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Itamar Glick,1 Ela Kadish,2 Misgav Rottenstreich1,3 1Department of Obstetrics & Gynecology, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 2Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 3Department of Nursing, Jerusalem College of Technology, Jerusalem, IsraelCorrespondence: Misgav RottenstreichDepartment of Obstetrics and Gynecology, 12 Bayit Shaare Zedek Medical Center, Jerusalem, 91031, IsraelTel +972 2- 655-5562Fax +972 2- 666-6053Email misgavr@gmail.comAbstract: Pregnancy at advanced maternal age (age > 35 years old) is considered a risk factor for adverse maternal and perinatal outcomes. Yet, pregnancies of advanced maternal age have become more prevalent over the last few decades. Possible maternal complications of pregnancy at age 35 or older include increased risk of spontaneous miscarriage, preterm labor, gestational diabetes mellitus, pre-eclampsia, stillbirth, chromosomal abnormalities, and cesarean delivery. Possible adverse fetal outcomes include infants small for gestational age and intrauterine growth restrictions, low Apgar score, admission to neonatal intensive care units, and an autism spectrum disorder. This paper aims to present an up-to-date review of the literature, summarizing the most current studies and implications for the management of pregnancy of advanced maternal age.Keywords: advanced maternal age, adverse maternal outcome, adverse perinatal outcome

Abstract Background Seizure control during pregnancy and obstetric outcomes are of important concerns for women with epilepsy (WWE) and their families. Advanced maternal age (≥35 years) shows a growing trend in the society with changes of lifestyle, which also occurs in diseased populations. The advanced maternal age is an independent factor for some unsatisfying obstetric outcomes. In this study we explored the seizure control and obstetric complications associated with advanced maternal age in WWE. Methods This study was based on the epilepsy pregnancy registry at West China Hospital. Patients with epilepsy in this registry who were aged 35 or older when starting pregnancy were included in this study. Their basic demographics and detailed information on epilepsy management and obstetric issues in all trimesters and during 1-year follow-up after birth were documented and reviewed. Data were processed by IBM SPSS version 22.0. The demographic characteristics, seizure frequency, treatment change, obstetric complications, and outcomes were analyzed and compared. Results Fifteen patients were included in this study, with an average age of 36.32 ± 2.39 years at pregnancy, and 73.33% of them were primiparas. The change of seizure frequency during pregnancy was not in a clear pattern, but there was an increased incidence of tonic-clonic seizures during the mid- and last trimesters. More than 20% of the patients had obstetric complications throughout the trimesters, including vaginal bleeding, hypothyroidism, and pre-eclampsia. The pre-eclampsia seemed extraordinarily complicated with other conditions. However, none of the complications were related with malformations or poor outcome of babies after 1-year follow-up. Conclusion Advanced maternal age combined with WWE is associated with frequent common obstetric complications. Future controlled studies with large sample sizes are needed to explore the related risks in comparison with other WWE and non-epileptic populations.

Abstract Background The number of women delivering at advanced maternal age (AMA; > = 35) continuously increases in developed and high‐income countries. Large cohort studies have associated AMA with increased risks of various pregnancy complications and adverse pregnancy outcomes, which raises great concerns about the adverse effect of AMA on the long‐term health of offspring. Specific acquired characteristics of parents can be passed on to descendants through certain molecular mechanisms, yet the underlying connection between AMA‐related alterations in parents and that in offspring remains largely uncharted. Methods We profiled the DNA methylomes of paired parental peripheral bloods and cord bloods from 20 nuclear families, including 10 AMA and 10 Young, and additional transcriptomes of 10 paired maternal peripheral bloods and cord bloods. Results We revealed that AMA induced aging‐like changes in DNA methylome and gene expression in both parents and offspring. The expression changes in several genes, such as SLC28A3, were highly relevant to the disorder in DNA methylation. In addition, AMA‐related differentially methylated regions (DMRs) identified in mother and offspring groups showed remarkable similarities in both genomic locations and biological functions, mainly involving neuron differentiation, metabolism, and histone modification pathways. AMA‐related differentially expressed genes (DEGs) shared by mother and offspring groups were highly enriched in the processes of immune cell activation and mitotic nuclear division. We further uncovered developmental‐dependent dynamics for the DNA methylation of intergenerationally correlated DMRs during pre‐implantation embryonic development, as well as diverse gene expression patterns during gametogenesis and early embryonic development for those common AMA‐related DEGs presenting intergenerational correlation, such as CD24. Moreover, some intergenerational DEGs, typified by HTRA3, also showed the same significant alterations in AMA MII oocyte or blastocyst. Conclusions Our results reveal potential intergenerational inheritance of both AMA‐related DNA methylome and transcriptome and provide new insights to understand health problems in AMA offspring.

Background: The number of nulliparous women over the age of 35 is consistently increasing, and the optimal delivery strategy is a subject of ongoing discussion. This study compares perinatal outcomes in nulliparous women aged ≥35 years undergoing a trial of labor (TOL) versus a planned cesarean delivery (CD). Methods: A retrospective cohort study including all nulliparous women ≥ 35 years who delivered a single term fetus at a single center between 2007–2019. We compared obstetric and perinatal outcomes according to mode of delivery—TOL versus a planned CD, in three different age groups: (1) 35–37 years, (2) 38–40 years, and (3) >40 years. Results: Out of 103,920 deliveries during the study period, 3034 women met the inclusion criteria. Of them, 1626 (53.59%) were 35–37 years old (group 1), 848 (27.95%) were 38–40 (group 2), and 560 (18.46%) were >40 years (group 3). TOL rates decreased as age increased: 87.7% in group 1, 79.3% in group 2, and 50.1% in group 3, p < 0.001. Rates of successful vaginal delivery were 83.4% in group 1, 79.0% in group 2, and 69.4% in group 3, p < 0.001). Neonatal outcomes were comparable between a TOL and a planned CD. Using multivariate logistic regression, maternal age was found to be independently associated with slightly increased odds for a failed TOL (aOR = 1.13, CI 95% 1.067–1.202). Conclusions: A TOL at advanced maternal age appears to be safe, with considerable success rates. As maternal age advances, there is a small additive risk of intrapartum CD.

