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What is the Purpose of a Literature Review?

What is the Purpose of a Literature Review?

4-minute read

  • 23rd October 2023

If you’re writing a research paper or dissertation , then you’ll most likely need to include a comprehensive literature review . In this post, we’ll review the purpose of literature reviews, why they are so significant, and the specific elements to include in one. Literature reviews can:

1. Provide a foundation for current research.

2. Define key concepts and theories.

3. Demonstrate critical evaluation.

4. Show how research and methodologies have evolved.

5. Identify gaps in existing research.

6. Support your argument.

Keep reading to enter the exciting world of literature reviews!

What is a Literature Review?

A literature review is a critical summary and evaluation of the existing research (e.g., academic journal articles and books) on a specific topic. It is typically included as a separate section or chapter of a research paper or dissertation, serving as a contextual framework for a study. Literature reviews can vary in length depending on the subject and nature of the study, with most being about equal length to other sections or chapters included in the paper. Essentially, the literature review highlights previous studies in the context of your research and summarizes your insights in a structured, organized format. Next, let’s look at the overall purpose of a literature review.

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Literature reviews are considered an integral part of research across most academic subjects and fields. The primary purpose of a literature review in your study is to:

Provide a Foundation for Current Research

Since the literature review provides a comprehensive evaluation of the existing research, it serves as a solid foundation for your current study. It’s a way to contextualize your work and show how your research fits into the broader landscape of your specific area of study.  

Define Key Concepts and Theories

The literature review highlights the central theories and concepts that have arisen from previous research on your chosen topic. It gives your readers a more thorough understanding of the background of your study and why your research is particularly significant .

Demonstrate Critical Evaluation 

A comprehensive literature review shows your ability to critically analyze and evaluate a broad range of source material. And since you’re considering and acknowledging the contribution of key scholars alongside your own, it establishes your own credibility and knowledge.

Show How Research and Methodologies Have Evolved

Another purpose of literature reviews is to provide a historical perspective and demonstrate how research and methodologies have changed over time, especially as data collection methods and technology have advanced. And studying past methodologies allows you, as the researcher, to understand what did and did not work and apply that knowledge to your own research.  

Identify Gaps in Existing Research

Besides discussing current research and methodologies, the literature review should also address areas that are lacking in the existing literature. This helps further demonstrate the relevance of your own research by explaining why your study is necessary to fill the gaps.

Support Your Argument

A good literature review should provide evidence that supports your research questions and hypothesis. For example, your study may show that your research supports existing theories or builds on them in some way. Referencing previous related studies shows your work is grounded in established research and will ultimately be a contribution to the field.  

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  • UConn Library
  • Literature Review: The What, Why and How-to Guide
  • Introduction

Literature Review: The What, Why and How-to Guide — Introduction

  • Getting Started
  • How to Pick a Topic
  • Strategies to Find Sources
  • Evaluating Sources & Lit. Reviews
  • Tips for Writing Literature Reviews
  • Writing Literature Review: Useful Sites
  • Citation Resources
  • Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

  • To develop a theory or evaluate an existing theory
  • To summarize the historical or existing state of a research topic
  • Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

  • A research paper assigned in a course
  • A thesis or dissertation
  • A grant proposal
  • An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

  • Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

  • Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

  • Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

  • Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

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A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . 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 in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

  • Give a new interpretation of old material or combine new with old interpretations,
  • Trace the intellectual progression of the field, including major debates,
  • Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
  • Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

  • Place each work in the context of its contribution to understanding the research problem being studied.
  • Describe the relationship of each work to the others under consideration.
  • Identify new ways to interpret prior research.
  • Reveal any gaps that exist in the literature.
  • Resolve conflicts amongst seemingly contradictory previous studies.
  • Identify areas of prior scholarship to prevent duplication of effort.
  • Point the way in fulfilling a need for additional research.
  • Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE : Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

  • An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
  • Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
  • An explanation of how each work is similar to and how it varies from the others,
  • Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

  • Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
  • Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
  • Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
  • Persuasiveness -- which of the author's theses are most convincing or least convincing?
  • Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through 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 explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. 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 environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from 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. However, sometimes you may 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. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

  • Current Situation : Information necessary to understand the current topic or focus of the literature review.
  • Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
  • History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
  • Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
  • Standards : Description of the way in which you present your information.
  • 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?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates 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 research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. 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. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

  • Sources in your literature review do not clearly relate to the research problem;
  • You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
  • Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
  • Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
  • Does not describe the search procedures that were used in identifying the literature to review;
  • Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
  • Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

  • How are they organizing their ideas?
  • What methods have they used to study the problem?
  • What theories have been used to explain, predict, or understand their research problem?
  • What sources have they cited to support their conclusions?
  • How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

  • Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
  • Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
  • Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

  • Provide a comprehensive and updated review of the literature;
  • Explain why this review has taken place;
  • Articulate a position or hypothesis;
  • Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

  • Demonstrate how a study fills a gap in research
  • Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

  • Organizes or describes a topic
  • Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

  • It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
  • It may be too focused. Some niche studies may miss the bigger picture.
  • It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
  • It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

Meryl Brodsky : Communication and Information Studies

Hannah Chapman Tripp : Biology, Neuroscience

Carolyn Cunningham : Human Development & Family Sciences, Psychology, Sociology

Larayne Dallas : Engineering

Janelle Hedstrom : Special Education, Curriculum & Instruction, Ed Leadership & Policy ​

Susan Macicak : Linguistics

Imelda Vetter : Dell Medical School

For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

  • October 26, 2022 recording
  • Last Updated: Oct 26, 2022 2:49 PM
  • URL: https://guides.lib.utexas.edu/literaturereviews

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Conducting a literature review: why do a literature review, why do a literature review.

  • How To Find "The Literature"
  • Found it -- Now What?

Besides the obvious reason for students -- because it is assigned! -- a literature review helps you explore the research that has come before you, to see how your research question has (or has not) already been addressed.

You identify:

  • core research in the field
  • experts in the subject area
  • methodology you may want to use (or avoid)
  • gaps in knowledge -- or where your research would fit in

It Also Helps You:

  • Publish and share your findings
  • Justify requests for grants and other funding
  • Identify best practices to inform practice
  • Set wider context for a program evaluation
  • Compile information to support community organizing

Great brief overview, from NCSU

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Literature reviews, what is a literature review, learning more about how to do a literature review.

  • Planning the Review
  • The Research Question
  • Choosing Where to Search
  • Organizing the Review
  • Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

  • Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

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Literature Review

  • What is a Literature Review?
  • What is NOT a Literature Review?
  • Purposes of a Literature Review
  • Types of Literature Reviews
  • Literature Reviews vs. Systematic Reviews
  • Systematic vs. Meta-Analysis

Literature Review  is a comprehensive survey of the works published in a particular field of study or line of research, usually over a specific period of time, in the form of an in-depth, critical bibliographic essay or annotated list in which attention is drawn to the most significant works.

Also, we can define a literature review as the collected body of scholarly works related to a topic:

  • Summarizes and analyzes previous research relevant to a topic
  • Includes scholarly books and articles published in academic journals
  • Can be an specific scholarly paper or a section in a research paper

The objective of a Literature Review is to find previous published scholarly works relevant to an specific topic

  • Help gather ideas or information
  • Keep up to date in current trends and findings
  • Help develop new questions

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.

All content in this section is from Literature Review Research from Old Dominion University 

Keep in mind the following, a literature review is NOT:

Not an essay 

Not an annotated bibliography  in which you summarize each article that you have reviewed.  A literature 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.

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.

As Kennedy (2007) notes*, it is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the original studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally that become part of the lore of field. In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews.

Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are several approaches to how they can be done, depending upon the type of analysis underpinning your study. Listed below are definitions of types of literature reviews:

Argumentative Review      This form examines literature selectively in order to support or refute an argument, deeply imbedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to to make summary claims of the sort found in systematic reviews.

Integrative Review      Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication.

Historical Review      Few things rest in isolation from historical precedent. Historical reviews are focused on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review      A review does not always focus on what someone said [content], but how they said it [method of analysis]. This approach provides a framework of understanding at different levels (i.e. those of theory, substantive fields, research approaches and data collection and analysis techniques), enables researchers to draw on a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection and data analysis, and helps highlight many ethical issues which we should be aware of and consider as we go through our study.

Systematic Review      This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyse data from the studies that are included in the review. Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?"

Theoretical Review      The purpose of this form is to concretely examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review help establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

* Kennedy, Mary M. "Defining a Literature."  Educational Researcher  36 (April 2007): 139-147.

All content in this section is from The Literature Review created by Dr. Robert Larabee USC

Robinson, P. and Lowe, J. (2015),  Literature reviews vs systematic reviews.  Australian and New Zealand Journal of Public Health, 39: 103-103. doi: 10.1111/1753-6405.12393

relevance of a literature review

What's in the name? The difference between a Systematic Review and a Literature Review, and why it matters . By Lynn Kysh from University of Southern California

relevance of a literature review

Systematic review or meta-analysis?

A  systematic review  answers a defined research question by collecting and summarizing all empirical evidence that fits pre-specified eligibility criteria.

A  meta-analysis  is the use of statistical methods to summarize the results of these studies.

Systematic reviews, just like other research articles, can be of varying quality. They are a significant piece of work (the Centre for Reviews and Dissemination at York estimates that a team will take 9-24 months), and to be useful to other researchers and practitioners they should have:

  • clearly stated objectives with pre-defined eligibility criteria for studies
  • explicit, reproducible methodology
  • a systematic search that attempts to identify all studies
  • assessment of the validity of the findings of the included studies (e.g. risk of bias)
  • systematic presentation, and synthesis, of the characteristics and findings of the included studies

Not all systematic reviews contain meta-analysis. 

Meta-analysis is the use of statistical methods to summarize the results of independent studies. By combining information from all relevant studies, meta-analysis can provide more precise estimates of the effects of health care than those derived from the individual studies included within a review.  More information on meta-analyses can be found in  Cochrane Handbook, Chapter 9 .

A meta-analysis goes beyond critique and integration and conducts secondary statistical analysis on the outcomes of similar studies.  It is a systematic review that uses quantitative methods to synthesize and summarize the results.

An advantage of a meta-analysis is the ability to be completely objective in evaluating research findings.  Not all topics, however, have sufficient research evidence to allow a meta-analysis to be conducted.  In that case, an integrative review is an appropriate strategy. 

Some of the content in this section is from Systematic reviews and meta-analyses: step by step guide created by Kate McAllister.

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Literature Reviews

  • Getting started

What is a literature review?

Why conduct a literature review, stages of a literature review, lit reviews: an overview (video), check out these books.

  • Types of reviews
  • 1. Define your research question
  • 2. Plan your search
  • 3. Search the literature
  • 4. Organize your results
  • 5. Synthesize your findings
  • 6. Write the review
  • Artificial intelligence (AI) tools
  • Thompson Writing Studio This link opens in a new window
  • Need to write a systematic review? This link opens in a new window

relevance of a literature review

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Definition: A literature review is a systematic examination and synthesis of existing scholarly research on a specific topic or subject.

Purpose: It serves to provide a comprehensive overview of the current state of knowledge within a particular field.

Analysis: Involves critically evaluating and summarizing key findings, methodologies, and debates found in academic literature.

Identifying Gaps: Aims to pinpoint areas where there is a lack of research or unresolved questions, highlighting opportunities for further investigation.

Contextualization: Enables researchers to understand how their work fits into the broader academic conversation and contributes to the existing body of knowledge.

relevance of a literature review

tl;dr  A literature review critically examines and synthesizes existing scholarly research and publications on a specific topic to provide a comprehensive understanding of the current state of knowledge in the field.

What is a literature review NOT?

❌ An annotated bibliography

❌ Original research

❌ A summary

❌ Something to be conducted at the end of your research

❌ An opinion piece

❌ A chronological compilation of studies

The reason for conducting a literature review is to:

relevance of a literature review

Literature Reviews: An Overview for Graduate Students

While this 9-minute video from NCSU is geared toward graduate students, it is useful for anyone conducting a literature review.

relevance of a literature review

Writing the literature review: A practical guide

Available 3rd floor of Perkins

relevance of a literature review

Writing literature reviews: A guide for students of the social and behavioral sciences

Available online!

relevance of a literature review

So, you have to write a literature review: A guided workbook for engineers

relevance of a literature review

Telling a research story: Writing a literature review

relevance of a literature review

The literature review: Six steps to success

relevance of a literature review

Systematic approaches to a successful literature review

Request from Duke Medical Center Library

relevance of a literature review

Doing a systematic review: A student's guide

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  • Last Updated: May 17, 2024 8:42 AM
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Writing a Literature Review

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. 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. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

  • An introductory paragraph that explains what your working topic and thesis is
  • A forecast of key topics or texts that will appear in the review
  • Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
  • Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically Evaluate: Mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

  • Summarize the key findings you have taken from the literature and emphasize their significance
  • Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

  • Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
  • Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
  • Qualitative versus quantitative research
  • Empirical versus theoretical scholarship
  • Divide the research by sociological, historical, or cultural sources
  • Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

  • It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
  • Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
  • Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
  • Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

A Guide to Literature Reviews

Importance of a good literature review.

  • Conducting the Literature Review
  • Structure and Writing Style
  • Types of Literature Reviews
  • Citation Management Software This link opens in a new window
  • Acknowledgements

A literature review is not only a summary of key sources, but  has an organizational pattern which combines both summary and synthesis, often within specific conceptual categories . 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 in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

  • Give a new interpretation of old material or combine new with old interpretations,
  • Trace the intellectual progression of the field, including major debates,
  • Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
  • Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

The purpose of a literature review is to:

  • Place each work in the context of its contribution to understanding the research problem being studied.
  • Describe the relationship of each work to the others under consideration.
  • Identify new ways to interpret prior research.
  • Reveal any gaps that exist in the literature.
  • Resolve conflicts amongst seemingly contradictory previous studies.
  • Identify areas of prior scholarship to prevent duplication of effort.
  • Point the way in fulfilling a need for additional research.
  • Locate your own research within the context of existing literature [very important].
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The Writing Center • University of North Carolina at Chapel Hill

Literature Reviews

What this handout is about.

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

Introduction

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 is likely to 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.

Let’s get to it! What should I do before writing the literature review?

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.

Keep in mind that UNC Libraries have research guides and to databases relevant to many fields of study. You can reach out to the subject librarian for a consultation: https://library.unc.edu/support/consultations/ .

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 90’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.

Strategies for writing the literature review

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.

Convey it to your reader

A literature review may not have a traditional thesis statement (one that makes an argument), but you do need to tell readers what to expect. Try writing a simple statement that lets the reader know what is your main organizing principle. Here are a couple of examples:

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 stated it clearly and directly. 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. The following provides a brief description of the content of each:

  • 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:

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.

Now consider some typical ways of organizing the sources into a review:

  • 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: 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?

Begin composing

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. For more information, please see our handout on plagiarism .

Revise, revise, revise

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. For tips on the revising and editing process, see our handout on revising drafts .

Works consulted

We consulted these works while writing 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 additional publications. 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. For guidance on formatting citations, please see the UNC Libraries citation tutorial . We revise these tips periodically and welcome feedback.

Anson, Chris M., and Robert A. Schwegler. 2010. The Longman Handbook for Writers and Readers , 6th ed. New York: Longman.

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

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

Rosen, Leonard J., and Laurence Behrens. 2003. The Allyn & Bacon Handbook , 5th ed. New York: Longman.

Troyka, Lynn Quittman, and Doug Hesse. 2016. Simon and Schuster Handbook for Writers , 11th ed. London: Pearson.

You may reproduce it for non-commercial use if you use the entire handout and attribute the source: The Writing Center, University of North Carolina at Chapel Hill

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What Is A Literature Review?

A plain-language explainer (with examples).

By:  Derek Jansen (MBA) & Kerryn Warren (PhD) | June 2020 (Updated May 2023)

If you’re faced with writing a dissertation or thesis, chances are you’ve encountered the term “literature review” . If you’re on this page, you’re probably not 100% what the literature review is all about. The good news is that you’ve come to the right place.

