Impact Of Maternal Age Research Articles

Impact of maternal age on oxidation-reduction potential in follicular fluid and assisted reproductive technology treatment outcomes

Background: Maternal age influenced the quantity and quality of oocytes. The composition of follicular fluid was changed in advanced maternal age. This study was conducted to evaluate changes in redox potential and blastocyst formation potential in older women. Methods and materials: Retrospective study collected data from December 2020 to October 2023 on patients treated with in vitro fertilization with follicular fluid surveyed at the Center for Reproductive Endocrinology and Infertility (HUECREI), Hue University of Medicine and Pharmacy, Hue. Results: Two cohorts comprised the 456 patients: Group 1, consisting of individuals younger than 35 years of age, and Group 2, comprising those 35 years or older. Anti-Müllerian hormone (AMH), initial follicle-stimulating hormone (FSH), and total FSH dose utilized differed significantly between Groups 1 and 2, with median values of 3.79 versus 2.10 ng/mL (P value < 0.001), 225.00 versus 277.50 IU/L (P value < 0.001), and 2025.00 versus 2325.00 IU/L (P value < 0.001), respectively. However, there were no significant differences in ORP, maturation rate, fertilization rate, or blastocyst formation rate between the two age groups. Variations in ORP were only observed among subgroups of patients with the ability to achieve an expected fertilization rate of ≥ 70% in Group 1. Specifically, the subgroup meeting expectations had a lower ORP of 83.00 ± 83.00 mV, in contrast to the non-expectation group which had an ORP of 96.14 ± 83.00 mV, accompanied by a P value of 0.005. The difference of ORP was not observed in the group that reached and did not reach the benchmark embryo formation ≥ 60% in the two age groups. Conclusion: Advanced maternal age have declined in ovarian function but no statistically significant difference in redox potential in follicular fluid has been observed. The fertilization rate and blastocyst formation rate were equivalent across the two age groups of women. The redox potential of follicular fluid was not statistically significant difference between cycles that reached and did not reach the benchmark of blastocyst formation ≥ 60% in the two age groups of women. Key words: Blastocyst, advanced maternal age, oxidative-reduction potential (ORP), in vitro fertilization.

Impact of maternal age and body mass index on the structure and function of the heart in newborns: a Copenhagen Baby Heart Study

BackgroundMaternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn.MethodsInfants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2) < 18.5; 18.5–24.9 (reference); 25–29.9; 30–34.9 and ≥ 35 and maternal age (years) < 25; 25–29; 30–34 (reference); 35–39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child’s weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa.ResultsThe study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30–34.9 kg/m2 [-0.11 ± 0.04 mm, p = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m2 had significantly smaller LV internal diameters in end-systole: BMI 25–29.9 kg/m2 [-0.04 ± 0.02 mm, p = 0.04], BMI 30–34.9 kg/m2 [-0.12 ± 0.03 mm, p = 0.001] and BMI ≥ 35 kg/m2 [-0.11 ± 0.05 mm, p = 0.03].Compared with infants in the age reference group, infants born to women ≥ 40 years had significantly smaller LV internal diameters in end-diastole [-0.15 ± 0.04 mm, p = 0.001] and end-systole [-0.09 ± 0.04 mm, p = 0.009].ConclusionsSystematic population-based echocardiography of infants showed that a maternal prepregnancy BMI ≥ 25 kg/m2 and maternal age ≥ 40 years were associated with smaller systolic and diastolic LV diameters. The long-term effects are unknown.Clinical trial registrationApril 2016, Copenhagen Baby Heart, NCT02753348.

Impact of maternal age on perinatal results

Background/Purpose: In our study, we aimed to evaluate maternal, fetal, and neonatal outcomes of pregnancies managed by our perinatologists, obstetricians, and pediatricians in 3 different centers over the past five years, by age group.&#x0D; &#x0D; Methods: In this retrospective study, we collected the maternal and neonatal data from the hospital electronic records of 403 adolescents (15-19 years of age), 491 women of advanced age (&gt;40 years of age), and 200 pregnant controls (20-39 years of age) who delivered in our obstetrics units between 2016 and 2021.&#x0D; &#x0D; Results: Obstetric and fetal outcomes affected from women bearing children early or late stages in life. According to our results, rates of one or more parity, cesarean section, gestational hypertension, and acute fetal distress in the women of advanced age were significantly higher than those in the controls (p34 gestational weeks in the adolescents were significantly lower than those in the controls (p

Trends in maternal ICU admissions at a quaternary centre in Montreal, Canada, and impact of maternal age on critical care outcomes.

