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Background: Hyaluronan (HA) sperm selection, utilizing the affinity of mature sperm for HA, has emerged as a technique to enhance the selection of sperm for intracytoplasmic sperm injection (ICSI). However, conflicting evidence exists regarding the impact of HA-ICSI on clinical outcomes including fertilization, embryo utilization, and pregnancy rates. The study aimed to compare clinical outcomes including fertilization, utilization, and pregnancy rates between paired ICSI and HA-ICSI cycles within patients, particularly for male factor and low utilization subgroups. Methods: A retrospective study from 3,988 ICSI treatment cycles was conducted between January 2018 and March 2022. A HA-ICSI cycle was paired with the preceding ICSI cycle from the same patient. Fertilization, utilization, and clinical pregnancy rates were compared based on infertility diagnosis and utilization rate (UR) from the initial ICSI cycle. Results: There were no differences in fertilization, utilization, embryo quality, euploidy, or pregnancy rates between ICSI and HA-ICSI in all paired cycles. However, for patients with male factor infertility UR increased from 25.0% to 38.5% in their HA-ICSI cycle ([Formula: see text]). There was no difference observed for female factor infertility patients. HA-ICSI use was of particular benefit for male factor infertility patients with low ([Formula: see text]) embryo utilization in their initial ICSI cycle, evident by an increased utilization from 14.3% to 25.0% in their HA cycle ([Formula: see text]). Conclusions: This is the first study to focus on the impact of HA-ICSI on embryo utilization, particularly in patients with male factor infertility. The efficacy of HA-ICSI as a sperm selection tool appears to be limited to improving UR in patients with male factor infertility, particularly those with low utilization in a previous ICSI cycle, with no significant effect on fertilization or pregnancy rates. Conclusion: HA-ICSI may be useful for sperm selection at the time of ICSI for a select subgroup of patients. Male factor infertility patients, who have previously undertaken an ICSI cycle with less than 40% utilization, should be considered as candidates for treatment.

Plain language summary Approximately 1 in 20 men are sub-fertile or infertile yet very little is known about the causes of male infertility. Research has suggested that lifestyle choices and environmental factors contribute to infertility, but more needs to be done to identify and verify the full suite of associations. We will recruit up to 1000 Australian male partners within couples who are seeking help from fertility clinics to get pregnant. They will be asked about their general health, lifestyle and environmental exposures at home or work over their lifespan. We will compare findings between men who are sub- or infertile with men who are not. Any differences will help us understand what factors may be associated with risk of infertility in men. This study will provide important information to clinicians and to inform public policy that will lead to prevention and improved treatment strategies for infertile men. The data gathered from this study will enable future research including the genetic and epigenetic basis of male infertility.

Background: The combination of microsurgical testicular sperm extraction (mTESE) and intracytoplasmic sperm injection (ICSI) has become a common management option, with sperm motility being positively associated with successful outcomes. However, few studies have investigated whether the use of fresh or thawed gamete combinations affect clinical outcomes. Objectives: To determine whether the clinical outcomes of ICSI cycles using mTESE recovered testicular sperm of non-obstructive azoospermia (NOA) patients are affected by using fresh or thawed gametes. Material and Methods: A retrospective study was conducted of NOA patients who underwent mTESE between 2017 and 2020 at Monash IVF assisted reproductive clinics in Melbourne, Australia. The impact of gamete fresh/frozen status and sperm motility was investigated on clinical outcomes such as fertilization, blastocyst formation, clinical pregnancy, and live birth rates (LBRs). Results:A total of 103 NOA patients underwent mTESE, with a 65.1% successful surgical-sperm-retrieval. In total 56 patients contributed to 68 ICSI cycles, with a 35.1% fertilization rate and 25% LBR per embryo transfer. Compared with fresh testicular sperm, thawed testicular sperm did not affect clinical outcomes, including LBRs [16.7% vs 12.0%; odds ratio (OR) 0.68 (0.18–2.70)]. However, the use of thawed oocytes had a negative effect on fertilization rates [fresh-oocytes, 37.8%; vitrified-oocytes, 34.5%; OR 0.86 (0.02–0.48)]. Cycles using only motile sperm had a greater fertilization rate than those using a combination of motile and non-motile sperm (49.6% vs 37.2%, p ¡ 0.05). Importantly, when exclusively non-motile sperm were available (n = 26 cycles) their injection resulted in a very low fertilization rate (2.7%) and no live births were recorded. Conclusion: Micro-TESE is an effective treatment for NOA patients, with no clear advantage of using fresh over thawed sperm, however, the use of vitrified compared with fresh oocytes requires further investigation. Importantly, patients should be informed of the poor outcomes with the use of non-motile sperm in mTESE ICSI cycles.