Literature Review 101

  • What (exactly) is a literature review
  • What’s the purpose of the literature review chapter
  • How to find high-quality resources
  • How to structure your literature review chapter
  • Example of an actual literature review

What is a literature review?

The word “literature review” can refer to two related things that are part of the broader literature review process. The first is the task of  reviewing the literature  – i.e. sourcing and reading through the existing research relating to your research topic. The second is the  actual chapter  that you write up in your dissertation, thesis or research project. Let’s look at each of them:

Reviewing the literature

The first step of any literature review is to hunt down and  read through the existing research  that’s relevant to your research topic. To do this, you’ll use a combination of tools (we’ll discuss some of these later) to find journal articles, books, ebooks, research reports, dissertations, theses and any other credible sources of information that relate to your topic. You’ll then  summarise and catalogue these  for easy reference when you write up your literature review chapter. 

The literature review chapter

The second step of the literature review is to write the actual literature review chapter (this is usually the second chapter in a typical dissertation or thesis structure ). At the simplest level, the literature review chapter is an  overview of the key literature  that’s relevant to your research topic. This chapter should provide a smooth-flowing discussion of what research has already been done, what is known, what is unknown and what is contested in relation to your research topic. So, you can think of it as an  integrated review of the state of knowledge  around your research topic. 

Starting point for the literature review

What’s the purpose of a literature review?

The literature review chapter has a few important functions within your dissertation, thesis or research project. Let’s take a look at these:

Purpose #1 – Demonstrate your topic knowledge

The first function of the literature review chapter is, quite simply, to show the reader (or marker) that you  know what you’re talking about . In other words, a good literature review chapter demonstrates that you’ve read the relevant existing research and understand what’s going on – who’s said what, what’s agreed upon, disagreed upon and so on. This needs to be  more than just a summary  of who said what – it needs to integrate the existing research to  show how it all fits together  and what’s missing (which leads us to purpose #2, next). 

Purpose #2 – Reveal the research gap that you’ll fill

The second function of the literature review chapter is to  show what’s currently missing  from the existing research, to lay the foundation for your own research topic. In other words, your literature review chapter needs to show that there are currently “missing pieces” in terms of the bigger puzzle, and that  your study will fill one of those research gaps . By doing this, you are showing that your research topic is original and will help contribute to the body of knowledge. In other words, the literature review helps justify your research topic.  

Purpose #3 – Lay the foundation for your conceptual framework

The third function of the literature review is to form the  basis for a conceptual framework . Not every research topic will necessarily have a conceptual framework, but if your topic does require one, it needs to be rooted in your literature review. 

For example, let’s say your research aims to identify the drivers of a certain outcome – the factors which contribute to burnout in office workers. In this case, you’d likely develop a conceptual framework which details the potential factors (e.g. long hours, excessive stress, etc), as well as the outcome (burnout). Those factors would need to emerge from the literature review chapter – they can’t just come from your gut! 

So, in this case, the literature review chapter would uncover each of the potential factors (based on previous studies about burnout), which would then be modelled into a framework. 

Purpose #4 – To inform your methodology

The fourth function of the literature review is to  inform the choice of methodology  for your own research. As we’ve  discussed on the Grad Coach blog , your choice of methodology will be heavily influenced by your research aims, objectives and questions . Given that you’ll be reviewing studies covering a topic close to yours, it makes sense that you could learn a lot from their (well-considered) methodologies.

So, when you’re reviewing the literature, you’ll need to  pay close attention to the research design , methodology and methods used in similar studies, and use these to inform your methodology. Quite often, you’ll be able to  “borrow” from previous studies . This is especially true for quantitative studies , as you can use previously tried and tested measures and scales. 

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How do I find articles for my literature review?

Finding quality journal articles is essential to crafting a rock-solid literature review. As you probably already know, not all research is created equally, and so you need to make sure that your literature review is  built on credible research . 

We could write an entire post on how to find quality literature (actually, we have ), but a good starting point is Google Scholar . Google Scholar is essentially the academic equivalent of Google, using Google’s powerful search capabilities to find relevant journal articles and reports. It certainly doesn’t cover every possible resource, but it’s a very useful way to get started on your literature review journey, as it will very quickly give you a good indication of what the  most popular pieces of research  are in your field.

One downside of Google Scholar is that it’s merely a search engine – that is, it lists the articles, but oftentimes  it doesn’t host the articles . So you’ll often hit a paywall when clicking through to journal websites. 

Thankfully, your university should provide you with access to their library, so you can find the article titles using Google Scholar and then search for them by name in your university’s online library. Your university may also provide you with access to  ResearchGate , which is another great source for existing research. 

Remember, the correct search keywords will be super important to get the right information from the start. So, pay close attention to the keywords used in the journal articles you read and use those keywords to search for more articles. If you can’t find a spoon in the kitchen, you haven’t looked in the right drawer. 

Need a helping hand?

relevance of a literature review

How should I structure my literature review?

Unfortunately, there’s no generic universal answer for this one. The structure of your literature review will depend largely on your topic area and your research aims and objectives.

You could potentially structure your literature review chapter according to theme, group, variables , chronologically or per concepts in your field of research. We explain the main approaches to structuring your literature review here . You can also download a copy of our free literature review template to help you establish an initial structure.

In general, it’s also a good idea to start wide (i.e. the big-picture-level) and then narrow down, ending your literature review close to your research questions . However, there’s no universal one “right way” to structure your literature review. The most important thing is not to discuss your sources one after the other like a list – as we touched on earlier, your literature review needs to synthesise the research , not summarise it .

Ultimately, you need to craft your literature review so that it conveys the most important information effectively – it needs to tell a logical story in a digestible way. It’s no use starting off with highly technical terms and then only explaining what these terms mean later. Always assume your reader is not a subject matter expert and hold their hand through a journe y of the literature while keeping the functions of the literature review chapter (which we discussed earlier) front of mind.

A good literature review should synthesise the existing research in relation to the research aims, not simply summarise it.

Example of a literature review

In the video below, we walk you through a high-quality literature review from a dissertation that earned full distinction. This will give you a clearer view of what a strong literature review looks like in practice and hopefully provide some inspiration for your own. 

Wrapping Up

In this post, we’ve (hopefully) answered the question, “ what is a literature review? “. We’ve also considered the purpose and functions of the literature review, as well as how to find literature and how to structure the literature review chapter. If you’re keen to learn more, check out the literature review section of the Grad Coach blog , as well as our detailed video post covering how to write a literature review . 

Literature Review Course

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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16 Comments

BECKY NAMULI

Thanks for this review. It narrates what’s not been taught as tutors are always in a early to finish their classes.

Derek Jansen

Thanks for the kind words, Becky. Good luck with your literature review 🙂

ELaine

This website is amazing, it really helps break everything down. Thank you, I would have been lost without it.

Timothy T. Chol

This is review is amazing. I benefited from it a lot and hope others visiting this website will benefit too.

Timothy T. Chol [email protected]

Tahir

Thank you very much for the guiding in literature review I learn and benefited a lot this make my journey smooth I’ll recommend this site to my friends

Rosalind Whitworth

This was so useful. Thank you so much.

hassan sakaba

Hi, Concept was explained nicely by both of you. Thanks a lot for sharing it. It will surely help research scholars to start their Research Journey.

Susan

The review is really helpful to me especially during this period of covid-19 pandemic when most universities in my country only offer online classes. Great stuff

Mohamed

Great Brief Explanation, thanks

Mayoga Patrick

So helpful to me as a student

Amr E. Hassabo

GradCoach is a fantastic site with brilliant and modern minds behind it.. I spent weeks decoding the substantial academic Jargon and grounding my initial steps on the research process, which could be shortened to a couple of days through the Gradcoach. Thanks again!

S. H Bawa

This is an amazing talk. I paved way for myself as a researcher. Thank you GradCoach!

Carol

Well-presented overview of the literature!

Philippa A Becker

This was brilliant. So clear. Thank you

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  • Steps in Conducting a Literature Review

What is a literature review?

A literature review is an integrated analysis -- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.  That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

A literature review may be a stand alone work or the introduction to a larger research paper, depending on the assignment.  Rely heavily on the guidelines your instructor has given you.

Why is it important?

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.
  • Discovers relationships between research studies/ideas.
  • Identifies major themes, concepts, and researchers on a topic.
  • Identifies critical gaps and points of disagreement.
  • Discusses further research questions that logically come out of the previous studies.

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1. Choose a topic. Define your research question.

Your literature review should be guided by your central research question.  The literature represents background and research developments related to a specific research question, interpreted and analyzed by you in a synthesized way.

  • Make sure your research question is not too broad or too narrow.  Is it manageable?
  • Begin writing down terms that are related to your question. These will be useful for searches later.
  • If you have the opportunity, discuss your topic with your professor and your class mates.

2. Decide on the scope of your review

How many studies do you need to look at? How comprehensive should it be? How many years should it cover? 

  • This may depend on your assignment.  How many sources does the assignment require?

3. Select the databases you will use to conduct your searches.

Make a list of the databases you will search. 

Where to find databases:

  • use the tabs on this guide
  • Find other databases in the Nursing Information Resources web page
  • More on the Medical Library web page
  • ... and more on the Yale University Library web page

4. Conduct your searches to find the evidence. Keep track of your searches.

  • Use the key words in your question, as well as synonyms for those words, as terms in your search. Use the database tutorials for help.
  • Save the searches in the databases. This saves time when you want to redo, or modify, the searches. It is also helpful to use as a guide is the searches are not finding any useful results.
  • Review the abstracts of research studies carefully. This will save you time.
  • Use the bibliographies and references of research studies you find to locate others.
  • Check with your professor, or a subject expert in the field, if you are missing any key works in the field.
  • Ask your librarian for help at any time.
  • Use a citation manager, such as EndNote as the repository for your citations. See the EndNote tutorials for help.

Review the literature

Some questions to help you analyze the research:

  • What was the research question of the study you are reviewing? What were the authors trying to discover?
  • Was the research funded by a source that could influence the findings?
  • What were the research methodologies? Analyze its literature review, the samples and variables used, the results, and the conclusions.
  • Does the research seem to be complete? Could it have been conducted more soundly? What further questions does it raise?
  • If there are conflicting studies, why do you think that is?
  • How are the authors viewed in the field? Has this study been cited? If so, how has it been analyzed?

Tips: 

  • Review the abstracts carefully.  
  • Keep careful notes so that you may track your thought processes during the research process.
  • Create a matrix of the studies for easy analysis, and synthesis, across all of the studies.
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Writing a Literature Review

About this guide, what is a literature review, trials and tribulations of writing.

  • Planning a review
  • Exploring the Literature
  • Managing the Review
  • Organizing and writing the review

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The guide instructs students on how to write the literature review in scientific research papers. It illustrates the principles and practices that enable students to write a cogent and relevant literature review that frames their research study in terms of structure, scope and content. Using steps delineated in this guide illustrates to the researcher the process of writing a literature review. It allows the reader, when reading the review, to understand the justification for the research study as supported through the literature.. 

The process of writing a literature review encompasses four phases:

1. P lanning the Review.  Provides a strategic roadmap for the writing process. 

2. Exploring the Literature.  Searching the literature for relevant sources for addition into their review.

3. Managing the Literature.  Compiling and evaluating relevant sources for inclusion into the review.

4. Organizing and   Writing the Review.  Involves outlining and writing the literature review.  

A literature review surveys the scholarly literature for relevant sources that address the scope of a research topic. Neither an annotated bibliography, nor a systematic review, it lays the groundwork for justification of the research study by identifying the research problem, formulating the study’s research questions, and defining the objectives of the study.

There are two types of literature reviews. The first type, article literature review, provides a comprehensive coverage of a research topic, problem or area of interest. The second type is a chapter embedded within a research article, which cites relevant literature sources that support the research study findings and discussion. This libguide focuses on how to write a literature review for a research article.

relevance of a literature review

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Conducting a Literature Review

Benefits of conducting a literature review.

  • Steps in Conducting a Literature Review
  • Summary of the Process
  • Additional Resources
  • Literature Review Tutorial by American University Library
  • The Literature Review: A Few Tips On Conducting It by University of Toronto
  • Write a Literature Review by UC Santa Cruz University Library

While there might be many reasons for conducting a literature review, following are four key outcomes of doing the review.

Assessment of the current state of research on a topic . This is probably the most obvious value of the literature review. Once a researcher has determined an area to work with for a research project, a search of relevant information sources will help determine what is already known about the topic and how extensively the topic has already been researched.

Identification of the experts on a particular topic . One of the additional benefits derived from doing the literature review is that it will quickly reveal which researchers have written the most on a particular topic and are, therefore, probably the experts on the topic. Someone who has written twenty articles on a topic or on related topics is more than likely more knowledgeable than someone who has written a single article. This same writer will likely turn up as a reference in most of the other articles written on the same topic. From the number of articles written by the author and the number of times the writer has been cited by other authors, a researcher will be able to assume that the particular author is an expert in the area and, thus, a key resource for consultation in the current research to be undertaken.

Identification of key questions about a topic that need further research . In many cases a researcher may discover new angles that need further exploration by reviewing what has already been written on a topic. For example, research may suggest that listening to music while studying might lead to better retention of ideas, but the research might not have assessed whether a particular style of music is more beneficial than another. A researcher who is interested in pursuing this topic would then do well to follow up existing studies with a new study, based on previous research, that tries to identify which styles of music are most beneficial to retention.

Determination of methodologies used in past studies of the same or similar topics.  It is often useful to review the types of studies that previous researchers have launched as a means of determining what approaches might be of most benefit in further developing a topic. By the same token, a review of previously conducted studies might lend itself to researchers determining a new angle for approaching research.

Upon completion of the literature review, a researcher should have a solid foundation of knowledge in the area and a good feel for the direction any new research should take. Should any additional questions arise during the course of the research, the researcher will know which experts to consult in order to quickly clear up those questions.

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Why is it important to do a literature review in research?

Why is it important to do a literature review in research?

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The importance of scientific communication in the healthcare industry

importance and role of biostatistics in clinical research, biostatistics in public health, biostatistics in pharmacy, biostatistics in nursing,biostatistics in clinical trials,clinical biostatistics

The Importance and Role of Biostatistics in Clinical Research

 “A substantive, thorough, sophisticated literature review is a precondition for doing substantive, thorough, sophisticated research”. Boote and Baile 2005

Authors of manuscripts treat writing a literature review as a routine work or a mere formality. But a seasoned one knows the purpose and importance of a well-written literature review.  Since it is one of the basic needs for researches at any level, they have to be done vigilantly. Only then the reader will know that the basics of research have not been neglected.

Importance of Literature Review In Research

The aim of any literature review is to summarize and synthesize the arguments and ideas of existing knowledge in a particular field without adding any new contributions.   Being built on existing knowledge they help the researcher to even turn the wheels of the topic of research.  It is possible only with profound knowledge of what is wrong in the existing findings in detail to overpower them.  For other researches, the literature review gives the direction to be headed for its success. 

