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What is a Literature Review?

A literature review is a body of text that aims to review the critical points of current knowledge on a particular topic. Most often associated with science-oriented literature, such as a thesis, the literature review usually proceeds a research proposal, methodology and results section. Its ultimate goals is to bring the reader up to date with current literature on a topic and forms that basis for another goal, such as the justification for future research in the area. (retrieved from  http://en.wikipedia.org/wiki/Literature_review )

Writing a Literature Review

The literature review is the section of your paper in which you cite and briefly review the related research studies that have been conducted. In this space, you will describe the foundation on which  your  research will be/is built. You will:

• discuss the work of others
• evaluate their methods and findings
• identify any gaps in their research
• state how  your  research is different

The literature review should be selective and should group the cited studies in some logical fashion.

If you need some additional assistance writing your literature review, the Knight Institute for Writing in the Disciplines offers a  Graduate Writing Service .

Demystifying the Literature Review

For more information, visit our guide devoted to " Demystifying the Literature Review " which includes:

• guide to conducting a literature review,
• a recorded 1.5 hour workshop covering the steps of a literature review, a checklist for drafting your topic and search terms, citation management software for organizing your results, and database searching.

Online Resources

• A Guide to Library Research at Cornell University
• Literature Reviews: An Overview for Graduate Students North Carolina State University 
• The Literature Review: A Few Tips on Conducting Written by Dena Taylor, Director, Health Sciences Writing Centre, and Margaret Procter, Coordinator, Writing Support, University of Toronto
• How to Write a Literature Review University Library, University of California, Santa Cruz
• Review of Literature The Writing Center, University of Wisconsin-Madison

Print Resources

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Literature Review Basics

• Literature Review Step-by-Step
• Common Questions about Literature Reviews
• How do I craft a basic citation?
• What is citation tracing?
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This video will provide a short introduction to literature reviews.

Steps For Writing a Literature Review

Recommended steps for writing a literature review:

• Review what a literature review is, and is not 
• Review your assignment and seek clarification from your instructor if needed
• Narrow your topic
• Search and gather literature resources. 
• Read and analyze literature resources
• Write the literature review
• Review appropriate  Citation and Documentation Style  for your assignment and literature review

Common Questions

What is a literature review?

A literature review is a type of scholarly, researched writing that discusses the already published information on a narrow topic . 

What is the purpose of a writing literature review?

Writing a literature review improves your personal understanding of a topic, and demonstrates your knowledge and ability to make connections between concepts and ideas. The literature review is a service to your reader, summarizing past ideas about a topic, bringing them up to date on the latest research, and making sure they have all any background information they need to understand the topic.  

What is "the literature"?

This already published information- called the literature- can be from primary information sources such as speeches, interviews, and reports, or from secondary information sources such as peer-reviewed journal articles, dissertations, and books. These type of sources are probably familiar to you from previous research projects you’ve done in your classes.

Is a literature review it's own paper?

You can write a literature review as a standalone paper , or as part of a larger research paper . When a standalone paper, the literature review acts as a summary, or snapshot, of what has been said and done about a topic in the field so far. When part of the a larger paper, a literature review still acts as a snapshot, but the prior information it provides can also support the new information, research, or arguments presented later in the paper.

Does a literature review contain an argument?

No, a literature review does NOT present an argument or new information. The literature review is a foundation that summarizes and synthesizes the existing literature in order for you and your readers to understand what has already been said and done about your topic.

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• What is a Literature Review?

What is a literature review?

A literature review surveys scholarly articles, books and other sources relevant to a particular issue, area of research, or theory. The purpose is to offer an overview of significant literature published on a topic.

A literature review may constitute an essential chapter of a thesis or dissertation, or may be a self-contained review of writings on a subject. In either case, its purpose is to:

• Place each work in the context of its contribution to the understanding of the subject under review
• Describe the relationship of each work to the others under consideration
• Identify new ways to interpret, and shed light on any gaps in, previous research
• Resolve conflicts amongst seemingly contradictory previous studies
• Identify areas of prior scholarship to prevent duplication of effort
• Point the way forward for further research
• Place one's original work (in the case of theses or dissertations) in the context of existing literature

A literature review can be just a simple summary of the sources, but it usually has an organizational pattern and combines both summary and synthesis. A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information. It might give a new interpretation of old material or combine new with old interpretations. Or it might trace the intellectual progression of the field, including major debates. And depending on the situation, the literature review may evaluate the sources and advise the reader on the most pertinent or relevant.

Similar to primary research, development of the literature review requires four stages:

• Problem formulation—which topic or field is being examined and what are its component issues?
• Literature search—finding materials relevant to the subject being explored
• Data evaluation—determining which literature makes a significant contribution to the understanding of the topic
• Analysis and interpretation—discussing the findings and conclusions of pertinent literature

Remember, this is a process and not necessarily a linear one. As you search and evaluate the literature, you may refine your topic or head in a different direction which will take you back to the search stage. In fact, it is useful to evaluate as you go along so you don't spend hours researching one aspect of your topic only to find yourself more interested in another.

The main focus of an academic research paper is to develop a new argument, and a research paper will contain a literature review as one of its parts. In a research paper, you use the literature as a foundation and as support for a new insight that you contribute. The focus of a literature review, however, is to summarize and synthesize the arguments and ideas of others without adding new contributions.

For additional information, including suggestions for the structure of your literature review, see this guide from the University of North Carolina's Writing Center: https://writingcenter.unc.edu/handouts/literature-reviews/

This <10 minute tutorial from North Carolina State University also provides a good overview of the literature review: https://www.lib.ncsu.edu/tutorials/lit-review/

Finding Examples

While we don't have any examples of an EEB JP literature review, it may be useful to look at other reviews to learn how researchers in the field "summarize and synthesize" the literature. Any research article or dissertation in the sciences will include a section which reviews the literature. Though the section may not be labeled as such, you will quickly recognize it by the number of citations and the discussion of the literature. Another option is to look for Review Articles, which are literature reviews as a stand alone article. Here are some resources where you can find Research Articles, Review Articles and Dissertations:

• Web of Science - If you'd like to limit your results to Review Articles, look to the left side of your results page. There you will see many options to refine your search including the section labeled Document Types. Select "Review" as the document type and click on Refine.
• Scopus - Similar to WoS, you can use the options on the left side of your results page if you'd like to limit the document type. Here you will again choose "Review" and then click on the Limit To button.
• Annual Reviews   - All articles in this database are review articles. You can search for your topic or browse in a related subject area.
• Dissertations @ Princeton - Provides access to many Princeton dissertations, full text is available for most published after 1996.

*** Note about using Review Articles in your research - while they are useful in helping you to locate articles on your topic, remember that you must go to and use the original source if you intend to include a study mentioned in the review. The only time you would cite a review article is if they have made an original insight in their work that you talk about in your paper. Going to the original research paper allows you to verify the information about that study and determine whether the points made in the review are valid and accurate.

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How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

You can also search for this author in PubMed   Google Scholar

Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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doi: https://doi.org/10.1038/d41586-020-03422-x

Interviews have been edited for length and clarity.

Updates & Corrections

Correction 09 December 2020 : An earlier version of the tables in this article included some incorrect details about the programs Zotero, Endnote and Manubot. These have now been corrected.

Hsing, I.-M., Xu, Y. & Zhao, W. Electroanalysis 19 , 755–768 (2007).

Article   Google Scholar  

Ledesma, H. A. et al. Nature Nanotechnol. 14 , 645–657 (2019).

Article   PubMed   Google Scholar  

Brahlek, M., Koirala, N., Bansal, N. & Oh, S. Solid State Commun. 215–216 , 54–62 (2015).

Choi, Y. & Lee, S. Y. Nature Rev. Chem . https://doi.org/10.1038/s41570-020-00221-w (2020).

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7 Writing a Literature Review

Hundreds of original investigation research articles on health science topics are published each year. It is becoming harder and harder to keep on top of all new findings in a topic area and – more importantly – to work out how they all fit together to determine our current understanding of a topic. This is where literature reviews come in.

In this chapter, we explain what a literature review is and outline the stages involved in writing one. We also provide practical tips on how to communicate the results of a review of current literature on a topic in the format of a literature review.

7.1 What is a literature review?

Literature reviews provide a synthesis and evaluation  of the existing literature on a particular topic with the aim of gaining a new, deeper understanding of the topic.

Published literature reviews are typically written by scientists who are experts in that particular area of science. Usually, they will be widely published as authors of their own original work, making them highly qualified to author a literature review.

However, literature reviews are still subject to peer review before being published. Literature reviews provide an important bridge between the expert scientific community and many other communities, such as science journalists, teachers, and medical and allied health professionals. When the most up-to-date knowledge reaches such audiences, it is more likely that this information will find its way to the general public. When this happens, – the ultimate good of science can be realised.

A literature review is structured differently from an original research article. It is developed based on themes, rather than stages of the scientific method.

In the article Ten simple rules for writing a literature review , Marco Pautasso explains the importance of literature reviews:

Literature reviews are in great demand in most scientific fields. Their need stems from the ever-increasing output of scientific publications. For example, compared to 1991, in 2008 three, eight, and forty times more papers were indexed in Web of Science on malaria, obesity, and biodiversity, respectively. Given such mountains of papers, scientists cannot be expected to examine in detail every single new paper relevant to their interests. Thus, it is both advantageous and necessary to rely on regular summaries of the recent literature. Although recognition for scientists mainly comes from primary research, timely literature reviews can lead to new synthetic insights and are often widely read. For such summaries to be useful, however, they need to be compiled in a professional way (Pautasso, 2013, para. 1).

An example of a literature review is shown in Figure 7.1.

Video 7.1: What is a literature review? [2 mins, 11 secs]

Watch this video created by Steely Library at Northern Kentucky Library called ‘ What is a literature review? Note: Closed captions are available by clicking on the CC button below.

Examples of published literature reviews

• Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review
• Traveler’s diarrhea: a clinical review
• Cultural concepts of distress and psychiatric disorders: literature review and research recommendations for global mental health epidemiology

7.2 Steps of writing a literature review

Writing a literature review is a very challenging task. Figure 7.2 summarises the steps of writing a literature review. Depending on why you are writing your literature review, you may be given a topic area, or may choose a topic that particularly interests you or is related to a research project that you wish to undertake.

Chapter 6 provides instructions on finding scientific literature that would form the basis for your literature review.

Once you have your topic and have accessed the literature, the next stages (analysis, synthesis and evaluation) are challenging. Next, we look at these important cognitive skills student scientists will need to develop and employ to successfully write a literature review, and provide some guidance for navigating these stages.

Analysis, synthesis and evaluation

Analysis, synthesis and evaluation are three essential skills required by scientists  and you will need to develop these skills if you are to write a good literature review ( Figure 7.3 ). These important cognitive skills are discussed in more detail in Chapter 9.

The first step in writing a literature review is to analyse the original investigation research papers that you have gathered related to your topic.

Analysis requires examining the papers methodically and in detail, so you can understand and interpret aspects of the study described in each research article.

An analysis grid is a simple tool you can use to help with the careful examination and breakdown of each paper. This tool will allow you to create a concise summary of each research paper; see Table 7.1 for an example of  an analysis grid. When filling in the grid, the aim is to draw out key aspects of each research paper. Use a different row for each paper, and a different column for each aspect of the paper ( Tables 7.2 and 7.3 show how completed analysis grid may look).

Before completing your own grid, look at these examples and note the types of information that have been included, as well as the level of detail. Completing an analysis grid with a sufficient level of detail will help you to complete the synthesis and evaluation stages effectively. This grid will allow you to more easily observe similarities and differences across the findings of the research papers and to identify possible explanations (e.g., differences in methodologies employed) for observed differences between the findings of different research papers.

Table 7.1: Example of an analysis grid

Table 7.3: Sample filled-in analysis grid for research article by Ping and colleagues

Source: Ping, WC, Keong, CC & Bandyopadhyay, A 2010, ‘Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot and humid climate’, Indian Journal of Medical Research, vol. 132, pp. 36–41. Used under a CC-BY-NC-SA licence.

Step two of writing a literature review is synthesis.

Synthesis describes combining separate components or elements to form a connected whole.

You will use the results of your analysis to find themes to build your literature review around. Each of the themes identified will become a subheading within the body of your literature review.

A good place to start when identifying themes is with the dependent variables (results/findings) that were investigated in the research studies.

Because all of the research articles you are incorporating into your literature review are related to your topic, it is likely that they have similar study designs and have measured similar dependent variables. Review the ‘Results’ column of your analysis grid. You may like to collate the common themes in a synthesis grid (see, for example Table 7.4 ).

Step three of writing a literature review is evaluation, which can only be done after carefully analysing your research papers and synthesising the common themes (findings).

During the evaluation stage, you are making judgements on the themes presented in the research articles that you have read. This includes providing physiological explanations for the findings. It may be useful to refer to the discussion section of published original investigation research papers, or another literature review, where the authors may mention tested or hypothetical physiological mechanisms that may explain their findings.

When the findings of the investigations related to a particular theme are inconsistent (e.g., one study shows that caffeine effects performance and another study shows that caffeine had no effect on performance) you should attempt to provide explanations of why the results differ, including physiological explanations. A good place to start is by comparing the methodologies to determine if there are any differences that may explain the differences in the findings (see the ‘Experimental design’ column of your analysis grid). An example of evaluation is shown in the examples that follow in this section, under ‘Running performance’ and ‘RPE ratings’.

When the findings of the papers related to a particular theme are consistent (e.g., caffeine had no effect on oxygen uptake in both studies) an evaluation should include an explanation of why the results are similar. Once again, include physiological explanations. It is still a good idea to compare methodologies as a background to the evaluation. An example of evaluation is shown in the following under ‘Oxygen consumption’.

7.3 Writing your literature review

Once you have completed the analysis, and synthesis grids and written your evaluation of the research papers , you can combine synthesis and evaluation information to create a paragraph for a literature review ( Figure 7.4 ).

The following paragraphs are an example of combining the outcome of the synthesis and evaluation stages to produce a paragraph for a literature review.

Note that this is an example using only two papers – most literature reviews would be presenting information on many more papers than this ( (e.g., 106 papers in the review article by Bain and colleagues discussed later in this chapter). However, the same principle applies regardless of the number of papers reviewed.

The next part of this chapter looks at the each section of a literature review and explains how to write them by referring to a review article that was published in Frontiers in Physiology and shown in Figure 7.1. Each section from the published article is annotated to highlight important features of the format of the review article, and identifies the synthesis and evaluation information.

In the examination of each review article section we will point out examples of how the authors have presented certain information and where they display application of important cognitive processes; we will use the colour code shown below:

This should be one paragraph that accurately reflects the contents of the review article.

Introduction

The introduction should establish the context and importance of the review

Body of literature review

The reference section provides a list of the references that you cited in the body of your review article. The format will depend on the journal of publication as each journal has their own specific referencing format.

It is important to accurately cite references in research papers to acknowledge your sources and ensure credit is appropriately given to authors of work you have referred to. An accurate and comprehensive reference list also shows your readers that you are well-read in your topic area and are aware of the key papers that provide the context to your research.

It is important to keep track of your resources and to reference them consistently in the format required by the publication in which your work will appear. Most scientists will use reference management software to store details of all of the journal articles (and other sources) they use while writing their review article. This software also automates the process of adding in-text references and creating a reference list. In the review article by Bain et al. (2014) used as an example in this chapter, the reference list contains 106 items, so you can imagine how much help referencing software would be. Chapter 5 shows you how to use EndNote, one example of reference management software.

Click the drop down below to review the terms learned from this chapter.

Copyright note:

• The quotation from Pautasso, M 2013, ‘Ten simple rules for writing a literature review’, PLoS Computational Biology is use under a CC-BY licence. 
• Content from the annotated article and tables are based on Schubert, MM, Astorino, TA & Azevedo, JJL 2013, ‘The effects of caffeinated ‘energy shots’ on time trial performance’, Nutrients, vol. 5, no. 6, pp. 2062–2075 (used under a CC-BY 3.0 licence ) and P ing, WC, Keong , CC & Bandyopadhyay, A 2010, ‘Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot and humid climate’, Indian Journal of Medical Research, vol. 132, pp. 36–41 (used under a CC-BY-NC-SA 4.0 licence ). 

Bain, A.R., Morrison, S.A., & Ainslie, P.N. (2014). Cerebral oxygenation and hyperthermia. Frontiers in Physiology, 5 , 92.

Pautasso, M. (2013). Ten simple rules for writing a literature review. PLoS Computational Biology, 9 (7), e1003149.

How To Do Science Copyright © 2022 by University of Southern Queensland is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License , except where otherwise noted.

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Literature Reviews, Theoretical Frameworks, and Conceptual Frameworks: An Introduction for New Biology Education Researchers

Julie a. luft.

† Department of Mathematics, Social Studies, and Science Education, Mary Frances Early College of Education, University of Georgia, Athens, GA 30602-7124

Sophia Jeong

‡ Department of Teaching & Learning, College of Education & Human Ecology, Ohio State University, Columbus, OH 43210

Robert Idsardi

§ Department of Biology, Eastern Washington University, Cheney, WA 99004

Grant Gardner

∥ Department of Biology, Middle Tennessee State University, Murfreesboro, TN 37132

Associated Data

To frame their work, biology education researchers need to consider the role of literature reviews, theoretical frameworks, and conceptual frameworks as critical elements of the research and writing process. However, these elements can be confusing for scholars new to education research. This Research Methods article is designed to provide an overview of each of these elements and delineate the purpose of each in the educational research process. We describe what biology education researchers should consider as they conduct literature reviews, identify theoretical frameworks, and construct conceptual frameworks. Clarifying these different components of educational research studies can be helpful to new biology education researchers and the biology education research community at large in situating their work in the broader scholarly literature.

INTRODUCTION

Discipline-based education research (DBER) involves the purposeful and situated study of teaching and learning in specific disciplinary areas ( Singer et al. , 2012 ). Studies in DBER are guided by research questions that reflect disciplines’ priorities and worldviews. Researchers can use quantitative data, qualitative data, or both to answer these research questions through a variety of methodological traditions. Across all methodologies, there are different methods associated with planning and conducting educational research studies that include the use of surveys, interviews, observations, artifacts, or instruments. Ensuring the coherence of these elements to the discipline’s perspective also involves situating the work in the broader scholarly literature. The tools for doing this include literature reviews, theoretical frameworks, and conceptual frameworks. However, the purpose and function of each of these elements is often confusing to new education researchers. The goal of this article is to introduce new biology education researchers to these three important elements important in DBER scholarship and the broader educational literature.

The first element we discuss is a review of research (literature reviews), which highlights the need for a specific research question, study problem, or topic of investigation. Literature reviews situate the relevance of the study within a topic and a field. The process may seem familiar to science researchers entering DBER fields, but new researchers may still struggle in conducting the review. Booth et al. (2016b) highlight some of the challenges novice education researchers face when conducting a review of literature. They point out that novice researchers struggle in deciding how to focus the review, determining the scope of articles needed in the review, and knowing how to be critical of the articles in the review. Overcoming these challenges (and others) can help novice researchers construct a sound literature review that can inform the design of the study and help ensure the work makes a contribution to the field.

The second and third highlighted elements are theoretical and conceptual frameworks. These guide biology education research (BER) studies, and may be less familiar to science researchers. These elements are important in shaping the construction of new knowledge. Theoretical frameworks offer a way to explain and interpret the studied phenomenon, while conceptual frameworks clarify assumptions about the studied phenomenon. Despite the importance of these constructs in educational research, biology educational researchers have noted the limited use of theoretical or conceptual frameworks in published work ( DeHaan, 2011 ; Dirks, 2011 ; Lo et al. , 2019 ). In reviewing articles published in CBE—Life Sciences Education ( LSE ) between 2015 and 2019, we found that fewer than 25% of the research articles had a theoretical or conceptual framework (see the Supplemental Information), and at times there was an inconsistent use of theoretical and conceptual frameworks. Clearly, these frameworks are challenging for published biology education researchers, which suggests the importance of providing some initial guidance to new biology education researchers.

Fortunately, educational researchers have increased their explicit use of these frameworks over time, and this is influencing educational research in science, technology, engineering, and mathematics (STEM) fields. For instance, a quick search for theoretical or conceptual frameworks in the abstracts of articles in Educational Research Complete (a common database for educational research) in STEM fields demonstrates a dramatic change over the last 20 years: from only 778 articles published between 2000 and 2010 to 5703 articles published between 2010 and 2020, a more than sevenfold increase. Greater recognition of the importance of these frameworks is contributing to DBER authors being more explicit about such frameworks in their studies.

Collectively, literature reviews, theoretical frameworks, and conceptual frameworks work to guide methodological decisions and the elucidation of important findings. Each offers a different perspective on the problem of study and is an essential element in all forms of educational research. As new researchers seek to learn about these elements, they will find different resources, a variety of perspectives, and many suggestions about the construction and use of these elements. The wide range of available information can overwhelm the new researcher who just wants to learn the distinction between these elements or how to craft them adequately.

Our goal in writing this paper is not to offer specific advice about how to write these sections in scholarly work. Instead, we wanted to introduce these elements to those who are new to BER and who are interested in better distinguishing one from the other. In this paper, we share the purpose of each element in BER scholarship, along with important points on its construction. We also provide references for additional resources that may be beneficial to better understanding each element. Table 1 summarizes the key distinctions among these elements.

