Allan A. Pacey

The evolutionary ecology of pre- and post-meiotic sperm senescence

Male reproductive success is an extremely variable fitness component. Understanding the maintenance of this variation is a key challenge in evolutionary biology. An often neglected source of variation in male reproductive success is determined by age-dependent patterns of decline in sperm fitness. Two pathways mediate sperm senescence: pre-meiotic senescence of somatic and germ cells of the ageing male, and post-meiotic ageing of the spermatozoon. Recently, theoretical and empirical studies have highlighted wide-ranging implications of both pathways. We clarify different mechanisms of sperm senescence, outlining their distinct evolutionary implications for the male, the female and the zygote, and their influence on fundamental evolutionary processes, including the evolution of anisogamy, sexual conflict, sexual selection, and applied issues such as assisted conception.

Can Chlamydia trachomatis directly damage your sperm

Although Chlamydia trachomatis causes symptomatic infection in the lower genital tract of approximately 50% of men, its role in the upper genital tract is less well known. Moreover, for a number of reasons, mostly based on methodological aspects, the impact of chlamydia on semen quality is controversial. Overall, in-vivo studies of C trachomatis in men have provided conflicting evidence as to whether it is associated with reduced fertility. By contrast, in-vitro studies show that co-incubation of spermatozoa with chlamydia causes a significant decline in numbers of motile sperm and results in premature sperm death. Since evidence suggests that chlamydial lipopolysaccharide is the principal factor leading to sperm apoptosis, a new line of inquiry would be to measure the levels of lipopolysaccharide in semen and relate these to parameters of semen quality, including that of sperm function. If these new lines of inquiry are proven, this could lead to potentially novel approaches in the treatment of infertile men.

Hydrodynamic propulsion of human sperm

The detailed fluid mechanics of sperm propulsion are fundamental to our understanding of reproduction. In this paper, we aim to model a human sperm swimming in a microscope slide chamber. We model the sperm itself by a distribution of regularized stokeslets over an ellipsoidal sperm head and along an infinitesimally thin flagellum. The slide chamber walls are modelled as parallel plates, also discretized by a distribution of regularized stokeslets. The sperm flagellar motion, used in our model, is obtained by digital microscopy of human sperm swimming in slide chambers. We compare the results of our simulation with previous numerical studies of flagellar propulsion, and compare our computations of sperm kinematics with those of the actual sperm measured by digital microscopy. We find that there is an excellent quantitative match of transverse and angular velocities between our simulations and experimental measurements of sperm. We also find a good qualitative match of longitudinal velocities and computed tracks with those measured in our experiment. Our computations of average sperm power consumption fall within the range obtained by other authors. We use the hydrodynamic model, and a prototype flagellar motion derived from experiment, as a predictive tool, and investigate how sperm kinematics are affected by changes to head morphology, as human sperm have large variability in head size and shape. Results are shown which indicate the increase in predicted straight-line velocity of the sperm as the head width is reduced and the increase in lateral movement as the head length is reduced. Predicted power consumption, however, shows a minimum close to the normal head aspect ratio.

Cross-border reproductive care: A review of the literature.

Cross-border reproductive care (CBRC) has attracted considerable attention in media and professional publications. The aim of this review is to present a critical narrative overview of the published evidence on CBRC. A systematic search of key academic databases was undertaken with no time restrictions set for publication. This was supplemented by additional searches of key websites, reference chaining and enquiries to people working in the field. A total of 54 items are included in the review, including both empirical research studies (18) and debate papers (36). The key themes discussed are: terminology and definitions; incidence; experiences; explanations; implications; and policy responses. Significant methodological limitations and gaps in the literature are identified. Evidence on incidence is scant, though it suggests that CBRC is increasing. The literature suggests legal, social and political drivers, which vary in importance geographically and between individuals. Limited findings on patient perceptions suggest a broadly positive patient experience. Suggested policy responses include prohibition, regulatory harmonization and harm minimization. There is a need for better international data collection tools and both quantitative and qualitative work which encompasses views of patients, donors, surrogates and professionals and which explores the implications for healthcare services in sending countries.

