scholarly journals Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

2022 ◽  
Author(s):  
Natalia V. Kovaleva ◽  
Philip D. Cotter
Keyword(s):  
Pregnancy Outcomes ◽  
Maternal Age ◽  
Chromosomal Rearrangements ◽  
Clinical Manifestations ◽  
Female Gender ◽  
Normal Pregnancy ◽  
Paternal Age ◽  
Preimplantation Embryos ◽  
Chromosomal Imbalance ◽  
Male Predominance

Abstract Mosaicism for unbalanced chromosomal rearrangements segmental mosaicism (SM) is rare, both in patients referred for cytogenetic testing and in prenatal diagnoses. In contrast, in preimplantation embryos SM is a frequent finding and, therefore, is even more challenging. However, there is no consistency among results of published studies on the clinical outcomes of embryos with SM, primarily due to the small number of reported cases. Moreover, there is the problem of predicting the potential for the optimal development of a mosaic embryo to a healthy individual. Therefore, we suggested comparing factors predisposing to favorable and poor prognoses, identified in postnatal and prenatal cohorts of SM carriers, with those obtained from studies on preimplantation embryos. We analyzed 580 published cases of SM including (i) postnatally diagnosed affected carriers, (ii) clinically asymptomatic carriers, (iii) prenatally diagnosed carriers, and (iv) miscarriages. We observed a concordance with preimplantation diagnoses regarding the clinical significance of the extent of mosaicism as well as a predominance of deletions over other types of rearrangements. However, there is no concordance regarding excessive involvement of chromosomes 1, 5, and 9 in unbalanced rearrangements and a preferential involvement of larger chromosomes compared to short ones. Paternal age was not found to be associated with SM in postnatally disease-defined individuals. We have identified maternal age and preferential involvement of chromosome 18 in rearrangements associated with clinical manifestations. Male predominance was found among normal pregnancy outcomes and among disease-defined carriers of rearrangements resulting in a gain of genomic material. Female predominance was found among abnormal pregnancy outcomes, among disease-defined carriers of loss and gain/loss rearrangements, and among transmitting carriers of gonadal SM, both affected and asymptomatic. According to data obtained from “post-embryo” studies, clinical manifestations of chromosomal imbalance are associated with a high proportion of abnormal cells, female gender, the type of rearrangement and involved chromosome(s), and maternal age. We believe these data are instructive in the challenging medical genetic counseling of parents faced with no option other than transfer of an embryo with segmental mosaicism.

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

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Setti ◽  
D Braga ◽  
P Guilherme ◽  
L Vingris ◽  
A Iaconelli ◽  
...  
Keyword(s):  
Intracytoplasmic Sperm Injection ◽  
Pregnancy Outcomes ◽  
Maternal Age ◽  
Implantation Rate ◽  
Paternal Age ◽  
Independent Variable ◽  
Interaction Term ◽  
Icsi Outcomes ◽  
Main Effects

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 < 0.001), top-quality blastocyst (B: - 0.003, OR: 0.997, CI: 0.996 – 0.999, p < 0.001), implantation rate (B: - 0.041, OR: 0.960, CI: 0.947 – 0.973, p < 0.001), pregnancy rate (B: - 0.004, OR: 0.996, CI: 0.995 – 0.997, p < 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

scholarly journals Parental age is related to the occurrence of cleft lip and palate in Brazilian populations

2017 ◽  
Vol 15 (2) ◽  
pp. 167
Author(s):  
Paulo Henrique Pimenta de Carvalho ◽  
Renato Assis Machado ◽  
Silvia Regina de Almeida Reis ◽  
Daniella Reis Barbosa Martelli ◽  
Verônica Oliveira Dias ◽  
...  
Keyword(s):  
Maternal Age ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Multinomial Logistic Regression ◽  
Female Gender ◽  
Paternal Age ◽  
Chi Square ◽  
Oral Cleft ◽  
Multinomial Logistic Regression Analysis ◽  
Increased Risk