The common perception of literature review and reality:

As per the common belief, literature reviews are only a summary of the sources related to the research. And many authors of scientific manuscripts believe that they are only surveys of what are the researches are done on the chosen topic.  But on the contrary, it uses published information from pertinent and relevant sources like

  • Scholarly books
  • Scientific papers
  • Latest studies in the field
  • Established school of thoughts
  • Relevant articles from renowned scientific journals

and many more for a field of study or theory or a particular problem to do the following:

  • Summarize into a brief account of all information
  • Synthesize the information by restructuring and reorganizing
  • Critical evaluation of a concept or a school of thought or ideas
  • Familiarize the authors to the extent of knowledge in the particular field
  • Encapsulate
  • Compare & contrast

By doing the above on the relevant information, it provides the reader of the scientific manuscript with the following for a better understanding of it:

  • It establishes the authors’  in-depth understanding and knowledge of their field subject
  • It gives the background of the research
  • Portrays the scientific manuscript plan of examining the research result
  • Illuminates on how the knowledge has changed within the field
  • Highlights what has already been done in a particular field
  • Information of the generally accepted facts, emerging and current state of the topic of research
  • Identifies the research gap that is still unexplored or under-researched fields
  • Demonstrates how the research fits within a larger field of study
  • Provides an overview of the sources explored during the research of a particular topic

Importance of literature review in research:

The importance of literature review in scientific manuscripts can be condensed into an analytical feature to enable the multifold reach of its significance.  It adds value to the legitimacy of the research in many ways:

  • Provides the interpretation of existing literature in light of updated developments in the field to help in establishing the consistency in knowledge and relevancy of existing materials
  • It helps in calculating the impact of the latest information in the field by mapping their progress of knowledge.
  • It brings out the dialects of contradictions between various thoughts within the field to establish facts
  • The research gaps scrutinized initially are further explored to establish the latest facts of theories to add value to the field
  • Indicates the current research place in the schema of a particular field
  • Provides information for relevancy and coherency to check the research
  • Apart from elucidating the continuance of knowledge, it also points out areas that require further investigation and thus aid as a starting point of any future research
  • Justifies the research and sets up the research question
  • Sets up a theoretical framework comprising the concepts and theories of the research upon which its success can be judged
  • Helps to adopt a more appropriate methodology for the research by examining the strengths and weaknesses of existing research in the same field
  • Increases the significance of the results by comparing it with the existing literature
  • Provides a point of reference by writing the findings in the scientific manuscript
  • Helps to get the due credit from the audience for having done the fact-finding and fact-checking mission in the scientific manuscripts
  • The more the reference of relevant sources of it could increase more of its trustworthiness with the readers
  • Helps to prevent plagiarism by tailoring and uniquely tweaking the scientific manuscript not to repeat other’s original idea
  • By preventing plagiarism , it saves the scientific manuscript from rejection and thus also saves a lot of time and money
  • Helps to evaluate, condense and synthesize gist in the author’s own words to sharpen the research focus
  • Helps to compare and contrast to  show the originality and uniqueness of the research than that of the existing other researches
  • Rationalizes the need for conducting the particular research in a specified field
  • Helps to collect data accurately for allowing any new methodology of research than the existing ones
  • Enables the readers of the manuscript to answer the following questions of its readers for its better chances for publication
  • What do the researchers know?
  • What do they not know?
  • Is the scientific manuscript reliable and trustworthy?
  • What are the knowledge gaps of the researcher?

22. It helps the readers to identify the following for further reading of the scientific manuscript:

  • What has been already established, discredited and accepted in the particular field of research
  • Areas of controversy and conflicts among different schools of thought
  • Unsolved problems and issues in the connected field of research
  • The emerging trends and approaches
  • How the research extends, builds upon and leaves behind from the previous research

A profound literature review with many relevant sources of reference will enhance the chances of the scientific manuscript publication in renowned and reputed scientific journals .

References:

http://www.math.montana.edu/jobo/phdprep/phd6.pdf

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Sperm DNA Damage and Its Relevance in Fertility Treatment: A Review of Recent Literature and Current Practice Guidelines

Sperm deoxyribonucleic acid (DNA) damage has recently emerged as one of the most controversial topics in male reproductive medicine. While level I evidence indicates that abnormal sperm DNA damage has substantial adverse effects on reproductive outcomes (including chance of pregnancy and risk of miscarriage), there is limited consensus on how sperm DNA fragmentation (SDF) testing should be performed and/or interpreted in clinical practice. In this article, we review: (1) how SDF is assessed, (2) cumulative evidence regarding its impact on reproductive outcomes, (3) methods for mitigating high SDF, and (4) the most recent practice guidelines available for clinicians regarding the use and interpretation of SDF testing.

1. Introduction

Infertility is defined as the inability to conceive after 12 months of regular, unprotected intercourse [ 1 ]. Approximately 15% of all couples are affected by infertility [ 2 ], with a male factor being solely responsible in about 20% of couples and contributory in another 30–40% [ 2 ]. While a semen analysis is an important initial part of a male fertility evaluation [ 3 ], this test alone cannot differentiate those who are fertile versus infertile (except in cases of azoospermia) [ 4 ]. Specifically, while a standard semen analysis (SA) provides information regarding the patency of the reproductive tract, sperm production, sperm motility, and sperm viability, it does not provide insight into the functional potential of sperm, including its ability to fertilize an oocyte and contribute to normal embryonic development [ 4 ].

Consequently, several tests have been developed to better assess the fertility potential of sperm, including those designed to measure sperm deoxyribonucleic acid (DNA) fragmentation (SDF). While sperm DNA damage is broadly defined as any defect in sperm chromatin structure, SDF relates specifically to the single- or double-stranded breaks (SSBs or DSBs) within DNA strands [ 5 ]. It is hypothesized that if this unrepaired DNA damage exceeds a certain threshold, it will block normal embryonic development and prevent a pregnancy [ 6 ]. Consistent with this hypothesis, studies have found that elevated SDF levels are associated with a series of adverse reproductive outcomes, including lower natural and assisted reproductive technology (ART) pregnancy rates, abnormal embryo development, and recurrent pregnancy loss [ 5 , 7 , 8 ]. However, due to conflicting studies and a lack of high-quality evidence, it is unclear how SDF testing should best be applied in the evaluation and treatment of infertile men. Given that SDF is an active area of research, we seek to: (1) review the literature that has made SDF such a controversial topic, (2) discuss newly published evidence contributing to this complex discussion, and (3) outline the most recent practice guidelines synthesizing this large body of evidence for providers. Ultimately, by presenting new evidence in the context of prior conflicting work, we hope to enable providers to better navigate this contested clinical question in their own practice.

2. Sperm DNA Fragmentation: Mechanisms and Clinical Tests

Sperm DNA fragmentation may be associated with a variety of intrinsic (intratesticular) and extrinsic (post-testicular) factors [ 9 ]. Intrinsically, such factors may include defective germ cell maturation, abortive apoptosis, and oxidative stress, while extrinsically, lifestyle factors (i.e., smoking, heat exposure, etc.), medications, environmental pollutants, and more may contribute to DNA damage primarily via oxidative stress [ 9 , 10 ]. Regardless of the factor associated with the induction of SDF, at the cellular level, such damage may act through at least one of three proposed mechanisms: abortive apoptosis, defective chromatin maturation, and/or oxidative attack [ 10 ].

Intrinsically, sperm are typically protected from DNA damage by the tight compaction of DNA allowed by replacement of somatic histone proteins by protamines during spermatogenesis. This process is facilitated by topoisomerase enzymes, which create DNA breaks to reduce torsional stress and allow for histone to protamine substitution [ 9 , 10 ]. If these breaks are not repaired, impaired chromatin packaging may result in defective sperm maturation and sperm with persistent DNA breakage [ 9 , 10 ].

Such chromatin immaturity may also induce SDF through the activation of apoptosis [ 11 ]. In a 2015 study by Muratori et al., the authors demonstrated that a large fraction of sperm concomitantly showed sperm DNA breaks, apoptotic traits (as indicated by the presence of caspase activity and cleaved PARP), and incomplete protamination (as indicated by aniline blue staining) [ 11 ]. Since SDF was rarely associated with markers of oxidative damage (as indicated by the presence of 8-hydroxyguanosine and malondialdehyde), the authors concluded that apoptosis plays a major role in the sperm DNA fragmentation that occurs within the testis [ 11 ].

While the onset of SDF in the testis is primarily due to defective chromatin maturation or apoptosis, such processes often lead to unviable sperm [ 10 ]. In contrast, among the viable sperm with DNA fragmentation, SDF is primarily due to the oxidative stress that occurs during transit through the reproductive tract [ 10 ]. In this case, reactive oxygen species (ROS) may induce DNA breaks by directly attacking the DNA backbone or triggering apoptosis, though either the direct activation of caspases and endonucleases or the MAPK pathway [ 9 , 10 ]. Clinically, delays in sperm transport that may subsequently increase the risk of SDF can occur with neurologic abnormalities [ 12 ], after microsurgical reconstruction [ 13 ], or due to abnormalities in emission and ejaculation associated with medications such as selective serotonin reuptake inhibitors (SSRIs) [ 14 ].

Regardless of the source of the DNA damage, several tests have been developed to effectively measure it. The four assays most commonly used to clinically evaluate SDF include: (1) terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay (TUNEL), (2) sperm chromatin structure assay (SCSA), (3) sperm chromatin dispersion (SCD) test, and (4) single-cell gel electrophoresis assay (SCGE/Comet) [ 5 , 9 ]. While all are recognized as common clinical tests for measuring SDF, they have different mechanisms for assessing DNA damage, leading to several unique pros and cons. Additionally, while not a test of sperm DNA fragmentation, sperm aneuploidy testing may also serve an important adjunct in assessing sperm genomic integrity.

The terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay (TUNEL) is the most commonly used test for evaluating SDF [ 15 ]. TUNEL uses the terminal deoxynucleotidyl transferase (TdT) enzyme to directly label the free 3′ ends of SSBs and DSBs [ 5 ]. Specifically, TdT is a polymerase that catalyzes the addition of fluoresceinated-dUTP at the 3′-OH end of the damaged DNA fragments [ 15 ]. These breaks are then identified via optical fluorescent microscopy or flow cytometry. Results are reported as the percentage of sperm exhibiting DNA fragmentation out of the total number of sperm analyzed (%SDF) [ 5 ]. If manual fluorescent microscopy is used, this test has the advantage of being performed on relatively few (one to several hundred) fresh or frozen sperm, making it suitable for patients with severe oligospermia [ 5 , 16 ]. The main disadvantages of TUNEL are: variable assay protocols among laboratories, a lack of standardization of normal versus abnormal thresholds, and the need for special equipment (i.e., fluorescent microscopy or flow cytometry) [ 17 ]. In meta-analyses of clinical data, TUNEL was most predictive of miscarriage rate [ 18 ] and birth rate with ART [ 19 ] compared to other SDF tests. Similarly, Cissen et al. found that the TUNEL test demonstrated a predictive value in clinical pregnancy rates after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), unlike SCSA and SCD tests, which only demonstrated a weak predictive value [ 15 , 20 ]. One study estimated the cost of this test to be approximately USD 330 [ 21 ].

Like TUNEL, the sperm chromatin structure assay (SCSA) is also a fluorescent assay [ 22 ]. SCSA was developed to assess both sperm DNA fragmentation and chromatin structure [ 22 ]. To perform this test, a mild acid treatment is used to denature DNA at the sites of existing SSBs or DSBs; then, the DNA is stained with acridine orange (AO) [ 5 ]. When bound to double-stranded (or intact) DNA, AO emits a green fluorescence; in contrast, when bound to single-stranded (or denatured) DNA, AO emits a red fluorescence [ 5 , 16 , 17 ]. These fluorescence patterns are captured by a flow cytometer, and the ratio of red to total (red + green) fluorescence intensity is used to calculate the DNA fragmentation index (DFI) [ 5 , 23 ]. SCSA also reports the percent of sperm with high DNA stainability (%HDS), which indicates an abnormally high level of DNA staining due to sperm chromatin defects [ 23 ]. Specifically, %HDS indicates that excess histones and proteins have prevented full condensation of the sperm chromatin [ 20 ]. This test has several benefits, including the ability to be performed on either fresh or frozen samples, a standardized protocol, and well-established clinical thresholds [ 5 , 16 ]. However, it does require expensive equipment, skilled technicians, and large numbers of sperm, making it less suitable for men with severe oligospermia than other SDF tests [ 16 , 17 ]. The cost of SCSA is estimated to be approximately USD 300 [ 21 ].

The sperm chromatin dispersion test (SCD; also known as the ‘halo test’) is a commercially available kit that assesses the dispersion of DNA fragments after denaturation [ 16 ]. This test indirectly estimates the level of DNA fragmentation by quantifying the amount of nuclear dispersion (“halo”) seen after sperm lysis and acid denaturation remove excess nuclear proteins [ 20 ]. Specifically, sperm are embedded in agarose gel and treated with a DNA denaturing solution to “melt” the DNA double helix; however, this “melting” will only occur if there is massive DNA breakage [ 24 ]. The sperm are then treated with a lysing solution to remove nuclear proteins, stained, and visualized using bright field or fluorescent microscopy [ 5 , 15 , 16 , 24 ]. This removal of nuclear proteins results in nucleoids with a central core and a peripheral ‘halo’ of dispersed DNA loops [ 25 ]. Sperm with intact DNA demonstrate large halos of dispersed DNA, while sperm with DNA fragmentation will not have a halo since it was dissolved during the denaturation step [ 22 , 24 ]. Ultimately, the size of the halo is proportional to the extent of the DNA damage [ 16 ]. While this is a relatively simple and affordable test (average cost USD 175) [ 21 ], it can be time consuming and prone to inter-observer variability [ 16 ].

Finally, the Comet assay is an assessment of SDF that utilizes electrophoresis to measure sperm DNA strand breaks [ 16 , 22 ]. Specifically, this test quantifies the shape of single cell nuclei after gel electrophoresis, with small, fragmented DNA migrating more quickly towards the anode than larger, non-fragmented DNA. This produces a typical ‘comet’ shape, with fragmented DNA in the ‘tail’ and non-fragmented DNA in the ‘head’ [ 20 ]. Mechanistically, sperm are embedded as a single-cell suspension in an agarose matrix and treated with a lysis buffer containing high salt and detergent to remove cell and nuclear membranes [ 26 ]. This processing leaves DNA attached to the nuclear matrix as nucleoids, which are then subjected to electrophoresis [ 26 ]. Electrophoresis is performed under either alkaline or neutral pH conditions, resulting in the migration of DNA fragments toward the anode. This allows for the migration of DNA fragments to form a comet ‘tail’, while intact DNA remains in the ‘head’. After electrophoresis, the samples are rinsed, stained with fluorescent dye, and quantitatively analyzed based on the distribution of the fluorescence pattern to determine the extent of the DNA damage [ 26 ]. The relative fluorescence of the tail versus the head corresponds to the amount of SDF, with increased fluorescence in the tail reflecting high levels of SDF [ 5 ]. Both DNA SSBs and DSBs can be detected using this technique if alkaline pH conditions are used, while neutral pH conditions can only detect DSBs [ 5 ]. Results are reported as average comet score (ACS), which represents the average SDF across 100 individual comets (individual sperm) analyzed [ 5 ]. The proportion of sperm with high DNA damage (high Comet score, HCS) and proportion of sperm with low DNA damage (low Comet Score, LCS) are also reported [ 5 ]. While this assay can be performed with only a small number of sperm, they must be from a fresh sample, and—like the SCD test—interpretation of the results may be time-consuming and prone to inter-observer variability if a manual analysis is performed [ 16 , 17 ]. To reduce such variability, a computerized image analysis system can be used to obtain images, compute the fluorescent intensity profile for each nucleoid, and estimate the relevant comet components [ 26 ]. Regarding cost, this test has been estimated to be approximately USD 400 [ 21 ].

2.5. Other Tests: Sperm Aneuploidy Testing

While sperm DNA fragmentation has been associated with adverse reproductive outcomes, sperm aneuploidy has similarly been associated with detrimental effects, particularly recurrent pregnancy loss (RPL) [ 27 , 28 ]. Aneuploidies are defined as chromosomal aberrations caused by disjunction failure of homologous chromosomes or sister chromatids during meiosis or mitosis, respectively [ 15 ]. Such chromosomal aberrations of sperm negatively affect pregnancy rates as well as fetal survival [ 15 ]. Consequently, recent AUA/ASRM guidelines state that sperm aneuploidy testing may be considered for those couples with RPL, particularly among the male partners with a normal somatic karyotype [ 3 ]. Through sperm aneuploidy testing, it is possible to identify those men with a defect resulting in improper chromosome segregation during meiosis and subsequent aneuploid sperm, leading ultimately to RPL [ 3 ]. Sperm aneuploidy testing involves the use of fluorescent molecular probes for chromosome 13, 18, 21, X, and Y, since the presence of an extra chromosome for these specific chromosomes is associated with viable but affected offspring; however, this test is not readily available nationwide [ 3 ]. Given the wider availability of SDF and karyotype testing, these are recommended first over sperm aneuploidy testing to evaluate the male partners of couples that have experienced RPL [ 3 ].

