Low oxygen concentrations for embryo culture in assisted reproductive technologies

Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands. .
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 07/2012; 7(7):CD008950. DOI: 10.1002/14651858.CD008950.pub2
Source: PubMed


During in vitro fertilisation (IVF) procedures, human preimplantation embryos are cultured in the laboratory. While some laboratories culture in an atmospheric oxygen concentration (˜ 20%), others use a lower concentration (˜ 5%) as this is more comparable to the oxygen concentration observed in the oviduct and the uterus. Animal studies have shown that high oxygen concentration could have a negative impact on embryo quality via reactive oxygen species causing oxidative stress. In humans, it is currently unknown which oxygen concentration provides the best success rates of IVF procedures, eventually resulting in the hightest birth rate of healthy newborns.
To determine whether embryo culture at low oxygen concentrations improves treatment outcome (better embryo development and more pregnancies and live births) in IVF and intracytoplasmic sperm injection (ICSI) as compared to embryo culture at atmospheric oxygen concentrations.
The Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO electronic databases were searched (up to 4th November 2011) for randomised controlled trials on the effect of low oxygen concentrations for human embryo culture. Furthermore, reference lists of all obtained studies were checked and conference abstracts handsearched.
Only truly randomised controlled trials comparing embryo culture at low oxygen concentrations (˜ 5%) with embryo culture at atmospheric oxygen concentrations (˜ 20%) were included in this systematic review and meta-analysis.
Two review authors selected the trials for inclusion according to the above criteria. After that two authors independently extracted the data for subsequent analysis, and one author functioned as a referee in case of ambiguities. The statistical analysis was performed in accordance with the guidelines developed by The Cochrane Collaboration.
Seven studies with a total of 2422 participants were included in this systematic review. Meta-analysis could be performed with the data of four included studies, with a total of 1382 participants. The methodological quality of the included trials was relatively low. Evidence of a beneficial effect of culturing in low oxygen concentration was found for live birth rate (OR 1.39; 95% CI 1.11 to 1.76; P = 0.005; I(2) = 0%); this would mean that a typical clinic could improve a 30% live birth rate using atmospheric oxygen concentration to somewhere between 32% and 43% by using a low oxygen concentration. The results were very similar for ongoing and clinical pregnancy rates. There was no evidence that culturing embryos under low oxygen concentrations resulted in higher numbers of adverse events such as multiple pregnancies, miscarriages or congenital abnormalities.
The results of this systematic review and meta-analysis suggest that culturing embryos under conditions with low oxygen concentrations improves the success rates of IVF and ICSI, resulting in the birth of more healthy newborns.

