GLOBAL ANDROLOGY FORUM
GLOBAL ANDROLOGY FORUM
Publications
Sperm DNA fragmentation in male infertility: From bench to bedside
“Sperm DNA fragmentation in male infertility: From bench to bedside”.
Authors:
Ala’a Farkouh, Ramadan Saleh, Rupin Shah & Ashok Agarwal
Arab Journal of Urology, Published online: 12 Nov 2023, DOI: 10.1080/20905998.2023.2278200
https://doi.org/10.1080/20905998.2023.2278200
Preamble:
Sperm DNA fragmentation (SDF) is a molecular sperm abnormality that can have detrimental impact on male reproductive potential. There has been a growing interest in SDF globally, both in clinical applications and research output. In fact, SDF testing was included as an extended sperm function test in the latest edition of the WHO laboratory manual for the examination and processing of human semen. The pathogenesis of SDF is attributable to several intrinsic and extrinsic factors that culminate in oxidative stress, abortive apoptosis, and defective sperm chromatin maturation. Many investigators have examined specific risk factors or etiologies that lead to increased SDF and impaired male fertility potential. Similarly, many studies have investigated methods to counteract these factors and reduce SDF or select spermatozoa that contain lower SDF levels.
In the past couple of years, the Global Andrology Forum (GAF) has gained a leadership in the andrology field in terms of research output on SDF, publishing several clinically relevant reviews, book chapters, clinical practice guidelines, global surveys, and metaanalyses. From personal experience of being involved in many of these projects, I noticed a very large amount of literature published on SDF but noticed a large gap in the quantity and quality of evidence pertaining to certain aspects, including some etiologies, certain
treatments, or certain testing methods. For example, many well designed and controlled studies have investigated the detrimental impact of SDF on assisted reproduction, including outcomes such as clinical pregnancy and miscarriage rates. In fact, many authors have published high quality systematic reviews and meta-analyses to further highlight these findings. However, studies on how to improve the outcomes of these assisted reproductive techniques when SDF is present in the male partner are lacking, with only few observational or small experimental studies available. Furthermore, one commonly highlighted theme in the published literature is the variability of SDF testing techniques and a lack of standardized cut-off and interpretation of the available SDF assays. This may create confusion to both researchers and clinicians and provide further challenges when attempting to combine or interpret data.
As GAF continues to publish on SDF global practices and up-to-date high-quality evidence, this short review presents the most recent evidence in a concise and straightforward manner, providing answers to important clinical questions.
CAPSULE
Contributors: Ala’a Farkouh, MD (USA), and Taha Hamoda, MD (Saudi Arabia)
SDF refers to single or double strand breaks of sperm DNA -triggered by several factors such as oxidative stress- that can eventually negatively impact the reproductive outcomes. Different testing technologies and lacking a universally accepted cut-off or reference values cloud the scene in both research and clinical practice. The presented GAF’s article concisely reviews the clinical indications of SDF testing, summarizes different testing techniques, and outlines the management options for elevated SDF.
Among many reputable scientific bodies heavily engaged in SDF research, the GAF is currently actively and efficiently leading the world-wide research on both SDF testing and management. The GAF has enriched the literature with numerous publications that may change the rules of the game.
Future Reflections:
When asked the question “What did you learn from working on the SDF global survey project?” My answer was “We need to do more research.” The future of SDF research is limitless, with many pertinent laboratory and clinical questions that need answers. Basic science research may focus on further understanding the pathogenesis at a molecular level. Observational studies may delineate and provide strong evidence on certain risk factors or etiologies that lead to elevated SDF. Laboratory research may standardize the SDF assays, allowing uniform analysis, reporting, and interpretation. Interventional studies and randomized controlled trials can provide the basis for evidence-based medicine when managing infertile couples with elevated SDF in the male partner.
Take Home Message:
The novelty of Sperm DNA Fragmentation (SDF) lies in its specific focus on genetic integrity. Unlike many other diagnostic markers that primarily assess sperm count, motility, or morphology, SDF evaluates the structural integrity of DNA within sperm cells. This focus on genetic quality provides unique insights into male fertility issues, directly linking to embryo quality, pregnancy success rates, and miscarriage risks. SDF serves as a predictive marker, guiding treatment decisions and interventions aimed at addressing underlying genetic factors affecting fertility outcomes in ways that no other markers could do. Integrating SDF testing into routine assessments offers a more personalized approach, potentially improving fertility outcomes through targeted interventions and treatment modifications. (Contributor: Ashok Agarwal, USA)
Ala’a Farkouh, MD: Short Biography
Ala’a Farkouh, MD
Researcher
Department of Urology
Loma Linda University Health
Loma Linda, CA, USA
Dr. Farkouh is a physician from Jordan and pursuing a career in Urology. He graduated from the University of Jordan in 2019 and worked in the Department of Surgery, King Hussein Cancer Center (KHCC), Jordan as a transitional resident for two years. He has been working with the Global Andrology Forum since 2020 and has published several projects, including reviews, book chapters, abstracts, original research, and global surveys.
He joined the Department of Urology at Loma Linda University in California in 2022 as a fulltime researcher working on benchtop research, basic research, clinical research, and physician safety research with a heavy focus on endourology. He aims to pursue a Urology residency in the United States, aiming to merge his clinical expertise and training with his demonstrated research acumen and strong analytical skills.
Taha Abdel-Meguid Hamoda, MD: Short Biography
Taha Abdel-Meguid Hamoda, MD
Professor/Consultant in Urology and
Andrology
Department of Urology
King Abdulaziz University
Jeddah, Saudi Arabia
E-mail: tahaaboalmagd@yahoo.com
ORCID: 0000-0002-8070-4088
Dr. Taha Hamoda is a Professor/Consultant in Urology and Andrology at the King Abdulaziz University, Jeddah, Saudi Arabia. He is an Honorary Professor of Urology/Andrology at Minia University, El Minia, Egypt. Taha is a senior member of the Global Andrology Forum and a former member of GAFs Core Management Council.
He has published over 100 peer reviewed publications and 12 books contributions. He holds a US patent for an invented surgical technique (2020) and is a member of several national and international scientific societies and associations. Taha serves as an expert reviewer for several high impact journals in urology and andrology and has served as a reviewer for the EAUs Clinical Guidelines on Male Infertility
Acknowledgement: Ala’a Farkouh and Taha Hamoda contributed to this week’s Management Special. We are grateful for their exceptional support as active members of the GAF.