Aim: To evaluate the association of environmental risk factors, particularly paternal and maternal age, with gender and type of oral cleft in newborn with nonsyndromic cleft lip with or without cleft palate (NSCL/P). Methods: This study included 1,346 children with NSCL/P of two Brazilian Services for treatment of craniofacial deformities. Parental ages were classified into the following groups: maternal age <35, 36-39, and ≥40 years; paternal age <39 and ≥40 years. The data was analyzed with chi-square test and multinomial logistic regression analysis. The odds ratios were estimated with a 95% confidence interval. Results: Of the 1,346 children included in this study, CLP was the type of NSCL/P with highest prevalence, followed by, respectively, CL and CP. There was a greater occurrence of NSCL/P in males compared to females (55.8% versus 44.2%). CLP was more common in men, while the CL and CP were more prevalent in women (p=0.000). No association between maternal age and clefts was observed (p=0.747). However, there was evidence of association between father’s aged ≥40 years old and NSCL/P (p=0.031). When patients with CP were analyzed separately, no association between the father’s age and the child’s gender (p=0.728) was observed, i.e. the female gender prevails among patients with CP, regardless of the father’s age. Conclusions: This study showed that there were differences in the distribution of the non-syndromic cleft lip and/or palate and the gender, and fathers aged ≥40 years old may have increased risk of oral cleft. Further studies involving different populations are needed for a better understanding of the effect of maternal and paternal ages as a risk factor for the occurrence of oral clefts.

Parental breeding age effects on descendants’ longevity interact over two generations in matrilines and patrilines

2019 ◽  
Author(s):  
Zac Wylde ◽  
Foteini Spagopoulou ◽  
Amy K Hooper ◽  
Alexei A Maklakov ◽  
Russell Bonduriansky
Keyword(s):  
Maternal Age ◽  
First Generation ◽  
Age Effects ◽  
Population Variation ◽  
Paternal Age ◽  
Interactive Effects ◽  
Competitive Environment ◽  
Larval Diet ◽  
Negative Effects ◽  
Two Generations

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does, and that breeding age effects can interact over two generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over two generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grandparental ages at breeding on descendants’ mortality rate and lifespan in both matrilines and patrilines. These breeding age effects were not modulated by grandparental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intra-population variation in mortality and longevity.

scholarly journals Advanced maternal age and adverse pregnancy outcomes: A cohort study

2021 ◽  
Vol 60 (1) ◽  
pp. 119-124
Author(s):  
M. Guarga Montori ◽  
A. Álvarez Martínez ◽  
C. Luna Álvarez ◽  
N. Abadía Cuchí ◽  
P. Mateo Alcalá ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnancy Outcomes ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
Adverse Pregnancy Outcomes ◽  
Adverse Pregnancy

scholarly journals Assessing the relationship between pregravid body mass index and risk of adverse maternal pregnancy and neonatal outcomes: prospective data in Southwest China

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yue Chen ◽  
Ke Wan ◽  
Yunhui Gong ◽  
Xiao Zhang ◽  
Yi Liang ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cesarean Delivery ◽  
Body Mass ◽  
Gestational Age ◽  
Pregnancy Outcomes ◽  
Maternal Age ◽  
Southwest China ◽  
Adverse Pregnancy Outcomes ◽  
Relative Importance ◽  
Adverse Pregnancy

AbstractThe relevance of pregestational body mass index (BMI) on adverse pregnancy outcomes remained unclear in Southwest China. This study aimed to investigate the overall and age-category specific association between pre-gestational BMI and gestational diabetes mellitus (GDM), preeclampsia, cesarean delivery, preterm delivery, stillbirth, macrosomia, and small-for-gestational age (SGA) or large-for-gestational age (LGA) neonates in Southwest China. Furthermore, it explores the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. 51,125 Chinese singleton pregnant women were recruited as study subjects. Multiple logistic regression models were used to examine the influence of pre-pregnancy BMI on adverse pregnancy outcomes. Gradient boosting machine was used to evaluate the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. It is found that women who were overweight or obese before pregnancy are at higher risk of adverse pregnancy outcomes except for SGA neonates, while pre-pregnancy underweight is a protective factor for GDM, preeclampsia, cesarean delivery, macrosomia and LGA, but not SGA. Younger mothers are more susceptible to GDM and macrosomia neonates, while older mothers are more prone to preeclampsia. Pre-pregnancy BMI has more influence on various pregnancy outcomes than maternal age. To improve pregnancy outcomes, normal BMI weight as well as relatively young maternal ages are recommended for women in child-bearing age.

scholarly journals Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells

2021 ◽  
pp. 1-11
Author(s):  
Pooja Khurana ◽  
Neil R. Smyth ◽  
Bhavwanti Sheth ◽  
Miguel A. Velazquez ◽  
Judith J. Eckert ◽  
...  
Keyword(s):  
Maternal Age ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Advanced Maternal Age ◽  
Preimplantation Embryos ◽  
Dependent Manner ◽  
Ki 67 ◽  
Altered Expression ◽  
Developmental Potential ◽  
Developmental Mechanisms

Abstract Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.

