Neonatal outcomes following fresh as compared to frozen/thawed embryo transfer in in vitro fertilization

Heertum, Kristin Van; Weinerman, Rachel S.

doi:10.1002/bdr2.1216

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…Concordantly, it has been described that ART increases the risk of some foetal overgrowth syndromes, such as large offspring syndrome in bovines and Beckwith-Wiedemann syndrome in humans, both associated with epigenetic changes [42][43][44][45]. In this sense, epigenetic studies point toward differential methylation of critical genes for growth that may be responsible for the increased incidence of body weight disorders following ART [46]. In addition, epigenetic variations in ART births can remain in adulthood [26].…”

Section: Discussionmentioning

confidence: 96%

Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits

García‐Domínguez

Vicente

Marco‐Jiménez

2020

Animals

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In this study, we evaluated the effect of embryo vitrification using two different devices on adulthood phenotype in rabbits. In vitro development, prenatal embryo survival, body weight, growth performance, haematological and biochemical peripheral blood analysis, reproductive performance, and lactation performance traits were compared between the experimental groups. They derived from naturally-conceived embryos (NC), fresh-transferred embryos (FT), vitrified-transferred embryos using mini-straw (VTs), or vitrified-transferred embryos using Cryotop (VTc). Straw-vitrified embryos exhibited lower in vitro developmental rates and in vivo survival rates following embryo transfer compared to its Cryotop-vitrified counterparts. Moreover, the VTs group exhibited higher foetal losses than VTc, FT, and NC groups. Independently of the vitrification device, vitrified-transferred (VT) offspring showed a skewed sex ratio in favour of males, and an increased birth bodyweight. In contrast, postnatal daily growth was diminished in all ART (i.e., FT and VT) animals. In adulthood, significant differences in body weight between all groups was founded—all ART progenies weighed less than NC animals and, within ART, VT animals weighed less than FT. For VT groups, weight at adulthood was higher for the VTs group compared with the VTc group. Peripheral blood parameters ranged between common values. Moreover, no differences were found in the fertility rates between experimental groups. Furthermore, similar pregnancy rates, litter sizes, and the number of liveborns were observed, regardless of the experimental group. However, decreased milk yield occurred for VTc and FT animals compared to VTs and NC animals. A similar trend was observed for the milk composition of dry matter and fat. Concordantly, reduced body weight was found for suckling kits in the VTc and FT groups compared to VTs and NC animals. Our findings reveal that developmental changes after the embryo vitrification procedure could be associated with an exhibition of the embryonic developmental plasticity. Moreover, to our best knowledge, this study reports the first evidence demonstrating that the vitrification device used is not a trivial decision, providing valuable information about how the cooling–warming rates during vitrification can be partly responsible of the postnatal phenotypic variations.

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Section: Discussionmentioning

confidence: 96%

Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits

García‐Domínguez

Vicente

Marco‐Jiménez

2020

Animals

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“…For example, weight of babies derived from frozen embryos has been reported to be greater than fresh embryo‐derived counterparts for their gestation period. 82 , 83 , 84 , 85 In a rabbit model, vitrification of embryos increased the birth body and liver wight of offsprings. 86 In addition, vitrification affected gene expression in sheep embryos, 87 and variation in methylation pattern of H19/Igf2 was reported.…”

Section: Long‐term Consequences Of Vitrificationmentioning

confidence: 99%

Resveratrol enhanced mitochondrial recovery from cryopreservation‐induced damages in oocytes and embryos

Iwata

2021

Reprod Medicine & Biology

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Embryo transfer (ET) is a major assisted reproductive technology (ART) used for domestic animals and humans worldwide. In industrialized countries, an increasing number of women get pregnant using ET technology. Success in ET depends on the quality of embryos, which are affected by physiological conditions of oocyte donors such as obesity and diabetes, maternal age, and an ART per se, including in vitro culture and cryopreservation. Cryopreservation is pivotal in ART and supports the widespread use of the embryos collected from genetically and/or commercially valuable domestic animals, as it increases opportunity for pregnancy. Cryopreservation methods have improved over decades; oocytes that are usually difficult to cryopreserve now have high survival rate (over 80%) after

