Increase In Paternal Age Research Articles

Sociodemographic Trends and Perinatal Outcomes in Fathers 50 Years and Older

The age of fathers at childbirth is rising, with an increasing number of births attributed to older fathers. While the impact of advanced paternal age has been documented, sociodemographic data about fathers aged 50 years and older remain scarce. To explore sociodemographic and temporal trends among the oldest US fathers (age ≥50 years) and their associations with perinatal outcomes. This retrospective cross-sectional study included data from all US births from 2011 to 2022 using the National Vital Statistics System. Data were analyzed from August 2023 and May 2024. Reported paternal age at childbirth. Outcomes of interest were sociodemographic factors, temporal trends in older fatherhood, and perinatal outcomes, including preterm birth, low birth weight, gestational diabetes, gestational hypertension, assisted reproductive technology (ART), rates of maternal primiparity, and the infant sex ratio. From 2011 to 2022, the US recorded 46 195 453 births, with an overall mean (SD) paternal age of 31.5 (6.8) years and 484 507 (1.1%) involving fathers aged 50 years or older, 47 785 (0.1%) aged 60 years or older, and 3777 (0.008%) aged 70 years or older. Births to fathers aged 50 years or older increased from 1.1% in 2011 to 1.3% in 2022 (P for trend < .001). Fathers aged 50 years or older were more diverse, with variations in educational achievement and race and ethnicity. Marital status and maternal racial and ethnic and educational backgrounds also varied by paternal age and race. Despite controlling for maternal age and other sociodemographic and perinatal factors, every 10-year increase in paternal age was consistently associated with greater use of ART (eg, age 50-59 years: adjusted odds ratio [aOR], 2.23; 95% CI, 2.19-2.27), higher likelihood of first maternal birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.17), and increased risks of preterm birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.18) and low birth weight (eg, age 50-59 years: aOR, 1.14; 95% CI, 1.13-1.15) compared with fathers aged 30 to 39 years. No significant changes in the infant sex ratio were observed, except among fathers aged 70 years or older (aOR, 0.92; 95% CI, 0.86-0.99) and 75 years or older (aOR, 0.84; 95% CI, 0.73-0.97), who showed a decreased likelihood of having male offspring. In this cross-sectional study of all US births from 2011 to 2022, the percentage attributed to older fathers, while small, increased. Notable variations in paternal and maternal race and education were identified. Older fatherhood was associated with increased ART use, first-time maternal births, adverse perinatal outcomes, and altered sex ratio. Further research of this population is crucial for improving patient counseling and family planning.

The Correlation of Paternal Age on Semen Parameters in Assisted Reproduction: A Retrospective Study in Qassim, Saudi Arabia.

In the past, fertility concerns have predominantly revolved around the effect of a woman's age on the quality of her eggs and the success of her pregnancy. While men generally retain their ability to father children throughout their lives, there is evidence suggesting a decline in natural conception rates as paternal age increases. A growing body of research indicates a potential link between advanced paternal age (APA) and various adverse outcomes, including changes in sperm genetics, reduced conception rates, higher rates of miscarriage, lower live birth rates, and even long-term health consequences in offspring. However, it remains unclear whether there is an association between APA and the effectiveness of assisted reproductive technology (ART). This study aims to shed light on the relationship between APA and semen parameters. This is a retrospective, descriptive study analyzing data from electronic medical records of men undergoing ART at a fertility clinic in Saudia Arabia(2017-2022). Men aged 21-60 with at least one semen analysis and no missing data/hormonal treatment were included. Data on age and semen parameters (count, motility, and morphology) were extracted and analyzed using Jeffreys's Amazing Statistics Program (JASP; University of Amsterdam, Amsterdam, Netherlands) (descriptive statistics, Spearman's rank correlation). Analysis of 1506 men undergoing ART revealed a mean age of 37 years (SD=6.94) and a mean sperm count of 55.0 million/mL (SD=46.05). The correlation between age and sperm count indicates a minimal association (r=0.075, p<0.01); moderate positive correlations were observed between sperm count and motility (r=0.406); count and morphology (r=0.543); and motility and morphology (r=0.458). Age may not be a major factor in overall sperm parametersfor this population, but a strong positive correlation was observed between sperm count, motility, and normal morphology. These findings suggest that these semen parameters are interconnected, with higher sperm counts potentially indicating better overall sperm quality.

