p = 0.06). Patients with cancer diagnosis had higher clinical miscarriage rate (25%) compared with other medical (7%) and non medical (10.5%), p < 0.01. However, cLBR did not differ between the indication groups (29.7% in cancer diagnosis, 35% in other medical and 38.1% in non medical, p = 0.5. Limitations, reasons for caution Retrospective data collection. Wider implications of the findings Our study offers comprehensive data that may assist patients desiring OC, and provides reassurance that even with a cancer diagnosis, outcomes are as favorable as those having non-medical OC. Given the substantial impact of age, health care providers should, when possible, advise to complete this procedure at a young age. Trial registration number Not applicable

P-152 The impact of one-step fast warming protocol on vitrified-warmed blastocysts on reproductive outcome

Abstract Study question Does the implementation of one-step fast warming protocol affect the post warming quality of embryos and/or the reproductive outcome in frozen embryo replacement cycles? Summary answer The implementation of a one-step fast warming protocol provides similar survival, pregnancy, and clinical pregnancy rates with standard warming protocols. What is known already Cryopreservation process presents a significant challenge for embryos, as the formation of ice crystals can be lethal to their cells. Therefore, effective cryopreservation protocols are essential to mitigate this risk. Vitrification method protects the cells during cryopreservation by transforming water from a liquid state to a glass-like phase, thereby preventing the ice crystals formation. Moreover, the warming procedure can itself contribute to ice crystal formation, particularly through recrystallization. Studies have shown that embryo survival is related to warming rate and a one-step fasting warming protocol can be equally or more effective than the conventional protocol. Study design, size, duration This prospective randomized study was performed at Embryolab Fertility Clinic, in Thessaloniki, Greece between July and December 2023 and included 118 frozen embryo transfers. Both study and control group included only expanded blastocysts of good quality (AA or AB according to Gardner’s criteria). Control group was matched to the study group according to treatment, time period, woman age, quality of embryos and number of transferred embryos. The embryos were vitrified using open system. Participants/materials, setting, methods Fast warming group included embryos that were warmed using the one-step warming protocol: the embryos were exposed to 1M sucrose solution for 1’ at 37 °C and then immediately placed into culture media where laser-assisted hatching was performed. Control group included embryos that were warmed using conventional protocol: 1’ in 1M, 2’ in 0.5M, 2’ in 0.25M and 3’ in washing solution at room temperature and then placed into culture media for laser-assisted hatching. Main results and the role of chance The analyzed cases were 118 in total, 59 in the fast-warming group and 59 in the control group. Survival rate was 100% in both groups. Pregnancy rate (positive b-HCG) was not significantly different between the two groups: 72.41% in the fast-warming group and 67.79% in the control group (p = 0.687). Clinical pregnancy rate was also not significant between the two groups: 78.26% in the fast-warming group and 81.81% in the control group (p = 0.753). Limitations, reasons for caution The study included a limited number of cases, and information on the live birth rate was still pending. To establish the efficacy of fast warming conclusively, it is recommended that additional prospective randomized studies be conducted to validate its potential benefits. Wider implications of the findings One-step fast warming protocol resulted in similar survival rates post warm compared to the conventional warming protocol, while pregnancy and clinical pregnancy rates were not significantly different. Furthermore, it is worth noting that by minimizing the duration of the warming protocol, the workflow efficiency in the IVF laboratory is enhanced. Trial registration number N/A

O-244 AMH levels in infertile women in APAC region - prospective study in multiple countries, ethnicities and centres

