Effects Of Advanced Paternal Age Research Articles

Effect of Advanced Paternal Age on Perinatal Outcomes in Assisted Reproductive Techniques

Amaç: İleri anne yaşının yardımcı üreme tekniklerinin (YÜT) başarı şansını düşürdüğü net bir şekilde ortaya konmuştur. İleri baba yaşının spontan gebeliklerde, olumsuz gebelik sonuçlarıyla ve perinatal sonuçlarla ilişkili olduğuna dair çalışmalar vardır. Ancak ileri paternal yaşın, YÜT sonuçlarına etkisine dair az sayıda çalışma vardır. Bu çalışmada in vitro fertilizasyon (IVF) tedavisi gören hastalarda, ileri paternal yaşın siklus sonuçlarına ve perinatal sonuçlara etkisini değerlendirmeyi amaçladık.
 
 Gereç ve Yöntemler: Bu çalışmada; Mayıs, 2021-Aralık,2022 yılları arasında Ankara’da özel bir tüp bebek merkezine başvuran IVF tedavisi alan çiftlerden erkek yaşının 45 ve üstü olduğu olguların retrospektif analizi yapılmıştır. Olguların siklus karakteristikleri değerlendirilerek gebelik olan ve olmayan olgular ile, canlı doğum ile sonuçlanan ve düşükle sonuçlanan olgular siklus özellikleri ve sperm parametreleri açısından karşılaştırılmıştır.
 
 Bulgular: Çalışmaya dahil edilen 76 siklustan 47’si(%61.8) embryo transferi (ET) ile sonuçlandı, geriye kalan 29(%38.2) siklusta, transfer yapılamadı. ET yapılan sikluslardan 29’u(%61.7) gebelik ile sonuçlanırken, 18’inde(%38.2) gebelik görülmedi. Gebelik olan 29 siklustan 13’ü düşük (%44.8), 16’sı (%55.2) ise canlı doğum ile sonuçlandı. Gebelik pozitif veya negatif olan sikluslarla, canlı doğum veya düşük ile sonuçlanan sikluslarda yıkama öncesi ve sonrası sperm parametreleri ile siklus sonuçları bakımından gruplar arasında fark gösterilemedi. Düşük oranı spontan gebelik ve YÜT gebeliklerinde görülenin üstünde bulundu.
 
 Sonuç: YÜT uygulanan hastalarda ileri baba yaşı artmış düşük oranlarıyla ilişkili olabilir, bu hasta grubunda siklus ve gebelik sonuçlarına etki eden faktörleri araştırırken kapsamlı semen analizleri yapılarak sperm sayısı ve motilitesi dışında YÜT sonuçlarını ve perinatal sonuçları etkileyebilecek ek parametrelerin değerlendirilmesi gereklidir.

Can Advanced paternal age affect global DNA methylation of human spermatozoa and ICSI outcome?

This study was performed to (I) evaluate the potential effect of advanced paternal age on global DNA methylation on spermatozoa, and (II) to investigate the association between the intracytoplasmic sperm injection (ICSI) outcomes, semen parameters, and advanced paternal age. This study comprised 230 semen samples collected from males with a mean age of 38.2 ± 8.5 years. The medical records were used to gather the medical information related to the female partner. The participants were divided into three groups depending on males' age: (age < 30; n = 50 "21.8%", age = 30-40; n = 90 "39.1%", and age > 40; n = 90 "39.1%"). The DNA was extracted from purified spermatozoa; then the sperm global DNA methylation, sperm DNA fragmentation, and chromatin decondensation were evaluated by an ELISA, TUNEL, and Chromomycin A3 staining, respectively. A significant variation has been found in the age of males included in this study (P < 0.001). A significant reduction has been observed in sperm count, total motility, and non-progressive motility in the older group compared to the younger group (P < 0.001). Additionally, a significant elevation in chromatin decondensation level, DNA fragmentation level, and global DNA methylation of spermatozoa in the older age group (P < 0.001) has been found. A significant positive correlation has been detected between the percentage of non-motile sperm, sperm chromatin decondensation, DNA fragmentation, global DNA methylation status, and paternal age (P < 0.001). This study pointed out that advanced paternal age increases the DNA fragmentation, chromatin decondensation, and global DNA methylation level in human spermatozoa which negatively affects the ICSI outcomes in couples undergoing ICSI cycles.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

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.

