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Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies. [ABSTRACT FROM AUTHOR]

The mean age at childbirth in Europe has gradually increased, and it is now around 29 years of age. It has been shown that older maternal age is associated with problems of fertility; in fact, with increasing age, the chance of conceiving diminishes, and fetal and obstetric complications grow. Research has focused particularly on the biological risks associated with late pregnancy, both for the child and the woman. Less space has been dedicated to the potential psychological and relational benefits of motherhood at an advanced age. The aim of this review was to summarize the existing literature on this issue. Qualitative and quantitative studies were sourced from Pubmed, Science Direct, PsycINFO, and SciELO. The selected works highlight that advanced maternal age can be associated with some advantages for both mothers and their offspring in terms of physical healthcare, parenting styles, and child developmental outcomes. Specifically, the review suggests that older mothers have greater emotional maturity and feel more prepared for motherhood; also, advanced maternal age appears to exert a protective influence on children's behavioral, social, and emotional functioning, compensating for the biological risks. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life). [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to explore the association between advanced maternal age and the clinical manifestations as well as laboratory parameters of preeclampsia with severe features. This study included 452 patients who were diagnosed with preeclampsia with severe features. The clinical and laboratorial characteristics of patients with preeclampsia with severe features aged ≥40 years old (study group) were compared to those of patients aged <40 years old (control group). Multivariant analysis was applied to assess the association between advanced maternal age and the manifestations of preeclampsia with severe features, adjusting for the variables that exhibited significant differences between the study and control groups. The multivariate analysis revealed that a maternal age of ≥40 years old was an independent risk factor for acute kidney injury (OR = 2.5, CI = 1.2–4.9, p = 0.011) and for new-onset postpartum preeclampsia (OR = 2.4, CI = 1.0–5.6, p = 0.046). Conversely, a maternal age ≥ 40 years old was associated with a reduced risk of HELLP syndrome (OR = 0.4, CI = 0.2–0.9, p = 0.018) and thrombocytopenia (OR = 0.5, CI = 0.3–0.9, p = 0.016) compared to that of the patients < 40 years of age. In conclusion, this study demonstrates that maternal age is significantly associated with the clinical manifestations and laboratory parameters of preeclampsia with severe features, highlighting the importance of age-specific management. [ABSTRACT FROM AUTHOR]

The aim of this multicenter retrospective cohort study was to examine the impact of maternal age on perinatal outcomes in multiparas, stratified according to maternal age in one- and two-year increments. The analysis involved 302,484 multiparas who delivered between the years 2003 and 2021 in four university-affiliated obstetrics departments. Maternal age was considered both as a continuous variable and in two-year intervals, as compared with a comparison group of parturients aged 25–30 years. The study focused on cesarean delivery and neonatal intensive care unit (NICU) admission as primary outcomes. The findings revealed that cesarean delivery rates increased as maternal age advanced, with rates ranging from 6.7% among 25–30 year olds, rising continuously from 13.5% to 19.9% between the age strata of 31 and 42, to exceeding 20% among those aged ≥ 43 years (p < 0.01 for each stratum when compared to 25–30 year old group). Similarly, NICU admission rates rose from 2.7% in the comparison group to 6% in parturients aged 45–46 years (p < 0.01 for each stratum when compared to 25–30 year old group). The study highlights the association between incrementally advanced maternal age and increased rates of maternal and neonatal complications, necessitating global awareness of these implications for family planning decisions and maternal care. [ABSTRACT FROM AUTHOR]

The decision to postpone parenting has gained momentum in recent years, a shift driven by evolving social dynamics and improved access to fertility treatments. Despite their increasing prevalence, pregnancies at advanced maternal ages are associated with increased risks of adverse maternal and neonatal outcomes. This article addresses the association between advanced maternal age and hypertensive disorders of pregnancies (HDPs), which are more prevalent and a significant cause of maternal morbidity and mortality in this population. This review explores the biological mechanisms and age-related risk factors that underpin this increased susceptibility and offers practical management strategies that can be implemented prior to, as well as during, each stage of pregnancy to mitigate the incidence and severity of HDPs in this group. Lastly, this review acknowledges both the short-term and long-term postpartum implications of HDPs in women of advanced maternal age. [ABSTRACT FROM AUTHOR]

