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Objective Methods Results Conclusions To evaluate whether extending embryo culture to day 5 (D5) affects pregnancy rates in women older than 38 years undergoing in vitro fertilization (IVF).This retrospective, observational cohort study included data from fresh IVF cycles of women over 38 years, during 2011–2021. The cohort was divided according to day 3 (D3) versus D5 embryo transfer (ET).A total of 346 patients (ages 38–45 years) who underwent 496 IVF cycles were included, each yielding one to six embryos. A total of 374 (75%) fresh D3 ETs were compared with 122 (25%) D5 ETs. Demographically, there were more nulliparas in the D3 group (189 [50.9%] vs 47 [38.8%], P = 0.021). Higher gonadotropin dosage was used (3512 ± 1346 vs 3233 ± 1212 IU, P = 0.045) and lower maximum estradiol levels were reached in the D3 group (1129 ± 685 vs 1432 ± 708 pg/mL, P = 0.002). Thirty‐three (27%) of the D5 cycles resulted in transfer cancelation due to failure of blastocyst formation (P = 0.001). However, clinical pregnancy rates (P = 0.958), live birth rates (P = 0.988), and miscarriage rates (P = 0.710) did not differ between D3 and D5 ETs. Multivariable logistic regression for clinical pregnancy rate showed that day of transfer did not have a significant effect on the odds (P = 0.376), but maternal age (P = 0.001) and number of retrieved oocytes (P = 0.009) were significant variables.In older women, culturing embryos to blastocyst stage can decrease invalid ETs without reducing pregnancy rates. Cancelation rates are higher but it may avoid interventions and conserve valuable time. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To describe maternal and fetal outcomes of pregnancies after 42 years and to compare maternal and fetal morbidities according to the conception mode; comparing pregnancies obtained spontaneously and those resulting from assisted reproductive technology (ART). Methods: This retrospective cohort study was conducted in a level 3 maternity hospital. This study covered all women, aged 42 years or older, who gave birth between January 1, 2014 and December 31, 2019. Univariate and multivariate analyses with logistic regression models were used to compare maternal and perinatal outcomes depending on conception mode: spontaneous or using ART. Results: A sample of 532 women, including 335 spontaneous pregnancies (63%) and 147 pregnancies after ART (27.6%) were studied. Conception mode was missing for 50 (9.4%). We found increased rates not only of maternal complications such as maternal overweight and obesity, pre‐eclampsia, and gestational diabetes, but also of interventions such as hospitalization during pregnancy, cesarean section, postpartum hemorrhage, and perinatal outcome like preterm birth. There were also more maternal and perinatal negative outcomes among the ART group. After multivariate analysis, pre‐eclampsia was predominant in the ART group (odds ratio 0.25, 95% confidence interval 0.07–0.85, P = 0.02). Conclusion: While maternal and fetal risks increase for late pregnancies, there also appears to be a difference depending on the conception mode, with pregnancies resulting from ART having more pregnancy‐related complications than those obtained spontaneously. Synopsis: Women aged 42 years or older have more maternal and fetal morbidities, and especially those from assisted reproductive technology group. [ABSTRACT FROM AUTHOR]

Objectives: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first‐trimester glycemic control on mCHD risk. Methods: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log‐binomial modeling. Results: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1–3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02–1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1–1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1–8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0–14.4) compared to those without diabetes and 5.5 (95% CI, 1.6–19.4) compared to PDM with normal HbA1c (≤ 6.1%). Conclusions: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high‐risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Jiang and Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Background and Aims: The prevalence of gestational diabetes mellitus (GDM) continues to increase, and the phenomenon of women giving birth at an older age is becoming more common worldwide. Less is known abouts the impact of GDM combined with advanced maternal age (AMA) on pregnancy outcomes. To explore the impact of AMA complicated with GDM on pregnancy outcomes. Methods: This study included 34,602 pregnancies between 2018 and 2020 in Hangzhou, China. The pregnant women were divided into four groups according to advanced age (≥35 years) and GDM as follows: AMA women without GDM (non‐AGDM) group (n = 2614), young pregnant women with GDM (YGDM) group (n = 4016), AMA women with GDM (AGDM) group (n = 850), and young pregnant women without GDM (non‐YGDM) group (n = 27,122). Univariate analysis was carried out by Mann–Whitney U test or Pearson's χ2 test. Multivariate logistic regression analysis was used to investigate the effect of AMA and GDM on pregnancy outcomes. Results: Multivariate logistic regression analysis showed that in the comparison against non‐YGDM garoup, the ORs of fetal chromosome abnormality, parity, urgent cesarean section, gravidity, scheduled cesarean section, body mass index (BMI) ≥30 kg/m2, pre‐eclampsia, thrombocytopenia, hyperlipidemia, BMI 25–29.9 kg/m2, blood urea nitrogen, fasting blood glucose, and creatinine in AGDM group were 16.044, 4.284, 3.530, 3.284, 3.257, 2.049, 1.935, 1.898, 1.690, 1.471, 1.304, 1.216, and 1.026 (all p < 0.05). Conclusions: The prevalence of pregnant women with AGDM was 2.46% in Hang Zhou, China. The increasing gravidity of AMA women was related to a greater risk of GDM. The AGDM group associated with a greater risks of chromosomal abnormality in offspring and cesarean section, especially urgent cesarean section. [ABSTRACT FROM AUTHOR]

During recent decades, the application of intracytoplasmic sperm injection has increased considerably worldwide, especially in couples with non‐male factor infertility. However, several studies analyzing the broad use of intracytoplasmic sperm injection, even in cases with a normal semen analysis, have collectively demonstrated no benefits compared to conventional in‐vitro fertilization. Currently, there is insufficient evidence to support the intracytoplasmic sperm injection technique vs. in‐vitro fertilization in cases of poor ovarian response or a low number of oocytes collected, or in patients with advanced maternal age. Since the intracytoplasmic sperm injection technique is more operator‐dependent and invasive, its use should only be recommended in cases of male‐factor infertility. There is some evidence showing that intracytoplasmic sperm injection is linked with an increased risk of birth defects. Albeit this evidence is limited, and currently it is not possible to draw a firm conclusion on these concerns, we do believe that these risks should be rigorously investigated. Thus, this review aims to clarify the debate on the application of the intracytoplasmic sperm injection procedure, as compared to standard in‐vitro fertilization, in those assisted reproductive technology cycles without a clear male factor infertility. Furthermore, we try to clarify whether intracytoplasmic sperm injection would result in a higher live birth rate than in‐vitro fertilization, in couples with non‐male factor infertility. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association of advanced maternal age with pregnancy complications in twin pregnancies and compare it with that observed in singleton pregnancies. Methods: A population‐based retrospective cohort study of all patients with a singleton or twin hospital birth in Ontario, Canada, between 2012 and 2019. The primary outcome was preterm birth (PTB) less than 34 weeks. Pregnancy outcomes were stratified by maternal age groups in twin pregnancies and, separately, in singleton pregnancies. Results: A total of 935 378 patients met the study criteria: 920503 (98.4%) had a singleton pregnancy and 14 875 (1.6%) had twins. In singletons, the rate of PTB less than 34 weeks increased progressively with increasing maternal age and was highest for patients aged 45 years or more (3.4%; adjusted risk ratio [aRR] 1.56, 95% confidence interval [CI] 1.05–2.33). By contrast, in twins, although the rate of PTB less than 34 was highest patients under 20 years of age (25.3%) and was lowest among patients aged 35–39 years (11.7%), the associations between maternal age group and the risk of PTB were not statistically significant in the adjusted analysis. Conclusion: Although the absolute rates of pregnancy complications are higher in twin pregnancies, there are considerable differences in the relationship between maternal age and the risk of certain complications between twin and singleton pregnancies. Synopsis: The relationship between maternal age and the risk of pregnancy complications differs between twin and singleton pregnancies. [ABSTRACT FROM AUTHOR]