Crossing borders for fertility treatment: motivations, destinations and outcomes of UK fertility travellers

BACKGROUND There are few systematic studies of the incidence of cross-border fertility care and even fewer reports of qualitative research with those undertaking treatment outside their country of origin. This paper reports findings from a qualitative study of UK residents with experience of cross-border care: the socio-demographic characteristics of UK travellers; their reasons for seeking treatment abroad; the treatments they sought; the destinations they chose and the outcomes of their treatment. METHODS Data regarding cross-border fertility treatment were collected from a purposive sample of 51 people by means of in-depth, semi-structured interviews between May 2009 and June 2010. Data were analysed using a systematic thematic coding method and also subjected to quantitative translation. RESULTS Patient motivations for travelling abroad are complex. A desire for timely and affordable treatment with donor gametes was evident in a high number of cases (71%). However, most people gave several reasons, including: the cost of UK treatment; higher success rates abroad; treatment in a less stressful environment and dissatisfaction with UK treatment. People travelled to 13 different countries, the most popular being Spain and the Czech Republic. Most organized their own treatment and travel. The mean age of women seeking treatment was 38.8 years (range 29-46 years) and the multiple pregnancy rate was 19%. CONCLUSIONS UK residents have diverse reasons for, and approaches to, seeking overseas treatment and do not conform to media stereotypes. Further research is needed to explore implications of cross-border treatment for donors, offspring and healthcare systems.

Infectivity of chlamydia trachomatis serovar LGV but not E is dependent on host cell heparan sulfate

ABSTRACT The ability of heparan sulfate, heparin, and other glycosaminoglycans to inhibit the infectivity of Chlamydia trachomatis serovars E and LGV was examined using a simple competitive inhibition assay with three cell types from the human female reproductive tract, including primary human endosalpingeal cells. With the majority of the glycosaminoglycans tested, LGV was more significantly inhibited than serovar E. We have compared chlamydial infectivity between a wild-type Chinese hamster ovary cell line and two glycosaminoglycan-deficient cell lines. LGV was shown to be unable to infect heparan sulfate-deficient and GAG-deficient Chinese hamster ovary cell lines, whereas the E serovar infected these cells as efficiently as the control (nondeficient) cells. These two sets of experiments confirmed that serovar LGV is more dependent on a heparan sulfate-related mechanism of infectivity than is serovar E. This is further supported by the fact that attempts to purify a heparan sulfate-like molecule from either serovar cultured in glycosaminoglycan-deficient cell lines were nonproductive. Previous reports have suggested that chlamydia are able to produce a heparan sulfate-like molecule that is important for attachment and infectivity. We have attempted to detect possible binding of a specific heparan sulfate antibody to C. trachomatis by flow cytometry. Results showed no binding of the heparan sulfate antibody to C. trachomatis serovar LGV or E. Our results strongly indicate that chlamydiae do not produce a heparan sulfate-like molecule but rather use host cell heparan sulfate in order to infect cells.

Impact of Chlamydia trachomatis in the reproductive setting: British Fertility Society Guidelines for practice.

Chlamydia trachomatis infection of the genital tract is the most common sexually transmitted infection and has a world-wide distribution. The consequences of infection have an adverse effect on the reproductive health of women and are a common cause of infertility. Recent evidence also suggests an adverse effect on male reproduction. There is a need to standardise the approach in managing the impact of C. trachomatis infection on reproductive health. We have surveyed current UK practice towards screening and management of Chlamydia infections in the fertility setting. We found that at least 90% of clinicians surveyed offered screening. The literature on this topic was examined and revealed a paucity of solid evidence for estimating the risks of long-term reproductive sequelae following lower genital tract infection with C. trachomatis. The mechanism for the damage that occurs after Chlamydial infections is uncertain. However, instrumentation of the uterus in women with C. trachomatis infection is associated with a high risk of pelvic inflammatory disease, which can be prevented by appropriate antibiotic treatment and may prevent infected women from being at increased risk of the adverse sequelae, such as ectopic pregnancy and tubal factor infertility. Recommendations for practice have been proposed and the need for further studies is identified.

Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study

STUDY QUESTION Are common lifestyle factors associated with low-motile sperm concentration (MSC)? SUMMARY ANSWER Common lifestyle choices make little contribution to the risk of low MSC. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Reviews of male subfertility often highlight how aspects of mens adult lifestyle can significantly increase their risk of subfertility but the strength of supporting evidence is weak. In this study, although low MSC was associated with a history of testicular surgery, being in manual work, not wearing loose underwear and black ethnicity, no relation was found to consumption of alcohol, use of tobacco or recreational drugs or high body mass index (BMI). These results suggest that delaying assisted conception to make changes to lifestyle is unlikely to enhance conception. DESIGN Unmatched case-referent study with 939 cases and 1310 referents. Cases had a low-MSC relative to the time since last ejaculation (<12 × 10(6) for 3 days of abstinence). Exposures included self-reported exposures to alcohol, tobacco, recreational drugs as well as occupational and other factors. PARTICIPANTS AND SETTING Eligible men, aged 18 or above, were part of a couple who had been attempting conception without success following at least 12 months of unprotected intercourse and also had no knowledge of any semen analysis. They were recruited from 14 fertility clinics across the UK during a 37-month period from 1 January 1999. MAIN RESULTS AND THE ROLE OF CHANCE Risk factors for low MSC, after adjustment for centre and confounding factors, included a history of testicular surgery [odds ratio = 2.39, 95% confidence interval (CI): 1.75, 3.28], being in manual work [odds ratio (OR) = 1.28, 95% CI: 1.07, 1.53] or not working (OR = 1.78, 95% CI: 1.22, 2.59) and having black ethnicity (OR = 1.99, 95% CI: 1.10, 3.63). Conversely, men who wore boxer shorts (OR = 0.76, 95% CI: 0.64, 0.92) or who had a previous conception (OR = 0.71, 95% CI: 0.60, 0.85) were less likely to be a case. No significant association was found with smoking and alcohol consumption, the use of recreational drugs, a high BMI or having a history of mumps or fever. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Data were collected blind to outcome, and exposure information should not have been subject to reporting bias. Among men attending the various clinics less than half met the study eligibility criteria and among those who did, two out of five were not recruited. It is not known whether any of those who refused to take part did so because they had a lifestyle they did not want subjected to investigation. Although the power of the study was sufficient to draw conclusions about common lifestyle choices, it cannot comment on exposures that are perhaps rare and poorly reported: the finding that use of street drugs was unrelated to low MSC cannot be assumed to apply to all such drugs and all patterns of use. The case definition did not consider sperm morphology or sperm DNA integrity. GENERALIZABILITY TO OTHER POPULATIONS All participating clinics saw patients at no cost (under the UK National Health Service) and the study population may differ from those in countries without such provision. Even within the UK, low-income couples may choose not to undertake any investigation believing that they would subsequently be unable to afford treatment.

Occupation and male infertility: glycol ethers and other exposures

Objectives: To investigate the relation between male infertility and occupational exposures, particularly glycol ethers. Methods: A case-referent study was designed in which men attending 14 fertility clinics in 11 centres across the UK in 1999–2002 were recruited following 12 months of unprotected intercourse and without a previous semen analysis. Cases were those with low motile sperm concentration (MSC) relative to the time since their last ejaculation (MSC <12×106 for 3 days of abstinence). Referents were other men attending these clinics and meeting the inclusion criteria. A single semen sample was collected at the clinic and analysed at the andrology laboratory serving each hospital. Concentration was determined manually with motility assessed centrally from video recordings. Exposures and confounding factors were assessed from self-completed and nurse–interviewer questionnaires, completed prior to the results of the semen analysis. The occupational histories were assessed for exposures relative to UK norms by a team of occupational hygienists blind to case status. Results: Of 2118 men in employment at the time of the interview, 874 (41.3%) were cases. Work with organic solvents, particularly glycol ethers, in the 3 months before the first clinic visit was associated with the likelihood of low motile sperm count. Unadjusted odds ratios (OR) for moderate and high glycol ether exposure (compared with none) were 1.70 (95% CI: 1.11 to 2.61) and 2.54 (95% CI: 1.24 to 5.21). Adjustment for potential confounders (surgery to the testes, previous conception, wearing boxer shorts, drinking alcohol, employed in manual work) reduced the risk associated with glycol ether exposure: moderate OR = 1.46 (95% CI: 0.93 to 2.28), high OR = 2.25 (95% CI: 1.08 to 4.69). No other occupational risk factor was identified. Conclusions: Glycol ether exposure was related to low motile sperm count in men attending fertility clinics. This suggests that, at the time of the study, glycol ethers continued to be a hazard for male fertility.

Health-related quality of life in survivors of lymphoma: a systematic review and methodological critique

Survival rates for Hodgkin lymphoma and non-Hodgkin lymphoma have improved in recent years. However, these improvements are associated with various late effects, which can compromise health-related quality of life (HRQoL). Improving HRQoL is a significant goal in oncology, and increasingly one of the primary outcomes in clinical trials, but is dependent on availability of reliable and sensitive measures. This review therefore aimed to: (i) identify and evaluate commonly used HRQoL measures; (ii) compare HRQoL in patients with lymphoma with the general population; and assess the association between (iii) HRQoL and different treatments; and (iv) HRQoL and demographic, medical, and psychological variables. Standardized systematic searches identified 18 eligible studies that included adult survivors of lymphoma and reported quantitative results by histological diagnosis. Information about design, sample, measures and findings was extracted from each study. Survivors of lymphoma experienced worse physical but comparable mental HRQoL to the general population. No conclusions could be drawn about the association between different treatments and HRQoL. Correlates of better HRQoL included younger age, educational level, being employed, male gender, earlier stage disease, not having co-morbid illnesses, and meeting public health exercise guidelines. Limitations of current research relating to research design, sample demographics, and reporting of descriptive statistics were identified. Given the increasing numbers of patients living with lymphoma, controlled studies using appropriate measures are required to determine the HRQoL consequences associated with the condition.