Background: A four-stream research program, Men and Infertility over the Lifecourse, is funded by the MRFF to address the medical, personal and social cost of idiopathic male infertility. This program includes a national case control study: AMIE. Designing and implementing AMIE poses both opportunities and challenges.

Background: Use of ICSI has escalated globally. Concerns include: 1) heritability of infertility, 2) effects of poor-quality spermatozoa on offspring health, 3) epigenetic effects of ICSI procedure. Aim: Compare reproductive and metabolic health of ICSI-conceived men to IVF-conceived and spontaneously conceived (SC) controls. Method: This study is part of a larger project investigating the health and development, reproductive and metabolic health, and epigenetic profiles of ICSI-conceived men (aged 18-25 years). Age-matched IVF-conceived controls were sourced from the Clinical review of the Health of 22–35-year-olds conceived with and without ART (CHART) study; SC controls were derived from the Western Australian Pregnancy Cohort (Raine) study. In subgroup analyses, ICSI-conceived men of fathers with spermatogenic failure (STF-ICSI) were compared with ICSI-conceived men whose fathers had an obstructive cause of infertility, and IVF- and SC controls. Semen parameters and serum reproductive hormones were compared between 120 ICSI-conceived men and 356 SC controls. Resting systolic and diastolic blood pressure (BP), height, weight, BMI, body surface area, and serum metabolic markers were compared between 121 ICSI-conceived men, and 74 IVF-conceived and 688 SC controls. Results: We found no compelling evidence of poorer reproductive health in ICSI-conceived men compared to age-matched SC controls, including a subgroup of STF-ICSI-conceived men. There was no correlation in any of the semen parameters between ICSI fathers and sons, including STF-ICSI father-son pairs. ICSI-conceived men compared with SC controls had higher resting diastolic BP and higher homeostasis model assessment for insulin resistance (HOMA-IR), but a similar proportion had insulin resistance. Metabolic parameters of ICSI-conceived men and IVF-conceived controls were comparable. Conclusion: This study is the largest to date and indicates comparable reproductive health of ICSI-conceived men, including men whose fathers had STF, to a similarly aged population-representative cohort of SC men. It shows few metabolic differences between ICSI-conceived men, and IVF-conceived and SC controls.

Use of Assisted Reproductive Technologies (ART) is increasing globally but their impact on long term health remains unclear. Here the authors show that ART-conceived individuals show variation in epigenetic profile at birth that largely resolves by adulthood, with no evidence of an impact on long term outcomes.

