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Abstract STUDY QUESTION What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards? SUMMARY ANSWER Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare. WHAT IS KNOWN ALREADY In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend. STUDY DESIGN, SIZE, DURATION The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: (‘advanced parental age’ OR ‘advanced maternal age’ OR ‘advanced paternal age’ OR ‘advanced reproductive age’ OR ‘late parent*’ OR ‘late motherhood’ OR ‘late fatherhood’) AND (‘IVF’ OR ‘in vitro fertilization’ OR ‘in-vitro-fertilization’ OR ‘fertilization in vitro’ OR ‘ICSI’ OR ‘intracytoplasmic sperm injection’ OR ‘reproductive techn*’ OR ‘assisted reproductive technolog*’ OR ‘assisted reproduction’ OR ‘assisted conception’ OR ‘reproduction’ OR ‘conception’ OR ‘birth*’ OR ‘pregnan*’) AND (‘wellbeing’ OR ‘well-being’ OR ‘psycho-social’ OR ‘social’ OR ‘ethical’ OR ‘right to reproduce’ OR ‘justice’ OR ‘family functioning’ OR ‘parental competenc*’ OR ‘ageism’ OR ‘reproductive autonomy’ OR ‘outcome’ OR ‘risk*’ OR ‘benefit*’). PARTICIPANTS/MATERIALS, SETTING, METHODS The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found. MAIN RESULTS AND THE ROLE OF CHANCE A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ultimately, 69 studies were included in the final sample. The key results concerned four aspects relevant to the research goals. (i) The studies showed discrepancies in defining who is an APA parent. (ii) There was an imbalance in the empirical evidence produced for different participant groups (mothers, fathers, and offspring), with offspring being the most studied study subjects. (iii) The research topics studied underlined the increased risks of neuro-developmental and psychotic disorders among offspring. (iv) The observed advantages and disadvantages were varied and could not be compared, especially for the offspring of APA parents. LIMITATIONS, REASONS FOR CAUTION Only English-language studies, published between 2000 and 2021, found in the above-mentioned databases were considered for this review. WIDER IMPLICATIONS OF THE FINDINGS More research is necessary to understand the risks and benefits of building a family at an APA for the offspring when they reach adulthood. Furthermore, studies that explore the perspective of older fathers and older parents from non-Western societies would be highly informative. STUDY FUNDING/COMPETING INTEREST(S) The writing of this manuscript was permitted by financial support provided by the Swiss National Science Foundation (Weave/Lead Agency funding program, grant number 10001AL_197415/1, project title ‘Family Building at Advanced Parental Age: An Interdisciplinary Approach’). The funder had no role in the drafting of this manuscript and the views expressed therein are those of the authors. The authors have no conflicts of interest. REGISTRATION NUMBER This systematic review is registered in Prospero: CRD42022304564.

Background: Declining fertility in a woman of advanced age is associated with a depletion in ovarian reserve as well as declining oocyte and embryo quality. Determining the predictors of embryo quality may assist in stimulation target and cycle prediction. Objective: This study aims to identify factors affecting embryo quality among women of advanced age receiving intracytoplasmic sperm injection (ICSI) cycles. Materials and Methods: This prospective cohort study was conducted over a period of 12 months, from January until December 2018, on 734 mature oocytes retrieved from 124 women of advanced age (35-45 yr old) receiving ICSI. The Society of Assisted Reproductive Techniques system was used to determine the morphological grading of embryo quality. The fertilization rate, cleavage rate, and pregnancy rate per cycle were expressed as a percentage per cycle for a total of 76 embryo transfers. Possible predictors of high-quality embryos were evaluated using single and multiple regression tests, with p < 0.05 considered as significant. Results: Out of the 586 available embryos, 288 (49.15%) high-quality embryos were obtained. The fertilization and cleavage rates were 86.18% and 97.83%, respectively. The total number of retrieved oocytes (R2 = 0.857) and the total available embryos (R2 = 0.857) were closely related to high-quality embryos. 76 embryo transfers were conducted, with 17 successful conceptions (implantation rate = 22.37% per transfer). There were no miscarriages among the pregnancies. Conclusion: Increasing the number of collected oocytes and the cleavage rate could increase the chance of obtaining more high-grade embryos. This could increase the success of ICSI among women of advanced age. Key words: Embryo development, Intracytoplasmic sperm injection, Ovarian hyperstimulation, Advanced age, Predictors.

Introduction As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. Material and methods This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40–44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. Results A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72–0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. Conclusions Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section. Patients and doctors need to be aware of the increasing chance of an unplanned cesarean section with advancing maternal age and of the possible risk factors, and to counsel at patient level whether vaginal birth seems feasible.

Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. Aims of the study were to investigate the effects of HG-chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells, using CaCo-2 cells. Moreover, we studied the effect of apple polyphenols on glyco-oxidative stress. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species (ROS), lipid peroxidation, AGEs, and increase of Glyoxalase I (GlxI) activity. On the contrary, Glyoxalase II (GlxII) activity was lower in HG-treated cells. We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress. The increase of total antioxidant capacity and glutathione (GSH) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity.

