Sheena E M Lewis

• BSc PhD
• Professor at Queen's University Belfast

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have hig...

The RCN would like to thank the project team for its commitment to developing this resource, including a wide range of stakeholders who provided valuable feedback in its development.

Approximately one in twenty men have sperm counts low enough to impair fertility but little progress has been made in answering fundamental questions in andrology or in developing new diagnostic tools or management strategies in infertile men. Many of these problems increase with age, leading to a growing population of men seeking help. To address...

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recom...

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to t...

Purpose Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit...

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such a...

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recomm...

Study question: What are the updates for the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature from 2017 to 2022? Summary answer: The guideline development group (GDG) updated 11 existing recommendations on investigations and treatments for RPL, and how care should be organ...

This review surveys the causes and consequences of DNA damage in the male germ line from spermatogonial stem cells to fully differentiated spermatozoa. Within the stem cell population, DNA integrity is well maintained as a result of excellent DNA surveillance and repair; however, a progressive increase in background mutation rates does occur with p...

(Abstracted from Hum Reprod 2022;37:1106–1125) With intracytoplasmic sperm injection (ICSI), many natural barriers that would normally prevent the entry of abnormal sperm are lost, increasing the importance of sperm DNA integrity for successful in vitro fertilization. There is currently no consensus on the optimal assay for measuring sperm DNA qual...

Varicocele is one of the most common yet treatable causes of male infertility. Varicoceles are present in more than 40% of infertile men with primary infertility; increasing with age. They impair semen parameters and sperm DNA and are linked with lower pregnancy rates and live births. Until recently men have seldom been examined in male fertility w...

Study question What is the incidence of sperm DNA damage in men attending tertiary (urological) healthcare with long histories of infertility? Summary answer The majority of these men (95%), all with normal semen analyses had high levels of sperm DNA damage. What is known already Conventional semen analysis assesses sperm concentration, motility,...

Study question Do sperm DNA quality measurements influence the blastocyst rate and/or euploid rates? Summary answer Sperm DNA fragmentation has a negative influence on the rate of blastulation. It does not impact on euploidy rates assessed by pre-implantation genetic testing (PGT-A). What is known already Some studies show that sperm DNA has no i...

Study question: What effects did treatment using hyaluronic acid (HA) binding/selection prior to ICSI have on clinical outcomes in the Hyaluronic Acid Binding sperm Selection (HABSelect) clinical trial? Summary answer: Older women randomized to the trial's experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same l...

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinic...

One of modern healthcare's most controversial areas, reproductive medicine is an emerging discipline that fosters hugely divergent opinions on topics such as laboratory techniques, clinical management and ethical considerations. Highlighting over 50 contentious topics in reproductive medicine, this book presents expertly argued opinions are present...

One of modern healthcare's most controversial areas, reproductive medicine is an emerging discipline that fosters hugely divergent opinions on topics such as laboratory techniques, clinical management and ethical considerations. Highlighting over 50 contentious topics in reproductive medicine, this book presents expertly argued opinions are present...

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing the effects of paternal exposures remain elusive. Animal experimental models have...

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing the effects of paternal exposures remain elusive. Animal experimental models have...

Semen analysis is the first, and frequently, the only step in the evaluation of male fertility. Although the laboratory procedures are conducted according to the World Health Organization (WHO) guidelines, semen analysis and especially sperm morphology assessment is very difficult to standardize and obtain reproducible results. This is mainly due t...

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with p...

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions....

The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation –as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and pr...

KEY MESSAGE Average Comet score, low Comet score and high Comet score measures of sperm DNA damage by the alkaline Comet may all be robust biomarkers for sporadic and recurrent miscarriage after either spontaneous or assisted conception and may provide pioneering diagnosis and guidance for future routes to fertility, if confirmed by other studies....

We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analy...

Clinical implications of sperm DNA frgmentation tetsing

all-than couples with values <15%. Thus, the SDF thresholds of 15% related to natural pregnancies rather than ICSI pregnancies. 10 Indeed, Evenson, 11 who developed the SCSA assay and was the leading author of the above study, has demonstrated that the odds for pregnancy by assisted reproductive technology (ART) decrease as SDF values increase, par...