2.6. Summary

Ultimately, while the mechanisms and results of the four clinical tests for sperm DNA fragmentation are not identical, there is generally a good correlation between them [ 5 ]. Despite these corollary results, there is no consensus regarding the normal reference range(s) for these tests. There is also little evidence for whether these tests are cost-effective in the management of infertile couples [ 29 ]. Given this controversy, we will review recent evidence regarding the impact of SDF on reproductive outcomes, as well as how SDF test results are best used in modern clinical practice.

3. Impact of SDF on Reproductive Outcomes: Recent Evidence

Elevated SDF has been associated with many adverse reproductive outcomes, including lower natural pregnancy rates, lower ART pregnancy rates (including IUI, IVF, and ICSI), abnormal embryo development, and a greater likelihood of recurrent pregnancy loss [ 5 , 7 , 8 ]. These poor outcomes are hypothesized to be due to unrepaired DNA damage exceeding a critical threshold and blocking normal embryo development [ 6 ]. In mice, cell cycle checkpoints play an important role at this point, reversibly turning off cell cycle processes to allow for DNA repair and then resuming embryonic development after the damage has been resolved [ 30 ]. While level I evidence [ 31 ] supports the correlation between elevated SDF and adverse outcomes in humans, these results have not been consistent in every study, leading researchers and clinicians to evaluate other factors that may affect the impact of elevated SDF.

3.1. Impact of Sperm DNA Fragmentation on ART Pregnancy and Live Birth Rates

Recent studies have evaluated the relationship between sperm DNA damage and ART pregnancy rates with mixed results. Specifically, several systematic reviews and meta-analyses have demonstrated conflicting findings regarding the overall relationships between SDF and ART outcomes, as well as in subgroup analyses comparing treatment type (i.e., IVF vs. ICSI) and SDF test used (i.e., TUNEL, SCSA, Comet, etc.) [ 8 , 19 , 32 , 33 , 34 , 35 , 36 ].

In one of the earliest meta-analyses investigating this question, Evenson and Wixon evaluated 15 studies assessing the relationship between SDF and pregnancy outcomes using IUI, conventional IVF, and ICSI and/or conventional IVF. They found that infertile couples were significantly more likely to achieve a pregnancy if DFI was <30% and they underwent IUI (OR 7.3, 95% CI 2.88–18.3, p = 0.0001) or conventional IVF (OR 2.0, 95% CI 1.02–2.84, p = 0.03); however, there was no relationship between pregnancy rates and DFI in the studies that did not distinguish between ICSI and/or conventional IVF (OR 1.6, 95% CI 0.92–2.94, p = 0.06) [ 32 ].

Similarly, another meta-analysis published that same year by Li et al. reviewed eight articles, all of which utilized IVF or ICSI. In pooled analyses using TUNEL tests only, the authors found that for couples treated with IVF, clinical pregnancy rate significantly decreased with high DFI (RR 0.68, 95% CI 0.54–0.85, p = 0.006), though there was no change in fertilization rate (RR 0.79, 95% CI 0.54–1.16, p = 0.23) [ 33 ]. For couples treated with ICSI, however, there was no difference in clinical pregnancy or fertilization rates between the high- and low-DFI groups [ 33 ].

While these early meta-analyses initially seemed to suggest that SDF had a variable impact depending on the ART treatment type utilized, not all studies have confirmed this difference. In a 2008 meta-analysis by Collins et al., the authors evaluated 13 studies assessing over 2100 cycles of IVF/ICSI [ 34 ]. They found a significant association between SDF and chance of non-pregnancy with IVF or ICSI (OR 1.44, 95% CI 1.03–2.03), with no significant differences noted based on treatment type (IVF versus ICSI) [ 34 ].

This relationship between SDF, ART treatment type, and pregnancy rate has become even less clear in recent meta-analyses including an assessment of miscarriage rates. In a 2014 study by Zhao et al., the authors evaluated 16 cohort studies which included over 3100 couples [ 8 ]. They found that overall, high SDF had a detrimental effect on the outcome of IVF/ICSI, resulting in decreased pregnancy rates (OR 0.81, 95% CI 0.70–0.95, p = 0.008; I 2 = 30%) and increased miscarriage rates (OR 2.28, 95% CI 1.55–3.35, p < 0.0001; I 2 = 44%) [ 8 ]. When stratified by conventional IVF versus ICSI, the authors found that elevated SDF was associated with lower pregnancy rates only for the IVF group (OR 0.66, 95% CI 0.48–0.90, p = 0.008) and not for the ICSI group (OR 0.94, 95% CI 0.70–1.25, p = 0.65). In evaluating miscarriage rates, the opposite result was found: specifically, elevated SDF was associated with higher miscarriage rates only in the ICSI group (OR 2.68, 95% CI 1.40–5.14, p = 0.003) and not in the conventional IVF group (OR 1.84, 95% CI 0.98–3.46, p = 0.06) [ 8 ].

The following year, Zhang et al. similarly evaluated 20 studies assessing SDF, pregnancy rate, and pregnancy loss for couples undergoing IVF or ICSI [ 35 ]. Unlike the study by Zhao et al., these authors found no significant association between SDF and pregnancy loss. However, couples did have a higher change of clinical pregnancy if DFI was <27% (OR 1.4, 95% CI 1.19–1.74, p = 0.000). On subgroup analysis, this increase in clinical pregnancy rate with DFI < 27% persisted only for the IVF group (OR 1.74, 95% CI 1.38–2.20, p = 0.000); there was no significant difference for the ICSI group in clinical pregnancy rate if DFI was <27% (OR 0.90, 95% CI 0.63–1.27, p = 0.54) [ 35 ]. In stratifying by type of SDF test, there was a higher chance of clinical pregnancy if DFI was <27%, as measured by TUNEL (OR 1.87, 95% CI 1.36–2.58, p = 0.000), but there was no significant relationship between DFI and clinical pregnancy rate in the SCSA subgroup (OR 1.24, 95% CI 0.98–1.58, p = 0.076).

Finally, in the largest, most recent meta-analysis evaluating the effect of SDF on clinical pregnancy rate, Simon et al. evaluated 56 studies and over 8000 IVF/ICSI cycles. Unlike prior, smaller meta-analyses where the majority of studies evaluated sperm DNA damage only by SCSA and TUNEL tests, these authors included more recent studies utilizing SCD and Comet assays. Overall, they identified a detrimental effect of sperm DNA damage on clinical pregnancy rate after IVF and/or ICSI (OR 1.68, 95% CI 1.49–1.89, p < 0.0001) [ 36 ]. This negative effect persisted regardless of the ART technique used. When stratifying by type of SDF test, sperm DNA damage appeared to have a significant impact on clinical pregnancy rates when TUNEL, Comet, or SCD tests were utilized; there was no significant effect on clinical pregnancy rates when DNA damage was measured by SCSA [ 36 ].

While there has clearly been conflicting data regarding the effect of SDF on pregnancy rates after ART treatment, few studies have evaluated the effect of SDF on live birth rates. In 2015, Osman et al. performed a meta-analysis of six studies to answer this question. They found that live birth rate (LBR) increased significantly for couples with low SDF compared to those with high SDF (RR 1.17, 95% CI 1.07–1.28, p = 0.0005) [ 19 ]. When stratifying by type of ART treatment (IVF versus ICSI), men with low SDF had a significantly higher LBR regardless of treatment type, though SDF seemed to have a larger impact on the IVF group (RR 1.27, 95% CI 1.05–1.52, p = 0.01) compared to the ICSI group (RR 1.11, 95% CI 1.00–1.23, p = 0.04). However, when accounting for female factors, lower SDF was associated with a significantly higher live birth rate in only the IVF group (RR 2.76, 95% CI 1.59 to 4.80; p = 0.0003; n = 3 studies); there was no significant difference noted for the ICSI group (RR 1.08, 95% CI 0.39–2.96, p = 0.88; n = 2 studies), though this finding is limited by the small number of studies included in the analysis. When stratifying by type of ART treatment and SDF test, no significant differences in LBR were noted between the IVF SCSA/TUNEL/Comet subgroups and the ICSI SCSA/Comet subgroups. Ultimately, the authors concluded that these findings were strong enough to suggest that high SDF is associated with lower LBR among couples undergoing ART [ 19 ].

While there is a suggestion that elevated ART may impact pregnancy and live birth rates for some couples, there is no consensus among these prior studies. Studies of a single factor (such as SDF) and its potential effect on ART outcomes must consider well-established and recognized factors that affect ART results, such as female age. Failure to consider such factors in single studies or meta-analysis could mitigate or reverse the adverse effects of SDF on reproductive outcomes. Additionally, significant variations in study design, sensitivity and types of DNA damage measured by each SDF assay, patient populations, and ART protocols may contribute to divergent outcomes. The discrepancies between IVF and ICSI outcomes may also be related to the fact that higher quality, lower SDF sperm are being selected more frequently for oocyte injection by embryologists during ICSI compared to conventional IVF, where fertilization is left more up to chance. This hypothesis is supported by evidence demonstrating that the morphologically normal, motile sperm typically chosen for ICSI may have lower levels of sperm DNA damage [ 19 , 37 ]. It is also important to consider that sperm samples with oxidative damage tend to propagate that damage in other sperm within the same population. So, even “undamaged” sperm (that do not have the threshold of abnormality to be detected in SDF tests) could still have sufficient SDF to adversely affect reproductive outcomes. The sperm used for ICSI are also not subject to the prolonged culture associated with conventional IVF, which may itself lead to oxidative stress and additional DNA damage [ 38 ]. Rather, these ICSI sperm are promptly injected into an oocyte within a few hours of ejaculation, thus protecting them from any significant laboratory-induced damage [ 38 ]. It is important to remember that most studies of SDF on reproductive outcomes have evaluated neat (unprocessed) sperm samples, not the sperm actually used for insemination or ICSI. Finally, others have suggested that the oocyte itself may have a significant role in compensating for DNA damage and impact outcomes [ 5 , 6 , 19 , 39 , 40 , 41 , 42 , 43 ]. This question has been more fully explored within the last several years, with several contemporary studies evaluating the effect of donor oocytes and maternal age on ICSI cycles performed with high-SDF sperm.

3.2. Role of the Oocyte

Given these mixed results regarding the impact of elevated SDF on ART outcomes, it has been suggested that ART success may depend on the balance between the extent of the sperm DNA damage and the oocyte’s DNA repair capacity [ 5 ]. This hypothesis builds upon prior evidence demonstrating that DNA-damaged sperm are able to fertilize oocytes and generate early embryos both in vivo and in vitro [ 39 ]. During and after fertilization, the oocyte and developing zygote can then repair sperm DNA damage [ 19 , 39 , 40 ], though the exact mechanism by which this repair occurs is unknown [ 19 ]. In a recent systematic review by Newman et al., the authors synthesized 36 studies evaluating the response of oocytes and embryos to sperm DNA damage [ 44 ]. While more completely reviewed in that publication, the collective evidence derived from human and animal models suggests that the early embryo has the capacity to repair sperm DNA damage by activating maternally driven mechanisms within the oocyte [ 44 ]. Though the oocyte can compensate for a significant amount of sperm DNA damage, this repair capacity is likely limited, declines with age, and is variable depending on the individual oocyte and type/extent of sperm DNA damage [ 6 , 44 ].

To better understand the role of the oocyte in mitigating sperm DNA damage, recent clinical studies have evaluated the reproductive outcomes associated with using high- versus low-quality oocytes in combination with high-SDF sperm. Specifically, researchers have examined donor oocytes and the impact of maternal age on ART outcomes among couples in which the male partner has known elevated sperm DNA damage.

One of the earliest studies evaluating the effect of SDF on donor oocytes was published in 2011 by Esbert et al. [ 41 ]. In this prospective study of 178 couples, 77 underwent IVF/ICSI with their own oocytes, while 101 utilized donor oocytes. Sperm DNA fragmentation was measured on the same processed, ejaculated semen samples utilized for IVF/ICSI using a TUNEL assay. Overall, DNA fragmentation was not related to fertilization rates—neither for all cycles analyzed, nor when stratified by only IVF or ICSI cycles [ 41 ]. Similarly, utilizing a threshold value of 36%, the authors found no correlation between an SDF >36% and any clinical outcomes, including embryo quality, clinical pregnancy rates, implantation rates, or miscarriage rates [ 41 ]. On logistic regression, SDF was not predictive of clinical pregnancy. While this study is limited by its lack of information regarding live birth rates and the demographic features of oocyte donors (all that is known is that they were healthy donors less than 35 years old), it brings into question the clinical significance of sperm DNA damage, regardless of the quality of the oocyte.

This effect of SDF on donor oocytes was revisited in 2019 by Antonouli et al. [ 37 ]. In this prospective, observational cohort, the authors identified 150 ICSI cycles that utilized only donor oocytes and fresh, ejaculated sperm from male partners without a history of infertility. SDF was measured using the SCD technique on the same samples as those utilized for ICSI, with >25% DFI considered abnormal. When examining ICSI outcomes, there was no significant correlation between DFI and any clinical outcomes, including fertilization rate, total number of blastocysts, number of good quality blastocysts, or clinical pregnancy rate [ 37 ]. While limited by a lack of an autologous oocyte comparator group, lack of information regarding ongoing pregnancy and/or live birth rates, and a relatively low number of cycles, this study suggests that when controlling for female factors and performing ICSI, SDF may not have a significant impact on clinical outcomes. However, whether this is related to the oocyte compensating for sperm DNA damage or embryologists selecting ‘better’ sperm for ICSI remains unclear.

Finally, in 2022, Hervas et al. evaluated over 1900 ICSI cycles utilizing donor oocytes and fresh ejaculated sperm at several fertility centers in Spain [ 42 ]. SDF was measured using a TUNEL assay on a fresh sample produced closest to the day of ICSI (though not on the same sample used for ICSI). Cycles were divided into low- (≤15%, n = 1626 cycles) versus high-SDF (>15%, n = 277 cycles) groups. When comparing outcomes per cycle, the authors found no difference in good quality blastocyst rate (24.8% vs. 23.5%, p = 0.4), implantation rate (86.9% vs. 86.6%, p = 0.89), clinical pregnancy rate (50.9% vs. 55.5%, p = 0.17), or live birth rate (36.9% vs. 43.3%, p = 0.29) between the low- and high-SDF groups, respectively [ 42 ]. When calculating the cumulative live birth rate (CLBR) per embryo transfer, per embryos replaced, and per MII oocytes used, there was again no difference between high- vs. low-SDF groups. When stratified by 10% SDF ranges, there was similarly no impact of elevated SDF on live birth rate. While this study has several limitations—i.e., its retrospective design, lack of TUNEL testing on the same sample utilized for ICSI, lack of information regarding any interventions that the male partner may have undertaken between receiving his TUNEL test results and undergoing ICSI, lack of autologous oocyte comparator, and limited number of ICSI cycles with highly elevated SDF—this large, multi-center study using a direct SDF assay (TUNEL) supports earlier evidence that ICSI cycles utilizing high-quality donor oocytes do not demonstrate the poor reproductive outcomes associated with high sperm SDF seen in other studies.