Comparison of literature reviews, theoretical frameworks, and conceptual reviews

This article is written for the new biology education researcher who is just learning about these different elements or for scientists looking to become more involved in BER. It is a result of our own work as science education and biology education researchers, whether as graduate students and postdoctoral scholars or newly hired and established faculty members. This is the article we wish had been available as we started to learn about these elements or discussed them with new educational researchers in biology.

LITERATURE REVIEWS

Purpose of a literature review.

A literature review is foundational to any research study in education or science. In education, a well-conceptualized and well-executed review provides a summary of the research that has already been done on a specific topic and identifies questions that remain to be answered, thus illustrating the current research project’s potential contribution to the field and the reasoning behind the methodological approach selected for the study ( Maxwell, 2012 ). BER is an evolving disciplinary area that is redefining areas of conceptual emphasis as well as orientations toward teaching and learning (e.g., Labov et al. , 2010 ; American Association for the Advancement of Science, 2011 ; Nehm, 2019 ). As a result, building comprehensive, critical, purposeful, and concise literature reviews can be a challenge for new biology education researchers.

Building Literature Reviews

There are different ways to approach and construct a literature review. Booth et al. (2016a) provide an overview that includes, for example, scoping reviews, which are focused only on notable studies and use a basic method of analysis, and integrative reviews, which are the result of exhaustive literature searches across different genres. Underlying each of these different review processes are attention to the s earch process, a ppraisa l of articles, s ynthesis of the literature, and a nalysis: SALSA ( Booth et al. , 2016a ). This useful acronym can help the researcher focus on the process while building a specific type of review.

However, new educational researchers often have questions about literature reviews that are foundational to SALSA or other approaches. Common questions concern determining which literature pertains to the topic of study or the role of the literature review in the design of the study. This section addresses such questions broadly while providing general guidance for writing a narrative literature review that evaluates the most pertinent studies.

The literature review process should begin before the research is conducted. As Boote and Beile (2005 , p. 3) suggested, researchers should be “scholars before researchers.” They point out that having a good working knowledge of the proposed topic helps illuminate avenues of study. Some subject areas have a deep body of work to read and reflect upon, providing a strong foundation for developing the research question(s). For instance, the teaching and learning of evolution is an area of long-standing interest in the BER community, generating many studies (e.g., Perry et al. , 2008 ; Barnes and Brownell, 2016 ) and reviews of research (e.g., Sickel and Friedrichsen, 2013 ; Ziadie and Andrews, 2018 ). Emerging areas of BER include the affective domain, issues of transfer, and metacognition ( Singer et al. , 2012 ). Many studies in these areas are transdisciplinary and not always specific to biology education (e.g., Rodrigo-Peiris et al. , 2018 ; Kolpikova et al. , 2019 ). These newer areas may require reading outside BER; fortunately, summaries of some of these topics can be found in the Current Insights section of the LSE website.

In focusing on a specific problem within a broader research strand, a new researcher will likely need to examine research outside BER. Depending upon the area of study, the expanded reading list might involve a mix of BER, DBER, and educational research studies. Determining the scope of the reading is not always straightforward. A simple way to focus one’s reading is to create a “summary phrase” or “research nugget,” which is a very brief descriptive statement about the study. It should focus on the essence of the study, for example, “first-year nonmajor students’ understanding of evolution,” “metacognitive prompts to enhance learning during biochemistry,” or “instructors’ inquiry-based instructional practices after professional development programming.” This type of phrase should help a new researcher identify two or more areas to review that pertain to the study. Focusing on recent research in the last 5 years is a good first step. Additional studies can be identified by reading relevant works referenced in those articles. It is also important to read seminal studies that are more than 5 years old. Reading a range of studies should give the researcher the necessary command of the subject in order to suggest a research question.

Given that the research question(s) arise from the literature review, the review should also substantiate the selected methodological approach. The review and research question(s) guide the researcher in determining how to collect and analyze data. Often the methodological approach used in a study is selected to contribute knowledge that expands upon what has been published previously about the topic (see Institute of Education Sciences and National Science Foundation, 2013 ). An emerging topic of study may need an exploratory approach that allows for a description of the phenomenon and development of a potential theory. This could, but not necessarily, require a methodological approach that uses interviews, observations, surveys, or other instruments. An extensively studied topic may call for the additional understanding of specific factors or variables; this type of study would be well suited to a verification or a causal research design. These could entail a methodological approach that uses valid and reliable instruments, observations, or interviews to determine an effect in the studied event. In either of these examples, the researcher(s) may use a qualitative, quantitative, or mixed methods methodological approach.

Even with a good research question, there is still more reading to be done. The complexity and focus of the research question dictates the depth and breadth of the literature to be examined. Questions that connect multiple topics can require broad literature reviews. For instance, a study that explores the impact of a biology faculty learning community on the inquiry instruction of faculty could have the following review areas: learning communities among biology faculty, inquiry instruction among biology faculty, and inquiry instruction among biology faculty as a result of professional learning. Biology education researchers need to consider whether their literature review requires studies from different disciplines within or outside DBER. For the example given, it would be fruitful to look at research focused on learning communities with faculty in STEM fields or in general education fields that result in instructional change. It is important not to be too narrow or too broad when reading. When the conclusions of articles start to sound similar or no new insights are gained, the researcher likely has a good foundation for a literature review. This level of reading should allow the researcher to demonstrate a mastery in understanding the researched topic, explain the suitability of the proposed research approach, and point to the need for the refined research question(s).

The literature review should include the researcher’s evaluation and critique of the selected studies. A researcher may have a large collection of studies, but not all of the studies will follow standards important in the reporting of empirical work in the social sciences. The American Educational Research Association ( Duran et al. , 2006 ), for example, offers a general discussion about standards for such work: an adequate review of research informing the study, the existence of sound and appropriate data collection and analysis methods, and appropriate conclusions that do not overstep or underexplore the analyzed data. The Institute of Education Sciences and National Science Foundation (2013) also offer Common Guidelines for Education Research and Development that can be used to evaluate collected studies.

Because not all journals adhere to such standards, it is important that a researcher review each study to determine the quality of published research, per the guidelines suggested earlier. In some instances, the research may be fatally flawed. Examples of such flaws include data that do not pertain to the question, a lack of discussion about the data collection, poorly constructed instruments, or an inadequate analysis. These types of errors result in studies that are incomplete, error-laden, or inaccurate and should be excluded from the review. Most studies have limitations, and the author(s) often make them explicit. For instance, there may be an instructor effect, recognized bias in the analysis, or issues with the sample population. Limitations are usually addressed by the research team in some way to ensure a sound and acceptable research process. Occasionally, the limitations associated with the study can be significant and not addressed adequately, which leaves a consequential decision in the hands of the researcher. Providing critiques of studies in the literature review process gives the reader confidence that the researcher has carefully examined relevant work in preparation for the study and, ultimately, the manuscript.

A solid literature review clearly anchors the proposed study in the field and connects the research question(s), the methodological approach, and the discussion. Reviewing extant research leads to research questions that will contribute to what is known in the field. By summarizing what is known, the literature review points to what needs to be known, which in turn guides decisions about methodology. Finally, notable findings of the new study are discussed in reference to those described in the literature review.

Within published BER studies, literature reviews can be placed in different locations in an article. When included in the introductory section of the study, the first few paragraphs of the manuscript set the stage, with the literature review following the opening paragraphs. Cooper et al. (2019) illustrate this approach in their study of course-based undergraduate research experiences (CUREs). An introduction discussing the potential of CURES is followed by an analysis of the existing literature relevant to the design of CUREs that allows for novel student discoveries. Within this review, the authors point out contradictory findings among research on novel student discoveries. This clarifies the need for their study, which is described and highlighted through specific research aims.

A literature reviews can also make up a separate section in a paper. For example, the introduction to Todd et al. (2019) illustrates the need for their research topic by highlighting the potential of learning progressions (LPs) and suggesting that LPs may help mitigate learning loss in genetics. At the end of the introduction, the authors state their specific research questions. The review of literature following this opening section comprises two subsections. One focuses on learning loss in general and examines a variety of studies and meta-analyses from the disciplines of medical education, mathematics, and reading. The second section focuses specifically on LPs in genetics and highlights student learning in the midst of LPs. These separate reviews provide insights into the stated research question.

Suggestions and Advice

A well-conceptualized, comprehensive, and critical literature review reveals the understanding of the topic that the researcher brings to the study. Literature reviews should not be so big that there is no clear area of focus; nor should they be so narrow that no real research question arises. The task for a researcher is to craft an efficient literature review that offers a critical analysis of published work, articulates the need for the study, guides the methodological approach to the topic of study, and provides an adequate foundation for the discussion of the findings.

In our own writing of literature reviews, there are often many drafts. An early draft may seem well suited to the study because the need for and approach to the study are well described. However, as the results of the study are analyzed and findings begin to emerge, the existing literature review may be inadequate and need revision. The need for an expanded discussion about the research area can result in the inclusion of new studies that support the explanation of a potential finding. The literature review may also prove to be too broad. Refocusing on a specific area allows for more contemplation of a finding.

It should be noted that there are different types of literature reviews, and many books and articles have been written about the different ways to embark on these types of reviews. Among these different resources, the following may be helpful in considering how to refine the review process for scholarly journals:

• Booth, A., Sutton, A., & Papaioannou, D. (2016a). Systemic approaches to a successful literature review (2nd ed.). Los Angeles, CA: Sage. This book addresses different types of literature reviews and offers important suggestions pertaining to defining the scope of the literature review and assessing extant studies.
• Booth, W. C., Colomb, G. G., Williams, J. M., Bizup, J., & Fitzgerald, W. T. (2016b). The craft of research (4th ed.). Chicago: University of Chicago Press. This book can help the novice consider how to make the case for an area of study. While this book is not specifically about literature reviews, it offers suggestions about making the case for your study.
• Galvan, J. L., & Galvan, M. C. (2017). Writing literature reviews: A guide for students of the social and behavioral sciences (7th ed.). Routledge. This book offers guidance on writing different types of literature reviews. For the novice researcher, there are useful suggestions for creating coherent literature reviews.

THEORETICAL FRAMEWORKS

Purpose of theoretical frameworks.

As new education researchers may be less familiar with theoretical frameworks than with literature reviews, this discussion begins with an analogy. Envision a biologist, chemist, and physicist examining together the dramatic effect of a fog tsunami over the ocean. A biologist gazing at this phenomenon may be concerned with the effect of fog on various species. A chemist may be interested in the chemical composition of the fog as water vapor condenses around bits of salt. A physicist may be focused on the refraction of light to make fog appear to be “sitting” above the ocean. While observing the same “objective event,” the scientists are operating under different theoretical frameworks that provide a particular perspective or “lens” for the interpretation of the phenomenon. Each of these scientists brings specialized knowledge, experiences, and values to this phenomenon, and these influence the interpretation of the phenomenon. The scientists’ theoretical frameworks influence how they design and carry out their studies and interpret their data.

Within an educational study, a theoretical framework helps to explain a phenomenon through a particular lens and challenges and extends existing knowledge within the limitations of that lens. Theoretical frameworks are explicitly stated by an educational researcher in the paper’s framework, theory, or relevant literature section. The framework shapes the types of questions asked, guides the method by which data are collected and analyzed, and informs the discussion of the results of the study. It also reveals the researcher’s subjectivities, for example, values, social experience, and viewpoint ( Allen, 2017 ). It is essential that a novice researcher learn to explicitly state a theoretical framework, because all research questions are being asked from the researcher’s implicit or explicit assumptions of a phenomenon of interest ( Schwandt, 2000 ).

Selecting Theoretical Frameworks

Theoretical frameworks are one of the most contemplated elements in our work in educational research. In this section, we share three important considerations for new scholars selecting a theoretical framework.

The first step in identifying a theoretical framework involves reflecting on the phenomenon within the study and the assumptions aligned with the phenomenon. The phenomenon involves the studied event. There are many possibilities, for example, student learning, instructional approach, or group organization. A researcher holds assumptions about how the phenomenon will be effected, influenced, changed, or portrayed. It is ultimately the researcher’s assumption(s) about the phenomenon that aligns with a theoretical framework. An example can help illustrate how a researcher’s reflection on the phenomenon and acknowledgment of assumptions can result in the identification of a theoretical framework.

In our example, a biology education researcher may be interested in exploring how students’ learning of difficult biological concepts can be supported by the interactions of group members. The phenomenon of interest is the interactions among the peers, and the researcher assumes that more knowledgeable students are important in supporting the learning of the group. As a result, the researcher may draw on Vygotsky’s (1978) sociocultural theory of learning and development that is focused on the phenomenon of student learning in a social setting. This theory posits the critical nature of interactions among students and between students and teachers in the process of building knowledge. A researcher drawing upon this framework holds the assumption that learning is a dynamic social process involving questions and explanations among students in the classroom and that more knowledgeable peers play an important part in the process of building conceptual knowledge.

It is important to state at this point that there are many different theoretical frameworks. Some frameworks focus on learning and knowing, while other theoretical frameworks focus on equity, empowerment, or discourse. Some frameworks are well articulated, and others are still being refined. For a new researcher, it can be challenging to find a theoretical framework. Two of the best ways to look for theoretical frameworks is through published works that highlight different frameworks.

When a theoretical framework is selected, it should clearly connect to all parts of the study. The framework should augment the study by adding a perspective that provides greater insights into the phenomenon. It should clearly align with the studies described in the literature review. For instance, a framework focused on learning would correspond to research that reported different learning outcomes for similar studies. The methods for data collection and analysis should also correspond to the framework. For instance, a study about instructional interventions could use a theoretical framework concerned with learning and could collect data about the effect of the intervention on what is learned. When the data are analyzed, the theoretical framework should provide added meaning to the findings, and the findings should align with the theoretical framework.

A study by Jensen and Lawson (2011) provides an example of how a theoretical framework connects different parts of the study. They compared undergraduate biology students in heterogeneous and homogeneous groups over the course of a semester. Jensen and Lawson (2011) assumed that learning involved collaboration and more knowledgeable peers, which made Vygotsky’s (1978) theory a good fit for their study. They predicted that students in heterogeneous groups would experience greater improvement in their reasoning abilities and science achievements with much of the learning guided by the more knowledgeable peers.

In the enactment of the study, they collected data about the instruction in traditional and inquiry-oriented classes, while the students worked in homogeneous or heterogeneous groups. To determine the effect of working in groups, the authors also measured students’ reasoning abilities and achievement. Each data-collection and analysis decision connected to understanding the influence of collaborative work.

Their findings highlighted aspects of Vygotsky’s (1978) theory of learning. One finding, for instance, posited that inquiry instruction, as a whole, resulted in reasoning and achievement gains. This links to Vygotsky (1978) , because inquiry instruction involves interactions among group members. A more nuanced finding was that group composition had a conditional effect. Heterogeneous groups performed better with more traditional and didactic instruction, regardless of the reasoning ability of the group members. Homogeneous groups worked better during interaction-rich activities for students with low reasoning ability. The authors attributed the variation to the different types of helping behaviors of students. High-performing students provided the answers, while students with low reasoning ability had to work collectively through the material. In terms of Vygotsky (1978) , this finding provided new insights into the learning context in which productive interactions can occur for students.

Another consideration in the selection and use of a theoretical framework pertains to its orientation to the study. This can result in the theoretical framework prioritizing individuals, institutions, and/or policies ( Anfara and Mertz, 2014 ). Frameworks that connect to individuals, for instance, could contribute to understanding their actions, learning, or knowledge. Institutional frameworks, on the other hand, offer insights into how institutions, organizations, or groups can influence individuals or materials. Policy theories provide ways to understand how national or local policies can dictate an emphasis on outcomes or instructional design. These different types of frameworks highlight different aspects in an educational setting, which influences the design of the study and the collection of data. In addition, these different frameworks offer a way to make sense of the data. Aligning the data collection and analysis with the framework ensures that a study is coherent and can contribute to the field.

New understandings emerge when different theoretical frameworks are used. For instance, Ebert-May et al. (2015) prioritized the individual level within conceptual change theory (see Posner et al. , 1982 ). In this theory, an individual’s knowledge changes when it no longer fits the phenomenon. Ebert-May et al. (2015) designed a professional development program challenging biology postdoctoral scholars’ existing conceptions of teaching. The authors reported that the biology postdoctoral scholars’ teaching practices became more student-centered as they were challenged to explain their instructional decision making. According to the theory, the biology postdoctoral scholars’ dissatisfaction in their descriptions of teaching and learning initiated change in their knowledge and instruction. These results reveal how conceptual change theory can explain the learning of participants and guide the design of professional development programming.

The communities of practice (CoP) theoretical framework ( Lave, 1988 ; Wenger, 1998 ) prioritizes the institutional level , suggesting that learning occurs when individuals learn from and contribute to the communities in which they reside. Grounded in the assumption of community learning, the literature on CoP suggests that, as individuals interact regularly with the other members of their group, they learn about the rules, roles, and goals of the community ( Allee, 2000 ). A study conducted by Gehrke and Kezar (2017) used the CoP framework to understand organizational change by examining the involvement of individual faculty engaged in a cross-institutional CoP focused on changing the instructional practice of faculty at each institution. In the CoP, faculty members were involved in enhancing instructional materials within their department, which aligned with an overarching goal of instituting instruction that embraced active learning. Not surprisingly, Gehrke and Kezar (2017) revealed that faculty who perceived the community culture as important in their work cultivated institutional change. Furthermore, they found that institutional change was sustained when key leaders served as mentors and provided support for faculty, and as faculty themselves developed into leaders. This study reveals the complexity of individual roles in a COP in order to support institutional instructional change.

It is important to explicitly state the theoretical framework used in a study, but elucidating a theoretical framework can be challenging for a new educational researcher. The literature review can help to identify an applicable theoretical framework. Focal areas of the review or central terms often connect to assumptions and assertions associated with the framework that pertain to the phenomenon of interest. Another way to identify a theoretical framework is self-reflection by the researcher on personal beliefs and understandings about the nature of knowledge the researcher brings to the study ( Lysaght, 2011 ). In stating one’s beliefs and understandings related to the study (e.g., students construct their knowledge, instructional materials support learning), an orientation becomes evident that will suggest a particular theoretical framework. Theoretical frameworks are not arbitrary , but purposefully selected.

With experience, a researcher may find expanded roles for theoretical frameworks. Researchers may revise an existing framework that has limited explanatory power, or they may decide there is a need to develop a new theoretical framework. These frameworks can emerge from a current study or the need to explain a phenomenon in a new way. Researchers may also find that multiple theoretical frameworks are necessary to frame and explore a problem, as different frameworks can provide different insights into a problem.

Finally, it is important to recognize that choosing “x” theoretical framework does not necessarily mean a researcher chooses “y” methodology and so on, nor is there a clear-cut, linear process in selecting a theoretical framework for one’s study. In part, the nonlinear process of identifying a theoretical framework is what makes understanding and using theoretical frameworks challenging. For the novice scholar, contemplating and understanding theoretical frameworks is essential. Fortunately, there are articles and books that can help:

• Creswell, J. W. (2018). Research design: Qualitative, quantitative, and mixed methods approaches (5th ed.). Los Angeles, CA: Sage. This book provides an overview of theoretical frameworks in general educational research.
• Ding, L. (2019). Theoretical perspectives of quantitative physics education research. Physical Review Physics Education Research , 15 (2), 020101-1–020101-13. This paper illustrates how a DBER field can use theoretical frameworks.
• Nehm, R. (2019). Biology education research: Building integrative frameworks for teaching and learning about living systems. Disciplinary and Interdisciplinary Science Education Research , 1 , ar15. https://doi.org/10.1186/s43031-019-0017-6 . This paper articulates the need for studies in BER to explicitly state theoretical frameworks and provides examples of potential studies.
• Patton, M. Q. (2015). Qualitative research & evaluation methods: Integrating theory and practice . Sage. This book also provides an overview of theoretical frameworks, but for both research and evaluation.

CONCEPTUAL FRAMEWORKS

Purpose of a conceptual framework.

A conceptual framework is a description of the way a researcher understands the factors and/or variables that are involved in the study and their relationships to one another. The purpose of a conceptual framework is to articulate the concepts under study using relevant literature ( Rocco and Plakhotnik, 2009 ) and to clarify the presumed relationships among those concepts ( Rocco and Plakhotnik, 2009 ; Anfara and Mertz, 2014 ). Conceptual frameworks are different from theoretical frameworks in both their breadth and grounding in established findings. Whereas a theoretical framework articulates the lens through which a researcher views the work, the conceptual framework is often more mechanistic and malleable.

Conceptual frameworks are broader, encompassing both established theories (i.e., theoretical frameworks) and the researchers’ own emergent ideas. Emergent ideas, for example, may be rooted in informal and/or unpublished observations from experience. These emergent ideas would not be considered a “theory” if they are not yet tested, supported by systematically collected evidence, and peer reviewed. However, they do still play an important role in the way researchers approach their studies. The conceptual framework allows authors to clearly describe their emergent ideas so that connections among ideas in the study and the significance of the study are apparent to readers.