Familial factors rather than paternal age contribute to the aetiology of epilepsy.

Whether paternal age associated with offspring's epilepsy risk is a cause of de novo mutation as men age, or just an association due to confounding factors, is still unclear. We performed a population-based, multi-generation and sibling comparison study in Taiwan, which included 2 751 232 singletons born in 2001-17 who were followed until 2020. Of these, 819 371/826 087 with information on paternal/maternal grandparents were selected for multi-generation analyses and 1 748 382 with sibling(s) were selected for sibling comparison. Cox proportional hazard regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). In the total cohort, there was an increased risk of epilepsy in individuals with advanced paternal age, e.g. the HR for paternal age ≥50 was1.36 (95% CI: 1.15-1.61) compared with paternal age 25-29, and fathers older than mothers, e.g. the HR for parental age difference ≥15 years was 1.29 (95% CI: 1.16-1.43). When accounting for parental age difference, the association between paternal age and epilepsy in offspring was attenuated (HR for paternal age ≥50 was 1.11, 95% CI: 0.93-1.34). Multi-generation analyses did not support the association of advanced grand-paternal age at childbirth of the parent with offspring's risk of epilepsy. Sibling comparison analyses did not support the association of older paternal age with increased risk of epilepsy (HR was 0.96 for per year increase in paternal age, 95% CI: 0.96-0.97). These results do not support the hypothesis that advanced paternal age is associated with epilepsy in offspring. Instead, familial factors may explain the observed paternal age association with the offspring's risk of epilepsy.

Impact of increased paternal age on neonatal outcomes in very-low-birth-weight infants

Objective Despite the trend of increasing paternal age, its impact on neonatal outcomes, particularly in preterm infants, has not been thoroughly investigated. We aimed to evaluate the perinatal characteristics and neonatal outcomes associated with paternal age. Methods Electronic medical records of very low-birthweight infants admitted to our unit from July 2013 to March 2022 were reviewed. Infants grouped according to paternal age (<35 years, 35–39 years, and ≥40 years) were analyzed for differences in perinatal findings and neonatal outcomes. Results A total of 637 infants were included (194, 294, and 149 in the <35, 35–39, and ≥40 years groups, respectively). The increase in paternal age paralleled the increase in maternal age. The Z-score of head circumference at birth was significantly different between the groups, showing the lowest median value in the ≥40 years group. Small-for-gestational age (Odds ratio 71.074, p < .001, 95% confidence interval 19.337 − 261.236) and male sex (Odds ratio 3.309, p < .034, 95% confidence interval 1.089 − 8.425), but not paternal or maternal age groups were significant factors associated with head circumference Z-scores less than −2 standard deviation based on the multivariable logistic regression analysis. Infants affected by chromosomal or genetic anomaly were more frequently identified (3.4 vs 0.0 vs 0.5%) in the ≥40 years group than in the other two groups. When infants with anomalies or critical illnesses were excluded, overall neonatal outcomes did not statistically differ according to paternal age. Conclusion Although increased paternal age ≥40 years may be associated with relatively smaller head circumferences, the impact on fetal head growth does not imply a definite risk for microcephaly. Nonetheless, based on the possible negative impact on chromosomal/genetic anomaly, increased paternal age warrants attention, even though neonatal outcomes concerning prematurity were not significantly affected. A large-scale longitudinal study is needed to further elucidate the impact of advanced paternal age in preterm infants and provide guidelines for appropriate antenatal counseling and surveillance.

The effect of advanced paternal age on the lifespan of male offspring in an ancient Chinese genealogical data set