Introduction—The purpose of this study was to determine the relative impact of modifiable and non-modifiable risk factors in the development of gestational diabetes mellitus (GDM), with a particular focus on maternal preconception body mass index (BMI) and age, two important determinants of insulin resistance. Understanding the factors that contribute most to the current escalation of GDM rates in pregnant women could help to inform prevention and intervention strategies, particularly in areas where this female endocrine disorder has an elevated prevalence. Methods—A retrospective, contemporary, large population of singleton pregnant women from southern Italy who underwent 75 g OGTT for GDM screening was enrolled at the Endocrinology Unit, “Pugliese Ciaccio” Hospital, Catanzaro. Relevant clinical data were collected, and the characteristics of women diagnosed with GDM or with normal glucose tolerance were compared. The effect estimates of maternal preconception BMI and age as risk factors for GDM development were calculated through correlation and logistic regression analysis by adjusting for potential confounders. Results—Out of the 3856 women enrolled, 885 (23.0%) were diagnosed with GDM as per IADPSG criteria. Advanced maternal age (≥35 years), gravidity, reproductive history of spontaneous abortion(s), previous GDM, and thyroid and thrombophilic diseases, all emerged as non-modifiable risk factors of GDM, whereas preconception overweight or obesity was the sole potentially modifiable risk factor among those investigated. Maternal preconception BMI, but not age, had a moderate positive association with fasting glucose levels at the time of 75 g OGTT (Pearson coefficient: 0.245, p < 0.001). Abnormalities in fasting glucose drove the majority (60%) of the GDM diagnoses in this study. Maternal preconception obesity almost tripled the risk of developing GDM, but even being overweight resulted in a more pronounced increased risk of developing GDM than advanced maternal age (adjusted OR for preconception overweight: 1.63, 95% CI 1.320–2.019; adjusted OR for advanced maternal age: 1.45, 95% CI 1.184–1.776). Conclusions—Excess body weight prior to conception leads to more detrimental metabolic effects than advanced maternal age in pregnant women with GDM. Thus, in areas in which GDM is particularly common, such as southern Italy, measures aiming to counteracting maternal preconception overweight and obesity may be efficient in reducing GDM prevalence.

Mitochondria transfer techniques were first designed to prevent the transmission of diseases due to mutations in mtDNA, as these organelles are exclusively transmitted to the offspring by the oocyte. Despite this, given the crucial role of mitochondria in oocyte maturation, fertilization and subsequent embryo development, these approaches have been proposed as new potential strategies to overcome poor oocyte quality in infertile patients. This condition is a very common cause of infertility in patients of advanced maternal age, and patients with previous in vitro fertilization (IVF) attempt failures of oocyte origin. In this context, the enrichment or the replacement of the whole set of the oocyte mitochondria may improve its quality and increase these patients' chances of success after an IVF treatment. In this short review, we will provide a brief overview of the main human studies using heterologous and autologous mitochondria transfer techniques in the reproductive field, focusing on the etiology of the treated patients and the final outcome. Although there is no current clearly superior mitochondria transfer technique, efforts must be made in order to optimize them and bring them into regular clinical practice, giving these patients a chance to achieve a pregnancy with their own oocytes. [ABSTRACT FROM AUTHOR]

Objective: To determine what patient and embryo characteristics are correlated with the developmental potential of the peri-implantation embryo.Design: Retrospective study.Setting: Research laboratory.Patients: Six hundred fifty-one cryopreserved human blastocysts donated for research with informed patient consent.Interventions: Not applicable.Main Outcome Measures: Blastocyst attachment to fibronectin-coated plates, trophectoderm outgrowth area, epiblast cell number, total cell number, human chorionic gonadotropin secretion.Results: Patients' body mass index, age, follicle-stimulating hormone: luteinizing hormone ratio on menstrual cycle day 3, antral follicle count on menstrual cycle day 3, antimüllerian hormone level on menstrual cycle day 3, and blastocyst morphological grade were correlated with peri-implantation development outcomes. After controlling for good-quality morphological grades, blastocysts from patients of advanced maternal age developed fewer epiblast cells than blastocysts from younger patients.Conclusions: Extended embryo culture during the peri-implantation period mirrors several disparities in fertility treatment outcome that we see clinically, including those from patients with advanced maternal age, high body mass index, and low ovarian reserve and from embryos with lower-quality morphological grades. This model system may be useful by providing an alternative or more sensitive endpoint assessment in studying patient, clinical, or laboratory factors that may influence preimplantation embryo developmental potential. [ABSTRACT FROM AUTHOR]

The average age of women at childbirth in high resource obstetric settings has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin in the presence of an additional risk factor for pre-eclampsia and offered serial ultrasounds for fetal growth and wellbeing. Given the increased risk of antepartum stillbirth, induction of labour from 39 weeks' gestation should be discussed with woman. [ABSTRACT FROM AUTHOR]

Copyright of Antropo is the property of Antropo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The distribution of the microbiome in women with advanced maternal age (AMA) is poorly understood. To gain insight into this, the vaginal and gut microbiota of 62 women were sampled and sequenced using the 16S rRNA technique. These women were divided into three groups, namely, the AMA (age ≥ 35 years, n = 13) group, the non-advanced maternal age (NMA) (age < 35 years, n = 38) group, and the control group (non-pregnant healthy women, age >35 years, n = 11). We found that the alpha diversity of vaginal microbiota in the AMA group significantly increased. However, the beta diversity significantly decreased in the AMA group compared with the control group. There was no significant difference in the diversity of gut microbiota among the three groups. The distributions of microbiota were significantly different among AMA, NMA, and control groups. In vaginal microbiota, the abundance of Lactobacillus was higher in the pregnant groups. Bifidobacterium was significantly enriched in the AMA group. In gut microbiota, Prevotella bivia was significantly enriched in the AMA group. Vaginal and gut microbiota in women with AMA were noticeably different from the NMA and non-pregnant women, and this phenomenon is probably related to the increased risk of complications in women with AMA. [ABSTRACT FROM AUTHOR]

Advanced maternal age (AMA) denotes an age of ≥35 years during the time of delivery. Maternal metabolism affects the offspring's physical and neurological development as well as their cognitive function. This study aimed to elucidate the effects of exercise training among old female animals on the cognitive function, hippocampal neuroplasticity, mitochondrial function, and apoptosis in the offspring. We found that the offspring of mothers with AMA without exercise training had decreased spatial learning and memory, brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95) protein levels, neurogenesis, and mitochondrial function, as well as hippocampal cell death. Contrastingly, offspring of mothers with AMA with exercise training showed improved spatial learning, memory, hippocampal neuroplasticity, and mitochondrial function. These findings indicate that despite the AMA, increasing fitness through exercise significantly contributes to a positive prenatal environment for fetuses. The maternal exercises augmented the hippocampal levels of BDNF, which prevents decreased cognitive function in the offspring of mothers with AMA. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess trends in maternal age in central China and to examine the relationship between maternal age and adverse pregnancy outcomes. This was a retrospective and observational study. Data were analysed from the Wuhan Maternal and Child Health Management Information System, which included all pregnant women who were at 24–42 weeks' gestation, with singleton pregnancies and who lived in Wuhan between 2010 and 2017. Joinpoint regression was used to analyse the trends in mean maternal age and the proportion of women with advanced maternal age. Adverse pregnancy outcomes, including pregnancy-induced hypertension (PIH) disorder, gestational diabetes mellitus (GDM), caesarean delivery, postpartum haemorrhage, preterm birth, small for gestational age, large for gestational age (LGA) and 5-min Apgar score <7 among women aged <20, 20–24, 30–35 and ≥40 years were compared with women aged 25–29 years using multivariate binary logistic regression analysis and stratified analysis. Among the 583,571 women included in this study, 1.2% were aged <20 years, 20.8% were aged 20–24 years, 47.9% were aged 25–29 years, 22.0% were aged 30–34 years, 6.9% were aged 35–39 years and 1.2% were aged ≥40 years. Between 2010 and 2017, the mean maternal age increased from 27.1 years to 29.7 years, and the proportion of women aged ≥35 years increased from 4.3% to 13.9%. Relative to women aged 25–29 years, women aged ≥30 years carried higher risks of PIH, GDM, caesarean delivery, preterm birth, LGA and 5-min Apgar score <7. Relative to older multiparous women, older nulliparous women were more likely to experience caesarean delivery, preterm birth and 5-min Apgar score <7. The average maternal age and the proportion of advanced maternal age showed increasing trends between 2010 and 2017, which may be related to the relaxation of the one-child policy in China. Older maternal age (≥30 years) is independently associated with various adverse pregnancy outcomes. The risks of adverse pregnancy outcomes may occur earlier than the commonly used definition of advanced maternal age (≥35 years) and may also differ by parity. Ensuring age- and parity-specific clinical counselling, antenatal surveillance and health interventions may significantly improve pregnancy outcomes in older mothers. [ABSTRACT FROM AUTHOR]

