Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS).

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

Rapid sperm capture: high-throughput flagellar waveform analysis.

STUDY QUESTION: Can flagellar analyses be scaled up to provide automated tracking of motile sperm, and does knowledge of the flagellar waveform provide new insight not provided by routine head tracking? SUMMARY ANSWER: High-throughput flagellar waveform tracking and analysis enable measurement of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses, which are not possible by tracking the sperm head alone. WHAT IS KNOWN ALREADY: The clinical gold standard for sperm motility analysis comprises a manual analysis by a trained professional, with existing automated sperm diagnostics [computer-aided sperm analysis (CASA)] relying on tracking the sperm head and extrapolating measures. It is not currently possible with either of these approaches to track the sperm flagellar waveform for large numbers of cells in order to unlock the potential wealth of information enclosed within. STUDY DESIGN, SIZE, DURATION: The software tool in this manuscript has been developed to enable high-throughput, repeatable, accurate and verifiable analysis of the sperm flagellar beat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the software tool [Flagellar Analysis and Sperm Tracking (FAST)] described in this manuscript, we have analysed 176 experimental microscopy videos and have tracked the head and flagellum of 205 progressive cells in diluted semen (DSM), 119 progressive cells in a high-viscosity medium (HVM) and 42 stuck cells in a low-viscosity medium. Unscreened donors were recruited at Birmingham Women's and Children's NHS Foundation Trust after giving informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: We describe fully automated tracking and analysis of flagellar movement for large cell numbers. The analysis is demonstrated on freely motile cells in low- and high-viscosity fluids and validated on published data of tethered cells undergoing pharmacological hyperactivation. Direct analysis of the flagellar beat reveals that the CASA measure 'beat cross frequency' does not measure beat frequency; attempting to fit a straight line between the two measures gives ${\mathrm{R}}^2$ values of 0.042 and 0.00054 for cells in DSM and HVM, respectively. A new measurement, track centroid speed, is validated as an accurate differentiator of progressive motility. Coupled with fluid mechanics codes, waveform data enable extraction of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses. We provide a powerful and accessible research tool, enabling connection of the mechanical activity of the sperm to its motility and effect on its environment. LARGE SCALE DATA: The FAST software package and all documentation can be downloaded from www.flagellarCapture.com. LIMITATIONS, REASONS FOR CAUTION: The FAST software package has only been tested for use with negative phase contrast microscopy. Other imaging modalities, with bright cells on a dark background, have not been tested but may work. FAST is not designed to analyse raw semen; it is specifically for precise analysis of flagellar kinematics, as that is the promising area for computer use. Flagellar capture will always require that cells are at a dilution where their paths do not frequently cross. WIDER IMPLICATIONS OF THE FINDINGS: Combining tracked flagella with mathematical modelling has the potential to reveal new mechanistic insight. By providing the capability as a free-to-use software package, we hope that this ability to accurately quantify the flagellar waveform in large populations of motile cells will enable an abundant array of diagnostic, toxicological and therapeutic possibilities, as well as creating new opportunities for assessing and treating male subfertility. STUDY FUNDING/COMPETING INTEREST(S): M.T.G., G.C., J.C.K-B. and D.J.S. gratefully acknowledge funding from the Engineering and Physical Sciences Research Council, Healthcare Technologies Challenge Award (Rapid Sperm Capture EP/N021096/1). J.C.K-B. is funded by a National Institute of Health Research (NIHR) and Health Education England, Senior Clinical Lectureship Grant: The role of the human sperm in healthy live birth (NIHRDH-HCS SCL-2014-05-001). This article presents independent research funded in part by the NIHR and Health Education England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The data for experimental set (2) were funded through a Wellcome Trust-University of Birmingham Value in People Fellowship Bridging Award (E.H.O.).The authors declare no competing interests.

[Disease-syndrome combination in integrated traditional Chinese and Western medicine in andrology: Confusions and countermeasures in studies].

Researches on the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine are becoming a hot spot in andrology, but many recent studies of this kind have failed to explain the connotation of integrated traditional Chinese and Western medicine in andrology. Related existing problems include repeated researches into the same indexes of action mechanisms of different therapeutic principles of traditional Chinese medicine (TCM), Chinese herbal compound and special prescriptions, studies focusing on individual diseases but ignoring symptoms, immature syndrome models for studies of mechanisms, and too much attention to uncertain or immature target mechanisms. The stress should be placed on the action mechanisms of Chinese herbal compound and special prescriptions on male diseases and, what is more important, on the clarification of the essential principles of differentiation and treatment of TCM syndromes. In the recent years, proteomics, genomics, transcriptomics and metabolomics have shed some light upon researches into the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine in andrology. An insight into the TCM syndrome, a macroscopic inductive analysis, and a comprehension of such microcosmic aspects as the gene, protein, metabolism and metagenome may contribute to some breakthroughs and new ideas in the studies of disease-syndrome combination in integrated traditional Chinese and Western medicine in andrology.

An easy, reproducible and cost-effective method for andrologists to improve the laboratory diagnosis of nonobstructive azoospermia: a novel microcentrifugation technique.

This study describes a new method of microcentrifugation as an improved, viable, cost-effective option to the classical Cytospin apparatus to confirm azoospermia. Azoospermic semen samples were evaluated for cryptozoospermia by a centrifugation method similar to that of World Health Organization guidelines (2010; entire specimen centrifuged at 3000g for 15 min, and aliquots of the pellet examined). Then, if no sperm were detected, the pellet from that procedure was resuspended in culture medium, centrifuged (2000g for 15 min), and the entire pellet spread on a 4 X 6mm area of a slide and stained using the Christmas tree method (Nuclear-Fast solution and picric acid). The entire stained area was examined for the presence or absence of sperm. A total of 148 azoospermic samples (after standard WHO diagnosis) were included in the study and 21 samples (14.2%) were identified as sperm-positive. In all microcentrifugation slides, intact spermatozoa could be easily visualized against a clear background, with no cellular debris. This novel microcentrifugation technique is clearly a simple and effective method, with lower cost, increasing both sensitivity and specificity in confirming the absence or presence of spermatozoa in the ejaculate. It may represent a step forward of prognostic value to be introduced by andrology laboratories in the routine evaluation of patients with azoospermia in the initial semen analysis.

[Traditional Chinese Medicine promotes the development of andrology].

Andrology is an ancient branch of science which has gained a new development in the recent years and therefore has both traditional and modern characteristics. On the one hand, andrology keeps benefiting from the achievements of modern medicine and, on the other hand, it relies on the support of the theories of Traditional Chinese Medicine (TCM). An integration of Chinese and Western medical principles may further facilitate the development of andrology. TCM may contribute to the development of andrology by giving full play to its advantage as a psychosomatic medicine, enriching treatment strategies for male diseases with comprehensive TCM therapies, integrating the advantages of Western medicine to improve clinical efficacy, and normalizing the use of patent TCM drugs.

[Organ-sparing surgery in andrology].

Penile and testicular tumors, especially those of the malignant nature, usually require radical excision, which alters the organ image, affects sexual and urinary functions, and consequently undermines the self-confidence and quality of life of the patient. Recent studies show that organ-sparing surgery can be an alternative to radical excision for superficial tumors and small masses. Penis-sparing surgery (PSS) has been indicated for superficial penile cancer, such as Tis and T1a lesions, and testis-sparing surgery (TSS) is feasible for benign small bilateral or solitary testicular masses (TIN). Long-term follow-ups after PSS or TSS show that the patients may retain a satisfactory appearance of the organ as well as desirable sexual and reproductive functions.

Basic diagnostics in andrology.

Basic andrological diagnosis consists of taking the patient's medical history and the couple's history as well as performing a physical examination including genital ultrasound, spermiogram, and hormonal analysis. If needed, a testicular biopsy and genetic testing may also be performed. Recent studies have shown the effect of lifestyle factors on male fertility. Thus, the patient history and clinical/andrological examinations have been broadened to include information on metabolic disorders like obesity and diabetes mellitus. The biggest changes occurred with the publication of the fifth edition of the WHO laboratory manual in 2010 and the introduction of a section on semen analysis in the German Medical Association guidelines (RiliBÄK). The reference values for almost all spermiogram parameters were adapted in an evidence-based approach using worldwide prospective population studies. For central parameters such as sperm motility and morphology, the assessment criteria were changed. New independent markers such as sperm DNA fragmentation rate are now routinely used in clinical diagnosis. For German andrological laboratories, there are now mandatory quality assurance measures for semen analysis (in the German "Rili-BÄK" guidelines). These include duplicate testing of all standard semen parameters and inter-laboratory comparison at regular intervals.

Andrology - reproductive years and beyond.

BACKGROUND: In recent years, significant advances have been made in our knowledge of the role of testosterone in male fertility and sexual function. In addition, new microsurgical techniques have improved outcomes in testicular biopsy for sperm retrieval, varicocoele treatment and vasectomy reversal. OBJECTIVE: This article provides an update on the assessment and treatment of male infertility, and the role of testosterone replacement therapy and erectile dysfunction. DISCUSSION: The evaluation of male infertility requires comprehensive history taking and a focused examination. Investigations that help form the basis for important treatment decisions include semen analysis and hormone testing. Further specialist assessment may be required to determine the need for genetic testing. There is increased evidence for the role of microsurgery in sperm retrieval, varicocelectomy and vasectomy reversal in men seeking paternity. Testosterone plays a role in both spermatogenesis and sexual functioning in a man. While testosterone replacement therapy can restore erections in androgen deficient men and treat other conditions related to hypogonadism, it can also result in male infertility.

[Erectile dysfunction: conservative treatment and new approaches]. / Dysfonction erectile: traitements conservateurs et nouvelles approches.

Recent societal evolutions have enabled more and more men to talk about erectile dysfunction (ED). There is a strong association between ED and cardiovascular disease and ED should now be considered as an early clinical evidence of vascular disorder. Inhibitors of the PDE-5 have revolutionized the treatment of ED. The three currently drugs (sildenafil, vardenafil and tadalafil) available as first-line therapeutic option, are well tolerated and highly effective in improving erectile function. All the potential cardiac and vascular effects of PDE-5 inhibitors have recently been reviewed. Despite the fact that million patients with ED worldwide have been successfully treated with one of these PDE5 inhibitors, some men are always difficult to treat. Several new PDE-5 inhibitors have recently been developed and are now being investigated in trials. However 30% of patients need alternative therapies and intracavernous injections are the most successful second-line treatment. Some of new therapeutic approaches are currently under investigation such as gene transfer therapy and stem cells therapy, melanocortin activators or extracorporeal shockwave therapy. Such approaches are still at an early stage but remain exciting new targets in difficult to treat patients.

Reliability of the sperm chromatin dispersion assay to evaluate sperm deoxyribonucleic acid damage in men with infertility.

OBJECTIVE: To investigate the intraindividual agreement of the sperm chromatin dispersion (SCD) assay results to assess sperm DNA fragmentation (SDF) in men with infertility. DESIGN: Diagnostic test reliability study. SETTING: Andrology laboratories. PATIENT(S): A total of 219 men with infertility. INTERVENTION(S): Sperm DNA fragmentation assessment in two ejaculates of the same subjects within a 3-month interval, using the SCD assay performed and analyzed by the same observers under similar testing conditions. MAIN OUTCOME MEASURE(S): Cohen's κ statistics to assess the degree of agreement between the pairs of results after converting the nominal SCD values into categorical data, that is, normal (<20%), intermediate (21%-29%), and high (≥30%) SDF rates. We also assessed the pairs of results using reliability measures for numerical variables (intraclass correlation coefficient for consistency using the two-way mixed-effects model and Bland-Altman plots). RESULT(S): The degree of agreement in classifying patients according to normal and pathological SDF classes was overall substantial (κ = 0.632; 95% confidence interval [CI], 0.546-0.718). A total of 76.7% of individuals were classified under the same class using paired ejaculates. The agreement rate was highest (approximately 80%) in ejaculates initially classified as either normal or high and lowest (approximately 60%) among those with intermediate SDF levels. The frequency of intermediate SDF ejaculates downgraded to normal or upgrade to high SDF classes in the second test was similar (approximately 20%). The intraclass correlation coefficient was 0.856 (95% CI, 0.812-0.887), and the mean difference between the pairs of observations was 0.80% (95% CI, -0.72 to 2.23), indicating no systematic difference between paired observations. CONCLUSION(S): Our study indicates a substantial intraindividual agreement of paired SCD assay results to classify men with infertility into three SDF categories: normal, intermediate, and high. The reliability of the SCD assay was adequate and exceeded 0.80 using two ejaculates analyzed within a 3-month interval under similar conditions. Although this evidence overall supports a single SCD test for patient classification using predefined SDF thresholds, particularly when the first test shows normal or high SDF levels, one in four men will have discordant values in paired ejaculates. Clinicians should be judicious when using SDF test results in decision-making.

Introduction: Rare and unusual andrologic syndromes that clinicians should be aware of.

There are conditions that are rare and that most providers are unaware of or conditions that consist of a series of symptoms for which there is no agreement that they are even a medical condition. These include painful nocturnal erections, post-orgasmic illness syndrome, body dysmorphic disorder, and post-finasteride syndrome. While some have a psychiatric basis, others clearly have an organic pathophysiology, while for others, there remains much controversy. This month's Views and Reviews will inform the reader of these conditions so they may recognize affected patients and direct them towards appropriate resources for their care.

New insights to guide patient care: the bidirectional relationship between male infertility and male health.

Male reproduction is a complex process, and numerous medical conditions have the potential to alter spermatogenesis. In addition, male factor infertility may be a biomarker for future health. In the present review, we discuss the current literature regarding the association between systemic diseases and fertility, which may impact clinical outcomes or semen parameters. A number of conditions that have systemic consequences were identified, including genetic (e.g., cystic fibrosis, DNA mismatch repair alterations), obesity, psychological stress, exogenous testosterone, and a variety of common medications. As such, the infertility evaluation may offer an opportunity for health counseling beyond the discussion of reproductive goals. Moreover, male infertility has been suggested as a marker of future health, given that poor semen parameters and a diagnosis of male infertility are associated with an increased risk of hypogonadism, cardiometabolic disease, cancer, and even mortality. Therefore, male fertility requires multidisciplinary expertise for evaluation, treatment, and counseling.

Testosterone therapy: where do the latest guidelines agree and differ?

PURPOSE OF REVIEW: The incidence of testosterone deficiency and number of men on testosterone therapy (TTh) has increased significantly over the past 3 decades. This rise has been accompanied by controversies surrounding the indications and possible adverse effects of therapy. To better inform prescribing habits among providers, many major medical associations have devised guidelines regarding the diagnosis and management of testosterone deficiency. While these guidelines agree in many areas, there are some key differences that should be identified. This review will explore the similarities, differences, and rationale for these guidelines. RECENT FINDINGS: Over the past 7 years, much attention has been devoted to the implications of TTh on cardiac health. All reviewed guidelines include dedicated sections discussing these implications and the society's position on prescribing testosterone considering recent findings, however, differ on specific contraindications to TTh and when to initiate therapy after a cardiovascular event. In addition, the American College of Physicians released its first guideline earlier this year which may impact prescribing habits among primary care physicians. SUMMARY: The differences between testosterone deficiency guidelines may indicate gaps in our knowledge of testosterone deficiency and focuses of future research efforts. Prescribers should be aware of these differences and discuss all treatment options with their patients.

Modern andrology: from semen analysis to postgenomic studies of the male gametes.

A male factor is implicated in about 50% of couples treated with advanced assisted reproductive techniques (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). An important function of spermatozoa is to deliver the paternal genome to the oocyte. However, neither the routine testing of male fertility potential, nor its treatment, addresses the specific mechanisms by which spermatozoal factors may impact reproductive outcome. Recently, a number of screening tests for DNA integrity have been proposed to assess sperm chromatin abnormalities. These include nonspecific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, and alterations in the epigenetic regulation of the paternal genome. This minireview discusses methods to assess the influence of the paternal genome on reproduction beyond that which can be appreciated by simple quantitative and morphologic evaluation of spermatozoa. Finally, new data on how to select the "best fit" sperm for ICSI will be presented.

[RNA interference and its application in andrology research].

RNA interference (RNAi), induced by double-strand RNA homologous to the silenced gene, is a process of post-transcriptional gene silencing in animals and plants. It plays an important role in fighting viral infection, inhibiting transposon activity and down-regulating the expression of the endogenous gene. As a focus of current biomedical research, RNAi has been applied to the studies of erectile dysfunction (ED), prostate cancer and spermatogenesis. This paper summarizes the mechanisms of RNAi, the latest progress in its researches and its application in andrology studies.

Changes in practice patterns in male infertility cases in the United States: the trend toward subspecialization.

OBJECTIVE: To assess changes in the practice patterns of urologists performing male infertility procedures (vasal reconstruction, sperm retrieval, varicocelectomy) from 2004 to 2015 in the United States. DESIGN: Examination of self-reported procedural volumes from urologists undergoing certification and recertification using case log data provided by the American Board of Urology. The study period was stratified into early (2004-2007) and recent (2012-2015) time periods. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Temporal variations in male infertility practice patterns among different urologic subspecialties between the early and recent time periods. RESULT(S): The overall proportion of total male infertility procedures performed by andrologists significantly increased between the early and recent groups (23% to 26%). This growth was driven by a significant increase in the proportion of varicocele repairs being performed by andrologists between the early and recent periods (19% to 25%). Most notably, an assessment of total number of male infertility procedures performed by newly certifying urologists showed that there was a significant increase in the overall proportion of all male infertility procedures being performed by recently trained andrologists (24% to 35%). This significant increase was seen individually among all three types of male infertility procedures. CONCLUSION(S): With the increased trend in urologists obtaining fellowship training, male infertility surgical volume is beginning to shift from general urologists to subspecialized andrologists.

Detecting subtle changes in sperm membranes in veterinary andrology.

Thanks to the increasing use of flow cytometry in research in veterinary spermatology, many new membrane integrity assays have been developed over the past decade. These assays are important because of their superior ability to forecast fertility when compared with other tests, such as sperm motility. This major component of the sperm quality assessment has generated new investigations with the aim of developing tests that can detect membrane damage in a very early state. Using phospholipid transposition tests, early changes in membrane permeability and fluidity can be assessed in a large number of spermatozoa using fluorescent probes in combination with flow cytometry.

Andrology.

Andrology is part of dermatology in Germany, as it arose from dermatology as a subspecialty. Accordingly training in andrology is part of the curriculum for specialty certification in dermatology. All dermatologists are required to "have experience in the diagnosis of andrologic disorders and their subsequent treatment". The specialty of andrology deals with male infertility problems including questions regarding fertility prophylaxis, contraception, erectile dysfunction, disturbance in libido, ejaculation and copulation, and primary and secondary hypogonadism, as well as male aging and diseases of the male breast. Evaluation and treatment of the partner may also be necessary. Ejaculate analysis is the most important laboratory tool and each dermatologist must be qualified in its performance.