BackgroundAdvanced paternal age has been reported to be associated with a variety of short-term outcomes in offspring, but long-term effects are rarely examined. The present study evaluated the impact of advanced paternal age on offspring's longevity. MethodsWe studied the effect of paternal reproductive age on the lifespan of male offspring using a Chinese genealogy data set that spans 226 years of the Qing Dynasty (1683–1909). Multivariable-adjusted Cox regression analyses of 1274 men with survival data were used to calculate hazard ratios (HRs) of advanced parental age at reproduction. We also evaluated whether the lifespan of brothers differed when they were born to the same parents at different ages. ResultsIn models adjusted for maternal age, advanced paternal age was negatively associated with the lifespan of male offspring. Individuals born to fathers aged >40 years had a 32 % higher HR of a lifespan shorter than those born to fathers aged 25–29 years (adjusted HR 1.320, 95 % CI: 1.066–1.634). The adjusted HR for offspring born to fathers aged 35–39 years was 1.232 (95 % CI: 1.013–1.500). Older brothers born to fathers aged 20–34 years had a significantly lower risk of a reduced lifespan compared with their younger brothers with fathers aged ≥35 years at reproduction (P < 0.01). ConclusionAdvanced paternal age at reproduction is a negative factor for male offspring's life expectancy. With the sustained increase in paternal age over the past generation, further investigation is warranted into the impact on birth outcomes and public health.

O-296 Paternal age does not affect obstetric and perinatal outcomes in IVF or ICSI cycles with autologous oocytes

Abstract Study question Does paternal age have any effect on obstetric and perinatal outcomes in in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles with autologous oocytes? Summary answer Gestational diabetes, delivery type, cranial circumference and preterm birth were significantly different between our age groups, although after adjusted analysis no significant differences were seen. What is known already In recent years, there has been an increase of the average male age at which the first child is conceived. Therefore, studies addressing paternal age and reproductive risks are increasing and results are controversial, so there is a need of more research about it, which this study tries to address. Although several studies suggest the threshold to consider paternal age ‘advanced’ at 40 years, this limit is not well established. The assessment of risks concerning the mother and offspring is important and, thus, so is the study of its association with paternal age. Study design, size, duration This retrospective observational multicentric cohort study has considered pregnancies and children conceived from IVF-ICSI performed to couples in Spain IVIRMA clinics between January 2008 and March 2020 using patients’ own sperm and autologous oocytes. Paternal age ranged from 18 to 51 years. The study population was categorized in three groups: &amp;lt;30(A, reference), 30-40(B) and &amp;gt;40(C) years. The data available included 14402 patients who had a delivery with a live birth and 16118 singleton newborns. Participants/materials, setting, methods We evaluated pregnancies and children from autologous IVF-ICSI with own semen, known age and resulting in delivery. Data was exported to obtain the clinical database followed by the statistical analysis of the study main outcomes. P &amp;lt; 0.05 was considered statistically significant. Obstetric and perinatal outcomes were measured including delivery type, incidence of preterm birth, gestational diabetes, anemia, hypertension and pre-eclampsia; and newborn sex, weight, length, cranial circumference, Apgar score and neonatal intensive care unit (NICU) admission. Main results and the role of chance Results are expressed as rate or mean with 95%CI. There were no statistically significant differences for the incidence of anemia, hypertension or pre-eclampsia; newborn sex, weight, length, Apgar score (1, 5 and 10 min) and NICU admission between the reference younger group (A) vs. the older paternal age groups (B and C). However, there were statistically significant differences for the incidence of gestational diabetes when comparing A 5.1%(3.5-7.2) with B 7.7%(7.1-8.3) with OR = 1.5(1.1-2.2)(p = 0.021) and with C 9.1%(7.1-11.4) with OR = 1.9(1.2-2.9)(p = 0.005); for delivery type when comparing A[cesarean 33.8%(31.3-36.4)] with B[cesarean 37.8%(37.0-38.7)] with OR = 1.2(1.1-1.3) (p = 0.004) and with C[cesarean 49.3%(46.7-52.0)] with OR = 1.9(1.6-2.2) (p &amp;lt; 0.001); for cranial circumference when comparing A 34.5(34.3-34.7) with C 34.8(34.6-35.0) with p = 0.03; and for the incidence of preterm birth when comparing A 7.9%(6.6-9.5) with C 5.9%(4.7-7.2) with OR = 0.7(0.5-1.0)(p = 0.034). These results suggest an increased risk of gestational diabetes and cesarean delivery as paternal age increases. Moreover, group C showed a larger cranial perimeter and a lower risk of preterm birth when compared to group A. However, after adjusted analysis (according to selected patients’, cycles’ and semen samples’ characteristics, gestational age, newborn sex and type of delivery) these differences were no longer statistically significant, so probably other clinical variables are involved in the differences seen. Limitations, reasons for caution Despite the retrospective nature of this study that leads to biases derived from the clinical practice and to the presence of missing data limiting sample size, the study includes a huge sample size. Wider implications of the findings Currently, fatherhood delay has led to a growing interest in studies addressing paternal age and reproductive risks. Our paternal age comparison showed significant differences for gestational diabetes, delivery type, cranial circumference and preterm, no longer significant after adjusted analysis, so probably other clinical variables were involved. Further studies are needed. Trial registration number Not applicable