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The current embryo selection methods rely on subjective grading of embryo morphology or a real-time monitoring of the embryonic development and assessment of multiple quantitative endpoints. Even up to 40% of morphologically normal embryos harbour aneuploidies. Preimplantation genetic testing (PGT) is a technology, which gives opportunity to identify euploid embryos before implantation. Aims: This study seeks to determine the role of PGT in poor prognosis patients, i.e., patients with advanced maternal age (AMA) (maternal age ≥35 years), recurrent pregnancy loss (RPL) (miscarriages ≥2) and recurrent implantation failures (RIFs) (in vitro fertilisation failures ≥3). Setting and Design: A retrospective case--control study was done on a group of patients who underwent intracytoplasmic sperm injection for the indications of AMA, RPL and RIF. Materials and Methods: In 33 cases who opted for PGT, day 5 blastocysts were subjected to trophectoderm biopsy with the help of next-generation sequencing. Euploid blastocyst was transferred in hormone replacement cycle at a later date. In 154 controls, blastocyst transfer was done based on morphological grading. Pregnancy outcomes are compared in terms of implantation rate, pregnancy rate, miscarriage rate and multiple pregnancy rate. Statistical Analysis Used: Chi-square test was used for comparisons between the study groups with respect to percentage. P < 0.05 was considered statistically significant. Results: The highest aneuploidy rate was found in embryos with AMA. Implantation rate was found to be statistically significantly higher in the PGT group as compared to the non-PGT group. However, take-home baby rates were not improved by PGT. There were less number of mean embryos transferred in the PGT group and lower multiple pregnancy rate. Conclusions: With the application of PGT, embryo selection rates and implantation rates improved in poor prognosis patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of maternal age on the rate of cesarean delivery in women undergoing induction at term.Study Design: Retrospective cohort study of term singleton gestations in nulliparous women induced for any indication at Lehigh Valley Health Network from July 2010 to July 2013. Exposure of interest was maternal age. Primary outcome was cesarean delivery. For every one woman ≥35 years of age (exposed), 2-3 women <35 years of age were selected as unexposed subjects for comparison. Statistical analysis included bivariate and multivariable techniques.Results: 406 patients were included; 101 women ≥35 years of age and 305 women <35 years of age. Women in the ≥35 group were more likely to be induced for maternal medical conditions and less likely to be induced for prolonged pregnancy; few inductions were elective. Few women were induced electively in either group. More than half of women in both groups required cervical ripening. Method of cervical ripening and/or induction and percentage of women with a Bishop score <5 were similar between groups. The primary outcome, cesarean delivery, was similar between groups (45.5% in age ≥35 group vs 40.0% in age <35 group, p = .33). After adjustment for potential confounders, the rate of cesarean delivery was not influenced by maternal age (AOR 1.21 [0.76, 1.91], p = .42) but was higher in women with a Bishop score <5 at the time of induction of labor [AOR 1.64 [1.09, 2.47], p = .02].Conclusion: In the wake of several recent trials underscoring the safety and potential maternal and fetal benefit of labor induction, identifying predictors of induction success (and failure) takes on increasing importance. Our findings suggest that maternal age is not an independent risk factor for cesarean delivery in women undergoing induction. [ABSTRACT FROM AUTHOR]

Background: During the last decades, the age of pregnant women significantly increased. The incidence of maternal and labor complications is higher among older women, but conclusive data have not been delivered whether labor epidural analgesia (EA) may affect the duration of labor and delivery outcomes in this population of patients. The aim of this study is to evaluate the effect of EA among women aged over 35 years.Methods: We retrospectively reviewed medical records of all, singleton, at term deliveries, laboring with EA, between December 2011 and October 2017. Women aged ≥35 years (study group) were compared with women aged <35 years (control group) to evaluate EA effects on the duration of labor and neonatal outcome.Results: The study enrolled 459 women with EA: 122 women were included in the study group and 337 in the control group. The multiple regression analysis showed that parity was an independent variable for a shorter dilation period (p = .002), second stage length (p = .0001) and for the total labor duration (p = .0001); neonatal weight was significant for a shorter dilation period (p = .005) and for the total labor duration (p = .002); maternal age and cervical dilatation at the beginning of EA did not influence neither the period of the labor stages nor the total labor duration (p > .05).Conclusions: Results of this study indicate that women aged ≥35 with EA may have labor duration and neonatal short-term outcomes similar to younger women with EA. [ABSTRACT FROM AUTHOR]

Purpose: To determine which factors predict pregnancy outcome in women aged 40 years and above who underwent in-vitro fertilization. Method: We conducted a retrospective case-control study of 631 women aged 40–46 years, who underwent a total of 904 IVF cycles with autologous gametes. We used stepwise logistic regression analysis to develop predictors of pregnancy, clinical pregnancy and live birth outcomes. Data are presented as mean ± SD, percentage and confidence intervals. Results: Predictors of live birth included maternal (95% CI: 0.36–0.78) and paternal (95% CI: 0.62–0.94) age, the number of follicels > 14 mm (95% CI: 1.2–3.2), the number of oocytes collected (95% CI: 1.3–2.9) the number of metaphase II oocytes (95% CI: 1.3–2.4) and the number of cleavage stage embryos (95% CI: 1.8–2.6). The predictors of pregnancy and clinical pregnancy were similar but did not include male age (P > 0.05). To further determine the role of male age in live birth a control group of women younger than 40 years was collected. Male age was not a significant predictor of live birth among younger women (P = 0.42). Conclusions: Female age and better ovarian stimulation were confirmed as predictors of outcomes in older women doing IVF. However, male age was also noted to be a significant individual predictor of live birth in women over 40 years of age, but not in younger women doing IVF.