IS THE USE OF DONATED SPERM ADVISABLE FOR PATIENTS WITH ADVANCED PATERNAL AGE?

Although it is well established that reproductive potential declines as women age, information regarding the effect of advanced paternal age (APA) is still conflicting. The use of sperm from healthy young donors has been proposed as a strategy to reduce harms associated with APA. The purpose of this study was to compare the IVF outcomes after the use of sperm samples from patients considered APA (defined as ≥ 45 years) with those found when donor sperm was used.

Does Advanced Paternal Age Increase the Rate of Paternally Derived Aneuploidy as Detected by SNP Array?

Objective: Recent studies have investigated the impact of paternal age on the incidence of embryo aneuploidy using young oocyte donors to control for maternal age, with conflicting results observed. This study takes a different approach, looking at the parental source of embryo aneuploidy as detected by SNP array. The aim was to determine whether the incidence and type of paternal-origin aneuploidy would increase with advancing paternal age. Design: A retrospective study of PGT outcomes from 1541 embryos with trio SNP array linkage-based testing from 2012-2020 across three paternal age groups: &lt;35yrs (n=410), 35-40yrs (n=789) and &gt;40yrs (n=315). The primary outcome was frequency of paternally derived aneuploidy in each age bracket. The secondary endpoint was comparison of the complex abnormality rate and the rates of specific trisomies and monosomies of paternal origin. Results: There was no association between advancing paternal age and prevalence of paternal-origin aneuploidy (&lt;35yrs: 17.8%, 35–40yrs: 16.2%; &gt;40yrs: 17.1%). Moreover, no differences were found between age cohorts in the occurrence of paternal-origin trisomy and paternal-origin monosomy. However, the rate of paternally derived complex abnormal embryos appeared increased with advancing paternal age (&lt;35yrs: 2.9%; 35-40yrs: 3.8%; &gt;40yrs: 4.4%) but did not reach statistical significance. Analysis of specific chromosomes showed the &gt;40yrs cohort had a marked increase in rates of trisomy 4 (2.22% vs. 1.22% &lt;35yrs; 0.63% 35–40yrs), trisomy 10 (0.95% vs. 0.49% &lt;35yrs; 0.38% 35-40yrs), trisomy 12 (1.27% vs. 0.49% &lt;35yrs; 0.51% 35-40yrs) and trisomy 19 (1.59% vs. 0.73% &lt;35yrs; 0.76% 35-40yrs). Unlike previously reports, no clear difference was observed in the rate of trisomy 21 with advancing paternal age. Conclusion: We conclude that there is no association between paternal age and the overall rate of paternal-origin aneuploidy. However, our findings suggest a possible effect of advanced paternal age (&gt;40yrs) on the rate of paternally derived complex abnormalities, as well as increased rate of specific paternal-origin trisomies (4, 10, 12, 19).

Is superiority to placebo the most appropriate measure of efficacy in trials of novel psychotropic medications?

Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We searched the MEDLINE, Scopus, Embase, PsycINFO online databases for original studies from inception, up to December 2021. Random-effects meta-analyses were conducted.Sixteen studies participated in the qualitative synthesis, of which k = 14 fetched quantitative data encompassing a total of 13,424,760 participants and 217,089 individuals with BD. Both fathers [adjusted for the age of other parent and socioeconomic status odd ratio – OR = 1.29(95%C.I. = 1.13–1.48)] and mothers aged ≤ 20 years [(OR = 1.23(95%C.I. = 1.14–1.33)] had consistently increased odds of BD diagnosis in their offspring compared to parents aged 25–29 years. Fathers aged ≥ 45 years [adjusted OR = 1.29 (95%C.I. = 1.15–1.46)] and mothers aged 35–39 years [OR = 1.10(95%C.I. = 1.01–1.19)] and 40 years or older [OR = 1.2(95% C.I. = 1.02–1.40)] likewise had inflated odds of BD diagnosis in their offspring compared to parents aged 25–29 years.Early and delayed parenthood are associated with an increased risk of BD in the offspring. Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial, genetic and biological factors, and with different impacts according to sex and age range. Evidence on the association between parental age and illness onset is still tentative but it points towards a possible specific effect of advanced paternal age on early BD-onset.