Advancing maternal age is increasingly prevalent and is associated with severe maternal morbidity often requiring intensive care unit (ICU) admission. To describe maternal ICU admissions at a quaternary care hospital in Montreal, Canada, and evaluate the association between maternal age and composite of: need for invasive interventions, ICU stay > 48 h, or maternal death. Chart review of ICU admissions during pregnancy/postpartum (2006-2016); logistic regressions to evaluate the impact of age on outcomes. With 5.1 ICU admissions per 1000 deliveries, we included 187 women (mean age 32 ± 6.3 years; 20 (10.7%) ≥ 40 years). The composite outcome occurred in 105 (56.2%) patients; there were two maternal deaths. Age ≥ 40 years increased the odds of invasive interventions (OR 4.03; 95% confidence interval [CI] 1.15-14.1) but not of the composite outcome (OR 2.30; 95% CI 0.66-8.02). Peripartum women aged ≥ 40 years had worse outcomes in ICU, with an increased need for invasive interventions.

The Impact of Maternal Age and Educational Level on Developmental Dysplasia of the Hip Diagnosis and Screening: A Descriptive Comparative Study.

Early and proper screening for developmental dysplasia of the hip (DDH) is very critical to prevent catastrophic complication on the developing hip joint. Many factors (either maternal or child-related) that hinder timely DDH screening have been previously investigated. A cross-sectional descriptive study design was adopted. 175 babies presented for DDH screening coming with their mothers were investigated. Maternal age, age group, and educational level were recorded. In addition, multiple child-related variables such as age of screening, gender, positive family history, preterm delivery, and mode of delivery were recorded as well. Analysis for association between delayed vs. early screening was made against the maternal and the child-related variables. A total number of 175 children with their mothers were investigated. The mean maternal age was 27.9 years, about one third of the mothers had a graduate level of education (36.3%), while 41.1% had high school education, and 22.3% had middle school education. On the other hand, 40.0% of the investigated babies were first born and two thirds of our sample babies were females (66.9%). Of the included babies, 100 (57.1%) were screened at the appropriate 4-month age, while 75 (42.9%) missed the 4-month screening. Chi-square analysis showed that delayed DDH screening was associated with a lower maternal educational level (P ≤ 0.001), younger maternal age (P ≤ 0.001), and first born baby (P ≤ 0.001). Positive family history was protective against delayed DDH screening (P = 0.032). The lower maternal educational level, younger maternal age group, and first born babies are risk factors for delayed DDH screening.

Effect of maternal age on neonatal outcomes in very low birth weight singleton infants: a population-based study.

Little is known on the impact of maternal age (MA) on very low birth weight (VLBW) infants' outcomes. We tested the hypothesis that at both ends of MA there are increased adverse neonatal outcomes in VLBW infants. We used the Israel National Neonatal Network VLBW (≤1500 g) database. Maternal age was stratified as: <20, 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses were univariate and multivariable logistic regression analysis. After adjustment, the infant outcomes of older mothers were similar to those of the reference group for mortality, RDS, severe ROP, NEC and sepsis. Mothers < 20 and 20-24 years old had higher odds of IVH grades 3-4 (OR 1.45, 95% CI 1.09-1.93 and OR 1.26, 95% CI 1.10-1.45, respectively), and BPD (OR 1.55, 95% CI 1.13-2.13 and OR 1.40, 95% CI 1.22-1.62, respectively). There were higher odds for PVL in infants of <20 year-old mothers (OR 1.83, 95% CI 1.26-2.65) and in infants of 35-39 year-old mothers (OR 1.38, 95% CI 1.12-1.69). Poor composite outcomes were significantly higher in the youngest maternal age categories (<20-year-old mothers (OR 1.63, 95% CI 1.28-2.08), and 20-24-year-old (OR 1.28, 95% CI 1.15-1.43). Neonatal outcomes differ in relation to maternal age among very low birth weight newborns, with adverse outcomes more predominant in infants of younger mothers.

A RESILIENT WOMB: MATERNAL AGE AT TRANSFER FOLLOWING AUTOLOGOUS OOCYTE (AO) CRYOPRESERVATION (CRYO) DOES NOT IMPACT ONGOING PREGNANCY + LIVE BIRTH RATES (LBRS)

AO cryo is widely used for fertility preservation, but the impact of maternal age on transfer outcomes is unknown. We reviewed our single embryo transfers (SETs) from AO cryo to understand the effect of maternal age at SET on LBR.

Faster Fertilization and Cleavage Kinetics Reflect Competence to Achieve a Live Birth: Data from Single-Embryo Transfer Cycles.