• In recent decades, there has been a noticeable increase in the number of women aged over 40 years choosing to pursue childbearing. • The main risk factors for intrapartum Cesarean delivery among older women include nulliparity, regional factors, labor induction, administration of antibiotics during labor, multiple gestation, prior cesarean delivery, and the presence of gestational diabetes or pre-eclampsia. • By utilizing our risk score, caregivers can provide more informed consultations to women aged over 40 years who are considering their options for mode of delivery. To determine risk factors and to develop a risk prediction score for intrapartum cesarean delivery (CD) in women over 40 years old. A retrospective cohort study, in a single university-affiliated tertiary medical center. All women aged 40 years or more who planned a trial of labor between 2012 and 2022. Women who opted for an elective CD and those with non-viable fetuses were excluded. Maternal and neonatal characteristics of women who delivered vaginally were compared to those who underwent an intrapartum CD. Risk factors were examined using univariate and multivariate analysis. A score was developed to predict the need for intrapartum CD. We assessed a receiver operating characteristic curve to evaluate the performance of our model. An unplanned intrapartum cesarean section. During the study period, 122,583 women delivered at our center, of whom 6122 (4.9 %) aged 40 years or more attempted a trial of labor. Of them, 428 (7 %) underwent intrapartum CD. Several independent risk factors were identified, including nulliparity, regional anesthesia, induction of labor, use of antibiotics during labor, multiple gestation, previous cesarean delivery, and the presence of gestational diabetes or preeclampsia. A risk score model, employing a cut-off of 7, demonstrated successful prediction of intrapartum CD, with an area under the curve of 0.86. The score model for intrapartum CD can be used by caregivers to offer a more informed consultation to women aged 40 years or more deciding on the mode of delivery. [ABSTRACT FROM AUTHOR]

The distribution of the microbiome in women with advanced maternal age (AMA) is poorly understood. To gain insight into this, the vaginal and gut microbiota of 62 women were sampled and sequenced using the 16S rRNA technique. These women were divided into three groups, namely, the AMA (age ≥ 35 years, n = 13) group, the non-advanced maternal age (NMA) (age < 35 years, n = 38) group, and the control group (non-pregnant healthy women, age >35 years, n = 11). We found that the alpha diversity of vaginal microbiota in the AMA group significantly increased. However, the beta diversity significantly decreased in the AMA group compared with the control group. There was no significant difference in the diversity of gut microbiota among the three groups. The distributions of microbiota were significantly different among AMA, NMA, and control groups. In vaginal microbiota, the abundance of Lactobacillus was higher in the pregnant groups. Bifidobacterium was significantly enriched in the AMA group. In gut microbiota, Prevotella bivia was significantly enriched in the AMA group. Vaginal and gut microbiota in women with AMA were noticeably different from the NMA and non-pregnant women, and this phenomenon is probably related to the increased risk of complications in women with AMA.

Background: A tertiary-hospital-based retrospective study (2011-2019) was conducted to determine the mediating role of hypertensive disorders of pregnancy and abnormal placentations between advanced maternal age and adverse neonatal outcomes. Methods: Data from a tertiary-hospital-based retrospective study (n= 23051) was used and conducted regression-based mediation analysis to assess the mediating role of hypertensive disorders of pregnancy and abnormal placentation between the advanced maternal age and adverse neonatal outcomes. Results: After adjusting for confounding factors, the indirect effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight mediated by hypertensive disorders of pregnancy was [aOR 4.95 (95% CI: 4.05, 5.85)], [aOR 2.82 (95% CI: 1.78, 3.86)], and [aOR 5.90 (95% CI: 4.93, 6.87)], respectively. The indirect effect of advanced maternal age on preterm births and low birth weight mediated by abnormal placentation was [aOR 6.83 (95% CI: 5.70, 7.97)] and [aOR 4.18 (95% CI: 3.26, 5.11)]. About, 23%, 37%, and 17% of the effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight was mediated by hypertensive disorders of pregnancy, respectively. Furthermore, abnormal placentation mediates the association between advanced maternal age and preterm births by 18% and low birth weight by 23%. Conclusion: Hypertensive disorders of pregnancy and abnormal placentation partially mediate the association between advanced maternal age and adverse neonatal outcomes.

Abstract Background Nulliparity is considered to be a risk factor of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). With the new two-child policy launched in 2016, more Chinese women have delivered their 2nd baby. Yet few studies have assessed the impact of parity on adverse birth outcomes in China. This study aimed to examine the association between parity and risks of PTB, LBW and SGA in a Chinese population. The combined effects of maternal age and parity on adverse birth outcomes were also assessed. Methods This retrospective study included all non-malformed live births born during January 1, 2014 and December 31, 2018 in Chengdu, China. A total of 746,410 eligible live singletons with complete information were included in the analysis. Parity was classified into nulliparity (i.e. has never delivered a newborn before) and multiparity (i.e. has delivered at least one newborn before). Log-binomial regression analyses were applied to evaluate the association between parity and PTB, LBW and SGA. We further divided maternal age into different groups (

Abstract Background In the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA. Methods This retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed. Results The overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies. Conclusion There is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.

Abstract Objective To assess the positive predictive value (PPV) of noninvasive prenatal testing (NIPT) as a screening test for sex chromosome aneuploidy (SCA) with different maternal characteristics and prenatal decisions in positive cases. Materials and methods We retrospectively analysed 45,773 singleton pregnancies with different characteristics that were subjected to NIPT in the Maternity and Child Health Hospital of Anhui Province. The results were validated by karyotyping. Clinical data, diagnostic results, and data on pregnancy outcomes were collected. Results In total, 314 cases were SCA positive by NIPT; among those, 143 underwent invasive prenatal diagnostic testing, and 58 were true-positive. Overall, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 12.5%, 51.72%, 66.67% and 83.33%, respectively. Interestingly, when only pregnant women of advanced maternal age (AMA) were screened, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 23.81%, 53.33%, 78.95%, and 66.67%, respectively. The frequency of SCA was significantly higher in the AMA group than in the non-AMA group. The frequencies of 47,XXX and 47,XXY were significantly correlated with maternal age. Conclusion NIPT performed better in predicting sex chromosome trisomies than monosomy X, and patients with 45,X positive foetuses were more eager to terminate pregnancy than those with 47,XXX and 47,XYY. AMA may be a risk factor of having a foetus with SCA. Our findings may assist in genetic counselling of AMA pregnant women. Our pre- and posttest counselling are essential for familiarizing pregnant women with the benefits and limitations of NIPT, which may ease their anxiety and enable them to make informed choices for further diagnosis and pregnancy decisions.

