Dataset Information

Assisted reproductive technology represents a possible risk factor for development of epimutation-mediated imprinting disorders for mothers aged ≥ 30 years.

ABSTRACT:

Backgrounds

The proportion of assisted reproductive technology (ART)-conceived livebirths of patients with imprinting disorders (IDs) is higher than that of the general population. Whether this is due to ART or confounding effects of advanced parental age was not investigated. We examined the association of ART and parental ages at childbirth for the development of eight epimutation-mediated imprinting disorders (epi-IDs).

Results

We enrolled 136 patients with epi-IDs and obtained general population ART data from the Japanese robust nationwide registry. We compared the proportion of ART-conceived livebirths and maternal childbearing ages between patients with epi-IDs and the general population. The proportion of ART-conceived livebirths in patients with epi-IDs was higher than that in mothers aged ≥ 30 years, the age group in which more than 90% of ART procedures performed. The maternal childbearing ages of patients with epi-IDs were widely distributed from 19 to 45 (median: 32) within the approximate 2.5th to 97.5th percentiles of maternal childbearing ages of the general population. In addition, we compared the proportion of ART-conceived livebirths and parental ages at childbirth across patients with eight epi-IDs. We demonstrated that more than 90% of ART-conceived patients with epi-IDs were found in Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) patients, and parental ages were almost consistent in patients with eight epi-IDs, except Prader-Willi syndrome.

Conclusions

According to the prerequisite that most of the ART procedures in Japan are performed on mothers aged ≥ 30 years, ART can be a risk factor for the development of epi-IDs, particularly SRS and BWS, for mothers aged ≥ 30 years.

SUBMITTER: Hara-Isono K

PROVIDER: S-EPMC7374921 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assisted reproductive technology represents a possible risk factor for development of epimutation-mediated imprinting disorders for mothers aged ≥ 30 years.

Hara-Isono Kaori K Matsubara Keiko K Mikami Masashi M Arima Takahiro T Ogata Tsutomu T Fukami Maki M Kagami Masayo M

Clinical epigenetics 20200722 1

<h4>Backgrounds</h4>The proportion of assisted reproductive technology (ART)-conceived livebirths of patients with imprinting disorders (IDs) is higher than that of the general population. Whether this is due to ART or confounding effects of advanced parental age was not investigated. We examined the association of ART and parental ages at childbirth for the development of eight epimutation-mediated imprinting disorders (epi-IDs).<h4>Results</h4>We enrolled 136 patients with epi-IDs and obtained ...[more]

PMID: 32698867

Similar Datasets

Project description:BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with abnormalities in 11p15.5 imprinted genes. The most common cause is loss of methylation (epimutation) at the imprinting control centre 2 (IC2/KvDMR1). Most IC2 epimutations occur sporadically but an association with conception after assisted reproductive technologies (ART) has been reported. A subgroup of IC2 epimutation cases also harbour epimutations at other imprinting centres (ICs) outside of 11p15.5. We have investigated the relationship between these multiple epimutation cases (ME+), history of ART and clinical phenotype in a cohort of 187 BWS IC2 epimutation patients. RESULTS: Methylation analysis at PLAGL1, MEST and IGF2R ICs demonstrated an over-representation of patients with abnormally low methylation (8.5%, 12% and 6% respectively). At IGF2R some patients (2%) had gain of methylation but this was also detected in controls. Though there were no significant correlations between the methylation index (MIs) at the three ICs tested, a subset of patients appeared to be susceptible to multiple epimutations (ME+) and 21.2% of ME?+?patients had been conceived by ART compared to 4.5% (P?=?0.0033) without additional epimutations. Methylation array profiling (Illumina Goldengate®) of patients and controls (excluding 11p15.5 loci) demonstrated significant differences between patients and controls. No significant associations were found between aspects of the BWS phenotype and individual epimutations but we describe a case presenting with a post-ART BWS-like phenotype in which molecular analysis demonstrated loss of paternal allele methylation at the 11p15.5 IC1 locus (IC1 regulates imprinting of IGF2 and H19). Loss of paternal allele methylation at the IC1 is the molecular finding associated with Silver-Russell syndrome whereas BWS is associated with gain of maternal allele methylation at IC1. Further analysis demonstrated epimutations at PLAGL1 and MEST consistent with the hypothesis that the presence of multiple epimutations may be of clinical relevance. CONCLUSIONS: These findings suggest that the ME?+?subgroup of BWS patients are preferentially, but not exclusively, associated with a history of ART and that, though at present, there are no clear epigenotype-phenotype correlations for ME?+?BWS patients, non-11p15.5 IC epimutations can influence clinical phenotype.