The aim of this study was to assess the relationship between early developmental kinetics and the competence to result in a live birth as well as the impact of maternal age and the number of retrieved oocytes. This retrospective cohort study included 3,021 single-embryo transfer cycles and assessed live birth outcomes paired with morphokinetic data; 1,412 transfers resulted in live births (LB), and 1,609 did not (NLB). Early morphokinetic parameters between LB and NLB embryos were compared from patients stratified into four age groups (20-25, 26-30, 31-36, and ≥37 years) and between embryos in the same competence groups within the age groups. Early morphokinetic parameters were also compared between LB and NLB embryos from patients stratified into four groups based on the number of oocytes harvested (≤7, 8-14, 15-21, and ≥22). The association between morphokinetic parameters and LB was tested using univariate and multivariate analyses. This study indicated that embryos resulting in LB generally exhibit faster developmental dynamic parameters than embryos that do not. However, this difference decreased in the younger (20-25 years) and older (≥37 years) age groups. In addition, when the number of harvested oocytes was low (≤7) or high (≥22), this difference was less obvious. The morphokinetic parameters of embryonic cleavage are an effective reference value for embryo selection strategies aimed at increasing live birth rates, especially for patients aged 26–36 years, with 8–21 harvested oocytes.

Impact of maternal age on neonatal outcomes among very preterm infants admitted to Chinese neonatal intensive care units: a multi-center cohort study.

BackgroundThe percentage of advanced maternal age (aged over 35 years) mothers has been rising across the world, the evidence of maternal age on neonatal outcomes from low- and middle-income countries is scarce. Our objective was to evaluate the effect of maternal age on mortality and major morbidity among very preterm infants admitted to Chinese neonatal intensive care units.MethodsData from a retrospective multi-center cohort of all complete care very preterm infants admitted to 57 neonatal intensive care units that participated in the Chinese Neonatal Network from January 1st to December 31st, 2019 were analyzed. Neonatal outcomes including mortality or any major morbidity, defined as necrotizing enterocolitis stage 2 or 3, moderate & severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. A multiple logistic regression model was constructed to analyze the independent association between maternal age and neonatal outcome.ResultsAmong 7,698 eligible newborns, 80.5% of very preterm infants were born to mothers between the ages of 21 and 35 years, with 18.0% born to mothers >35 years and 1.5% born to mothers <21 years. Higher rates of maternal hypertension, maternal diabetes, cesarean deliveries, antenatal steroid usage were noted as maternal age increased. The proportion of prenatal care, cesarean section, antenatal steroid usage and inborn for very preterm infants born to mothers <21 years was lower than those of mothers of other ages. Compared to the ages of 21–35 years group, the odds of severe intraventricular hemorrhage (adjusted odd ratio: 2.00, 95% CI: 1.08–3.71) was significantly higher in the ages of 15–20 years group. Increasing maternal age was associated with higher rates of small for gestational age and lower birth weight of very preterm infants, but no correlation between advanced maternal age and very preterm infants mortality or major morbidity.ConclusionsAmong very preterm infants, increasing maternal age was associated with higher rates of small for gestational age but not neonatal mortality or major morbidity. Young maternal age may increase the risk of severe intraventricular hemorrhage of very preterm infants.