P-098 Male age does not affect sperm motility rate after thawing and laboratory outcomes of transnational oocyte donation programs

Abstract Study question Can outcomes of transnational egg donation treatments, which involves the shipping of cryopreserved partner semen, be affected by advanced paternal age? Summary answer Male age does not affect percentage of motile spermatozoa after thawing. Advanced paternal age does not affect IVF laboratory outcomes of transnational egg donation treatments What is known already Studies on advanced paternal age are limited and a clear definition of advanced paternal age is still missing. The separation between advanced paternal and maternal age effects is hampered by the collinearity of maternal age with paternal age, since older males are often associated with older women. Many studies have focused on egg donation treatments, to overcome this problem. However, these studies reported conflicting results, such as a putative effect of advanced paternal age on ICSI outcomes, while some others not. This study analyzes paternal age in transnational egg donation program, which involves the shipping of cryopreserved partner semen Study design, size, duration A multicentric retrospective cohort study involving 101 couples and 327 blastocysts was performed from June 2018 up to December 2021. Two Italian IVF centers involved a Spanish center to perform a transnational fresh oocyte donation program. The aim of the study was to analyze the putative effect of male age on (i) semen parameters, (ii) fertilization rate and (iii) blastocyst rate. Participants/materials, setting, methods Donations of both male and female gametes were excluded. We performed sperm cryopreservation of the male partner of the recruited couples. Frozen samples were shipped with a authorized courier, which certified the safety of the whole procedure. The day of donor’s egg retrieval, semen samples were thawed and ICSI was performed on fresh donated oocytes. Resulted blastocysts were vitrified and shipped to the centers where the frozen embryo transfers in the recipient patients were performed. Main results and the role of chance The mean of male partners age was 42.6 ± 6.5 (min 26- max 63). Overall fertilization rate was 81.6% (686/840), and blastocyst rate was 47.6% (327/686). Male age was analyzed as a continuous variable and divided into five groups calculated for 5-year intervals. No differences in terms of fertilization rates nor blastocysts rates were found (85.3% and 43.7% for &amp;lt;35-years; 84.7% and 54.0% for 36-39-years; 79.7% and 44.2% for 40-44-years; 89.6 and 48.1% for 45-49-years; 74.5% and 56.5 for &amp;gt;50-years). Although advanced paternal age has been correlated to the decrease of most of sperm parameters, in the present study we found that only progressive rapid motility was significantly affected by advanced paternal age (coefficient -0.261 , P = 0.009). To evaluate the predictive value of advanced paternal age and sperm parameters on fertilization and blastocysts formation, we performed a multiple linear regression analysis. We found that sperm parameters and male age in our sample are not predictive of the number of fertilized oocytes nor the number of obtained blastocysts. Importantly for the setting of the study, the percentage of progressive motile sperm at the thawing was not influenced by paternal age. Limitations, reasons for caution The main limitation of the study is the small sample size, which might mask the paternal age effect on the sperm parameters, as the volume, which tend to decrease in the classes of age, but did not reached the statistical significance. The multicentric nature of the study represent a strength Wider implications of the findings The discomfort for couples that need oocyte donation in countries where there is a low availability of egg donors is often underestimated. This study demonstrate that, independently of male age, the shipping of frozen sperm and the ICSI of freshly donated oocytes represent a valid option for these couples. Trial registration number not applicable

Understanding discrepancy in autism epidemiology in view of underpinning genetic architecture: Lessons learnt from studies in consanguineous populations

This short commentary aims to shed light on the discrepancy in the epidemiological findings and underlying genetic architecture of Autism Spectrum Disorder (ASD) between demographically distinct populations; consanguineous and non-consanguineous. Here we discuss the effect of advanced paternal age as a risk factor acting as a proxy for potential underlying genetic mechanisms. On that account, this narrative postulates that disparity might possibly be explained in the context of the differences in genetic makeup and abundance of recessive mutations in the highly consanguineous populations.

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.

Male fertility: a review of the publications from April – June 2021

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 works published in the II quarter (April – June) of 2021 was formed. The review includes articles on the following issues: the effectiveness of repeated micro-TESE in non-obstructive azoospermia, the role of COVID-19 in male fertility, the effect of testosterone therapy on spermatogenesis, testicular microlithiasis, electroejaculation as a method of obtaining spermatozoa, harm from carrying cell phones near the genitals, prediction of the effectiveness of intrauterine insemination, the effect of advanced paternal age on sperm aneuploidy, and the importance of the microbiome for male fertility.