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

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

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

Advanced maternal age (AMA) poses the single greatest risk to a successful pregnancy. Apart from the impact of AMA on oocyte fitness, aged female mice often display defects in normal placentation. Placental defects in turn are tightly correlated with brain and cardiovascular abnormalities. It therefore follows that placenta, brain and heart development may be particularly susceptible to the impact of AMA. In the current study, we compared global transcriptomes of placentas, brains, hearts, and facial prominences from mid-gestation mouse conceptuses developed in young control (7–13 wks) and aging (43–50 wks) females. We find that AMA increases transcriptional heterogeneity in all tissues, but particularly in fetal brain. Importantly, even overtly normally developed embryos from older females display dramatic expression changes in neurodevelopmental genes. These transcriptomic alterations in the brain are likely induced by defects in placental development. Using trophoblast stem cells (TSCs) as a model, we show that exposure to aging uterine stromal cell-conditioned medium interferes with normal TSC proliferation and causes precocious differentiation, recapitulating many of the defects observed in placentas from aged females. These data highlight the increased risk of AMA on reproductive outcome, with neurodevelopment being the most sensitive to such early perturbations and with potential for lifelong impact. [ABSTRACT FROM AUTHOR]

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA. [ABSTRACT FROM AUTHOR]

Advanced maternal age (≥35 years) is associated with pregnancy complications. Aging impairs vascular reactivity and increases vascular stiffness. We hypothesized that uterine artery adaptations to pregnancy are impaired with advanced age. Uterine arteries of nonpregnant and pregnant (gestational day 20) young (4 months) and aged (9 months; ~35 years in humans) Sprague-Dawley rats were isolated. Functional (myogenic tone, n = 6–10/group) and mechanical (circumferential stress-strain, n = 10–24/group) properties were assessed using pressure myography and further assessment of elastin and collagen (histology, n = 4–6/group), and matrix metalloproteinase-2 (MMP-2, zymography, n = 6/group). Aged dams had worse pregnancy outcomes, including smaller litters and fetal weights (both p < 0.0001). Only in arteries of pregnant young dams did higher pressures (>100 mmHg) cause forced vasodilation. Across the whole pressure range (4–160 mmHg), myogenic behavior was enhanced in aged vs. young pregnant dams (p = 0.0010). Circumferential stress and strain increased with pregnancy in young and aged dams (p < 0.0001), but strain remained lower in aged vs. young dams (p < 0.05). Arteries from young nonpregnant rats had greater collagen:elastin ratios than the other groups (p < 0.05). In aged rats only, pregnancy increased MMP-2 active capacity. Altered functional and structural vascular adaptations to pregnancy may impair fetal growth and development with advanced maternal age. [ABSTRACT FROM AUTHOR]

Advanced maternal age (≥35 years) increases the risk of vascular complications in pregnancy that can result in fetal growth restriction and preeclampsia. Endoplasmic reticulum (ER) stress has been linked to adverse pregnancy outcomes in these complicated pregnancies. However, the role of ER stress in advanced maternal age is not known. We hypothesize that increased ER stress contributes to altered vascular function and poor pregnancy outcomes, and that treatment with the ER-stress inhibitor TUDCA will improve pregnancy outcomes. First, young and aged non-pregnant/pregnant rats were used to assess ER stress markers in mesenteric arteries; mesenteric artery phospho-eIF2α and CHOP expression were increased in aged dams compared to young dams. In a second study, young and aged control and TUDCA-treated dams were studied on gestational day (GD) 20 (term = 22 days). TUDCA treatment was provided via the drinking water throughout pregnancy (GD0-GD20; calculated dose of 150 mg/kg/day TUDCA). ER stress markers were quantified in mesenteric arteries, blood pressure was measured, pregnancy outcomes were recorded, mesenteric and main uterine arteries were isolated and vascular function was assessed by wire myography. Aged dams had increased phospho-eIF2α and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2α and CHOP expression, reduced blood pressure, improved fetal body weight, and tended to improve uterine artery function compared to control-treated aged dams. In conclusion, our data illustrate the role of ER stress, as well as TUDCA as a potential therapeutic that may benefit pregnancy outcomes in advanced maternal age. [ABSTRACT FROM AUTHOR]