Impact of Maternal Age on Obstetric and Neonatal Outcome in Primiparous Women

Background: Pregnancy at extremes of age can be very challenging. The reflex of a woman to pregnancy is influenced by various factors through which woman's age at pregnancy time can be known as the single most important factor that has undeniable effect on pregnancy process and labour. Both adolescent and elderly pregnancy are considered to be high risk as they have unique outcomes. Objective: To assess the effect of maternal age on obstetric and neonatal outcome. Methods: This prospective observational study was conducted on 250 primiparous women who attended at Department of Obstetrics &amp; Gynaecology, 300 Bed Hospital, Narayanganj, Bangladesh from March 2019-February 2020. A detailed history regarding maternal age, period of gestation, development of any signs and symptoms of various comorbidities is taken and antenatal examination is done. Routine antenatal investigations were done and all the cases were followed till delivery. Development of various maternal co-morbidities, mode of delivery and neonatal outcome was assessed. Results: Majority of our study population were in 20-34 years age group (72.0%), teenagers constituted 19.2%, advanced maternal age constituted 8.8%.The number of pre- term births in gestational age between 28 to 36 weeks were similar in teenage mothers (12.5%) and elderly primi (13.6%) where as in normal age group it was only 3.8%. Post term pregnancy where comparatively higher in elderly primi (18.8%) than teenagers (10.4%) Association of gestational age with maternal age is statistically significant (P &lt;0.05). In our study 11% patients had Gestational Hypertension. Association of Hypertension in pregnancy with maternal age is statistically significant (p &lt;0.05). In our study, GDM was present in 7.6%; in teenage mothers 2.1% and in elderly mothers 28.5%. In teenage 12.5% and in elderly mothers it is 31.8%. Association of Hypothyroid and maternal age is statistically significant (p&lt;0.05). In our study anemia was seen in 4.1% of teenagers, 4.5% advanced maternal age, 3.3% in age group 20 to 34 years. In our study, 47.9% of teenage mothers delivered vaginally and 52.1% of them delivered by cesarean section. In age group 20 to 34 years, vaginal delivery was 50.2% and caesarean delivery was 49.7%. Whereas in elderly primis the rate of cesarean delivery was 71.4% and vaginal delivery was 28.5%. Association of mode of delivery with maternal age is statistically significant (p&lt;0.05). In our study teenagers, term babies were 78.7%, pre-term babies were 12.7%, IUGR babies were 6.3% and IUD 2.1%. In advanced maternal age; term babies were 68.1%, pre- term were 13.6%, IUGR were 13.6% and IUD were 4.5%. Association of outcome of baby is statistically significant (p&lt;0.05). In our study the babies which got admitted in NICU were 33.7% in teenage mothers and in elderly is 13.3%. Association of NICU admission among teenage and advanced maternal age is statistically significant. (p&lt;0.05). Conclusion: Teenage pregnancy is an essential public health issue as it is associated with poor maternal and fetal outcome. Teenage and Elderly pregnancy are associated increased maternal and perinatal mortality and morbidity early detection of risk factors and prevention is necessary to reduce the morbidity.

Impact of Maternal Age on Singleton Birthweight in Frozen Embryo Transfer Cycles.

BackgroundPrevious studies have investigated the effect of maternal age on assisted reproductive technology success rates. However, little is known about the relationship between maternal age and neonatal birthweight in frozen embryo transfer (FET) cycles. Whether maternal age influences singleton birthweight in FET cycles remains to be elucidated.MethodsThis study was conducted at a tertiary care center, involving singleton live births born to women undergoing frozen–thawed embryo transfer during the period from January 2010 to December 2017. A total of 12,565 women who fulfilled the inclusion criteria were enrolled and grouped into four groups according to the maternal age: <30, 30–34, 35–39, and ≥40 years old. A multivariable linear regression analysis was conducted to reveal the relationship between maternal age and neonatal birthweight with controlling for a number of potential confounders.ResultsThe highest proportions of low birthweight (LBW, 4.1%), high birthweight (1.2%), preterm birth (PTB, 5.9%), and very PTB (0.9%) were found in the group over 40 years old, but no significant difference was observed among the four groups. Additionally, the 35–39-year-old group had the highest rate of very LBW (0.6%), whereas the 30–34-year-old group had the lowest rate of small for gestational age (SGA, 2.7%). However, multivariate analyses revealed that neonatal outcomes including PTB, LBW, and SGA were similar between the different maternal age groups.ConclusionGrouping with different maternal age was not associated with mean birthweight and Z-scores of singletons resulting from FET.

Impact of Maternal Age on Singleton Pregnancy Outcomes in Primiparous Women in South Korea.

We aimed to determine the association between maternal age and pregnancy outcomes in singleton primigravidae in South Korea. We reviewed the medical data of singleton primigravidae women who gave birth between 2013 and 2018 and underwent the National Health Screening Examination using the administrative database from the National Health Insurance claims data. As advanced maternal age is associated with various comorbidities that could affect pregnancy outcomes, we divided the patients according to their age and comparatively analyzed the prevalence of high-risk pregnancy complications including rates of cesarean delivery, after adjusting for maternal demographics. Perinatal and postpartum complications according to maternal age were also investigated. Overall, 548,080 women were included in this study: 441,902 were aged <35 years; 85,663, 35–39 years; 20,515, ≥40 years. Patients’ demographics differed according to their age. Increasing maternal age was significantly associated with higher income levels and higher rates of obesity, pre-existing diabetes, and hypertension. With the increasing maternal age, the rate of obstetric complications, including gestational diabetes, preeclampsia, placenta previa, placental abruption, and cesarean delivery, increased. Maternal age was also positively correlated with perinatal morbidity including preterm birth and low birth weight. Additionally, advanced maternal age was a risk factor for hospitalization before delivery, more frequent outpatient visits, and readmission after delivery. These observations were maintained in the multivariate analysis results. Advanced maternal age appears to be associated with various adverse obstetric outcomes for primigravidae women, and the frequency of hospitalizations was higher in this group. Considering the current social environment of late pregnancies and childbirth in South Korea, effective policy consideration is required to support safe childbirth in women with advanced maternal age.