Paternal ageing impacts blastulation and the outcomes of pregnancy at different levels of maternal age: A clustering analysis of 21,960 oocytes and 3837 ICSI cycles.

The objective of this cross-sectional study was to investigate the impact of paternal age on the outcomes of intracytoplasmic sperm injection (ICSI) cycles at different values of maternal age. A total of 21,960 injected oocytes deriving from 3837 ICSI cycles performed between January 2014 and October 2020, performed in a private university-affiliated in vitro fertilization centre was included. The main effects of maternal and paternal age, as well as the effect of their product (interaction term) on embryo development and pregnancy outcomes were investigated considering the clustering of data. The coefficients for the interaction term were statistically significant for blastocyst development, top-quality blastocyst, implantation, pregnancy, miscarriage, and live-birth rates. For every 1-year increase in paternal age, the odds ratio of live-birth reduces by 1% in females aged 37 years, 1.6% in those aged 38 years, 2.4% in 39-year-old females, 5% in 42-year-old females and so on. An increase in the interaction term by 1 year decreases the pregnancy rate by 0.4% and live-birth rate by 0.8 and increases the miscarriage rate by 1.2%. The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy, miscarriage, and live-birth rate significantly changed (worsened) for every year increase in paternal age.

Parental Age and Childhood Lymphoma and Solid Tumor Risk: A Literature Review and Meta-Analysis.

BackgroundAlthough advanced parental age has been definitively linked to pediatric acute lymphoblastic leukemia, studies of parental age and pediatric solid tumors have not reached firm conclusions. This analysis aimed to elucidate the relationship between parental age and pediatric solid tumors through meta-analysis of existing studies based in population registries.MethodsWe searched Medline (PubMed) and Embase for registry-based studies of parental age and solid tumors through March 2022. We performed random-effects meta-analysis to estimate pooled effects and 95% confidence intervals (CIs). All statistical tests were 2-sided.ResultsA total of 15 studies covering 10 childhood solid tumor types (30 323 cases and 3 499 934 controls) were included in this analysis. A 5-year increase in maternal age was associated with an increased risk of combined central nervous system tumors (odds ratio [OR] = 1.07, 95% CI = 1.04 to 1.10), ependymoma (OR = 1.19, 95% CI = 1.09 to 1.31), astrocytoma (OR = 1.10, 95% CI = 1.05 to 1.15), rhabdomyosarcoma (OR = 1.14, 95% CI = 1.03 to 1.25), and germ cell tumors (OR = 1.06, 95% CI = 1.00 to 1.12). A 5-year increase in paternal age was associated with an increased risk of non-Hodgkin lymphoma (OR = 1.06, 95% CI = 1.00 to 1.12).ConclusionsThis meta-analysis of registry-based analyses of parental age and childhood cancer supports the association between older maternal age and certain childhood solid cancers. There is also some evidence that paternal age may be associated with certain cancers such as non-Hodgkin lymphoma. However, as maternal and paternal age are highly correlated, disentangling potential independent causal effects of either factor will require large studies with extensive data on potential confounders.