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

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

Advanced maternal age is associated with adverse pregnancy outcomes and the decline of female fertility in mammals. A potential reason for reduced fertility is metabolic changes due to protein modifications by advanced glycation end products. To elucidate the aging process in female reproduction, we analysed a key enzyme for detoxification of reactive dicarbonyls, the glyoxalase 1 (GLO1), in reproductive organs and blastocysts of young and old rabbits at the preimplantation stage. At day 6 post coitum, uterine, oviductal, ovarian tissue and blastocysts from young (16–20 weeks) and old rabbits (>108 weeks) were characterised for GLO1 expression. GLO1 amounts, enzymatic activity and localisation were quantified by qPCR, Simple Western, activity assay and immunohistochemistry. The GLO1 enzyme was present and active in all reproductive tract organs in a cell-type-specific pattern. Ovarian follicle and uterine epithelial cells expressed GLO1 to a high extent. In tertiary follicles, GLO1 expression increased, whereas it decreased in the endometrium of old rabbits at day 6 of pregnancy. In blastocysts of old animals, GLO1 expression remained unchanged. In early pregnancy, advanced maternal age leads to modified GLO1 expression in ovarian follicles and the endometrium, indicating an altered metabolic stress response at the preimplantation stage in older females. [ABSTRACT FROM AUTHOR]

Advanced maternal age (AMA) poses the single greatest risk to a successful pregnancy. Apart from the impact of AMA on oocyte fitness, aged female mice often display defects in normal placentation. Placental defects in turn are tightly correlated with brain and cardiovascular abnormalities. It therefore follows that placenta, brain and heart development may be particularly susceptible to the impact of AMA. In the current study, we compared global transcriptomes of placentas, brains, hearts, and facial prominences from mid-gestation mouse conceptuses developed in young control (7-13 wks) and aging (43-50 wks) females. We find that AMA increases transcriptional heterogeneity in all tissues, but particularly in fetal brain. Importantly, even overtly normally developed embryos from older females display dramatic expression changes in neurodevelopmental genes. These transcriptomic alterations in the brain are likely induced by defects in placental development. Using trophoblast stem cells (TSCs) as a model, we show that exposure to aging uterine stromal cell-conditioned medium interferes with normal TSC proliferation and causes precocious differentiation, recapitulating many of the defects observed in placentas from aged females. These data highlight the increased risk of AMA on reproductive outcome, with neurodevelopment being the most sensitive to such early perturbations and with potential for lifelong impact.

Pregnant women of advanced maternal age (AMA) are vulnerable to exposure to the surrounding environment. Assessment of trace elements in pregnant women living in specific areas is important for biomonitoring. However, exposure levels and variation patterns during pregnancy remains controversial and attracts extensive public concern. Therefore, we aimed to evaluate exposure of 18 toxic and/or essential trace elements in maternal plasma and in paired cord plasma during pregnancy at AMA. A total of 48 pregnant women of AMA were recruited in Peking University Third Hospital from 2018 to 2021. Eighteen elements found in maternal plasma during the 1st, 2nd, or 3rd trimester of pregnancy and paired cord plasma were measured by 7700x ICP-MS (Agilent Technologies, Palo Alto, CA, USA) and Elan DRC type II ICP-MS (The Perkin-Elmer Corporation, Waltham, MA USA). Concentrations of Pb, Se, Fe, Zn, and Mo all decreased during pregnancy, while Cu increased. Interestingly, concentrations of Rb decreased initially but then increased. Elements as Al, Co, Se, Cu, and Ni showed significantly lower levels in cord than in maternal plasma, while elements as Sr, Fe, Rb, Mn and Zn displayed significantly higher levels in cord than in maternal plasma. Moreover, positively- interacted clusters were found in Ni-Co-Cu-Al-Rb-Zn and Zn-Mn-Al-Pb in maternal blood. Similar positively-interacted clusters were found in Zn-Ni-Co, Zn-Ni-Fe, Mn-Al-Pb, Fe-Pb-Mn, Fe-Ni-Cu, and Rb-Cu-Sb-Fe-Mn in cord plasma. Furthermore, correlations between paired maternal and cord blood samples for As, Sr, and Mo were statistically significant, indicating that the fetus burden may reflect maternal exposure to some extent. Admittedly, levels of toxic and essential elements in our cohort study were comparatively lower than those in the scientific literature.