Objectives: To assess the association between advanced maternal age and adverse perinatal outcomes in single pregnancies. Materials and methods: A cohort study was conducted using data from 27,455 singleton births attended at our hospital between 2007 and 2018. Three maternal age groups were established, and perinatal outcomes were compared between-groups (40 years (n = 846; 3.1%). The data were compared using chi-square analysis and the results were adjusted using a logistic regression model. Decision trees were designed to examine the fetal mortality and caesarean section variables. We used the SPSS 23 statistical software program for the statistical analysis. Results: The mean age of the women was 31.21 years. No differences were found associated with age for neonatal acidosis, an Apgar score 35 years of age had worse perinatal outcomes, compared with younger women. This finding was more evident in patients >40 years of age, which highlighted the greater risk of fetal death and serious maternal complications in this group.

According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth? Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35–40 years, using real-world data from the Deutsches IVF-Register. Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35–40 years with normal ovarian reserve. Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials. [ABSTRACT FROM AUTHOR]

The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along with preimplantation genetic testing, although developed to improve the live birth rate (LBR) and reduce the risk of multiple pregnancies, are drawing attention to the possible increase in obstetric and perinatal risks, and adverse epigenetic consequences in offspring. Furthermore, ethical–legal concerns are growing regarding the increase in cryopreservation and storage of frozen embryos. In an attempt to reduce the risk associated with prolonged embryo culture and avoid embryo storage, we have chosen to inseminate a limited number of oocytes not exceeding the number of embryos to be transferred, after two days or less of culture. We retrospectively analyzed 245 ICSI cycles performed in 184 infertile couples with a female partner aged ≥40 from January 2016 to July 2021. The results showed a fertilization rate of 95.7%, a miscarriage rate of 48.9%, and a LBR of 10% with twin pregnancies of 16.7%. The cumulative LBR in our group of couples was 13%. No embryos were frozen. In conclusion, these results suggest that oocyte selection and embryo transfer at the cleaving stage constitute a practice that has a LBR comparable to that of the more commonly used protocols in older women who have reduced ovarian reserve.

Purpose: Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach. Methods: All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted. Results: The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€. Conclusions: During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts. [ABSTRACT FROM AUTHOR]

Objective: To compare pregnancy rates of donor versus partner sperm in intrauterine insemination (IUI) cycles in women aged 38 years and above. Methods: A retrospective cohort study was performed using data from 944 women aged 38–43 years old who underwent a combined 1596 IUI cycles at an academic fertility clinic in Montreal, Canada between February 2009 to April 2018. Results: Partner sperm was used in 1421 cycles (89.0%), and donor sperm was inseminated in 175 cycles (11.0%). Mean ages of the women were 39.8 (±1.5) and 40.2 (±1.6) years in the partner and donor insemination groups, respectively (P < 0.001). Positive serum (β human chorionic gonadotropin) pregnancy rate in the partner sperm group was 9.0% (n = 128) whereas that in the donor insemination group was 9.7% (n = 17) (P = 0.759). Clinical pregnancy rates were 5.8% (n = 83) and 8.0% (n = 14) in the respective groups (P = 0.260). There were five multiple gestation (twin) pregnancies in the cohort, three in those undergoing IUI with partner sperm and two in those undergoing IUI with donor sperm. Conclusion: In women aged 38–43 years undergoing IUI with controlled ovarian stimulation, using donor sperm, compared with partner sperm, did not increase rate of pregnancy. Donor sperm, when compared with partner sperm, does not increase pregnancy rates from intrauterine insemination in women with advanced reproductive ages 38–42 years old. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation.Methods: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS).Results: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester.Conclusion: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age. [ABSTRACT FROM AUTHOR]

Women of advanced maternal age (AMA) with pregnancies resulting from assisted reproductive technology (ART) have a high risk of the onset and progression of anxious and depressive disorders, associated with adverse obstetric and perinatal outcomes. The aim. To improve the mental well-being of pregnant AMA women after ART using the developed algorithm of preventive psychological support. Materials and methods. The prospective study comprised 150 patients divided into three equal groups of 50 nulliparous women aged 35-45 years with a singleton pregnancy in the cephalic presentation: the main group consolidated of pregnant women after ART who have got routine psychological support; patients with a pregnancy after ART included to the comparison group and patients with a spontaneous pregnancy from the control group were not consulted routinely. To estimate the psychological condition of the patients the level of maternal anxiety using the Spielberg State-Trait Anxiety Inventory (STAI); sleep quality using Pittsburgh Sleep Quality Index (PSQI); the presence of depressive manifestations using Edinburgh Postnatal Depression Scale (EPDS) were assessed. Results. We did not observe a significant difference in trait (TA) and state anxiety (SA) levels between the main and comparison groups at terms of 22-24 weeks of gestation; however, these values were significantly lower in the control group. The numbers of patients with high TA and SA levels in the main and comparison groups were also significantly higher than in the control group (p < 0.05). We observed no significant increase in TA and SA levels in the main group at gestational terms of 35-37 weeks, in contrast to the comparison and control group. The number of patients with high TA and SA levels in the main group remained significantly lower than in the comparison group. A gradual decrease in TA and SA levels in all groups was observed in the postpartum period, but the differences between the groups remained consistent. We did not observe a significant difference in sleep quality score between the study groups at terms of 22-24 weeks of gestation. Patients of all study groups reported sleep disturbance with the pregnancy progression, but average PSQI values at terms of 35-37 weeks of gestation and 6-8 weeks after delivery were significantly lower in the main group compared to the comparison group. The incidence and severity of postnatal depressive symptoms, along with the number of patients at high risk of developing depression in the postpartum, were significantly lower in the main group than in the comparison group. Conclusions. AMA patients after ART formed a high-risk group for developing anxious and depressive disorders during the pregnancy and postpartum. High anxiety levels compromised sleep patterns have leaded to poorer quality of life of women. Preventive psychological support for patients during the pregnancy and postpartum enabled early detection and correction of depressive symptoms; validly reduced anxiety levels, improved sleep quality and consequently improved the quality of life of women and prevented adverse obstetric, perinatal, and psychiatric outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To discover the profiles of different steroid hormones at the maternal-fetal interface and reveal the change characteristics in pregnant women at advanced maternal age (AMA). Methods: Forty pregnant women were recruited in the study, including 20 AMA women (age ≥ 35) and 20 normal controls (age < 35 and without pregnancy complications). Among AMA women, 6 (AMA2) had pregnancy complications, and 14 (AMA1) had no complications. Their maternal blood (MB), placental tissue (P), and fetal cord blood (CB) were collected, and 18 different steroid hormone metabolites were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: The estradiol (E2) levels in MB were higher than those in P and CB. In contrast, the estrone (E1) and estriol (E3) levels were higher in P and CB. Compared with the progesterone levels (P4) in MB, those in P and CB were higher; however, cortisol (F) levels were deficient. In contrast, F in MB was maintained at an elevated level. Further, cortisone (E) levels in CB were higher than those in MB and P. Except for the decline of testosterone (T), androstenedione (A2) and Dihydrotestosterone (DHT), there were no significant differences in the other 15 steroid hormones in MB between the AMA1 and the control group (p>0.05). Compared with the AMA1 group, androgen levels were significantly higher in AMA2, especially in T (1.55 vs. 0.68 ng/ml, p=0.023), A2 (2.27 vs. 0.92 ng/ml, p=0.011) and Dehydroepiandrosterone (DHEA) (2.39 vs. 1.50 ng/ml, p=0.028). However, there were no significant changes in P and CB between two groups. Conclusion: There are distribution rules and cascade changes of steroid profiles in maternal-fetal compartments. Significantly high androgen levels in AMA women have a positive relationship with adverse pregnancy complications. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the influence of advanced maternal age on the maternal and neonatal outcomes of preterm pregnancies. Material and methods: The characteristics of patients admitted to the Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University between January 2015 and March, 2019 were retrospectively reviewed. The maternal and neonatal outcomes were compared between advanced maternal age group (≥ 35 years) and younger age group (18-34 years). Statistical analysis was performed by applying the SPSS software. Results: The study population consisted of 986 pregnancies with preterm delivery and 1094 liveborn preterm infants. Multivariate analyses demonstrated that mothers of advanced age were more likely to suffer iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus and postpartum hemorrhage, but less likely to suffer multiple gestation. In terms of neonatal outcomes, advanced maternal age was associated with a decreased rate of low birthweight in an adjusted model without multiple gestation. However, with multiple gestation included in the adjusted model, advanced maternal age was only associated with an increased rate of hyperbilirubinemia. Conclusions: Advanced maternal age was a risk factor for adverse pregnancy outcomes including iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus, postpartum hemorrhage, and a protective factor for multiple gestation. Regarding neonatal outcomes, advanced maternal age was related to a decreased rate of low birthweight or an increased rate of hyperbilirubinemia depending on the adjustment for multiple gestation. [ABSTRACT FROM AUTHOR]