Constructing Conceptual Frameworks

Including a conceptual framework in a research study is important, but researchers often opt to include either a conceptual or a theoretical framework. Either may be adequate, but both provide greater insight into the research approach. For instance, a research team plans to test a novel component of an existing theory. In their study, they describe the existing theoretical framework that informs their work and then present their own conceptual framework. Within this conceptual framework, specific topics portray emergent ideas that are related to the theory. Describing both frameworks allows readers to better understand the researchers’ assumptions, orientations, and understanding of concepts being investigated. For example, Connolly et al. (2018) included a conceptual framework that described how they applied a theoretical framework of social cognitive career theory (SCCT) to their study on teaching programs for doctoral students. In their conceptual framework, the authors described SCCT, explained how it applied to the investigation, and drew upon results from previous studies to justify the proposed connections between the theory and their emergent ideas.

In some cases, authors may be able to sufficiently describe their conceptualization of the phenomenon under study in an introduction alone, without a separate conceptual framework section. However, incomplete descriptions of how the researchers conceptualize the components of the study may limit the significance of the study by making the research less intelligible to readers. This is especially problematic when studying topics in which researchers use the same terms for different constructs or different terms for similar and overlapping constructs (e.g., inquiry, teacher beliefs, pedagogical content knowledge, or active learning). Authors must describe their conceptualization of a construct if the research is to be understandable and useful.

There are some key areas to consider regarding the inclusion of a conceptual framework in a study. To begin with, it is important to recognize that conceptual frameworks are constructed by the researchers conducting the study ( Rocco and Plakhotnik, 2009 ; Maxwell, 2012 ). This is different from theoretical frameworks that are often taken from established literature. Researchers should bring together ideas from the literature, but they may be influenced by their own experiences as a student and/or instructor, the shared experiences of others, or thought experiments as they construct a description, model, or representation of their understanding of the phenomenon under study. This is an exercise in intellectual organization and clarity that often considers what is learned, known, and experienced. The conceptual framework makes these constructs explicitly visible to readers, who may have different understandings of the phenomenon based on their prior knowledge and experience. There is no single method to go about this intellectual work.

Reeves et al. (2016) is an example of an article that proposed a conceptual framework about graduate teaching assistant professional development evaluation and research. The authors used existing literature to create a novel framework that filled a gap in current research and practice related to the training of graduate teaching assistants. This conceptual framework can guide the systematic collection of data by other researchers because the framework describes the relationships among various factors that influence teaching and learning. The Reeves et al. (2016) conceptual framework may be modified as additional data are collected and analyzed by other researchers. This is not uncommon, as conceptual frameworks can serve as catalysts for concerted research efforts that systematically explore a phenomenon (e.g., Reynolds et al. , 2012 ; Brownell and Kloser, 2015 ).

Sabel et al. (2017) used a conceptual framework in their exploration of how scaffolds, an external factor, interact with internal factors to support student learning. Their conceptual framework integrated principles from two theoretical frameworks, self-regulated learning and metacognition, to illustrate how the research team conceptualized students’ use of scaffolds in their learning ( Figure 1 ). Sabel et al. (2017) created this model using their interpretations of these two frameworks in the context of their teaching.

Conceptual framework from Sabel et al. (2017) .

A conceptual framework should describe the relationship among components of the investigation ( Anfara and Mertz, 2014 ). These relationships should guide the researcher’s methods of approaching the study ( Miles et al. , 2014 ) and inform both the data to be collected and how those data should be analyzed. Explicitly describing the connections among the ideas allows the researcher to justify the importance of the study and the rigor of the research design. Just as importantly, these frameworks help readers understand why certain components of a system were not explored in the study. This is a challenge in education research, which is rooted in complex environments with many variables that are difficult to control.

For example, Sabel et al. (2017) stated: “Scaffolds, such as enhanced answer keys and reflection questions, can help students and instructors bridge the external and internal factors and support learning” (p. 3). They connected the scaffolds in the study to the three dimensions of metacognition and the eventual transformation of existing ideas into new or revised ideas. Their framework provides a rationale for focusing on how students use two different scaffolds, and not on other factors that may influence a student’s success (self-efficacy, use of active learning, exam format, etc.).

In constructing conceptual frameworks, researchers should address needed areas of study and/or contradictions discovered in literature reviews. By attending to these areas, researchers can strengthen their arguments for the importance of a study. For instance, conceptual frameworks can address how the current study will fill gaps in the research, resolve contradictions in existing literature, or suggest a new area of study. While a literature review describes what is known and not known about the phenomenon, the conceptual framework leverages these gaps in describing the current study ( Maxwell, 2012 ). In the example of Sabel et al. (2017) , the authors indicated there was a gap in the literature regarding how scaffolds engage students in metacognition to promote learning in large classes. Their study helps fill that gap by describing how scaffolds can support students in the three dimensions of metacognition: intelligibility, plausibility, and wide applicability. In another example, Lane (2016) integrated research from science identity, the ethic of care, the sense of belonging, and an expertise model of student success to form a conceptual framework that addressed the critiques of other frameworks. In a more recent example, Sbeglia et al. (2021) illustrated how a conceptual framework influences the methodological choices and inferences in studies by educational researchers.

Sometimes researchers draw upon the conceptual frameworks of other researchers. When a researcher’s conceptual framework closely aligns with an existing framework, the discussion may be brief. For example, Ghee et al. (2016) referred to portions of SCCT as their conceptual framework to explain the significance of their work on students’ self-efficacy and career interests. Because the authors’ conceptualization of this phenomenon aligned with a previously described framework, they briefly mentioned the conceptual framework and provided additional citations that provided more detail for the readers.

Within both the BER and the broader DBER communities, conceptual frameworks have been used to describe different constructs. For example, some researchers have used the term “conceptual framework” to describe students’ conceptual understandings of a biological phenomenon. This is distinct from a researcher’s conceptual framework of the educational phenomenon under investigation, which may also need to be explicitly described in the article. Other studies have presented a research logic model or flowchart of the research design as a conceptual framework. These constructions can be quite valuable in helping readers understand the data-collection and analysis process. However, a model depicting the study design does not serve the same role as a conceptual framework. Researchers need to avoid conflating these constructs by differentiating the researchers’ conceptual framework that guides the study from the research design, when applicable.

Explicitly describing conceptual frameworks is essential in depicting the focus of the study. We have found that being explicit in a conceptual framework means using accepted terminology, referencing prior work, and clearly noting connections between terms. This description can also highlight gaps in the literature or suggest potential contributions to the field of study. A well-elucidated conceptual framework can suggest additional studies that may be warranted. This can also spur other researchers to consider how they would approach the examination of a phenomenon and could result in a revised conceptual framework.

It can be challenging to create conceptual frameworks, but they are important. Below are two resources that could be helpful in constructing and presenting conceptual frameworks in educational research:

• Maxwell, J. A. (2012). Qualitative research design: An interactive approach (3rd ed.). Los Angeles, CA: Sage. Chapter 3 in this book describes how to construct conceptual frameworks.
• Ravitch, S. M., & Riggan, M. (2016). Reason & rigor: How conceptual frameworks guide research . Los Angeles, CA: Sage. This book explains how conceptual frameworks guide the research questions, data collection, data analyses, and interpretation of results.

CONCLUDING THOUGHTS

Literature reviews, theoretical frameworks, and conceptual frameworks are all important in DBER and BER. Robust literature reviews reinforce the importance of a study. Theoretical frameworks connect the study to the base of knowledge in educational theory and specify the researcher’s assumptions. Conceptual frameworks allow researchers to explicitly describe their conceptualization of the relationships among the components of the phenomenon under study. Table 1 provides a general overview of these components in order to assist biology education researchers in thinking about these elements.

It is important to emphasize that these different elements are intertwined. When these elements are aligned and complement one another, the study is coherent, and the study findings contribute to knowledge in the field. When literature reviews, theoretical frameworks, and conceptual frameworks are disconnected from one another, the study suffers. The point of the study is lost, suggested findings are unsupported, or important conclusions are invisible to the researcher. In addition, this misalignment may be costly in terms of time and money.

Conducting a literature review, selecting a theoretical framework, and building a conceptual framework are some of the most difficult elements of a research study. It takes time to understand the relevant research, identify a theoretical framework that provides important insights into the study, and formulate a conceptual framework that organizes the finding. In the research process, there is often a constant back and forth among these elements as the study evolves. With an ongoing refinement of the review of literature, clarification of the theoretical framework, and articulation of a conceptual framework, a sound study can emerge that makes a contribution to the field. This is the goal of BER and education research.

Supplementary Material

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What is a Literature Review?

Literature review video.

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In Research Articles 

What is a literature review? Rather than describing original research results, literature reviews summarize the research on a particular topic by synthesizing information from many primary sources.

Why should I read literature reviews? Review articles can be helpful for gathering background information and identifying key articles in a particular field.

How can I find a literature review? Many library databases, including Scopus, Web of Science, and PubMed, allow you to filter search results to include only "review articles" or "literature reviews."  

For Class Assignments 

In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research.

Source: The Writing Lab & The OWL at Purdue. (n/a). What is a literature review? Purdue University.  Writing a Literature Review // Purdue Writing Lab

• Writing a Literature Review - Purdue OWL A great place to learn more about Literature Reviews to help you write a literature. Consult Purdue OWL.

To better understand what is a literature review, watch the video from the NC State University Libraries. 

Watch  Literature Reviews: An Overview for Graduate Students  00:09:37

Source: NC State University Libraries(n.a.)  Literature Reviews: An Overview for Graduate Students . Retrieved from   https://www.lib.ncsu.edu/tutorials/lit-review  

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Biology: Literature Reviews

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• Literature Reviews
• About Scholarly Articles
• Finding Scholarly Articles
• Evidence in Biology
• Open Access Resources

What is a Literature Review?

What is a literature review?

Before you start your research paper you need to find out what other research has been done on the topic.  A literature review will include the works you consulted in order to understand and investigate your research problem.  A good literature review is not simply a summary of other research articles. The sources listed should be organized logically with the sources dealing with the same aspects of the topic grouped together.  You should also evaluate the sources, show the relationships among them and explain why they are important (or not) for your own research.  

Literature reviews analyze  critically this segment of a published body of knowledge through summary, classification, and comparison of prior research studies, reviews of literature, and theoretical articles.

A literature review is an overview of the previously published works on a specific topic. The term can refer to a full scholarly paper or a section of a scholarly work such as a book, or an article. Either way, a literature review is supposed to provide the researcher/author and the audiences with a general image of the existing knowledge on the topic under question. A good literature review can ensure that a proper research question has been asked and a proper theoretical framework and/or research methodology have been chosen. To be precise, a literature review serves to situate the current study within the body of the relevant literature and to provide context for the reader. In such case, the review usually precedes the methodology and results sections of the work.

• Literature Reviews - Handout

A literature review is important because it:

• Explains the background of research on a topic.
• Demonstrates why a topic is significant to a subject area.
• Helps focus your own research questions or problems
• Discovers relationships between research studies/ideas.
• Suggests unexplored ideas or populations
• Identifies major themes, concepts, and researchers on a topic.
• Tests assumptions; may help counter preconceived ideas and remove unconscious bias.
• Identifies critical gaps, points of disagreement, or potentially flawed methodology or theoretical approaches.
• Indicates potential directions for future research.

Questions to Ask

Some questions to think about as you develop your literature review:

• What is known about the subject?
• Are there any gaps in the knowledge of the subject?
• Have areas of further study been identified by other researchers that you may want to consider?
• Who are the significant research personalities in this area?
• Is there consensus about the topic?
• What aspects have generated significant debate on the topic?
• What methods or problems were identified by others studying in the field and how might they impact your research?
• What is the most productive methodology for your research based on the literature you have reviewed?
• What is the current status of research in this area?
• What sources of information or data were identified that might be useful to you?
• How detailed? Will it be a review of ALL relevant material or will the scope be limited to more recent material, e.g., the last five years.
• Are you focusing on methodological approaches; on theoretical issues; on qualitative or quantitative research?

Additional Help:

“Literature Reviews", The Writing Center at University of North Carolina at Chapel Hill

The Literature Review: A Few Tips On Conducting It

Patricia Cronin, Frances Ryan, and Michael Coughlan, “Undertaking a Literature Review: A Step-by-Step Approach,” British Journal of Nursing, 17, no 1 (2008), 38-43.

A Literature Review is NOT

Keep in mind that a literature review defines and sets the stage for your later research.  While you may take the same steps in researching your literature review, your literature review is not:

Not an annotated bibliography  in which you summarize each article that you have reviewed.  A lit review goes beyond basic summarizing to focus on the critical analysis of the reviewed works and their relationship to your research question.

Not a research paper   where you select resources to support one side of an issue versus another.  A lit review should explain and consider all sides of an argument in order to avoid bias, and areas of agreement and disagreement should be highlighted.

Steps to Conduct a Literature Review

Finding the literature.

• What Literature?
• Grey Literature
• Conference Papers

When someone talks about “the literature” they are referring to the body of research, scholarly articles, books and other sources (e.g. dissertations, conference proceedings) relevant to a particular issue, area of research, or theory.  A literature review is a descriptive summary of research on a topic that has previously been studied. The purpose of a literature review is to inform readers of the significant knowledge and ideas that have been established on a topic. Its purpose is to compare, contrast and/or connect findings that were identified when reviewing researchers' work.

The word  literature  (in 'literature review') broadly refers to the scholarly or scientific writing on a topic.

Common sources of written works include:

•     peer-reviewed journal articles
•     books and book chapters
•     conference papers and government reports 
•     theses / dissertations

A good quality literature review involves searching a number of databases individually.

The  Library databases  are an excellent resource for finding  peer-reviewed journal articles  (and also book chapters and conference papers).

Databases may be multidisciplinary or discipline-specific. The best way to find the relevant databases for your review is to consult a list of databases such as the ones found in:

• The  Databases by Subject library guide
• Relevant subject-based library guides within your faculty area

Books  are often useful for background information when learning about a topic. They may be general, such as textbooks, or specialised.

A good way to find books is to use an online catalog such as the Felician University Library catalog.

• More recent editions may include information not found in previous editions
• Authors may discuss different aspects of a topic or present the information in different ways - reading widely can help understanding
• Once you have a basic understanding of the topic, searching for journal articles may help you to learn more and access the most current information.

Grey literature  is information which has been published informally or non-commercially (where the main purpose of the producing body is not commercial publishing) or remains unpublished.

It can include a range of material, such as government reports, policy documents, statistics, discussion papers, dissertations, conference proceedings and unpublished trial data. The quality of grey literature can vary greatly - some may be peer-reviewed whereas some may not have been through a traditional editorial process.

Grey literature may be included in a literature review to minimize  publication bias .

Key ways of  finding grey literature  include using search engines, databases, government or organization websites and grey literature directories. For example:

• Analysis and Policy Observatory
• OpenGrey (European)
• New York Academy of Medicine grey literature report (US)
• The Global Science Gateway

Additional statistics are available from many government websites. Try limiting by site or domain in  Google Advanced Search  and using the keyword Statistics.

Data Sources (includes Biological Sciences Data/Sets)

re3data.org (Registry of Research Data Repositories)

Dryad Digital Repository

U.S. Government Open Data

NIH Data Sharing Repositories

DataONE (Earth and environmental data)

EPA Environmental dataset gateway

OpenDOAR : Directory of Open Access Repositories is a browsable directory of open access repositories. Search by subject, country of origin and content type.

Health Statistics

CDC SNAPS (county and state level)

Centers for Disease Control and Prevention (CDC)  

Community Health Status Indicators Report

County Health Rankings (Robert Wood Johnson Foundation)

National Center for Health Statistics (NCHS)  

Partners in Information Access for the Public Health Workforce  

State Health Facts Online (Kaiser Family Foundation)

Dissertation Databases

PQDT Open (ProQuest)

Open Access Theses and Dissertations

OpenDissertations (EBSCO)

Dissertation Search

Limit to Thesis/Dissertation under Content

Conference papers  are typically published in conference proceedings (the collection of papers presented at a conference), and may be found on an organization or Society's website, as a journal, or as a special issue of journal.

In some disciplinary areas (such as computer science), conference papers may be a particularly well regarded as a form of scholarly communication; the conferences are highly selective, the papers are generally peer-reviewed, and papers are published in proceedings affiliated with high-quality publishing houses.  

Tips for finding conference papers:

• The year of publication may be different to the year the conference was held. If applying a date limit to your search, try a range of years.
• Try searching for the conference title rather than the title or author of the paper. The entire conference proceedings may be cited under a special title. You can also try searching for the conference location or sponsoring organization.

When you are writing your own primary literature review you must:

(a) use recent articles that report research tightly connected to the same specific current research problem (not simply any primary articles somehow related to the same general topic), and;

(b) write paragraphs that explicitly compare the objectives, methods, and findings of the articles with each other and with your proposed research project or findings*

*A literature review is not simply summarizing each article separately one after the other -- that would be more like an annotated bibliography and does not connect the details to your own methods/findings in your research proposal (BIO 450) or discussion/conclusion (BIO 451).

Write about how the specific research objectives, methods, and findings of the articles are similar and how are they different from each other as well as yours. 

Literature Review vs. Systematic Review

It is common to confuse systematic and literature reviews as both are used to provide a summary of the existent literature or research on a specific topic.  Even with this common ground, both types vary significantly.  Please review the following chart (and its corresponding poster linked below) for a detailed explanation of each as well as the differences between each type of review.

What's in a name? The difference between a Systematic Review and a Literature Review, and why it matters by Lynn Kysh, MLIS, University of Southern California - Norris Medical Library

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BIO 3800: Biological Research

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Need Assistance?

Find your librarian, schedule a research appointment, today's hours : , what is a literature review.

A literature review ought to be a clear, concise synthesis of relevant information. A literature review should introduce the study it precedes and show how that study fits into topically related studies that already exist. Structurally, a literature review ought to be something like a funnel: start by addressing the topic broadly and gradually narrow as the review progresses.

from Literature Reviews by CU Writing Center

Why review the literature?

Reference to prior literature is a defining feature of academic and research writing. Why review the literature?

• To help you understand a research topic
• To establish the importance of a topic
• To help develop your own ideas
• To make sure you are not simply replicating research that others have already successfully completed
• To demonstrate knowledge and show how your current work is situated within, builds on, or departs from earlier publications

from Literature Review Basics from University of La Verne

Literature Review Writing Tips

Synthesize your findings . Your findings are your evaluation of the literature reviewed: what you consider the strengths and weakness of the studies reviewed; the comparison you did between studies; research trends and gaps in the research that you found while researching your topic, etc...

Across the articles that you read, pay attention to what are the:

• Common/contested findings
• Important trends
• Influential theories

Lectures & Slides

• Literature Reviews | CU Writing Center
• Writing a Literature Review | CU Writing Center
• Revising a Literature Review | CU Writing Center

How-To Guides

• Literature Reviews | Purdue OWL A how-to guide from Purdue OWL
• Literature Reviews | University of North Carolina
• Literature Reviews (University of Wisconsin-Madison)
• Literature Review: The What, Why and How-to Guide | University of Connecticut
• Literature Reviews | Florida A & M
• Conduct a Literature Review | SUNY
• Literature Review Basics | University of LaVerne

Organizing a Literature Review

Your literature review should have the following components:

• Introduction : Provide an overview of your topic, including the major problems and issues that have been studied.
• Thematic : You may have noticed specific themes emerge as you did your reading; if so, this may be a good way to organize your literature review. 
• Chronological : To use the example above, you may have observed that the way principals deal with behavioral problems has changed over time. If that's the case, perhaps you want to give a historical overview of the literature.
• Methodological : There are a number of different types of methodologies used in research.
• Conclusion/Discussion : Summarize what you've found in your review of literature, and identify areas in need of further research. Make sure to mention any gaps in the literature - things you think should have been researched, but were not.

Sample Literature Reviews

• Sample Literature Reviews | University of West Florida
• Sample APA Papers: Literature Review | Purdue OWL

Other Libguides

• Literature Reviews | Webster University
• Write a Literature Review | UC Santa Cruz
• Literature Reviews | California State University

A literature review may exist as:

• part of a larger whole like a section of a journal article or dissertation, or chapter of a book
• a self-contained entity, like an entire journal article 
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Biology 231 - Research Methods

• Verifying If An Article Is Peer-Reviewed
• Should I Trust Internet Sources?
• Suggested Databases for Finding Sources
• Critical Analysis
• Creating an Annotated Bibliography
• Creating a Literature Review
• Resources for Writing Research Proposals
• Off-Campus Access

Structure of an Evidence Matrix

The purpose of a literature review is to demonstrate your familiarity with existing research and how your proposed research fits within it.  It should consist of at least 4-5 peer-reviewed articles and provide an integration of ideas, concepts, theories and findings.

Constructing an Evidence Matrix will assist in the dissection of the articles being reviewed and provide a system that easily organizes common themes for later discussion.

Create a spreadsheet with the following fields: 

Themes are items of interest to you found within the article and are points of comparison between articles.

• Has the subject or style of research evolved over time?
• Are there any approaches or variables that have been consistently examined?  Do the articles ask the same questions?  Can you identify any gaps in research or inquiry?
• Are you aware of any specific common theoretical models used?

NOTE:  It is crucial that when summarizing any content that you appropriate paraphrase the text entered into your matrix. If not, use quotation marks for any words that are not your own and provide page numbers for your quotes.  This will help avoid plagiarism.