Abstract Secretary General, Asia Pacific Initiative on Reproductive (ASPIRE) President, Taiwan Endometriosis Society Founder & CEO, Taipei Fertility Center AMH is produced by granulosa cells of small growing follicles in the ovary and serum AMH levels strongly correlate with the number of growing follicles, AMH has been used clinically as a marker for ovarian reserve. Despite being of similar ages, with similar AMH levels, durations of ovarian stimulation, and gonadotropin doses, Asian women have been documented as having decreased AFCs and lower yields of total and mature oocytes after ovarian stimulation compared to their Caucasian counter- parts. These earlier data suggested that the effect of ethnicity was as an independent marker of ovarian reserve and potentially subsequent reproductive outcomes. We conducted the first multi-nation, multi-centre, and multi-ethnicity prospective cohort study from January 2020 to May 2021 to investigate serum AMH profiles among infertile Asian women. A total of 4613 women who visited fertility clinics at 12 IVF centres in 11 regions throughout Asia were recruited from Taiwan, China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia (2 centres), Thailand, Vietnam, and Singapore. The inclusion criteria were female partners aged 20–43years and naive to any ovarian stimulation cycle. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. Among the 12 centres that joined the study, most demonstrated racial homogeneity except for Singapore and Malaysia which presented a highly diverse ethnic profile, while others were supposedly monoethnic communities. Unexplained or male infertility is the most common infertility cause in most countries, except for China with a notably high incidence of tubal disease. Age, ethnicity, obesity, and PCOS are significantly associated with ovarian reserve. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%), yet remarkably lean with lower obesity rate was found in Vietnamese. Serum AMH levels are not affected by smoking or GnRHa and OCPs pretreatment but are affected by endometrioma surgery. Moreover, the assay can be conveniently conducted on any day of the menstrual cycle and is not influenced by the use of fresh or frozen samples. The rate of decline in ovarian reserve increases with age in Asian women, at 0.13ng/ml/year at 25–33years old and 0.31ng/ ml/year at 33–43 years old. We also found that a cut-off at 4.0 ng/ml could be considered for PCOS diagnosis in the Asian region. Despite limitations, the results can help guide clinicians for personalized infertility treatment, and call for further investigation into the effects of genetic, environmental and lifestyle factors on ovarian reserve.

Static and dynamic analysis of cerebral blood flow in fifty-six large arterial vessel networks

Objective. The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset. Approach. We analysed a publicly available vessel dataset from a cohort of 56 (32/24F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort. Main results. Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (<6°) between blood pressure and blood flow at the cardiac frequency. Significance. These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

Management and outcomes for older women with early breast cancer treated with primary endocrine therapy (PET)

BackgroundThis study reports the detailed management and outcomes of women treated with Primary Endocrine Therapy (PET) in a large prospective UK cohort of older women (≥70) with breast cancer. MethodsThis was an unplanned secondary analysis of a prospective, multicentre, observational study (The Age Gap study). Data were collected at baseline and regular intervals on patient, tumour and treatment characteristics with tumour RECIST response category recorded. Direct study follow-up was 24 months with longer-term survival data obtained from the UK cancer registry. ResultsThe Age Gap study recruited 3316 women across 56 breast units. Primary endocrine therapy (PET) was initiated for 505/3316 (15 %) women; median age was 84 (IQR 79–88) with median follow-up 41.9 months (IQR 27–60). Death occurred in 205/505(40.6 %) patients, 160/205; 78 % non- Breast Cancer related, 45/205; 21.9 % Breast Cancer related. Multivariate analysis identified older age (HR-1.055(95 % Confidence Interval: 1.029–1.084); P < 0.001) and higher Charlson Index (HR-1.166 (1.086–1.252); P < 0.001) as risk factors for all-cause mortality, but conversion to surgery (HR-0.372(0.152–0.914); P = 0.031) was protective. Grade 3 cancer (G1 vs G3 HR-0.28 (0.094–0.829); P = 0.022 & G2 vs G3 HR-0.469 (0.226–0.973); P = 0.042), axillary positivity (axilla positivity HR-2.548 (1.321–4.816); P = 0.005) and change of endocrine therapy (HR-3.010 (1.532–5.913); P = 0.001) were associated with worse breast cancer specific survival (BCSS). RECIST category was not significantly associated with either overall survival or BCSS (P > 0.05). ConclusionEarly disease response and change of endocrine therapy are not significantly associated with overall survival, conversion to surgery is linked to improved outcome. Prognosis is largely determined by age and comorbidity in older women treated with PET.

Sex- and age-related shift of relapse phenotypes in a cohort of relapsing multiple sclerosis patients: Post hoc analysis from the OPERA phase 3 trials.

Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men. Using the large well-defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open-label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex- and age-related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35-44, ≥45 years). Exact p-values are given for this exploratory analysis. Frequencies of mono- versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35-44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35-44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only. We describe sex-specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations.

Laparoscopic Indocyanine Green-Guided Sentinel Lymph Node Biopsy for Gallbladder Neoplasms.

