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Influence of genital heat stress on semen quality in humans
Andrologia
Abstract
The concept that an elevation of testicular temperature results in impairment of spermatogenesis is widely accepted. Here, current knowledge concerning genital heat stress and its consequences in men is reviewed. Duration of sitting during work positively correlates with daytime scrotal temperatures and daytime scrotal temperature negatively correlates with semen quality. However, the assumed negative correlation between duration of sitting and semen quality could not be shown in the available studies. Fertility parameters of professional drivers with long periods of sitting in vehicles were impaired; however, for predominantly affected drivers of vans, trucks or industrial heavy machinery potential confounders have to be considered. Wearing tight fitting compared with loose-fitting underwear is associated with significantly higher scrotal temperatures. However, available observations suggesting a link between tight-fitting underwear or trousers and impaired semen quality are not convincing. Studies addressing professional exposure to high temperatures delivered conflicting results concerning fertility parameters. The postulated negative impact of sauna visits on semen quality is not sufficiently underlined by the available studies. Oligozoospermic men with a varicocele have significantly higher scrotal temperatures than normozoospermic men, and according to several studies varicocelectomy normalises scrotal temperatures. A further link has been reported between fever and deteriorated semen quality. Contraception via genital heat stress has been demonstrated using hot sitting baths or insulating suspensors. However, down-regulation of spermatogenesis is inconsistent and unsafe. On the other hand, scrotal and consecutively testicular cooling is able to improve semen quality.
... Hyperthermia and fever in adult men has long been recognized for its adverse effects on spermatogenesis [28][29][30][31][32] , but to the best of our knowledge this is the first study of long-term male reproductive effects of fetal exposure to fever. This large-scale population-based study did not support the hypothesis of a detrimental effect on male reproductive health by maternal fever during pregnancy, neither in terms of timing, duration, nor temperature and we found no consistent indications of effect modification by concurrent use of medications. ...
... High-grade profession 334 [34] 256 [34] 78 [34] 44 [33] 34 [35] Low grade professional 320 [32] 244 [32] 76 [33] 45 [34] 31 [32] Skilled or unskilled worker 288 [29] 224 [30] 64 [ 1 unit 303 [31] 244 [32] 59 [26] 31 [24] 28 [29] 2+ units 161 [16] 116 [16] 45 [19] 24 [18] 21 [21] Use of antipyretics* during a fever episode, yes n [%] --49 [21] 18 [14] 21 [32] Use of antibiotics** during a fever episode, yes n [%] --23 [10] 9 [7] 14 [14] Use of antipyretics and/or antibiotics --62 [26] 26 [20] 36 [37] *Antipyretics cover all painkillers asked about in the 2 nd interview in DNBC (see www.dnbc.dk) **Antibiotics cover abboticin, calcipen, erycin, erythromycin, imadrax, lucosil, penicillin, pondocillin, primcillin, rocolin, rovamycin, selexid, sulfa, and vepicombin ...
... High-grade profession 334 [34] 256 [34] 78 [34] 44 [33] 34 [35] Low grade professional 320 [32] 244 [32] 76 [33] 45 [34] 31 [32] Skilled or unskilled worker 288 [29] 224 [30] 64 [ 1 unit 303 [31] 244 [32] 59 [26] 31 [24] 28 [29] 2+ units 161 [16] 116 [16] 45 [19] 24 [18] 21 [21] Use of antipyretics* during a fever episode, yes n [%] --49 [21] 18 [14] 21 [32] Use of antibiotics** during a fever episode, yes n [%] --23 [10] 9 [7] 14 [14] Use of antipyretics and/or antibiotics --62 [26] 26 [20] 36 [37] *Antipyretics cover all painkillers asked about in the 2 nd interview in DNBC (see www.dnbc.dk) **Antibiotics cover abboticin, calcipen, erycin, erythromycin, imadrax, lucosil, penicillin, pondocillin, primcillin, rocolin, rovamycin, selexid, sulfa, and vepicombin ...