Background: Advanced maternal age, single status and use of assisted reproductive technology (ART) are increasing in mothers in high-income countries, and all are known risk factors for negative obstetric outcomes. Less is known about their long-term consequences for childhood morbidity. Thus, the aim of this study was to investigate morbidity up to five years of age, in the children of older, single, and/or ART-treated mothers.Methods: A cross-sectional using Swedish registers was performed comprising 23 772 children. The prevalence of diagnosis and the number of hospital visits for specialist care, were compared and analyzed in relation to maternal age at childbirth, maternal civil status, and mode of conception. The odds ratio for specialized care within each ICD-chapter were estimated using single and multiple logistic regression.Results: Children born to single mothers and children conceived using ART had significantly more outpatient visits for specialist care and significantly more diagnoses compared to children with married/cohabiting mothers, and spontaneously conceived children. Children born to mothers of advanced maternal age (≥40) had fewer in- and outpatient visits. However, they were significantly more often diagnosed within ICD-chapters XVI, XVII i.e., they experienced more morbidity in the neonatal period.Conclusion: The results indicate that children born to single mothers and children of ART-treated mothers have a higher morbidity and consume more specialist care than children of married/cohabiting and spontaneously pregnant mothers. We conclude that the use of ART, maternal single status and advanced maternal age are risk factors of importance to consider in pediatric care and when counseling women who are considering ART treatment. [ABSTRACT FROM AUTHOR]

In women at the advanced age of 43–45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? A retrospective cohort study was conducted at a university hospital reproductive centre. The computerized database of 394 women aged 43–45 years undergoing 1528 non-donor IVF or intracytoplasmic sperm injection cycles between 2010 and 2019 was analysed. A decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. The cumulative clinical pregnancy rate was 15.0% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women who should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and body mass index. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. Women over 43.5 years old with fewer than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Methods: Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non‐personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non‐AMA (<38 years old) patients was also conducted. Results: The CPR and LBR of the pET group were significantly higher than those of the npET group (37.7% vs. 20.0%, adjusted OR: 2.64; 95%CI, 1.70–4.11, p < 0.001 and 29.9% vs. 9.7%, adjusted OR: 4.13; 95%CI, 2.40–7.13, p < 0.001, respectively). Furthermore, in the subanalyses, the CPR and LBR of the pET group were significantly higher than those of the npET group in both the AMA non‐AMA patients. Conclusions: The new ERPeakSM endometrial receptivity test is a useful alternative diagnostic tool for poor‐prognosis patients, regardless of age.Personalized embryo transfer guided by a new endometrial receptivity test significantly improved clinical pregnancy rate and live birth rate in patients with recurrent implantation failure, regardless of age. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The main detrimental factor in female fertility is maternal age. Clinical pregnancy and live birth rates decline gradually with age and this decline is dramatical over 40 years. In this study, we examined the in vitro fertilization/intracytoplasmic sperm injection cycle outcomes of women aged 40 years and over. STUDY DESIGN: This retrospective cohort study included 336 fresh in vitro fertilization/ICSI cycles of women aged =40 years. Six groups, stratified by one-year intervals were composed according to age: 40 years; 41 years; 42 years; 43 years; 44 years, and =45 years. The primary outcomes were the clinical pregnancy and live birth rates. RESULTS: The clinical pregnancy rate was 18.6% in 40 years old women and it decreased to 4% in women aged =45 years. The live birth rates in women aged 40 and 41 years (10% and 6.1% respectively) were higher than the live birth rates in women aged 42 and 43 years (4.3% and 3.8% respectively). There was no live birth in women aged 44 and over. The miscarriage rate was 46.2% at age 40 and it increased to 100% at age 44 and over. CONCLUSION: The clinical pregnancy and the live birth rates decreased significantly with every single year after 40 years of age. In patients between the ages of 40-43, the live birth rate is acceptable but starting an in vitro fertilization cycle beyond 43 years of age does not seem to be reasonable. [ABSTRACT FROM AUTHOR]