Association of advanced paternal age with lung function at school age

BackgroundEpidemiological studies suggest that advanced paternal age impact offspring health, but its impact on respiratory health is unclear. This study aimed to investigate the association of paternal age with lung function and fraction of exhaled nitric oxide (FeNO) in children.MethodsWe analyzed data from 1330 single-born children (576 girls, 43.3%; mean age, 6.4 years), who participated in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort and received measurements of lung function and FeNO at 6-year follow-up visits. Covariate-adjusted regression analyses were applied.ResultsEvery 5-year increase in paternal age at birth was associated with 0.51% decrease in FEV1/FVC ratio (95% CI − 0.86 to − 0.15; p = 0.005) and 19.86 mL/s decrease in FEF75 (95% CI: − 34.07 to − 5.65; p = 0.006). Stratified analyses revealed that increasing paternal age at birth was associated with decreasing FEV1/FVC ratio and FEF75 only among children with prenatal exposure to environmental tobacco smoke (ETS) or not being breastfed. Sensitivity analyses using paternal age as a categorical variable found decreasing FEV1/FVC ratio and FEF75 in the groups of paternal age 35–39 and ≥ 40 years. There was no association of paternal age at birth with FeNO.ConclusionOur findings provide novel evidence linking advanced paternal age at birth with decreasing lung function in children at school age. Children with prenatal exposure to ETS or not being breastfed are more vulnerable to the adverse effect of advanced paternal age on childhood lung function. Further studies are warranted to confirm this novel adverse effect of advanced paternal age.

Parental age and retinoblastoma-a retrospective study of demographic data and genetic analysis.

To determine the association between the parental age gap and the absolute parental age with the risk of retinoblastoma (RB) development in an offspring. RB individuals diagnosed between March 2013 and December 2019 in a single tertiary eye care centre were included. We recorded the demographic data, parental age and RB1 gene mutation status in the patient's tumour, blood and the parental blood. We categorised RB1 mutation inheritance as sporadic RB with somatic mutations (only present in tumour), heritable RB with de novo (present in patient's blood) and familial (present in patient and parents' blood) germline mutations. The statistical significance was confirmed by Fisher's exact/Chi-square test. Out of 259 RB patients, 247 were included in our study. Heritable RB with de novo germline mutations was significantly less common (p value: 0.0387; 95% CI: 0.2676-0.9329) and sporadic RB with somatic mutations was more common (p value: 0.0545; 95% CI: 1.025-3.39), if the parental age gap was <10 years. There were increased odds of a heritable RB with de novo germline mutation with an increase in paternal age and this was more intensified when combined with parental age gap of more than ≥10 years. The heritable RB with de novo germline mutations significantly increased as maternal age progressed, only when it was adjusted to ≥10 years parental age gap (p value: 0.0262; 95% CI: 1.26-17.91). An increased parental age gap and increased paternal age are independent risk factors for the development of heritable RB with de novo germline mutation.

O-224 Paternal ageing impacts blastulation and pregnancy outcomes at different levels of maternal age: a clustering analysis of 21,960 injected oocytes and 3837 ICSI cycles

Abstract Study question Are the morphological parameters and development of in vitro cultured embryos, and intracytoplasmic sperm injection (ICSI) outcomes influenced by maternal and paternal ageing? Summary answer The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy and miscarriage rates significantly changed (worsened) for every year increase in paternal age. What is known already Due to the vast literature demonstrating that female age interferes with intracytoplasmic sperm injection (ICSI) outcomes, there is an imposition, in numerous countries, regarding maternal age limit for assisted reproduction. Despite several studies have underscored the negative impact of paternal age and lifestyle factors on reproductive health, the influence of paternal age on ICSI outcomes is still a matter of debate. The aim of this study was to investigate if the effect of paternal age on embryo development differs at different values of maternal age, thus creating a rationale for the data to reach physicians, patients, and public health recommendations. Study design, size, duration This historical cohort study included 3837 couples undergoing their first ICSI cycle from January/2014 to October/2020. A total of 21960 oocytes were injected and embryos were evaluated until day 5 of development. The main effects of maternal and paternal ages, as well as the effect of their product (interaction term) on embryo growth and development, and on pregnancy outcomes were investigated taking into account clustering of data (multiple embryos per cycle), using generalized mixed models. Participants/materials, setting, methods The study was performed in a private university-affiliated in vitro fertilization center. Zygotes were morphologically evaluated 17h post ICSI. For days 2 and 3 of development, the number of blastomeres, blastomere symmetry, percentage of fragmentation and presence of multinucleation were recorded. On day 5 of development, successful blastulation, and inner cell mass and trophectoderm qualities were recorded. Pregnancy was calculated per transfer, and miscarriage was defined as pregnancy loss before 20 weeks gestation. Main results and the role of chance The coefficients for the interaction term were statistically significant for blastocyst development (B: - 0.005, OR: 0.995, CI: 0.994 – 0.996, p &amp;lt; 0.001), top-quality blastocyst (B: - 0.003, OR: 0.997, CI: 0.996 – 0.999, p &amp;lt; 0.001), implantation rate (B: - 0.041, OR: 0.960, CI: 0.947 – 0.973, p &amp;lt; 0.001), pregnancy rate (B: - 0.004, OR: 0.996, CI: 0.995 – 0.997, p &amp;lt; 0.001), and miscarriage rate (B: 0.011, OR: 1.012, CI: 1.005 – 1.018, p = 0.001). These values describe the changes in slopes such that, the slope of one independent variable (e.g. maternal age) on the dependent variable (e.g. implantation rate) changes by the value of B (- 0.041) for every unit change on the other independent variable (e.g. paternal age). No significant results were observed for the influence of the interaction term on embryo morphological features on days 1, 2 and 3 of development. Two post hoc power analyses were calculated, given α of 5%, sample size of 21960 zygotes and 3315 ICSI cycles with embryo transfer and effect sizes for blastulation and pregnancy outcomes, respectively. The achieved power was superior to 99% in both analyses. Limitations, reasons for caution The retrospective and monocentric nature of the study are its major limitations. Wider implications of the findings Our results underscore the importance of both maternal and paternal ages for blastulation and successful pregnancy. Main effects of paternal and maternal ages should no longer be interpreted as the relationship between each independent variable and a given outcome, but rather be conditional on the values of the interaction term. Trial registration number Not applicable