Background:
Maternal fever during pregnancy has been associated with increased risk of genital malformations, but the implication for long-term reproductive health in the offspring is unknown.
Objectives:
To investigate associations between timing, duration, and temperature of fetal exposure to maternal fever and sons' semen quality, testicular volume, and levels of reproductive hormones in early adulthood. Further, to examine whether concurrent use of antipyretics and/or antibiotics modified the effect.
Materials and methods:
We used the Fetal Programming of Semen Quality cohort consisting of men born to women enrolled in the Danish National Birth Cohort. Self-reported information on maternal fever was collected twice during pregnancy (median 16 and 31 pregnancy weeks) and categorized as any fever during pregnancy, fever during early pregnancy (week 1-15), and fever exclusively during late pregnancy (week 16-42). Semen quality and concentrations of reproductive hormones were measured at a clinical examination at the age of 18.9 years. We used negative binomial regression to examine the associations, adjusting for maternal age at birth, maternal smoking, family occupational status, and precision variables related to semen quality and hormonal levels e.g., abstinence time.
Results:
986 men were included in the study, of which 23% had mothers reporting at least one episode of fever. We found no strong indications of associations between maternal fever during pregnancy and male reproductive health in the young men. Concurrent use of antipyretics and antibiotics did not modify the association.
Discussion:
Strengths include the large sample size, prospectively collected data, and the adjustment for maternal factors during pregnancy and important precision variables. A limitation is the crude self-reported information on maternal fever.
Conclusion:
We found no evidence to support that timing, duration, or temperature of maternal fever during pregnancy have long-term impact on semen characteristics, testicular volume, or level of reproductive hormones in male offspring. This article is protected by copyright. All rights reserved.
... The most commonly identified risk factors for male infertility include aging, stress, smoking, chemotherapy, occupational toxins, environmental pollution, nutrition, and genetics (Aşır et al., 2024). These issues, either separately or in combination, may have an impact on sperm production and contribute to overall male infertility and subfertility ( Jung and Schuppe, 2007). Furthermore, around 30% of cases of male infertility are caused by abnormalities in the sperm (Cavallini, 2006). ...
... [6] Heat stress (HS) caused oxidative stress modifications and an assault on sperm production by eliminating spermatogenic cells and causing Sertoli and Leydig cells to degenerate. [7,8] Sperm dysfunction can be the result of testicular hyperthermia in humans, [9] which can cause sperm cells to undergo apoptosis, interfere with sperm production and lower sperm concentration. [10] The HS that people experience is one of the key factors contributing to infertility around the world. ...
A BSTRACT
Background
Male sterility results from high testicular temperatures, which affect mammalian spermatogenesis. High testicular temperatures affect sperm motility, morphology and fertility according to their magnitude and duration.
Aims
The aim of the current study is to examine the effects of heat-induced oxidative stress and cinnamaldehyde on Wistar rat testicular structure and function.
Settings and Design
The rats used in this experiment were Wistar albino rats.
Materials and Methods
This research has six animals per group. Male Wistar albino rats of 2.5–3 months old and 275–300 g. (I) control, (II) heat stress (HS) in a closed chamber at 41°C for 14 days and (III) HS with cinnamaldehyde (CA) 50 mg/kg body weight for 14 days. (IV) CA alone. After the study, the animals were euthanised, and test samples were taken for sperm count, morphology, haematoxylin and eosin stain for normal cellular morphology, antioxidants and DNA integrity assessments.
Statistical Analysis Used
The data were analysed statistically using one- and two-way ANOVA tests for comparisons between groups.
Results
The stress group had significantly lower sperm counts and poor sperm morphology. The stress group’s antioxidant capacity is much lower than that of the control group. Animals under stress have fragmented DNA. Treatment with cinnamaldehyde increased overall antioxidant capacity and seminal parameters, and rats behaved most like controls.
Conclusion
CA restores malondialdehyde levels, total antioxidant capacity, sperm characteristics and mitigates testicular damage in rats exposed to experimental HS.
... This may be explained by the biological activity of the vaccine, as mentioned above [20]. In addition, spermatogenesis takes 74 days and another 12-21 days to be transported through the epididymis to the ejaculatory ducts [25]. Thus, the specific semen analysis examined may have represented sperm parameters before exposure to the vaccine. ...
Background
Although there are some data regarding the COVID-19 vaccine and in in vitro fertilization (IVF) treatments, its potential impact in terms of serum immunoglobulin G (IgG) levels has not been evaluated prospectively. This study aimed to assess the effect of COVID-19 vaccine and IgG levels on IVF outcomes.
Methods
This observational, cohort study was conducted at a referral IVF unit. Couples undergoing IVF treatment during the COVID-19 vaccination period were recruited from March–April 2021. The study compared 38 women who had received the Pfizer mRNA COVID-19 vaccination to 10 women who had not and were not infected by the virus. We also compared pre- and post-vaccination IVF treatments for 24 women. The relation between serologic titers and IVF treatment outcomes was also assessed.
Results
No significant difference was found between the vaccinated and unvaccinated/uninfected groups regarding the main outcome measures. However, there was a trend toward a higher pregnancy rate for the unvaccinated group (57% vs. 23%, p = 0.078) but no difference in delivery rate (p = 0.236), gestational week (p = 0.537) or birth rate (p = 0.671).
Conclusion
We cautiously state that the COVID-19 mRNA vaccine does not affect fertility outcomes, including fertilization, pregnancy and delivery rates, obstetric outcomes, and semen parameters, regardless of measured IgG levels.
... Other subjects were service holders (6), carpenters (5), policemen (2,) and unemployed (6). Jung A et al also concluded that the fertility parameters of professional drivers with long periods of sitting in vehicles were impaired [17] . Nearly half of the subjects, 24, were found to be subjected to occupational exposure to heat to the scrotum whereas 14 of them were exposed to heavy metals/ dyes/ pesticides. ...
Background: Infertility remains an ongoing reproductive problem and about half of infertile couples have a component of male factor infertility. Male factor infertility is seen as an alteration in sperm concentration and/or motility and/or morphology in sperm analysis. A wide variety of etiological factors are involved in the causation of those sperm abnormalities. This study was designed to determine the association between risk factors and different semen parameter abnormalities. Methodology: A descriptive study was conducted amongst the male partners of infertile couples who presented to the Outpatient Department for infertility evaluation. All the men were advised for semen analysis as a part of routine infertility work-up. Those men who had abnormal semen parameters and consented to the study were enrolled. A detailed interview of each subject was conducted focusing on risk factors causing different semen parameter abnormalities. Analysis of data was conducted to evaluate the presence of risk factors and the association of risk factors to specific sperm abnormalities was determined. Results: A total of 50 subjects with abnormal semen analysis reports were included in the study. The mean age was 32.14 years ± 5.95 years, and the mean BMI was 24.38 ± 2.07 kg/m 2. The mean duration of infertility was 5.94 ± 3.66 years. The median sperm concentration was calculated to be 6.75 million/ml (IQR 3-12). The mean sperm motility was 26.3% (SD ± 19.00). 30% of the subjects had oligozoospermia and 20% had asthenozoospermia whereas 50% had both oligozoospermia and asthenozoospermia. Men with a sedentary lifestyle and cigarette smokers were twice (OR 2.122) and four times (OR 4.133) more likely to have oligozoospermia respectively. Cigarette smokers were nearly seven times (OR 7.171) more likely to have asthenozoospermia. Similarly, driver men and laborer men were almost six times (OR 5.629) and eight times (OR 8.551) more likely to develop asthenozoospermia respectively. However, these observations were not statistically significant. Conclusion: Cigarette smoking is seen to be associated with both oligozoospermia and asthenozoospermia. Driver and laborer men were more likely to have asthenozoospermia. However, further study with a larger sample size is required to analyze the statistical significance of these associations.
