BACKGROUND: Human spermatogenesis is a complex process that transforms spermatogonial stem cells through mitosis and meiosis to spermatozoa. Testosterone is the key regulator of the terminal stages of meiosis, adherence of spermatids to Sertoli cells, and spermiation. Follicle-stimulating hormone (FSH) may be required for early spermatogenesis and is important for maintaining normal spermatogenesis in men. Hormonal contraception suppresses FSH, luteinizing hormone, and intratesticular testosterone concentration, resulting in marked suppression of sperm output.
RESULTS: Clinical trials using testosterone alone or testosterone plus progestin demonstrate that sustained suppression of sperm concentration to ≤1 million/mL is sufficient to prevent pregnancy in the female partner. New agents that target spermatogenesis could use this as a target for contraceptive efficacy while others that block sperm function or transport may require a lower threshold. When sperm concentrations are suppressed to such low levels, measurement of sperm motility and morphology is technically difficult and unnecessary. With current data from fertile and infertile men, it is not possible to establish a lower limit of sperm motility or percent normal morphology that equates to the prevention of conception. New compounds that decrease sperm motility or alter sperm morphology may need to demonstrate a complete absence of sperm motility or altered morphology in all spermatozoa in the ejaculate. Sperm function tests may be useful depending on the mechanism of action of each new compound.
CONCLUSIONS: Monitoring of sperm surrogate markers to ensure effective contraception relies on laboratories experienced in semen analyses. The development of at-home tests to assess sperm parameters has progressed rapidly. Some tests have been assessed in clinical trials and approved by regulatory agencies for at-home use for fertility assessment. However, caution must be exercised in using these tests as many have not been rigorously validated against semen parameters measured in laboratories by trained technologists using standardized tests defined in the World Health Organization Semen Manual.

BACKGROUND: Sperm quality has decreased over the last decades worldwide. It is affected, among others, by season and heat. This study aimed to address the association between ambient temperature and sperm quality by assessing its shape using flexible multivariate models and identifying distinct time-dynamic patterns of temperature change based on unsupervised analysis.
METHODS: A retrospective population-based study has been conducted, including all samples of males attending the Fertility and In-Vitro-Fertilization unit at a single medical center during 2016-2022. Flexible generalized models were fitted to characterize the relations between sperm quality and temperature while accounting for patients characteristics, and to identify temperature levels that correspond with the optimal sperm quality. This information was then used to estimate adjusted slope coefficients at specified time-windows.
RESULTS: In total, 4555 sperm samples were provided by 3229 individuals. Sperm concentration, motility and progressive motility were higher by 8 %, 11 % and 16 %, respectively, during the spring versus the fall season. Furthermore, their quality during early spermatogenesis improved with temperature, until a certain optimum around 23 °C-24 °C. Increasing temperature at later developmental stages was associated with lower sperm concentration and higher motility. Sperm concentration and motility were highest following a period of moderate gradual warming. Motility was higher and sperm concentration was lower, following a period with heatwaves or summer.
CONCLUSIONS: This study assessed temperature role in sperm production quality by considering both average and time-dynamic temperatures. It identified several temperature change patterns over time and stratified the analysis by them. The differences in the relations across stages of spermatogenesis were addressed. Several mechanisms may explain the associations found, including heat-induced apoptosis of the sperm cells, and destruction of sperm cells DNA integrity by over-production of reactive oxygen species. The gradual global warming necessitates exploration of individual response to outdoor temperature in relations to genetic predisposition, lifestyle, and other health characteristics.

The effect of paternal age on fertility remains unclear. This retrospective study aims to examine the impact of male age on semen parameters and the reproductive outcomes of men admitted to an infertility center over a 9-year period. A total of 8046 patients were included in the study. Men were divided into four age groups. The groups were evaluated for semen parameters and reproductive outcome. The 21-30 year group presented lower sperm concentrations in comparison to those aged 31-40 and 41-50, yet shared a similar concentration to those over 50 years of age. Moreover, grades A and B decreased significantly in men aged over 50 years. The highest progressive motility and normozoospermia were observed in the age group 31-40 years while men over 50 years of age had the highest rates of asthenozoospermia and oligoasthenozoospermia. Furthermore, live birth results were reported in 5583 of the patients who underwent intracytoplasmic sperm injection (ICSI) and were found highest between 31-40 years of age. To our knowledge, this is the largest study in Turkey focusing on male age-related semen parameters and ICSI pregnancy outcomes. The study demonstrates that age is a significant factor for semen quality and live birth.