Aim: In this review, We compared clinical characteristics of pregnant women aged 50 and older with those aged 45–49. Pregnant women ≥45 years are strongly associated with pregnancy‐related complications, such as cesarean section rate, gestational hypertension, gestational diabetes mellitus, and preterm birth. Although pregnant women ≥50 years are considered more high‐risk, differences in pregnancy outcomes between those over 45 and 50 years of age are unclear. Methods: Our source strategy included using PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science databases to include studies published between January 1, 2010 and September 30, 2022. The study population was pregnant women 50 years and older; the control group was pregnant women aged 45–49 years. Primary outcomes were cesarean section, gestational hypertension, gestational diabetes mellitus, and preterm birth. The secondary outcomes were small‐for‐gestational age, 5‐min Apgar score < 7, neonatal intensive care unit admission (as neonatal outcomes), nulliparity, assisted reproductive technology (ART), and multifetal pregnancy (as maternal backgrounds). Results: The incidence of cesarean section, gestational hypertension, and preterm delivery was significantly higher in those 50 years and older; however, significant differences disappeared when pooled analyses were limited to singleton pregnancies. ART was significantly more likely to be used for conception of pregnant women ≥50 years. Infants of women ≥50 years were more likely to be admitted to NICUs. Conclusions: The differences in outcomes between the two groups are obviously influenced by multiple pregnancies, therefore, reproductive medicine specialists should aim for singleton pregnancies in ART. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk levels for maternal and perinatal complications at > 40, > 45 and > 50 years old compared with younger controls. Methods: Electronic databases were searched from their inception until March 2021. We included studies reporting pregnancy outcome in pregnant women aged 40, 45, and 50 years or older compared with controls at the time of delivery. Case reports and case series were excluded. The primary outcome was the incidence of stillbirth. Meta‐analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Heterogeneity was measured using I2 (Higgins I2). Subgroup analyses in women older than 45 years and in those older than 50 years were performed. Results: Twenty‐seven studies, including 31 090 631 women, were included in the meta‐analysis. The overall quality of the included studies was moderate to high. Most of the included studies were retrospective cohort studies (21/27), four were population‐based studies, and two were cross‐sectional studies. Women aged ≥40 years had significantly higher risk of stillbirth (RR 2.16, 95% CI 1.86–2.51), perinatal mortality, intrauterine growth restriction, neonatal death, admission to neonatal intensive care unit, pre‐eclampsia, preterm delivery, cesarean delivery, and maternal mortality compared with women younger than 40 years old (RR 3.18, 95% CI 1.68–5.98). The increased risks for maternal mortality were 42.76 and 11.60 for women older than 50 years and for those older than 45 years, respectively, whereas those for stillbirth were 3.72 and 2.32. The risk of stillbirth and cesarean delivery was significantly higher in women >45 years compared with those aged 40–45 years, and in those aged >50 years compared with those aged 45–50 years. The risk of maternal mortality was significantly higher in women aged >50 years compared with those aged 40–45 (RR 60.40, 95% CI 13.28–274.74). Conclusion: The risk of stillbirth, cesarean delivery, and maternal mortality increases with advancing maternal age. The risk ratios for maternal mortality were 3.18, 11.60, and 42.76 in women older than 40, older than 45, and older than 50 years, respectively. These data should be used when women with advanced maternal age are counseled regarding their risk in pregnancy. Systematic Review Registration: The review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration No.: CRD42020208788). The risk ratios for maternal mortality were 3.18, 11.60, and 42.76 in women 40 years, 45 years, 50 years, respectively. [ABSTRACT FROM AUTHOR]

Aim: Cesarean section is known to be increased with advanced maternal age in women undergoing induction of labor (IOL), but there is less information regarding other possible adverse maternal and fetal outcomes. Methods: Retrospective cohort study of singleton, nulliparous, at‐term women undergoing IOL between January 2007 and September 2020. Outcomes studied were: cesarean section, failed induction rate, fetal distress, post‐partum hemorrhage, post‐partum hysterectomy, and need of transfusion. Neonatal variables analyzed were: Apgar score, umbilical cord pH, need of admission to neonatal intensive care unit, and mortality. Results: A total of 4027 women met the inclusion criteria; 1968 (48.9%) of mothers were <35 years, 1283 (31.9%) were 35–39 years, 658 (16.3%) were 40–44 years, and 118 (2.9%) were ≥45 years. Results showed a significantly increased incidence of c‐section in women ≥35 years, with an OR 1.79 (95% CI 1.50–2.14) for women 40–44 years and OR 3.95 (95% CI 2.66–5.98) for women ≥45 years. The main indication for cesarean delivery was failed IOL, and this risk was also significantly increased in women ≥40 years. These differences remained significant after adjustment for confounding factors. No other adverse maternal or fetal outcomes showed an association with age. Conclusion: Maternal age ≥40 years was associated with an increased risk of c‐section after IOL at term compared with younger women, mainly because of failed induction, but no association with other adverse maternal or neonatal outcomes were found in our population. Risks and benefits of IOL in older women should be individually evaluated and adequately discussed with mothers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To assess the independent risk factors and pregnancy outcomes of hypertensive disorders of pregnancy (HDPs) in Chinese advanced age pregnancy women. Design: Secondary analysis of international published data. Materials and Methods: PubMed, Web of Science, Scopus, Embase, Cochrane library, and Chinese databases from inception to February 23, 2022 were searched to identify eligible studies. Meta‐analysis was conducted to provide meaningful summative outcomes. The quality evaluation of included study was performed. The analyses were done with Review Manager 5.3 and Stata 14.0 software. Results: Totally, 13 eligible articles were included, among which 3 articles investigated the risk factors, 6 articles studied pregnancy outcomes, and 4 articles examined both risk factors and pregnancy outcomes. Chinese older pregnant women with the HDPs had high pooled incidences of abnormal body mass index, maternal education, family history of hypertension, history of chronic hypertension, gestational diabetes, irregular delivery inspection, psychosocial factors, and primiparity compared to those without HDPs. The incidence of cesarean delivery, placental abruption, premature rupture of membranes, postpartum hemorrhage, preterm birth, fetal asphyxia, fetal distress, fetal growth restriction, and low birth weight in Chinese older pregnant women with HPDs were significantly higher than those without HDPs. Conclusion: This study identified several possible risk factors which promoted the onset of HDPs in Chinese older pregnant women, and HDPs significantly increases risk of adverse pregnancy outcomes (APOs). Further research is needed to take targeted measures to prevent HDPs and explore efficient management methods to minimize the risk of APOs associated with HDPs in Chinese older pregnant women. [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]

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]