Surgical resection, the only potentially curative treatment for gallbladder cancer (GBC), entails an extended cholecystectomy with portal lymphadenectomy. Lymph node dissection is a key staging procedure, but its therapeutic value is unclear. Additionally, it is technically challenging and potentially harmful. Methods for better assessment of lymph node status are needed. This report presents a case of indocyanine green (ICG)-guided sentinel lymph node biopsy (SNLB) for a patient with a gallbladder mass suspicious for GBC. An 81-year-old woman consulted for abdominal discomfort. Abdominal ultrasound showed an intraluminal gallbladder mass suspicious for GBC. Staging imaging did not show liver invasion, lymphadenopathy, or distant metastasis. Given the woman's advanced age and limited extent of disease, a laparoscopic extended cholecystectomy with an ICG-guided SLNB was performed. Injection of 1 ml of ICG (0.125 mg/mL) into the gallbladder bed was performed using a 22-gauge needle, avoiding direct injection into the gallbladder wall. A near-infrared camera was used to visualize real-time ICG flow through the lymphatic vessels of the gallbladder toward the cystic node. Then, a sentinel lymph node posterolateral to the bile duct (station 12b) was identified. The node was resected and sent for permanent section. The procedure continued with an extended cholecystectomy. Pathology showed an intracholecystic papillary neoplasm with high-grade dysplasia. Cystic and sentinel lymph nodes were negative for malignancy. For patients with gallbladder neoplasms, ICG-guided SLNB is a feasible technique that could allow for treatment de-escalation. Further evaluation in clinical trials is needed.

The role of bacterial genital infections in spontaneous preterm delivery: a case-control study.

Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth. The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed. The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of Chlamydia trachomatis, Neisseria gonorrhea, Listeria monocytogenes, and Mycoplasma genitalium infections was zero in both groups. The highest prevalence of Gardnerella vaginalis was 19 (19%) in the case group and Ureaplasma parvum 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between Gardnerella vaginalis bacteria and spontaneous preterm delivery. The results of our study showed that except for Gardnerella vaginalis bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers.

Quality of hospital labour and delivery care: A multilevel analysis in Southern Nations and Nationalities People's Region of Ethiopia.

Ethiopia has one of the highest maternal mortality ratios in Africa. Few have examined the quality of labour and delivery (L&D) care in the country. This study evaluated the quality of routine L&D care and identified patient-level and hospital-level factors associated with the quality of care in a subset of government hospitals. This was a facility-based, cross-sectional study using direct non-participant observation carried out in 2016. All mothers who received routine L&D care services at government hospitals (n = 20) in one of the populous regions of Ethiopia, Southern Nations Nationalities and People's Region (SNNPR), were included. Mixed effects multilevel linear regression modeling was employed in two stages using hospital as a random effect, with quality of L&D care as the outcome and selected patient and hospital characteristics as independent variables. Patient characteristics included woman's age, number of previous births, number of skilled attendants involved in care process, and presence of any danger sign in current pregnancy. Hospital characteristics included teaching hospital status, mean number of attended births in the previous year, number of fulltime skilled attendants in the L&D ward, whether the hospital had offered refresher training on L&D care in the previous 12 months, and the extent to which the hospital met the 2014 Ethiopian Ministry of Health standards regarding to resources available for providing quality of L&D care (measured on a 0-100% scale). These standards pertain to availability of human resource by category and training status, availability of essential drugs, supplies and equipment in L&D ward, availability of laboratory services and safe blood, and availability of essential guidelines for key L&D care processes. On average, the hospitals met two-thirds of the standards for L&D care quality, with substantial variation between hospitals (standard deviation 10.9 percentage points). While the highest performing hospital met 91.3% of standards, the lowest performing hospital met only 35.8% of the standards. Hospitals had the highest adherence to standards in the domain of immediate and essential newborn care practices (86.8%), followed by the domain of care during the second and third stages of labour (77.9%). Hospitals scored substantially lower in the domains of active management of third stage of labour (AMTSL) (42.2%), interpersonal communication (47.2%), and initial assessment of the woman in labour (59.6%). We found the quality of L&D care score was significantly higher for women who had a history of any danger sign (β = 5.66; p-value = 0.001) and for women who were cared for at a teaching hospital (β = 12.10; p-value = 0.005). Additionally, hospitals with lower volume and more resources available for L&D care (P-values < 0.01) had higher L&D quality scores. Overall, the quality of L&D care provided to labouring mothers at government hospitals in SNNPR was limited. Lack of adherence to standards in the areas of the critical tasks of initial assessment, AMTSL, interpersonal communication during L&D, and respect for women's preferences are especially concerning. Without greater attention to the quality of L&D care, regardless of how accessible hospital L&D care becomes, maternal and neonatal mortality rates are unlikely to decrease substantially.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

The Correlation of Paternal Age on Semen Parameters in Assisted Reproduction: A Retrospective Study in Qassim, Saudi Arabia.