Background: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. Method: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). Results: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03–1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04–1.79). Conclusion: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of parity and interpregnancy interval (IPI) on perinatal outcomes in advanced maternal age (AMA) parturients. Methods: A population-based retrospective cohort study of all women older than 40 years, who had a singleton live birth after 24 weeks in the United States in 2017 Women were categorized to three groups by parity and interval from last delivery: primiparas, multiparas with IPI ≤ 5 years, and multiparas with IPI > 5 years. Primary outcome was composite adverse neonatal outcome (preterm delivery <34 weeks, birthweight <2000 g, neonatal seizure, neonatal intensive care unit admission, Apgar score <7 at 5 min, or assisted ventilation >6 h). Secondary outcome was composite adverse maternal outcome and other adverse perinatal outcomes. Univariate and multivariate analysis were used to compare between groups. Results: During 2017, 3,864,754 deliveries were recorded into the database. Following exclusion, 109,564 AMA gravidas entered analysis. Of them, 24,769 (22.6%) were nulliparas, 39,933 (36.4%) were multiparas with IPI ≤ 5 years, and 44,862 (40.9%) were multiparas with IPI > 5 years. Composite neonatal outcome was higher in nulliparas and in multiparas with IPI > 5 years, in comparison to multiparas with IPI ≤ 5 years (16% vs. 13% vs. 10%, respectively, p < 0.05). Maternal composite outcome was similar between groups. In the multivariable analysis, relative to nulliparas, only multiparity with IPI ≤ 5 years had a protective effect against the composite neonatal outcome (aOR 0.97, 95% CI 0.95–0.99, p < 0.001). Conclusion: Among AMA gravidas, multiparity with IPI ≤ 5 years has a significant protective effect against adverse neonatal outcomes when compared to nulliparas. Multiparity with IPI > 5 years is no longer protective. [ABSTRACT FROM AUTHOR]

Advanced maternal age (AMA) is associated with reduced fertility due in part to diminished ovarian follicle quantity, inferior oocyte quality, chromosome aneuploidy, and lower implantation rates. Ovarian aging is accompanied by increased oxidative stress and blunted antioxidant signaling, such that antioxidant intervention could improve reproductive potential. The first aim of this study was to determine the molecular effects of antioxidant intervention in the ovaries and oocytes of aged mice, utilizing a supplement containing only naturally occurring açaí (Euterpe oleracea) with an oxygen radical absorbance capacity of 208,628 μmol Trolox equivalent (TE)/100 g indicating high antioxidant activity. Nine month old female CF-1 mice were administered 80 mg/day antioxidants (n = 12) or standard diet (n = 12) for 12 weeks. In the ovary, antioxidant treatment upregulated β-adrenergic signaling, downregulated apoptosis and proinflammatory signaling, and variably affected cell growth and antioxidant pathways (p < 0.05). Exogenous antioxidants also increased the oocyte expression of antioxidant genes GPX1, SOD2, and GSR (p < 0.05). A feasibility analysis was then conducted on female AMA infertility patients as a proof-of-principle investigation. Patients (n = 121; <45 years old) consented to receiving 600 mg antioxidants three times daily for ≥8 weeks preceding infertility treatment. Preliminary results indicate promising outcomes for AMA patients, warranting further investigation. [ABSTRACT FROM AUTHOR]

Multiple gestations have become an increasing phenomenon that has impacted public health globally, largely due to the application of assisted reproductive technologies. The objective of this work was to find out the discourse that the health professionals involved in its follow-up have in our context. For this, a qualitative methodology was chosen, with semi-structured interviews recorded in audio, prior authorisation, and transcribed verbatim. It was based on a script designed for this purpose, with the following analysis categories: the current trend of multiple gestations, impact, and follow-up. The content analysis was based on the experiences, knowledge, and perceptions of the professionals interviewed. Professionals stated that the current socioeconomic and legal context hinders a single embryo transfer policy that decreases multiple gestation rates. They emphasised the importance of the psychic impact of such gestations on the couple, on the mother in particular, as well as the economic effect on families, health, and society in general. They expressed the need to create specific protocols to assist these gestations. Midwives, in particular, demanded that the health administration recognise and support the differentiated care they perform with this type of gestation. Work on specific models is needed to adequately size the impact of multiple gestations, as well as to generate social health policies that lead to co-responsible reconciliation measures that favour women having one pregnancy at a time.