The Impact of Maternal Age on Chromosomal Aneuploidy, Blastocyst Quality, and Pregnancy Outcomes During Intracytoplasmic Sperm Injection Cycles

Background &amp; Objective: Assisted reproduction techniques and preimplantation genetic testing (PGT) for aneuploidies help infertile couples achieve a healthy live birth. The objective of this study was to investigate if there is a correlation between chromosomal aneuploidy and maternal age. Materials &amp; Methods: We used 277 embryos with 6-8 cells and graded A derived from intracytoplasmic sperm injection cycles. There were two subgroups: fresh-PGT cycles (n = 38) and Frozen Embryo Transfer (FET) cycles (n = 38). The PGT cycles results were evaluated by fluorescence in situ hybridization and polymerase chain reaction assays. Couples (n = 76) with PGT on the third day were classified into four maternal age groups: ≤35 years (n = 35), 36-40 years (n = 24), 41-45 years (n = 11), and ≥46 years (n = 6). The rate of aneuploidy, blastocyst quality, and pregnancy was assessed in FET and fresh-PGT cycle. Results: Aneuploidy rate in 13, 18, 21, X, and Y chromosomes in FET and fresh-PGT cycles are not significantly related to maternal age (p = 0.1). Significant differences were found in a decreased chemical pregnancy (p = 0.001), clinical pregnancy (p = 0.001), ongoing pregnancy (p = 0.001), and live birth rate (p = 0.001) among both groups. Decreased blastocyst rate increased maternal age in fresh PGT and FET PGT (p = 0.02). Early and clinical pregnancy loss was not related significantly to maternal age. Conclusion: After evaluating cycle characteristics, an association was found between maternal age and declined pregnancy outcomes in embryos. There was a significant relationship between increasing female age with decreasing blastocyst rate.

Impact of maternal age on perinatal outcomes in twin pregnancies: a systematic review and meta-analysis.

Current evidence of the maternal, perinatal and neonatal outcomes in twin pregnancies among mothers with advanced age is unclear, especially for mothers with age above 40 years. A systematic search was conducted using the PubMed, Scopus, and Google Scholar databases. Studies that were observational in design or analysed retrospective data were considered for inclusion. The included studies had to be conducted in twin pregnancies and should have documented the effect of maternal age on obstetric and/or neonatal outcomes. Statistical analysis was performed using STATA software. A total of 20 studies were considered for inclusion. All the studies were based on retrospective data. Compared to mothers aged under 40 years, those with advanced age (≥40 years) had increased risk of caesarean delivery [RR 1.20, 95% CI: 1.05, 1.37], gestational hypertension [RR 2.71, 95% CI: 1.72, 4.27], gestational diabetes mellitus [RR 2.03, 95% CI: 1.28, 3.21], preterm birth [RR 2.47, 95% CI: 1.09, 5.80], neonatal admission to intensive care unit [RR 1.78, 95% CI: 1.21, 2.64] and perinatal and/or neonatal mortality [RR 5.76, 95% CI: 1.11, 29.7]. The risk of gestational diabetes mellitus [RR 1.52, 95% CI: 1.21, 1.90] and having caesarean delivery [RR 1.19, 95% CI: 1.10, 1.28] was higher in mothers with ≥35 years of age, compared to those <35 years. There were no significant differences in the risk of adverse neonatal outcomes among the mothers with age ≥35 years. However, in these mothers, the risk of perinatal/neonatal mortality [RR 0.82, 95% CI: 0.76, 0.88] was comparatively lower than in mothers under 35 years of age. There appeared no significant risk of advanced maternal age for postpartum haemorrhage, hospitalization during pregnancy and premature rupture of membranes. The increased risk of maternal, neonatal and perinatal outcomes in mothers with advanced age highlights the need for close follow-up, early detection and management of medical complications in twin pregnancies.

The impact of maternal age on gene expression during the GV to MII transition in euploid human oocytes.