Writing a Literature Review

In a full-length paper or thesis the literature review tends to be 4-5 paragraphs long and explains how your original research topic fits into the existing body of scholarship on the topic. 

A basic format is as follows:

Paragraph #1.  Introduction of the research topic.  "The purpose of the study is to...".

Paragraph #2.  Describe how others have studied the subjects (Methods column).  Include any sampling techniques, strategies and limitations to research processes.

Paragraph #3.  Discuss a common theme from two or more articles (identified in evidence matrix).

Paragraph #4.   Discuss a common theme from two or more articles (identified in evidence matrix).

Paragraph #5.  Discuss the existing research identified in previous paragraphs, then your research topic and why it is important.  Give strong examples why your research is relevant and necessary to build a stronger understanding of the subject.

TIPS: 

• Do not summarize each article read in a separate paragraph.  The purpose here is to critically analyze them as a whole and reflect.
• When referencing an article in the literature, do not refer to it by its title.  Instead relate the article to the author and date.

Source: https://libguides.sonoma.edu/c.php?g=202672&p=1354272 (Downloaded 17AUG2022)

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Steps involved in completing a literature review

Collecting information, further reading.

• Writing Guides and Style Manuals
• Related Research Guides

Adapted from NCSU Libraries - Literature Reviews: An Overview for Graduate Students

Formulate a winning search strategy:

Once you have identified your research topic or question:

• Identify your key concepts and some keywords;
• Essentially it’s a formula you develop to conduct your search.
• Sample search strategy:

(coast* OR shoreline) AND (evolution OR change)

"sea level" AND (rise OR change)

“climate change”

• Test your search string in a few databases and modify if necessary;
• Run your final search.

Remember that the research process is iterative.

Research tips:

Choose the right database.

• Identify the broad subject area of your topic.
• Determine  the type of information source  you need (articles, books, statistics, etc.)
• Select the relevant search tool(s) in order to be thorough

Ensure your database searches will be reproducible:

• Any additional screening criteria such as a language, date range, etc.
• Note any problematic terms.
• Though this does not seem essential at the time, you may need to redo some of your searches at a later date.  Having a detailed record will ensure consistency and will save time.

Online Resources

• Literature Reviews: An Overview for Graduate Students (video)
• The Literature Review: A Few Tips On Conducting It (University of Toronto)
• Write a Literature Review (University of California Santa Cruz)

Guidelines and Standards for Evidence Synthesis in Environmental Management (Collaboration for Environmental Evidence)

Journal Articles

Bolderston, A.  (2008).  Writing an Effective Literature Review.  Journal of Medical Imaging and Radiation Sciences , 39 (2), 86-92.  http://dx.doi.org/10.1016/j.jmir.2008.04.009

Pautasso, M.  (2013).  Ten Simple Rules for Writing a Literature Review.  PLOS Computational Biology , 9(7).  Retrieved from http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003149 .

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Graduate Biology: Literature Reviews

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What is a Literature Review?

This handout will explain what a literature review is and offer insights into the form and construction of a literature review in the humanities, social sciences, and sciences.

OK. You've got to write a literature review. You dust off a novel and a book of poetry, settle down in your chair, and get ready to issue a "thumbs up" or "thumbs down" as you leaf through the pages. "Literature review" done. Right?

Wrong! The "literature" of a literature review refers to any collection of materials on a topic, not necessarily the great literary texts of the world. "Literature" could be anything from a set of government pamphlets on British colonial methods in Africa to scholarly articles on the treatment of a torn ACL. And a review does not necessarily mean that your reader wants you to give your personal opinion on whether or not you liked these sources.

What is a literature review, then?

A literature review discusses published information in a particular subject area, and sometimes information in a particular subject area within a certain time period.

A literature review can be just a simple summary of the sources, but it usually has an organizational pattern and combines both summary and synthesis. A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information. It might give a new interpretation of old material or combine new with old interpretations. Or it might trace the intellectual progression of the field, including major debates. And depending on the situation, the literature review may evaluate the sources and advise the reader on the most pertinent or relevant.

But how is a literature review different from an academic research paper?

The main focus of an academic research paper is to develop a new argument, and a research paper will contain a literature review as one of its parts. In a research paper, you use the literature as a foundation and as support for a new insight that you contribute. The focus of a literature review, however, is to summarize and synthesize the arguments and ideas of others without adding new contributions.

Why do we write literature reviews?

Literature reviews provide you with a handy guide to a particular topic. If you have limited time to conduct research, literature reviews can give you an overview or act as a stepping stone. For professionals, they are useful reports that keep them up to date with what is current in the field. For scholars, the depth and breadth of the literature review emphasizes the credibility of the writer in his or her field. Literature reviews also provide a solid background for a research paper's investigation. Comprehensive knowledge of the literature of the field is essential to most research papers.

Who writes these things, anyway?

Literature reviews are written occasionally in the humanities, but mostly in the sciences and social sciences; in experiment and lab reports, they constitute a section of the paper. Sometimes a literature review is written as a paper in itself.

If your assignment is not very specific, seek clarification from your instructor:

• Roughly how many sources should you include?
• What types of sources (books, journal articles, websites)?
• Should you summarize, synthesize, or critique your sources by discussing a common theme or issue?
• Should you evaluate your sources?
• Should you provide subheadings and other background information, such as definitions and/or a history?

Find models

Look for other literature reviews in your area of interest or in the discipline and read them to get a sense of the types of themes you might want to look for in your own research or ways to organize your final review. You can simply put the word "review" in your search engine along with your other topic terms to find articles of this type on the Internet or in an electronic database. The bibliography or reference section of sources you've already read are also excellent entry points into your own research.

Narrow your topic

There are hundreds or even thousands of articles and books on most areas of study. The narrower your topic, the easier it will be to limit the number of sources you need to read in order to get a good survey of the material. Your instructor will probably not expect you to read everything that's out there on the topic, but you'll make your job easier if you first limit your scope.

And don't forget to tap into your professor's (or other professors') knowledge in the field. Ask your professor questions such as: "If you had to read only one book from the 70's on topic X, what would it be?" Questions such as this help you to find and determine quickly the most seminal pieces in the field.

Consider whether your sources are current

Some disciplines require that you use information that is as current as possible. In the sciences, for instance, treatments for medical problems are constantly changing according to the latest studies. Information even two years old could be obsolete. However, if you are writing a review in the humanities, history, or social sciences, a survey of the history of the literature may be what is needed, because what is important is how perspectives have changed through the years or within a certain time period. Try sorting through some other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to consider what is currently of interest to scholars in this field and what is not.

Find a focus

A literature review, like a term paper, is usually organized around ideas, not the sources themselves as an annotated bibliography would be organized. This means that you will not just simply list your sources and go into detail about each one of them, one at a time. No. As you read widely but selectively in your topic area, consider instead what themes or issues connect your sources together. Do they present one or different solutions? Is there an aspect of the field that is missing? How well do they present the material and do they portray it according to an appropriate theory? Do they reveal a trend in the field? A raging debate? Pick one of these themes to focus the organization of your review.

Construct a working thesis statement

Then use the focus you've found to construct a thesis statement. Yes! Literature reviews have thesis statements as well! However, your thesis statement will not necessarily argue for a position or an opinion; rather it will argue for a particular perspective on the material. Some sample thesis statements for literature reviews are as follows:

The current trend in treatment for congestive heart failure combines surgery and medicine.

More and more cultural studies scholars are accepting popular media as a subject worthy of academic consideration.

Consider organization

You've got a focus, and you've narrowed it down to a thesis statement. Now what is the most effective way of presenting the information? What are the most important topics, subtopics, etc., that your review needs to include? And in what order should you present them? Develop an organization for your review at both a global and local level:

First, cover the basic categories Just like most academic papers, literature reviews also must contain at least three basic elements: an introduction or background information section; the body of the review containing the discussion of sources; and, finally, a conclusion and/or recommendations section to end the paper. Introduction: Gives a quick idea of the topic of the literature review, such as the central theme or organizational pattern. Body: Contains your discussion of sources and is organized either chronologically, thematically, or methodologically (see below for more information on each). Conclusions/Recommendations: Discuss what you have drawn from reviewing literature so far. Where might the discussion proceed? Organizing the body Once you have the basic categories in place, then you must consider how you will present the sources themselves within the body of your paper. Create an organizational method to focus this section even further. To help you come up with an overall organizational framework for your review, consider the following scenario and then three typical ways of organizing the sources into a review: You've decided to focus your literature review on materials dealing with sperm whales. This is because you've just finished reading Moby Dick , and you wonder if that whale's portrayal is really real. You start with some articles about the physiology of sperm whales in biology journals written in the 1980's. But these articles refer to some British biological studies performed on whales in the early 18th century. So you check those out. Then you look up a book written in 1968 with information on how sperm whales have been portrayed in other forms of art, such as in Alaskan poetry, in French painting, or on whale bone, as the whale hunters in the late 19th century used to do. This makes you wonder about American whaling methods during the time portrayed in Moby Dick , so you find some academic articles published in the last five years on how accurately Herman Melville portrayed the whaling scene in his novel. Chronological If your review follows the chronological method, you could write about the materials above according to when they were published. For instance, first you would talk about the British biological studies of the 18th century, then about Moby Dick, published in 1851, then the book on sperm whales in other art (1968), and finally the biology articles (1980s) and the recent articles on American whaling of the 19th century. But there is relatively no continuity among subjects here. And notice that even though the sources on sperm whales in other art and on American whaling are written recently, they are about other subjects/objects that were created much earlier. Thus, the review loses its chronological focus. By publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on biological studies of sperm whales if the progression revealed a change in dissection practices of the researchers who wrote and/or conducted the studies. By trend A better way to organize the above sources chronologically is to examine the sources under another trend, such as the history of whaling. Then your review would have subsections according to eras within this period. For instance, the review might examine whaling from pre-1600-1699, 1700-1799, and 1800-1899. Under this method, you would combine the recent studies on American whaling in the 19th century with Moby Dick itself in the 1800-1899 category, even though the authors wrote a century apart.

Thematic reviews of literature are organized around a topic or issue, rather than the progression of time. However, progression of time may still be an important factor in a thematic review. For instance, the sperm whale review could focus on the development of the harpoon for whale hunting. While the study focuses on one topic, harpoon technology, it will still be organized chronologically. The only difference here between a "chronological" and a "thematic" approach is what is emphasized the most: the development of the harpoon or the harpoon technology.

But more authentic thematic reviews tend to break away from chronological order. For instance, a thematic review of material on sperm whales might examine how they are portrayed as "evil" in cultural documents. The subsections might include how they are personified, how their proportions are exaggerated, and their behaviors misunderstood. A review organized in this manner would shift between time periods within each section according to the point made.

Methodological

A methodological approach differs from the two above in that the focusing factor usually does not have to do with the content of the material. Instead, it focuses on the "methods" of the researcher or writer. For the sperm whale project, one methodological approach would be to look at cultural differences between the portrayal of whales in American, British, and French art work. Or the review might focus on the economic impact of whaling on a community. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Once you've decided on the organizational method for the body of the review, the sections you need to include in the paper should be easy to figure out. They should arise out of your organizational strategy. In other words, a chronological review would have subsections for each vital time period. A thematic review would have subtopics based upon factors that relate to the theme or issue.

Sometimes, though, you might need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. Put in only what is necessary. Here are a few other sections you might want to consider:

Current Situation : Information necessary to understand the topic or focus of the literature review.

History : The chronological progression of the field, the literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.

Methods and/or Standards : The criteria you used to select the sources in your literature review or the way in which you present your information. For instance, you might explain that your review includes only peer-reviewed articles and journals.

Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

Once you've settled on a general pattern of organization, you're ready to write each section. There are a few guidelines you should follow during the writing stage as well. Here is a sample paragraph from a literature review about sexism and language to illuminate the following discussion:

However, other studies have shown that even gender-neutral antecedents are more likely to produce masculine images than feminine ones (Gastil, 1990). Hamilton (1988) asked students to complete sentences that required them to fill in pronouns that agreed with gender-neutral antecedents such as "writer," "pedestrian," and "persons." The students were asked to describe any image they had when writing the sentence. Hamilton found that people imagined 3.3 men to each woman in the masculine "generic" condition and 1.5 men per woman in the unbiased condition. Thus, while ambient sexism accounted for some of the masculine bias, sexist language amplified the effect. (Source: Erika Falk and Jordan Mills, "Why Sexist Language Affects Persuasion: The Role of Homophily, Intended Audience, and Offense," Women and Language19:2.

Use evidence

In the example above, the writers refer to several other sources when making their point. A literature review in this sense is just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence to show that what you are saying is valid.

Be selective

Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the review's focus, whether it is thematic, methodological, or chronological.

Use quotes sparingly

Falk and Mills do not use any direct quotes. That is because the survey nature of the literature review does not allow for in-depth discussion or detailed quotes from the text. Some short quotes here and there are okay, though, if you want to emphasize a point, or if what the author said just cannot be rewritten in your own words. Notice that Falk and Mills do quote certain terms that were coined by the author, not common knowledge, or taken directly from the study. But if you find yourself wanting to put in more quotes, check with your instructor.

Summarize and synthesize

Remember to summarize and synthesize your sources within each paragraph as well as throughout the review. The authors here recapitulate important features of Hamilton's study, but then synthesize it by rephrasing the study's significance and relating it to their own work.

Keep your own voice

While the literature review presents others' ideas, your voice (the writer's) should remain front and center. Notice that Falk and Mills weave references to other sources into their own text, but they still maintain their own voice by starting and ending the paragraph with their own ideas and their own words. The sources support what Falk and Mills are saying.

Use caution when paraphrasing

When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. In the preceding example, Falk and Mills either directly refer in the text to the author of their source, such as Hamilton, or they provide ample notation in the text when the ideas they are mentioning are not their own, for example, Gastil's. 

Draft in hand? Now you're ready to revise. Spending a lot of time revising is a wise idea, because your main objective is to present the material, not the argument. So check over your review again to make sure it follows the assignment and/or your outline. Then, just as you would for most other academic forms of writing, rewrite or rework the language of your review so that you've presented your information in the most concise manner possible. Be sure to use terminology familiar to your audience; get rid of unnecessary jargon or slang. Finally, double check that you've documented your sources and formatted the review appropriately for your discipline. 

We consulted these works while writing the original version of this handout. This is not a comprehensive list of resources on the handout's topic, and we encourage you to do your own research to find the latest publications on this topic. Please do not use this list as a model for the format of your own reference list, as it may not match the citation style you are using. 

Anson, Chris M. and Robert A. Schwegler, The Longman Handbook for Writers and Readers. Second edition. New York: Longman, 2000.

Jones, Robert, Patrick Bizzaro, and Cynthia Selfe. The Harcourt Brace Guide to Writing in the Disciplines. New York: Harcourt Brace, 1997.

Lamb, Sandra E. How to Write It: A Complete Guide to Everything You'll Ever Write. Berkeley, Calif.: Ten Speed Press, 1998.

Rosen, Leonard J. and Laurence Behrens. The Allyn and Bacon Handbook. Fourth edition. Boston: Allyn and Bacon, 2000.

Troyka, Lynn Quitman. Simon and Schuster Handbook for Writers. Upper Saddle River, N.J.: Prentice Hall, 2002.

Originally written and publised by the The Writing Center, University of North Carolina at Chapel Hill

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Open Access

Ten Simple Rules for Writing a Literature Review

* E-mail: [email protected]

Affiliations Centre for Functional and Evolutionary Ecology (CEFE), CNRS, Montpellier, France, Centre for Biodiversity Synthesis and Analysis (CESAB), FRB, Aix-en-Provence, France

• Marco Pautasso

Published: July 18, 2013

• https://doi.org/10.1371/journal.pcbi.1003149
• Reader Comments

Citation: Pautasso M (2013) Ten Simple Rules for Writing a Literature Review. PLoS Comput Biol 9(7): e1003149. https://doi.org/10.1371/journal.pcbi.1003149

Editor: Philip E. Bourne, University of California San Diego, United States of America

Copyright: © 2013 Marco Pautasso. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was funded by the French Foundation for Research on Biodiversity (FRB) through its Centre for Synthesis and Analysis of Biodiversity data (CESAB), as part of the NETSEED research project. The funders had no role in the preparation of the manuscript.

Competing interests: The author has declared that no competing interests exist.

Literature reviews are in great demand in most scientific fields. Their need stems from the ever-increasing output of scientific publications [1] . For example, compared to 1991, in 2008 three, eight, and forty times more papers were indexed in Web of Science on malaria, obesity, and biodiversity, respectively [2] . Given such mountains of papers, scientists cannot be expected to examine in detail every single new paper relevant to their interests [3] . Thus, it is both advantageous and necessary to rely on regular summaries of the recent literature. Although recognition for scientists mainly comes from primary research, timely literature reviews can lead to new synthetic insights and are often widely read [4] . For such summaries to be useful, however, they need to be compiled in a professional way [5] .

When starting from scratch, reviewing the literature can require a titanic amount of work. That is why researchers who have spent their career working on a certain research issue are in a perfect position to review that literature. Some graduate schools are now offering courses in reviewing the literature, given that most research students start their project by producing an overview of what has already been done on their research issue [6] . However, it is likely that most scientists have not thought in detail about how to approach and carry out a literature review.

Reviewing the literature requires the ability to juggle multiple tasks, from finding and evaluating relevant material to synthesising information from various sources, from critical thinking to paraphrasing, evaluating, and citation skills [7] . In this contribution, I share ten simple rules I learned working on about 25 literature reviews as a PhD and postdoctoral student. Ideas and insights also come from discussions with coauthors and colleagues, as well as feedback from reviewers and editors.

Rule 1: Define a Topic and Audience

How to choose which topic to review? There are so many issues in contemporary science that you could spend a lifetime of attending conferences and reading the literature just pondering what to review. On the one hand, if you take several years to choose, several other people may have had the same idea in the meantime. On the other hand, only a well-considered topic is likely to lead to a brilliant literature review [8] . The topic must at least be:

• interesting to you (ideally, you should have come across a series of recent papers related to your line of work that call for a critical summary),
• an important aspect of the field (so that many readers will be interested in the review and there will be enough material to write it), and
• a well-defined issue (otherwise you could potentially include thousands of publications, which would make the review unhelpful).

Ideas for potential reviews may come from papers providing lists of key research questions to be answered [9] , but also from serendipitous moments during desultory reading and discussions. In addition to choosing your topic, you should also select a target audience. In many cases, the topic (e.g., web services in computational biology) will automatically define an audience (e.g., computational biologists), but that same topic may also be of interest to neighbouring fields (e.g., computer science, biology, etc.).

Rule 2: Search and Re-search the Literature

After having chosen your topic and audience, start by checking the literature and downloading relevant papers. Five pieces of advice here:

• keep track of the search items you use (so that your search can be replicated [10] ),
• keep a list of papers whose pdfs you cannot access immediately (so as to retrieve them later with alternative strategies),
• use a paper management system (e.g., Mendeley, Papers, Qiqqa, Sente),
• define early in the process some criteria for exclusion of irrelevant papers (these criteria can then be described in the review to help define its scope), and
• do not just look for research papers in the area you wish to review, but also seek previous reviews.

The chances are high that someone will already have published a literature review ( Figure 1 ), if not exactly on the issue you are planning to tackle, at least on a related topic. If there are already a few or several reviews of the literature on your issue, my advice is not to give up, but to carry on with your own literature review,

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The bottom-right situation (many literature reviews but few research papers) is not just a theoretical situation; it applies, for example, to the study of the impacts of climate change on plant diseases, where there appear to be more literature reviews than research studies [33] .

https://doi.org/10.1371/journal.pcbi.1003149.g001

• discussing in your review the approaches, limitations, and conclusions of past reviews,
• trying to find a new angle that has not been covered adequately in the previous reviews, and
• incorporating new material that has inevitably accumulated since their appearance.

When searching the literature for pertinent papers and reviews, the usual rules apply:

• be thorough,
• use different keywords and database sources (e.g., DBLP, Google Scholar, ISI Proceedings, JSTOR Search, Medline, Scopus, Web of Science), and
• look at who has cited past relevant papers and book chapters.

Rule 3: Take Notes While Reading

If you read the papers first, and only afterwards start writing the review, you will need a very good memory to remember who wrote what, and what your impressions and associations were while reading each single paper. My advice is, while reading, to start writing down interesting pieces of information, insights about how to organize the review, and thoughts on what to write. This way, by the time you have read the literature you selected, you will already have a rough draft of the review.

Of course, this draft will still need much rewriting, restructuring, and rethinking to obtain a text with a coherent argument [11] , but you will have avoided the danger posed by staring at a blank document. Be careful when taking notes to use quotation marks if you are provisionally copying verbatim from the literature. It is advisable then to reformulate such quotes with your own words in the final draft. It is important to be careful in noting the references already at this stage, so as to avoid misattributions. Using referencing software from the very beginning of your endeavour will save you time.

Rule 4: Choose the Type of Review You Wish to Write

After having taken notes while reading the literature, you will have a rough idea of the amount of material available for the review. This is probably a good time to decide whether to go for a mini- or a full review. Some journals are now favouring the publication of rather short reviews focusing on the last few years, with a limit on the number of words and citations. A mini-review is not necessarily a minor review: it may well attract more attention from busy readers, although it will inevitably simplify some issues and leave out some relevant material due to space limitations. A full review will have the advantage of more freedom to cover in detail the complexities of a particular scientific development, but may then be left in the pile of the very important papers “to be read” by readers with little time to spare for major monographs.