Advanced maternal age (AMA) pregnancies are rapidly increasing and are associated with aberrant trophoblast cell function, poor placentation, and unfavorable pregnancy outcomes, presumably due to premature placental senescence. SIRT1 is an NAD+‐dependent deacetylase with well‐known antiaging effects, but its connection with placental senescence is unreported. In this study, human term placentas and first‐trimester villi were collected from AMA and normal pregnancies, and a mouse AMA model was established by cross breeding young and aged male and female C57 mice. SIRT1 expression and activity in HTR8/SVneo cells were genetically or pharmacologically manipulated. Trophoblast‐specific Sirt1‐knockout (KO) mouse placentas were generated by mating Elf5‐Cre and Sirt1fl/fl mice. Trophoblast cell mobility was assessed with transwell invasion and wound‐healing assays. SIRT1‐binding proteins in HTR8/SVneo cells and human placental tissue were identified by mass spectrometry. We identified SIRT1 as the only differentially expressed sirtuin between AMA and normal placentas. It is downregulated in AMA placentas early in the placental life cycle and is barely impacted by paternal age. SIRT1 loss upregulates P53 acetylation and P21 expression and impairs trophoblast invasion and migration. Sirt1‐KO mouse placentas exhibit senescence markers and morphological disruption, along with decreased fetal weight. In trophoblasts, SIRT1 interacts with vimentin, regulating its acetylation. In conclusion, SIRT1 promotes trophoblast epithelial−mesenchymal transition (EMT) to enhance invasiveness by modulating vimentin acetylation. AMA placentas are associated with premature senescence during placentation due to SIRT1 loss. Therefore, SIRT1 may be an antiaging therapeutic target for improving placental development and perinatal outcomes in AMA pregnancies. [ABSTRACT FROM AUTHOR]

Advanced maternal age (AMA) pregnancy is associated with higher risks of adverse perinatal outcomes, which may result from premature senescence of the placenta. α‐Klotho is a well‐known antiaging protein; however, its expression and effect on the placenta in AMA pregnancies have not yet been fully elucidated. The expression patterns of α‐Klotho in mouse and human placentas from AMA pregnancies were determined by Western blotting and immunohistochemistry (IHC) staining. α‐Klotho expression in JAR cells was manipulated to investigate its role in trophoblastic senescence, and transwell assays were performed to assess trophoblast invasion. The downstream genes regulated by α‐Klotho in JAR cells were first screened by mRNA sequencing in α‐Klotho‐knockdown and control JAR cells and then validated. α‐Klotho‐deficient mice were generated by injecting klotho‐interfering adenovirus (Ad‐Klotho) via the tail vein on GD8.5. Ablation of α‐Klotho resulted in not only a senescent phenotype and loss of invasiveness in JAR cells but also a reduction in the transcription of cell adhesion molecule (CAM) genes. Overexpression of α‐Klotho significantly improved invasion but did not alter the expression of senescence biomarkers. α‐Klotho‐deficient mice exhibited placental malformation and, consequently, lower placental and fetal weights. In conclusion, AMA results in reduced α‐Klotho expression in placental trophoblasts, therefore leading to premature senescence and loss of invasion (possibly through the downregulation of CAMs), both of which ultimately result in placental malformation and adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) can result in developmental defects that include growth restriction, craniofacial anomalies, and cognitive behavioral deficits, though the presence and severity of these adverse outcomes can vary dramatically among exposed individuals. Preclinical animal models have demonstrated that the dose and timing of PAE account for much, but not all, of this phenotypic variation, suggesting that additional factors mitigate the effects of PAE. Here, we used a mouse model to investigate whether maternal age modulates the effects of PAE on the severity and variation in offspring growth and craniofacial outcomes. Methods: Nulliparous C57BL/6N dams received either an intraperitoneal injection of ethanol (EtOH) or vehicle solution on gestational day 7.5. Dams were divided into four groups: (1) EtOH‐treated young dams (6 to 10 weeks); (2) control young dams; (3) EtOH‐treated old dams (6 to 7 months); and (4) old control dams. Neonate offspring growth restriction was measured through body mass and organ‐to‐body mass ratios, while skeletal craniofacial features were imaged using micro‐CT and analyzed for size, shape, and variation. Results: PAE and advanced maternal age each increased the risk of low birthweight and growth restriction in offspring, but these factors in combination changed the nature of the growth restriction. Similarly, both PAE and advanced maternal age individually caused changes to craniofacial morphology such as smaller skull size, dysmorphic skull shape, and greater skull shape variation and asymmetry. Interestingly, while the combination of PAE and advanced maternal age did not affect mean skull shape or size, it significantly increased the variation and asymmetry of those measures. Conclusion: Our results indicate that maternal age modulates the effects of PAE, but that the effects of this combination on offspring outcomes are more complex than simply scaling the effects of either factor. [ABSTRACT FROM AUTHOR]

Female fertility is inversely correlated with maternal age due to a depletion of the oocyte pool and a reduction in oocyte developmental competence. Few studies have addressed the effect of maternal age on the human mature oocyte (MII) transcriptome, which is established during oocyte growth and maturation, however, the pathways involved remain unclear. Here, we characterize and compare the transcriptomes of a large cohort of fully grown germinal vesicle stage (GV) and in vitro matured (IVM‐MII) oocytes from women of varying reproductive age. First, we identified two clusters of cells reflecting the oocyte maturation stage (GV and IVM‐MII) with 4445 and 324 putative marker genes, respectively. Furthermore, we identified genes for which transcript representation either progressively increased or decreased with age. Our results indicate that the transcriptome is more affected by age in IVM‐MII oocytes (1219 genes) than in GV oocytes (596 genes). In particular, we found that transcripts of genes involved in chromosome segregation and RNA splicing significantly increased representation with age, while genes related to mitochondrial activity showed a lower representation. Gene regulatory network analysis facilitated the identification of potential upstream master regulators of the genes involved in those biological functions. Our analysis suggests that advanced maternal age does not globally affect the oocyte transcriptome at GV or IVM‐MII stages. Nonetheless, hundreds of genes displayed altered transcript representation, particularly in IVM‐MII oocytes, which might contribute to the age‐related quality decline in human oocytes. [ABSTRACT FROM AUTHOR]

Introduction: The age at which women give birth is rising steadily in the western world. Advanced maternal age has been associated with adverse pregnancy outcomes. We assessed the association between advanced maternal age and the risk of adverse maternal and perinatal outcome in primigravid and multigravid women.Material and Methods: The study was a population-based cohort study and included women giving birth between January 2000 and December 2018 using data from the Dutch perinatal registration of Perined. Women were divided into age groups. We compared outcomes between women of 40-44, 45-49, and over 50 years old (the study groups) with women of 25-29 years old (reference group), stratified for parity. We employed multivariable regression to correct for possible confounders including methods of conception, multiple pregnancies, ethnicity, and socio-economic status. Our primary outcomes were maternal and perinatal mortality. Secondary outcomes included common maternal and perinatal complications, as well as cesarean section rate.Results: A cohort of 3 700 326 women gave birth during the study period. Of these women, 3.2% were above 40 years of age. Maternal mortality was rare in all groups, but significantly higher in multigravid women over 50 years old. Perinatal mortality was significantly higher in all pregnancies of women over 40 years old, but not for primigravida over 50 years old. The most notable results with the steepest increase were in maternal complications. Both primigravida and multigravida over 40 years old were at a two times higher risk of perinatal mortality, cesarean section, gestational diabetes, hypertensive disorders, and a low Apgar score after 5 minutes. The risk for women over 45 was almost tripled for perinatal mortality and gestational diabetes and six times higher for cesarean section. Women over 50 years old had a seven times higher risk of cesarean section, a four times higher risk of gestational diabetes, postpartum hemorrhage, and neonatal intensive care unit admission, and a 10 times higher risk of hypertensive disorders.Conclusions: The risk of adverse maternal and perinatal outcomes for women over 40 years old surges as age increases. A novel aspect was the consistent increased risks not only for primigravid women but also for multigravida. [ABSTRACT FROM AUTHOR]

