Do studies published in two leading reproduction journals between 2011 and 2020 demonstrate that they followed WHO5 recommendations for basic semen analysis?

STUDY QUESTION: Do publications that involve the interpretation of the results of a basic semen analysis, published in Human Reproduction and Fertility & Sterility between 2011 and 2020, give sufficient evidence in their methodology to demonstrate that they followed the technical methods recommended in the fifth edition of the World Health Organization (WHO) laboratory manual, entitled WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO5)? SUMMARY ANSWER: Evidence of methodological agreement of studies with the WHO5 recommendations was low, despite 70% of papers stating that they followed WHO5 recommendations. WHAT IS KNOWN ALREADY: A basic semen analysis is currently an integral part of infertility investigations of the male, but method standardization in laboratories remains an issue. The different editions of the WHO manual for the basic semen analysis (WHO1-6) have attempted to address this by providing increasingly rigorous methodological protocols to reduce experimental error. However, to what extent these methods are followed by studies that involve the interpretation of the results of basic semen analysis remains unknown. STUDY DESIGN, SIZE, DURATION: A survey of the technical methods used to perform a basic semen analysis was conducted on studies published in two leading reproduction journals (Human Reproduction and Fertility & Sterility) between 2011 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: The literature search was performed on the electronic databases PUBMED and MEDLINE Ovid between January 2021 and March 2021. The MeSH terms included in the search were 'sperm concentration' OR 'sperm motility' OR 'sperm morphology' OR 'sperm vitality' OR 'male fertility' AND 'human spermatozoa' NOT 'animals'. A total of 122 studies were available for analysis. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 70% of the studies cited WHO5 in their methods section. Of the remaining studies, 10% cited the fourth edition of the WHO laboratory manual (WHO4), 7% cited both WHO4 and WHO5, 1% cited the third edition of the WHO laboratory manual (WHO3), and 12% did not cite the WHO at all. Overall methodological agreement with WHO5 recommendations was poor, with the main reason for this lack of agreement being that the research studies did not disclose specific details of the technical methods and equipment used. LIMITATIONS, REASONS FOR CAUTION: In the case of studies that did not disclose any specific technical methods that they used, we did not attempt to contact these authors and so were unable to confirm the agreement between their technical methods and WHO5 recommendations. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest there is an urgent need to develop strategies to address standardization in reporting the results of a semen analysis for publication. This is particularly timely given the recent publication of WHO6 and ISO standard 23162 for the basic examination of human semen. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this project. C.L.R.B., as an employee of the University of Dundee, serves on the Scientific Advisory board of ExSeed Health (from October 2021, financial compensation to the University of Dundee) and is a scientific consultant for Exscientia (from September 2021, financial compensation to the University of Dundee). C.L.R.B. has previously received a fee from Cooper Surgical for lectures on scientific research methods outside the submitted work (2020) and Ferring for a lecture on male reproductive health (2021). C.L.R.B. is Editor for RBMO. TRIAL REGISTRATION NUMBER: N/A.

Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro.

STUDY QUESTION: Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER: AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY: Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION: This study included population-based samples from men (23-50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017-September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P < 0.003). LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS: Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S): AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012-2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap.

BACKGROUND: There is a global crisis in male reproductive health. Evidence comes from globally declining sperm counts and increasing male reproductive system abnormalities, such as cryptorchidism, germ cell tumors, and onset of puberty. Male factor infertility occurs in ~40% of couples experiencing infertility. Data demonstrate an association between male infertility and overall health. Associated significant health conditions include diabetes mellitus, metabolic disorders, and cardiovascular disease. Adding to the complexity is that men typically do not seek health care unless there is acute medical need or, as in the case of the infertile couple, the male goes for a reproductive examination and semen analysis. However, 25% of the time a reproductive health examination does not occur. Couples are increasingly utilizing IVF at more advanced ages, and advanced paternal age is associated with increased risk for (i) adverse perinatal outcomes for both offspring and mother; (ii) early child mortality, cancer, and mental health issues. In addition to age, paternal lifestyle factors, such as obesity and smoking, impact not only the male fertility but also the offspring wellness. OBJECTIVES: The purpose of this paper was (i) to spotlight emerging and concerning data on male reproductive health, the relationship(s) between male reproductive and somatic health, and the heritable conditions father can pass to offspring, and (ii) to present a strategic roadmap with the goals of increasing (a) the awareness of men and society on the aforementioned, (b) the participation of men in healthcare seeking, and (c) advocacy to invigorate policy and funding agencies to support increased research into male reproductive biology. CONCLUSIONS: The Male Reproductive Health Initiative (MRHI) is a newly established and rapidly growing global consortium of key opinion leaders in research, medicine, funding and policy agencies, and patient support groups that are moving forward the significant task of accomplishing the goals of the strategic roadmap.

Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic, personal care and air care products.

As part of a joint project between the Research Institute for Fragrance Materials (RIFM) and Creme Global, a Monte Carlo model (here named the Creme RIFM model) has been developed to estimate consumer exposure to ingredients in personal care products. Details of the model produced in Phase 1 of the project have already been published. Further data on habits and practises have been collected which enable the model to estimate consumer exposure from dermal, oral and inhalation routes for 25 product types. . In addition, more accurate concentration data have been obtained which allow levels of fragrance ingredients in these product types to be modelled. Described is the use of this expanded model to estimate aggregate systemic exposure for eight fragrance ingredients. Results are shown for simulated systemic exposure (expressed as µg/kg bw/day) for each fragrance ingredient in each product type, along with simulated aggregate exposure. Highest fragrance exposure generally occurred from use of body lotions, body sprays and hydroalcoholic products. For the fragrances investigated, aggregate exposure calculated using this model was 11.5-25 fold lower than that calculated using deterministic methodology. The Creme RIFM model offers a very comprehensive and powerful tool for estimating aggregate exposure to fragrance ingredients.

Use of an aggregate exposure model to estimate consumer exposure to fragrance ingredients in personal care and cosmetic products.

Ensuring the toxicological safety of fragrance ingredients used in personal care and cosmetic products is essential in product development and design, as well as in the regulatory compliance of the products. This requires an accurate estimation of consumer exposure which, in turn, requires an understanding of consumer habits and use of products. Where ingredients are used in multiple product types, it is important to take account of aggregate exposure in consumers using these products. This publication investigates the use of a newly developed probabilistic model, the Creme RIFM model, to estimate aggregate exposure to fragrance ingredients using the example of 2-phenylethanol (PEA). The output shown demonstrates the utility of the model in determining systemic and dermal exposure to fragrances from individual products, and aggregate exposure. The model provides valuable information not only for risk assessment, but also for risk management. It should be noted that data on the concentrations of PEA in products used in this article were obtained from limited sources and not the standard, industry wide surveys typically employed by the fragrance industry and are thus presented here to illustrate the output and utility of the newly developed model. They should not be considered an accurate representation of actual exposure to PEA.

Novel database for exposure to fragrance ingredients in cosmetics and personal care products.

Exposure of fragrance ingredients in cosmetics and personal care products to the population can be determined by way of a detailed and robust survey. The frequency and combinations of products used at specific times during the day will allow the estimation of aggregate exposure for an individual consumer, and to the sample population. In the present study, habits and practices of personal care and cosmetic products have been obtained from market research data for 36,446 subjects across European countries and the United States in order to determine the exposure to fragrance ingredients. Each subject logged their product uses, time of day and body application sites in an online diary for seven consecutive days. The survey data did not contain information on the amount of product used per occasion or body measurements, such as weight and skin surface area. Nevertheless, this was found from the literature where the likely amount of product used per occasion or body measurement could be probabilistically chosen from distributions of data based on subject demographics. The daily aggregate applied consumer product exposure was estimated based on each subject's frequency of product use, and Monte Carlo simulations of their likely product amount per use and body measurements. Statistical analyses of the habits and practices and consumer product exposure are presented, which show the robustness of the data and the ability to estimate aggregate consumer product exposure. Consequently, the data and modelling methods presented show potential as a means of performing ingredient safety assessments for personal care and cosmetics products.

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels.