P–087 Paternal age clinical effect on cumulative live birth rates (CLBR) per inseminated oocyte, embryo transfer and embryo transferred in autologous IVF-ICSI cycles of infertile males

Abstract Study question Is reproductive success measured as CLBR per inseminated oocyte, per embryo transfer and per embryo transferred affected by paternal age in autologous IVF-ICSI cycles? Summary answer The number of embryo transfers and embryos transferred until live birth, but not the number of inseminated oocytes, were significantly different among the age groups. What is known already In recent years, there has been an increase of the average paternal age at which the first child is conceived. Therefore, there is a growing interest on the study of the impact of male age on the reproductive outcomes in assisted reproduction cycles (ART). Several studies have shown negative effects of advanced paternal age on semen parameters, embryo aneuploidy, miscarriage, male infertility,.... However, other studies have found no association between them. Hence, the impact of paternal age on reproductive outcomes still remains uncertain, leading to a need of more research on this topic, which this study tries to address. Study design, size, duration This retrospective observational multicentric cohort study has included autologous IVF-ICSI treatments (n = 6295) performed to couples with etiology of male infertility (non-normozoospermic) in Spain IVIRMA clinics between January 2008 and March 2020 using patients’ own sperm sample. Paternal age ranged from 20 to 75 years. The study population was categorized in 5 groups following the criterion of homogenizing the number of observations between groups: 20–34 (A), 34–37 (B), 37–39 (C), 39–42 (D) and 42–75 (E) years. Participants/materials, setting, methods Considering that male age could be a factor affecting reproductive outcomes, we evaluated men with different age that performed an autologous IVF-ICSI treatment with their own semen, etiology of male infertility and known age. Data was exported in order to obtain the clinical database and Kaplan-Meier was used for data analysis. P &amp;lt; 0.05 was considered statistically significant. We measured reproductive success by CLBR per embryo transfer, per embryo transferred and per inseminated oocytes until live birth. Main results and the role of chance This study considered approximately 2976 patients and 4385 embryo transfers. The CLBR per inseminated oocyte showed no significant difference between the study groups: A (6.43%, 48.24%, 81.38%), B (5.74%, 52.14%, 82.87%), C (6.14%, 49.83%, 83.69%), D (5.89%, 53.60%, 81.16%) and E (6.61%, 47, 52%, 77.85%) for 4, 13 and 21/22 inseminated oocytes, respectively. In terms of CLBR per embryo transfer, the results obtained for each of the age groups were: A (31.81%, 71.89%, 87.63%), B (28.89%, 67.87%, 82.63%), C (27.10%, 68.87%, 88.17%), D (23.45%, 64.63%, 100.00%) and E (22.88%, 55.48%, 63.31%) for 1, 4 and 7 embryo transfers, respectively. There were statistically significant differences in the CLBR per embryo transfer between the studied age groups (p &amp;lt; 0.0001). CLBR per embryo transferred for each age group was as follows: A (10.85%, 60.53%, 80.88%), B (9.34%, 59.75%, 78.23%), C (11.89%, 57.63%, 74.97%), D (10.25%, 52.71%, 77.76%) and E (11.71%, 51.50%, 71.51%) for 1, 4 and 7 embryos transferred, respectively. As in the case before, there were statistically significant differences in the CLBR per embryo transferred between the age groups (p &amp;lt; 0.05). The findings presented highlight that the increase in paternal age could be affecting the reproductive outcomes in IVF-ICSI cycles using autologous oocytes. Limitations, reasons for caution The retrospective nature of this study leads to biases derived from the clinical practice and to the presence of missing data (limiting sample size). Moreover, this study considered autologous cycles, therefore the results were not adjusted for female factors. Wider implications of the findings: Our study showed that reproductive outcomes measured by CLBR per embryo transfer and embryo transferred until live birth were significantly different between the paternal age groups in autologous IVF-ICSI cycles of infertile males. Hence, paternal age could be affecting reproductive outcomes and it should be considered for improving infertility counselling. Trial registration number NA