This article aims to explore prenatal diagnostic strategies in the context of increasing maternal age. We calculated the proportion of advanced maternal age (AMA) pregnancies in the Luohe region from 2019 to 2023 and evaluated the indications, abnormal fetal karyotypes, and pregnancy outcomes among 3681 pregnant women (3700 samples) who underwent amniocentesis. The prenatal diagnostic indications, abnormal fetal karyotypes, and pregnancy outcomes of 3681 pregnant women (3700 samples) were determined. The rates of abnormal amniotic fluid karyotypes for different indications and termination of pregnancy (TOP) rates with different types of abnormalities were compared. From 2019 to 2023, the proportion of AMA pregnancies in Luohe region increased from 11.30 to 16.03%. The most common prenatal diagnosis was AMA (54.50%), followed by abnormal maternal serum screening (35.83%). Among the 3700 samples, 97 exhibited numerical abnormalities, 32 structural abnormalities, and 2 had both numerical and structural abnormalities. The highest TOP rates were observed for combined numerical and structural abnormalities, followed by isolated numerical abnormalities and isolated structural abnormalities. Among numerical abnormalities, sex chromosome aneuploidies had a lower TOP rate than common trisomies and rare autosomal aneuploidies. AMA have become the primary prenatal diagnostic indication. In addition to noninvasive prenatal testing (NIPT), fetal karyotyping can also detect mosaicism, structural abnormalities, and triploidy. The combination of karyotyping and molecular detection has increased the detection rate of chromosomal abnormalities. However, NIPT cannot replace amniocentesis.

Background This study aims to investigate differences in pregnancy outcomes and potential risk factors between women of advanced maternal age (AMA, 35–39 years) and those of very advanced maternal age (vAMA, 40 years and older). Methods This retrospective cohort study included women (age ≥ 35) who were single pregnancy and delivered at a tertiary comprehensive hospital in China between 2014 and 2020 at a major urban Chinese medical center. Patient medical records were reviewed, and relevant clinical data were collected and organized into a structured data spreadsheet for analysis. Categorical variables were compared using chi-square analyses, while continuous variables were compared using either the Student t-test or Wilcoxon tests, depending on the data distribution. Logistic regression was employed to identify and evaluate risk factors. Results This study encompassed 19,560 pregnant, and divided into two groups: the AMA group with 16,131 patients and the vAMA group with 3,429 patients. A lower rate of gravidity and parity were observed in the vAMA group ( P  < 0.001). Preexisting hypertension, diabetes, and assisted reproductive technologies (ART) were more prevalent. The AMA group exhibited an increased rate of spontaneous deliveries, and precipitated labor ( P  < 0.001), while the vAMA group had a higher rate of cesarean delivery (CD) ( P  < 0.001). Additionally, the vAMA group had a significantly shorter gestational age at delivery ( P  < 0.001). Differences in birth outcomes between the AMA and vAMA groups were primarily observed in very preterm births (28–34 weeks) ( P  = 0.004) and low birth weight (LBW, 1,500-2,500 g) ( P  < 0.001). Incidences of gestational hypertension, pre-eclampsia, gestational diabetes, placenta previa, and adherent placenta were all significantly higher in the vAMA group ( P  < 0.001). Logistic regression analysis identified that gestational hypertension and placenta previa are risk factors for adverse birth outcomes in AMA women, while gestational hypertension and adherent placenta are in vAMA women. Conclusions Our study suggests that vAMA women have an increased risk of developing gestational hypertension, gestational diabetes, CD, placenta previa, and adherent placenta compared to women of AMA. Gestational hypertension, placenta previa, and adherent placenta were identified as the most important risks for preterm birth and LBW in AMA and vAMA women. Subgroup analysis of birth outcomes suggests that gestational diabetes is a risk factor for LBW and moderate preterm birth in AMA women. These results provide valuable data for prenatal counseling of patients with advanced maternal age.