There is probably a continuum between mini- and full reviews. The same point applies to the dichotomy of descriptive vs. integrative reviews. While descriptive reviews focus on the methodology, findings, and interpretation of each reviewed study, integrative reviews attempt to find common ideas and concepts from the reviewed material [12] . A similar distinction exists between narrative and systematic reviews: while narrative reviews are qualitative, systematic reviews attempt to test a hypothesis based on the published evidence, which is gathered using a predefined protocol to reduce bias [13] , [14] . When systematic reviews analyse quantitative results in a quantitative way, they become meta-analyses. The choice between different review types will have to be made on a case-by-case basis, depending not just on the nature of the material found and the preferences of the target journal(s), but also on the time available to write the review and the number of coauthors [15] .

Rule 5: Keep the Review Focused, but Make It of Broad Interest

Whether your plan is to write a mini- or a full review, it is good advice to keep it focused 16 , 17 . Including material just for the sake of it can easily lead to reviews that are trying to do too many things at once. The need to keep a review focused can be problematic for interdisciplinary reviews, where the aim is to bridge the gap between fields [18] . If you are writing a review on, for example, how epidemiological approaches are used in modelling the spread of ideas, you may be inclined to include material from both parent fields, epidemiology and the study of cultural diffusion. This may be necessary to some extent, but in this case a focused review would only deal in detail with those studies at the interface between epidemiology and the spread of ideas.

While focus is an important feature of a successful review, this requirement has to be balanced with the need to make the review relevant to a broad audience. This square may be circled by discussing the wider implications of the reviewed topic for other disciplines.

Rule 6: Be Critical and Consistent

Reviewing the literature is not stamp collecting. A good review does not just summarize the literature, but discusses it critically, identifies methodological problems, and points out research gaps [19] . After having read a review of the literature, a reader should have a rough idea of:

• the major achievements in the reviewed field,
• the main areas of debate, and
• the outstanding research questions.

It is challenging to achieve a successful review on all these fronts. A solution can be to involve a set of complementary coauthors: some people are excellent at mapping what has been achieved, some others are very good at identifying dark clouds on the horizon, and some have instead a knack at predicting where solutions are going to come from. If your journal club has exactly this sort of team, then you should definitely write a review of the literature! In addition to critical thinking, a literature review needs consistency, for example in the choice of passive vs. active voice and present vs. past tense.

Rule 7: Find a Logical Structure

Like a well-baked cake, a good review has a number of telling features: it is worth the reader's time, timely, systematic, well written, focused, and critical. It also needs a good structure. With reviews, the usual subdivision of research papers into introduction, methods, results, and discussion does not work or is rarely used. However, a general introduction of the context and, toward the end, a recapitulation of the main points covered and take-home messages make sense also in the case of reviews. For systematic reviews, there is a trend towards including information about how the literature was searched (database, keywords, time limits) [20] .

How can you organize the flow of the main body of the review so that the reader will be drawn into and guided through it? It is generally helpful to draw a conceptual scheme of the review, e.g., with mind-mapping techniques. Such diagrams can help recognize a logical way to order and link the various sections of a review [21] . This is the case not just at the writing stage, but also for readers if the diagram is included in the review as a figure. A careful selection of diagrams and figures relevant to the reviewed topic can be very helpful to structure the text too [22] .

Rule 8: Make Use of Feedback

Reviews of the literature are normally peer-reviewed in the same way as research papers, and rightly so [23] . As a rule, incorporating feedback from reviewers greatly helps improve a review draft. Having read the review with a fresh mind, reviewers may spot inaccuracies, inconsistencies, and ambiguities that had not been noticed by the writers due to rereading the typescript too many times. It is however advisable to reread the draft one more time before submission, as a last-minute correction of typos, leaps, and muddled sentences may enable the reviewers to focus on providing advice on the content rather than the form.

Feedback is vital to writing a good review, and should be sought from a variety of colleagues, so as to obtain a diversity of views on the draft. This may lead in some cases to conflicting views on the merits of the paper, and on how to improve it, but such a situation is better than the absence of feedback. A diversity of feedback perspectives on a literature review can help identify where the consensus view stands in the landscape of the current scientific understanding of an issue [24] .

Rule 9: Include Your Own Relevant Research, but Be Objective

In many cases, reviewers of the literature will have published studies relevant to the review they are writing. This could create a conflict of interest: how can reviewers report objectively on their own work [25] ? Some scientists may be overly enthusiastic about what they have published, and thus risk giving too much importance to their own findings in the review. However, bias could also occur in the other direction: some scientists may be unduly dismissive of their own achievements, so that they will tend to downplay their contribution (if any) to a field when reviewing it.

In general, a review of the literature should neither be a public relations brochure nor an exercise in competitive self-denial. If a reviewer is up to the job of producing a well-organized and methodical review, which flows well and provides a service to the readership, then it should be possible to be objective in reviewing one's own relevant findings. In reviews written by multiple authors, this may be achieved by assigning the review of the results of a coauthor to different coauthors.

Rule 10: Be Up-to-Date, but Do Not Forget Older Studies

Given the progressive acceleration in the publication of scientific papers, today's reviews of the literature need awareness not just of the overall direction and achievements of a field of inquiry, but also of the latest studies, so as not to become out-of-date before they have been published. Ideally, a literature review should not identify as a major research gap an issue that has just been addressed in a series of papers in press (the same applies, of course, to older, overlooked studies (“sleeping beauties” [26] )). This implies that literature reviewers would do well to keep an eye on electronic lists of papers in press, given that it can take months before these appear in scientific databases. Some reviews declare that they have scanned the literature up to a certain point in time, but given that peer review can be a rather lengthy process, a full search for newly appeared literature at the revision stage may be worthwhile. Assessing the contribution of papers that have just appeared is particularly challenging, because there is little perspective with which to gauge their significance and impact on further research and society.

Inevitably, new papers on the reviewed topic (including independently written literature reviews) will appear from all quarters after the review has been published, so that there may soon be the need for an updated review. But this is the nature of science [27] – [32] . I wish everybody good luck with writing a review of the literature.

Acknowledgments

Many thanks to M. Barbosa, K. Dehnen-Schmutz, T. Döring, D. Fontaneto, M. Garbelotto, O. Holdenrieder, M. Jeger, D. Lonsdale, A. MacLeod, P. Mills, M. Moslonka-Lefebvre, G. Stancanelli, P. Weisberg, and X. Xu for insights and discussions, and to P. Bourne, T. Matoni, and D. Smith for helpful comments on a previous draft.

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What is a Literature Review?

Why write a literature review.

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A literature review is an explanation of what has been published on a subject. Occasionally you will be asked to write one as a separate assignment (sometimes in the form of an annotated bibliography), but more often it is part of the introduction to a research report, essay, thesis, or dissertation. It's not just a summary of sources. You should provide a new interpretation of old material. It should:

• Connect your references
• Synthesize what you've read
• Evaluate your resources.

A literature review should do these things:

• Be organized around and related directly to the thesis or research question you are developing
• Synthesize results into a summary of what is and is not known
• Identify areas of controversy in the literature
• Formulate questions that need further research
• To trace the progression of a field
• To evaluate your sources. Does one article have different conclusions or results from your other resources?
• To develop a better understanding of the field. It can be very helpful if you want to do your own research in the field.
• To give a new interpretation to previous research.
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Biochemistry & Molecular Biology

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What is a Literature Review?

A literature review is a comprehensive and up-to-date overview of the principal research about the topic being studied.

The aim of a literature review is to show "that the writer has studied existing work in the field with insight" (Haywood and Wragg, 1982). It is not enough merely to show what others in your field have discovered. You need to view the work of others with insight to review critically. An effective review analyses and synthesizes material, and it should meet the following requirements: (Caulley, 1992)

• Compare and contrast different authors' views on an issue
• Group authors who draw similar conclusions,
• Criticise aspects of methodology,
• Note areas in which authors are in disagreement,
• Highlight exemplary studies,
• Identify patterns or trends in the literature
• Highlight gaps in and omissions in previous research or questions left unanswered
• Show how your study relates to previous studies,
• Show how your study relates to the literature in general,
• Conclude by summarising what the literature says.

A literature review has a number of purposes. It enables you to:

• Set the background on what has been researched on a topic.
• Show why a topic is significant to a subject area.
• Discover relationships between ideas.
• Identify major themes & concepts.
• Identify critical gaps & points of disagreement.
• Help the researcher turn a network of articles into a coherent view of the literature.

Source: University of Melbourne's Literature Review Libguide

Organizing the Review

Categorizing the Literature

When categorizing the writings in the review, the researcher might consider

• the methodology employed;
• the quality of the findings or conclusions;
• the document’s major strengths and weaknesses;
• any other pivotal information.

He/She might consider such questions as:

• what beliefs are expressed?
• Is there an ideological stance?
• What is being described? Is it comprehensive or narrow?
• Are the results generalizable?

Remember that you are relating other studies to your study. How do the studies in your lit. review relate to your thesis? How are the other studies related to each other?

From http://libguides.redlands.edu/content.php?pid=32380&sid=239161

Literature Review Samples

• Otterbein's Institutional Repository You can browse by collection and then department and student scholarship. Look up samples of literature reviews in theses and dissertations.
• OhioLink's ETD Browse by institution and look up samples of literature review in the students' theses and dissertations

Planning your Literature Review

While planning your review, in addition to finding and analyzing the reviews in dissertations, you might ask yourself questions such as the following:

What is my central question or issue that the literature can help define?

What is already known about the topic?

Is the scope of the literature being reviewed wide or narrow enough?

Is there a conflict or debate in the literature?

What connections can be made between the texts being reviewed?

What sort of literature should be reviewed? Historical? Theoretical? Methodological? Quantitative? Qualitative?

What criteria should be used to evaluate the literature being reviewed?

How will reviewing the literature justify the topic I plan to investigate?

From: Writing the successful thesis and dissertation: entering the conversation, by Irene L. Clark

source: Kent State University's Literature Reviews Libguide

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Chemistry and Chemical Biology Resources

Literature review.

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Reviewing the Literature: Why do it?

• Personal: To familiarize yourself with a new area of research, to get an overview of a topic, so you don't want to miss something important, etc.
• Required writing for a journal article, thesis or dissertation, grant application, etc.

Literature reviews vary; there are many ways to write a literature review based on discipline, material type, and other factors.

Background:

• Literature Reviews - UNC Writing Center
• Literature Reviews: An Overview for Graduate Students  - What is a literature review? What purpose does it serve in research? What should you expect when writing one? - NCSU Video

Where to get help (there are lots of websites, blogs , articles,  and books on this topic) :

• The Center for writing and Communicating Ideas (CWCI)
• (these are non-STEM examples: dissertation guidance , journal guidelines )
• How to prepare a scientific doctoral dissertation based on research articles (2012)
• Writing a graduate thesis or dissertation (2016)
• The good paper : a handbook for writing papers in higher education (2015)
• Proposals that work : a guide for planning dissertations and grant proposals (2014)
• Theses and dissertations : a guide to planning, research, and writing (2008)
• Talk to your professors, advisors, mentors, peers, etc. for advice

READ related material and pay attention to how others write their literature reviews:

• Dissertations
• Journal articles
• Grant proposals
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BIOL 356: Microbiology: Literature Review

• Getting Started
• Literature Review
• Key Resources
• Organizing Research
• LibKey Nomad

Books about Literature Reviews

Related Guides

• Writing a Literature Review by Conrad Woxland Last Updated Mar 22, 2024 74 views this year
• Lit Review Guide--University of Pittsburgh

What is a Literature Review?

• A literature review is a comprehensive and up-to-date overview of the principal research about the topic being studied.
• The review helps form the intellectual framework for the study.
• The review need not be exhaustive; the objective is not to list as many relevant books, articles, reports as possible.
• However, the review should contain the most pertinent studies and point to important past and current research and practices in the field.

Purpose of a Literature Review

A literature review serves several purposes. For example, it

• provides thorough knowledge of previous studies; introduces seminal works.
• helps focus one’s own research topic.
• identifies a conceptual framework for one’s own research questions or problems; indicates potential directions for future research.
• suggests previously unused or underused methodologies, designs, quantitative and qualitative strategies.
• identifies gaps in previous studies; identifies flawed methodologies and/or theoretical approaches; avoids replication of mistakes.
• helps the researcher avoid repetition of earlier research.
• suggests unexplored populations.
• determines whether past studies agree or disagree; identifies controversy in the literature.
• tests assumptions; may help counter preconceived ideas and remove unconscious bias.

What is "the literature"?

You'll often hear "explore the literature" or "what does the literature say?"  So, what is "the literature?"

Most simply put, "the literature" is a collection of scholarly writings on a topic. This includes:

• peer-reviewed journal articles
• conference proceedings
• dissertations

How do you know when you are done researching?

Are you seeing the same articles over and over?

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Molecular and Cellular Biology: Literature Review

• Literature Review
• Protocols and Methods
• 3-D Visualizations

Recommended Databases

• PubMed This link opens in a new window The most comprehensive medical database. This resource covers medicine, dentistry, nursing, physical therapy, biomedical research, clinical practice, administration, policy issues, and health care services. It also includes extra life sciences journals and ebooks in addition to MEDLINE.
• ScienceDirect This link opens in a new window Excellent place to start a literature review. Get peer-reviewed journals, articles, book chapters on a wide variety of scientific topics, including the life sciences and health topics, as well as engineering content related to biology, including chemical engineering.
• Academic Search Complete This link opens in a new window Offers coverage of many areas of academic study including: biology, chemistry, food science & technology, general science, psychology, etc. Useful for building contextual knowledge of your research topic.
• Web of Science This link opens in a new window Covers topics in the sciences, social sciences, and humanities.
• American Society for Microbiology This link opens in a new window Full-text of the Society's 11 journals, from molecular and cellular biology to biomedical research and technology.
• SciFinder This link opens in a new window Indexes the literature of chemistry, including journal articles, patents, substance data, chemical reactions, chemical regulatory data, and chemical suppliers. Registration is required. Note: Access to SciFinder includes access to ChemZent and PatentPak.
• Dissertations & Theses This link opens in a new window Graduate dissertations from over 1,000 North American graduate schools and selected European universities, dating from 1861- present.

Journal Search

• Journal Search Use this search to find a journal in our library. You can search by name or ISSN. You can also use the "search by citation" tab for more searching options, including by an article's DOI. The majority of our journals are accessible online.

Recommended Journals

• Cell Biology
• Cellular and Molecular Immunology
• Nature Reviews: Cancer
• Nature Reviews: Molecular Cell Biology

Article Pre-prints

• Cell: new articles Access articles published just ahead of final publication in an issue. The articles have been copyedited and incorporate the authors' final corrections.
• bioRxiv Pre-print server for the biological sciences, including cellular biology and related fields. Hosted at the Cold Spring Harbor Laboratory.
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Human Biology: Literature Review

Searching & reviewing the literature.

• Literature Review
• Search Strategy
• Database search tips

A literature review is an evaluation of relevant literature on a topic and is usually the starting point for any undergraduate essay or postgraduate thesis. The focus for a literature review is on scholarly published materials such as books, journal articles and reports.

A search and review of relevant sources may be extensive and form part of a thesis or research project. Postgraduate researchers will normally focus on primary sources such as research studies in journals.

A literature review also provides evidence for an undergraduate assignment. Students new to a discipline may find that starting with an overview or review of relevant research in books and journals, the easiest way to begin researching a topic and obtaining the necessary background information.

Source materials can be categorised as:

Primary source : Original research from journals articles or conference papers, original materials such as historical documents, or creative works.

Secondary source : Evaluations, reviews or syntheses of original work. e.g. review articles in journals.

Tertiary source : Broadly scoped material put together usually from secondary sources to provide an overview, e.g. a book.

The Literature Review Structure : Like a standard academic essay, a literature review is made up of three key components: an introduction, a body and a conclusion. Most literature reviews can follow the following format: • Introduction: Introduce the topic/problem and the context within which it is found. • Body: Examine past research in the area highlighting methodological and/or theoretical developments, areas of agreement, contentious areas, important studies and so forth. Keep the focus on your area of interest and identify gaps in the research that your research/investigation will attempt to fill. State clearly how your work builds on or responds to earlier work. • Conclusion: Summarise what has emerged from the review of literature and reiterate conclusions.

This information has been adapted from the Edith Cowan University Literature review: Academic tip sheet .

Steps in searching and reviewing the literature:

• Define the topic and scope of the assignment. Ensure you understand the question and expectations of the assignment. It's useful to develop a plan and outline, headings, etc.  
• Check terminology. e.g. dictionaries, encyclopedias, thesauruses  
• Identify keywords for searching (include English and American spelling and terminology)  
• Identify types of publications. e.g. books, journal articles, reports.  
• Search relevant databases (refer to the relevant subject guide for key databases and sources)  
• Select and evaluate relevant sources  
• Synthesise the information  
• Write the review following the structure outlined.  
• Save references used. e.g. from the databases save, email, print or download references to EndNote.  
• Reference sources (APA 7th) (see Referencing Library Guide )

When you are writing for an academic purpose such as an essay for an assignment, you need to find evidence to support your ideas. The library is a good place to begin your search for the evidence, as it acquires books and journals to support the disciplines within the University. The following outlines a list of steps to follow when starting to write an academic assignment:

Define your topic and scope of the search

• This will provide the search terms when gathering evidence from the literature to support your arguments.
• Sometimes it is a good idea to concept map key themes.

The scope will advise you:

• How much information is required, often identified by the number of words ie 500 or 3000 words
• What sort of writing you are to do eg essay, report, annotated bibliography
• How many marks are assigned. This may indicate the amount of time to allocate to the task.

Gather the information - Before writing about your topic, you will need to find evidence to support your ideas. 

Books provide a useful starting point for an introduction to the subject. Books also provide an in-depth coverage of a topic.

Journal Articles: For current research or information on a very specific topic, journal articles may be the most useful, as they are published on a regular basis. It is normally expected that you will use some journal articles in your assignment. When using journal articles, check whether they are from a magazine or scholalry publication. Scholarly publications are often peer reviewed, which means that the articles are reviewed by expert/s before being accepted for publication.

Reports : useful information can also be found in free web publications from government or research organizations (e.g. reports). Any web publications should be carefully evaluated. You are also required to view the whole publication, not just the abstract, if using the information in your assignment.

Remember to ensure that you note the citation details for references that you collect, at the time of locating the items. It is often time consuming and impossible to track the required data later.

Analyse the information collected

• Have I collected enough information on the topic?

Synthesise your information

Write the report or essay

• Check the ECU Academic tip sheet: the Academic Essay for some useful pointers
• Remember, in most cases you will need an introduction, body and conclusion
• Record details of references used for referencing. Information on referencing can be located on the ECU Referencing Guide.

Database search tips:

1. Identify main concepts and keywords . Search the main concepts first, then limit further as necessary.

2. Find Synonyms (Boolean  OR broadens the search to include alternative keywords or subject thesaurus terms):

• pediatrics  OR children
• teenagers  OR adolescents

3. AND (Boolean AND  joins concepts and narrows the                search):

• occupational therapy  AND children
• stress  AND (occupation OR job)

4. Be aware of differences in American and English spelling and terminology. Most databases use American spelling and terminology as preferred subject terms.

5. Use Truncation (putting * at the end of a word stem will search all forms of the word):

• disab * (disability, disabilities, disabled)
• child * (child, children, childhood, children's)

6. "...." (inverted commas) use for a phrase

• "mental health"
• "occupational therapy"

7. Wildcard ? will search for any single letter in the space. e.g. wom?n will search women, woman, organi?ation will search organisation, organization.

8. Wildcard * can also be used where alternate spelling may contain an extra character. e.g. p*ediatric, will search paediatric or pediatric, behavio*r, will search behaviour or behavior.

• Search strategy planner
• MEDLINE database guide
• CINAHL database guide
• SPORTDiscus database guide
• Web of Science database guide

Literature review

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20 Topics For A Biology Literature Review

Advanced Stem Cell And Developmental Biology – Experimental Design

Finding Articles And Books Using Database For Your Discipline

• The literature review writing service helps the researchers to complte their medical researches. In most research areas literature reviews are in high demand. A need stems from the ever-increasing output of scientific publications .
• Although recognition for scientists mainly comes from primary research, timely literature reviews and the topic selected can lead to new synthetic insights and are often widely read.

The building block of all academic research activities , regardless of discipline, is to base the work on existing knowledge and link it up. Hence, doing so correctly should be a priority for all academics. However, the task has got more and more complicated. Development of knowledge within the field of business research is growing at a tremendous pace while remaining fragmented and interdisciplinary at the same time. This makes it difficult to keep up with state of the art studies and be at the forefront, as well as analyse the accumulated evidence in a specific area of research. Therefore, the literature review as a method of research is more relevant than ever. A review of literature can be generally defined as a more or less systematic way of collecting and synthesizing prior research.

A successful and well-done analysis as a research method provides a firm foundation for the advancement of knowledge and the growth of theory. Scientific research support service offer the medical analysis data that are related to research work. Through combining observations and insights from many scientific studies, a review of the literature will answer research questions with a strength that no single study has (Boyd & Solarino , 2016).