Is there still a rationale for non-invasive PGT-A by analysis of cell-free DNA released by human embryos into culture medium?

2021 ◽  
Vol 36 (5) ◽  
pp. 1186-1190
Author(s):  
Raoul Orvieto ◽  
Adva Aizer ◽  
Norbert Gleicher
Keyword(s):  
Culture Media ◽  
Chromosomal Rearrangements ◽  
Primary Source ◽  
Normal Pregnancy ◽  
Early Embryo ◽  
Human Embryos ◽  
Cell Debris ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna

Abstract Human embryos utilise an array of processes to eliminate the very high prevalence of aneuploid cells in early embryo stages. Human embryo self-correction was recently demonstrated by their ability to eliminate/expel abnormal blastomeres as cell debris/fragments. A whole genome amplification study has demonstrated that 63.6% of blastocysts expelled cell debris with abnormal chromosomal rearrangements. Moreover, 55.5% of euploid blastocysts expel aneuploid debris, strongly suggesting that the primary source of cell free DNA in culture media is expelled aneuploid blastomeres and/or their fragments. Such a substantial ability to self-correct downstream from the blastocyststage, therefore, renders any chromosomal diagnosis at the blastocyststage potentially useless, and this, unfortunately, also must particularly include non-invasive PGT-A based on cell-free DNA in spent medium. High rates of false-positive diagnoses of human embryos often lead to non-use and/or disposal of embryos with entirely normal pregnancy potential. Before adopting yet another round of unvalidated PGT-A as a routine adjunct to IVF, we here present facts that deserve to be considered.

Effect of Advanced Maternal Age on Pregnancy Outcomes and Vascular Function in the Rat

Hypertension ◽  
2015 ◽  
Vol 65 (6) ◽  
pp. 1324-1330 ◽  
Author(s):  
Alison S. Care ◽  
Stephane L. Bourque ◽  
Jude S. Morton ◽  
Emma P. Hjartarson ◽  
Sandra T. Davidge
Keyword(s):  
Pregnancy Outcomes ◽  
Vascular Function ◽  
Maternal Age ◽  
Advanced Maternal Age

DEFINING ELIGIBILITY CRITERIA FOR FUNDING POLICIES AROUND IN VITRO FERTILIZATION

2015 ◽  
Vol 31 (6) ◽  
pp. 426-433 ◽  
Author(s):  
Devidas Menon ◽  
Alexa A. Nardelli ◽  
Tarek Motan ◽  
Kristin Klein ◽  
Tania Stafinski
Keyword(s):  
Maternal Age ◽  
Smoking Status ◽  
Cochrane Collaboration ◽  
Assessment Tools ◽  
Paternal Age ◽  
Eligibility Criteria ◽  
Vitro Fertilization ◽  
Funding Policies ◽  
The Impact

Objectives: This review aims to assess the state of the science around the potential impact of certain patient characteristics on the safety and effectiveness of in vitro fertilization (IVF).Methods: Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of reviews and recent primary studies examining the impact of paternal age and maternal age, smoking, and body mass index (BMI) on the safety and effectiveness of IVF was performed. Papers, published between January 2007 and June 2014, were independently reviewed and critically appraised by two researchers using published quality assessment tools for reviews and primary studies. Due to heterogeneity across papers (different study designs and patient selection criteria), a qualitative analysis of extracted information was performed.Results: Seventeen papers (ten systematic reviews and seven primary studies) were included. They comprised evidence from retrospective observational studies in which maternal age, BMI, and smoking status were explored as part of secondary analyses of larger studies. The majority of papers found that the likelihood of achieving a pregnancy was lower among women who were >40 years, had a BMI ≥ 25 and smoked. Advanced maternal age and BMI were also associated with higher rates of preterm birth and low birth weight.Conclusions: Based on available evidence, it may be appropriate to consider “maternal age” and “morbid obesity” in public funding policies that aim to maximize the effectiveness of IVF. However, given inconsistencies in the effect of smoking across different pregnancy-related outcomes, support for incorporating it into funding conditions appears weak.

Pregnancy Outcomes in HIV-Infected Women of Advanced Maternal Age

2013 ◽  
Vol 14 (3) ◽  
pp. 110-119 ◽  
Author(s):  
Giuseppina Liuzzi ◽  
Carmela Pinnetti ◽  
Marco Floridia ◽  
Enrica Tamburrini ◽  
Giulia Masuelli ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Maternal Age ◽  
Advanced Maternal Age
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