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    • "Similarly, Waldenströ m et al. (2009) reported a 10% increase in live birth rate when embryos were cultured in 5% oxygen. A recent Cochrane evaluation of whether culturing preimplantation human embryos in a physiological oxygen compared to atmospheric improves the treatment outcome concluded; 'The results of this systematic review and meta-analysis suggest that culturing embryos under low oxygen concentrations improves the success rates of IVF/ICSI, resulting in an increase in the live birth rate' (Bontekoe et al., 2012). This conclusion is consistent with the data from other species (mouse, cow, sheep, goat and pig) where employment of physiological oxygen concentration throughout development results in superior embryo transfer outcomes. "
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    ABSTRACT: Although laboratory procedures, along with culture media formulations, have improved over the past two decades, the issue remains that human IVF is performed in vitro (literally 'in glass'). Using PubMed, electronic searches were performed using keywords from a list of chemical and physical factors with no limits placed on time. Examples of keywords include oxygen, ammonium, volatile organics, temperature, pH, oil overlays and incubation volume/embryo density. Available clinical and scientific evidence surrounding physical and chemical factors have been assessed and presented here. Development of the embryo outside the body means that it is constantly exposed to stresses that it would not experience in vivo. Sources of stress on the human embryo include identified factors such as pH and temperature shifts, exposure to atmospheric (20%) oxygen and the build-up of toxins in the media due to the static nature of culture. However, there are other sources of stress not typically considered, such as the act of pipetting itself, or the release of organic compounds from the very tissue culture ware upon which the embryo develops. Further, when more than one stress is present in the laboratory, there is evidence that negative synergies can result, culminating in significant trauma to the developing embryo. It is evident that embryos are sensitive to both chemical and physical signals within their microenvironment, and that these factors play a significant role in influencing development and events post transfer. From the viewpoint of assisted human reproduction, a major concern with chemical and physical factors lies in their adverse effects on the viability of embryos, and their long-term effects on the fetus, even as a result of a relatively brief exposure. This review presents data on the adverse effects of chemical and physical factors on mammalian embryos and the importance of identifying, and thereby minimizing, them in the practice of human IVF. Hence, optimizing the in vitro environment involves far more than improving culture media formulations. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
    Human Reproduction Update 07/2015; DOI:10.1093/humupd/dmv034 · 10.17 Impact Factor
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    • "pH of the culture medium is an important variable that can significantly impact gamete function and embryo development (Swain, 2012). Additionally, reduced O 2 concentration in the culture environment has, for many years, repeatedly been found beneficial for both animal and human embryo development and outcomes (Bavister, 2004; Bontekoe et al., 2012; Mantikou et al., 2013), most notably when used throughout the entire culture period to the blastocyst stage (Kovacic and Vlaisavljevic, 2008; Meintjes et al., 2009; Waldenstrom et al., 2009). Thus, modern IVF incubators should monitor and regulate both CO 2 and O 2 concentrations. "
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    ABSTRACT: Incubators in the IVF laboratory play a pivotal role in providing a stable and appropriate culture environment required for optimizing embryo development and clinical outcomes. With technological advances, several types of incubators are now available and careful consideration is required for selection. Examination of variables, such as recovery/stabilization of temperature, gas atmosphere and humidity; as well as understanding various approaches utilized by each device to regulate these variables is critical. Additionally, a comprehensive examination of clinical studies that compare various incubators may provide insight into their efficacy. Other factors, both technical and practical, must also be considered when selecting an incubator. Importantly, proper management, including patient volume and workflow, is paramount in optimizing function of any incubator, regardless of the technology incorporated. This review highlights incubator function and reviews key environmental variables controlled and the technology utilized in various units. Additionally, existing comparative studies focused on incubator recovery and clinical outcomes are critically analysed. Finally, strategies employed for incubator management, as well as future potential incubator improvements, are discussed. While existing reports indicate that smaller benchtop/topload incubators provide faster recovery of environmental variables, there is no clear advantage of any particular incubator based on clinical outcomes.
    Reproductive biomedicine online 05/2014; 28(5). DOI:10.1016/j.rbmo.2014.01.004 · 3.02 Impact Factor
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    ABSTRACT: The state of tissue oxygenation is widely recognized as a major microenvironmental cue that is known to regulate the expression of coding genes. Recent works have extended that knowledge to demonstrate that the state of tissue oxygenation may potently regulate the expression of microRNAs (miRs). Collectively, such miRs that are implicated in defining biological outcomes in response to a change in the state of tissue oxygenation may be referred to as oxymiRs. Broadly, oxymiRs may be categorized into three groups: (A) the existence (expression and/or turnover) of which is directly influenced by changes in the state of tissue oxygenation; (B) the existence of which is indirectly (e.g. oxygen-sensitive proteins, metabolites, pH, etc.) influenced by changes in the state of tissue oxygenation; and (C) those that modify biological outcomes to changes in the state of tissue oxygenation by targeting oxygen sensing pathways. This work represents the first review of how oxymiRs may regulate development, repair and regeneration. Currently known oxymiRs may affect the functioning of a large number of coding genes which have hitherto fore never been linked to oxygen sensing. Many of such target genes have been validated and that number is steadily growing. Taken together, our understanding of oxymiRs has vastly expanded the implications of changes in the state of tissue oxygenation. This emerging paradigm has major implications in untangling the complexities underlying diseases associated with ischemia and related hypoxic insult such as chronic wounds.
    Seminars in Cell and Developmental Biology 10/2012; 23(9). DOI:10.1016/j.semcdb.2012.09.012 · 6.27 Impact Factor
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