... In reviewing scale items at the data analysis phase, we identified that based on updated evidence regarding lifestyle factors related to male infertility, some items required re-categorization as "decoy" and/or relevant fertility risk factors. Specifically, there is ample recent literature to suggest that poor diet and lack of physical exercise are established risk factors for developing male infertility, while the evidence for "frequent" bicycling and use of a laptop is less conclusive (e.g., Benatta et al., 2020;Durairajanayagam, 2018;Gan et al., 2021;Ilacqua et al., 2018;Jung & Schuppe, 2007;Salas-Huetos et al., 2018). For this study, then, we present two sets of analyses: (a) original scale scores and (b) revised scale scores according to our re-classification of scale items as "decoys" or established risk factors (refer to Supplementary Information for re-classified survey items and justification). ...
Background and Aims: Men desire to be actively involved in preconception care. However, health systems do not consistently or proactively engage men and there is little acknowledgement of their needs during this time. The lack of gender-specific service provision in infertility treatment likely contributes to men’s poorer mental wellbeing following infertility diagnosis and infertility treatment. This research sought to understand males’ psychosocial and support needs when diagnosed with male-factor infertility.
Method: Mixed methods design, assessing men who had undergone diagnosis and/or treatment for male-factor infertility in past five years within Australia. Study comprised: 1) online survey (assessing psychological functioning, fertility knowledge, information sources, social support and perception of resources) and 2) semi-structured interviews to further explore participants’ lived experiences of male-factor infertility. Participants were recruited through Andrology clinics, social media, infertility support pages and ANZICA counsellors.
Results: During their infertility journeys, participants mostly received information fertility doctors/nurses and the internet. However, their preferred method of informational knowledge would be through a verified male infertility website. Qualitative data were analysed by reflexive thematic analysis, which resulted in three key themes, each with two sub-themes, summarising pertinent aspects of men’s lived experiences when diagnosed with male-factor infertility (Figure 1). The majority of participants were in later stages of their fertility journey, indicating they felt more prepared to discuss their experiences given most (or all) of the initial-stage emotional and physical intensity of their diagnosis and active treatment had passed.
Conclusion: There is a clear need for in/fertility services to implement proactive support approaches that engage directly with male patients and acknowledge the complexity of lived experiences when receiving a diagnosis of male-factor infertility.
... Infertility is a significant global public health concern, affecting 15% of couples [1], with ∼20%-30% of cases attributed to male factors characterized by reduced sperm quantity and quality [2][3][4]. Previous studies have reported that spermatogenesis is heat vulnerable and high-temperature environments are widely recognized as a critical factor that has adverse effects on male fertility [5][6][7]. Elevated scrotal temperatures arise from a range of factors encompassing lifestyle, occupational, environmental, and pathophysiological origins, with complete avoidance being challenging [8]. ...
Heat stress induces testicular oxidative stress, impairs spermatogenesis, and increases the risk of male infertility. Recent studies have highlighted the antioxidative properties of the Sestrins family in reducing cellular oxidative damage. However, the role of Sestrins (Sestrin1, 2, and 3) in the testicular response to heat stress remains unclear. Here, we found that Sestrin2 and 3 were highly expressed in the testis relative to Sestrin1. Then, the Sestrin2−/− and Sestrin3−/− mice were generated by CRISPR/Cas9 to investigate the role of them on spermatogenesis after heat stress. Our data showed that Sestrin2−/− and Sestrin3−/− mice testes exhibited more severe damage manifested by exacerbated loss of germ cells and higher levels of oxidative stress as compared to wild-type counterparts after heat stress. Notably, Sestrin2−/− and Sestrin3−/− mice underwent a remarkable increase in heat-induced spermatocyte apoptosis than that of controls. Furthermore, the transcriptome landscape of spermatocytes and chromosome spreading showed that loss of Sestrin2 and Sestrin3 exacerbated meiotic failure by compromising DNA double-strand breaks repair after heat stress. Taken together, our work demonstrated a critical protective function of Sestrin2 and Sestrin3 in mitigating the impairments of spermatogenesis against heat stress.