Literature Search, Topics, Journals, Coronavirus, Biology

The Process of Conducting a Literature Review

There are a number of steps that need to be taken and decisions are taken to produce a study that satisfies the publication criteria.  The basic steps and essential choices involved in conducting a literature review will be suggested and addressed in four phases; (1) Planning of the review, (2) Conducting of the review, (3) Analyses and (4) Writing the review (Palmatier et al., 2018).

Interesting topics to Choose in Biology

Here we have discussed 20 topics to choose in biology, which can be quite interesting. The first 10 topics are explained to the point where we can work and the remaining 10 articles are stated on general themes.

1.Obesity related to Genetic Phenomenon

Obesity is a heterogeneous disease whose biological causes are complex. The increasing frequency of obesity over the last few decades is attributed to environmental factors such as sedentary lifestyles and overnutrition, but that is obese at an individual level is determined by genetic susceptibility (Venkatesan & Mohan, 2016).

2.Is Paleo diet the healthiest choice

Paleolithic diet has been gaining worldwide popularity due to its putative health benefits. “Paleo” was Google’s most wanted diet word in 2014. Nonetheless, a 2015 US News and World Report ranking of 35 diets with feedback from a panel of health experts ranked the Paleolithic diet dead last, citing a lack of evidence of clinical benefits from research (Manheimer et al., 2015).

3.Resistant to Antibiotics

Antibiotics are the’ wonder medicines’ used for battling microbes. Numerous types of antibiotics have been not only used for therapeutic purposes for decades but have been used prophylactically across other fields such as livestock and animal husbandry. Uncertainty has emerged as microbes have become immune to specific antibiotics while the host remains unaware of the development of antibiotic resistance (Zaman et al., 2017).

4.The Need of the Hour – Coronavirus

A cluster of identified-cause pneumonia patients was related to a wholesale market for seafood in Wuhan, China, in December 2019. A previously unknown betacoronavirus was discovered from patients with pneumonia by using objective sequencing in the samples .

5.Impact of Tobacco Use

Cigarettes smoked in the form of either smoke or smokeless is dangerous for the human body. Globally, the death toll from cigarettes has risen to around 6.4 million annually and is on a steady rise (Shah et al., 2018).

6.The need to review HIV

Human Immunodeficiency Virus / Acquired Immunodeficiency Syndrome (HIV / AIDS) is a global health problem: more than 70 million people were diagnosed with HIV, 35 million died, and 36.7 million people are currently living with the disease (Fajardo-Ortiz et al., 2017).

7.The Unsolved Leprosy

Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae, is an infectious disease that has destroyed human societies for thousands of years. This ancestral pathogen causes cutaneous lesions to disfigure, peripheral nerve damage, ostearticular deformity, loss of limbs and weakness, blindness and stigma (Franco-Paredes & Rodriguez-Morales, 2016).

8.Tuberculosis – The Disease without Boundaries

An airborne disease of Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), which usually affects the lungs causing severe coughing, fever, and chest pain. While current research has provided valuable insight into the transmission, diagnosis, and treatment of TB over the past four years, much remains to be learned to effectively decrease the occurrence of and ultimately eliminate TB (Levine et al., 2015).

9.The Epidemic of the Century – Diabetes

It studies the epidemic essence of diabetes mellitus in various regions. The North Africa and the Middle East region has the lowest prevalence of diabetes in adults (10.9 percent), while the Western Pacific region has the highest number of diabetes-diagnosed adults and countries with the highest incidence of diabetes (37.5 per cent) (Kharroubi, 2015).

10.Parkinson’s Disease

The disease of Parkinson is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurological disorder. Male sex and advancing age are independent risk factors, and rising productivity and medical resources are taking on increasing toll as the population ages (Hayes, 2019).

General Topics to Focus

• Challenges faced in Research of Herbal Medicines.
• The Global Burden of Periodontitis.
• The new Addiction of the Era – Gaming.
• The prevalence of Road Traffic Accidents among Food Delivery Workers.
• Diet and Nutrition assessment among School Children
• The Boon and Ban of self-medication in India.
• Zombie – A Psychological concept of old tales.
• Backpain among weavers and farmers in India.
• Trends of Oral Cancer in India.
• Self-examination for Breast Cancer among women

Future Scopes

A review of the literature may be thorough or limited, but it should discuss landmark or principal works and works that have been important in the field. The complexity of a review of the literature can vary according to assignment and discipline. The analysis of literature may be part of a larger piece of work or a stand-alone post, meaning it’s a paper entirely. Moreover, literature reviews can pave a way to numerous research questions and research ideas.

References:

• Boyd, B. K., & Solarino, A. M. (2016). Ownership of Corporations. Journal of Management, 42(5), 1282–1314. https://doi.org/10.1177/0149206316633746
• Fajardo-Ortiz, D., Lopez-Cervantes, M., Duran, L., Dumontier, M., Lara, M., Ochoa, H., & Castano, V. M. (2017). The emergence and evolution of the research fronts in HIV/AIDS research. PLOS ONE, 12(5), e0178293. https://doi.org/10.1371/journal.pone.0178293
• Franco-Paredes, C., & Rodriguez-Morales, A. J. (2016). Unsolved matters in leprosy: a descriptive review and call for further research. Annals of Clinical Microbiology and Antimicrobials, 15(1), 33. https://doi.org/10.1186/s12941-016-0149-x
• Hayes, M. T. (2019). Parkinson’s Disease and Parkinsonism. The American Journal of Medicine, 132(7), 802–807. https://doi.org/10.1016/j.amjmed.2019.03.001
• Kharroubi, A. T. (2015). Diabetes mellitus: The epidemic of the century. World Journal of Diabetes, 6(6), 850. https://doi.org/10.4239/wjd.v6.i6.850
• Levine, D. M., Dutta, N. K., Eckels, J., Scanga, C., Stein, C., Mehra, S., Kaushal, D., Karakousis, P. C., & Salamon, H. (2015). A tuberculosis ontology for host systems biology. Tuberculosis, 95(5), 570–574. https://www.sciencedirect.com/science/article/pii/S1472979214205890
• Manheimer, E. W., van Zuuren, E. J., Fedorowicz, Z., & Pijl, H. (2015). Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. The American Journal of Clinical Nutrition, 102(4), 922–932. https://doi.org/10.3945/ajcn.115.113613
• Palmatier, R. W., Houston, M. B., & Hulland, J. (2018). Review articles: purpose, process, and structure. Journal of the Academy of Marketing Science, 46(1), 1–5. https://doi.org/10.1007/s11747-017-0563-4
• Shah, S., Dave, B., Shah, R., Mehta, T., & Dave, R. (2018). Socioeconomic and cultural impact of tobacco in India. Journal of Family Medicine and Primary Care, 7(6), 1173. https://doi.org/10.4103/jfmpc.jfmpc_36_18
• Venkatesan, R., & Mohan, V. (2016). Obesity – Are we continuing to play the genetic “blame game”? Advances in Genomics and Genetics, Volume 6, 11–23. https://doi.org/10.2147/AGG.S52018
• Zaman, S. Bin, Hussain, M. A., Nye, R., Mehta, V., Mamun, K. T., & Hossain, N. (2017). A Review on Antibiotic Resistance: Alarm Bells are Ringing. Cureus. https://doi.org/10.7759/cureus.1403

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• Open access
• Published: 14 May 2024

Effect of cytoplasmic fragmentation on embryo development, quality, and pregnancy outcome: a systematic review of the literature

• Ariella Yazdani 1 , 3 ,
• Iman Halvaei 2 ,
• Catherine Boniface 1 &
• Navid Esfandiari   ORCID: orcid.org/0000-0003-0979-5236 1 , 4  

Reproductive Biology and Endocrinology volume  22 , Article number:  55 ( 2024 ) Cite this article

30 Accesses

Metrics details

The role of cytoplasmic fragmentation in human embryo development and reproductive potential is widely recognized, albeit without standard definition nor agreed upon implication. While fragmentation is best understood to be a natural process across species, the origin of fragmentation remains incompletely understood and likely multifactorial. Several factors including embryo culture condition, gamete quality, aneuploidy, and abnormal cytokinesis seem to have important role in the etiology of cytoplasmic fragmentation. Fragmentation reduces the volume of cytoplasm and depletes embryo of essential organelles and regulatory proteins, compromising the developmental potential of the embryo. While it has been shown that degree of fragmentation and embryo implantation potential are inversely proportional, the degree, pattern, and distribution of fragmentation as it relates to pregnancy outcome is debated in the literature. This review highlights some of the challenges in analysis of fragmentation, while revealing trends in our evolving knowledge of how fragmentation may relate to functional development of the human embryos, implantation, and pregnancy outcome.

Introduction

Human preimplantation embryo scoring systems have been widely used to predict blastocyst development and implantation rate after in-vitro fertilization (IVF). The grading of embryos on day-2 and -3 after fertilization is largely subjective and interpretation varies across IVF laboratories, as it is commonly based on morphological appearance. Characteristics in early embryo grading schema include the amount of cytoplasmic fragmentation (CF) during early cleavage, speed of cellular division, number, size, and symmetry of cells (blastomeres). As defined by the Istanbul consensus workshop on embryo assessment, a fragment is “an extracellular membrane-bound cytoplasmic structure that is < 45 µm diameter in a day-2 embryo and < 40 µm diameter in a day-3 embryo” [ 1 ]. There are several different systems to evaluate embryo morphology including Hill’s scoring system [ 2 ] Cummins' grading system [ 3 ] ASEBIR grading system [ 1 ], the UK/ACE grading scheme [ 4 ]; each system has its own classification for degree of fragmentation as well as embryo grade. This heterogeneity further complicates analysis of fragmentation in relation to outcomes.

CF has been shown to occur early in embryonic division and is a common phenomenon seen in embryos cultured in vitro. CF has traditionally been used as a metric of embryo implantation potential [ 3 , 5 , 6 , 7 ]. The amount and pattern of fragments are analyzed in early development, incorporated into the embryo grade depending on grading system, and used to help select the most developmentally competent embryo to be transferred during an IVF cycle. This classification system is important as a proportion of embryos within a single cohort will not successfully develop to the blastocyst stage in vitro. Although there are various contributing factors to an embryo’s developmental capacity and viability, it is largely agreed upon that fragmentation plays an important role. It seems that the etiology of embryo fragmentation is not fully understood but it may be related to several factors like gamete quality, culture condition, and genetic abnormalities in the embryo [ 8 ]. It is difficult to directly compare and quantify relative degrees of fragmentation across studies. However, it has been repeatedly shown that the extent of fragmentation and implantation potential are inversely proportional [ 5 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. While a low degree of fragmentation does not seem to significantly impact embryo viability, severe fragmentation does [ 7 , 22 , 23 ]. Alongside the cell to cytoplasmic ratio, the pattern and distribution of fragmentation influence the developmental quality of the embryo [ 7 , 24 ]. There are two main patterns of embryo cytoplasmic fragments: scattered and concentrated. The former is characterized by fragment contact within several blastomeres and is related to aneuploidy [ 25 ]. Time-lapse studies have shown that fragmentation is thought to be a dynamic process, where some fragments can be expelled or reintroduced into the cells as the embryo continues to divide [ 25 , 26 ]. Fragments can also easily move or rotate around the associated blastomere and change their position in the embryo [ 27 ].

Current grading systems used to evaluate cleavage-stage embryos are largely based on day-2 or -3 morphology. This can be problematic, as developmental growth of an embryo is variable and the grade of a developing embryo at one point in time is not guaranteed to persist. For example, studies have suggested that embryo selection on day-2 or -3 based on morphological grade can be unreliable and lead to negative pregnancy outcomes [ 28 , 29 , 30 ]. Accordingly, new parameters for predicting implantation success have been proposed including extended embryo culture to the blastocyst stage to day-5, -6 or -7 [ 31 ]. Delaying embryo transfer to the blastocyst stage is advantageous as it can limit the number of unsuccessful embryo transfers and biochemical pregnancies or clinical pregnancy losses in IVF. While there are multiple reports on the impact of cleavage-stage embryo quality on blastocyst formation and blastocyst quality [ 32 , 33 ], few have specifically looked at the degree of fragmentation as a predictive variable.

In this systematic review, we comprehensively reviewed the available literature on the origin and characteristics of CF, factors affecting CF, and the effect of CF and fragment removal on embryo development and pregnancy rate.

Materials and methods

A search was conducted on October 10, 2023, using PubMed and Google Scholar databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines [ 34 ]. In PubMed, the search terms “embryo*[tw] OR cleavage stage [tw] OR "Embryonic Structures"[Mesh] OR "Embryonic Development"[Mesh] OR "Embryo, Mammalian"[Mesh] OR "Cleavage Stage, Ovum"[Mesh]” AND “cytoplasm*[tw] AND fragment*[tw] AND “(Blastocyst*[tw] OR "Blastocyst"[Mesh]) AND (form* OR develop* OR quality*)” were used. A title search in Google Scholar using search terms as above and “embryo cytoplasm fragmentation”, “blastocyst quality”, “blastocyst development” was performed. Only full-text publications in English were included. Full-text articles which did not have any mention of cytoplasmic or embryo fragmentation were excluded, however articles which mentioned both DNA fragmentation and CF were included. Since most of the studies discussing CF also discussed other morphologic features of the embryo, studies that mention embryo morphology, grade or quality were also included. Articles that looked at non-human embryo fragmentation, case reports, case series, book chapters and review papers were excluded. Titles and abstracts were screened, and study quality and bias were assessed. The primary outcomes of interest were embryo quality, blastocyst formation, and pregnancy outcome.

Figure 1 provides details of study screening and inclusion. There were 206 studies screened between the two search engines PubMed ( n =106) and Google Scholar ( n =100). There were 18 duplicates giving a total of 188 articles. Due to the small number of studies from the search criteria, no filter of time was placed. After removal of non-full text articles, articles that used non-human embryos, and articles not relevant to the topic, 20 articles were eligible for inclusion. Forty relevant references from the articles were also extracted, reviewed, and included in this review. These additional articles were reviewed with the same inclusion and exclusion criteria as mentioned above. A total of 60 articles were included in the qualitative synthesis of this review.

Article Identification and Screening

Origin and etiology of CF

The etiology of CF is not completely understood. There are several proposed theories as to why embryos display variable degrees of fragmentation. Fragmentation has been shown to be a natural, unpredictable process both in vitro and in vivo and is documented in various species [ 35 , 36 ]. This suggests that embryo fragmentation is neither species-specific nor solely a byproduct of in vitro culture. Assisted reproductive technology (ART) and IVF techniques, such as time-lapse microscopy (TLM) and transmission electron microscopic (TEM) analyses, have recently allowed for further understanding of embryo developmental potential and fragmentation (Figs.  2 and 3 ). Seven of the included studies in this review propose potential hypotheses as to the origin of CF (Table 1 ). Three of the articles evaluated gamete quality as related to fragmentation in a developing embryo [ 37 , 38 , 39 ].

Human cleavage stage embryos a) Day-2 embryo at 4-cell stage with no fragmentation, b) fragmented Day-2 embryo, c) Day-3 embryo at 8-cell stage with no fragmentation, d) fragmented Day-3 embryo, e) Day-5 cavitating Morula with no fragmentation, f) fragmented Day-5 cavitating Morula

Ultrastructure and organelle microtopography of an embryo fragment by transmission electron microscopy. Ly: primary lysosome, M: mitochondrion, rM: remnant of regressing mitochondrion, MV: mitochondria-vesicle complex, V: vesicle; scale bar: 1 µM

An early study showed that sperm DNA oxidation has been associated with embryo development and quality, and therefore linked to CF [ 37 ]. Nucleolar asynchrony in the zygote from sperm DNA fragmentation has previously been shown to predict future low-quality blastocyst development. A positive correlation has also been found between the percentage of sperm OxiDNA-stained cells with embryo fragmentation on day-2 and -3 of development. Sperm DNA oxidation may therefore be associated with fragmented, nonviable, poor-quality embryos [ 37 ] . A recent study also showed the negative correlation between sperm DNA fragmentation and blastomere DNA fragmentation and blastulation rate [ 40 ]. Further studies are needed to confirm the impact of sperm DNA oxidation on embryo fragmentation.

An observational study documented the degree of fragmentation of human embryos as they progressed through mitotic cell cycles [ 38 ]. In this study, the authors analyzed nearly 2,000 oocytes and 372 embryos, and found that increased embryo fragmentation (>50%) was associated with a specific pattern of development: delayed first division (oocyte spindle detected at 36.2 hours after hCG injection vs. 35.5 hours in low fragmentation), a significantly earlier start of the second mitosis (8.9 hours vs. 10.8 hours after the first mitosis), and a significant delay of the third mitosis after the second mitosis (2.2. hours vs. 0.6 hours). The authors did not comment on whether fragmentation could be a result of the cell dividing before proper chromosome alignment, or if existing aneuploidy resulted in erroneous cleavage patterns [ 38 ].

Polar body (PB) fragmentation has also been investigated in relation to cytoplasmic fragmentation. Ebner et al., in a prospective study analyzed the relationship between a fragmented first PB and embryo quality in patients undergoing ICSI. Two groups of oocytes were analyzed according to PB fragmentation: intact first PBs and those with fragmented PBs. Forty-two hours after ICSI, embryo morphology (i.e., number of blastomeres and degree of fragmentation) was recorded. Overall, a significantly higher percentage of cytoplasmic fragmentation was seen in day-2 embryos that originated from oocytes with fragmented first PBs than those with intact PBs ( P < 0.05). This study further supports the concept that oocyte quality contributes to overall embryo fragmentation and provides evidence that preselection of oocytes may contribute to the prognosis of embryo quality and blastocyst development [ 39 ]. The role of PB fragmentation on embryo quality was confirmed in other studies [ 41 , 42 ], however, a recent study has not recommended considering PB status as a tool for embryo selection [ 43 ].

Beyond analysis of gamete quality, other studies have shown a biochemical relationship between embryo competence and fragmentation. One study showed that disturbances in E-cadherin, a cell adhesion protein that plays a critical role in morphogenesis, occur in embryos with cleavage abnormalities and extensive cytoplasmic fragmentation, suggesting a possible mechanism to the loss of embryonic viability [ 44 ]. Further, by using mitochondrial fluorescence techniques, Van Blerkom et al., found that mitochondrial distribution at the pronuclear stage may be an epigenetic factor related to the organization of the embryo and further embryonic development [ 45 ]. Blastomeres that were deficient in mitochondria and thus ATP at the first or second cell division remained undivided and often died during subsequent culture. Although this study examined morphologically normal (unfragmented) cleavage-stage embryos, it may support the idea that perinuclear mitochondrial distribution and microtubular organization influence developmental capacity of early cleavage-stage embryos [ 45 ]. Higher numbers of mitochondria reported in fragmented compared to the normal blastomeres show the rapid depletion of ATP in the fragmented embryos [ 21 ]. There have also been reports of increased gene transcription of mitochondrial factors like OXPHOS complexes, ATP synthase, and mtDNA content in highly fragmented embryos compared to controls [ 46 ]. Mitochondrial activity is lower and more centralized in fragmented embryos compared to good quality embryos on day-3 [ 47 ]. Mitochondria are the main source of ATP for embryo mitosis, and their proper function is essential for embryo development. More research is needed to elucidate the morphology and role of mitochondria in embryo development, especially in relation to fragmentation.

A subsequent study by Van Blerkom et al., analyzed the temporal and spatial aspects of fragmentation through TLM and TEM analyses from the pronuclear to the 10-12-cell stage. Through TLM, the authors visualized the non-discrete, dynamic nature of fragments and noted that many were “bleb-elaborations” of the plasma membrane and cytoplasm. They characterized two patterns of fragmentation: definitive and pseudo-fragmentation. Definitive fragmentation was described as fragments detached from a blastomere, and pseudo-fragmentation was assigned when the fragments were no longer detectable during subsequent development. Often one developing embryo would show both fragmentation patterns at different stages of development, suggesting that these patterns may have different etiologies and effects on embryo development competence [ 47 ]. Hardarson et al., similarly used TLM to document that fragments are dynamic and can be internalized throughout cleavage during culture periods. The contents of the fragments were noted to be internalized and released into the cytoplasm of the blastomere and seen on multiple time-lapse photographs as a cytoplasmic turbulence. This is the first reported evidence that cellular fragments can “disappear” during the culture period in human IVF [ 26 ]. It seems that in mild to moderate CF, the timing of embryo evaluation and grading can affect the reported percent of fragmentation.

Lastly, we have included a preliminary study performed by Sermondade et al., that suggests a specific subgroup of patients who have had repeated IVF failures (presumably due to a recurring high rate of fragmented embryos) may benefit from early intrauterine embryo transfer at the zygote stage (2PN) [ 48 ]. Data showed a delivery rate per oocyte retrieval of 18.9%, which was significantly higher than the delivery rate of 7.5% in the matched control group. The results were encouraging and suggestive of a safe, non-invasive rescue strategy for patients who experience recurrent highly fragmented embryos and failed IVF attempts. The data further suggests that fertilized oocytes of this subgroup may have deficiencies in certain maternal factors (i.e., stress-response factors) that do not allow normal embryo development in culture environments [ 48 ]. Another study was also confirmed application of zygote transfer in patients with history of low-quality embryos [ 49 ]. However, further studies are required to verify the impact of this technique for patients with history of fragmented embryos.