Covid and male infertility investigations

Study question: Do the Comet parameters of the proportions of sperm with low or high DNA damage improve the power of the test in the diagnosis of male infertility and/or prediction of IVF and ICSI live birth rates? Summary answer: The mean Comet score and the scores for proportions of sperm with high or low DNA damage were useful in diagnosing m...

Background Sperm selection strategies aimed at improving success rates of intracytoplasmic sperm injection (ICSI) include binding to hyaluronic acid (herein termed hyaluronan). Hyaluronan-selected sperm have reduced levels of DNA damage and aneuploidy. Use of hyaluronan-based sperm selection for ICSI (so-called physiological ICSI [PICSI]) is report...

Background Sperm selection for intracytoplasmic sperm injection (ICSI) has traditionally relied on standardised methods of sperm processing combined with subjective sperm selection (motility/morphology). In 2012, live birth rates (LBRs) stood at ≈24% per cycle started (32% per cycle reaching embryo transfer). Objective(s) The main clinical objecti...

Mycotoxins are secondary toxic metabolites produced by Aspergillus, Penicillium, and Fusarium species of fungi, when they infect and proliferate on various agricultural commodities either in the field and/or during storage. The well-known detrimental health effects of mycotoxins in humans include liver cancer, Balkan endemic nephropathy, child grow...

STUDY QUESTION What is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature? SUMMARY ANSWER The guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized. WHAT IS KNOWN...

Despite more cancers in young men over the past two decades, improvements in therapies give a greater chance to live full lives following treatment. Sperm genomic quality is variable following cancer diagnosis, so its assessment is important if sperm cryopreservation is being considered. Here, we evaluated DNA damage using two DNA damage assays: an...

Cryoinjury is a consequence of cryopreservation and may have a negative impact on sperm quality regarding motility, morphology, and viability. This study was designed to identify potential proteomic changes in human sperm cells throughout the cryopreservation process. Comparisons made within this study included the detection of the sperm proteomic...

Abstracts of the 39th Annual Meeting of the United Kingdom Environmental Mutagen Society, 26th - 29th June 2016 at King’s College London, UK . Mutagenesis (2016) 31 (6): 703-734. DOI:https://doi.org/10.1093/mutage/gew044

Introduction The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Bindi...

P-007 Characterization of sperm DNA quality in men presenting with reproductive and non-reproductive cancers Study question: Do men presenting with cancer have different types of sperm DNA damage, dependant on disease origin? Summary answer: Men with both types of cancer had higher levels of both single stranded (SS) and double stranded (DS) DNA da...

There is increasing evidence for the deterioration of male sperm quality worldwide. Of emerging concern is the contribution of environmental and food toxins, especially mycotoxins and persistent organochlorides, in causing developmental and reproductive disorders in males. Currently, toxicity studies evaluating mixtures of contaminants are often re...

Objective: Research indicates that parents of twins have poorer psychosocial outcomes than parents of singletons. Parents who have conceived using assisted reproductive technology (ART) have been found to be at higher risk of negative psychosocial outcomes compared to parents who have conceived spontaneously. The current study aimed to model the f...

Mycotoxins are toxic metabolites produced by Aspergillus, Penicillium, and Fusarium species of fungi, which can infect and proliferate on various agricultural commodities in the field and/or during storage. The well known detrimental health effects of mycotoxins in humans include liver cancer, Balkan Endemic Nephropathy, child growth impairment, im...

A response to the editorial 'Are we ready to incorporate sperm DNA fragmentation testing into our male infertility work-up? A plea for more robust studies' by Erma Drobnis and Martin Johnson. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

As a number of children born by assisted reproductive technology (ART) are increasing each year across the developed world, the health of such offspring is a matter of public concern. Does the integrity of the paternal genome impact on offspring health? In societal terms, as birth rates fall, and the Western population become unsustainable, do the...

Sperm DNA damage has been shown to be a valuable diagnostic and prognostic biomarker for male infertility and assisted reproductive treatment (ART) outcome. It is linked to every fertility checkpoint from reduced fertilization rates, lower embryo quality and pregnancy rates to higher rates of spontaneous miscarriage and childhood diseases. It is mo...

Reports on the influence of semen parameters on natural or assisted pregnancy are contradictory, suggesting that the many confounding variables which contribute to outcome have not been taken into account. However, it is possible to derive some consensus for both natural and assisted conception by focussing on studies which use WHO-recommended seme...

Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the...

In this debate article, I am going to set out the case that sperm DNA fragmentation testing is essential in current day fertility management because- • Our current semen analysis testing is unfit for purpose • Sperm DNA damage testing has strong associations with every fertility check point • Sperm DNA damage testing has strong associations with mi...

Male infertility is a major cause of problems for many couples in conceiving a child. Recently, lifestyle pastimes such as alcohol, tobacco and marijuana have been shown to have further negative effects on male reproduction. The endocannabinoid system (ECS), mainly through the action of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at cannabin...

Study question: Is there a need for a specific guide addressing studies of seminal quality? Summary answer: The proposed guidelines for the appraisal of SEMinal QUAlity studies (SEMQUA) reflect the need for improvement in methodology and research on semen quality. What is known already: From an examination of other instruments used to assess t...

Sperm DNA damage has a negative impact on pregnancy rates following assisted reproduction treatment (ART). The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation i...

Study question: Is there an association between high levels of sperm DNA damage and miscarriage? Summary answer: Miscarriage rates are positively correlated with sperm DNA damage levels. What is known already: Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or singl...

Recent societal acceptance of cannabinoids as recreational and therapeutic drugs has posed a potential hazard to male reproductive health. Mammals have a highly sophisticated endogenous cannabinoid (ECS) system that regulates male (and female) reproduction and exo-cannabinoids may influence it adversely. Therefore it is imperative to determine thei...

The exchange of histones with protamines in sperm DNA results in sperm chromatin compaction and protection. Variations in sperm protamine expression are associated with male infertility. The aim of this study was to investigate relationships between DNA fragmentation, sperm protamines and assisted reproduction treatment. Semen and spermatozoa prepa...

Sperm DNA damage is associated with poorer assisted reproductive treatment (ART) outcomes including reduced fertilization rates, embryo quality, and pregnancy rates and higher rates of spontaneous miscarriage and childhood diseases. It shows promise as a more robust biomarker of infertility than conventional semen parameters. Among the sperm DNA te...

Here, an overview of the various clinical uses of processing of semen samples and cryopreservation is given. The effects of sperm processing on conventional semen parameters are discussed along with the ramifications of removing seminal plasma, oxidative stress and potential benefits of antioxidant addition in laboratory processing of testicular an...

To evaluate sperm DNA fragmentation and semen parameters to diagnose male factor infertility and predict pregnancy after IVF. Prospective study. Academic research laboratory. Seventy-five couples undergoing IVF and 28 fertile donors. Sperm DNA fragmentation was measured by the alkaline Comet assay in semen and sperm after density gradient centrifug...

Sperm progressive motility has been reported to be one of the key factors influencing in vitro fertilization rates. However, recent studies have shown that sperm DNA fragmentation is a more robust predictor of assisted reproductive outcomes including reduced fertilization rates, embryo quality, and pregnancy rates. This study aimed to compare the u...

Traditionally, the diagnosis of male infertility has relied upon microscopic assessment and biochemical assays to determine human semen quality. These tests are essential to provide the fundamental information on which clinicians base their initial diagnosis. However, none of these parameters addresses sperm function and their clinical value in pre...

Protamines are the major nuclear proteins condensing DNA in the sperm nucleus. One of their proposed functions is the protection of the genetic message delivered by the sperm. To date, evidence of their involvement in DNA protection has been obtained by correlating the protamine P1/P2 ratio, protamine concentrations, or chromomycin A3 staining with...

Marijuana smokers and animals treated with Δ9-tetrahydrocannabinol, the principal component of marijuana, show alterations of sperm morphology suggesting a role for cannabinoids in sperm differentiation and/or maturation. Because the cannabinoid receptor 1 (CNR1) activation appears to play a pivotal role in spermiogenesis, the developmental stage w...

Protamines are the major nuclear proteins condensing DNA in the sperm nucleus. One of their proposed functions is the protection of the genetic message delivered by the sperm. To date, evidence of their involvement in DNA protection has been obtained by correlating the protamine P1/P2 ratio, protamine concentrations, or chromomycin A3 staining with...