Advancing maternal age causes a progressive reduction in fertility. The decline in developmental competence of the oocyte with age is likely to be a consequence of multiple contributory factors. Loss of epigenetic quality of the oocyte could impair early developmental events or programme adverse outcomes in offspring that manifest only later in life. Here, we undertake joint profiling of the transcriptome and DNA methylome of individual oocytes from reproductively young and old mice undergoing natural ovulation. We find reduced complexity as well as increased variance in the transcriptome of oocytes from aged females. This transcriptome heterogeneity is reflected in the identification of discrete sub‐populations. Oocytes with a transcriptome characteristic of immature chromatin configuration (NSN) clustered into two groups: one with reduced developmental competence, as indicated by lower expression of maternal effect genes, and one with a young‐like transcriptome. Oocytes from older females had on average reduced CpG methylation, but the characteristic bimodal methylation landscape of the oocyte was preserved. Germline differentially methylated regions of imprinted genes were appropriately methylated irrespective of age. For the majority of differentially expressed transcripts, the absence of correlated methylation changes suggests a post‐transcriptional basis for most age‐related effects on the transcriptome. However, we did find differences in gene body methylation at which there were corresponding changes in gene expression, indicating age‐related effects on transcription that translate into methylation differences. Interestingly, oocytes varied in expression and methylation of these genes, which could contribute to variable competence of oocytes or penetrance of maternal age‐related phenotypes in offspring. [ABSTRACT FROM AUTHOR]

Background: Increasing numbers of women ≥40 years old are accessing assisted reproductive technology (ART) due to age‐related infertility. There is limited population‐based evidence about the impact on the cumulative live birth rate (CLBR) of women aged ≥40 years using their own oocytes, compared to women of a similar age, using donor oocytes. Aims: To compare the CLBR for women ≥40 years undergoing ART using autologous oocytes and women of similar age using donor oocytes. Materials and Methods: This population‐based retrospective cohort study used data from all women aged ≥40 years undergoing ART with donated (n = 987) or autologous oocytes (n = 19 170) in Victoria, Australia between 2009 and 2016. A discrete‐time survival model was used to evaluate the CLBR following ART with donor or autologous oocytes. The odds ratio, adjusted for woman's age; male age; parity; cause of infertility; and the associated 95% confidence intervals (CI), were calculated. The numbers needed to be exposed (NNEs) were calculated from the adjusted odds ratio (aOR) and the CLBR in the autologous group. Results: The CLBR ranged from 28.6 to 42.5% in the donor group and from 12.5% to 1.4% in the autologous group. The discrete‐time survival analysis with 95% CI demonstrated significant aOR on CLBR across all ages (range aOR: 2.56, 95% CI: 1.62–4.01 to aOR: 15.40, 95% CI: 9.10–26.04). Conclusions: Women aged ≥40 years, using donor oocytes had a significantly higher CLBR than women using autologous oocytes. The findings can be used when counselling women ≥40 years about their ART treatment options and to inform public policy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate how many pregnant women would prefer to undergo prenatal genetic testing (GT) if they received adequate information during early gestation. Methods: We examined the preferences for prenatal GT among pregnant women visiting our general outpatient clinic before 16 weeks' gestation between September 2014 and September 2017. We provided them with informational brochures about prenatal GT at their first visit. Women always received genetic counseling (GC) before undergoing GT of their own choice. Results: Among 5700 pregnant women, 2077 (36.4%) received GC, and 1983 (34.8%) underwent some form of prenatal GT. The percentage undergoing GT was 9.4% (50/531) for women <30 years old, 19.0% (309/1623) for those 30–34 years old, 43.1% (989/2294) for those 35–39 years old, and 50.7% (635/1252) for those ≥40 years old. Older pregnant women tended to receive GC and GT more often than younger women (P < 0.001). The most common reason for receiving GC was advanced maternal age (79.7%). The most common prenatal GT was noninvasive prenatal testing (NIPT) (50%), followed by the combined test (29.0%) and quadruple test (11.2%). Pregnant women ≥35 years old tended to choose NIPT (60.5%), while those <35 years old tended to choose the combined test (52.9%). Conclusion: About one‐third of the pregnant women preferred to receive prenatal GT by their own choice. Women's preferences for prenatal GT increased with maternal age; however, half of pregnant women with an advanced maternal age preferred not to undergo GT, even if they were well informed. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk factors and pregnancy outcomes in women aged 40 years and older at the Korle-Bu Teaching Hospital, Accra, Ghana.Methods: A descriptive case-control study comparing women aged 40 years and older at the time of delivery with those between 20 and 34 who delivered at the Korle-Bu Teaching Hospital between April 1, 2014 and March 31, 2015. Data were collected using interviewer-administered questionnaires and supplemented with information from patients' medical records. A multivariate logistic regression was used to estimate the odds ratio and the 95% confidence interval of various risk factors and complications associated with delivery in women aged 40 years or older. Statistical significance was set at P<0.05.Results: There were 339 women in the study of which 113 were aged 40 years or older and 226 were aged between 20 and 34 years. Delivery at age 40 years or older was associated with grand multiparity, and unplanned and undesirable pregnancy. There was a higher incidence of gestational diabetes (7.1% vs 2.2%, P=0.036), cesarean delivery (70.1% vs 57.1%, P=0.018), and venous thromboembolism (VTE) (7.1% vs 1.3%, P=0.008) among women older than 40 years. VTE risk was increased sixfold in the women older than 40 years compared with the younger ones.Conclusion: Women delivering after age 40 years had a higher incidence of gestational diabetes, cesarean delivery, and VTE compared with younger women. VTE risk increased sixfold in the older women. [ABSTRACT FROM AUTHOR]

Aim: To describe changed epidemiological features of advanced maternal age (AMA) and to examine the effect of AMA on the risk for Cesarean section (CS) in a Chinese pregnant population. Methods: This retrospective single‐center cohort study investigated the changes of epidemiological features of AMA parturients with respect to the revised reproductive policy in China in 43 702 singleton deliveries with live birth at ≥28 weeks managed from January 2005 to December 2016. We also evaluated the pregnancy outcomes in different age groups and risk factors of CS with multivariate analysis. Results: In this 12‐year study period, the average maternal age increased from 28.5 to 30.2 years, and the proportion of AMA raised from 6.5% to 17.2%. AMA was significantly associated with increased risk of adverse pregnancy outcomes, and after adjustment for confounding factors, AMA remained a significant independent risk factor for CS. Furthermore, the effect of AMA in nulliparous women on the risk of CS was more significant than in multiparous women, while the history of previous CS (adjusted odds ratio 39.85) and interdelivery interval ≥10 years (adjusted odds ratio 1.52) also increased the risk of CS in multiparous women. Conclusion: AMA increased the risk of a number of adverse pregnancy outcomes, and was independently associated with increased risk for CS. The increasing number of AMA parturients with risk factors is likely to increase CS rate in China in the near future, thus it is imperative to reduce the rate of primary CS as a matter of policy. [ABSTRACT FROM AUTHOR]

