Relationship between paternal factors and embryonic aneuploidy of paternal origin

Bonus, Marissa L.; McQueen, Dana B.; Ruderman, Rachel; Hughes, Lydia; Merrion, Katrina; Maisenbacher, Melissa; Feinberg, Eve C.; Boots, Christina E.

doi:10.1016/j.fertnstert.2022.04.020

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…Therefore, we suggest that advanced paternal age does not likely contribute to the development of sperm aneuploidy leading to UPDs. Consistent with this, previous systematic reviews focusing on embryos derived from young oocyte donors concluded that advanced paternal age was not associated with aneuploidy rates [ 20 , 21 ].…”

Section: Discussionsupporting

confidence: 67%

“… UPD, uniparental disomy; IDs, imprinting disorders; UPD-IDs, uniparental disomy-mediated imprinting disorders; Hetero, heterodisomy; Iso, isodisomy; UPD(6)mat, maternal uniparental disomy of chromosome 6; UPD(6)pat, paternal uniparental disomy of chromosome 6; UPD(7)mat, maternal uniparental disomy of chromosome 7; UPD(7)pat, paternal uniparental disomy of chromosome 7; UPD(14)mat, maternal uniparental disomy of chromosome 14; UPD(14)pat, paternal uniparental disomy of chromosome 14; UPD(15)mat, maternal uniparental disomy of chromosome 15; UPD(15)pat, paternal uniparental disomy of chromosome 15; UPD(20)mat, maternal uniparental disomy of chromosome 20; UPD(20)pat, paternal uniparental disomy of chromosome 20 a 9 out of 25 UPD(7)mat patients were reported by Fuke et al [ 20 ] b 17 out of 18 UPD(14)mat patients were reported by Kagami et al [ 22 ] c 19 out of 27 UPD(14)pat patients were reported by Kagami et al [ 21 ] d 27 out of 48 UPD(15)mat patients were reported by Matsubara et al [ 17 ] e 5 out of 6 UPD(20)mat patients were reported by Kawashima et al [ 23 ] …”

Section: Resultsmentioning

confidence: 99%

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Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes

et al. 2023

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Background Our previous study suggested that assisted reproductive technology (ART) may be a possible risk factor for the development of epimutation-mediated imprinting disorders (epi-IDs) for mothers aged ≥ 30 years. However, whether ART or advanced parental age facilitates the development of uniparental disomy-mediated IDs (UPD-IDs) has not yet been investigated. Results We enrolled 130 patients with aneuploid UPD-IDs including various IDs confirmed by molecular studies and obtained ART data of the general population and patients with epi-IDs from a robust nationwide database and our previous report, respectively. We compared the proportion of ART-conceived livebirths and maternal childbearing age between patients with UPD-IDs and the general population or patients with epi-IDs. The proportion of ART-conceived livebirths in patients with aneuploid UPD-IDs was consistent with that in the general population of maternal age ≥ 30 years and was lower than that in the patients with epi-IDs, although there was no significant difference. The maternal childbearing age of patients with aneuploid UPD-IDs was skewed to the increased ages with several cases exceeding the 97.5th percentile of maternal childbearing age of the general population and significantly higher than that of patients with epi-IDs (P < 0.001). In addition, we compared the proportion of ART-conceived livebirths and parental age at childbirth between patients with UPD-IDs caused by aneuploid oocytes (oUPD-IDs) and that by aneuploid sperm (sUPD-IDs). Almost all ART-conceived livebirths were identified in patients with oUPD-IDs, and both maternal age and paternal age at childbirth were significantly higher in patients with oUPD-IDs than in patients with sUPD-IDs. Because maternal age and paternal age were strongly correlated (rs = 0.637, P < 0.001), higher paternal age in oUPD-IDs was explained by the higher maternal age in this group. Conclusions Different from the case of epi-IDs, ART itself is not likely to facilitate the development of aneuploid UPD-IDs. We demonstrated that advanced maternal age can be a risk factor for the development of aneuploid UPD-IDs, particularly oUPD-IDs.

