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      The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study

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          Abstract

          Abstract STUDY QUESTION Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth? SUMMARY ANSWER There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses. WHAT IS KNOWN ALREADY In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health. Although some studies have shown an impact of culture medium type on BW, the interaction between culture medium type and associated culture conditions on both treatment success rates (LBR) and offspring BW is largely unexplored. This study aimed to examine these factors in a large multicentre national survey capturing the range of clinical practice. STUDY DESIGN, SIZE, DURATION In this cross-sectional study, data from a survey circulated to all UK IVF clinics requesting information regarding culture medium type, incubator type, and oxygen level used in ART between January 2011 and December 2013 were merged with routinely recorded treatment and outcome data held in the Human Fertilisation and Embryology Authority Register up to the end of 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-six (62%) UK clinics responded to the survey. A total of 75 287 fresh IVF/ICSI cycles were captured, including 18 693 singleton live births. IVF success (live birth, singleton or multiple; LB), singleton gestation and singleton gestation-adjusted BW were analysed using logistic and linear regression models adjusting for patient/treatment characteristics and clinic-specific effects. MAIN RESULTS AND THE ROLE OF CHANCE Culture medium type was shown to have some impact on LBR (multivariable logistic regression, (MRL); post-regression Wald test, P < 0.001), but not on BW (MLR; post-regression Wald test, P = 0.215). However, blastocyst culture had the largest observed effect on odds of LBR (odds ratio (OR) = 1.35, CI: 1.29–1.42), increased the risk of pre-term birth even when controlling for oxygen tension (MLR; OR = 1.42, CI: 1.23–1.63), and gestation-adjusted BW (MLR, β = 38.97 g, CI: 19.42–58.53 g) when compared to cleavage-stage embryo culture. We noted a very strong effect of clinic site on both LBR and BW, thus confounding between treatment practices and clinic site may have masked the effect of culture conditions. LIMITATIONS, REASONS FOR CAUTION Larger datasets with more inter-centre variation are also needed, with key embryo culture variables comprehensively recorded in national treatment registries. WIDER IMPLICATIONS OF THE FINDINGS This study is the largest investigation of laboratory environmental effects in IVF on both LBR and singleton BW. Our findings largely agree with the literature, which has failed to show a consistent advantage of one culture media type over another. However, we noted some association of LBR with medium type, and the duration of embryo exposure to laboratory conditions (blastocyst culture) was associated with both LBR and singleton health at birth. Because of the strong effect of clinic site noted, further randomized controlled trials are needed in order to reliably determine the effect of embryo culture on IVF success rates and the growth and health of subsequent offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the EU FP7 project grant EpiHealthNet (FP7-PEOPLE-2012-ITN -317 146). The authors have no competing interests to declare.

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          Birth weight and subsequent risk of type 2 diabetes: a meta-analysis.

          The "small baby syndrome hypothesis" suggests that an inverse linear relation exists between birth weight and risk of type 2 diabetes. The authors conducted a meta-analysis to examine this association. They included studies that reported odds ratios and 95% confidence intervals (or data with which to calculate them) for the association of type 2 diabetes with birth weight. Fourteen studies involving a total of 132,180 persons were identified. Low birth weight ( /=2,500 g, was associated with increased risk of type 2 diabetes (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.06, 1.64). High birth weight (>4,000 g), as compared with a birth weight of
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            Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology.

            Advances in cell culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage stage embryo transfer to blastocyst stage transfer. The rationale for blastocyst transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates.
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              Large offspring syndrome in cattle and sheep.

              Bovine and ovine embryos exposed to a variety of unusual environments prior to the blastocyst stage have resulted in the development of unusually large offspring which can also exhibit a number of organ defects. In these animals, the increased incidence of difficult parturition and of fetal and neonatal losses has limited the large-scale use of in vitro embryo production technologies commonly used in humans and other species. Four different situations have been identified that result in the syndrome: in vitro embryo culture, asynchronous embryo transfer into an advanced uterine environment, nuclear transfer and maternal exposure to excessively high urea diets. However, programming of the syndrome by all of these situations is unpredictable and not all of the symptoms described have been observed universally. Neither the environmental factors inducing the large offspring syndrome nor the mechanisms of perturbation occurring in the early embryo and manifesting themselves in the fetus have been identified.
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                Author and article information

                Journal
                Hum Reprod Open
                Hum Reprod Open
                hropen
                Human Reproduction Open
                Oxford University Press
                2399-3529
                2020
                10 February 2020
                10 February 2020
                : 2020
                : 1
                : hoz031
                Affiliations
                [1 ] Maternal & Fetal Health Research Centre , Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Sciences Centre, Oxford Rd., Manchester M13 9WL, UK
                [2 ] Institute for Women’s Health , University College London, London WC1E 6HX, UK
                [3 ] Maternal & Fetal Health Research Centre , St. Mary’s Hospital, Manchester University National Health Service (NHS) Foundation Trust, Manchester Academic Health Sciences Centre, Oxford Rd., Manchester M13 9WL, UK
                [4 ] Department of Reproductive Medicine , Old St Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Oxford Rd., Manchester M13 9WL, UK
                [5 ] Centre for Biostatistics, Division of Population Health , Health Services Research & Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Oxford Rd., Manchester M13 9PL, UK
                Author notes
                Correspondence address. Department of Reproductive Medicine, Old St. Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Oxford Rd., Manchester M13 9WL, UK. E-mail: Daniel.Brison@ 123456manchester.ac.uk
                Author information
                http://orcid.org/0000-0002-7204-6169
                http://orcid.org/0000-0001-6364-2367
                https://orcid.org/0000-0002-4307-1293
                Article
                hoz031
                10.1093/hropen/hoz031
                7016773
                32083189
                5df5cb82-cc78-4dca-b0bf-3bcbd3910b6a
                © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 30 March 2019
                : 13 September 2019
                : 27 September 2019
                Page count
                Pages: 13
                Funding
                Funded by: EU FP7
                Award ID: FP7-PEOPLE-2012-ITN-317146
                Categories
                Original Article

                fertilization in vitro,birth weight,art,culture media,blastocyst embryo culture,icsi,live birth rate,pre-term birth,developmental origins of health and disease,assisted reproduction

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