Project description:Study questionIs the Patient Health Questionnaire-8 (PHQ-8) a valid and reliable measure of depression in first-time mothers who conceived via ART?Summary answerThe results from this study provide initial support for the reliability and validity of the PHQ-8 as a measure of depression in mothers who have conceived using ART.What is known alreadyWomen who achieved a clinical pregnancy using ART experience many stressors and may be at an increased risk of depression. The PHQ-8 is a brief measure designed to detect the presence and severity of depressive symptoms. It has been validated in many populations; however, it has not been validated for use in this population.Study design size durationThis is a cross-sectional study of 171 first-time mothers in the USA, recruited through Amazon's Mechanical Turk (MTurk).Participants/materials setting methodsThe reliability of the PHQ-8 was measured through a Cronbach's alpha, the convergent validity was measured through the correlation between the PHQ-8 and the Generalized Anxiety Disorder-7 (GAD-7) measure of anxiety symptoms, and the structural validity was measured through a Confirmatory Factor Analysis.Main results and the role of chanceThe Cronbach's alpha for the total PHQ-8 was acceptable (α = 0.922). The correlation between the PHQ-8 and the GAD-7 was large (r = 0.88) indicating good convergent validity. Ultimately, a bifactor model provided the best model fit ( χ2 (13) = 23.8, P = 0.033; Comparative Fit Index = 0.987; Root Mean Square Error of Approximation = 0.07, Tucker-Lewis Index = 0.972).Limitations reasons for cautionThe results are limited by: the predominantly white and well-educated sample, a lack of causation between the use of artificial reproductive technology and depressive symptoms, including mothers with children up to 5 years old, convergent validity being based on associations with a related construct instead of the same construct, lack of test-retest reliability, divergent validity and criterion-related validity, data collected through MTurk, and the fact that the measures used were all self-report and therefore may be prone to bias.Wider implications of the findingsConsistent with previous literature, a bifactor model for the PHQ-8 was supported. As such, when assessing depression in first-time mothers who conceived via ART, using both the PHQ-8 total score and subdomain scores may yield the most valuable information. The results from this study provide preliminary support for the reliability and validity of the PHQ-8 as a measure of depression in first-time mothers who conceived using ART.Study funding/competing interestsNo specific funding was used for the completion of this study. Throughout the study period and manuscript preparation, the authors were supported by the department funds at Baylor University. The authors declare that they have no conflicts of interest.Trial registration numberN/A.

Project description:BackgroundIn the last few years, an increase in imprinting anomalies has been reported in children born from Assisted Reproductive Technology (ART). Various clinical and experimental studies also suggest alterations of embryo development after ART. Therefore, there is a need for studying early epigenetic anomalies which could result from ART manipulations, especially on single embryos. In this study, we evaluated the impact of superovulation, in vitro fertilization (IVF) and embryo culture conditions on proper genomic imprinting and blastocyst development in single mouse embryos. In this study, different experimental groups were established to obtain embryos from superovulated and non-superovulated females, either from in vivo or in vitro fertilized oocytes, themselves grown in vitro or not. The embryos were cultured either in M16 medium or in G1.2/G2.2 sequential medium. The methylation status of H19 Imprinting Control Region (ICR) and H19 promoter was assessed, as well as the gene expression level of H19, in individual blastocysts. In parallel, we have evaluated embryo cleavage kinetics and recorded morphological data.ResultsWe show that: 1. The culture medium influences early embryo development with faster cleavage kinetics for culture in G1.2/G2.2 medium compared to M16 medium. 2. Epigenetic alterations of the H19 ICR and H19 PP are influenced by the fertilization method since methylation anomalies were observed only in the in vitro fertilized subgroup, however to different degrees according to the culture medium. 3. Superovulation clearly disrupted H19 gene expression in individual blastocysts. Moreover, when embryos were cultured in vitro after either in vivo or in vitro fertilization, the percentage of blastocysts which expressed H19 was higher in G1.2/G2.2 medium compared to M16.ConclusionCompared to previous reports utilizing pools of embryos, our study enables us to emphasize a high individual variability of blastocysts in the H19 ICR and H19 promoter methylation and H19 gene expression, with a striking effect of each manipulation associated to ART practices. Our results suggest that H19 could be used as a sensor of the epigenetic disturbance of the utilized techniques.

Dataset Information

Assisted reproductive technology represents a possible risk factor for development of epimutation-mediated imprinting disorders for mothers aged ≥ 30 years.

Backgrounds

Results

Conclusions

Publications

Assisted reproductive technology represents a possible risk factor for development of epimutation-mediated imprinting disorders for mothers aged ≥ 30 years.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets