Ralf Henkel

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• PhD, Habil.
• Professor (Full) at University of the Western Cape

Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could...

Objective To develop a core outcome set for male infertility trials. Design A two-round Delphi survey and consensus development workshop were undertaken with healthcare professionals, researchers and clinicians globally. Subjects 334 participants from 39 countries participated in the Delphi Survey, while 44 participants from 21 countries participat...

Study question: Can a core outcome set be developed through a global consensus to standardize outcome selection, collection, comparison, and reporting in future male infertility trials? Summary answer: A minimum dataset, known as a 'core outcome set', has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating pote...

Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could...

Objective: Different aspects of the functions of free fatty acid (FFA) in seminal plasma and their implications on male fertility are known. However, the profile of FFA in seminal plasma in asthenozoospermic patients following antioxidant therapy has not been studied. Methods: In this case-control study, the total antioxidant capacity (TAC) and FFA...

Objectives: Several studies have demonstrated racial variations in various diagnostic clinical parameters in different fields of medicine including andrology. Yet, clinical andrological diagnostic is following the lower reference values recommended by the World Health Organization irrespective of the racial descent of men. Therefore, this study aim...

Objective: Different aspects of the functions of free fatty acid (FFA) in seminal plasma and their implications on male fertility are known. However, the profile of FFA in seminal plasma in asthenozoospermic patients following antioxidant therapy has not been studied. Methods: In this case-control study, the total antioxidant capacity (TAC) and FFA...

Objective: Different aspects of the functions of free fatty acid (FFA) in seminal plasma and their implications on male fertility are known. However, the profile of FFA in seminal plasma in asthenozoospermic patients following antioxidant therapy has not been studied. Methods: In this case-control study, the total antioxidant capacity (TAC) and FFA...

Oxidative stress is characterized by the diminished capacity of a biological system to overcome the overproduction of reactive species (RS) and free radicals (FR). This process has been related to the pathogenesis of virtually every disease. Since this process is a leading cause of many diseases (e.g., ischemic stroke, heart failure, hypertension,...

Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could...

Background: Semen analysis is the standard test for evaluating male fertility. However, it may not address all aspects of male infertility. This review explores the role of leukocyte elastase (LE) as a possible biomarker for male fertility by evaluating 28 corresponding studies. Objectives: We aimed to explore how leukocyte elastase levels in semen...

Since the landmark paper on the production of hydrogen peroxide by human sperm published by MacLeod in 1943, reports on oxidative stress and its involvement in numerous diseases including cardiovascular diseases, cancers, endometriosis, aging, obesity, or infertility have significantly increased to 315,251 entries on PubMed on 26 September 2023. Su...

In their recent 2021 manual for the examination of human semen, the World Health Organization recommends the testing for sperm DNA fragmentation (SDF) in the section “Extended Examination.” SDF is an endpoint parameter for which one has to distinguish between test systems that measure real DNA damage, that is, actual strand breaks of the DNA, such...

It is without question that pro-oxidant agents mediate oxidative stress (OS) and are at the epicenter of biological functions and pathophysiological events. Because of the importance of oxidative events to normal and abnormal cell functions, it has become imperative to develop appropriate analytical techniques to facilitate the estimation and quant...

Reactive species (RS) have long been known as undesired compounds to be avoided at all costs. This view has changed with the realization that RS, which are constantly produced in all cells, are important actors in physiology. RS can regulate several cellular pathways, having a key role in the homeostasis of all organisms. Cells contain multiple sig...

It is well known that oxidative stress is involved in many diseases as well as in the aging process. Therefore, people are using antioxidants to counteract the detrimental effects of free radicals (FR), often with highly dosed tablets of individual antioxidants. Under normal healthy conditions, a certain, limited amount of FR or reactive oxygen spe...

Reproductive failure is a substantial public health apprehension and globally totally underestimated public health issue. Oxidative stress has an impact on reproductive processes like spermatogenesis, ovulation, steroidogenesis, and reproductive functions, the disturbance of which may contribute to infertility. In the male reproductive system, a sm...

Background Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochond...

The effects of smoking on human health have long been documented. However, only a few studies have highlighted the direct effects of nicotine on sperm function. Nicotine, as a chemical compound found in tobacco, has been shown to modulate different aspects of spermatogenesis and sperm functions. Nicotine can lead to a reduction in the number of spe...

Study question What is the prevalence of patients with high oxidation-reduction potential (ORP) and high sperm DNA fragmentation (SDF) in different patient groups with and without varicocele? Summary answer A large percentage of normozoospermic patients and patients who are normally considered of manageable in assisted reproduction show high SDF a...

Introduction: Mondia whitei (Mw) is a prominent African medicinal plant that is widely used as traditional treatment in the management of sexual dysfunction and male infertility. Yet, there is a paucity of scientific evidence to support its medicinal use. Therefore, the aim of this study was to investigate the in vitro effect of aqueous root extrac...

Infertility is a globally underestimated public health concern affecting almost 190 million people, i.e., about 17.5% of people during their lifetime, while the prevalence of male factor infertility is about 7%. Among numerous other causes, the prevalence of male genital tract infections reportedly ranges between 10% and 35%. Leukocytospermia is fo...

Poor semen quality increase risks of infertility and recurrent pregnancy loss (RPL) in couples. Global, reported sperm counts have more than halved since the 1970s. Canonical genitourinary microbes such as gonorrhoea are known to impair semen quality. Furthermore, several recent, small studies have highlighted trends in semen microbiome characteris...

Poor semen quality increase risks of infertility and recurrent pregnancy loss (RPL) in couples. Global, reported sperm counts have more than halved since the 1970s. Canonical genitourinary microbes such as gonorrhoea are known to impair semen quality. Furthermore, several recent, small studies have highlighted trends in semen microbiome characteris...

Objective Different aspects of the functions of free fatty acid (FFA) in seminal plasma and their implications on male fertility are known. However, the profile of FFA in seminal plasma in asthenozoospermic patients following antioxidant therapy has not been studied. Methods In this case-control study, the total antioxidant capacity (TAC) and FFA p...

Raised leptin levels induce oxidative stress, which negatively impacts male reproduction. Profortil® is an antioxidant formulation clinically used to improve sperm quality. Whether Profortil® supplementation can prevent the detrimental effects of leptin on spermatozoa is not known. Thus, the aim of this study was to examine the effects of Profortil...

Background Testicular cancer (TC) is a relatively rare type of cancer in men. Early diagnosis of TC remains challenging. Metabolomics holds promise in offering valuable insights in this regard. In this study, a metabolic fingerprinting approach was employed to identify potential biomarkers in both serum and seminal plasma of TC patients. Methods A...

Poor semen quality increase risks of infertility and recurrent pregnancy loss (RPL) in couples. Global, reported sperm counts have more than halved since the 1970s. Canonical genitourinary microbes such as gonorrhoea are known to impair semen quality. Furthermore, several recent, small studies have highlighted trends in semen microbiome characteris...

Infertility affects about 25% of couples worldwide, and oxidative stress (OS) is linked to its idiopathic etiology. Green, black, white, and oolong teas are produced from Camellia sinensis, depending on their oxidation level, and contain antioxidant properties that may enhance male reproductive functions. The study aimed to investigate the effects...

Background Male infertility is usually determined by the manual evaluation of the semen, namely the standard semen analysis. It is currently impossible to predict sperm fertilizing ability based on the semen analysis alone. Therefore, a more sensitive and selective diagnosis tool is required. Methods Twelve fresh semen samples were collected from...

Objective: In this study, it was aimed to examine the microbial content and diversity in semen samples of obese men, to determine the differences between infertile and fertile groups, and to investigate the effects of seminal microbiota on semen parameters, sperm DNA fragmentation (SDF), sperm chromatin condensation, and total antioxidant capacity...

In this study, we performed the stereological examination of rat testes and evaluated the protective effect of testosterone against atrazine (ATZ) toxicity in TM3 Leydig and TM4 Sertoli cells. Testosterone intake in rats increased the volumetric density of the seminiferous tubules; tubular diameter; germinal epithelial height; number of spermatogon...

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...

Background Extractions ofLessertia frutescens (Lf) are shown to have immune modulation, anti-inflammatory and antioxidant properties. However, Lf is also cytotoxic, antiproliferative, and pro-apoptotic in vitro. Furthermore, Lf extractions may influence steroidogenesis. Nevertheless, the impact on Leydig cell function has not previously been invest...

Introduction: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that low energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. Methods: Men with obesity (18-60 years) with normal sperm concentration (n...

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...

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and methods: The met...

Identifying the metabolome of human seminal plasma (HSP) is a new research area to screen putative biomarkers of infertility. This case–control study was performed on HSP specimens of 15 infertile patients with teratozoospermia (defined as normal sperm morphology < 4%) and 12 confirmed fertile normozoospermic men as the control group to investigate...

Infertility affects millions of couples worldwide. Oxidative stress (OS) causes peroxidation of lipids and damage to spermatozoa, thus, reducing the quality of seminal parameters. In addition, the differences in the levels of antioxidants and reactive oxygen species (ROS) caused by intrinsic and extrinsic variables linked to lifestyle, diet, geneti...

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...

Abstract There are conflicting reports on trends of semen parameters from different parts of the globe. However, in recent times there is dearth of information on the trend in Sub-Saharan countries. Therefore, in this study we aimed at determining the trends in semen parameters in Nigeria and South Africa between 2010 and 2019. A retrospective stud...

The emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic necessitated the development of adequate vaccines. Despite vaccines being demonstrated to be safe and effective for preventing severe disease and death, vaccine hesitancy remains. Reasons include concerns over adverse effects on male fertility, which have not been widely investigated....

In recent years, intracytoplasmic sperm injection (ICSI) has become the most performed method of assisted reproduction for infertile couples with severe male-factor infertility. Evidence supports that normal sperm morphology positively correlates with desired ICSI outcomes. Severe morphological defects of spermatozoa, especially of the head, are as...

Background: Male infertility is a disease of public health relevance contributing to 50% of infertility cases globally. However, there is dearth of information on the prevalence of male-factor infertility in Sub-Saharan countries. Therefore, in this study we aimed at identifying the prevalence, and trends of male factor infertility in Nigeria and S...

Introduction Metabolic Age (MetAge) and body composition analysis may reflect an individual’s metabolic status, which is believed to influence male sexual and gonadal functions. Although erectile dysfunction (ED) and hypogonadism are increasingly prevalent with age, they are also detected among younger men. This study aims to assess the impact of M...

Purpose Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varico...

Infertility is a globally under-recognized public health problem significantly impacting individual health and socioeconomics affecting millions of couples. The reasons for infertility are manifold and not only include many couples decision to postpone having children but also diseases (e.g., diabetes, infections, or varicocele), lifestyle (e.g., o...

Naringenin, a flavone with a growing body of evidence as an anti-cancer agent, is found in Typha capensis, an indigenous South African plant commonly used in traditional medicine. However, despite favourable in vitro results, clinical usage of naringenin remains restricted due to notoriously poor oral bioavailability, rapid metabolism and poor tumo...

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly usi...

Background: Idiopathic causes of infertility is associated with oxidative stress. Antioxidants are known to scavenge the excessive production of reactive oxygen species (ROS). Green tea (Camellia sinensis) contains polyphenols that enhance its antioxidant potential. Aim: This study focused on the impact of aqueous green tea extract on normozoosper...

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination a...

This study aims to evaluate the expression of genes associated with the fertilisation potential and embryo development, sperm DNA fragmentation (SDF), and acrosome reaction in male partners of infertile couples with different sperm parameters compared to fertile men. First, male partners of infertile couples with abnormal (N = 25) and normal sperm...

We would like to thank F. Pallotti and his colleagues for their positive comments [...].

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in...

Recurrence following varicocelectomy is an important cause of treatment failure and persistence of subnormal semen parameters. This original study was combined with a systemic review and meta‐analysis aiming to evaluate the efficacy of redo varicocelectomy on male fertility potential and pregnancy outcome. The retrospective study included 32 patien...

Study question How does computer-assisted semen analysis (CASA) (Lenshooke, LOGIXX) and at-home sperm testing (ExSeed) compare with manual methodology assessment of male fertility based on WHO criteria (5thEdition); a three-method comparison study. Summary answer All methods showed good agreement for concentration and limited agreement for motilit...

Study question Do seminal oxidation-reduction potential (ORP) and sperm DNA fragmentation (SDF) predict ICSI cycle outcomes? Summary answer Both SDF and seminal ORP have strong prognostic value in predicting good fertilization (≥80%), blastocyst development (≥60%), clinical pregnancy and live birth. What is known already Seminal oxidative stress...

Male infertility is considered as a multifactorial complex reproductive illness, and male urogenital infection and inflammation are crucial etiologies contributing up to 35% of all cases. Mostly triggered by sexually transmitted diseases and uropathogens, chronic manifestation of such infection may cause irreversible infertility in the male. Male u...

Since the discovery by John MacLeod in 1943 that spermatozoa produce small amounts of hydrogen peroxide, a member of the so-called reactive oxygen species (ROS), the importance and functions of these highly reactive oxygen derivatives in physiology and pathology are a subject of numerous studies. It has been shown that they play essential roles, no...