Apoptosis is another proposed etiology of fragmentation. Apoptosis may occur in blastomeres with defective cytoplasm or abnormal chromosomes, leading to embryo fragmentation [ 50 ]. There are several studies reporting apoptosis in both fragments and neighboring blastomeres in a fragmented embryo [ 24 , 50 ]. Chi et al., showed that fragments are associated with both apoptosis and necrosis [ 21 ]. One of the factors that appears to induce apoptosis in blastomeres is suboptimal culture conditions such as hypoxia [ 51 ]. In addition, there are controversial reports on the role of reactive oxygen species (ROS) in embryo fragmentation [ 52 , 53 ]. It has been shown that ROS are present at high levels in the culture media of fragmented embryos [ 52 , 54 ]. Chen et al., recently showed that embryo culture in 5% oxygen, from days 1 to 3, is associated with higher embryo quality and live birth rate compared to 20% oxygen [ 55 ]. The effects of culture condition modifications, such as hypoxia and ROS, on embryo fragmentation need to be clarified to understand the importance of culture condition in this process.

Membrane compartmentalization of DNA, abnormal cytokinesis, and extra vesicular formation are other proposed theories for embryo fragmentation [ 8 ]. Defects or damages in mitochondria are associated with low ATP and high ROS production leading to a compromised cell division and cytokinesis [ 27 ]. In addition, there is a correlation between embryo fragmentation and ploidy status. Chavez et al., showed that CF was seen in a high proportion of aneuploid embryos, and that meiotic and mitotic errors may cause fragmentation in different cell development stages. Meiotic errors were associated with fragmentation at one-cell stage while mitotic errors were associated with fragmentation at interphase or after first cytokinesis [ 56 ]. Chromosomally abnormal embryos often have severe fragmentation, which may be another cause of CF [ 55 , 57 ].

Overall, the precise cause of CF has yet to be clearly defined. The above investigations have elucidated potential sources and associations of what is likely a complex and multifactorial process and represent our current understanding of CF origin.

What is contained in CF?

Four of the included studies used various technological advances to study the contents of CF in human embryos (Table 2 ). Two studies used TEM methods to evaluate fragment ultrastructure (Fig.  3 ) [ 21 , 58 ]. Fragments were extracted from embryos with 10-50% fragmentation and the ultrastructure evaluated by TEM. Micrographs showed that the fragments had a distinct membrane containing cytoplasmic organelles including mitochondria, mitochondria-vesicle complexes, Golgi apparatus, primary lysosomes, and vacuoles. Mitochondria were the most abundant structure.

In an additional evaluation of CF contents, Johansson et al., analyzed DNA content of fragments to define a cutoff diameter for an anucleate fragment or blastomere. Findings showed that 98% of fragments <45 µm on day-2 and 97% of those <40 µm on day-3 contained no DNA and, if not reabsorbed into a blastomere, showed a loss of cytoplasm. Presence of essential blastomere organelles such as mitochondria, mRNA, and proteins within cytoplasmic fragments were related to embryo development arrest [ 59 ]. Lastly, Chi et al., also used TEM to examine ultrastructure of the human fragmented embryos and found that blastomeres with anucleate fragments contained fewer mitochondria in their cytoplasm compared to normal blastomeres [ 21 ].

Cell death and CF

Eight of the included studies analyzed the relationship between cell death and embryo fragmentation (Table 3 ). Five studies analyzed the status of chromatin in arrested fragmented embryos through a combined technique for simultaneous nuclear and terminal transferase-mediated DNA end labelling (TUNEL) [ 24 , 60 , 61 , 62 , 63 ]. Two studies used a comet assay to analyze DNA fragmentation [ 21 , 63 ]. Four of the eight studies used Annexin V staining [ 21 , 61 , 62 , 63 ] with three including the presence of propidium iodide (PI) to compare apoptosis to necrosis [ 21 , 61 , 63 ].

Jurisicova et al., used a combined nuclear and fragmented DNA labeling approach which allowed distinction between chromatin status and DNA fragmentation, which serve as markers of apoptosis versus necrosis respectively [ 60 ]. After fertilization, embryos were stained with 4,6-diamidino-2-phenylindole (DAPI). In cases of compromised cell membrane integrity, DAPI stain was observed in the cytoplasm as a sign of necrosis. Concomitant use of TUNEL labeling reflected the integrity of the DNA and allowed distinction between necrotic and apoptotic cells. Through combined techniques of DAPI/TUNEL, TEM, scanning electron microscopy (SEM) and stereomicroscopic observations, 153 of 203 (75.4%) fragmented early cleavage-stage embryos displayed signs of apoptosis (i.e., chromatin condensation, cellular shrinkage, DNA fragmentation, presence of cell corpses) with or without normal nuclei [ 60 ].

Similarly, Levy et al., analyzed early arrested or fragmented preimplantation embryos and the pattern of DNA fragmentation using TUNEL assay and the presence of phosphatidylserine through Fluorescein isothiocyanate (FITC)-labelled Annexin V, a phosphatidylserine binding protein. The authors observed TUNEL staining in one or more nuclei of 15 out of 50 (30%) arrested embryos from the 2-cell stage to uncompacted morulae, all of which had high degrees of CF. Furthermore, embryos with regular-sized blastomeres without fragmentation were all TUNEL negative [ 50 ].

A separate prospective study by Antczak et al., explored the possible association between fragmentation and apoptosis using PI and Annexin V staining of plasma membrane phosphatidylserine and TUNEL analysis of blastomere DNA [ 24 ]. In contradistinction to prior studies, these authors found no direct correlation between fragmentation and apoptosis. Virtually all blastomeres that were PI negative, intact or fragmented, showed no TUNEL or annexin V fluorescence, suggesting no signs of apoptosis [ 24 ].

Liu et al., used a similar methodology of TUNEL labeling and Annexin V staining to detect markers of apoptosis in fragmented human embryos derived from IVF [ 61 ]. Overall, highly fragmented embryos had apoptotic features including bright fluorescence (positive TUNEL labeling signifying DNA fragmentation) on the cell corpses and in intact blastomeres [ 61 ]. By staining cells with both annexin V and PI, this study was able to demonstrate that apoptosis occurs frequently in fragmented human embryos and the coexistence of apoptotic, necrotic and viable sibling blastomeres can occur. Sibling blastomeres within an embryo often showed apoptotic features that led to secondary necrosis while others did not initiate apoptosis. The authors did not find a significant difference in the expression frequency of apoptotic genes between viable and nonviable or arrested embryos [ 61 ].

Chi et al., stained human embryos ( n =10) with annexin V and PI and found that human fragmented embryos exhibited characteristics of both necrosis and apoptosis [ 20 ]. Rather than TUNEL assay, these authors used a modified sperm comet assay to investigate DNA fragmentation of human fragmented embryos. They found that 6/7 human fragmented embryos (85.1%) stained positively for PI with the intensity of staining increasing with the degree of fragmentation. Of note, DNA fragmentation was observed in fragmented human embryos but not in the normal embryo [ 21 ].

Metcalfe et al., analyzed the expression of 11 BCL-2 family genes in normally developing embryos and in severely fragmented embryos [ 64 ]. They found that the expression of BCL-2 family genes was highest in the pronuclear stage and eight-cell stages, and lowest at the two-cell, four-cell, and blastocyst stages in developmentally intact embryos. Furthermore, the expression did not change in fragmented embryos, suggesting that embryo fragmentation does not likely compromise mRNA integrity and gene detection [ 64 ]. However, like Liu et al., [ 61 ] these authors did detect far fewer pro-apoptotic BCL-2 genes in fragmented embryos at the eight-cell stage. The authors noted that these findings do not distinguish between iatrogenic apoptosis from suboptimal in-vitro culture conditions [ 64 ]. A separate study by Jurisicova et al. similarly analyzed gene expression at the 2-, 4- and 8-cell stage of fragmented embryos. Embryos that had 30-50% fragmentation showed a significant increase in Hrk mRNA levels, a BCL-2 protein encoding gene ( P = 0.016). Further, these authors found an increase in Caspase-3 mRNA in fragmented embryos, as well as induction of Caspase-3-like enzyme activity in nucleated fragments, although this finding was not statistically significant [ 65 ].

Van Blerkom et al., also used TUNEL assay in conjunction with the comet assay as a method of identifying the specific pattern of cell death (necrosis, lysis or apoptosis) and the extent of DNA damage in developing embryos [ 47 ]. They analyzed the integrity of the plasma membrane through annexin V staining with PI. They examined both transient and persistent fragment clusters at day-3 and 3.5 embryos for evidence of programed cell death using time-lapse video and TEM. In contrast to previous studies, they found no indication of nuclear DNA damage or loss of membrane integrity. These results, led the authors to hypothesize that the fragmentation observed was not characteristic of programed cell death, but rather resembled features of oncosis. The culture in this study was not severely oxygen-deprived and thus the authors concluded that this oncosis-like process was potentially a result of disproportionate mitochondrial segregation during the first cleavage division. Without sufficient mitochondria, the early blastomeres did not maintain adequate ATP for normal cell function which may have precipitated an ATP-driven oncosis-like process [ 47 ].

Lastly, a study by Bencomo et al., found correlations between the degree of apoptosis in human granulosa-lutein (GL) cells, the outcome of IVF-ET cycle, the percentage of embryo fragmentation, and patient’s age [ 66 ]. Human GL cells were collected from follicular fluid, cultured for 48 hours, and marked with caspACE FITC-VAD-FMK, a fluorescent marker for activated caspases. Results showed that GL cells of older women (>38 years old) were significantly more susceptible to apoptosis at 43.2 ± 18.0% compared to the younger group (<38 years old) with a mean percentage of apoptotic cells 33 ± 17.2%. Women who had a positive pregnancy had a lower level of apoptosis in GL cultures than those who did not get pregnant (30.2 ± 14% vs. 40.4 ± 19.5%). There was a positive correlation between embryo fragmentation and GL cell apoptosis ( r = 0.214). Overall, the level of apoptosis of cultured GL cells was correlated with IVF outcome [ 66 ].

These studies demonstrate the diversity among techniques to evaluate cell death in the developing embryo. TUNEL labeling, sperm comet assay, annexin V staining or some combination of these techniques have been described. Furthermore, there are discrepancies between the stage at which apoptosis might occur, with majority of studies cited here suggesting that cell death occurs in early stages of development before blastocyst formation. While some studies suggest that fragmented embryos display signs of apoptosis, these findings are still disputed and the distinction between apoptosis and necrosis is not clearly defined in the literature.

Patient age and CF

There are inconsistencies within the literature regarding the relationship between maternal age and CF. A total of six studies in this review focused on this relationship (Table 4 ). Three of the studies found a positive correlation between patient age and degree of embryo fragmentation [ 67 , 68 , 69 ]. The other three studies found no age-related correlation between embryo fragmentation or quality [ 7 , 70 , 71 ].

A retrospective study by Ziebe et al., compared the relationship between age of women undergoing IVF and the proportion of anucleate fragmentation in cleavage-stage embryos. Using a logistic regression analysis, the authors compared the percentage of transfers using fragmented embryos with age; the odds of fragmentation increased by 3% per year (OR 1.033 [95% CI 0.996, 1.071]). There was a linear relationship between age and embryo fragmentation rate, with an increase in fragmentation of 0.76% per year (95% CI -0.09%, 1.61%) [ 68 ].

Keltz et al., assessed various predictors of embryo fragmentation in IVF and found that increased maternal age and lower number of oocytes and embryos were associated with increased embryo fragmentation. There was a significant difference between cycles with fragmented embryos ( n =74) at a mean age of 36.9 ± 4.24 years as compared to cycles with no fragmented embryos ( n =234) at a mean age of 35.4 ± 4.74 years. Overall, this retrospective analysis of fresh IVF cycles found that embryo fragmentation is indeed associated with older age and ultimately poor cycle outcome [ 67 ].

Contrary to these findings, an early study by Alikani et al., showed no relationship between maternal age and CF [ 7 ]. In a retrospective analysis of degree and pattern of embryo fragmentation on days 2 and 3, they defined five patterns of fragmentation. Both the degree and pattern of fragmentation impacted pregnancy and implantation rate, but the authors found no correlation between appearance of any CF pattern and maternal age. The average maternal age in their population was 35.7 ± 4.25 years [ 7 ]. Another study by Stensen et al., analyzed the effect of chronological age on oocyte quality (assessed by maturity) and embryo quality (assessed by cleavage-stage, blastomere size and embryo fragmentation). Women were divided into five age groups: ≤25, 26–30, 31–35, 36–40 and ≥41 years. The embryo morphological score was based on fragmentation and blastomere size with score of 0-4 where score of 4 being equally sized blastomeres and no fragmentation and score of 0 being cleavage arrest or morphologically abnormal embryo. The mean oocyte score and embryo morphology score were not found to be significantly different across the age groups [ 70 ]. Wu et al., also showed that age does not influence embryo fragmentation. Patient ages ranged from 20 to 44 years with a mean age of 30.6 ± 4.6 years and were divided into age groups of ≤29, 30–34, 35–37, 38–40, and ≥41 years of age. Analysis of embryos with similar degrees of fragmentation was used to assess whether maternal age was associated with embryo fragmentation and blastocyst development. There was no correlation between age and embryo fragmentation as a continuous variable ( r = 0.02; P = 0.25) nor was there a correlation when age was divided into the groups ( P = 0.2). They also found that neither age ( r = -0.08; P =0.16) nor degree of fragmentation ( r = -0.01; P = 0.81) had a significant impact on blastocyst development [ 71 ].

Recently, a retrospective time-lapse study evaluated the implantation rate of 379 fragmented embryos. The results showed that there was an association between advanced maternal age and fragmentation. Fragmentation rate was higher in patients ˃35 compared to patients ≤35 years old. It seems that the lower quality of oocytes in older patients results in increasing fragmentation [ 69 ]. Overall, the included studies have differing conclusions on the effect of maternal age and CF; varying definitions and analysis of CF remain a limitation.

IVF vs ICSI procedures and CF

Five of the included studies compared embryo quality between conventional IVF and intracytoplasmic sperm injection (ICSI) procedures (Table 5 ). Two of these studies found that ICSI was associated with impaired embryo morphology compared to IVF [ 72 , 73 ], while the other three showed no difference in embryo quality between the two fertilization modalities [ 74 , 75 , 76 ]. There were no studies within our search that identified embryos created by ICSI having greater morphology grade, or less embryo fragmentation, than IVF.

Frattarelli et al., directly examined the effect of ICSI on embryo fragmentation and implantation rate compared to IVF. There was a significant difference in mean embryo grade between IVF and ICSI. IVF patients had significantly more grade I, or non-fragmented, embryos compared to the ICSI group ( P < 0.01). However, there was no significant difference in mean number of embryos per embryo grade II – IV [ 72 ].

Similarly, Hsu et al., compared embryo quality, morphology, and cleavage after ICSI with standard IVF patients. They defined the grading system from 1 – 5, ranging from no fragments (grade 1) to severe or complete fragmentation (grade 5). They found that for the overall population, when comparing ICSI and IVF patients after matching for age and number of embryos transferred, the number of embryos with good morphology was significantly greater in the IVF group compared to ICSI ( P < 0.006). The average morphology scores, similar to the results of Frattarelli et al., were significantly different between the ICSI group and the IVF group. They also found IVF patients’ embryos to have significantly better cleavage rate than those from ICSI patients ( P < 0.001) [ 73 ].

Garello et al., evaluated if fertilization via ICSI influences pronuclear orientation, PB placement, and embryo quality when compared to IVF. Embryos were assessed using morphology, and grouped as good (grades 1-2), average (grades 3-4), or poor (grades 5-6). Embryos were also assessed for cleavage regularity and proportion of fragmentation (0, <20%, 20–50%, >50%). There was no statistically significant difference in mean morphology (good, average, poor) between the groups, although they did note an apparent increase in grade 4 versus grade 3 embryos after ICSI procedure. The two groups had similar proportions of fragmentation [ 74 ].

Two other studies took a unique approach in comparing embryo quality in ICSI and IVF patients by using randomized sibling oocytes [ 75 , 76 ]. Yoeli et al., studied oocytes retrieved from patients with a less than 40% fertilization rate in a previous standard IVF cycle and divided these oocytes into a conventional insemination group and an ICSI group. Each group had over 1400 oocytes. Overall, there was no significant difference between the IVF and ICSI groups in terms of cleavage rate or rate of high-quality embryos (both Grade A embryos with ≤10% fragmentation and embryos with ≤20% fragmentation) [ 75 ]. Ruiz et al., also analyzed sibling oocytes in patients who had failed intrauterine insemination attempts. The authors similarly found no significant difference in fertilization rates and degree of fragmentation between ICSI and standard IVF groups [ 76 ]. Most studies included in the search criteria showed that ART techniques such as ICSI do not significantly impact fragmentation rate in developing embryos, suggesting that ICSI is not a significant contributor to poorer outcomes by way of embryo fragmentation. Of note, the timing of cumulus cell denudation after conventional IVF is a matter of debate; none of the included studies in this review performed short-time insemination. In a meta-analysis reviewing denudation times, the number of good quality embryos produced after retaining cumulus cells was similar to those produced after early removal of these cells, suggesting that brief insemination has no impact on CF [ 77 ]. Liu et al. also showed that short insemination time is not associated with different outcomes in terms of embryo development [ 78 ].

Effect of CF on embryo development

It is commonly believed that CF has detrimental effects on embryo development. Thirteen of the included studies found a negative effect of CF on embryo development (Table 6 ). Various approaches have been used to propose a hypothesis as to how increased fragmentation impedes embryo development.

Van Blerkom et al., showed through time-lapse video and TEM that fragments physically impede cell-cell interactions, interfering with compaction, cavitation, and blastocyst formation [ 63 ]. In an ultrastructural observational study by Sathananthan et al., 15 embryos were cultured with human ampullary cell lines and TEM used to evaluate embryo development. They noted degeneration of blastomeres, including incomplete incorporation of chromatin into nuclei and formation of micronuclei, which was possibly a consequence of being adjacent to blastomere fragments [ 79 ]. A much larger prospective study by Antczak and Van Blerkom analyzed 2293 fertilized eggs from 257 IVF cycles to examine the effect of fragmentation on the distribution of eight regulatory proteins. Fragmentation reduced the volume of cytoplasm and depleted embryos of essential organelles or regulatory proteins, compromising the embryo developmental potential. They also found that specific fragmentation patterns during various stages of embryo development, i.e., 2- and 4-cell stages, were associated with embryo viability and therefore could have clinical application in the selection of embryos for transfer [ 24 ]. As previously mentioned, fragmentation may affect compacted/morula and blastocyst quality [ 80 ]. Cell exclusion at this stage is due to failure or abnormal expression of proteins involved in compaction [ 44 , 81 ]. Blastomeres may also irregularly divide, resulting in fragmentation and exclusion from compaction [ 82 ], and excluded cells have a high rate of aneuploidy [ 83 ]. Blastocyst quality from fully compacted embryos has been reported to be higher than blastocysts with partial compaction [ 84 ].

The hypothesis that fragmentation reflects inherent embryogenetic abnormalities, such as aneuploidy, increased mosaicism, or polyploidy, is supported by multiple studies in this review [ 55 , 57 , 85 ]. Morphologically poor-quality embryos, defined by amount of fragmentation, were often found to have concomitant chromosomal abnormalities [ 57 , 85 ]. Culture environment has also been implicated in presence and degree of fragmentation. For example, Morgan et al., using video-cinematography found that embryos cultured on a monolayer of feeder cells had fewer fragments than did embryos cultured alone [ 86 ]. In addition to aneuploidy and external environment, degree of fragmentation also appears to be related to embryo quality. Both Alikani et al., and Hardy et al., have shown that a small degree of fragmentation (<15%) on day-2 embryos did not affect blastocyst formation but increased (> 15%) fragmentation was associated with significantly reduced blastocyst development [ 23 , 87 ]. Similarly, a prospective study of over 4000 embryos by Guerif et al., showed that the rate of blastocyst formation increased significantly with decreased fragmentation (<20%) on day-2 embryos [ 32 ].

A separate study by Ivec et al., graded day-4 and -5 morulae based on the degree of fragmentation (<5%, 5%–20%, or >20%) and compared their blastocyst development rate. They found a negative correlation between degree of fragmentation and clinically usable blastocysts, optimal blastocysts, and those with a hatching zona pellucida. Through logistic regression analysis, they found that with each increase in percentage of fragmentation in morulae, there was a 4% decrease in the odds of hatching (OR: 0.96, 95% CI: 0.95–0.98;  P < 0.001) and optimal blastocyst formation (OR: 0.96, 95% CI: 0.94–0.97;  P < 0.001) [ 88 ]. It is important to point out that the degree of embryo fragmentation, no matter at what stage of development, is measured subjectively without standardized methods. One study from Hnida et al., included here recognized this limitation and used a computer-controlled system for multilevel embryo morphology analysis [ 89 ]. The degree of fragmentation was evaluated based on digital image sequences and correlated to the blastomere size. Fragments were defined to be anucleate with an average diameter of <40 µm. Not surprisingly, the mean blastomere volume decreased significantly with increasing degree of fragmentation ( P < 0.001). In addition, average blastomere size was significantly affected by the degree of fragmentation and multinuclearity which may function as a biomarker for embryo quality [ 89 ]. Furthermore, Sjöblom et al., analyzed the relationship of morphological characteristics to the developmental potential of embryos [ 90 ]. These authors, similar to Hnida et al., found that a large cytoplasmic deficit, i.e., blastomeres not filling the space under the zona, was detrimental to blastocyst development (P < 0.044). However, this is the only study in which the extent of CF observed was not significantly associated with blastocyst development [ 90 ]. Another study using time-lapse imaging showed an association between cytoplasmic fragments at the two-cell stage and perivitelline threads. Perivitelline threads can be observed as the cytoplasmic membrane withdraws from the zona pellucida during embryo cleavage. Ultimately, the presence of these threads, despite the level of fragmentation, did not affect embryo development [ 91 ]. As demonstrated by the studies described here, the degree of CF has a largely negative effect on embryo development.