In terms of maternal age, a recent study published in 2021 by Setti et al. stratified 540 couples undergoing ICSI by both maternal age as well as SDF [ 43 ]. SDF was measured using an SCD test (Halosperm) immediately before ICSI, utilizing the same fresh, unprocessed sample that was used in the ICSI cycle. The authors found that for younger female patients (≤40 years old), there was no significant difference in laboratory or clinical outcomes for cycles with low (<30%) or high (≥30%) SDF [ 43 ]. However, for couples in which the female partner was >40 years old, there was a significantly lower blastocyst development rate (30.2% vs. 49.6%, p = 0.035), lower high-quality blastocyst rate (44.6% vs. 70.6%, p = 0.014), lower pregnancy rate (7.7% vs. 20.0%, p = 0.040), lower implantation rate (11.9% vs. 19.7%, p < 0.001), and higher miscarriage rate (100% vs. 12.5%, p < 0.001) for cycles with high SDF compared to those with low SDF [ 43 ]. While this study did not provide any information regarding live birth rates, the authors concluded that when older oocytes (>40 years) are injected with high-SDF sperm, the embryos that develop are of poorer quality, leading to lower implantation rates, lower pregnancy rates, and higher miscarriage rates than ICSI cycles using oocytes from younger women [ 43 ].

While the precise mechanism(s) behind these results remains under investigation, these findings support the hypothesis that higher-quality oocytes likely have better DNA repair capabilities, allowing them to compensate for sperm DNA damage and produce higher-quality embryos that can develop normally [ 42 ]. However, even if this theory is correct, current evidence does not suggest what degree of SDF is too high for an oocyte to overcome [ 42 ]. Additionally, the sperm selection process associated with ICSI itself (rather than the oocyte) may still be playing a key role in these better outcomes—though this seems to be of less significance in light of the most recent study by Setti et al., in which SDF had a significant impact on the ICSI cycle outcomes for older women, but no difference on the ICSI cycle outcomes for younger women [ 43 ]. Ultimately, additional prospective, randomized, controlled trials are needed to delineate the precise DNA repair capabilities of the oocyte and delineate the extent of their abilities to overcome sperm DNA fragmentation.

4. Methods for Overcoming High SDF

While new evidence is still emerging about the effect of SDF on pregnancy rates and other reproductive outcomes, given the current body of evidence suggesting that elevated SDF likely has a detrimental (or at best, neutral) impact on outcomes, many researchers have explored methods for reducing sperm DNA fragmentation. The methods include: lifestyle modifications, oral antioxidant therapies, alterations in ejaculatory abstinence interval, new sperm processing methods (such as microfluidic sperm sorting), and even surgical therapies, including varicocelectomy and surgical sperm retrieval.

4.1. Lifestyle Modifications

As we know, it is well-recognized that sperm DNA fragmentation is caused by a variety of intrinsic and extrinsic factors [ 9 ]. Intrinsically, SDF may be induced by sperm chromatin packaging defects, defective germ cell maturation, apoptosis, and oxidative stress, while extrinsically, oxidative stress is primarily responsible [ 5 , 9 , 16 ]. These extrinsic risk factors may include environmental/lifestyle factors (i.e., cigarette smoking, radiation, chemotherapy, heat exposure, medications), pathologic conditions (i.e., varicocele, malignancy, infections, obesity, chronic illness), and even iatrogenic causes (i.e., sperm cryopreservation)—all of which have been associated with sperm DNA damage [ 5 , 45 ].

Though intrinsic factors are likely difficult to modify, infertile men with high sperm DNA fragmentation may have some control over extrinsic risk factors. Specifically, given that cigarette smoking [ 46 , 47 , 48 , 49 ], air pollution [ 50 , 51 , 52 ], pesticides [ 53 , 54 ], cancer treatments (including chemotherapy and/or radiation) [ 55 , 56 ], occupational radiation [ 57 ], selective serotonin reuptake inhibitor medications (SSRIs) [ 14 ], and sperm cryopreservation [ 58 ] have all been associated with elevated SDF, it is reasonable to assume that avoidance of such exposures will have a positive impact on SDF, though high-quality data are lacking for some of these factors [ 9 ].

It is important to note that the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) guidelines concede that there are limited data on specific lifestyle factors that affect male fertility [ 3 ], and some of these factors will be unavoidable (i.e., chemotherapy and/or radiation for cancer treatment). However, if making a healthy lifestyle change will improve sperm DNA fragmentation as well as provide other health benefits (i.e., smoking cessation), clinicians should consider recommending this change before moving on to other aggressive or invasive treatment strategies. Ultimately, additional high-quality studies are needed to fully understand and quantify the impact of lifestyle changes on SDF and birth outcomes.

4.2. Oral Antioxidant Therapies

Over the last several decades, the global dietary supplement market has experienced tremendous growth, and it is projected to exceed USD 200 billion by the early 2020s [ 59 ]. In the United States alone, dietary supplements are common, with nearly half of adult men (45%) reporting supplement use between 1999 and 2012 [ 60 ]. When evaluating only those men attempting to conceive, the percentage of men using dietary supplements was nearly identical (43.5%) [ 61 ].

Given this widespread supplement use, many researchers, clinicians, and patients have questioned the efficacy of these products in enhancing fertility. Specifically, since oxidative stress is a known contributor to sperm DNA damage, it seems logical that antioxidant therapy would help to offset this damage. Consistent with this hypothesis, several studies have demonstrated a positive effective of antioxidant therapy on SDF [ 62 , 63 , 64 , 65 , 66 , 67 , 68 ]; however, this has not been reproduced in all studies [ 69 , 70 ].

Several recent Cochrane reviews have been complied to synthesize the current evidence and more clearly delineate the role of antioxidants in treating male subfertility. The 2019 review included 61 studies and over 6200 subfertile men from couples referred to a fertility clinic for evaluation [ 71 ]. Studies were included if they were randomized controlled trials (RCTs) that compared any type, dose, or combination of an oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant [ 71 ]. A total of 44 of these 61 studies were included in the meta-analysis. Unfortunately, only four studies analyzed reported on DNA fragmentation. With this limited evidence, the authors found that men treated with antioxidants had on average a 5% lower SDF compared with placebo or no treatment, but the confidence interval was broad and crossed zero (95% CI −12.61 to 2.61, p < 0.0001, I 2 = 89%), making it difficult to draw any significant conclusions about the impact of antioxidants on SDF from this analysis [ 71 ].

In addition to SDF, the authors also examined the effect of antioxidants on live birth and clinical pregnancy rates. They found that antioxidants resulted in a statistically significant improvement in live birth rate (OR 1.79, 95% CI 1.20 to 2.67, p = 0.005, I 2 = 40%) compared to placebo or no treatment; however, these findings were based on limited data from only 124 live births from 750 couples in seven small studies, making the overall evidence low-quality [ 71 ]. Additionally, when studies at a high risk of bias were removed from the analysis, there was no evidence of increased live birth with antioxidants (OR 1.38, 95% CI 0.89 to 2.16, p = 0.15, I 2 = 0%; participants = 540 men, 5 RCTs) [ 71 ].

Similarly, antioxidants were associated with an increased chance of clinical pregnancy (OR 2.97, 95% CI 1.91 to 4.63, p < 0.0001, I 2 = 0%), but these findings were based on low-quality evidence, with only 105 clinical pregnancies from 786 couples in 11 small studies reported [ 71 ]. Fortunately, this analysis did not find any increase in miscarriage rate between the antioxidant and placebo/no treatment groups, and while gastrointestinal (GI) upset was increased with antioxidants, this was generally mild and estimated to occur in a minority of men (only 2% to 9% of the antioxidant group, versus 2% of the placebo/no treatment group) [ 71 ]. Overall, while this review did demonstrate some improvement in sperm DNA fragmentation, pregnancy rates, and live birth rates for infertile men treated with antioxidants, the quality of evidence was low, and the findings were considered to be inconclusive due to a high risk of bias [ 71 ].

Since 2019, several new RCTs studying the effect of antioxidants on sperm DNA fragmentation and reproductive outcomes have been published. One of these studies is the Males, Antioxidants, and Infertility (MOXI) trial, published in 2020 [ 69 ]. This double-blind, randomized, placebo-controlled trial was performed at nine fertility centers throughout the United States and tested a combination antioxidant formulation containing vitamin C, vitamin E, selenium, L-carnitine, zinc, folic acid, and lycopene. Men from infertile couples with at least one abnormal semen parameter were included. Participants were requested to provide a semen sample on the day of randomization as well as 90 days after treatment. While the primary study outcome was live birth, the protocol was designed to include an internal pilot examining the effect of antioxidants on semen parameters and SDF at 3 months. If this internal pilot did not reject the null hypothesis (i.e., if there was no difference in semen parameters between the treatment and control groups), the study would be closed.

Ultimately, 144 men completed the study. Interestingly, at 3 months, there was a statistically significant change in sperm concentration ( p = 0.029), total sperm count ( p = 0.021), and total motile sperm count ( p = 0.043) between the two groups, with the placebo group demonstrating an increase in these parameters and the antioxidant group demonstrating a decrease [ 69 ]. There was no difference between the two groups regarding percent normal morphology ( p = 0.470), percent total motility ( p = 0.822), and DNA fragmentation, as measured by SCSA (median 0.8, IQR −3.4 to 3.8 for antioxidant group; median 0.2, IQR −5.7 to 6.4 for placebo group; p = 0.548). When examining the 44 men who had an elevated SDF at baseline (defined as DFI > 25% as measured by SCSA), there was no significant difference between the antioxidant and placebo groups after 3 months (median −2.0, IQR −6.6 to 3.7 for antioxidant group; median −6.5, IQR −12.5 to 0.7 for placebo group; p = 0.197). Because this internal pilot failed to reject the null hypothesis, the study was ended.

While the reasons for these negative findings are unknown, the authors offer several hypotheses: (1) the excessive use of antioxidants could alter the balance between oxidation and reduction, leading to detrimental reductive stress; (2) interacting effects between the different antioxidants in the formulation could limit the overall efficacy of the treatment; (3) the study did not select for men most likely to benefit from antioxidants, such as those with high levels of reactive oxygen species (ROS) [ 69 ]. While the results of the MOXI trial are limited by the small sample size (especially those men with an elevated SDF at baseline), the strong study design adds to the body of evidence demonstrating no significant improvement in male fertility with the use of oral antioxidants.

In addition to MOXI, another randomized, multi-centered, double-blind, placebo-controlled trial examining the effect of antioxidants on semen quality and birth outcomes was also published in 2020, called “FAZST” (“Folic Acid and Zinc Supplementation Trial”). Unlike MOXI—which evaluated a combination formulation of seven different antioxidants—FAZST only evaluated a combination of folic acid and zinc. This combination was selected based on previous evidence that both compounds are essential for spermatogenesis and may have synergistic properties [ 59 ].

In this study, 2370 men were randomized to either the folic acid and zinc combination or placebo. Primary outcomes included both live births and semen parameters (including SDF) at 6 months after randomization. Only about two-thirds of the initial group ( n = 1629 men) presented for a semen analysis at 6 months. Of those that provided a repeat sample, there was no significant difference in most semen quality parameters, including sperm concentration, motility, morphology, volume, and total motile sperm count [ 59 ]. However, there was a significant increase in SDF in the treatment group versus placebo (mean percentage of DNA fragmentation 29.7% vs. 27.2%; mean difference 2.4%, 95% CI 0.5% to 4.4%) [ 59 ]. There were no significant differences in any semen parameters (including SDF) when accounting for participants lost to follow-up and when analyzing only men with known infertility or low semen quality at baseline [ 59 ].

In evaluating birth outcomes, there was no difference in live birth rates between the placebo and treatment groups: neither among the entire cohort (34% supplementation group vs. 35% placebo group; risk difference −0.9%, 95% CI −4.7% to 2.8%) nor the subset of patients undergoing infertility treatment [ 59 ].

Overall, this study is strengthened by its blinded, randomized, placebo-controlled design and large sample size. However, the authors concede that the findings may not be generalizable to other populations. Specifically, since most participants were white, non-Hispanic men with a high socioeconomic status, these findings may not be generalizable to men from other demographic backgrounds. Similarly, since this study did not focus on infertile men specifically, it has limited generalizability to that subgroup.

The authors also recognized that these findings were limited by the fact that nearly one-third (31%) of participants did not provide a semen sample at 6 months, leading to the potential for type 1 (false positive) error. Specifically, because the sample size was reduced by one-third and did not include all participants, there was an opportunity for bias and a statistically significant difference when in fact, such a difference may have been due only to random variation [ 72 ]. Consequently, the authors noted that all “statistically significant findings should be considered exploratory” [ 59 ]. Despite these limitations, this study further strengthens the argument that oral supplements do not significantly improve sperm DNA fragmentation—and in some analyses, may contribute to DNA damage [ 59 ].

Both MOXI and FAZST were included in the most recent version of the Cochrane review, published in 2022 [ 73 ]. Of the 90 studies and over 10,000 subfertile men included in the updated systematic review, 65 studies were included in the meta-analysis. Thirteen studies (1813 men) had data on DNA fragmentation; however, due to high heterogeneity, pooling of these results was not possible. Regarding reproductive outcomes, like the previous 2019 Cochrane review, the authors found that antioxidants may lead to increased live birth rates (OR 1.43, 95% CI 1.07 to 1.91, p = 0.02, I 2 = 44%) [ 73 ]. Again, however, only a limited number of studies included live birth rate as an endpoint (246 live births from 1283 couples in 12 small- or medium-sized studies), leading the authors to consider this increase in live birth rate “very low-certainty evidence”. Additionally, when studies at high risk for bias were removed from the analysis, there was no evidence of increased live birth rates for men taking antioxidants (OR 1.22, 95% CI 0.85 to 1.75, p = 0.27, I 2 =32%; participants = 827 men, eight RCTs) [ 73 ].

Similarly, the authors concluded that—based on low-certainty evidence—antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, p < 0.00001, I 2 = 3%; participants =1706 men, 20 RCTs) [ 73 ]. There was no difference in miscarriage rates between the antioxidant and placebo/no treatment group (OR 1.46, 95% CI 0.75 to 2.83, p = 0.27, I 2 = 35%; participants = 664 men, six RCTs; very low-certainty evidence). Men taking antioxidants did have an increase in mild GI upset versus placebo/no treatment (OR 2.70 95% CI 1.46 to 4.99, p = 0.002, I 2 = 40%; participants = 1355 men, 16 RCTs; low-certainty evidence).

Not included in the 2022 Cochrane review was a secondary analysis of the MOXI trial by Knutson et al., assessing the relationship between plasma antioxidant levels and semen parameters [ 74 ]. Specifically, these authors used multivariable linear regression models to determine if serum levels of vitamin E, zinc, and selenium were correlated with semen parameters and SDF. The authors found no correlation between serum levels of any of these antioxidants and semen parameters (concentration, motility, total motile) or SDF at either baseline or 3 months after treatment ( p > 0.05 for all). Baseline antioxidant levels were also not predictive of pregnancy or live birth outcomes ( p > 0.05 for all). While this study was limited by the fact that all men had normal baseline antioxidant levels and the initial trial was not powered to perform this secondary analysis, it does suggest that among infertile men with normal baseline antioxidant levels, additional antioxidant supplementation is unlikely to enhance semen parameters or clinical outcomes [ 74 ].

Ultimately, while the most recent 2022 version of the Cochrane review determined that antioxidant supplementation in subfertile males may improve clinical pregnancy and live birth rates for couples attending fertility clinics, these conclusions are based on low-certainty and very low-certainty evidence, respectively [ 73 ]. The authors recommend that subfertile couples be advised that the overall current evidence is inconclusive, due to poor reporting of methods, failure to report on live birth and clinical pregnancy rate(s), imprecision due to low event rates, high numbers of study dropouts, and small study group sizes [ 73 ]. It is important to consider not only this review, but also the individual trials (such as the MOXI and FAZST trials) within the context of their limitations. While the MOXI and FAZST trials did not demonstrate the efficacy of antioxidant therapy for most men, these findings may not be applicable to infertile men with high ROS or DNA fragmentation. Large, adequately powered, randomized, placebo-controlled trials reporting on pregnancy and live birth rates are needed to fully understand which men may benefit from antioxidant therapy and justify the out-of-pocket costs associated with it. Despite these data, given the high rate of baseline use of supplements, it is likely that patients will seek vitamins or supplements to use to enhance fertility. Unfortunately, there is no combination of antioxidants with sufficient data to support clinicians to specifically recommend.