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“…Medically assisted reproduction procedures may subject gametes and early embryos to environmental stress which may impact the development of the foetus, for example, by disruptions in the expression of imprinted genes ( Sakian et al , 2015 ). Gamete and embryo cryopreservation methods can also affect DNA methylation ( Van Heertum and Weinerman, 2018 ; Cao et al , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Association of medically assisted reproduction with offspring cord blood DNA methylation across cohorts

et al. 2021

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STUDY QUESTION Is cord blood DNA methylation associated with having been conceived by medically assisted reproduction? SUMMARY ANSWER This study does not provide strong evidence of an association of conception by medically assisted reproduction with variation in infant blood cell DNA methylation. WHAT IS KNOWN ALREADY Medically assisted reproduction consists of procedures used to help infertile/subfertile couples conceive, including ART. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with medically assisted reproduction could reveal new insights into the biological effects of assisted reproductive technologies and potential adverse offspring outcomes. STUDY DESIGN, SIZE, DURATION We investigated the association of DNA methylation and medically assisted reproduction using a case–control study design (N = 205 medically assisted reproduction cases and N = 2439 naturally conceived controls in discovery cohorts; N = 149 ART cases and N = 58 non-ART controls in replication cohort). PARTICIPANTS/MATERIALS, SETTINGS, METHODS We assessed the association between medically assisted reproduction and DNA methylation at birth in cord blood (205 medically assisted conceptions and 2439 naturally conceived controls) at >450 000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N = 149 ART conceptions and N = 58 controls). MAIN RESULTS AND THE ROLE OF CHANCE The ALSPAC and MoBa meta-analysis revealed evidence of association between conception by medically assisted reproduction and DNA methylation (false-discovery-rate-corrected P-value < 0.05) at five CpG sites which are annotated to two genes (percentage difference in methylation per CpG, cg24051276: Beta = 0.23 (95% CI 0.15,0.31); cg00012522: Beta = 0.47 (95% CI 0.31, 0.63); cg17855264: Beta = 0.31 (95% CI 0.20, 0.43); cg17132421: Beta = 0.30 (95% CI 0.18, 0.42); cg18529845: Beta = 0.41 (95% CI 0.25, 0.57)). Methylation at three of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of medically assisted reproduction-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling. LIMITATIONS, REASONS FOR CAUTIONS While insufficient power is likely, heterogeneity in types of medically assisted reproduction procedures and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to medically assisted reproduction. WIDER IMPLICATIONS OF THE FINDINGS Newborns conceived with medically assisted procedures present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health. STUDY FUNDING/COMPETING INTERESTS(S) This study has been supported by the US National Institute of Health (R01 DK10324), the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 669545, European Union’s Horizon 2020 research and innovation programme under Grant agreement no. 733206 (LifeCycle) and the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES, http://www.ariesepigenomics.org.uk). D.C., J.J., C.L.R. D.A.L and H.R.E. work in a Unit that is supported by the University of Bristol and the UK Medical Research Council (Grant nos. MC_UU_00011/1, MC_UU_00011/5 and MC_UU_00011/6). B.N. is supported by an NHMRC (Australia) Investigator Grant (1173314). ALSPAC GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (Contract no. N01-ES-75558), NIH/NINDS (Grant nos. (i) UO1 NS 047537-01 and (ii) UO1 NS 047537-06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (Grant no. 221097). This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, Project no. 262700. D.A.L. has received support from national and international government and charity funders, as well as from Roche Diagnostics and Medtronic for research unrelated to this study. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

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Neonatal outcomes following fresh as compared to frozen/thawed embryo transfer in in vitro fertilization

Cited by 13 publications

References 21 publications

Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits

Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits

Resveratrol enhanced mitochondrial recovery from cryopreservation‐induced damages in oocytes and embryos

Association of medically assisted reproduction with offspring cord blood DNA methylation across cohorts

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