STUDY QUESTIONAre there age-related differences in gene expression during the germinal vesicle (GV) to metaphase II (MII) stage transition in euploid human oocytes?SUMMARY ANSWERA decrease in mitochondrial-related transcripts from GV to MII oocytes was observed, with a much greater reduction in MII oocytes with advanced age.WHAT IS KNOWN ALREADYEarly embryonic development is dependent on maternal transcripts accumulated and stored within the oocyte during oogenesis. Transcriptional activity of the oocyte, which dictates its ultimate developmental potential, may be influenced by age and explain the reduced competence of advanced maternal age (AMA) oocytes compared with the young maternal age (YMA). Gene expression has been studied in human and animal oocytes; however, RNA sequencing could provide further insights into the transcriptome profiling of GV and in vivo matured MII euploid oocytes of YMA and AMA patients.STUDY DESIGN, SIZE, DURATIONFifteen women treated for infertility in a single IVF unit agreed to participate in this study. Five GV and 5 MII oocytes from 6, 21–26 years old women (YMA cohort) and 5 GV and 6 MII oocytes from 6, 41–44 years old women (AMA cohort) undergoing IVF treatment were donated. The samples were collected within a time frame of 4 months. RNA was isolated and deep sequenced at the single-cell level. All donors provided either GV or MII oocytes.PARTICIPANTS/MATERIALS, SETTING, METHODSCumulus dissection from donated oocytes was performed 38 h after hCG injection, denuded oocytes were inserted into lysis buffer supplemented with RNase inhibitor. The samples were stored at −80°C until further use. Isolated RNA from GV and MII oocytes underwent library preparation using an oligo deoxy-thymidine (dT) priming approach (SMART-Seq v4 Ultra Low Input RNA assay; Takara Bio, Japan) and Nextera XT DNA library preparation assay (Illumina, USA) followed by deep sequencing. Data processing, quality assessment and bioinformatics analysis were performed using source-software, mainly including FastQC, HISAT2, StringTie and edgeR, along with functional annotation analysis, while scploid R package was employed to determine the ploidy status.MAIN RESULTS AND THE ROLE OF CHANCEFollowing deep sequencing of single GV and MII oocytes in both YMA and AMA cohorts, several hundred transcripts were found to be expressed at significantly different levels. When YMA and AMA MII oocyte transcriptomes were compared, the most significant of these were related to mitochondrial structure and function, including biological processes, mitochondrial respiratory chain complex I assembly and mitochondrial translational termination (false discovery rate (FDR) 6.0E−10 to 1.2E−7). These results indicate a higher energy potential of the YMA MII cohort that is reduced with ageing. Other biological processes that were significantly higher in the YMA MII cohort included transcripts involved in the translation process (FDR 1.9E−2). Lack of these transcripts could lead to inappropriate protein synthesis prior to or upon fertilisation of the AMA MII oocytes.LARGE SCALE DATAThe RNA sequencing data were deposited in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo), under the accession number: GSE164371.LIMITATIONS, REASONS FOR CAUTIONThe relatively small sample size could be a reason for caution. However, the RNA sequencing results showed homogeneous clustering with low intra-group variation and five to six biological replicates derived from at least three different women per group minimised the potential impact of the sample size.WIDER IMPLICATIONS OF THE FINDINGSUnderstanding the effects of ageing on the oocyte transcriptome could highlight the mechanisms involved in GV to MII transition and identify biomarkers that characterise good MII oocyte quality. This knowledge has the potential to guide IVF regimes for AMA patients.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Medical Research Council (MRC Grant number MR/K020501/1).

Impact of maternal age on obstetric and neonatal morbidity: a retrospective cohort study

BackgroundPregnancies in women over 35 years of age are becoming more frequent. The majority of studies point to an age of 35 as a provider of obstetric and neonatal complications. But several confounding factors are not taken into account and this results in contradictory results.MethodsThe objective was to quantify the strength of the association between maternal age and obstetric and neonatal morbidity. This observational study was based on systematic records of 9 years of pregnancies managed in the Obstetrics and Gynaecology Department of Antoine Béclère Hospital, Clamart, France. In all, 24,674 pregnancies were managed at Antoine Béclère Hospital between April 1, 2007 and December 31, 2015, including 23,291 singleton pregnancies. Maternal age was the age at the beginning of pregnancy, taken as a quantitative variable. The main outcome measure was a composite “unfavourable” pregnancy outcome that included miscarriage, induced abortion, in utero foetal death, stillborn or newborn infant weighing under 500 g or delivered before 24 weeks of gestational age. Obstetric and neonatal morbidity comprised hospitalisation during pregnancy for more than 1 day, pre-eclampsia, gestational diabetes requiring hospitalisation, caesarean delivery, preterm birth, small-for-gestational age, and newborn transfer to the paediatric unit or neonatal intensive care unit.ResultsAnalyses were conducted among singleton pregnancies (n = 23,291) and were adjusted for obesity, assisted reproductive technology and geographical origin of the mother. Unfavourable pregnancy outcome rate tripled with age, from 5% among women aged 25 to 34 to 16% among those over 45. Women over 40 were twice as likely to be hospitalised as those aged 25 to 34. The caesarean section rate reached more than 40% among women over 40 and more than 60% in women over 45. The rate of newborn transfer to paediatric intensive care or a neonatal intensive care unit was doubled in women over 40 and small-for-gestational age was more frequent with age, reaching 34% in women over 45.ConclusionsThe risk of maternal-foetal complications increases steadily with age and is particularly high after 35 years and closer monitoring appears to be necessary. These results provide additional evidence and information for public health decision-makers.