4.3. Abstinence Interval

While the World Health Organization (WHO) currently recommends a 2- to 7-day abstinence period prior to a semen analysis [ 75 ], this interval is based largely on the need to standardize semen analysis results rather than on clinical outcomes [ 76 ]. This has prompted researchers to further investigate the optimal abstinence period for infertile men, including its relationship to sperm DNA fragmentation and impact on pregnancy and live birth rates.

In one of three recent systematic reviews evaluating the effect of ejaculatory abstinence interval on semen quality, Ayad et al. found that shorter abstinence was associated with a decrease in semen volume and sperm concentration, but a significant increase in sperm motility [ 77 ]. While the small number of studies evaluating the effect of abstinence on SDF prohibited any definitive conclusions, the authors noted that in half of the studies measuring SDF, a longer abstinence interval was associated with greater DNA fragmentation [ 77 ].

Similarly, another systematic review published in the same year concluded that semen parameters improve with shorter abstinence [ 78 ]. Specifically, abstinence of less than 3 days was associated with higher fertilization and pregnancy rates using ART, and abstinence of less than 24 h was associated with the lowest rates of sperm DNA fragmentation (SDF) [ 78 ].

Finally, the most recent meta-analysis published in 2021 found that in the majority of studies (15 of 20, 75%), a shorter abstinence period was associated with a lower SDF [ 76 ]. In pooled analyses, the authors concluded that a short abstinence interval consistently improves sperm motility, morphology, and SDF, and is associated with a trend towards better clinical pregnancy and live birth rates with IVF and ICSI [ 76 ].

However, it is important to note that most of the studies included in this most recent meta-analysis were of either prospective observational or retrospective design, with only one study being a randomized clinical trial (RCT). In this RCT, Kabukcu et al. prospectively randomized 120 couples with unexplained infertility planning to undergo IUI into two groups depending on ejaculatory abstinence interval. Specifically, male partners were instructed to provide an ejaculated semen sample for IUI after either 1 day of abstinence (Group A) or 3 days of abstinence (Group B). Sperm DNA fragmentation was measured on the day of IUI using a TUNEL assay. Using this experimental design, the authors found no difference in mean sperm DNA fragmentation for Group A (20.71 ± 11.01) versus Group B (23.78 ± 12.64; p = 0.187) [ 79 ]. Similarly, there was no difference in pregnancy rate between Group A (17.3%) and Group B (18.5%, p = 0.803) [ 79 ]. There was also no difference in mean sperm DNA fragmentation rate between pregnant couples (24.89 ± 12.89) and non-pregnant couples (21.71 ± 11.69; p = 0.288) [ 79 ].

While this most recent RCT suggests no difference in SDF with a 1- versus 3-day abstinence period, the bulk of the available evidence suggests that semen parameters (including SDF) improve with shorter abstinence. Additionally, recent work has sought to build on the prior studies demonstrating an improvement in sperm quality after a very short (≤3 h) abstinence period for normospermic [ 80 ] and infertile men [ 81 , 82 , 83 ].

Specifically, an Italian study published in 2020 compared semen parameters from 30 normozoospermic and 34 oligoasthenoteratozoospermic (OAT) men after (1) a 2-to-7-day abstinence period and (2) a 1 h abstinence period. Both groups demonstrated a significant improvement in normal morphology and a decrease in SDF with a shorter abstinence period; however, only the OAT group demonstrated an improvement in motility, suggesting that OAT men in particular may benefit from a very short abstinence interval [ 84 ].

In another Canadian study published in 2021, the authors evaluated a prospective cohort of 112 men presenting for their first semen analysis as part of an infertility evaluation. These men were requested to provide a semen sample after 3 days of abstinence and again after 3 h of abstinence. Both samples had SDF assessed by a sperm chromatin dispersion (SCD, HaloSperm) test. The authors found that among all participants, DNA fragmentation was significantly lower in the second ejaculated sample (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001) [ 85 ]. In evaluating only those subjects with an initially high SDF (>35%, n = 49), the authors again found a significant improvement in SDF with a shorter abstinence interval (52 ± 16% vs. 36 ± 17%, p < 0.0001), with 55% of subjects ( n = 27 of 49) improving into the normal SDF range [ 85 ]. While clinical outcomes such as pregnancy and live birth rates were not assessed, this study suggests that a short (3 h) abstinence interval may be a low-cost, effective way to reduce SDF, and should be attempted before any consideration of more invasive procedures (such as testicular sperm retrieval).

Finally, a 2022 study from India analyzed 67 men with oligospermia who provided a fresh ejaculated semen sample after 2 to 7 days of abstinence and another sample 1 to 3 h later [ 86 ]. The second sample had a significantly higher total motility ( p < 0.05), progressive motility ( p < 0.05), and sperm concentration ( p < 0.05). While only 17 men had SDF measured in both specimens, there was a significant decrease in SDF noted in the second sample ( p < 0.05). While this study did not report clinical outcomes, it adds to the overall body of literature suggesting that a very short abstinence interval improves both traditional semen parameters and sperm DNA fragmentation.

While there are few studies that have evaluated both sperm DNA fragmentation and clinical outcomes after a very short abstinence interval, two studies published in 2021 sought to evaluate the effect of a very short abstinence interval on ICSI outcomes.

The first study by Barbagallo et al. evaluated the effect of a 1 h abstinence interval on ICSI outcomes for oligoasthenospermic (OA) men [ 87 ]. In this retrospective review of 313 ICSI cycles, the authors compared men with normal semen parameters or mild OA (Group 1, n = 233) to men with severe OA (Group 2, n = 90). While all men provided a fresh semen sample for ICSI after a standard abstinence interval of 2 to 7 days, only men with severe OA (Group 2) provided a second semen sample after 1 h of abstinence. For these men, the second sample demonstrated better total motility ( p < 0.0001) and progressive motility ( p < 0.0001) compared to the initial sample [ 87 ]. Unfortunately, sperm DNA fragmentation was not measured.

Regarding clinical outcomes, the authors found that severe OA couples (Group 2) had a higher clinical pregnancy rate (31% vs. 20%, p = 0.001) and higher embryo quality ( p = 0.003) compared to Group 1; there was no difference in fertilization, implantation, live birth, or miscarriage rates [ 87 ]. While limited by its retrospective nature and lack of information regarding sperm DNA fragmentation, this study suggests that a very short abstinence interval provides at least comparable (and in some respects, improved) ICSI outcomes for men with severe OA.

Similarly, Ciotti et al. retrospectively compared 64 men with severe OAT (Group 1) to 52 men with normal semen parameters or mild OAT (Group 0) [ 88 ]. All men provided a fresh semen sample after 2–3 days of abstinence for use in an ICSI cycle. Men with severe OAT also provided a second semen sample after 2 h of abstinence. When comparing the first and second samples produced by OAT men, the second sample demonstrated significantly better total motility ( p < 0.001), progressive motility ( p < 0.001), and normal morphology ( p = 0.020); SDF was not measured. While Group 0 (control) demonstrated significantly better fertilization rates versus Group 1 (OAT) ( p < 0.001), there was no difference in pregnancy, implantation, or miscarriage rates. While this study is again limited by its retrospective design and lack of information regarding sperm DNA fragmentation, the authors concluded that requesting men with severely abnormal semen parameters to provide a second ejaculated sample after a very short abstinence period is an effective way to achieve better sperm quality and pregnancy rates comparable to those of normozoospermic men.

While it may be challenging for some men with severe infertility to provide two ejaculated samples within 1 to 3 h, these studies offer promising results. Specifically, these studies have confirmed that a very short abstinence interval results in a lower SDF [ 84 , 85 , 86 ]. Additionally, for men with severe OAT who may not reliably have sperm suitable for ICSI in their ejaculate, this may be an effective way to enhance ejaculated sperm quality. While it is unclear in the severe OAT population if a change in sperm DNA fragmentation is contributing to these enhanced outcomes, additional randomized, controlled, prospective studies will more fully elucidate the relevance of reducing sperm DNA fragmentation on clinical outcomes. It is important to remember that instructions for collection of semen samples were not proposed to optimize sperm quality for reproduction, but rather to standardize evaluations. With this information, researchers will be closer to delineating the optimal abstinence interval for infertile men.

4.4. Microfluidic Sperm Sorting (MSS)

Regardless of ART technique utilized, high-quality sperm first need to undergo processing to separate them from the surrounding seminal fluid and debris. Given that ICSI only requires one sperm to fertilize an oocyte, it is essential that embryologists select the highest-quality sperm to achieve optimal outcomes using this technique. To achieve this goal, several sperm processing techniques have been developed to identify and isolate high-quality sperm. Traditionally, density gradient centrifugation (DGC) and the swim-up method have been the most commonly used techniques to isolate high-quality sperm from defective sperm, as well as surrounding seminal plasma, debris, and other cells [ 89 ]. However, the centrifugation associated with these techniques has previously been shown to increase reactive oxygen species and induce sperm DNA fragmentation [ 90 , 91 ], leading researchers to investigate alternative, less damaging strategies for sperm selection.

Microfluidic sperm sorting (MSS) is a newer method of sperm processing that has generated increasing interest. With this technique, high-quality sperm are isolated based on fluid dynamics, allowing them to avoid any additional mechanical stress or physical damage from external forces, such as centrifugation [ 92 ]. While several MSS devices have been developed to separate motile, morphologically normal sperm from the rest of the semen sample without centrifugation, initial utilization and implementation of this technique was limited due to the complexity of the devices, their reliance on laminar flow and need for a pump or gravity-dependent structure, prolonged processing time, inability to remove all dead sperm and debris without a filtering step, and unsatisfactory selection efficiency for samples with low sperm counts [ 93 ].

As technology has evolved, however, simpler, commercially available MSS devices have emerged, making it possible for MSS to be used in a clinical setting. These modern MSS devices are typically designed to consist of a single-use chip with inlet and outlet chambers connected by a microfluidic channel. The microchannels between these chambers hydrodynamically constrain abnormal sperm near the inlet chamber while allowing motile sperm to progress to the outlet chamber [ 93 ].

In an early study published in 2016 by Shirota et al., the authors aimed to evaluate the efficacy of a commercially available MSS device in minimizing sperm DNA damage. In this study, semen samples were obtained from 37 healthy volunteers and processed using either (1) the centrifugation and swim-up method (CS) or (2) an MSS sperm sorting chip (the ‘QUALIS sperm sorter’, manufactured by Menicon Co. and approved for use in ART procedures by the US FDA) [ 92 ]. Sperm DNA damage was measured after both processing methods using an SCSA assay. The authors found that samples processed via MSS had a significantly lower mean sperm DNA fragmentation index (DFI) compared to the samples processed via CS (0.8 ± 1.9 vs. 10.1 ± 8.5, respectively; p < 0.05) [ 92 ]. The samples processed by MSS also had a significantly higher mean sperm motility (95.4 ± 3.0 vs. 60.3 ± 19.4, p < 0.05) and lower sperm concentration (3.6 ± 4.0 million versus 49.4 ± 46.4 million, p < 0.05) [ 92 ]. Given that the MSS protocol only required about 30 to 45 min to complete (versus up to 2 h with CS), the authors concluded that MSS could efficiently and reliably select sperm with a higher motility and lower SDF than conventional methods. In fact, this was the first study to demonstrate that it was possible to decrease sperm DFI to <1% using MSS methods.

Additional studies have expanded on this early evidence to evaluate infertile men (versus healthy volunteers) as well as other commercially available MSS chips. In 2018, Quinn et al. compared unprocessed semen samples from 70 infertile men to those processed by (1) density gradient centrifugation with swim-up (CS) and (2) sorting by a microfluidic chip. In this study, the authors used the FERTILE device, manufactured by ZyMot [ 93 ]. Sperm DNA fragmentation was measured after processing using an SCD assay.

Again, these authors found that the samples processed by MSS had a significantly lower DFI compared to those processed by CS ( p = 0.0029), as well as unprocessed samples ( p < 0.0001) [ 93 ]. Specifically, the median DFI for MSS-processed specimens was 0% (IQR 0–2.4%), compared to 6% (IQR 2–11%) for those processed by CS [ 93 ]. Similarly, the median progressive motility of the samples processed by MSS was 100% (IQR 100–100%), which was significantly greater than the samples processed by CS (median: 91%, IQR 86–95%, p < 0.0001). While this study did not evaluate any clinical outcomes after processing, it confirms prior results demonstrating that MSS allows for the selection of clinically usable, highly motile sperm with nearly undetectable levels of sperm DNA fragmentation [ 93 ].

More recent studies have built on this prior data to understand if MSS leads to meaningful improvement in ART outcomes. In 2019, Parrella et al. tested 23 semen samples obtained from men undergoing an initial semen analysis. TUNEL assay was used to assess the degree of sperm DNA fragmentation in the raw sample and after processing, either with density gradient selection (DGS) or MSS. MSS was performed using a ZyMot Multi sperm separation device. Like the previous studies, Parrella et al. found that MSS resulted in a significantly lower mean SDF (1.8 ± 1) compared to DGS (12.5 ± 5; p < 0.001) and the raw sample (20.7 ± 10; p < 0.0001) [ 94 ].

To further understand the impact of these findings on reproductive outcomes, the authors similarly analyzed 25 couples undergoing ICSI. Specifically, they assessed the semen characteristics and SDF of the 25 male partners before and after processing with DGS and MSS. Again, they found a significant decrease in SDF with MSS (1.3 ± 0.7%) versus DGS (21 ± 9%) or the raw sample (28.8 ± 9%; p < 0.0001) [ 94 ]. There were also significant improvements in total motility, progressive motility, and normal morphology for the samples that underwent MSS ( p < 0.0001).

Of these twenty-five couples, four couples were identified as having very high baseline SDF (mean 34.1 ± 9%). Again, SDF decreased slightly after DGS processing (26 ± 4%); however, this improvement was more dramatic after MSS processing (1.6 ± 0.7%, p < 0.02) [ 94 ]. Among these four couples, there were 11 ICSI cycles performed with DGS-processed sperm, which resulted in a fertilization rate of 59.0%, a good quality embryo rate of 26.3%, a clinical pregnancy rate of 25%, and no live births. There were also four ICSI cycles performed with MSS-processed sperm, which resulted in a similar fertilization rate (61.2%), but a higher percentage of good-quality embryos (57.1%), a higher clinical pregnancy rate (50%), and higher live birth rate (50%). While none of these improvements were statistically significant, they suggest that MSS may be associated with meaningful improvements in clinical outcomes for some men with high SDF and could be considered a non-invasive alternative to utilizing other strategies (such as using surgically retrieved testicular sperm) for overcoming the negative outcomes associated with high sperm DNA fragmentation.

Subsequent studies have similarly attempted to clarify the impact of MSS on ART outcomes. In a 2019 study by Gode et al., the authors retrospectively evaluated 265 couples who underwent IUI at a single center in Turkey [ 95 ]. Of these, sperm were prepared using a density gradient centrifugation technique for 132 couples, and MSS was used for 133 couples (Fertile Plus ® ; KOEK Biotechnology). While baseline semen parameters were similar between the two groups, after processing, sperm motility was significantly higher in the MSS group (96.34 ± 7.29% vs. 84.42 ± 10.87%, p < 0.05); sperm DNA fragmentation was not measured. While pregnancy rates and ongoing pregnancy rates were not significantly different between MSS and density gradient groups, respectively (pregnancy: 18.04% vs. 15.15%, p > 0.05; ongoing pregnancy: 15.03% vs. 9.09%, p > 0.05), on multivariable logistic regression, there was a significant increase in ongoing pregnancy rate for the MSS group (OR 3.49, 95% CI 1.12–10.89, p < 0.05). Ultimately, while limited by its retrospective design, the authors concluded that MSS improves motile sperm rates and ongoing pregnancy rates after IUI, though additional, well-designed studies are needed to support this finding.