Introduction: The number of women postponing childbirth until an advanced age is increasing. Our aim was to study the outcome of labor in nulliparous women ≥40 years, compared with women 25-29 years, after both spontaneous onset and induction of labor.Material and Methods: The nationwide population-based Swedish Medical Birth Register was used to study the perinatal outcome in nulliparous women with a singleton, term (gestational weeks 37-44), live fetus in cephalic presentation and a planned vaginal delivery from 1992 to 2011. We included 7796 nulliparous women ≥40 years and 264 262 nulliparous women 25-29 years. Prevalence and risk of intrapartum cesarean section, operative vaginal delivery, obstetric anal sphincter injury and a 5-minute Apgar score <7 were calculated for women ≥40 years stratified for spontaneous onset and induction of labor, using women 25-29 years as the reference in both strata. Crude and adjusted odds ratios (aOR) were calculated by unconditional logistic regression and presented with 95% confidence intervals (CI).Results: Overall, 79% of women ≥40 years with a trial of labor reached a vaginal delivery. After spontaneous onset, intrapartum cesarean section was performed in 15.4% of women ≥40 years compared with 5.4% of women 25-29 years (aOR 3.07, 95% CI 2.81-3.35). Operative vaginal delivery was performed in 22.3% of women ≥40 years compared with 14.2% of women 25-29 years (aOR 1.71, 95% CI 1.59-1.85). After induction of labor, an intrapartum cesarean section was performed in 37.2% women ≥40 years compared with 20.2% women 25-29 years (aOR 2.51, 95% CI 2.24-2.81). Operative vaginal delivery was performed in 22.6% of women ≥40 years compared with 18.4% women 25-29 years (aOR 1.45, 95% CI 1.28-1.65). The risk of obstetric anal sphincter injury or a 5-minute Apgar score <7 was not increased in women ≥40 years, regardless of onset of labor.Conclusions: Trial of labor ended in vaginal delivery in 79% of nulliparous women ≥40 years. The risks of intrapartum cesarean section and operative vaginal delivery were higher in women ≥40 years compared with women 25-29 years, after both spontaneous onset and induction of labor. The risk of obstetric anal sphincter injury or a 5-minute Apgar score <7 was not increased. [ABSTRACT FROM AUTHOR]

To support people with Down syndrome (DS), it is essential to know and predict the number of live births of children with this condition. In this study, we estimated DS live birth rates on the basis of maternal age distribution and numbers of births in the general population, the maternal‐age specific chance for a live birth of a child with DS, and the prenatal diagnosis/termination rate. The total number of live births in Japan decreased to less than 1 million in 2016 and the percentage of women aged 35 years old or over giving birth has increased by sixfold. Prenatal genetic testing in Japan has gradually become more widespread, and 20% of all cases of DS were diagnosed prenatally in 2016. Meanwhile, the annual projected number of DS live births has remained steady at around 2,200 (22 per 10,000 births). In 2016, it was estimated that 70% of all DS babies were born to women of advanced maternal age (AMA). Given that Japan is facing a decreasing birth rate and an aging population, adoption of the practice of prenatal genetic testing for AMA has balanced the number of DS births over the last 7 years from 2010. [ABSTRACT FROM AUTHOR]

More women postpone childbearing nowadays while female fertility begins to decline with advancing age. Furthermore, with the rolling out of the two‐child policy, there is a huge demand for a second child for Chinese aged women. There are various assisted reproductive technology (ART) strategies applied for age‐related infertility without solid evidence. On behalf of the Society of Reproductive Medicine, Chinese Medical Association, we would like to develop a Chinese guideline of ART strategies for age‐related infertility. This guideline was produced following the recommendations for standard guidelines described in the 2012 WHO Handbook for guideline development. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was also followed. A protocol was formulated and a Guideline Development Group was formed with specialists of reproductive medicine, methodologists from Chinese GRADE working group, and patient representative. Questions regarding the ART strategies for aged infertility were formulated and 8 most important ones were chosen to be structured in PICO format (Population, Intervention, Comparison, Outcomes). Comprehensive search and review of the literature were performed and the quality of the evidence was assessed and rated based on certain criteria and be categorized as high, moderate, low, or very low. Twenty‐five recommendations were formulated among members of the Guidelines Development Group (Delphi method) basing on the overall quality of the evidence, in addition to the balance between benefits and harms, values and preferences, and resource implications. The final recommendations were agreed on by consensus during face‐to‐face meetings. This is the first Chinese practice guideline in reproductive medicine developed following the standard and scientific method. [ABSTRACT FROM AUTHOR]

Background: An ever‐increasing number of women in our country with advanced maternal age are choosing to achieve pregnancy. This means effective strategies are needed for infertile patients. Questions arise, however, concerning the need for ovarian stimulation, and, if so, whether intracytoplasmic sperm injection (ICSI) is better than conventional insemination for those women who may have only one mature oocyte. Methods: We evaluated our data to answer these questions. Herein, we also introduce our strategy for patients who show unsynchronized follicular growth. Main findings: Ovarian stimulation in ART treatment for patients with advanced maternal age has resulted in the achievement of higher pregnancy rates, and therefore, this form of stimulation is often selected. Based on our data, ICSI as an insemination procedure has not improved clinical pregnancy rates compared with conventional insemination and has actually decreased the clinical pregnancy rates. Conclusion: In this article, we reviewed and compared the protocols and strategies that are available to increase the number of developed embryos for the patients with advanced maternal age. We hope that this review will be helpful for both patients and clinicians. [ABSTRACT FROM AUTHOR]

Key points: Advanced maternal age increases the risk of pregnancy complications such as fetal growth restriction, hypertension and premature birth.Offspring born from compromised pregnancies are at increased risk of cardiovascular disease as adults. However, the effect of advanced maternal age on later‐onset disease in offspring has not been investigated.In adulthood, male but not female offspring born to dams of advanced maternal age showed impaired recovery from cardiac ischaemia/reperfusion injury.Endothelium‐dependent relaxation was also impaired in male but not female offspring born from aged dams.Oxidative stress may play a role in the developmental programming of cardiovascular disease in this model.Given the increasing trend toward delayed parenthood, these findings have significant population and health care implications and warrant further investigation. Exposure to prenatal stressors, including hypoxia, micro‐ and macronutrient deficiency, and maternal stress, increases the risk of cardiovascular disease in adulthood. It is unclear whether being born from a mother of advanced maternal age (≥35 years old) may also constitute a prenatal stress with cardiovascular consequences in adulthood. We previously demonstrated growth restriction in fetuses from a rat model of advanced maternal age, suggesting exposure to a compromised in utero environment. Thus, we hypothesized that male and female offspring from aged dams would exhibit impaired cardiovascular function as adults. In 4‐month‐old offspring, we observed impaired endothelium‐dependent relaxation in male (P < 0.05) but not female offspring born from aged dams. The anti‐oxidant polyethylene glycol superoxide dismutase improved relaxation only in arteries from male offspring of aged dams (ΔEmax: young dam –1.63 ± 0.80 vs. aged dam 11.75 ± 4.23, P < 0.05). Furthermore, endothelium‐derived hyperpolarization‐dependent relaxation was reduced in male but not female offspring of aged dams (P < 0.05). Interestingly, there was a significant increase in nitric oxide contribution to relaxation in females born from aged dams (ΔEmax: young dam –24.8 ± 12.1 vs. aged dam –68.7 ± 7.7, P < 0.05), which was not observed in males. Recovery of cardiac function following an ischaemia‐reperfusion insult in male offspring born from aged dams was reduced by ∼57% (P < 0.001), an effect that was not evident in female offspring. These data indicate that offspring born from aged dams have an altered cardiovascular risk profile that is sex‐specific. Given the increasing trend toward delaying pregnancy, these findings may have significant population and health care implications and warrant further investigation. Key points: Advanced maternal age increases the risk of pregnancy complications such as fetal growth restriction, hypertension and premature birth.Offspring born from compromised pregnancies are at increased risk of cardiovascular disease as adults. However, the effect of advanced maternal age on later‐onset disease in offspring has not been investigated.In adulthood, male but not female offspring born to dams of advanced maternal age showed impaired recovery from cardiac ischaemia/reperfusion injury.Endothelium‐dependent relaxation was also impaired in male but not female offspring born from aged dams.Oxidative stress may play a role in the developmental programming of cardiovascular disease in this model.Given the increasing trend toward delayed parenthood, these findings have significant population and health care implications and warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To examine the intrapartum cesarean delivery rate following failure of induction of labor (IOL) as well as risk factors associated with failed IOL among nulliparous women of advanced maternal age (AMA). Methods: This was a retrospective cohort study conducted at a single perinatal care center. We retrospectively reviewed the medical records of nulliparous AMA women (aged 35 years or older) with singleton vertex pregnancy who underwent IOL at term. Data regarding maternal baseline characteristics and pregnancy course, including complications during pregnancy and maternal status at time of IOL, were collected. Rate of emergency cesarean section (eCS) as well as risk factors associated with failed IOL were investigated by means of logistic regression analysis. Results: Among 234 women included in this study, 103 (44%) had failed IOL and delivered by eCS. Hypertensive disorder during pregnancy (adjusted odds ratio [aOR], 2.01; 95% confidence interval [CI], 1.0–4.12; P = 0.025) and unfavorable cervical status (aOR, 1.92; 95% CI, 1.08–3.41; P = 0.038) were identified as independent risk factors for failed IOL. Conclusion: IOL failed in 44% of nulliparous AMA women. Hypertensive disorder and immature cervical status should be considered as independent risk factors for eCS among such women. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to determine the effect of maternal age on emergency cesarean section (CS) during labor, and to identify the independent risk factors for emergency CS. Methods: This was a retrospective cohort study using data from 2009 to 2014 from a tertiary perinatal care center in Japan. Inclusion criteria were maternal age ≥ 35 years, nulliparous singleton pregnancy at term and a cephalic presentation without indication of elective CS at onset of labor. The primary outcome was rate of emergency CS, while independent risk factors were elucidated using multivariate logistic regression analysis. Results: Of 953 women, 199 (20.9%) delivered by emergency CS. Rates of emergency CS were 18.3% (129/706) in women aged 35–39 years and 28.3% (70/247) in those aged ≥ 40 years (P < 0.01). Adjusted odds ratios (95% confidence intervals) of independent risk factors were 1.50 (1.03–2.18) for maternal age ≥ 40 years, 1.51 (1.06–2.17) for body mass index ≥ 25 kg/m2, 2.22 (1.24–3.98) for hypertensive disorder during pregnancy, 3.43 (1.31–8.95) for large‐for‐date fetus and 4.64 (3.23–6.69) for induction of labor. Conclusions: The rate of intrapartum emergency CS in older nulliparous women at term was approximately 21%. Induction of labor should be recognized as a significant factor for emergency CS. [ABSTRACT FROM AUTHOR]