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

EFFECTS OF SPERM AGE ON EMBRYO PLOIDY IN PGT-A

PGT-A is routinely offered to patients undergoing IVF. Advanced maternal age (AMA), defined as ≥35 years, has a known significant effect on embryo ploidy status. The effects of advanced paternal age (APA), defined as ≥40 years, on ploidy have been studied less. This study assesses euploid and mosaic rates of embryos created with donor sperm (DS), non-APA sperm, and APA sperm, stratified by use of donor egg (DE), non-AMA eggs, and AMA eggs. Retrospective analysis. All samples received 5/2018 - 5/2020 were included, except for those sent for PGT-SR or with suspected rearrangements. Samples created with known donor gametes were categorized with their respective age groups. Whole-genome amplification, next generation sequencing, and data analysis was performed using the Ion ReproSeqTM PGS Kit and Ion ReporterTM software (Thermo Fisher Scientific). Results were reported as 1) no abnormal cells detected, 2) abnormal cells detected (with percentages if mosaicism was identified), or 3) did not pass quality control (QC) metrics, leading to embryo categories euploid, aneuploid, mosaic, and QC failure. Results were tallied and chi square analyses were performed to compare euploid and mosaic rates between DS samples and non-APA and APA sperm samples. A total of 23,239 samples from 4,691 cycles were included. Table 1 displays ploidy rates for each group and corresponding chi square p-values. Our data shows that sperm age can have an effect on embryos’ ploidy status, as shown by a significantly higher euploid rate in embryos created with DE and DS compared to those created using DE and either non-APA or APA sperm; this effect was noted even with a small sample size. Amongst embryos created with AMA eggs, DS has less of an effect, demonstrating that egg age is still the primary factor affecting embryo ploidy. Clinicians can use this information when counseling patients on the effects of AMA and APA on embryo ploidy.Tabled 1Table 1. Euploid & Mosaic Rates by GroupEmbryo Categories% Euploidχ2 p-value (Euploid)% Mosaicχ2 p-value (Mosaic)Average Egg Age (years)Average Sperm Age (years)DE + DS97/146-19/146-25.228.266.44%13.01%DE + S<401770/3146p = 0.015581/3146NS25.834.656.26%18.47%DE + S≥401478/2593p = 0.025456/2593NS264657.00%17.59%E<35 + DS265/494-99/494-31.626.353.64%20.04%E<35 + S<402662/4808NS757/4808p = 0.01331.833.755.37%15.74%E<35 + S≥40455/829NS129/829p = 0.03732.146.254.89%15.56%E≥35 + DS396/1145-129/1145-39.427.434.59%11.27%E≥35 + S<402122/5251p = 0.0003646/5251NS37.736.340.41%12.30%E≥35 + S≥401559/4827NS458/4827NS39.445.132.30%9.49%DE: donor egg; DS: donor sperm; S<40: non-APA sperm; S≥40: APA sperm; E<35: non-AMA egg; E≥35: AMA egg; NS: not significant Open table in a new tab

Mitochondria-related miR-574 reduces sperm ATP by targeting ND5 in aging males.

Couples are delaying childbearing in recent decades. While women experience a notable decrease in oocyte production in their late thirties, the effect of advanced paternal age on reproduction is incompletely understood. Herein, we observed that numerous miRNAs, including miR-574, increased in the sperm of aging males, as indicated by high-throughput sequencing. We demonstrated that miR-574 was upregulated in the sperm of two aging mouse models and was related to inferior sperm motility as an adverse predictor. Moreover, we proved that miR-574 suppressed mitochondrial function and reduced cellular ATP production in GC2 cells. Mechanistically, we demonstrated that miR-574 regulated mitochondrial function by directly targeting mt-ND5. Our study revealed an important role of miR-574 in sperm function in aging males and provided a fresh view to comprehend the aging process in sperm.

Advanced paternal age as a risk factor for autism spectrum disorder in a Mexican population

Introduction. Risk factors for autism spectrum disorders (ASD) have been identified, as is the case of advanced parental age. Advanced parental age as an ASD risk factor has been studied in Scandinavian populations; there are no reports for Mexican children. Objective. The present work aim is to analyze if advanced parental age is a risk factor for ASD in a Mexican children sample. Method. Mexican children (N = 1 068) participated in a case-control study, 162 had an ASD diagnosis. Multivariate logistic regression adjusted by cofounders was performed to explore the effect of paternal age on ASD risk. Results. Advanced paternal age in Mexican children increases the risk for ASD, and also, a difference of 10 years between parental ages have a higher risk. Discussion and conclusion. The effect of advanced paternal age in Mexican children was lower than those reported previously for other populations. Advanced paternal age and difference between parental ages could be a risk factor for ASD in Mexican population. Nevertheless, the analysis of larger sample sizes is required.

