Implementation of World Health Organization Recommendations for Semen Analysis: A Survey of Laboratories in the United Kingdom

The standard method for identification of male fertility status is a semen analysis. This is performed in fertility and pathology laboratories accredited by different bodies in the UK such as the HFEA or UKAS, and is based on whether they perform licenced clinical treatment or diagnostic testing. The WHO laboratory semen analysis criteria provide the most comprehensive guidance for best practice, yet this is not strictly adhered to. Our objective was to determine any differences in semen analyses between laboratories in the UK, based on the regulatory body they are registered with. A cross-sectional survey was sent to NEQAS for andrology registrants (n=184 laboratories), HFEA (n=117 clinics), and individual ARCS members (n=682). Most ARCS members are associated with NEQAS and/or the HFEA. A ∼50% laboratory response rate (n=106 included responses) was found. Results were grouped based on accreditation: Group 1, UKAS accredited only (n=38); Group 2, both UKAS accredited and HFEA licenced (n=17); Group 3, HFEA licenced only (n=42); and Group 4, no accreditation (n=9). Over 85%of UKAS accredited laboratories (Groups 1 and 2) state they perform semen analysis according to WHO 2010 recommendations and adhere to best practice guidelines. A significantly fewer number of HFEA only laboratories (<74% Group 3, p <0:01) adhere to both guidelines. Non-HFEA laboratories (Groups 1 and 4) are almost all performing sperm counts according to WHO criteria, while <60% HFEA clinics (Groups 2 and 3) perform counts according to regulation (Group 1 vs. Groups 2 and 3: Fixed sperm, p <0:05; Neubauer chamber: p <0:005). QC is implemented in most laboratories, however there is a significant difference (p <0:01) between non- UKAS (Groups 3 and 4) and UKAS laboratories (Groups 1 and 2). There is a significant difference in semen analysis performance between UKAS and HFEA laboratories with regards to implementation of best practice guidelines and QC procedures. This may have a detrimental effect on result accuracy and consequently lead to patient misdiagnosis and mismanagement

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

Artificial intelligence in andrology: From Semen Analysis to Image Diagnostics

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 as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: A global survey, current guidelines, and expert recommendations

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 the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

Safety issues in assisted reproduction technology: Should men undergoing ICSI be screened for chromosome abnormalities in their sperm?

The incidence of aneuploidy in gametes of men undergoing ICSI has raised the prospect of there being risks associated with ICSI and the question of whether or not to screen men for sperm aneuploidy before treatment. We report results of a questionnaire undertaken to address how IVF staff perceive this problem, whether ICSI men are already being screened for sperm aneuploidy and the extent to which IVF specialists feel that there is merit in such a test. The results suggest that this is seen as a problem but most feel the risks outweigh the benefits. Most claimed their clinics do not screen sperm for aneuploidy but feel that there is merit in doing so. There are considerable benefits to screening i.e. couples would get additional information about the genetic repercussions of ICSI and could make informed decisions before treatment; screening would also facilitate the design of a large research study to give clearer answers on the safety of ICSI. However, we acknowledge counter arguments i.e. families would not necessarily benefit as most would have the ICSI procedure regardless of screen results; sex chromosome trisomies clinically are not severe enough to worry about in this context and there are other potential risks of ICSI that screening would not address

Plants Used in Chinese Medicine for the Treatment of Male Infertility Possess Antioxidant and Anti-Oestrogenic Activity