Objective: To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age.Methods: The present retrospective study included data from singleton pregnancies of women aged at least 40 years who delivered between January 1, 1991, and December 31, 2013, at Soroka University Medical Center, Beer Sheva, Israel. Demographic, obstetric, and perinatal data were compared between pregnancies conceived with ART (in vitro fertilization [IVF] or ovulation induction) and those conceived spontaneously. Multiple regression models were used to define independent predictors of adverse outcomes.Results: A total of 8244 singleton pregnancies were included; 229 (2.8%) following IVF, 86 (1.0%) following ovulation induction, and 7929 (96.2%) were spontaneous. Preterm delivery (P<0.001), fetal growth restriction (FGR) (P<0.001), and cesarean delivery (P<0.001) demonstrated linear associations with the conception mode; the highest rates for each were observed for IVF, with decreased rates for ovulation induction and spontaneous conception. The incidence of gestational diabetes and hypertensive disorders were highest among pregnancies following ART. No association was observed between conception mode and perinatal mortality. Multivariate logistic regression demonstrated that IVF was independently associated with increased odds of preterm delivery (P<0.001) and FGR (P=0.027) compared with spontaneous conception.Conclusions: Among patients of advanced maternal age, ART were independently associated with increased FGR and preterm delivery rates compared with spontaneous pregnancies; perinatal mortality was comparable. [ABSTRACT FROM AUTHOR]

Objective To identify characteristics of mothers who face difficulties with childrearing. Design and Sample Cross-sectional study. During 2014, 221 mothers and 248 children living in City A within the Tokyo metropolis were registered as requiring help with childrearing. Nursing records of 205 mothers (92.8%) and their 227 children (91.5%) were available. We excluded 29 mothers and children owing to incomplete data for a final sample of 176 mothers (79.6%) and 198 children (79.8%). Measures Difficulties with childrearing were assessed by self-reported questionnaires at the newborn child's 4-month health checkups. Data on maternal and child variables were collected from nursing records. Results The 'Difficulties group' included 59 mothers (35.4%) and their 70 children. Logistic regression analysis showed that mothers who were aged 40 years or older, who had a total score on the Edinburgh Postnatal Depression Scale of 9 or greater, who used more child-care support services, and who were monitored more frequently by public health nurses had a high risk of facing difficulties with childrearing. Conclusions Periodic monitoring by PHNs is a key strategy to improve the impact of the difficulties of childrearing for mothers of yoshien jido and their children. [ABSTRACT FROM AUTHOR]

Objective: To study factors influencing the number of ovulations in reproductive life as risk factors for common trisomies.Methods: The present observational study examined data from genetic counseling sessions performed at the 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary, between September 1, 2013, and September 1, 2015, and retrieved data on patients of advanced maternal age (≥35 years) who had fetal trisomy 21, 18, or 13 confirmed. Consecutive patients of advanced maternal age with genetic amniocentesis-confirmed healthy fetal karyotypes were also included as a control group. Medical record details were confirmed through telephone interviews with patients; the estimated ovulation number was calculated and compared among patients, as were factors contributing to the number of ovulations each patient had.Results: Data from 12 776 genetic counseling situations were examined; 35 patients with fetal trisomies and 100 patients in the control group were interviewed. Shorter mean length of oral contraceptive pill use before trisomic pregnancy (P<0.001) and a higher estimated ovulation number (P=0.012) were identified among patients with pregnancies with fetal trisomies.Conclusion: Fewer ovulatory cycles, potentially resulting from longer oral contraceptive pill use, was associated with healthy fetal karyotypes among patients of advanced reproductive age. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the factors associated with maternal mortality among women aged ≥35 years.Design: Unmatched population based case-control study.Setting: United Kingdom.Population: Between 2009 and 2012, 105 cases of maternal deaths aged ≥35 years were extracted from the surveillance database of the MBRRACE-UK confidential enquiries into maternal deaths in the UK. In addition, 766 controls aged ≥35 years were identified from the UK Obstetric Surveillance System (2005-2012).Methods: Risk factors known to be associated with maternal mortality and morbidity and for which data were available were examined for their association with maternal mortality among women ≥35 years using logistic regression analysis.Main Outcome Measures: Odds ratios and 95% confidence intervals associated with maternal death.Results: Five factors were found to be significantly associated with increased odds of death among women aged ≥35 years: smoking during pregnancy (adjusted odds ratio (aOR) 2.06, 95% CI 1.13-3.75), inadequate use of antenatal care (aOR 23.62, 95% CI 8.79-63.45), medical co-morbidities (aOR 5.92, 95% CI 3.56-9.86) and previous pregnancy problems (aOR 2.06, 95% CI 1.23-3.45). The odds associated with death increased by 12% per year increase in age (aOR 1.12, 95% CI 1.02-1.22).Conclusion: Age was associated with maternal mortality even after adjusting for other known risk factors. Importantly, this study showed an association between maternal mortality and smoking among women aged 35 years or older. It emphasises the importance of public health action to reduce smoking levels and address trends in rising maternal age.Tweetable Abstract: Smoking is a risk factor for maternal death for those aged over 35 years. [ABSTRACT FROM AUTHOR]