Three other studies from 2019 similarly attempted to clarify the impact of MSS on ICSI outcomes. The first by Kalyan et al. utilized a sibling oocyte study design to control for any relevant female factors. Specifically, the MII oocytes from each patient were split equally into two groups: half were injected with sperm sorted by a conventional swim-up method, and half were injected with sperm sorted by MSS (Fertile Plus ® ; KOEK Biotechnology, Turkey); no centrifugation was performed in either technique. Male partners with a total motile sperm count <1 million were excluded. Overall, 81 couples met criteria and were enrolled in the study. Of these 81 couples, there were no statistically significant differences in any of the laboratory outcomes measured, including: number of MII oocytes, number of fertilized oocytes, number of good-quality embryos, number of total blastocysts, and number of top-quality blastocysts (all p > 0.05) [ 96 ]. Of the 49 couples who underwent embryo transfers, there was no significant difference between the swim-up group (Group 1, n = 26) and the Fertile Plus ® group (Group 2, n = 23) in regard to overall pregnancy rate (65% vs. 61%, p > 0.05), clinical pregnancy rate (50% vs. 48%, p > 0.05), or miscarriage rate (15% vs. 13%, p > 0.05) [ 96 ]. While this study is limited by its small sample size and lack of information regarding SDF and other male factors (such as lifestyle factors, varicocele status, etc.), it does suggest that MSS may not have a significant impact compared to conventional swim-up sorting methods in unselected populations without elevated baseline SDF undergoing ICSI.

Also in 2019, Yetkinel et al. performed a prospective, randomized, controlled study at a single academic center evaluating the effect of MSS on ICSI outcomes for couples with unexplained infertility [ 97 ]. They identified 122 couples with unexplained infertility and assigned them to either conventional swim-up semen processing (control group) or MSS processing (Fertile Chip ® ; KOEK Biotechnology). The swim-up method included 10 min of centrifugation. Sperm DNA fragmentation was not measured in either group. Ultimately, while the authors found a significantly higher number of grade 1 embryos in the MSS group versus the control (1.45 ± 1.62 vs. 0.83 ± 1.03, p = 0.01), there was no significant difference in fertilization rate (63.6% and 57.4%, p = 0.098), clinical pregnancy rate (48.3% and 44.8%, p = 0.35), or live birth rate (38.3% versus 36.2%, p = 0.48) between the MSS group and the control group, respectively [ 97 ]. While limited by a small study population, the prospective, randomized design does offer compelling evidence that MSS does not change clinical outcomes associated with ICSI treatment for couples with unexplained infertility. Further studies evaluating specific populations that are most likely to benefit from MSS (i.e., men with high baseline sperm DNA fragmentation) are needed to fully inform providers on the utility of MSS.

Finally, Yildiz et al. performed a prospective, randomized study of 428 infertile couples presenting to a single center with a history of unexplained infertility for IVF/ICSI [ 98 ]. For most patients, sperm were prepared using a density gradient centrifugation method ( n = 312), while the rest were prepared using a microfluidic chip ( n = 116) (Fertile Plus Chip ® , Koek Biotechnology). The patients were then divided into groups depending on whether they were presenting for their first ICSI cycle ( n = 336) or if they had previously failed two IVF cycles ( n = 92). For those presenting for their first ICSI cycle, there was no significant difference in fertilization rate or pregnancy rate between the density gradient and microchip groups, respectively (fertilization rate: 70.2% vs. 69.4%, p = 0.650; pregnancy rate: 50.7% vs. 53.75%, p = 0.640). However, when evaluating those couples who had previously failed two or more IVF cycles, there was a significant improvement in fertilization rate for the MSS group (73.4% vs. 62.9%, p = 0.002), but no difference in pregnancy rate (52% vs. 50%, p = 0.900). Sperm DNA fragmentation was measured in only a subset of patients, including 10 unprocessed samples, 10 samples from the gradient group, and 10 samples from the microchip group. In this subset, MSS was associated with a significantly lower mean SDF (22.3 ± 13.9%) versus the gradient group (29.5 ± 21.9%; p = 0.01). Ultimately, while weakened by a small sample size, limited follow-up, and lack of data regarding live birth outcomes, this study does confirm that MSS is associated with lower SDF and may improve some clinical outcomes for couples with a history of recurrent IVF failure, though this may not have an impact on live birth rates.

Recent evidence published after 2020 has been similarly mixed. In 2021, Anbari et al. performed a prospective, randomized study in which participants were assigned to sperm processing with MSS (Group 1; n = 45) or direct swim-up (DSU) (Group 2; n = 50); no centrifugation was performed in either technique. MSS was performed using culture dishes available in the ART lab rather than a commercially available chip. Men with severe male factor infertility were excluded, and all samples utilized were normozoospermic, ejaculated specimens. Sperm DNA fragmentation was assessed after processing for both groups using a sperm chromatin dispersion (SCD) test. Consistent with prior studies, rates of sperm DNA fragmentation were significantly lower for the MSS group (20.17 ± 4.08%, vs. 24.82 ± 5.06, p < 0.001), while progressive motility was significantly higher for the MSS group (87.80 ± 7.48, vs. 83.13 ± 9.46, p < 0.01) [ 89 ]. In terms of clinical outcomes, there were significantly higher rates of high-quality embryo formation (81.9% vs. 57.6%, p < 0.001), implantation (48.7% vs. 25.6%, p = 0.04), and clinical pregnancy (44.7% vs. 23.1%, p = 0.05) in the MSS group versus the DSU group; live birth rates were not reported [ 89 ]. Overall, the authors concluded that MSS is an easy, non-invasive way to decrease SDF and improve clinical outcomes among infertile couples with normozoospermic semen parameters.

In 2022, Mirsanei et al. sought to re-evaluate the question of whether or not MSS could be beneficial for couples with a history of low fertilization rate (<25%) or total fertilization failure during a prior IVF cycle compared to those undergoing their first ICSI cycle [ 99 ]. Couples were excluded if the male partner had a history of an abnormal semen analysis, varicocele, or other known cause of male infertility. A total of 10 couples with a prior fertilization failure and 15 couples undergoing their first ICSI cycle (control) fit criteria and were included in the study. Approximately half of the oocytes from each group were fertilized using sperm prepared by MSS (Fertile Plus, Koek Biotechnology), and the remainder were fertilized using sperm prepared by density gradient centrifugation (DGC). SDF was measured using an SCD test on the samples before and after processing. The authors found no difference in SDF between the fertilization failure and control groups before processing; however, after processing, SDF decreased significantly for the MSS group ( p < 0.001). In comparing ICSI outcomes, there was no significant difference in fertilization rate between the MSS and DGC groups for couples undergoing their first IVF/ICSI cycle ( p > 0.05). For those couples who had previously experienced a fertilization failure, fertilization rates were significantly higher after MSS processing compared to DGC processing ( p < 0.001). Similarly, MSS significantly improved embryo quality for both the fertilization failure and control groups ( p < 0.001). However, there was no significant difference in overall clinical pregnancy rate between the fertilization failure group and control group ( p > 0.05). While limited by a small sample size, this study confirmed that SDF decreases significantly after MSS (even among men without known infertility), and MSS may contribute to increased fertilization rates and better embryo development, particularly among couples with a prior history of fertilization failure. Additional large, well-designed studies are needed to confirm these conclusions.

Finally, in another study from 2022, Quinn et al. attempted to further delineate whether or not processing sperm for ICSI with MSS improves embryo quality (compared to DGC) [ 91 ]. In this single-center, prospective, randomized, controlled trial, 192 patients were assigned to sperm processing with MSS, and 194 were assigned to standard DGC. Male partners were excluded if they had severe oligoasthenospermia. MSS was performed using the ZyMot ® ICSI Sperm Separation Device. SDF was not measured. In an intention to treat analysis, the authors found no difference in the mean fertilization rate (79.4 ± 19.4% control, versus 75.2 ± 17.8% MSS, p = 0.055), mean high-quality day 3 embryo rate (66.0 ± 25.8% control, vs. 68.0 ± 30.3% MSS, p = 0.541), mean high-quality blastocyst rate (37.4 ± 25.4% control vs. 37.4 ± 26.2% MSS, p = 0.985), clinical pregnancy rate (55.7% control vs. 52.2% MSS, p = 0.445), or ongoing pregnancy rate (42.9% control vs. 44.6%, p = 0.764). Ultimately, the authors concluded that MSS leads to similar ICSI outcomes as DGC in an unselected population. While these results may differ among selected populations (i.e., men with high SDF, couples with recurrent IVF failure, etc.), these findings suggest that among a general IVF/ICSI population, MSS performs just as well as the traditional, standard-of-care processing techniques that have been widely used. Therefore, while it may not have a significant benefit compared to traditional techniques in regard to ICSI outcomes, if MSS is more efficient, cost-effective, and easy to perform, these reasons alone may be sufficient to broadly implement it in clinical IVF practices.

While these prior studies are somewhat heterogeneous regarding patient population, MSS techniques, SDF assays used, and conventional sperm processing techniques used as ‘control’ populations, there is strong evidence that MSS significantly decreases SDF—even eliminating it in some circumstances. While the impact of this reduction in SDF on clinical outcomes remains unclear, further large, well-designed studies specifically evaluating subgroups such as those with male factor infertility, known elevated SDF, and prior IVF failures will be useful for delineating who may most benefit from MSS processing. In the meantime, for an unselected population, MSS has no significant detrimental effect and may even enhance some clinical outcomes among a subset of patients, though this has not been widely proven.

4.5. Varicocelectomy

It is well-established that varicoceles are the most common, correctable cause of male infertility and subfertility [ 100 ]. Defined as an abnormal dilation of the pampiniform plexus of the spermatic cord, varicoceles are present in about 15% of adult men in the general population, but up to 40% of men with primary infertility and up to 80% of men with secondary infertility [ 100 , 101 ]. Specifically, recent evidence has confirmed that varicoceles are associated with poor semen quality, sperm function, reproductive hormone levels, and pregnancy outcomes [ 100 ]. Given the convincing clinical evidence that varicoceles are detrimental to male fertility, recent AUA/ASRM guidelines recommend treating varicoceles in men attempting to conceive who have palpable varicocele(s), infertility, and abnormal semen parameters [ 102 ].

Several mechanisms for this varicocele-associated subfertility have been proposed, including scrotal hyperthermia, testicular hypoxia, and reflux of adrenal and renal metabolites, among others [ 100 , 103 ]. While the precise mechanism(s) by which varicoceles cause subfertility is still under investigation, it is strongly suspected that increased oxidative stress underlies all of these etiologies and acts as a common pathway in the pathogenesis of varicocele-associated male subfertility [ 100 , 103 ].

Consistent with this theory, men with varicoceles have consistently been found to have elevated levels of reactive oxygen species (ROS) in seminal plasma. In one meta-analysis of four studies measuring ROS and total antioxidant capacity (TAC), the authors found that men with varicoceles had significantly higher concentrations of ROS (mean difference 0.73, 95% CI 0.40–1.06, p < 0.0001) and lower concentrations of TAC (mean difference −386 trilox equivalents, 95% CI −556.56 to −216.96, p < 0.00001) compared to controls [ 104 ]. More recent studies have similarly suggested that men with varicoceles have higher levels of ROS and lower levels of antioxidants compared to men without varicoceles [ 105 , 106 ]. Further strengthening this relationship is recent evidence that higher grades of varicoceles in infertile men correlate with higher levels of oxidative stress [ 107 , 108 ], though this has been refuted in other series of fertile men with varicoceles [ 109 ].

Overall, the current body of evidence generally agrees that clinical varicoceles in infertile men are strongly associated with elevated levels of oxidative stress. Such oxidative stress has been shown to negatively impact sperm in several ways, including inducing apoptosis, damaging cell membranes, and damaging nuclear and mitochondrial DNA [ 103 ]. This results in elevated sperm DNA fragmentation which, if substantial enough, may negatively impact embryonic development and reproductive outcomes.

Given that elevated SDF may be a contributing factor to the poor reproductive outcomes associated with clinical varicoceles, several recent meta-analyses have sought to understand the impact of varicocele repair on reversing this DNA damage. In one early meta-analysis from 2012, Wang et al. evaluated 12 studies which included a total of 240 men with clinical varicoceles and 176 normal controls. These authors found that men with clinical varicoceles had significantly higher levels of sperm DNA damage (mean difference 9.84%; 95% CI 9.19–10.49; p < 0.00001); however, varicocelectomy was able to significantly improve SDF, with a mean difference of −3.37% (95% CI −4.09 to −2.65, p < 0.00001) [ 110 ].

More recent work has built on this finding. In 2020, Birowo et al. performed a systematic review and meta-analysis which included seven prospective studies (289 patients) evaluating adult men with clinical varicoceles who underwent a surgical varicocelectomy procedure by any technique (retroperitoneal, inguinal, subinguinal) [ 111 ]. The authors then compared pre- and postoperative SDF and semen analyses. SDF was measured by SCSA, SCD, or TUNEL. Overall, varicocelectomy significantly reduced SDF (mean difference −6.86%, 95% CI −10.04% to −3.69%, p < 0.00001) and improved several conventional semen parameters, including sperm concentration (mean difference 9.59 million/mL, 95% CI 7.80–11.38, p < 0.00001), progressive motility (mean difference 8.66%, 95% CI 6.96–10.36, p < 0.00001), and normal morphology (mean difference 2.73%, 95% CI 0.65–4.80, p = 0.01) [ 111 ]. While this meta-analysis was limited by heterogeneity regarding samples sizes, methods of surgical intervention, and evaluation of SDF, it was strengthened by its inclusion of only prospective studies and offers compelling evidence regarding the effect of varicocelectomy on SDF and semen parameters. In fact, the authors even argue that the analysis demonstrates that an abnormal SDF should be considered as an indication for varicocelectomy, though this is not in line with current guidelines [ 111 ].

In 2021, Qiu et al. similarly performed a systematic review and meta-analysis evaluating the effect of varicocelectomy on sperm DNA integrity [ 112 ]. They included 11 prospective studies (394 patients) evaluating infertile men with clinical varicoceles. Unlike the study by Birowo et al., this group compared (1) SDF before and after varicocelectomy (same patient), as well as (2) patients with and without intervention (varicocele repair). Any SDF test was acceptable for inclusion, including SCSA, TUNEL, Comet, SCD, AOT, or a combination. After analyzing all 11 studies, the average DNA fragmentation index (DFI, %) of clinical varicocele patients decreased by 5.79% (95% CI, −7.39 to −4.19) after varicocelectomy, though heterogeneity was significant (I 2 = 73.7%, p < 0.0001). After excluding one study with high heterogeneity, mean DFI decreased by 6.14% (95% CI −6.90 to −5.37), and heterogeneity was no longer significant (I 2 = 40.6%, p = 0.087). Like the study by Birowo et al., these authors suggested that their results strongly show that varicocelectomy significantly reduces SDF, and elevated SDF should be considered a molecular indicator for varicocelectomy among men with clinical varicoceles [ 112 ].