Whilst fertilizing capacity depends upon a K(+) conductance (GK) that allows the spermatozoon membrane potential (Vm) to be held at a negative value, the characteristics of this conductance in human sperm are virtually unknown. We therefore studied the biophysical/pharmacological properties of the K(+) conductance in spermatozoa from normal donors held under voltage/current clamp in the whole cell recording configuration. Our standard recording conditions were designed to maintain quasi-physiological, Na(+), K(+) and Cl(-) gradients. Experiments that explored the effects of ionic substitution/ion channel blockers upon membrane current/potential showed that resting Vm was dependent upon a hyperpolarizing K(+) current that flowed via channels that displayed only weak voltage dependence and limited (∼7-fold) K(+) versus Na(+) selectivity. This conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium (50 µM), NNC55-0396 (2 µM) and mibefradil (30 µM), but not by 4-aminopyridine (2 mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K(+) current. Repolarization after a test depolarization consistently evoked a transient inward 'tail current' (ITail) that flowed via a second population of ion channels with poor (∼3-fold) K(+) versus Na(+) selectivity. The activity of these channels was increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore dependent upon a hyperpolarizing K(+) current that flows via channels that most closely resemble those encoded by Slo3. Although 0.5 µM progesterone had no effect upon these channels, this hormone did activate the pharmacologically distinct channels that mediate ITail. In conclusion, this study reveals three functionally and pharmacologically distinct cation channels: Ik, ITail, ICatSper.

Incremental effect of a calcium salt of cis-monounsaturated fatty acids supplement on milk fatty acid composition in cows fed maize silage-based diets.

In most Western countries, saturated fatty acid (SFA) intake exceeds recommended levels, which is considered a risk factor for cardiovascular disease (CVD). As milk and dairy products are major contributors to SFA intake in many countries, recent research has focused on sustainable methods of producing milk with a lower saturated fat concentration by altering dairy cow diets. Human intervention studies have shown that CVD risk can be reduced by consuming dairy products with reduced SFA and increased cis-monounsaturated fatty acid (MUFA) concentrations. This milk fatty acid profile can be achieved by supplementing dairy cow diets with cis-MUFA-rich unsaturated oils. However, rumen exposure of unsaturated oils also leads to enhanced milk trans fatty acid (TFA) concentrations. Because of concerns about the effects of TFA consumption on CVD, feeding strategies that increase MUFA concentrations in milk without concomitant increases in TFA concentration are preferred by milk processors. In an attempt to limit TFA production and increase the replacement of SFA by cis-MUFA, a preparation of rumen-protected unsaturated oils was developed using saponification with calcium salts. Four multiparous Holstein-Friesian cows in mid-late lactation were used in a 4 × 4 Latin square design with 21-d periods to investigate the effect of incremental dietary inclusion of a calcium salt of cis-MUFA product (Ca-MUFA; 20, 40, and 60 g/kg of dry matter of a maize silage-based diet), on milk production, composition, and fatty acid concentration. Increasing Ca-MUFA inclusion reduced dry matter intake linearly, but no change was observed in estimated ME intake. No change in milk yield was noted, but milk fat and protein concentrations were linearly reduced. Supplementation with Ca-MUFA resulted in a linear reduction in total SFA (from 71 to 52 g/100 g of fatty acids for control and 60 g/kg of dry matter diets, respectively). In addition, concentrations of both cis- and trans-MUFA were increased with Ca-MUFA inclusion, and increases in other biohydrogenation intermediates in milk fat were also observed. The Ca-MUFA supplement was very effective at reducing milk SFA concentration and increasing cis-MUFA concentrations without incurring any negative effects on milk and milk component yields. However, reduced milk fat and protein concentrations, together with increases in milk TFA concentrations, suggest partial dissociation of the calcium salts in the rumen.

Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA).