UNASSIGNED: To examine the impact of tobacco smoking on seminal parameters in men with both primary and secondary infertility.
UNASSIGNED: This cross-sectional study analyzed 1938 infertile men from China who were categorized as nonsmokers (n=1,067) and smokers (n=871), with the latter group further divided into moderate smokers (1-10 cigarettes per day) (n=568) and heavy smokers (>10 cigarettes per day) (n=303). We assessed semen volume, concentration, total sperm count, progressive motility, and normal morphology following World Health Organization (WHO 2010) guidelines. A logistic regression model was used to analyze the relationships between smoking and seminal parameters while also controlling for lifestyle factors.
UNASSIGNED: The analysis demonstrated a statistically significant correlation between smoking and adverse seminal parameters in both primary and secondary infertility patients. Specifically, primary infertile men who smoked had a lower semen concentration, with heavy smokers showing a median sperm concentration of 59.2×10^6/ml compared to 68.6×10^6/ml in nonsmokers (P=0.01). The secondary infertile men who smoked exhibited reduced forward sperm motility, with heavy smokers demonstrating a median progressive motility of 44.7%, which was significantly lower than the 48.1% observed in nonsmokers (P=0.04).
UNASSIGNED: Smoking is significantly associated with detrimental effects on seminal parameters in infertile men, thus highlighting the need for cessation programs as part of fertility treatment protocols. Encouraging smoking cessation could substantially improve semen quality and fertility outcomes in this population.

BACKGROUND: Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated.
RESULTS: Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5 nmol and 4.5 nmol PROK2 intracerebroventricularly for 7 days via an osmotic mini pump (1 µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7 days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups.
CONCLUSIONS: The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.

BACKGROUND: The objective of this study was to investigate the relationship between the activity of neutral α-glucosidase in seminal plasma and semen quality and to explore the effect of secretory capability of the epididymis on male fertility.
METHODS: A retrospective analysis of 542 men treated in the Center for Reproductive Medicine and Infertility from February to December 2022, the semen parameters and neutral α-glucosidase were tested and compared among different groups. These 542 men included normozoospermia, oligospermia, asthenospermia, and teratozoospermia.
RESULTS: There was statistical difference in neutral alpha-glucosidase (NAG) level among different groups with different sperm concentration, motility, and morphology (p < 0.001). The NAG activity in seminal plasma was positively correlated with ejaculate volume and sperm concentration; meanwhile, a very weak positive correlation was found between NAG level and sperm motility, sperm morphology, respectively.
CONCLUSIONS: Our results indicated that the secretion of NAG affected the volume, concentration, motility, and morphology of sperm to a certain extent. Given that NAG is a specific and marker enzyme in epididymis, where is the site of sperm maturation, we can conclude that there is a close relationship between NAG and sperm quality. Therefore, seminal plasma NAG has a definite clinical value in helping diagnosis of male infertility.

Often associated with obesity, male infertility represents a widespread condition that challenges the wellbeing of the couple. In this article, we provide a comprehensive and critical analysis of studies exploring the association between obesity and male reproductive function, to evaluate the frequency of this association, and establish the effects of increased body weight on conventional and biofunctional sperm parameters and infertility. In an attempt to find possible molecular markers of infertility in obese male patients, the numerous mechanisms responsible for infertility in overweight/obese patients are reviewed in depth. These include obesity-related functional hypogonadism, insulin resistance, hyperinsulinemia, chronic inflammation, adipokines, irisin, gut hormones, gut microbiome, and sperm transcriptome. According to meta-analytic evidence, excessive body weight negatively influences male reproductive health. This can occurr through a broad array of molecular mechanisms. Some of these are not yet fully understood and need to be further elucidated in the future. A better understanding of the effects of metabolic disorders on spermatogenesis and sperm fertilizing capacity is very useful for identifying new diagnostic markers and designing therapeutic strategies for better clinical management of male infertility.