P–550 Clinical outcomes of mosaic embryos are similar between young and older women

Abstract Study question Are there differences in the clinical outcomes of mosaic embryos depending on the female age? Summary answer Clinical outcomes of mosaic embryo transfers are similar regardless female age. What is known already Chromosomal abnormalities are common in embryos analyzed in preimplantation genetic testing for aneuploidy (PGT-A) cycles. Mosaicism (the presence of two or more chromosomally distinct cell lines) is a usual event in embryos derived from IVF cycles. Several studies show that mosaic embryos have reduced potential to reach term, compared to euploid embryos. The factors affecting the implantation potential and development of mosaic embryos are controversial. Recently, Victor et al. (2019) argued that mosaic blastocysts generated at younger ages show better outcomes compared to older ages. The aim of this study was to test this hypothesis in our centre. Study design, size, duration A total of 136 mosaic embryos from patients undergoing PGT-A cycles from May 2014 to October 2020 were retrospectively analyzed in this study. The blastocyst trophoectoderm biopsies of day 5 and 6 were analysed by aCGH (n = 47, 30.1%) and NGS (n = 109, 69.9%). An embryo was considered mosaic when the percentage of aneuploid cells were 25–50% in aCGH and 20–50% in NGS. Only single embryo transfer cycles were included in the analysis. Participants/materials, setting, methods Embryo analysis were performed using Agilent SurePrint G3 8x60K CGH microarrays or Veriseq NGS (Illumina), with previous whole genome amplification. We evaluated if clinical results of mosaic embryos transfers in IVF cycles were correlated with female age. The main outcome measures were β-hCG, implantation rate and ongoing pregnancy rate. β-hCG was measured in blood 14 days after the embryo transfer and was considered positive when it was &amp;gt;2 mUI/ml.The statistical analysis was performed with SPSSv20.0. Main results and the role of chance A total of 136 mosaic embryos were included in this study. Overall, we evaluated factors affecting embryo mosaicism implantation potential. Neither the percentage of mosaicism nor the segmental mosaicism were related to mosaic embryo implantation, pregnancy and ongoing pregnancy rates. To evaluate the impact of female age in clinical outcomes, we established two different groups depending on whether mosaic blastocysts were generated from oocytes retrieved at young maternal ages (≤35 years; n = 62) or at older ages (&amp;gt;35years; n = 74). No differences were found between groups. Nonetheless, to reduce bias, embryo quality, percentage of mosaicism, segmental mosaicism and whether the transferred embryo was frozen or fresh were included as confounding factors. The rate of positive β-hCG was similar between groups: 45.2% in ≤ 35y group vs 54.1% in &amp;gt; 35y (p = 0.476). The implantation rate was also similar: 30.6% vs 39.2%% (p = 0.855), respectively. Furthermore, the ongoing pregnancy rate was higher in the &amp;gt;35y group (35.1%), compared to the ≤35y group (19.4%) without reaching statistically significant differences (p = 0.245). Limitations, reasons for caution The sample size is a limitation. aCGH test and a different definition for mosaic embryo in terms of percentage of abnormal cells was employed in this study compared to Victor et. al. (2019) study. Larger prospective studies should evaluate the impact of maternal age in the outcome of mosaic embryos. Wider implications of the findings: Our results challenge that female age is associated with clinical outcomes after the transfer of mosaic embryos. Comparable results were obtained in young and older women. Therefore, in the absence of euploid embryos, mosaic embryos might be considered for transfer and similar outcomes are expected regardless of the maternal age. Trial registration number Not applicable

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy.