Simple Summary: In this study, we examined the anti-oxidative effect of human adipose stem cell conditioned medium (ASC-CM) on the ovary and uterus of mice in advanced maternal age (AMA) and the optimal conditions of intravenous injection for ASC-CM administration. Human ASC-CM upregulated expression of antioxidant genes, restored the quality of oocytes derived from aged ovaries and resulted in improved in vitro and in vivo embryo development. The anti-oxidative effect human ASC-CM was optimized with high frequency of administration. Comprehensively, our study successfully introduced the potential of ASC-CM as an antioxidant intervention against age-related infertility in AMA. Advanced maternal age (AMA) has become prevalent globally. With aging, weakened antioxidant defense causes loss of normal function in the ovary and uterus due to oxidative stress. Here, we aimed to improve embryo development in AMA mice by intravenous injection (IV) of human adipose stem cell conditioned medium (ASC-CM) at various frequencies and intervals as an antioxidant intervention. Four- and six-month-old female ICR (Institute of Cancer Research) mice were randomly divided into groups IV treated with human ASC-CM under different conditions, and in vitro and in vivo embryo development were evaluated. Consequently, compared to the control group, blastocyst formation rate of parthenotes was significantly promoted in 4-month-old mice and the mean number of implanted fetuses after natural mating was significantly increased by approximately two-fold in 6-month-old mice. Through gene analysis, the anti-apoptotic and anti-oxidative effects of human ASC-CMs were confirmed in the ovaries and uterus of pregnant mice at both ages. In particular, ovarian expression of gpx1 and catalase drastically increased in 6-month-old mice. Furthermore, the levels of gpx1 and catalase were further increased, with a high frequency of injection regardless of age. Thus, we demonstrated for the first time the anti-oxidative effect of human ASC-CM administration against ovarian aging and the optimal injection condition. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and presents with genetic and clinical heterogeneity. ADPKD can also manifest extra-renally, and seminal cysts have been associated with male infertility in some cases. ADPKD-linked male infertility, along with female age, have been proposed as factors that may influence the clinical outcomes of preimplantation genetic testing (PGT) for monogenic disorders (PGT-M). Large PGT for aneuploidy assessment (PGT-A) studies link embryo aneuploidy to increasing female age; other studies suggest that embryo aneuploidy is also linked to severe male-factor infertility. We aimed to assess the number of aneuploid embryos and the number of cycles with transferable embryos in ADPKD patients after combined-PGT. The combined-PGT protocol, involving PGT-M by PCR and PGT-A by next-generation sequencing, was performed in single trophectoderm biopsies from 289 embryos in 83 PGT cycles. Transferable embryos were obtained in 69.9% of cycles. The number of aneuploid embryos and cycles with transferable embryos did not differ when the male or female had the ADPKD mutation. However, a significantly higher proportion of aneuploid embryos was found in the advanced maternal age (AMA) group, but not in the male factor (MF) group, when compared to non-AMA and non-MF groups, respectively. Additionally, no significant differences in the percentage of cycles with transferable embryos were found in any of the groups. Our results indicate that AMA couples among ADPKD patients have an increased risk of aneuploid embryos, but ADPKD-linked male infertility does not promote an increased aneuploidy rate. [ABSTRACT FROM AUTHOR]

Background and objecives : Adverse cardiovascular outcomes during pregnancy have increased over the past few decades, with increased numbers of women delivering later in their reproductive life. Other factors include higher rates of female obesity, diabetes, hypertension, cardiovascular diseases and assisted reproductive technology, which has extended fertility. Those at risk require extensive prenatal maternal screening, constant pregnancy supervising, monitoring during labor, delivery and puerperium and careful anesthetic evaluation during delivery. Materials and Methods : The present review reports the relevant information available on cardiovascular outcomes in advanced maternal age delivering women and related medico-legal issues. The search was performed on Pubmed, Cochrane, Semantic Scholar, Medline and Embase databases, accessed by Ovid, including among others the terms "cardiomyopathy", "ischaemic heart disease", "arrhythmias", "hypertension", "peripartum period", "diabetes", "advanced maternal age" "anesthesia", "maternal morbidity and mortality" and "litigation". Results : To the extent that underestimating risk factors for peripartum cardiomyopathy (PPCM) can adversely impact maternal and fetal outcomes, the legal implications of misdiagnosis or mismanagement can result in high compensatory damages. Substantial indemnity payments drive up costs of insurance coverage. Conclusions : Multidisciplinary approaches are necessary from obstetricians, cardiologists, anesthesiologists and perinatologists for pregnancy monitoring and delivery outcomes.