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 the quality of diagnostic studies, there was no guideline on studies of seminal quality. STUDY DESIGN, SIZE AND DURATION: Through systematic bibliographic search, potential items were identified and grouped into four blocks: participants, analytical methods, statistical methods and results. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our findings were presented to a panel of experts who were asked to identify opportunities for improvement. Then, a checklist was designed containing the questions generated by the items that summarize the essential points that need to be considered for the successful outcome of a SEMQUA. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen items were identified, from which 19 questions, grouped into four blocks, were generated to constitute the final checklist. An explanation for the inclusion of each item was provided and some examples found in the bibliographic search were cited. LIMITATIONS AND REASONS FOR CAUTION: We consider that not all items are equally applicable to all study designs, and so the hypothetical results are not comparable. For that reason, a score would not be fair to critically appraise a study. This checklist is presented as an instrument for appraising SEMQUAs and therefore remains open to constructive criticism. It will be further developed in the future, in parallel with the continuing evolution of SEMQUAs. WIDER IMPLICATIONS OF THE FINDINGS: The final configuration of the SEMQUA is in the form of a checklist, and includes the items generally considered to be essential for the proper development of a SEMQUA. The final checklist produced has various areas of application; for example, it would be useful for designing and constructing a SEMQUA, for reviewing a paper on the question, for educational purposes or as an instrument for appraising the quality of research articles in this field. STUDY FUNDING/COMPETING INTEREST(S): None.

The Concise Guide to PHARMACOLOGY 2013/14: overview.

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

ESHRE special interest group for andrology basic semen analysis course: a continued focus on accuracy, quality, efficiency and clinical relevance.

ESHRE has been running courses for basic semen analysis since 1994 and course material has been updated regularly in response to new findings and publications. Following publication of the 5th edition of the WHO laboratory manual, entitled WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO5), the Subcommittee for training of the ESHRE Special Interest Group for Andrology evaluated potential amendments to its course. In respect of the updated ESHRE course, there are eight particular areas of discourse that are reviewed (i) maintaining the four-class differential motility count allowing distinction between rapid and slow progressive sperm for assisted reproduction technology. (ii) Maintaining the four-category assessment for sperm morphology with calculation of the teratozoospermic index. (iii) Continuing to advocate the use of three categories of results: 'normal', 'borderline' and 'abnormal' with respect to the clinical interpretation of the data. (iv) Presenting clear and unequivocal methods for performing assessments e.g. morphology. (v) Correcting the inconsistencies in WHO5, some of which are actually erroneous. (vi) Reducing the requirements for substantial extra work for what are unestablished improvements in accuracy and/or precision in the final results. (vii) Presentation of logical methods of sperm preparation. (viii) Discussion of the suddenly changed limits between fertile and subfertile men.

Understanding the physiology of pre-fertilisation events in the human spermatozoa--a necessary prerequisite to developing rational therapy.

Sperm dysfunction is the single most common defined cause of infertility. One in 15 men is sub-fertile and the condition is increasing in frequency. However, the diagnosis is poor and, excluding assisted conception, there is no treatment. The reason for this is our limited understanding of the biochemical, molecular and genetic functions of the spermatozoon. The underlying premise of our research programme is to establish a rudimentary understanding of the processes necessary for successful fertilisation. In this manuscript, we detail advances in our understanding of calcium signalling in the cell and outline genetic and proteomic technologies that are being used to improve the diagnosis of the condition.

Patch-clamp 'mapping' of ion channel activity in human sperm reveals regionalisation and co-localisation into mixed clusters.

Ion channels are pivotal to many aspects of sperm physiology and function. We have used the patch clamp technique to investigate the distribution of ion channels in the plasma membrane of the head of human spermatozoa. We report that three types of activity are common in the equatorial and acrosomal regions of the sperm head. Two of these (a chloride-permeable anion channel showing long stable openings and a second channel which flickered between open and closed states and was dependent upon cytoplasmic factors for activity) were localised primarily to the equatorial segment. A third type, closely resembling the flickering activity but with different voltage sensitivity of P(open), was more widely distributed but was not detectable over the anterior acrosome. In the anterior acrosomal area channels were present but showed very low levels of spontaneous activity. A unique feature of channel activity in the sperm equatorial region was co-localisation into mixed clusters, most patches were devoid of activity but 'active' patches typically contained two or more types of activity (in a single 200-300 nM diameter patch). We conclude that ion channels in the sperm membrane show regionalisation of type and activity and that the channels are clustered into functional groups, possibly interacting through local effects on membrane potential.

Detection of previously unrecognized daytime desaturation in children with chronic lung disease.