The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism.

Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well-defined etiology. We sought to determine parental age associations with ASD-related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced parental age with clinical ASD diagnosis, Social Responsiveness Scale, or Vineland Adaptive Behavior Scales scores. Instead, increased odds of ASD were found with paternal age < 30 years (adjusted odds ratio [AOR] = 2.83 and 95% confidence intervals [CI] = 1.14-7.02). Likewise, younger age (<30 years) for both parents was associated with decreases in Mullen Scales of Early Learning early learning composite (MSEL-ELC) scores (adjusted β = -9.62, 95% CI = -17.1 to -2.15). We also found significant increases in cognitive functioning based on MSEL-ELC scores with increasing paternal age (adjusted β associated with a 10-year increase in paternal age = 5.51, 95% CI = 0.70-10.3). Results suggest the potential for a different relationship between parental age and ASD-related outcomes in families with elevated ASD risk than has been observed in general population samples. Autism Res 2020, 13: 998-1010. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous work suggests that older parents have a greater likelihood of having a child with autism. We investigated this relationship in the younger siblings of families who already had a child with autism. In this setting, we found a higher likelihood of autism, as well as poorer cognitive scores, in the siblings with younger fathers, and higher cognitive scores in the siblings with older parents. These results suggest that parental age associations may differ based on children's familial risk for autism.

Effects of paternal age on human embryo development in in vitro fertilization with preimplantation genetic screening.

ObjectiveAs paternal age increases, the quality of sperm decreases due to increased DNA fragmentation and aneuploidy. Higher levels of structural chromosomal aberrations in the gametes ultimately decrease both the morphologic quality of embryos and the pregnancy rate. In this study, we investigated whether paternal age affected the euploidy rate.MethodsThis study was performed using the medical records of patients who underwent in vitro fertilization (IVF) procedures with preimplantation genetic screening (PGS) from January 2016 to August 2017 at a single center. Based on their morphological grade, embryos were categorized as good- or poor-quality blastocysts. The effects of paternal age were elucidated by adjusting for maternal age.ResultsAmong the 571 total blastocysts, 219 euploid blastocysts were analyzed by PGS (38.4%). When the study population was divided into four groups according to both maternal and paternal age, significant differences were only noted between groups that differed by maternal age (group 1 vs. 3, p=0.031; group 2 vs. 4, p=0.027). Further analysis revealed no significant differences in the euploidy rate among the groups according to the morphological grade of the embryos.ConclusionPaternal age did not have a significant impact on euploidy rates when PGS was performed. An additional study with a larger sample size is needed to clarify the effects of advanced paternal age on IVF outcomes.