Finally, also in 2021, Lira Neto et al. published a systematic review and meta-analysis evaluating the effect of varicocelectomy on sperm DNA fragmentation. In the largest meta-analysis to date on this topic, the authors included 19 studies (both prospective and retrospective; 1070 patients) comparing SDF rates before and after varicocelectomy among infertile men with clinical varicoceles [ 113 ]. Any of the four most common SDF tests were considered acceptable (SCSA, TUNEL, SCD, Comet). Overall, pooled resulted demonstrated that varicocelectomy was associated with reduced postoperative SDF (weighted mean difference −7.23%; 95% CI: −8.86 to 5.59; I 2 = 91%; p < 0.001; 19 studies, 1070 patients). Subgroup analyses resulted in similar, statistically significant reductions in postoperative SDF rates regardless of the type of SDF test, surgical technique, varicocele grade, or whether data were obtained from prospective or retrospective studies. However, subgroup analyses did find that the treatment effect was more pronounced among men with elevated (versus normal) preoperative SDF levels: specifically, the postoperative weighted mean difference for men with a preoperative SDF ≥20% was −8.34% (95% CI: −10.50% to −6.17%; I2 = 88%, p < 0.0001) versus −3.92% for men with a preoperative SDF < 20% (95% CI: −5.36% to −2.48%; I2 = 79%, p < 0.0001). Similarly, on meta-regression analysis, SDF decreased after varicocelectomy as a function of preoperative levels (coefficient: 0.23; 95% CI: 0.07 to 0.39). Ultimately, the authors concluded that these pooled results confirm that varicocelectomy significantly reduces SDF for infertile men with clinical varicoceles—particularly for men with elevated SDF preoperatively.

It is important to consider that these meta-analyses have several limitations, including significant heterogeneity due to different study designs, different varicocelectomy techniques, different SDF assays, and different patient populations and sample sizes. Additionally, while these meta-analyses included only or mostly prospective studies, there are no randomized trials that have previously investigated this topic, namely due to the ethical problems associated with a surgical procedure being performed in one group but not another. Despite these methodological limitations, these studies strongly suggest that varicocelectomy is an effective way to reduce SDF in infertile men with clinical varicoceles.

However, the clinical implications associated with this reduction in SDF remain unclear. While prior studies have demonstrated an improvement in pregnancy rates after varicocelectomy [ 114 ], few studies have also correlated these outcomes with sperm DNA fragmentation. Specifically, few studies have assessed the difference in pregnancy outcomes after varicocelectomy for infertile men with elevated SDF [ 115 ]. In a recent study from 2021, Fathi et al. sought to further answer this clinical question by evaluating the effect of microsurgical subinguinal varicocelectomy on SDF and pregnancy rates among subfertile men with normal semen parameters, high SDF (>25%, as measured by SCD), and clinical varicoceles. The authors identified 85 men meeting these criteria; 45 underwent a microsurgical varicocele repair, while 40 had no intervention (control). At 6 months, mean SDF was decreased from baseline in both the varicocelectomy (25.75 ± 5.14%, vs. 34.93 ± 5.56% baseline) and control groups (31.26 ± 5.34% vs. 35.33 ± 6.12% baseline), though the decrease in SDF was significantly greater among the varicocelectomy group ( p < 0.001) [ 116 ]. After 1 year of follow-up, the spontaneous pregnancy rate was significantly higher among the varicocelectomy group (62%) compared to the control group (30%, p = 0.009) [ 116 ]. Ultimately, the authors concluded that microsurgical varicocelectomy has a beneficial role in reducing SDF and increasing the chance of spontaneous pregnancy for subfertile men with elevated SDF and otherwise normal semen parameters.

While this study offers interesting results, it is important to consider that it is limited by a small sample size and non-randomized control group. Similarly, it does not answer why the men who underwent a varicocelectomy had a higher pregnancy rate: was this purely the result of a decrease in sperm DNA fragmentation, or was it related to improvements in other semen parameters? Did additional lifestyle factors or female factors serve as confounders? Even if this improvement in pregnancy rates was directly related to a decrease in SDF, could a similar improvement be achieved by less invasive means, such as a short ejaculatory abstinence interval [ 115 ]? To understand who may benefit from a surgical varicocelectomy procedure, further studies are needed to delineate the relationship and mechanism between sperm DNA fragmentation, varicocelectomy, and live birth rates. In the final analysis, most studies evaluating the benefit of varicocele repair on SDF suggest that DNA damage only decreases by 5–10% after varicocele repair, a difference that may not return abnormal SDF levels to normal.

4.6. Surgical Sperm Retrieval

Surgical sperm retrieval is a well-established, effective method for helping couples with azoospermia conceive; however, recent evidence suggests that it may also be useful for some couples in which the male partner has a history of elevated ejaculated SDF [ 117 , 118 , 119 , 120 , 121 , 122 ]. While controversial, this practice is based upon the fact that sperm retrieved from the testis and/or epididymis are known to have lower levels of SDF compared to ejaculated sperm [ 119 , 120 , 123 ]. This is likely because sperm are exposed to oxidative stress during their transit through the male genital tract [ 11 ]: by retrieving sperm directly from the testis and/or epididymis, this oxidative stress is avoided, leading to lower SDF levels and better reproductive outcomes using this sperm for ICSI compared to ejaculated sperm [ 7 , 117 ].

In a 2017 meta-analysis evaluating the reproductive outcomes associated with using testicular versus ejaculated sperm for ICSI among men with elevated SDF, Esteves et al. evaluated four studies reporting the clinical outcomes of over 500 ICSI cycles performed with either testicular (Testi-ICSI) or ejaculated sperm (Ejac-ICSI). Men were classified as having “high SDF” based on the thresholds initially used in each study. In pooled analyses, the clinical pregnancy rate was higher (50.0% vs. 29.4%, p < 0.001; OR 2.42, 95% CI 1.57–3.73, I 2 = 34%, p < 0.001) and miscarriage rates were lower (9.4% vs. 29.1%, p = 0.002; OR 0.28, 95% CI 0.11–0.68, I 2 = 11%, p = 0.005) for Testi-ICSI cycles versus Ejac-ICSI cycles [ 117 ]. While only two studies reported on live birth rates (272 ICSI cycles), live birth rates were higher for Testi-ICSI cycles (46.9% vs. 25.6%, p < 0.001; OR 2.58, 95% CI 1.54–4.35, I 2 = 0, p < 0.001) [ 117 ]. Overall, the authors concluded that among men with confirmed high SDF in the ejaculate, using testicular sperm for ICSI may result in enhanced reproductive outcomes, including better live birth rates.

Prospective, large-scale, randomized controlled trials are needed to validate these outcomes; however, no such high-quality study yet exists. Given the invasive nature of a sperm retrieval procedure and current low level of evidence (i.e., no randomized trials) to support using testicular and/or epididymal sperm from non-azoospermic men with elevated SDF, the routine application of this practice remains controversial. Current European Association of Urology (EAU) guidelines recommend approaching this practice with caution, given the risks to the patient associated with an invasive procedure [ 29 ]. These guidelines clearly state that this technique should only be used when other possible causes of SDF have been excluded, and patients should be counseled on the low-quality evidence available to support this approach [ 29 ]. Similarly, AUA/ASRM guidelines note the controversial nature of this practice and limited evidence available to support it; however, they acknowledge that “in a patient with high sperm DNA fragmentation, a clinician may consider using surgically obtained sperm in addition to ICSI” [ 3 ]. The most recent European Academy of Andrology (EAA) guidelines may provide the most concrete guidance to clinicians on this topic. The EAA formally recommends that in cases of two or more ICSI failures using ejaculated sperm with uncorrectable, elevated SDF, couples should be offered the option of using testicular sperm for ICSI along with counseling that this approach is based on low-quality evidence [ 124 ].

Given the controversial nature of this practice, collaboration between reproductive endocrinologists and reproductive urologists likely presents the best opportunity to identify the couples who will benefit from this procedure. Without clear guidelines or high-level evidence, combining both male and female reproductive expertise may be the best way to ensure that couples receive the optimal, evidence-based care for their unique infertility challenges.

5. Current Guidelines

In addition to the current guidelines outlining the use of surgically retrieved sperm for ICSI in the setting of elevated SDF, subspecialty organizations have proposed additional guidelines regarding SDF testing and interpretation. In the most recent iteration of the American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) joint guidelines, the authors explicitly state that “sperm DNA fragmentation analysis is not recommended in the initial evaluation of the infertile couple” [ 3 ]. The authors acknowledge that SDF may adversely affect both natural conception and ART outcomes; however, given the lack of prospective studies directly evaluating the impact of SDF on the clinical management of infertile men, SDF testing should not be routinely performed as part of an initial evaluation [ 3 ].

Rather, SDF testing should be reserved for couples with failed ART treatment or a history of recurrent pregnancy loss [ 3 ]. While the level of evidence behind this recommendation is only considered to be ‘expert opinion,’ it is supported by a recent meta-analysis of 13 studies that demonstrated, in pooled analysis, the male partners of couples with recurrent pregnancy loss had a higher rate of SDF than partners of fertile controls (mean difference 11.91, 95% CI 4.97–18.86) [ 125 ].

The European Association of Urology (EAU) guidelines published in 2022 offer similar recommendations regarding SDF testing. Specifically, these guidelines recommend that SDF testing be performed to assess couples with a history of recurrent pregnancy loss, either from natural conception or after ART [ 7 ]. However, the EAU guidelines also recommend that testing be performed for men with unexplained infertility [ 7 ]. Taken together, these are classified as ‘strong’ recommendations.

Additionally, the EAU guidelines also suggest that varicocelectomy should be considered for men with elevated SDF who have experienced ART failures (including recurrent pregnancy loss, failure of embryogenesis, and/or failure of implantation) and/or otherwise unexplained infertility [ 7 ]. While this is considered to be a ‘weak’ recommendation, given that varicocele repair has been shown to improve pregnancy rates and ART success rates among infertile men with clinical varicoceles, the authors acknowledge that it may increase a couple’s chance of reproductive success, though additional prospective studies are needed to validate this practice [ 7 ].

Regarding the use of testicular sperm for non-azoospermic men with elevated SDF, as mentioned, the EAU guidelines do not routinely recommend this practice outside of clinical trials. While they concede that urologists may offer the option of using testicular sperm for ICSI in the setting of high SDF, this should only be considered after all other causes of oxidative stress have been excluded/treated, and patients should be counseled that the level of evidence for this practice is low [ 7 ].

In addition to these subspeciality societies, several other groups of reproductive urology experts have proposed their own algorithms for evaluating and treating elevated SDF. In a recent 2021 review by Esteves et al., the authors established clear recommendations regarding SDF testing and management [ 5 ]. Generally, these guidelines agree with those published by the AUA/ASRM and EAU; however, they provide additional, more granular evidence for providers. While the authors acknowledge that there is limited high-quality evidence regarding the role of SDF in the management of male infertility, they argue that this alone does not negate its clinical value. For example, these guidelines provide more explicit recommendations regarding how SDF tests should be performed and at which thresholds SDF tests should be considered abnormal. They also suggest that SDF testing may be considered in men with risk factors and/or as a part of fertility counseling and family planning; if SDF is elevated, this should prompt a full male evaluation, lead to additional counseling regarding possible lifestyle modifications, and potentially impact the choice of ART (i.e., proceeding directly to ICSI) [ 5 ]. Again, while these recommendations are not currently supported by high-level evidence, they do provide an opportunity for clinicians to understand what a panel of expert reproductive urologists may do in a particular situation given the available information.

Similarly, Loloi et al. published a new treatment algorithm for managing infertility associated with elevated SDF in early 2022 [ 21 ]. Specifically, the authors described their treatment strategy as a combination of behavior and medical/surgical interventions, which may be representative of what reproductive urologists do in clinical practice. In this algorithm, if a man is found to have an elevated SDF, they first recommend repeating an SDF test with a short (~24 h) abstinence interval. If SDF normalizes, they recommend that the couple continue using a short abstinence interval for either natural conception or ART. If SDF remains elevated, they recommend other non-invasive strategies for reducing SDF (including oral antioxidants and/or microfluidic sperm sorting) and/or varicocele repair (if indicated). If SDF normalizes, they recommend planning for either natural conception or ART, still utilizing a short ejaculatory abstinence interval. Finally, if SDF is still elevated, they recommend proceeding with a testicular sperm retrieval and ICSI (TESE-ICSI). Similarly, if the male partner has a history of elevated SDF and a history of prior failed IVF due to poor embryo development and/or failed implantation, they recommend proceeding directly to TESE-ICSI. Again, while this algorithm may be deviating from the more stringent recommendations of the AUA/ASRM and EAU guidelines, it may provide “real-world” advice for providers who encounter complex infertility patients, particularly those who have experienced the frustration and disappointment of failing prior ART therapies.

The algorithm that we have proposed is similar to those previously published [ 21 ] ( Figure 1 ). For couples with infertility, both the male and female partner should undergo a concurrent assessment, as recommended by AUA/ASRM guidelines. For those with a history of recurrent pregnancy loss, prior ART failure, and/or unexplained infertility, sperm DNA fragmentation (SDF) testing is recommended. While not outlined in current AUA/ASRM or EAU guidelines, evidence-based methods to decrease SDF include utilizing a short or very short abstinence interval and adjusting lifestyle factors. These interventions should be attempted first, as they are non-invasive and may have a large magnitude of benefit.

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An Evidence-Based Approach to the Evaluation and Management of an Infertile Couple with Elevated Sperm DNA Fragmentation (SDF). ( * = Interventions supported by current literature but not explicitly supported by current AUA/ASRM or EAU guidelines. References [ 3 , 7 ] refer to AUA/ASRM and EAU guidelines, respectively.)

For those men who do not improve with these interventions and have clinical varicocele(s), otherwise unexplained infertility, and/or a history of failed ARTs (including RPL, failure of embryogenesis, and/or implantation), EAU guidelines recommend considering varicocelectomy [ 7 ]. For those without clinical varicoceles or those who do not have a significant improvement in SDF after varicocelectomy, utilizing sperm sorting methods such as microfluidics prior to ART may be useful; however, since microfluidics only select sperm from the ‘damaged sample’ and have poor quality evidence, this intervention may provide only limited benefit. Oral antioxidants may also help, but well-designed studies evaluating these supplements in men with elevated SDF are limited.

For those men who continue to have an elevated SDF and adverse reproductive outcomes, surgical sperm retrieval with ICSI may be considered based on current AUA/ASRM and EAU guidelines [ 3 , 7 ]; however, patients should be counseled that this intervention is only supported by low-quality evidence.

6. Conclusions

Ultimately, while there is growing evidence related to SDF and its impact on fertility, it remains a controversial topic. Given that the AUA/ASRM and EAU guidelines recognize that there is limited high-quality evidence related to this topic, other groups of reproductive urology experts have collaborated to synthesize the prior literature and devise their own, more comprehensive guidelines. What seems to be clear from the available literature is that a shorter abstinence interval, use of microfluidic sperm sorting, use of testicular sperm, and varicocelectomy all decrease sperm DNA fragmentation. However, it is unknown exactly how these factors affect important clinical outcomes, such as live birth rates. It is also unknown exactly how and to what extent modifying these factors improves outcomes.

Given the current low levels of evidence and controversy surrounding SDF, the best course of action may be collaboration between reproductive urologists and reproductive endocrinologists to recognize the role of sperm in reproductive failure. Such collaboration will allow both providers to get a broader sense of the couple as a whole. By fully understanding the couple and leveraging their respective expertise, clinicians can more easily navigate the conflicting literature as it relates to sperm DNA fragmentation and devise an optimal treatment plan for the couple. While we anticipate that future randomized, controlled trials examining the effect of sperm DNA fragmentation on reproductive outcomes will provide more definitive guidance for clinicians, in the meantime, collaboration and a broad understanding of the available literature are likely the best methods for ensuring optimal outcomes ( Table 1 ).

Sperm DNA fragmentation has emerged as one of the most controversial topics in male reproductive medicine. Included here are several key points that are discussed in greater depth throughout the article.

Funding Statement

Author J.A.M. is supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.

Author Contributions

Conceptualization (P.N.S.); writing, original draft preparation (J.A.M.); writing, review and editing (P.N.S. and J.A.M.); supervision (P.N.S.). All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Conflicts of interest.

The authors declare no conflict of interest.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

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