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Section: Discussionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes

et al. 2023

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“…18,19 In addition, paternal obesity was also not found to be associated with higher rates of preimplantation embryonic aneuploidy. 20 In support of these findings, several other clinical, human studies have evaluated products of conception after an early pregnancy loss and come to the same conclusion. Boots et al found that obese women with a diagnosis of recurrent early pregnancy loss (at least two losses at less than 10 weeks of gestation) were 60% more likely to have a euploid rather than an aneuploid loss (58 vs. 37%, relative risk: 1.63; 95% CI: 1.08-2.47).…”

Section: Embryomentioning

confidence: 60%

“…18 19 In addition, paternal obesity was also not found to be associated with higher rates of preimplantation embryonic aneuploidy. 20…”

Section: Pathophysiology Between Obesity and Miscarriagementioning

confidence: 99%

Obesity and Miscarriage

McLean,

Boots

2023

Semin Reprod Med

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Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index (BMI) have higher rates of anovulation and irregular menses, lower success with fertility treatment, and significantly higher rates of pregnancy complications, such as hypertension/preeclampsia, gestational diabetes, and preterm delivery. Many studies have also shown an association between obesity and early pregnancy loss. However, the causal association between BMI and miscarriage has not been elucidated, likely due to the multifactorial effects that BMI may have on early pregnancy development. In addition, BMI as an isolated variable fails to capture other relevant confounding health risk factors, such as nutrition, physical activity, and insulin resistance. In this review, we will summarize the current literature demonstrating the association between BMI and miscarriage, highlight the research that attempts to explain the association, and finally provide data on therapeutic interventions to improve reproductive outcomes in women suffering from obesity and early pregnancy loss.

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“…However, it is interesting to see a trend in the association of aneuploidy of paternal origin with increasing paternal age. Particularly in the case of age, the p -value closely approached significance ( 21 ).…”

Section: Discussionmentioning

confidence: 95%

The impact of paternal age on cumulative assisted reproductive technology outcomes

Farabet,

Pirtea,

Benammar

et al. 2024

Front. Med.

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ObjectiveTo investigate the impact of paternal age on cumulative live birth rate in ART.DesignRetrospective single-center cohort study.Patient(s)All female patients aged 18–43 years and male patients aged 18–60 years, who performed their first ART cycle between January 2018 and December 2020, were included.Main outcome measure(s)The primary outcome, cumulative live birth rate (cLBR), was estimated following fresh or frozen embryo transfers issued from an ART cycle. Secondary outcomes included the cumulative pregnancy rate (cPR) and miscarriage rate. Subgroup analyzes were performed as follows: men <45 and ≥ 45; female <35, 35–38, and > 38 years.Result(s)A total of 2,358 couples were included in this study. The sperm quantity of male patients within both age groups was divided in two groups: normal and abnormal, which were found to be in significantly equal proportions. There were significantly fewer current smokers in the male group ≥45. The cPR was 0.5301 in the group <45 and 0.3111 in the group ≥45, with a p-value <0.001. Analysis according to the female age revealed that, in the female group >38, the cLBR rate was 0.26 for men <45 and 0.19 for men ≥45, with a p-value of 0.061. Additionally, the cPR was 0.34 in the male group <45 and 0.21 in the group ≥45, with a p-value <0.001. In the female group between 35 and 38 years of age, the cLBR was 0.44 in the male group <45 and 0.3 in the male group ≥45, with a p-value of 0.031. The cPR was 0.49 in the male group <45 and 0.34 in the group ≥45, p = 0.036. Within the female group <35, we observed non-significant results. The miscarriage rate results were not significantly different for women ≤38.ConclusionAccording to the results from our study, male age ≥ 45 has a significant impact on cumulative ART outcomes.

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Relationship between paternal factors and embryonic aneuploidy of paternal origin

Cited by 14 publications

References 34 publications

Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes

Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes

Obesity and Miscarriage

The impact of paternal age on cumulative assisted reproductive technology outcomes

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