Advanced Paternal Age and Early Onset of Schizophrenia in Sporadic Cases: Not Confounded by Parental Polygenic Risk for Schizophrenia

BackgroundWhether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium. MethodsAmong 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents’ genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients’ early onset of schizophrenia (≤18 years old) on paternal age was conducted. ResultsAdvanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients’ early onset of schizophrenia remained (odds ratio = 1.29, p = .04). ConclusionsThe association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

Paternal age negatively predicts offspring physical attractiveness in two, large, nationally representative datasets

The effect of paternal age on offspring attractiveness has recently been investigated. Negative effects are predicted as paternal age is a strong proxy for the numbers of common de novo mutations found in the genomes of offspring. As an indicator of underlying genetic quality or fitness, offspring attractiveness should decrease as paternal age increases, evidencing the fitness-reducing effects of these mutations. Thus far results are mixed, with one study finding the predicted effect, and a second smaller study finding the opposite. Here the effect is investigated using two large and representative datasets (Add Health and NCDS), both of which contain data on physical attractiveness and paternal age. The effect is present in both datasets, even after controlling for maternal age at subject's birth, age of offspring, sex, race, parental and offspring (in the case of Add Health) socio-economic characteristics, parental age at first marriage (in the case of Add Health) and birth order. The apparent robustness of the effect to different operationalizations of attractiveness suggests high generalizability, however the results must be interpreted with caution, as controls for parental levels of attractiveness were indirect only in the present study.

Advancing paternal age at birth is associated with poorer social functioning earlier and later in life of schizophrenia patients in a founder population

Consistent associations have been found between advanced paternal age and an increased risk of psychiatric disorders, such as schizophrenia, in their offspring. This increase appears to be linear as paternal age increases. The present study investigates the relationship between early deviant behaviour in the first 10 years of life of patients as well as longer term functional outcome and paternal age in sporadic Afrikaner founder population cases of schizophrenia. This might improve our understanding of Paternal Age-Related Schizophrenia (PARS). Follow-up psychiatric diagnoses were confirmed by the Diagnostic Interview for Genetic Studies (DIGS). An early deviant childhood behaviour semi-structured questionnaire and the Specific Level of Functioning Assessment (SLOF) were completed. From the logistic regression models fitted, a significant negative relationship was found between paternal age at birth and social dysfunction as early deviant behaviour. Additionally, regression analysis revealed a significant negative relationship between paternal age at birth and the SLOF for interpersonal relationships later in life. Early social dysfunction may represent a phenotypic trait for PARS. Further research is required to understand the relationship between early social dysfunction and deficits in interpersonal relationships later in life.

Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring.

Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenital anomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAs according to paternal age at birth in an unselected population covering cohort of children. A register-based prospective study of 1,605,885 children born in Denmark, 1978-2004, using information from record-linked health and administrative registers. The association between paternal age and overall musculoskeletal CAs, limb anomalies, craniosynostosis, skeletal dysplasias, syndromic musculoskeletal CAs, and other musculoskeletal CAs were investigated by multiple logistic regression analysis. For overall musculoskeletal CAs, a slightly higher risk per 10-year increase in paternal age was found (odds ratio [OR] = 1.06 [95% CI: 1.01-1.11; where CI is confidence interval]). A 26% (95% CI: 2-56%) excess risk was found for fathers aged 50+ years compared to fathers aged 30-34 years. For syndromic musculoskeletal CAs, excess risks were found for fathers aged 40+ years, compared to fathers aged 30-34 years (40-44: OR = 1.38 [95% CI: 1.01-1.88], 45-49: OR = 1.45 [95% CI: 0.89-2.34], 50+: OR = 1.42 [95% CI: 0.73-2.79]). The risks in all other subgroups of musculoskeletal CAs were increased for fathers aged 50+ years. A slightly higher risk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess risk of syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years and increased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role in the etiology of these anomalies.

Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders

Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and separate associations of paternal age and offspring IQ with the risk of SSD. We used IQ routinely measured at conscription in Danish males (n=138,966) from cohorts born in 1955–84 and in 1976–1993 and followed them from a year after the conscription through 2010. We used Cox regression to estimate the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10–1.60 per a ten-year increase in paternal age). A higher IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63–0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (<20% of the men). Overall, there was little evidence of lower premorbid IQ in APA-related SSD (individuals who developed SSD and were also offspring of older fathers). Our results do not support the notion that risk gradient for offspring SSD associated with paternal age is mediated by offspring IQ.

Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort

The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID). The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD. Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (≥99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID. We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.