In this study Chinese herbs commonly used in the treatment of male infertility were investigated for relevant biochemical activity. Male factor infertility predominantly arises via barriers to, or defects in, spermatogenesis. The process of spermatogenesis is under strict endocrine control; in addition oxidative stress has been implicated in male infertility with significant levels of reactive oxygen species detected in 25% of infertile males. A total of 37 individual herbs and seven herb decoctions used in the treatment of male factor infertility were therefore tested for endocrine activity using a recombinant yeast based assay and antioxidant activity using the FRAP (ferric reducing antioxidant potential) assay. Individual herbs tested did not show androgenic properties, 20 showed strong and 10 weak anti-oestrogenic activity (per g of dried herb tamoxifen equivalents ranged from 1.18-1280.66 mg and 0.06-0.98 mg, respectively). Oestrogenic responses were elicited for two herbs (85.30-550 g oestradiol equivalents/g dried herb), with seven and three herbs exhibiting a strong or weak anti-androgenic response (per g of dried herb DHT equivalents ranged from 1.54-66.78 mg and 0.17-0.32 mg), respectively. Of these 37 herbs, strong (15 herbs), intermediate (7 herbs) and weak/no (15 herbs) antioxidant activity was detected (ranging from 0.912-1.26; 0.6-0.88 and 0-0.468 g ascorbate equivalent/mg dried herb, respectively). The seven decoctions (previously used to treat patients) tested elicited strong (5 herbs) and weak (2 herbs) anti-oestrogenic responses (per g of dried herb tamoxifen equivalents ranged from 1.14-13.23 mg and 0.22-0.26 mg, respectively), but not oestrogenic, androgenic nor anti-androgenic, consistent with their individual composition. With regard to antioxidant activity the following responses were recorded: three strong, three intermediate and one weak (ranging from 1.02-1.2; 0.72-0.76 and 0.44 g ascorbate equivalent/mg dried herb, respectively). The prospects for introducing Chinese herbal treatments into the Western-based medicine are discussed

The association between male infertility and sperm disomy: Evidence for variation in disomy levels among individuals and a correlation between particular semen parameters and disomy of specific chromosome pairs

BACKGROUND: The association between infertility and sperm disomy is well documented. Results vary but most report that men with severely compromised semen parameters have a significantly elevated proportion of disomic sperm. The relationship between individual semen parameters and segregation of specific chromosome pairs is however less well reported as is the variation of disomy levels in individual men. METHODS: In order to address these questions the technique of fluorescent in-situ hybridisation (FISH) was utilised to determine the disomy levels of chromosomes X, Y and 21 in 43 sperm samples from 19 infertile males. The results generated from this study were analysed using logistic regression. RESULTS: In this study we compared levels of sperm concentration, motility and morphology with levels of sperm disomy for chromosome 21 and the sex chromosomes. Our results suggest that there is considerable variation in disomy levels for certain men. They also suggest that oligozoospermic males have significantly elevated levels of sex chromosome disomy but not disomy 21; they suggest that severe asthenozoospermic males have significantly elevated levels of disomy 21 but not sex chromosome disomy. Surprisingly, severe teratozoopsermic males appeared to have significantly lower levels of sperm disomy for both the sex chromosomes and chromosome 21. CONCLUSION: We suggest that the association between sex chromosome disomy and oligozoospermia may be due to reduced recombination in the XY pairing region and discuss the relevance of our findings for the correlations between sperm disomy and sperm motility and morphology

A Comparison Between Two Assays for Measuring Seminal Oxidative Stress and their Relationship with Sperm DNA Fragmentation and Semen Parameters

Oxidative stress (OS) is a significant cause of DNA fragmentation and is associated with poor embryo development and recurrent miscarriage. The aim of this study was to compare two different methods for assessing seminal OS and their ability to predict sperm DNA fragmentation and abnormal semen parameters. Semen samples were collected from 520 men attending for routine diagnostic testing following informed consent. Oxidative stress was assessed using either a chemiluminescence assay to measure reactive oxygen species (ROS) or an electrochemical assay to measure oxidation reduction potential (sORP). Sperm DNA fragmentation (DFI) and sperm with immature chromatin (HDS) were assessed using sperm chromatin structure assay (SCSA). Semen analysis was performed according to WHO 2010 guidelines. Reactive oxygen species sORP and DFI are negatively correlated with sperm motility (p = 0.0012, 0.0002, &lt;0.0001 respectively) and vitality (p &lt; 0.0001, 0.019, &lt;0.0001 respectively). The correlation was stronger for sORP than ROS. Reactive oxygen species (p &lt; 0.0001), sORP (p &lt; 0.0001), DFI (p &lt; 0.0089) and HDS (p &lt; 0.0001) were significantly elevated in samples with abnormal semen parameters, compared to those with normal parameters. Samples with polymorphonuclear leukocytes (PMN) have excessive ROS levels compared to those without (p &lt; 0.0001), but sORP and DFI in this group are not significantly increased. DNA fragmentation was significantly elevated in samples with OS measured by ROS (p = 0.0052) or sORP (p = 0.004). The results demonstrate the multi-dimensional nature of oxidative stress and that neither assay can be used alone in the diagnosis of OS, especially in cases of leukocytospermia