Systemic lupus erythematosus (SLE) often affects females of reproductive age and Cyclophosphamide, an alkylating agent leading to premature ovarian insufficiency (POF) and labelled category D for pregnancy is used as induction therapy for severe manifestations of lupus. There have been multiple case series reflecting variable outcomes of pregnancies after cyclophosphamide use for cancers and autoimmune diseases. With increasing maternal age, we have an increasing population of lupus patients who may wish to conceive after having received cyclophosphamide therapy. The objective of our study was to improve our understanding of the impact of cyclophosphamide exposure on fertility and pregnancy outcomes in patients with SLE.We retrospectively reviewed the charts of all patients who had received intravenous cyclophosphamide at our academic institute in the time period from 2000-2018 and identified 440 patients which included 157 female patients of reproductive age. There were 37 documented pregnancies after the cyclophosphamide infusion, of which 23 patients had successful outcomes; 4 elective abortion and 10 miscarriages. There were 17 patients who developed POF, of which 7 also had end stage renal disease. The average cumulative dose of cyclophosphamide in the patients who had successful pregnancy was 4080.37 mg compared to 2806.25 mg in those who had a miscarriage (p 0.164) and 5526.47 mg in those who developed POF (p 0.046). Using multiple regressions to evaluate risk factors impacting pregnancy outcomes, when taken as a set, the predictors including race, serological profile, exposure to steroids and Mycophenolate mofetil, age at cyclophosphamide infusion, age at pregnancy, and cumulative cyclophosphamide dose accounted for 46.29% of the variance in outcome of pregnancy (p 0.23) and 39.58% of the variance in development of premature ovarian failure (p 0.008). We noted statistical significance in the impact of maternal age at time of pregnancy (p 0.04) and duration of time between the last infusions to subsequent pregnancy (p 0.02) to pregnancy outcome.Our findings suggest that a longer time interval between the last cyclophosphamide infusion and subsequent pregnancy was favorable for a successful outcome and higher cumulative cyclophosphamide dose is more likely to be associated with premature ovarian failure.

Impact of maternal age on infants' emotional regulation and psychomotor development.

Maternal age has progressively increased in industrialized countries. Most studies focus on the consequences of delayed motherhood for women's physical and mental health, but little is known about potential effects on infants' neurodevelopment. This prospective study examines the association between maternal age and offspring neurodevelopment in terms of both psychomotor development (Ages & Stages Questionnaires-3) and emotional competences (Early Childhood Behavior Questionnaire). We evaluated a cohort of healthy pregnant women aged 20-41 years and their offspring, assessed at 38 weeks gestation (n = 131) and 24 months after birth (n = 101). Potential age-related variables were considered (paternal age, education level, parity, social support, maternal cortisol levels, and maternal anxiety and depressive symptoms). Bayesian ordinal regression models were performed for each neurodevelopmental outcome. Maternal age was negatively associated with poor child development in terms of personal-social skills [odds ratio (OR) -0.13, 95% confidence interval (CI) 0.77-0.99] and with difficult temperament in terms of worse emotional regulation (OR -0.13, 95% CI 0.78-0.96) and lower positive affect (OR 0.16, 95% CI 0.75-0.95). As for age-related variables, whereas maternal anxiety symptoms and cortisol levels were also correlated with poor child development and difficult temperament, maternal social support and parental educational level were associated with better psychomotor and emotional competences. Increasing maternal age may be associated with child temperament difficulties and psychomotor delay in terms of social interaction skills. Early detection of neurodevelopment difficulties in these babies would allow preventive psychosocial interventions to avoid future neuropsychiatric disorders.

Oocyte ability to repair sperm DNA fragmentation: the impact of maternal age on intracytoplasmic sperm injection outcomes

To study the impact of sperm DNA fragmentation (SDF) on clinical outcomes of assisted reproductive technology in women with different age ranges. Historical cohort study. Private university-affiliated invitro fertilization center. Five hundred forty couples undergoing intracytoplasmic sperm injection cycles. Cycles were split into three groups according to maternal age: ≤36 years old (n = 285), 37-40 years old (n = 147), and >40 years old (n = 108). Semen samples were evaluated for SDF using the Sperm Chromatin Dispersion test and, for each age group, the cycles were subdivided according to SDF index: low fragmentation index (<30% SDF) and high fragmentation index (≥30% SDF). Implantation, pregnancy, and miscarriage rates. For younger patients (≤36 years old) and those between 37 and 40 years of age, no significant differences were noted in laboratory and clinical outcomes for cycles with <30% SDF or ≥30% SDF. When maternal age was >40 years of age, significantly lower high-quality day-3 embryos (54.4% vs. 33.1% and blastocyst development rates (49.6% vs. 30.2%), lower pregnancy (20.0% vs. 7.7%) and implantation rates (19.7% vs. 11.9%), and increased miscarriage rate (12.5% vs. 100.0%) were observed for cycles with ≥30% SDF compared with <30% SDF, respectively. Older oocytes, when injected with sperm derived from samples with high SDF index, develop into embryos of poor quality that lead consequently to lower implantation and pregnancy rates and higher miscarriage rates, in intracytoplasmic sperm injection cycles from women with advanced maternal age.