Sperm DNA damage shows great promise as a biomarker of infertility. The study aim is to determine the usefulness of DNA fragmentation (DF), including modified bases (MB), to predict assisted reproduction treatment (ART) outcomes. DF in 360 couples (230 IVF and 130 ICSI) was measured by the alkaline Comet assay in semen and in sperm following densit...

This article reports the results of the most recent in a series of EHSRE workshops designed to synthesize the current state of the field in Andrology and provide recommendations for future work (for details see Appendix). Its focus is on methods for detecting sperm DNA damage and potential application of new knowledge about sperm chromatin organiza...

In this review, we shall summarize the current knowledge on the endocannabinoid system (ECS), and on its involvement in the multifaceted process of male reproduction. In particular, we shall discuss the role of ECS in sperm biology and Sertoli cell proliferation and death, showing how endocannabinoids may regulate spermatogenesis and reproductive p...

The vast number of chemicals existing or being added into the environment, have globally aroused great concern regarding their adverse effects in human population. Development and validation of sensitive and better test systems which can assess the adverse effects of chemicals at an early stage for intervention strategies to be implemented in time...

Undergraduate medical education has been revolutionized by the publication of the GMC document entitled Tomorrow's Doctors. Special study modules form part of the new curriculum.These modules are aimed at providing students with an opportunity to study subjects outside the realms of the core course and pursue areas of special interest to them. This...

The aim of this study was to determine the relationship between sperm morphology and fertilization rates in vitro. Semen samples were obtained from 50 couples undergoing IVF treatment. Sperm morphology was classified by strict criteria (Tygerberg) according to head, midpiece and tail defects in neat semen and after sperm selection by Percoll gradie...

The aims of this study were to compare the in vitro effects of 3.6 mM and 7.2 mM pentoxifylline on the ability of spermatozoa to generate reactive oxygen species (ROS) and on lipid peroxidation (LPO). Semen samples were obtained from 10 asthenozoospermic men who had been previously identified as producing ROS after addition of Phorbol 12-myristate...

A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been e...

BACKGROUND: The sperm chromatin structure assay (SCSA) parameter DNA fragmentation index (DFI) has been shown to predict in vivo and in vitro fertility. So far most SCSA studies have been based on SCSA analysis performed on neat semen. The aim of this study is to assess whether SCSA analysis of sperm prepared by density gradient centrifugation (DGC...

Infertility affects one in six couples in Europe during their reproductive years with dysfunctional sperm being one of the most common causes. Conventional semen analysis has proven variable and lacking in prognostic value so, over the past decade, more useful molecular fertility biomarkers have been explored. Among the tests showing most promise a...

Male infertility has traditionally been diagnosed by microscopic assessment of concentration, motility and morphology of sperm in the ejaculate. Most laboratories use sperm isolated by various methods such as density gradient centrifugation to enrich for subpopulations of sperm believed to have greater fertilization potential. These tests are essen...

To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time p...

The effects of diabetes mellitus on male reproductive health have not been clearly defined. A previous publication from this group reported significantly higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in spermatozoa from men with type 1 diabetes. This study compared semen profiles, sperm DNA fragmentation and levels of o...

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Concerns about the adverse effects of chemicals present in the environment have created a need for better systems to assess their potential consequences on human health. One potential solution is the versatile and state-of-the-art Comet assay. Simple, sensitive, rapid and visual, this modern toxicological method allows quantitative and qualitative...

Traditionally, the diagnosis of male infertility has relied upon microscopic assessment and biochemical assays to determine human semen quality. The conventional parameters given most importance have been the concentration, motility, and morphology of sperm in the ejaculate. Most laboratories also include 'sperm suitability' tests where the subpopu...

Diabetes mellitus (DM) is increasing in men of reproductive age. Despite this, the prevalence of diabetes in men attending fertility clinics is largely unknown. Furthermore, studies examining the effects of DM on sperm fertility potential have been limited to conventional semen analysis. Conventional semen analysis (semen volume, sperm count, motil...

This paper describes a hybrid methodology to study users in ongoing relationships based on three levels of user data analysis. Most user-centered design methods are ideal for the analysis of users' needs, wants, and expectations at a specific point in time. However, nowadays, most online applications and services have recurrent users whose characte...

To determine whether sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. Laboratory analysis of sperm motility after exposure to sildenafil citrate using computer-assisted semen analysis and acrosome reaction by fluorescein isothiocyanate-labeled peanut agglutin...