Effect of CF on embryo implantation and pregnancy

In addition to evaluating the effect of CF on preimplantation embryo development, it is important to assess the effect of CF on implantation and pregnancy outcomes. Five of the included studies have shown a negative effect of CF on implantation or pregnancy outcome (Table 7 ). Assuming that increased fragmentation is detrimental to embryo development, implantation, and pregnancy outcome, it is important to understand the embryo scoring system that determines the best embryo for transfer. Giorgetti et al., used single embryo transfers to devise an embryo scoring pattern to best predict successful implantation. Not surprisingly, higher pregnancy rates were observed with embryos that displayed no fragmentation. The authors found that both pregnancy rate and live birth rate were significantly correlated with a 4-point score based on cleavage rate, fragmentation, irregularities displayed, and presence of a 4-cell embryo on day-2 [ 12 ].

Racowsky et al., assessed if multiple evaluations of an embryo improve selection quality and thus implantation and pregnancy success. They noted that an increased level of fragmentation on both day-2 and -3 was associated with a significant reduction in the number of fetuses that developed to 12 weeks. They also noted that severe fragmentation (>50%) impaired overall embryo viability and may be related to low pregnancy rates and high risk of congenital malformations. The authors ultimately concluded that single day morphological evaluation on day-2 or day-3 has the same predictive value to a multi-day scoring system [ 22 ].

Another retrospective analysis of 460 fresh embryo transfers by Ebner et al., sought to determine the impact of embryo fragmentation on not just pregnancy, but also obstetric and perinatal outcomes. There was a significant relationship between fragmentation and implantation and clinical pregnancy rate, but not with multiple pregnancy rate or ongoing pregnancy rate [ 10 ]. Alikani et al., also studied embryo fragmentation and its implications for implantation and pregnancy rate and included fragmentation pattern into their discussion. They too found a significant decrease in implantation and pregnancy rate as the degree of fragmentation increased. They identified an effect on pregnancy rate when the degree of fragmentation was greater than 35%. The authors went on to discuss that not all fragmentations are detrimental to the embryo development and that the pattern of fragmentation matters. They found that fragmentation pattern type IV, defined as having large fragments distributed randomly and associated with uneven cells, had significantly lower implantation and clinical pregnancy rates when compared to types I-III. They concluded that detaching blastomere cytoplasm as large fragments is most detrimental to embryo development and implantation rate. In contrast, small, scattered fragments (type III) did not seem to appreciably affect the cell number or pose a serious threat to further development [ 7 ].

Lastly, Paternot et al., used sequential imaging techniques and a computer-assisted scoring system to study blastocyst development and the effect of fragmentation on clinical pregnancy. The authors reviewed the volume reduction over time as a measure of embryo fragmentation. They analyzed volumes on day-1 to -3 and found a significant association between total embryo volume and pregnancy rate on both day-2 ( P = 0.003) and day-3 ( P = 0.0003), with the total volume measured on day-3 being the best predictor of pregnancy outcome [ 92 ]. In contrast, Lahav-Baratz recently showed that there was no association between fragmentation rate and abortion or live birth rate. It was concluded that fragmented embryos still have implantation potential and could be considered for transfer when applicable [ 69 ].

Effect of CF removal on embryo development

The effect of fragment removal on IVF outcomes has been controversial. Six of the studies included in this review discussed the impact of removing fragments on embryo development (Table 8 ) [ 7 , 67 , 93 , 94 , 95 , 96 ]. The literature is mixed, with some studies showing improvement in embryo development quality after fragmentation removal [ 7 , 93 ], and others showing no difference at all [ 70 , 94 , 95 ].

Alikani et al., were one of the first investigators to define various patterns of fragmentation and perform microsurgical fragment removal to improve implantation potential [ 7 ]. The authors found that the pattern and degree of fragmentation, and not merely the presence of fragmentation, was significant. When assisted hatching and microsurgical fragment removal was performed, there was an overall 4% increase in implantation rate. They concluded that the removal of the fragments possibly restored the spatial relationship of the cells and limited the interference of cell-cell contact. Further, their preliminary data showed that blastocysts formed after fragment removal were better organized than their unmanipulated counterparts [ 7 ].

Eftekhari-Yazdi et al., similarly studied the effect of fragment removal on blastocyst formation and quality of embryos [ 93 ]. They compared day-2 embryos without removal of fragments to those that fragments were microsurgically removed. There were significantly higher quality embryos in defragmented group compared to the control. Furthermore, fragment removal improved the blastocyst quality compared to the control group. There was also a reduction of apoptotic and necrotic cells in experimental group when compared with the control group [ 93 ].

Two separate studies by Keltz et al., assessed implantation, clinical pregnancy, and birth outcomes after defragmentation [ 67 ], as well as embryo development and fragmentation rate after day-3 embryo defragmentation [ 94 ]. The authors first compared cycle outcomes between low-grade embryos that underwent micromanipulation for fragment removal (>10% fragmentation) and high-grade embryos that did not undergo defragmentation but were hatched on day 3. When compared, the defragmented group showed no difference in rates of implantation, clinical pregnancy, live birth, spontaneous abortion, or fetal defects as compared to the cycles that included all top-grade embryos. Factors associated with poor IVF prognosis and formation of embryo fragments included advanced age, decreased number of oocytes and embryos, and embryo grade [ 67 ].

A separate prospective randomized study by Keltz et al., looked more specifically at day-5 fragmentation, compaction, morulation and blastulation rates after low grade day-3 embryo defragmentation [ 94 ]. Paired embryos from the same patient, not intended to be transferred, were randomly placed in either the experimental group, assisted hatching and embryo defragmentation, or control group (assisted hatching alone). Paired embryos had no difference in mean cell number, percent fragmentation, and grade before randomization. Results showed that on day-5, embryos in the defragmentation group had significantly diminished fragmentation when compared with controls; however, there was no difference in compaction rate, morula formation rate or blastocyst formation rate. Embryo grade generally improved in the treatment group, but this was not statistically significant. Overall, in both groups, improved embryo development was significantly associated with lower levels of fragmentation in the day-3 embryos, supporting the idea that defragmented embryos maintain their reduced fragmented state throughout preimplantation development. Of note, this study had 35 embryos in each group and was limited to lower grade embryos not intended for transfer [ 94 ].

Another, larger prospective randomized study by Halvaei et al., compared the effect of microsurgical removal of fragments on ART outcomes. The authors divided 150 embryos with 10-50% fragmentation into three groups, case ( n =50), sham ( n =50), and control ( n =50). They found no significant difference in rates of clinical pregnancy, miscarriage, live birth, multiple pregnancies, or congenital anomalies between these groups, ultimately showing that cosmetic microsurgery on preimplantation embryos to remove CFs had no beneficial effect [ 95 ].

Lastly, a pilot study by Yumoto et al., aimed to decrease CF in developing embryos by removing the zona pellucida of abnormally fertilized (3PN) donated oocytes [ 96 ]. Although they did not attempt to remove fragments themselves, this study is included as ZP-free oocytes are sometimes encountered in or because of ART procedures, i.e., ICSI. The results suggest that the rate of fragmentation is decreased after mechanical ZP removal. The authors concluded that ZP is not always necessary for normal embryo development since the ZP-free embryos developed normally, maintained their cell adhesions, and had a decreased rate of fragmentation [ 96 ]. It seems that defragmentation of an aneuploid or severely fragmented embryo, only improves the embryo morphology grade but the quality and fate of embryo is not changed [ 97 ].

CF and chromosomal abnormalities in embryo

Although the relationship between DNA fragmentation and chromosomal abnormalities has been more commonly explored in the literature, CF may also be related to intrinsic chromosomal abnormalities in developing embryos. Fourteen studies included in this review explored this relationship (Table 9 ) [ 55 , 56 , 85 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ].

CF was rarely seen in embryos with normal chromosomal content. Findikli et al., studied DNA fragmentation and aneuploidy in poor quality embryos by TUNEL and fluorescent in situ hybridization (FISH) techniques. Within seven chromosomally abnormal embryos, each had variable degrees of CF [ 98 ]. This study suggests that DNA fragmentation, being a sign of chromosomal abnormalities, may exist together with CF.

An earlier study by Munne et al., examined 524 embryos using FISH analysis for three to five chromosomes. While controlling for age, they divided the embryos into three groups: arrested, slow and/or fragmented, or morphologically and developmentally normal. They found that polyploidy was the most common chromosomal abnormality in the arrested embryo group and decreased with increasing embryonic competence, with 44.5% polyploidy in arrested compared to 2.1% in morphologically normal embryos. Maternal age was not associated with polyploidy rates, but aneuploidy significantly increased with maternal age in morphologically normal human embryos [ 57 ]. Another early study by Almeida and Bolton also examined the relationship between chromosomal abnormalities and embryonic developmental potential. They found that cleavage-stage embryos with poor morphology, defined as irregular shaped blastomeres with severe fragmentation, showed a higher incidence of chromosomal abnormalities than those with good morphology [ 100 ]. Magli et al., found a more direct relationship between chromosomal abnormalities and embryo fragmentation in a larger retrospective study of nearly 1600 embryos. There was a strong association between percentage of fragmentation and chromosomal abnormalities (monosomies and trisomies), where 90% of chromosomal abnormalities were found in embryos with greater than 40% fragmentation [ 101 ].

Another retrospective study comparing maternal age to embryo morphology and chromosomal abnormalities was conducted by Moayeri et al., By examining nine chromosomes in day-3 embryos, they found that morphology predicted chromosomal status in the advanced maternal age group (≥38 years old), but not in younger patients. Fragmentation alone predicted euploidy in both the advanced maternal age and younger groups. This suggests that cellular fragmentation may be a predictor of chromosomal competence and thus embryo developmental potential [ 102 ].

In contrast, Baltaci et al., examined 1,000 embryos and concluded that embryo morphology was not predictive of euploidy and that a considerable number of chromosomally abnormal embryos with good development potential may be selected for embryo transfer. They used FISH for five chromosomes and found that a large proportion of both normal and aneuploid embryos were evaluated as top quality (grade I). For example, 66% of chromosomally abnormal embryos were of good quality (grade I and II). They found no significant difference among aneuploid embryos when distributed by age. However, a higher embryo quality found in normal compared to aneuploid embryos [ 103 ].

In addition, Pellestor et al., compared the relationship between morphology and chromosomal abnormalities in two separate studies. The first study found that aneuploidy was the most frequently observed abnormality after cytogenetic analysis of preimplantation embryos [ 55 ]. They defined the quality of embryos as good (grade I and II) and poor (grades III and IV). There was an increased chromosomal abnormality in poor quality embryos (84.3%) when compared to embryos with good quality (33.9%). Both aneuploidy and fragmentation were shown to be predominant in poor quality embryos, whereas mosaicism and polyploidy were the most frequent abnormalities in good quality embryos [ 55 ]. Pellestor et al., also performed cytogenetic analysis on 411 poor-quality embryos (grade IV) [ 85 ]. Ninety percent of the successfully analyzed cases showed abnormal chromosome complements, with aneuploidy being the most frequently observed. These results further support that a large majority of poor grade embryos are chromosomally abnormal and ultimately offer low chance of reproductive success for either embryo transfer or cryopreservation [ 85 ].

A separate study by Chavez et al., combined time-lapse imaging with karyotypic status of blastomeres in the 4-cell embryo to test whether blastomere behavior may reflect chromosomal abnormalities, using array comparative genomic hybridization (aCGH), during early cleavage [ 56 ]. In time-lapse observations, a large proportion of aneuploid and triploid, but not euploid embryos, exhibited cellular fragmentation. They showed that the probability of aneuploidy increased with higher fragmentation and only 65% of the fragmented embryo would be expected to form blastocyst. Furthermore, all the aneuploid embryos with additional unbalanced sub-chromosomal errors exhibited CF. The authors concluded that although fragmentation alone at a single point in time does not predict embryo developmental potential, time-lapse imaging with dynamic fragmentation screening may help detect embryonic aneuploidy [ 56 ].

Two more recent studies also used aCGH to evaluate the association between embryo ploidy and fragmentation. Vera-Rodriguez et al., in a retrospective study, compared the rate of embryo aneuploidy between two groups of high (≥25%) and low (˂25%) fragmentation. They found that the rate of aneuploidy in high and low fragmentation was 62.5 and 46.3%, respectively. However, the difference was not statistically significant concluding that using degree of fragmentation alone is not suggested to predict the embryo ploidy status [ 107 ]. Minasi et al., in a case series evaluated 1730 blastocyst ploidy with aCGH. They showed that there is no significant difference between day-3 embryo morphology and embryo ploidy. However, the quality of blastocyst (inner cell mass grade, trophectoderm grade, degree of expansion) was associated with embryo ploidy [ 106 ].

In a recent meta-analysis, it was shown there is trend between degree of fragmentation and rate of aneuploidy [ 109 ]. A major source of controversy in both early and recent studies on aneuploidy and fragmentation is the variation in the methods and criteria used to evaluate these factors. One of the aspects that differ across studies include the technique for detecting aneuploidy; FISH vs aCGH. Recent studies have used aCGH to detect aneuploidy and found no clear relationship in this regard. Also, the quality of the matching between groups, the design of the study (retrospective vs prospective), the timing of the fragmentation assessment, the use of time-lapse imaging to monitor the fate of fragments are the other reasons for this discrepancy. There is still the lack of a clear cut-off point for the percentage of fragmentation to predict aneuploidy. Further powerful studies using new methods like next gene sequencing and tile-lapse systems are recommended to shed light on the relationship between fragmentation and aneuploidy.

The literature highlights that poor quality embryos have a higher incidence of chromosomal abnormalities. Notably, CF is rarely observed in embryos with normal chromosomal content. Technological advancements, such as TLM, offer promising avenues to enhance our understanding and detection of embryonic aneuploidy. Overall, these studies underscore the complexity of the relationship between fragmentation and chromosomal abnormalities, emphasizing the need for continued research to refine embryo selection strategies and improve reproductive outcomes.

Discussion and conclusion

The role of fragmentation in human embryo development and reproductive potential is widely recognized, albeit without standard definition nor agreed upon implication. While it has been shown that degree of fragmentation and embryo implantation potential are inversely proportional [ 5 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], the degree, pattern, and distribution of fragmentation as it relates to pregnancy outcome is debated in the literature. Our qualitative synthesis of 60 articles related to the study of embryo fragmentation and reproductive outcomes highlighted some of the challenges in analysis of fragmentation, while revealing trends in our evolving knowledge of how fragmentation may relate to functional development of the human embryo.

While fragmentation is best understood to be a natural process across species, the origin of fragmentation remains incompletely understood and likely multifactorial. Degree of fragmentation has been plausibly correlated to sperm DNA oxidation [ 37 ], errors in division [ 37 ], mitochondrial distribution [ 45 ], and overall embryo quality [ 39 ]. However, some causes of fragmentation are based on outdated studies and require validation in future research with higher quality and more advanced techniques. While cause of fragmentation remains a focus of investigation, advances in technology have allowed for more detailed analysis of its effect on embryo development and reproductive outcome. At the cellular level, increased fragmentation has been shown to be associated with higher rates of apoptosis, necrosis, and programmed cell death of cleavage-stage embryos [ 60 , 61 , 62 ]. Given the recognized significance of fragmentation on embryo development, it follows that many studies have been focused on IVF and ART impacts on fragmentation, as well as determining quantitative reproductive outcomes. In terms of other influences on degree of fragmentation, patient age was not universally found to be significantly associated with fragmentation [ 7 , 70 , 71 ] although age is certainly known to influence embryo quality. Most studies included in the search criteria showed that ART such as ICSI do not significantly impact fragmentation rate in developing embryos [ 74 , 75 , 76 ]. Those studies that found significant differences in embryo grading either between conventional fertilization and ICSI either did not find a difference in implantation or pregnancy rate or did not study it, suggesting that ICSI is not a significant contributor to poorer ART outcomes by way of embryo fragmentation.

In synthesizing the available data on ART and pregnancy outcomes with varying degrees of embryo fragmentation, most included studies did find a negative impact of increasing fragmentation on reproductive success while severe fragmentation does appear to be associated with poorer implantation rate and clinical pregnancy rate. This association may be related to the observation that increased fragmentation at the cleavage-stage embryo is related to chromosomal abnormalities incompatible with ongoing development or pregnancy.

The reviewed studies have several limitations. There are different grading systems in use that may impact detecting and reporting the degree of CF. Different criteria and terminology used in different studies may in turn make the comparison of outcome measures difficult. Another factor is the distribution pattern of CF. There are two types of scattered and concentrated fragments with different prognoses that is not considered in grading systems. Therefore, due to the lack of a standard cleavage-stage embryo grading system, comparing different studies should be done with caution. In addition, evaluation of embryo fragmentation is mostly based on individual observation which is subjective and has inter- and intra-observer subjectivity leading to high variable results even if performed by an experienced embryologist [ 110 ]. TLM is considered as a non-invasive tool and evaluates the embryo quality continuously and without the need to remove the embryo from the incubator [ 111 ]. The use of this technology allows for the analysis of embryo morphokinetics and has advanced knowledge of the developing embryo. Recently, artificial intelligence (AI) including machine learning and neural network has gained popularity in various fields of medicine including IVF and embryology. Accuracy of AI in prediction of fragmentation has been studied with encouraging results [ 112 ]. Further advances in technology will promote the use of AI as a tool in defining the effect of fragmentation on human embryo development and reproductive potential.

Although the precise origin and the importance of external or iatrogenic factors on fragmentation of cleavage-stage embryos varies in the literature, there is more consensus regarding severe fragmentation worsening reproductive outcomes. Given this important pattern, and the availability of increasingly sophisticated embryologic technology, further research is warranted to characterize more completely preventative or rescue techniques to improve reproductive outcomes.

Availability of data and materials

No datasets were generated or analysed during the current study.

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Yazdani, A., Halvaei, I., Boniface, C. et al. Effect of cytoplasmic fragmentation on embryo development, quality, and pregnancy outcome: a systematic review of the literature. Reprod Biol Endocrinol 22 , 55 (2024). https://doi.org/10.1186/s12958-024-01217-7

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Received : 20 November 2023

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DOI : https://doi.org/10.1186/s12958-024-01217-7

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SYSTEMATIC REVIEW article

The view of synthetic biology in the field of ethics: a thematic systematic review provisionally accepted.

• 1 Ankara University, Türkiye
• 2 Department of Medical History and Ethics, School of Medicine, Ankara University, Ankara, Türkiye, Türkiye

The final, formatted version of the article will be published soon.

Synthetic biology is designing and creating biological tools and systems for useful purposes. It uses knowledge from biology, such as biotechnology, molecular biology, biophysics, biochemistry, bioinformatics, and other disciplines, such as engineering, mathematics, computer science, and electrical engineering. It is recognized as both a branch of science and technology. The scope of synthetic biology ranges from modifying existing organisms to gain new properties to creating a living organism from non-living components. Synthetic biology has many applications in important fields such as energy, chemistry, medicine, environment, agriculture, national security, and nanotechnology. The development of synthetic biology also raises ethical and social debates. This article aims to identify the place of ethics in synthetic biology. In this context, the theoretical ethical debates on synthetic biology from the 2000s to 2020, when the development of synthetic biology was relatively faster, were analyzed using the systematic review method. Based on the results of the analysis, the main ethical problems related to the field, problems that are likely to arise, and suggestions for solutions to these problems are included. The data collection phase of the study included a literature review conducted according to protocols, including planning, screening, selection and evaluation. The analysis and synthesis process was carried out in the next stage, and the main themes related to synthetic biology and ethics were identified. Searches were conducted in Web of Science, Scopus, PhilPapers and MEDLINE databases. Theoretical research articles and reviews published in peer-reviewed journals until the end of 2020 were included in the study. The language of publications was English. According to preliminary data, 1453 publications were retrieved from the four databases. Considering the inclusion and exclusion criteria, 58 publications were analyzed in the study. Ethical debates on synthetic biology have been conducted on various issues. In this context, the ethical debates in this article were examined under five themes: the moral status of synthetic biology products, synthetic biology and the meaning of life, synthetic biology and metaphors, synthetic biology and knowledge, and expectations, concerns, and problem solving: risk versus caution.

Keywords: Synthetic Biology, Ethics, Bioethics, Systematic review, Technology ethics, Responsible research and innovation

Received: 08 Mar 2024; Accepted: 10 May 2024.

Copyright: © 2024 Kurtoglu, Yıldız and Arda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Ayse Kurtoglu, Ankara University, Ankara, Türkiye

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