Ukba Asefa,1 Wolde Melese Ayele2 1Department of Gynecology and Obstetrics, Dessie Specialized Referral Hospital, Dessie, Amhara Regional State, Ethiopia; 2Department of Epidemiology and Biostatistics, Wollo University, Dessie, Amhara Regional State, EthiopiaCorrespondence: Wolde Melese AyeleDepartment of Epidemiology and Biostatistics, Wollo University, Dessie 1145, EthiopiaTel +251921885231Email wolde400@gmail.comPurpose: It is known that being pregnant at any reproductive age is not risk-free. Aside from this, older gravidity usually ends up with adverse outcomes both to the mother and newborn. Hence, the aim of this study was to investigate the association of adverse maternal and perinatal outcomes with advanced maternal age pregnancy in Northeastern Ethiopia.Methods: A hospital-based comparative cross-sectional study was employed among pregnant mothers. The study was conducted among advanced age (≥ 35 years, n= 398) mothers and adult age (20– 34 years, n=398) mothers. Socio-demographic, obstetrics, and pregnancy outcomes were checked from patient records. Descriptive statistics were used to describe parameters collected from patient records and comparing the two groups. Bivariable and multivariable logistic regressions were done to determine factors associated with maternal and perinatal outcomes. The magnitude of the association was measured using odds ratio at 95% confidence level and statistical significance was declared at a P-value of < 0.05.Results: Advanced age mothers had significantly higher adverse pregnancy outcomes (64.6% vs 37.8%) compared with adult age mothers. This study shows that advanced maternal age is statistically associated with pregnancy-induced hypertension (AOR=3.14, 95% CI: 1.931– 5.089), antepartum hemorrhage (AOR=2.22, 95% CI: 1.245– 3.942), a cesarean delivery (AOR=2.59, 95% CI: 1.775– 3.790), and postpartum hemorrhage (AOR=2.01, 95% CI: 1.445– 2.819). Moreover, advanced maternal age pregnancy was also a risk factor for preterm delivery (AOR=3.01, 95% CI: 1.441– 6.297), low birth weight (AOR=3.08, 95% CI: 1.735– 5.492), low fifth minute Apgar score (AOR=3.99, 95% CI: 2.099– 7.618), and perinatal death (AOR= 2.46, 95% CI: 1.360– 4.42).Conclusion: In this study, adverse pregnancy and perinatal outcomes among advanced aged mothers were high in a specialized hospital where emergency obstetric and newborn care is set and quality obstetric care is expected. Therefore, healthcare providers, the specialized hospital, and policymakers should give due emphasis to the effective intervention of advanced age pregnant mothers.Keywords: advanced maternal age, pregnancy, adverse obstetric outcome, adverse perinatal outcomes, Ethiopia

Abstract Background To determine whether advanced maternal age (AMA) causes changes in the maternal serum markers of Trisomy 21, 18 and open neural tube defects (ONTD) during the second trimester of pregnancy. Our research aims to develop new cut-off values for AMA in order to reduce the need for further invasive testing. Methods This retrospective cohort study involved 12,739 pregnant women with AMA and 197,101 pregnant women with non-AMA. We then compared the two groups with respect to the positive rate and positive predictive value (PPV) of Trisomy 21, 18 and ONTD. Pregnant women with Trisomy 21, 18 and ONTD were diagnosed by karyotyping the amniotic fluid and by ultrasound diagnosis. Results Compared to the non-AMA group, the multiple of the median (MOM) of free beta- human chorionic gonadotropin (free β-hCG), alpha-fetoprotein (AFP), and the risk value forTrisomy 21, were significantly higher in the AMA group (all P

Abstract Background Globally, delayed childbearing to the advanced age is a growing option. It is an emerging public health issue in developing countries. Currently, adverse perinatal outcomes significantly increased. A few studies showed the effect of advanced maternal age on adverse perinatal outcomes. However, most used secondary data or chart reviews, and this increases the risk of biases. Besides, there are limited studies in-country Ethiopia as advanced maternal age steadily increased. Therefore, this study aimed to assess the status of advanced maternal age and its effect on perinatal outcomes in the study setting. Methods A community-based prospective cohort study was conducted among 709 study participants from October 15, 2018, to September 30, 2019, in Arba Minch zuria, and Gacho Baba district, southern Ethiopia. The data were collected by a pretested interviewer-administered structured Open Data Kit survey tool and analyzed by SPSS version 25. The log-linear regression model was used to compare perinatal outcomes among women aged 20–34 years and ≥ 35 years. The log-likelihood ratio tested for the goodness of fit. In this study, P-value

Abstract Background This study aimed to evaluate the incidence rates and risks of pregnancy complications among nulliparous and multiparous women with advanced maternal age (AMA, ≥35 years) in China. Methods We performed a community-based prospective cohort study of 10,171 pregnant women in selected two sub-districts and 11 towns of Liuyang from 2013 to 2015. All subjects were followed up from the first prenatal care (at ≤12 weeks) to delivery, and risks of pregnancy complications were compared by parity and maternal age groups. Results Among nulliparas, women with AMA showed significantly increased risks for gestational hypertension (OR 8.44, 95%CI 1.68–2.88), preeclampsia/eclampsia (OR 9.92, 95%CI 4.87–18.78), premature rupture of membrane (OR 6.84, 95%CI 2.00–17.69), as compared to women in the 20–29-year age group. Among multiparas with AMA, increased risks were found for gestational diabetes mellitus (OR 3.29, 95%CI 1.76–5.94), anemia (OR 1.85, 95%CI 1.25–2.69), polyhydramnios (OR 3.29, 95%CI 1.56–6.64), premature rupture of membrane (OR 5.14, 95%CI 2.12–12.29), and preterm labor (OR 1.89, 95CI 1.42–2.50). Conclusions Women with AMA were associated with increased risks of pregnancy complications, and complications with increased risks differed in nulliparas and multiparas. Women with AMA should be identified as a high-risk group in clinical practice.

The effects of advanced maternal age (AMA) on the neurodevelopment of offspring are becoming increasingly important. Myelination is an important aspect of brain development; however, a limited number of studies have focused on the effects of AMA on myelination in offspring. The current study aims to evaluate the association between AMA and myelin sheath development in offspring. We studied the learning and memory function of immature offspring using the novel object recognition test. Then, we investigated the expression of myelin basic protein (MBP) in the immature offspring of young (3-month-old) and old (12-month-old) female rats at different time points (14, 28, and 60 days) after birth with immunofluorescence and western blotting. The myelin sheath ultrastructure was observed with transmission electron microscopy in immature and mature offspring. Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were investigated by western blot in immature offspring at the above time points. AMA impaired the memory function of offspring during early postnatal days. The MBP expression level gradually increased with postnatal development in the offspring of both the AMA and Control (Ctl) groups, but the MBP level in the offspring of the AMA group was lower than that of the Ctl group at 14 days after birth. In addition, the ultrastructure of the myelin sheath was defective in AMA offspring during the early postnatal period; however, the myelin sheath was not significantly affected in offspring during adulthood. Interestingly, ERK phosphorylation at 14 days after birth was lower in AMA offspring than in Ctl offspring. However, ERK phosphorylation at 28 days after birth was higher in AMA offspring than in Ctl offspring. The peak of ERK phosphorylation in the AMA group was abnormal and delayed. Our results indicated that AMA is associated with poor developmental myelin formation in offspring. The ERK signaling pathway may play an essential role in the adverse effects of AMA on the offspring myelin sheath development.