Background Advanced maternal age (AMA), defined as pregnancy in people aged ≥ 35 years, is associated with an increased risk of adverse perinatal outcomes. Although the outcomes of AMA pregnancies have been reported, detailed information on the specific outcomes in pregnant individuals aged ≥ 45 years, particularly those reaching full term, remains limited. Therefore, this study aimed to investigate the perinatal outcomes of full-term pregnant individuals aged ≥ 45 years. Methods We conducted a retrospective cohort study involving full-term pregnant individuals aged ≥ 35 years who attempted vaginal delivery at our facility between January 2019 and December 2023. Participants were categorized into the AMA (35–39 years, n  = 947), moderate AMA (40–44 years, n  = 387), and very AMA (≥ 45 years, n  = 34) groups. The primary outcomes included maternal outcomes, such as intrapartum cesarean delivery (CD) rate and indications, blood loss, and additional interventions (e.g., uterine artery embolization [UAE]). Secondary outcomes included neonatal outcomes such as birth weight, Apgar score, umbilical artery pH, need for respiratory support, and neonatal intensive care unit (NICU) admission within 24 h of birth. Results The intrapartum CD rate increased significantly with age (AMA: 17.0%, moderate AMA: 27.1%, very AMA: 35.3%; p  < 0.01). However, more than half of the deliveries were vaginal, even in the very AMA group. No significant differences in intrapartum CD indications were found between the groups. The amount of blood loss was significantly higher in the moderate AMA group than in the other groups ( p  < 0.001). UAE and cesarean hysterectomy incidences showed no significant differences across the groups ( p  = 0.52 and p  = 0.78, respectively). Regarding neonatal outcomes, no significant differences in birth weight were observed, along with low Apgar score, low umbilical artery pH, need for respiratory support, or NICU admission within 24 h of birth between the groups ( p  = 0.61, p  = 0.62, p  = 0.52, p  = 1.00, and p  = 0.44, respectively). Conclusions Although the risk of intrapartum CD increases in pregnant individuals aged ≥ 45 years, those delivering at full term have neonatal outcomes similar to those of younger AMA pregnancies. Importantly, nearly two-thirds of this cohort achieved vaginal delivery. This information may be helpful for consultations with pregnant individuals aged ≥ 45 years in the clinical setting.

Objective To explore the application and value of chromosomal karyotype analysis combined with Chromosomal Microarray Analysis (CMA) in the amniotic fluid of advanced maternal age. Methods A total of 817 advanced maternal age (AMA) who underwent amniocentesis at the Prenatal Diagnosis Center of Huizhou Central People's Hospital between January 2018 and July 2024 were enrolled in this study. The women were grouped based on different age ranges and prenatal diagnosis factors. These groups were used to compare the detection rates and differences between chromosomal karyotype analysis and CMA. Result The overall chromosomal abnormality rates detected by karyotype analysis in the 35–39 years age group and the ≥ 40 years age group were 8.81% and 13.79%, respectively, with a statistically significant difference (p < 0.05). For CMA, the overall abnormality rates in the same age groups were 10.79% and 15.33%, respectively, but the difference was not statistically significant (p > 0.05). The non‐solely advanced‐age group (those with additional factors beyond just advanced age) had higher overall chromosomal abnormality rates, aneuploidy rates, structural abnormality rates, and mosaicism rates compared to the solely advanced‐age group, with statistically significant differences (p < 0.05). Additionally, the non‐solely advanced‐age group had a higher overall abnormality rate detected by CMA compared to the solely advanced‐age group, with a statistically significant difference (p < 0.05). However, there were no statistically significant differences between the two groups in terms of the detection of pathogenic, likely pathogenic, and variants of uncertain significance (p > 0.05). In this study, a total of 68 cases were identified where the results of karyotype analysis and CMA were inconsistent. Conclusion The overall abnormal rate of chromosomal karyotype analysis increases with maternal age, while the overall abnormal rate of CMA shows no significant correlation with maternal age. The abnormal rates are significantly higher in AMA with additional factors. The combination of chromosomal karyotype analysis and CMA can validate and complement each other, thereby improving the detection rates of chromosomal abnormalities in amniotic fluid samples of AMA. This provides a diagnostic basis for subsequent pregnancy choices, which effectively reduces the birth of fetuses with chromosomal abnormalities and enhances population quality. The pregnant women with advanced maternal age who underwent amniocentesis at the Prenatal Diagnosis Center of Huizhou Central People's Hospital were enrolled in this study. The women were grouped based on different age ranges and prenatal diagnosis factor. These groups were used to compare the detection rates and differences between chromosomal karyotype analysis and array comparative genomic hybridization (a‐CGH) testing.

PurposeTo study the impact of advanced paternal age on embryo aneuploidy.MethodsThis is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients.ResultsData from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome.ConclusionsThis is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.

The aim of the Postponing Parenthood project was to investigate several aspects of the delaying of childbearing phenomenon in Sweden and Norway, such as medical risks and parental experiences. Data were retrieved from the Swedish and Norwegian Medical Birth Registers and three different cohorts: the Swedish Young Adult Panel Study, the Norwegian Mother and Child Cohort, and the Swedish Women's Experiences of Childbirth cohort. Postponing childbirth to age 35 years and later increased the risk of rare but serious pregnancy outcomes, such as stillbirth and very preterm birth. Older first-time parents were slightly more anxious during pregnancy, and childbirth overall was experienced as more difficult, compared with younger age groups. First-time mothers' satisfaction with life decreased from about age 28 years, both when measured during pregnancy and early parenthood. Delaying parenthood to mid-30 or later was more related to lifestyle than socioeconomic factors, suggesting that much could be done in terms of informing young persons about the limitations of fertility and assisted reproductive techniques, and the risks associated with advanced parental age.