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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.

ABSTRACT: Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (-0.5 SD [95% CI: -0.7, -0.2]), lighter (-0.6 SD [-0.9, -0.3]) and have lower skinfold thicknesses (e.g. -14% [-24%, -3%] suprailiac), and blood pressure (-3 mmHg [-6, -0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.

SUBMITTER: Huang JY

PROVIDER: S-EPMC8460697 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.

Huang Jonathan Yinhao JY Cai Shirong S Huang Zhongwei Z Tint Mya Thway MT Yuan Wen Lun WL Aris Izzuddin M IM Godfrey Keith M KM Karnani Neerja N Lee Yung Seng YS Chan Jerry Kok Yen JKY Chong Yap Seng YS Eriksson Johan Gunnar JG Chan Shiao-Yng SY

Nature communications 20210923 1

Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum m ...[more]

PMID: 34556649

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Project description:BackgroundThis study sought to determine the impact of pregnancy or assisted reproductive technologies (ART) on breast-cancer-specific survival among breast cancer survivors.MethodsThe authors performed a cohort study using a novel data linkage from the California Cancer Registry, the California birth cohort, and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data sets. They performed risk-set matching in women with stages I-III breast cancer diagnosed between 2000 and 2012. For each pregnant woman, comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics were matched at the time of pregnancy. After matching, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pregnancy with breast-cancer-specific survival. We repeated these analyses for women who received ART.ResultsAmong 30,021 women with breast cancer, 553 had a pregnancy and 189 attempted at least one cycle of ART. In Cox proportional hazards modeling, the pregnancy group had a higher 5-year disease-specific survival rate; 95.6% in the pregnancy group and 90.6% in the nonpregnant group (HR, 0.43; 95% CI, 0.24-0.77). In women with hormone receptor-positive cancer, we found similar results (HR, 0.43; 95% CI, 0.2-0.91). In the ART analysis, there was no difference in survival between groups; the 5-year disease-specific survival rate was 96.9% in the ART group and 94.1% in the non-ART group (HR, 0.44; 95% CI, 0.17-1.13).ConclusionPregnancy and ART are not associated with worse survival in women with breast cancer.Lay summaryWe sought to determine the impact of pregnancy or assisted reproductive technologies (ART) among breast cancer survivors. We performed a study of 30,021 women by linking available data from California and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. For each pregnant woman, we matched at the time of pregnancy comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics. We repeated these analyses for women who received ART. We found that pregnancy and ART were not associated with worse survival.

Project description:Societal changes and the increasing desire and opportunity to preserve fertility have increased the demand for effective assisted reproductive technologies (ART) and have increased the range of scenarios in which ART is now used. In recent years, the "freeze-all" strategy of cryopreserving all oocytes or good quality embryos produced in an IVF cycle to transfer later-at a time that is more appropriate for reasons of medical need, efficacy, or desirability-has emerged as an accepted and valuable alternative to fresh embryo transfer. Indeed, improvements in cryopreservation techniques (vitrification) and the development of more efficient ovarian stimulation protocols have facilitated a dramatic increase in the practice of elective frozen embryo transfer (eFET). Alongside these advances, debate continues about whether eFET should be a standard treatment option available to the whole IVF population or if it is important to identify patient subgroups who are most likely to benefit from such an approach. Achieving successful outcomes in ART, whether by fresh or frozen embryo transfer, is influenced by a wide range of factors. As well as the efficiency of IVF and embryo transfer protocols and techniques, factors affecting implantation include maternal aging, sperm quality, the vaginal and endometrial microbiome, and peri-implantation levels of serum progesterone. The safety of eFET, both during ART cycles and on longer-term obstetric and neonatal outcomes, is also an important consideration. In this review, we explore the benefits and risks of freeze-all strategies in different scenarios. We review available evidence on the outcomes achieved with elective cryopreservation strategies and practices and how these compare with more traditional IVF cycles with fresh embryo transfers, both in the general IVF population and in subgroups of special interest. In addition, we consider how to optimize and individualize "freeze-all" procedures to achieve successful reproductive outcomes.

Project description:Biodiversity is defined as the presence of a variety of living organisms on the Earth that is essential for human survival. However, anthropogenic activities are causing the sixth mass extinction, threatening even our own species. For many animals, dwindling numbers are becoming fragmented populations with low genetic diversity, threatening long-term species viability. With extinction rates 1000-10,000 times greater than natural, ex situ and in situ conservation programmes need additional support to save species. The indefinite storage of cryopreserved (-196°C) viable cells and tissues (cryobanking), followed by assisted or advanced assisted reproductive technology (ART: utilisation of oocytes and spermatozoa to generate offspring; aART: utilisation of somatic cell genetic material to generate offspring), may be the only hope for species' long-term survival. As such, cryobanking should be considered a necessity for all future conservation strategies. Following cryopreservation, ART/aART can be used to reinstate lost genetics back into a population, resurrecting biodiversity. However, for this to be successful, species-specific protocol optimisation and increased knowledge of basic biology for many taxa are required. Current ART/aART is primarily focused on mammalian taxa; however, this needs to be extended to all, including to some of the most endangered species: amphibians. Gamete, reproductive tissue and somatic cell cryobanking can fill the gap between losing genetic diversity today and future technological developments. This review explores species prioritisation for cryobanking and the successes and challenges of cryopreservation and multiple ARTs/aARTs. We here discuss the value of cryobanking before more species are lost and the potential of advanced reproductive technologies not only to halt but also to reverse biodiversity loss.Lay summaryThe world is undergoing its sixth mass extinction; however, unlike previous events, the latest is caused by human activities and is resulting in the largest loss of biodiversity (all living things on Earth) for 65 million years. With an extinction rate 1000-10,000-fold greater than natural, this catastrophic decline in biodiversity is threatening our own survival. As the number of individuals within a species declines, genetic diversity reduces, threatening their long-term existence. In this review, the authors summarise approaches to indefinitely preserve living cells and tissues at low temperatures (cryobanking) and the technologies required to resurrect biodiversity. In the future when appropriate techniques become available, these living samples can be thawed and used to reinstate genetic diversity and produce live young ones of endangered species, enabling their long-term survival. The successes and challenges of genome resource cryopreservation are discussed to enable a move towards a future of stable biodiversity.

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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.

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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.

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