PRIMARY OBJECTIVE: The prime rationale of this research is to investigate the possible occurrence of previously unrecognized episodes of desaturation apparent in preterm infants with chronic lung disease as they freely move around a non-artificial environment. RESEARCH DESIGN: The study comprises 58 hours of telemetric recordings of SpO2, heart rate, body movement and temperature, along with full ECG and photoplethysmographic waveforms for eight preterm subjects in their home environment. MAIN OUTCOME/RESULTS: The data is analysed for remarkable events, more particularly periods of spontaneous desaturation. Statistical results for all case studies are collated into a table along with examples of graphical analysis. CONCLUSIONS: This study has shown that some patients are prone to episodes of hypoxemia during the course of normal daily activity or daytime sleep that would usually go unrecognized and that more effective management of supplemental oxygen treatment may be possible with continual unobtrusive monitoring.

Patterns of [Ca2+](i) mobilization and cell response in human spermatozoa exposed to progesterone.

Human spermatozoa stimulated with progesterone (a product of the cumulus and thus encountered by sperm prior to fertilization in vivo) apparently mobilize Ca(2+) and respond very differently according to the way in which the steroid is presented. A progesterone concentration ramp (0-3 microM) induces [Ca(2+)](i) oscillations (repetitive store mobilization) which modify flagellar beating, whereas bolus application of micromolar progesterone causes a single large transient (causing acrosome reaction) which is apparently dependent upon Ca(2+) influx. We have investigated Ca(2+)-mobilization and functional responses in human sperm exposed to 3 muM progesterone. The [Ca(2+)](i) response to progesterone was abolished by 4 min incubation in 0 Ca(2+) medium (2 mM EGTA) but in nominally Ca(2+)-free medium (no added Ca(2+); 0 EGTA) a smaller, slow response occurred. Single cell imaging showed a similar effect of nominally Ca(2+)-free medium and approximately 5% of cells generated a small transient even in the presence of EGTA. When cells were exposed to EGTA-containing saline (5 min) and then returned to nominally Ca(2+)-free medium before stimulation, the [Ca(2+)](i) transient was greatly delayed (approximately 50 s) and rise time was doubled in comparison to cells not subjected to EGTA pre-treatment. We conclude that mobilization of stored Ca(2+) contributes a 'slow' component to the progesterone-induced [Ca(2+)](i) transient and that incubation in EGTA-buffered saline is able rapidly to deplete this store. Analysis of flagellar activity induced by 3 muM progesterone showed an effect (modified beating) associated with the [Ca(2+)](i) transient, in >80% of cells bathed in nominally Ca(2+)-free medium. This was reduced greatly in cells subjected to 5 min EGTA pre-treatment. The store-mediated transient showed a pharmacological sensitivity similar to that of progesterone-induced [Ca(2+)](i) oscillations (consistent with filling of the store by an SPCA) suggesting that the transient induced by micromolar progesterone is a 'single shot' activation of the same store that generates Ca(2+) oscillations.

Is there a real risk of transmitting variant Creutzfeldt-Jakob disease by donor sperm insemination?

Although >99% of cases of Creutzfeldt-Jakob disease (CJD) are caused by spontaneous or inherited mutations in the prion protein, 'variant' CJD (vCJD) arose from dietary exposure to meat products infected with the bovine spongiform encephalopathy prion. While European and Canadian sperm donor candidates are rejected for significant CJD risk factors, American sperm donors are managed like blood donors (excluding all men who spent > or =3 months in the UK during 1980-1996 or > or =5 years in Europe since 1980), even though no evidence exists for sexual transmission of prion disease. This study surveyed international experts on either prions/prion disease or donor sperm/cryobanking as to the risk of vCJD transmission via semen/donor spermatozoa (45/104 replied). Consensus expert opinion was that the risk of transmission was <1:10,000,000, even for UK men, hence ultra-conservative risk avoidance would have minimal impact on public safety. Defining 'high vCJD risk' should be based on knowledge rather than fear, and due caution founded upon quantifying real risks rather than avoiding theoretical risks. Women seeking treatment using donor spermatozoa should be allowed to judge the negligible risk of vCJD infection in comparison with acceptable everyday risks, and given the choice of accepting spermatozoa from donors screened according to European-style criteria.