Age-related changes in human sperm DNA integrity.

Abnormal standard semen characteristics and reduced sperm chromatin maturity can appear with increasing male age. However, the influence of paternal age on semen parameters is still controversial. Therefore, this study was designed to estimate the influence of paternal age not only on conventional semen characteristics but also on sperm DNA integrity. This research was carried out on ejaculated sperm cells obtained from men (n = 1124) aged ≥40 y and <40 y. Our data revealed a decreased semen volume and an increased percentage of DFI (sperm DNA fragmentation index) in older men compared to younger men in the entire study cohort, in men with normozoospermia and in men with abnormal semen parameters. Moreover, there was a higher incidence of sperm DNA damage (>10% DFI, low fertility potential) in the groups of men aged ≥40 y than in the groups of men aged <40 y. Older men had over twice the odds ratio for high sperm DNA damage as younger men. Our findings suggest a detrimental effect of advanced paternal age on sperm chromatin integrity. The data show that the evaluation of sperm DNA has greater clinical utility than standard semen analysis in case of male fertility potential assessment.

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.

Effects of advanced paternal age and maternal age on the outcome of ICSI using testicular sperm

Effects of advanced paternal age and maternal age on the outcome of ICSI using testicular sperm

Advanced paternal age alone does not adversely affect pregnancy or live-birth rates or sperm parameters following intrauterine insemination.

PurposeThis study aimed to evaluate the effect of advanced paternal age on pregnancy outcomes and sperm parameters following intrauterine insemination (IUI). We used IUI data rather than assisted reproductive technology data, which might mask the effects of sperm impairments.MethodsWe retrospectively analyzed 1576 IUI cycles in women under 40 years old between April 2012 and May 2016 at the National Center for Child Health and Development in Japan. The main outcomes were clinical pregnancy and live birth.ResultsThe mean male age was significantly lower in cycles that resulted in pregnancy compared with those without pregnancy (38.0 vs 39.1 years; P < 0.001), with a similar trend for live‐birth cycles. However, there was no relationship between advanced paternal age and pregnancy outcomes after adjusting for confounding factors and correlations within patients using generalized estimating equations, and the age of the female partner was the only factor affecting pregnancy rate. Furthermore, advanced paternal age had no effect on sperm parameters.ConclusionsAdvanced paternal age alone does not adversely affect pregnancy or live‐birth rates or sperm parameters following IUI.

Children born to mothers in their 20s and fathers in their 40s: Evidence for an increased low birth weight and Cesarean Section deliveries in Lebanon

PurposeMuch less is known about the effect of advanced paternal age (APA) (≥40 years) than advanced maternal age on neonatal morbidity. More specifically, the correlation with low birth weight remains inconsistent. This study aims to determine whether APA among mothers aged 20–29 years is associated with a higher risk of low birth weight and other neonatal outcomes. MethodsData from 2004 to 2008 database of the National Collaborative Perinatal Neonatal Network were used. Fifteen thousand two hundred eighteen live birth singleton pregnancies by primigravida mothers aged 20–29 years were analyzed. Study variables include paternal age (years), C-section delivery (yes/no), low birth weight (<2500 g), and preterm births (<37 weeks of gestation). Regressions were generated controlling for birth defects, consanguinity, maternal education, prenatal care, gender, and maternal smoking. ResultsAdjusted odds of Low Birth Weight (LBW) and Cesarean Section Deliveries (CSD) were significantly higher in infants of APA fathers compared to those of fathers aged 30–35 years [adjusted odds ratio (95% confidence interval) = 1.5 (1.1, 2.3) and 1.4 (1.1, 1.7), respectively]. Paternal ages of 35–39 years compared to less than 30 years were associated with higher odds of CSD [adjusted odds ratio = 1.4 (1.2, 1.5)]. APA was not associated with preterm birth after adjustment. ConclusionsThis study supports the association between APA and increased risk for LBW and CSD.