Abstract Background Effective interventions are required to prevent the current rapid increase in the prevalence of Type 2 diabetes. Clinical trials of large-scale interventions to prevent Type 2 diabetes are essential but recruitment is challenging and expensive, and there are limited data regarding the most cost-effective and efficient approaches to recruitment. This paper aims to evaluate the cost and effectiveness of a range of promotional strategies used to recruit men to a large Type 2 diabetes prevention trial. Methods An observational study was conducted nested within the Testosterone for the Prevention of Type 2 Diabetes (T4DM) study, a large, multi-centre randomised controlled trial (RCT) of testosterone treatment for the prevention of Type 2 diabetes in men aged 50–74 years at high risk of developing diabetes. Study participation was promoted via mainstream media—television, newspaper and radio; direct marketing using mass mail-outs, publicly displayed posters and attendance at local events; digital platforms, including Facebook and Google; and online promotions by community organisations and businesses. For each strategy, the resulting number of participants and the direct cost involved were recorded. The staff effort required for each strategy was estimated based on feedback from staff. Results Of 19,022 men screened for the study, 1007 (5%) were enrolled. The most effective recruitment strategies were targeted radio advertising (accounting for 42% of participants), television news coverage (20%) and mass mail-outs (17%). Other strategies, including radio news, publicly displayed posters, attendance at local events, newspaper advertising, online promotions and Google and Facebook advertising, each accounted for no more than 4% of enrolled participants. Recruitment promotions cost an average of AU$594 per randomised participant. The most cost-effective paid strategy was mass mail-outs by a government health agency (AU$745 per participant). Other paid strategies were more expensive: mail-out by general practitioners (GPs) (AU$1104 per participant), radio advertising (AU$1081) and newspaper advertising (AU$1941). Conclusion Radio advertising, television news coverage and mass mail-outs by a government health agency were the most effective recruitment strategies. Close monitoring of recruitment outcomes and ongoing enhancement of recruitment activities played a central role in recruitment to this RCT. Trial registration ANZCTR, ID: ACTRN12612000287831. Registered on 12 March 2012.

Abstract Background Children conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood. Early life epigenetic variation may play a role in this process. However little is known about the long-term health of individuals conceived by ART. In a previous study, based on telephone-interviews, we found that young adults conceived by in vitro fertilization (IVF) had significantly more maternal reported atopic respiratory, endocrine, nutritional, and metabolic conditions than non-IVF conceived matched controls. Here we outline the protocol for a follow-up biomedical assessment of this cohort and a questionnaire to obtain information on potential confounders. Methods We are conducting a clinical review of an existing, well characterised cohort comprising 547 IVF-conceived adults and 549 matched controls. We are measuring cardiovascular intermediate phenotypes, metabolic parameters and respiratory function, complemented by epigenome-wide DNA methylation analysis. A pilot study demonstrated the feasibility of our proposed protocol and its acceptability to participants. Participants attend a 2–3 h clinical assessment and complete a study-specific online questionnaire. Measurements include: 1) cardiovascular phenotypes: carotid artery intima-media thickness and distensibility, retinal vascular calibre, resting blood pressure, pulse wave velocity and pulse wave analysis; 2) respiratory function: spirometry, plethysmography, multiple breath washout; 3) auxology: height, weight, waist circumference, bio-impedance. Blood is collected for 4) biomarkers of cardiometabolic profile including inflammatory markers and 5) epigenetic analysis. Discussion Recruitment for this clinical review is challenging as many of the participants have moved to regional, interstate or international locations. Additionally, many female participants are pregnant or breastfeeding, and are therefore ineligible. Nevertheless, comprehensive strategies have been developed to optimize recruitment. Given the increasing use of IVF and related technologies, the potential long-term consequences for risk of common adult diseases is an important clinical and public health issue.

Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated “free” serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20–22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at −80°C, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry. TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = −0.22) and sums of DEHP and DiNP metabolites (r = −0.24) and the sum of the metabolites of the high molecular weight phthalates (r = −0.21) were negatively correlated with TV (all p

In long-time numerical integration of Hamiltonian systems, and especially in molecular dynamics simulation, it is important that the energy is well conserved. For symplectic integrators applied with sufficiently small step size, this is guaranteed by the existence of a modified Hamiltonian that is exactly conserved up to exponentially small terms. This article is concerned with the simplified Takahashi-Imada method, which is a modification of the St?rmer-Verlet method that is as easy to implement but has improved accuracy. This integrator is symmetric and volume-preserving, but no longer symplectic. We study its long-time energy conservation and give theoretical arguments, supported by numerical experiments, which show the possibility of a drift in the energy (linear or like a random walk). With respect to energy conservation, this article provides empirical and theoretical data concerning the importance of using a symplectic integrator. [ABSTRACT FROM AUTHOR]

We show that while Runge-Kutta methods cannot preserve polynomial invariants in general, they can preserve polynomials that are the energy invariant of canonical Hamiltonian systems. [ABSTRACT FROM AUTHOR]