In the past, fertility concerns have predominantly revolved around the effect of a woman's age on the quality of her eggs and the success of her pregnancy. While men generally retain their ability to father children throughout their lives, there is evidence suggesting a decline in natural conception rates as paternal age increases. A growing body of research indicates a potential link between advanced paternal age (APA) and various adverse outcomes, including changes in sperm genetics, reduced conception rates, higher rates of miscarriage, lower live birth rates, and even long-term health consequences in offspring. However, it remains unclear whether there is an association between APA and the effectiveness of assisted reproductive technology (ART). This study aims to shed light on the relationship between APA and semen parameters. This is a retrospective, descriptive study analyzing data from electronic medical records of men undergoing ART at a fertility clinic in Saudia Arabia(2017-2022). Men aged 21-60 with at least one semen analysis and no missing data/hormonal treatment were included. Data on age and semen parameters (count, motility, and morphology) were extracted and analyzed using Jeffreys's Amazing Statistics Program (JASP; University of Amsterdam, Amsterdam, Netherlands) (descriptive statistics, Spearman's rank correlation). Analysis of 1506 men undergoing ART revealed a mean age of 37 years (SD=6.94) and a mean sperm count of 55.0 million/mL (SD=46.05). The correlation between age and sperm count indicates a minimal association (r=0.075, p<0.01); moderate positive correlations were observed between sperm count and motility (r=0.406); count and morphology (r=0.543); and motility and morphology (r=0.458). Age may not be a major factor in overall sperm parametersfor this population, but a strong positive correlation was observed between sperm count, motility, and normal morphology. These findings suggest that these semen parameters are interconnected, with higher sperm counts potentially indicating better overall sperm quality.

Indirect Determination of Hematological Reference Intervals in Healthy Moroccan Adults Using Outpatient Data.

Reference intervals are essential for the interpretation of clinical laboratory tests and patient management. This study aims to determine age and gender reference intervals of complete blood count (CBC) in the Moroccan population by using the indirect approach. The study used data of ostensibly healthy adults collected retrospectively using the laboratory information system (LIS) of the Laboratory for Research and Medical Analysis of the Fraternal Royal Gendarmerie in Rabat (Morocco), between January 2018 and February 2020. The study included 5,898 men and 10,172 women ranging in age from 18 to 90 years. The lower and upper reference limits of CBC parameters were calculated using the nonparametric technique, as suggested by the Clinical and Laboratory Standards Institute (CLSI). All hematological parameters showed no clinically significant gender-related differences, except small differences in the values of hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). There were also no clinically significant agerelated differences for median values of all hematology analytes in both genders, except for platelet count (PLT) that continued to decline with increasing age in men and women, and Red blood cell count (RBC), Hematocrit (HCT), and hemoglobin (HB) that tended to increase with age but decrease in older age groups in men while they tended to increase with age in women. The indirect method can be used to establish reference intervals for CBC, with appropriate selection criteria and statistical tools. Our findings differed from the reference ranges provided in the textbook and also in other countries' reports.

Commentary on “Age and postoperative opioid use in women undergoing pelvic organ prolapse surgery”

Commentary on “Age and postoperative opioid use in women undergoing pelvic organ prolapse surgery”

Associations between use of chemical hair products and epigenetic age: Findings from the Sister Study

Background: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women. Methods: In a subset of 4358 participants aged 35–74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003–2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions. Associations were estimated both overall and by self-identified race and ethnicity, adjusting for chronological age, socioeconomic and lifestyle factors, body mass index, menopausal status, and DNA methylation platform. Results: Associations between the use of hair products and the three epigenetic age measures were largely null. Use of hair permanents/body waves was modestly associated with higher DunedinPACE among all participants (β ever-never = 0.010; 95% confidence interval [CI] = 0.001, 0.019) and with lower PhenoAgeAccel among Black women (β ever-never = −1.53; 95% CI = −2.84, −0.21). Conclusion: In this US-based study, we found little evidence of associations between chemical hair product use and epigenetic age in Black and non-Hispanic White women. Observed associations were modest and largely not supported by dose–response relationships or were inconsistent across epigenetic age measures. Previously observed associations between chemical hair product use and aging-related health outcomes may not be explained by the biological aging pathways captured by DunedinPACE, GrimAgeAccel, or PhenoAgeAccel. Alternative biological pathways are worth investigating in racially diverse samples.

Brentuximab vedotin therapy followed by autologous peripheral stem cell transplantation as a viable treatment option for an older adult with transformed lymphoma: a case report and literature review.

This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.