The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis

Oldereid, Nan Birgitte; Wennerholm, Ulla‐Britt; Pinborg, Anja; Loft, Anne; Laivuori, Hannele; Petzold, Max; Romundstad, Liv Bente; Söderström‐Anttila, Viveca; Bergh, Christina

doi:10.1093/humupd/dmy005

Cited by 182 publications

(156 citation statements)

References 243 publications

(199 reference statements)

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“…They found that duration of subfertility was one of the prognostic factors for the likelihood of live birth along with abnormal post‐coital test, tubal defect and ovulation defect . As a whole, our present finding that the longer DI, the older the patient, is coupled with everything recently published in meta‐analytical terms regarding the risks of advanced paternal age .…”

Section: Discussionsupporting

confidence: 82%

The duration of infertility affects semen parameters in primary infertile men: results of a single‐centre, cross‐sectional study

et al. 2018

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ObjectiveTo assess the relationship between the duration of infertility (DI) and the seminal parameters of a cohort of White-European primary infertile men. Patients and MethodsData from 1644 infertile men were analysed. Patients were grouped according to the self-reported DI into 12-month time frames. Semen analysis values were assessed based on 2010 World Health Organisation reference criteria. Descriptive statistics tested the difference in clinical, hormonal and seminal parameters between groups. Logistic regression models assessed the impact of DI on semen parameters. ResultsA DI of <12, 13-24, 25-36, 37-48, 49-60 and >60 months was found in 207 (12.6%), 651 (39.6%), 387 (23.5%), 168 (10.2%), 92 (5.6%) and 139 (8.4%) men, respectively. Patient's age (P < 0.001) and body mass index (P < 0.001) significantly increased along with DI. Hormonal values were similar across groups. Sperm concentration significantly decreased with DI (P = 0.01). Similarly, a higher rate of non-obstructive azoospermia (NOA) was more frequently found in men with a longer DI (P = 0.03). There were no differences in semen volume, sperm progressive motility, total motile sperm count (TMSC), and normal morphology across groups. Multivariable logistic regression analysis showed that DI was significantly associated with the risk of oligozoospermia (P < 0.001), TMSC <5 9 10 6 (P < 0.001), and NOA (P < 0.001). ConclusionsThis cross-sectional study showed that DI had a negative impact on semen parameters in primary infertile men. Sperm concentration was negatively associated with DI and patients with a longer DI reported higher rates of azoospermia. Furthermore, DI was significantly associated with a higher risk of oligozoospermia, low TMSC, and NOA.

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Section: Discussionsupporting

confidence: 82%

The duration of infertility affects semen parameters in primary infertile men: results of a single‐centre, cross‐sectional study

et al. 2018

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“…Oldereid et al () published results from a recent systematic review and meta‐analysis investigating paternal age on neonatal and pediatric outcomes. Overall, they concluded that paternal age‐associated increases in offspring serious adverse outcomes were modest.…”

Section: The Aging Male and Offspring Wellnessmentioning

confidence: 99%

The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap

2019

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Background: There is a global crisis in male reproductive health. Evidence comes from globally declining sperm counts and increasing male reproductive system abnormalities, such as cryptorchidism, germ cell tumors, and onset of puberty. Male factor infertility occurs in~40% of couples experiencing infertility. Data demonstrate an association between male infertility and overall health. Associated significant health conditions include diabetes mellitus, metabolic disorders, and cardiovascular disease. Adding to the complexity is that men typically do not seek health care unless there is acute medical need or, as in the case of the infertile couple, the male goes for a reproductive examination and semen analysis. However, 25% of the time a reproductive health examination does not occur. Couples are increasingly utilizing IVF at more advanced ages, and advanced paternal age is associated with increased risk for (i) adverse perinatal outcomes for both offspring and mother; (ii) early child mortality, cancer, and mental health issues. In addition to age, paternal lifestyle factors, such as obesity and smoking, impact not only the male fertility but also the offspring wellness.Objectives: The purpose of this paper was (i) to spotlight emerging and concerning data on male reproductive health, the relationship(s) between male reproductive and somatic health, and the heritable conditions father can pass to offspring, and (ii) to present a strategic roadmap with the goals of increasing (a) the awareness of men and society on the aforementioned, (b) the participation of men in healthcare seeking, and (c) advocacy to invigorate policy and funding agencies to support increased research into male reproductive biology. Conclusions: The Male Reproductive Health Initiative (MRHI) is a newly established and rapidly growing global consortium of key opinion leaders in research, medicine, funding and policy agencies, and patient support groups that are moving forward the significant task of accomplishing the goals of the strategic roadmap.

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“…Animal models of high fat diet-induced paternal obesity and diabetes have found associations with impaired offspring development (11) and offspring metabolic phenotypes and DNA methylation in pancreatic islets (12). In humans, a recent systematic review (13) found conflicting evidence on the association between paternal body mass index (BMI) and offspring birthweight, and some evidence of an association with greater offspring BMI, weight or body fat mass in childhood. A small number of studies have also found links between paternal BMI and sperm or offspring neonatal blood DNA methylation, but these have been based on candidate genes and/or had very limited sample sizes (14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

Sharp

Alfano

Ghantous

et al. 2020

Preprint

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Background: Accumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. Methods and findings: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes. Conclusion: Our findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.

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The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis

Abstract: Although the increased risks of adverse outcome in offspring associated with paternal factors and identified in this report represent serious health effects, the magnitude of these effects seems modest.

Cited by 182 publications

References 243 publications

The duration of infertility affects semen parameters in primary infertile men: results of a single‐centre, cross‐sectional study

The duration of infertility affects semen parameters in primary infertile men: results of a single‐centre, cross‐sectional study

The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap

Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

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