Advanced Paternal Age With Risk of Lifespan in Male Offspring Using Chinese Genealogical Data

Background Advanced paternal age has been associated with a variety of adverse reproductive outcomes. However, the effects of paternal age on offspring lifespan are still controversial. Result Here, we studied the correlation between parental reproductive age and offspring lifespan using a Chinese specific genealogy data. We chose a “Ding” genealogy data across 130 years during the Qing Dynasty (1726-1855). The present study showed that fathers aged more than 35 years were more likely to have male offspring with lower lifetime compared with fathers aged 20-35 years. The significant negative correlation between paternal age and male offspring lifespan existed after adjusted for maternal age. We proposed a new evidence that advanced paternal age is a risk for male offspring survival.

Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study

PurposeWhile it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation).MethodsA large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight.ResultsAdvanced paternal age was associated with a higher risk for a preterm birth [35–44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35–44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery.ConclusionsOur study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.

Improving Sperm Oxidative Stress and Embryo Quality in Advanced Paternal Age Using Idebenone In Vitro—A Proof-of-Concept Study

Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm from men aged >40 years and older CBAF1 mice (12–18 months), were treated with 5 µM and 50 µM of idebenone and intracellular and superoxide ROS concentrations assessed. Following in vitro fertilization (IVF), embryo development, blastocyst differentiation, DNA damage and cryosurvival, pregnancy and implantation rates and fetal and placental weights were assessed. Five µM of idebenone given to aged human and mouse sperm reduced superoxide concentrations ~20% (p < 0.05), while both 5 and 50 µM reduced sperm intracellular ROS concentrations in mice ~30% (p < 0.05). Following IVF, 5 µM of idebenone to aged sperm increased fertilization rates (65% vs. 60%, p < 0.05), blastocyst total, trophectoderm and inner cell mass cell numbers (73 vs. 66, 53 vs. 47 and 27 vs. 24, respectively, p < 0.01). Treatment with idebenone also increased blastocyst cryosurvival rates (96% vs. 78%, p < 0.01) and implantation rates following embryo transfer (35% vs. 18%, p < 0.01). Placental weights were smaller (107 mg vs. 138 mg, p < 0.05), resulting in a larger fetal to placental weight ratio (8.3 vs. 6.3, p = 0.07) after sperm idebenone treatment. Increased sperm ROS concentrations associated with advanced paternal age are reduced with the addition of idebenone in vitro, and are associated with improved fertilization rates, embryo quality and implantation rates after IVF.

P–566 Advanced paternal age can influence aneuploidy rate in egg donation cycles with poor sperm quality

Study question Could advanced paternal age influences the embryos aneuploidy rate in eggs donation cycles with poor sperm quality? Summary answer In case of severe male factors increased paternal age can affect embryos aneuploidy rate in egg donation cycles. What is known already While the impact of advanced maternal age on reproductive is well understood, the effect of paternal age on reproductive function is controversial. Many studies have shown that Advanced Paternal Age (APA) could impact on male fertility potential affecting testicular function and sperm quality. Moreover, APA also has been associated with increased epigenetics changes and DNA mutations. Increased paternal age could be associated with different types of disorders such as autism, schizopherenia and bipolar disorders. Egg donation cycles, controlling female variables, represent the ideal model for the study of the impact of paternal age on reproductive outcomes. Study design, size, duration We retrospectively analyzed 43 egg donation cycles (October 2014-January 2020) with ≥ 50% survival rate of vitrified/warmed oocyte. Only cycles with poor sperm quality were considered. Cycles were divided in two GROUPS: group–1 included male paternal age ≤ 45 while group–2 included male paternal age &gt;45. Data, shown as avarage±SD, were analyzed with Chi square or Student-t test. Participants/materials, setting, methods Group–1 included 20 cycles and 219 oocytes, male age was 40,89 ±6.12; Group–2 included 17 cycles and 173 oocytes, male age was 51±6.06. Respectively, in Group 1 and in Group 2, donor age were 22.4±2.65 and 24.8±3.88 (NS). All oocytes were injected with abnormal sperm samples according to WHO 2010. Embryos were cultured in time-lapse system until blastocyst stage. Trophectoderm biopsy and PGT-A analysis were performed according to standardized laboratory protocols. Main results and the role of chance Oocytes survival rates in Group1 and 2 were 86% (188/219) and 90.7% (157/173) (NS), respectively. Fertilization rates in Group1 and –2 were 71.42 (135/189) and 73.45% (119/162) (NS), respectively. The total number of obtained embryos (transferred + frozen) were 81 and 801 in Group–1 and –2, respectively. The rates of obtained embryos per reiceved occytes were 37% (81/219) and 46.24% (80/173) in Group–1 and –2 (p &lt; 0.7), respectively. The PGT-A analysis showed 38.7% (31/80) and 31.17% (24/77) of euploid (NS) and 25% (20/80)and 42.85% (33/77) of aneuploid embryos (P &lt; 0.05) in Group–1 and –2, respectively. Mosaic embryos were 33.5% (26/80) and 27.27%(21/77), in Group–1 and –2, respectively. (NS). These results indicate that in presence of severe male factor, advanced paternal age could increase embryos aneuploidy rate raising incidence of chromosomal abnormalities. Limitations, reasons for caution Each donor was stimulated with different protocols according to her history and hormones levels. Nothing is known about which type of sperm parameters (semen amount, morphology or motility) have a major impact when focusing on the embryos genetic outcome. Wider implications of the findings: To better known the effect of APA, it could be necessary identify embryos chromosomal abnormalities and the correlation with specific sperm parameters. Further studies should be done to confirm the APA effect in patients with severe male factors and define a cut-off male age where PGT-A should be recommended. Trial registration number Not applicable