Objectives: To describe the characteristics, management and outcomes of women giving birth at advanced maternal age (≥48 years).Design: Population-based cohort study using the UK Obstetric Surveillance System (UKOSS).Setting: All UK hospitals with obstetrician-led maternity units.Population: Women delivering at advanced maternal age (≥48 years) in the UK between July 2013 and June 2014 (n = 233) and 454 comparison women.Methods: Cohort and comparison group identification through the UKOSS monthly mailing.Main Outcome Measures: Pregnancy complications.Results: Older women were more likely than comparison women to be overweight (33% versus 23%, P = 0.0011) or obese (23% versus 19%, P = 0.0318), nulliparous (53% versus 44%, P = 0.0299), have pre-existing medical conditions (44% versus 28%, P < 0.0001), a multiple pregnancy (18% versus 2%, P < 0.0001), and conceived following assisted conception (78% versus 4%, P < 0.0001). Older women appeared more likely than comparison women to have pregnancy complications including gestational hypertensive disorders, gestational diabetes, postpartum haemorrhage, caesarean delivery, iatrogenic and spontaneous preterm delivery on univariable analysis and after adjustment for demographic and medical factors. However, adjustment for multiple pregnancy or use of assisted conception attenuated most effects, with significant associations remaining only with gestational diabetes (adjusted odds ratio [aOR] 4.81, 95% CI 1.93-12.00), caesarean delivery (aOR 2.78, 95% CI 1.44-5.37) and admission to an intensive care unit (aOR 33.53, 95% CI 2.73-412.24).Conclusions: Women giving birth at advanced maternal age have higher risks of a range of pregnancy complications. Many of the increased risks appear to be explained by multiple pregnancy or use of assisted conception.Tweetable Abstract: The pregnancy complications in women giving birth aged 48 or over are mostly explained by multiple pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Induction of labour at 39 weeks for nulliparous women aged 35 years and over may prevent stillbirths and does not increase caesarean births, so it may be popular. But the overall costs and benefits of such a policy have not been compared.Design: A cost-utility analysis alongside a randomised controlled trial (the 35/39 trial).Setting: Obstetric departments of 38 UK National Health Service hospitals and one UK primary-care trust.Population: Nulliparous women aged 35 years or over on their expected due date, with a singleton live fetus in a cephalic presentation.Methods: Costs were estimated from the National Health Service and Personal Social Services perspective and quality-adjusted life-years (QALYs) were calculated based on patient responses to the EQ-5D at baseline and 4 weeks.Main Outcome Measures: Data on antenatal care, mode of delivery, analgesia in labour, method of induction, EQ-5D (baseline and 4 weeks postnatal) and participant-administered postnatal health resource use data were collected.Results: The intervention was associated with a mean cost saving of £263 and a small additional gain in QALYs (though this was not statistically significant), even without considering any possible QALY gains from stillbirth prevention.Conclusion: A policy of induction of labour at 39 weeks for women of advanced maternal age would save money.Tweetable Abstract: A policy of induction of labour at 39 weeks of gestation for women of advanced maternal age would save money. [ABSTRACT FROM AUTHOR]

Objective: To estimate the frequency of unexpected first-trimester ultrasound findings that would alter prenatal management in pregnant women eligible for cell-free (cf) DNA screening because of advanced maternal age (AMA).Methods: This was a retrospective cohort study of all AMA women at a tertiary care center who had a 10-14-week ultrasound examination between 1 January 2012 and 27 April 2015. Information on pregnancy dating, obstetric ultrasound examination, prenatal screening and genetic testing were collected from a perinatal database. The primary outcome was an unexpected ultrasound finding in the first trimester that would alter the prenatal screening/testing strategy.Results: In total, 2337 women met the inclusion criteria, with a total of 2462 fetuses. Sixty-eight (2.9%) women had an anomalous fetus, of which 44 (64.7%) had diagnostic testing. In the entire cohort, a non-viable pregnancy was identified in 153 (6.5%) women. Multiple gestation was identified in 32 (1.4%) women; five had a cotwin demise. Gestational dating was revised for 126 (5.4%) women. Among those who opted for aneuploidy screening (n = 1806), 68.5% had cfDNA screening and 31.5% had first-trimester screening by analysis of maternal serum biomarkers and nuchal translucency thickness. Among those eligible for cfDNA screening, 16.1% (95% CI, 15.0-18.0%; 377/2337) had an ultrasound finding (anomaly, incorrect dating, multiple gestation, non-viable pregnancy) at the time of testing that would have altered the provider's counseling regarding the prenatal screening/testing strategy.Conclusions: A substantial proportion of AMA women eligible for cfDNA screening have fetal ultrasound findings that could alter genetic testing strategy and clinical management. This study recommends ultrasound examination prior to cfDNA screening in AMA women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate the long-term consequences to women's health and the onset of menopause in healthy women of advanced reproductive age who conceived by assisted reproductive technologies (ART). Methods Healthy women who conceived by ART (72) and controls (80) were selected among 320 women ≥ 43 years, who delivered between January 2010 and December 2011 in the Department of Gynecological and Obstetrical Sciences and Urological Sciences of 'Sapienza' University of Rome. Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and presence of hypertension and diabetes were analyzed at three days, six months, and three years after delivery. The onset of menopause was analyzed after three years. Results In the ART group, SBP, DBP and hypertension were higher at three days, six months, and three years after delivery. Menopausal age was significantly lower. Conclusion The impact of ART in healthy women of advanced reproductive age in the years after delivery is not limited to the possible development of cardiovascular risk factors, such as hypertension, but can also influence the age of onset of menopause. [ABSTRACT FROM AUTHOR]

Key Clinical Message Few successful pregnancies after age 45 years with low ovarian reserve have been reported. We report a 46-year-old woman with basal FSH 20.36 mIU/ mL and an antral follicle count of four obtained two embryos and delivered a healthy infant with IVF using a microdose Gn RH-a flare-up protocol combined with Gn RH-ant. [ABSTRACT FROM AUTHOR]

Introduction: It is poorly understood if there are specific ages at which adverse outcomes during pregnancy and childbirth start to increase (threshold-ages). The purpose of this study was to examine at which maternal ages the use of maternity care and the risks for adverse maternal and infant outcomes increase.Material and Methods: National data from the Finnish Medical Birth Register including all first-time mothers aged 20 years or over with singleton pregnancies in 2005-2014 were analyzed (n = 228 348). Odds ratios for each outcome at different ages were calculated by logistic regression, using women aged 20-24 (n = 56 282) as the reference and adjusting for socioeconomic position and urbanity of residence. The threshold-age was defined as the first significant adjusted odds ratio after which the risk remained significant.Results: The threshold-ages for use of maternity care varied from 25 years for cesarean section (OR 1.08, 95% CI 1.03-1.14) to 38 years for having 16 or more antenatal visits (1.13, 1.04-1.21). Four threshold-ages were found for maternal health outcomes: 25 years for gestational diabetes (OR 1.15, 1.09-1.23), 27 years for placenta previa (OR 1.75, 1.11-2.75), 33 years for gestational hypertension (1.14, 1.03-1.27), and 38 years for preeclampsia (OR 1.48, 1.12-1.96). The threshold-ages for infant health outcomes varied from 28 years for preterm birth (37 weeks, OR 1.10, 1.02-1.19) to 36 years for perinatal mortality (OR 2.10, 1.44-3.07).Conclusions: Different threshold-ages were identified. Most adverse outcomes occurred earlier than the traditional cut-off ages for high risk pregnancy, which have been set at 35 or 40 years. [ABSTRACT FROM AUTHOR]