The inability to conceive is a baleful experience for thousands of couples worldwide. Among different well‐known reproductive techniques, medicinal plants have been utilized to treat male infertility. Medicinal plants, provide a therapeutic alternative, which is available and affordable for infertile couples. We investigated the direct effect of un...

Research question Has seminal oxidation-reduction potential (ORP) clinical relevance for reproductive outcome. Design In this prospective observational study a total of 144 couples who had an ICSI cycle between June 2018 and December 2020 were included. The study included patients undergoing fresh ICSI cycles with autologous gametes. Cycles that h...

Study question: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. What is known already: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform cl...

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) te...

Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, organelles, and DNA, alteration of enzymatic f...

American Center for Reproductive Medicine Reasearch Collaborators-2018

The present study aimed to investigate the clinical role of standard sperm diagnosis parameters (sperm concentration, motility, morphology) as well as aniline blue staining of histones, 8‐OHdG, TUNEL assay were performed on semen samples in infertile men with oligoasthenoteratozoospermia (OAT). Thirty‐two infertile and ten proven fertile men were i...

With the advance of assisted reproduction techniques, and the trend towards blastocyst culture and single embryo transfer, gamete and embryo assessment have gained greater importance in ART treatment. Embryo quality depends mainly on gamete quality and culture conditions. Oocyte maturity identification is necessary in order to plan fertilization ti...

Purpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. Materials and methods: Varicocele studies published between 1988 and 2020 were retrieved f...

Purpose: Azoospermia is defined as the absence of spermatozoa in the pellet of a centrifuged semen sample. In fact, when a basic semen analysis fails to detect sperm in the ejaculate, there is still the possibility of detecting rare sperm after centrifugation of the sample and examination of the pellet. In this study, we assessed the role of Cytos...

Varicocele, a condition associated with increased oxidative stress, negatively affects sperm DNA integrity and reduces pregnancy rates. However, the molecular mechanisms related to DNA integrity, damage, and repair in varicocele patients remain unclear. This study aimed to determine the role of DNA repair molecular mechanisms in varicocele-related...

Semen analysis is the cornerstone of male fertility evaluation with WHO guidelines providing the basis for procedural standardization and reference values worldwide. The first WHO manual was published in 1980, and five editions have been subsequently released over the last four decades. The 6th Edition was published in July 2021. In this review, we...

This retrospective cohort study aimed to explore whether paternal age and semen quality parameters affect the embryological and clinical outcomes of ICSI with oocyte donation. A total of 339 oocyte donation (OD)-ICSI cycles were categorized into four groups according to the semen parameter profiles of the male counterparts: normozoospermia (NS, n =...

To identify the most prevalent chromosomal abnormalities in patients with non‐obstructive azoospermia (NOA), consolidate their surgical sperm retrieval (SSR) rates and determine the significant predictors of positive SSR in this patient population. A systematic review and meta‐analysis were performed following the Preferred Reporting Items for Syst...

Background : The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a t...

Purpose: In response to the COVID-19 pandemic, the American Center for Reproductive Medicine (ACRM) transitioned its annual training in assisted reproductive technology (ART) from a hands-on, laboratory-based training course to a fully online training endorsed by the American College of Embryology. Here we describe our experience and assess the qu...

Androgens, testosterone and dihydrotestosterone (DHT) are endocrine regulators of spermatogenesis and act via androgen receptor (AR). The aim of this study was to investigate the association(s) of AR (CAG repeat length), SRD5A2 (rs523349, V89L) and TNF‐α (rs1800629, ‐308G/A) polymorphisms with idiopathic male infertility in Turkish men. This case‐c...

Immunological infertility contributes significantly to the etiology of idiopathic male infertility. Shielding the spermatogenic cells from systemic immune responses is fundamental to secure normal production of spermatozoa. The body’s immune system is tuned with the host self-components since the early postnatal period, while sperm first develops d...

Objective : To examine the effect of paternal age on intracytoplasmic sperm injection (ICSI) outcomes in unexplained infertility Subjects and Methods : This retrospective study, done at the Hamad Medical Corporation, Doha, Qatar screened infertile couples who underwent ICSI between 2014 and 2019 for the inclusion and exclusion criteria defining ‘u...

Our study objective was to assess the effect of various sperm DNA fragmentation levels on clinical intracytoplasmic sperm injection outcome. This retrospective study included 392 patients who underwent ICSI and performed sperm DNA fragmentation testing before the procedure. Based on sperm DNA fragmentation cut-off values, the patients were differen...