OBJECTIVE: The Neubauer hemocytometer, as well as the Makler chamber, are devices commonly used in andrology laboratories. The present study aimed to verify if both methods yield comparable results, and whether they can be used interchangeably to determine sperm concentration.
METHODS: Sperm and latex beads concentration measurements were performed with the Neubauer hemocytometer and the Makler chamber. Fixed and proportional biases were estimated, and the method agreement was determined by assessing sperm concentration results with the Bland and Altman plot. The Coefficient of Variation (CV) and relative bias were calculated as an index of precision and accuracy, respectively, by measuring latex beads target concentrations in both chambers.
RESULTS: The Makler chamber systematically overestimated the Neubauer hemocytometer concentration measurements by a mean of -7.99%, with limits of agreement (LOA) between -41% to 25.61% (p<0.001). The fixed bias was found for concentration values inferior to 40 x 106/ml range (p<0.001), but not higher concentration results (p>0.05). Measurements with the Neubauer hemocytometer showed the greatest consistency in the study with the CV ranging from 3.01% to 6.67%; while the CV with the Makler chamber ranged from 8.46% to 25.64%. The relative bias for the Neubauer hemocytometer determinations varied from 0.12% to 8.40%, while for the Makler chamber varied from 7.6% to an overestimation of 38.0%.
CONCLUSIONS: Measurements made with the Makler chamber demonstrated more variability and a higher degree of overestimation. The Makler chamber is a poor substitute to the Neubauer hemocytometer for evaluation of oligozoospermic samples, although both chambers render similar results for highly concentrated samples.

Semen sexing is among one of the most remarkable inventions of the past few decades in the field of reproductive biotechnology. The urge to produce offspring of a desired sex has remained since traditional times. Researchers have tried many methods for accurate semen sexing, but only the flow cytometry method has proved to be effective for commercial utilization. However, there were always concerns about the effects of sexed semen, especially on fertility and the rate of genetic gain. Some concerns were genuine because of factors such as low semen dosage in sexed semen straws and damage to sperm during the sorting process. Various researchers have conducted numerous studies to find out the effect of sexed semen on fertility and, in this article, we reflect on their findings. Initially, there were comparatively much lower conception rates (∼70% of conventional semen) but, with refinement in technology, this gap is bridging and the use of sexed semen will increase over time. Concerning genetic gain with use of sexed semen, a positive effect on rate of genetic progress with the use of sexed semen has been observed based on various simulation studies, although there has been a mild increase in inbreeding.

OBJECTIVE: Does the choice of sperm-counting chamber affect the proportion of samples generating results with an erroneous interpretation?
METHODS: Laboratories in an external quality assurance programme were sent 141 semen samples over a 12-year period and asked to return the sperm concentration and whether or not the result was abnormal. Only those using 5th edition of the World Health Organization manual (WHO5) interpretation criteria were included. Submissions from specialist fertility laboratories were used to calculate assigned values for each sample. Laboratory50 values determined the sperm concentration at which the laboratories reported a majority transition from abnormal to normal interpretations, i.e. the tipping point, which should coincide with the lower reference limit.
RESULTS: The median and range of bias from the assigned values of each sample were determined for the Makler (-3.3%; -88.6% to +332.8%), haemocytometer (10.6%; -93.3% to +645.5%), Kova (+65.3%; -71.7% to +581.8%) and Vetriplast (+72.4%; -100.0% to +709.1) chambers. Laboratory50 values for the Makler (17.3  ×  106/ml), haemocytometer (13.6  ×  106/ml), Kova (10.0  ×  106/ml) and Vetriplast chambers (8.8  ×  106/ml) reflected the under- and overestimation of the chambers and confirmed a shift in the adjusted lower reference limit then used. The proportion of laboratories reporting erroneous interpretations of the four chambers for oligozoospermic samples were 10.9%, 15.1.%, 40.1% and 44.0%, respectively, and rose as the adjusted lower reference limit decreased.
CONCLUSIONS: The between-laboratory and within-sample variation for all the chambers was high and remains a concern. The main impact of an increasing bias of the chambers was a lowering of the laboratory50 tipping point, resulting in an under-reporting of abnormal semen samples.