ObjectivesTo discover the profiles of different steroid hormones at the maternal-fetal interface and reveal the change characteristics in pregnant women at advanced maternal age (AMA).MethodsForty pregnant women were recruited in the study, including 20 AMA women (age ≥ 35) and 20 normal controls (age < 35 and without pregnancy complications). Among AMA women, 6 (AMA2) had pregnancy complications, and 14 (AMA1) had no complications. Their maternal blood (MB), placental tissue (P), and fetal cord blood (CB) were collected, and 18 different steroid hormone metabolites were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsThe estradiol (E2) levels in MB were higher than those in P and CB. In contrast, the estrone (E1) and estriol (E3) levels were higher in P and CB. Compared with the progesterone levels (P4) in MB, those in P and CB were higher; however, cortisol (F) levels were deficient. In contrast, F in MB was maintained at an elevated level. Further, cortisone (E) levels in CB were higher than those in MB and P. Except for the decline of testosterone (T), androstenedione (A2) and Dihydrotestosterone (DHT), there were no significant differences in the other 15 steroid hormones in MB between the AMA1 and the control group (p>0.05). Compared with the AMA1 group, androgen levels were significantly higher in AMA2, especially in T (1.55 vs. 0.68 ng/ml, p=0.023), A2 (2.27 vs. 0.92 ng/ml, p=0.011) and Dehydroepiandrosterone (DHEA) (2.39 vs. 1.50 ng/ml, p=0.028). However, there were no significant changes in P and CB between two groups.ConclusionThere are distribution rules and cascade changes of steroid profiles in maternal-fetal compartments. Significantly high androgen levels in AMA women have a positive relationship with adverse pregnancy complications.

Abstract Purpose To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Methods Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non‐personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non‐AMA (

Research Question: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF?, Design: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight., Results: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates., Conclusions: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to determine the effect of advanced maternal age (AMA) on maternal and neonatal outcomes in pregnant women aged >35 years compared with patients aged 30-34 years. Also, we aimed to analyze the risk estimates of potential confounders to identify whether these variables contributed to the development of adverse pregnancy outcomes or not. Methods: This retrospective cohort study included 2284 pregnant women aged >35 years at the time of delivery who was delivered in a tertiary referral hospital from January 1,2016, to December 31, 2020. We further classified these women into two subgroups: 35-39 years as early AMA (EAMA), and >40 years as very AMA (VAMA). Pregnancy complications and adverse neonatal outcomes were recorded. Results: Compared to younger women, pregnant AMA women had significantly higher risks of complicated pregnancies, including a higher risk of gestational diabetes mellitus (GDM, p<0.001), polyhydramnios (p<0.001), cesarean section (p<0.001), stillbirths (p<0.001), major fetal abnormality (p<0.001), preterm delivery (p<0.001), lower birth weight (p<0.001), lower 5-minute Apgar scores (p<0.001), lower umbilical artery blood pH values (p<0.001), neonatal intensive care unit (NICU) admission (p<0.001), and length of NICU stay (p<0.001). Conclusion: We found a strong and significant association between VAMA and adverse pregnancy outcomes, including an increased risk of GDM, polyhydramnios, cesarean section, and adverse neonatal outcomes, including a higher risk of stillbirths, preterm delivery, lower birth weight, lower 5-minute Apgar scores, and NICU admission. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities are often detected in women with reproductive problems. This study aimed to investigate the presence and type of chromosomal aberrations in peripheral blood of women undergoing in vitro fertilization (IVF) and their possible association with advanced maternal age (AMA). A total of 1,837 women undergoing IVF between 2016 and 2019 were enrolled in the study. Women were further divided in AMA (≥35 years) and younger women (<35 years). Chromosomal abnormalities were detected by peripheral blood karyotyping using standard cytogenetic techniques. Chromosomal abnormalities were detected in 13.5% of the enrolled women; 1.1% had autosomal abnormalities including reciprocal translocations, inversions, Robertsonian translocations, and a supernumerary marker chromosome, while 12.4% had X chromosome abnormalities. The frequency of chromosomal abnormalities was significantly higher in AMA women than in younger ones (17.4% vs. 3.9%, p < 0.05). Women of AMA exhibited X chromosome mosaicism with a frequency of 16.1%, and mosaic karyotypes with 2 and 3 aneuploid cell lines were more frequently detected. X chromosome mosaicism is the most common karyotypic aberration in women undergoing IVF and has 6-fold increased incidence in AMA women compared to younger ones. The present study verifies previous observations that low-level peripheral blood X chromosome mosaicism and the number of aneuploid cell lines observed in women of AMA could be an indication of aneuploidy and poor quality of oocytes contributing to infertility. [ABSTRACT FROM AUTHOR]

Objective: To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies. Methods: This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications. The subsequent management and pregnancy outcomes of these women were followed up. Results: The rate of cell-free DNA test failure at the first sampling was 1.49%, and 78.4% of failures were due to a low fetal fraction. Of the 66 women who refused any subsequent management, an adverse pregnancy outcome was seen in 5 cases, all belonging to the high-risk group. Of the 13 low-risk women who chose second-trimester maternal serum screening, all obtained a low-risk maternal serum screening result and an unaffected pregnancy outcome. A redraw was chosen by 171 women, which yielded a result in 75.4% and their pregnancy outcomes were unaffected; 42 women had an uninformative result again and received an amniocentesis. As 158 women had an amniocentesis after the first sampling, this procedure was offered in 200 cases altogether. Abnormal genetic testing results were shown in six (3%, 6/200) cases, all in the high-risk group. Conclusions: High-risk pregnant women with cell-free DNA test failure are at increased risk of adverse pregnancy outcomes. A second sampling for cell-free DNA test or maternal serum screening might be suggested to low-risk women. Invasive prenatal diagnosis should be offered to the high-risk patients, especially those with a second cell-free DNA test failure. [ABSTRACT FROM AUTHOR]

Introduction: With the implementation of the universal two-child policy, the number of pregnant women of advanced maternal age (AMA) will increase steadily. We aimed to investigate whether the effect of gestational weight gain on insulin resistance (IR) before delivery was mediated by serum adipokine concentrations in AMA.Material and Methods: This cross-sectional study included 80 pregnant women of AMA recruited consecutively before delivery from the Department of Obstetrics and Gynecology between August 2016 and July 2017. At delivery, maternal weight during the third trimester was recorded and serum adipokines were measured. IR was calculated using the homeostasis model assessment 2 (HOMA2) method.Results: Weight gain (WG) during the third trimester was positively associated with serum leptin concentrations (r = 0.34, p = 0.0018) and HOMA-IR indices (r = 0.25, p = 0.025), but not related with serum concentration of adiponectin (r = 0.12, p = 0.28). WG during the third trimester and serum concentration of leptin were independently associated with the level of HOMA-IR by multivariate analysis. Subsequently, according to mediation analysis, the association between WG during the third trimester and HOMA-IR mediated by serum leptin concentrations was statistically significant (z = 1.588, p < 0.05).Conclusions: Taken together, our findings suggest that the relationship between WG during the third trimester and IR was mediated by serum leptin concentrations in AMA, but not serum adiponectin concentrations. [ABSTRACT FROM AUTHOR]