Aim Our purpose was to assess the background of couples who were undergoing non-invasive prenatal testing (NIPT) in Japan. Methods The characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode. Results Compared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35-39 years: 21.2% vs 7.5%, 40-45 years: 36.2% vs 12.6%), compared with the controls. Conclusion Knowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that disomic oocyte-mediated uniparental disomy 15 ( UPD(15)mat) is increased in patients with Prader-Willi syndrome ( PWS) born after medically assisted reproduction ( MAR). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients ( PWS-NC group) and 13 MAR-conceived patients ( PWS-MAR group). The relative frequency of disomic oocyte-mediated UPD(15)mat was significantly higher in PWS-MAR group than in PWS-NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS-MAR group than in PWS-NC group [median (range), 38 (26-45) vs 30 (19-42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte-mediated UPD(15)mat and MAR, after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology ( ART)-conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10−16). These results argue against a positive association of MAR procedure itself with the development of UPD(15)mat. [ABSTRACT FROM AUTHOR]

The number of pregnant women of advanced maternal age has increased worldwide. Women in this group have an increased chance of fetal abnormality. To explore Japanese women's experiences regarding maternal age-specific risks and prenatal testing, we conducted a descriptive qualitative study. Semi-structured interviews were conducted with 16 women aged 35 years or over who had given birth within the previous three months to a healthy, term infant. Thematic analysis of transcribed interview data was performed and three major themes were identified: inadequate understanding of genetic risks; insufficiently informed choice regarding prenatal testing; and need for more information from health professionals. Some participants were not aware of maternal age-specific risks to the fetus. Many took their cues from health professionals and did not raise the topic themselves, but would have considered prenatal testing if made aware of the risks. Nurses, midwives and other health professionals need to adequately inform pregnant women about the genetic risks to the fetus and offer testing at an appropriate stage early in the pregnancy. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the factors that affect the decision of pregnant women at risk for foetal Down syndrome (DS) to undergo amniocentesis, pre-natal screening, and triple serum screening. Topics include conducting semi-structured phone interviews to assess risk estimates and recall of results for DS screening, the impact of age on the decision process, and advanced maternal age (AMA).

Placental abruption occurs clinically in approximately 1% of births although placental pathology assessment suggests a higher incidence. Ultrasound rarely plays a role in the diagnosis or clinical management of patients with suspected placental abruption. A patient with an incidental sonographic finding of a large concealed abruption at 36 weeks' gestation, led to induction of labor. This case and the established association of increased stillbirth with placental abruption among patients of advanced maternal age, suggest that at term, following sonographic findings of abruption, consideration should be given to elective delivery of these patients even in the absence of clinical symptomatology. [ABSTRACT FROM AUTHOR]

ABSTRACT The present study aimed to (a) characterize the personal competencies, the social resources, and the psychosocial adjustment (psychological distress, quality of life, and parenting self-perceptions) during the early postpartum period of primiparous women of advanced age (≥35 years at the time of delivery) and their partners (older parents) compared with that of younger first-time mothers (20-34 years) and their partners (younger parents); and (b) explore the role of personal competencies and social resources in couples' psychosocial adjustment, depending on the age group. Older ( n = 74) and younger parents ( n = 71) completed self-report measures to assess personal competencies and social resources (third trimester of pregnancy), psychological distress, and quality of life (third trimester of pregnancy and 1-month' postpartum) and parenting self-perceptions (1-month' postpartum). Older parents were more similar than different from younger parents regarding personal competencies, social resources, and psychosocial adjustment during the first postnatal month. Regardless of the age group, higher personal competencies and social resources predicted lower anxiety and more positive parenting self-perceptions in women. Beyond higher personal competencies, older maternal age also predicted higher quality of life. In men, higher personal competencies were protective against anxiety, but only at older maternal age. [ABSTRACT FROM AUTHOR]

Background Trisomy 13 is one of the three autosomal trisomies compatible with viability. It is associated with structural anomalies, learning disability and poor survival. Advanced maternal age is the most frequently suggested risk factor. This is a population based register study to investigate the temporal trends of trisomy 13. Methods Chromosomal trisomies were reviewed by the Welsh Congenital Anomaly Register using data from 1998-2012. All pregnancy outcomes were included. Prevalence rates and trends for all cases and for cases with mothers aged below 35 years and those aged 35 years and older were plotted for trisomy 13, 18 and 21. Possible risk factors contributing to the trend in older mothers were compared in the early and late period of the study. Results There were 124 cases of trisomy 13 over the 15 year period with 55 mothers aged 35 years and older. Overall prevalence was 2.5 per 10,000 total births. A significant declining trend in the prevalence of trisomy 13 in mothers aged 35 and older (χ2 trend = 4.98, p=0.026) was noted. Rates for younger mothers were lower and remained stable. Prevalence of trisomy 18 and 21 in older mothers remained stable. Conclusion The unexpected declining trend in trisomy 13 in older mothers could not be explained by the risk factors examined in this study. There have been no other reports of trends in the prevalence of trisomy 13 in older mothers in recent years. There is further need for surveillance of trends in future and in other populations. Birth Defects Research (Part A) 103:610-616, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the proportion of women with advanced maternal age (AMA) undergoing amniocentesis and assess the recommended indication of 35years or older in China. Methods: Data were retrospectively evaluated from 9641 patients who underwent diagnostic prenatal amniocentesis in Beijing, China, between January 2001 and December 2012. Maternal age, indication for testing, and karyotype data were collected. Patients referred for AMA were stratified in 2 ways: 35–37years, 38–40years, and 41years or older; and indication of AMA alone or combined with other screening. Outcomes and safety performance were compared among the groups. Results: From 2001 to 2012, the annual rate of amniocentesis and the proportion of AMA-related indications increased (P <0.01). Overall, 82 abnormalities were detected. In the AMA group, the spontaneous abortion rate was 0.5% (22/4748). The positive predictive value (PPV) of AMA alone was 0.5% for women aged 35–37years. Only among women aged 41years or older was the PPV of AMA alone better than that of AMA plus other indications (2.3% vs 1.5%, respectively). Conclusion: The PPV of 35years or older did not offset the risk of spontaneous abortion. AMA alone should not be used as an indication for amniocentesis especially among women aged 35–40years. [Copyright &y& Elsevier]

Objective To assess the association between advanced maternal age ( AMA) and adverse pregnancy outcomes. Design Secondary analysis of the facility-based, cross-sectional data of the WHO Multicountry Survey on Maternal and Newborn Health. Settings A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East. Sample A total of 308 149 singleton pregnant women admitted to the participating health facilities. Methods We estimated the prevalence of pregnant women with advanced age (35 years or older). We calculated adjusted odds ratios of individual severe maternal and perinatal outcomes in these women, compared with women aged 20-34 years, using a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities. The confounding factors included facility and individual characteristics, as well as country (classified by maternal mortality ratio level). Main outcome measures Severe maternal adverse outcomes, including maternal near miss ( MNM), maternal death ( MD), and severe maternal outcome ( SMO), and perinatal outcomes, including preterm birth (<37 weeks of gestation), stillbirths, early neonatal mortality, perinatal mortality, low birthweight (<2500 g), and neonatal intensive care unit ( NICU) admission. Results The prevalence of pregnant women with AMA was 12.3% (37 787/308 149). Advanced maternal age significantly increased the risk of maternal adverse outcomes, including MNM, MD, and SMO, as well as the risk of stillbirths and perinatal mortalities. Conclusions Advanced maternal age predisposes women to adverse pregnancy outcomes. The findings of this study would facilitate antenatal counselling and management of women in this age category. [ABSTRACT FROM AUTHOR]