... Numerous studies have shown that a variety of factors, such as fever, using a sauna or steam room, sleeping position, spending a lot of time sitting or driving, using a polyester-lined athletic support, using a laptop on one's lap, an electric blanket, have been reported to negatively affect spermatogenesis (Garolla et al., 2013). In addition, it has been demonstrated that medical diseases such cryptorchidism, varicocele, and acute febrile illnesses raise testicular temperature and inhibit spermatogenesis (Jung & Schuppe, 2007). ...
Male fertility is critical around the world, including in Nigeria, where infertility rates range between 20% and 30%. Male infertility is caused by a variety of factors, including genetics, lifestyle, and environmental pollutants, which frequently involve oxidative stress and reactive oxygen species (ROS). ROS imbalance is linked to idiopathic male infertility, which has no clear cause. Understanding the complexities of these issues is critical for diagnosis and treatment. Internal (endogenous) and external (exogenous) sources generate reactive oxygen species (ROS). External factors include pollutants, ultraviolet (UV) radiation, heavy metals, and smoking. Sources within the body include mitochondria, nicotinamide adenine dinucleotide phosphate oxidase (NAPDH oxidase; NOX) enzymes, and immune cells. Controlled ROS production serves signaling pathways, but imbalances can damage cellular components, leading to cell death. Reactive oxygen species (ROS) negatively affect sperm via both internal and external pathways. External factors such as psychological stress, exercise, heat stress, smoking, and a poor diet increase ROS production. Psychological stress raises norepinephrine and cortisol, intensifying ROS. Exercise, especially vigorous exercise, generates excessive ROS, potentially harming sperm. Heat stress from various sources elevates ROS through hormonal disruptions. Smoking, alcohol, and unhealthy foods also contribute to ROS production, damaging sperm health. Reproductive tract infections and immature spermatozoa, along with conditions like varicocele, leukocytes, inflammation, and cytokines, further exacerbate oxidative damage to sperm internally. In conclusion, oxidative equilibrium is essential for preserving the health of sperm. Male infertility can result from oxidative stress, which drastically reduces the quality of sperm. It has been demonstrated that antioxidant therapy has positive impacts on sperm characteristics and pregnancy outcomes. Maintaining oxidative balance is therefore crucial for male reproductive health, and antioxidant supplementation may be a helpful tactic to enhance sperm quality in situations of male infertility.
... On the one hand, several studies demonstrated that postconception exposure to hot temperatures increases the chance of pregnancy losses (Basu et al., 2016;Bonell et al., 2023;Davenport et al., 2020;Hajdu & Hajdu, 2021aMcElroy et al., 2022;Sexton et al., 2021), leads to shorter gestation and lowers the health of newborns (Andalón et al., 2016;Barreca & Schaller, 2020;Chen et al., 2020;Deschênes et al., 2009;Grace et al., 2015;Hajdu & Hajdu, 2021b;Sun et al., 2019). On the other hand, others have found that heat impairs spermatogenesis and has a negative effect on various sperm parameters (Garolla et al., 2013;Jung & Schuppe, 2007;Kumar & Singh, 2022;Zhang et al., 2015), and related to this, a recent study reported that pre-conception heat stress results in less conception (Hajdu & Hajdu, 2022b). ...
Using data from 32 European countries for nearly 244 million live births between 1969 and 2021, this paper examines the effects of temperatures on birth rates. The results show that exposure to hot days slightly reduces birth rates five to eight months later, while much stronger negative effects are observed nine to ten months after exposure to hot temperatures. Thereafter, a partial recovery is observed, with slightly increased birth rates. This study also shows that the effect of high-humidity hot days is much stronger than that of hot days with low humidity. Besides, the effect of heatwave days has been found to be more severe than that of hot days that are not preceded by other hot days. This study finds that some adaptation to heat might be expected only in the long run.
... However, the presumed negative correlation between sitting duration and semen quality was not shown in the accessible studies. Nevertheless, they mentioned that the fertility parameters of drivers with more extended periods of sitting, mostly vans, trucks, and industrial heavy machinery drivers, were predominantly impaired [50] . Also, a relationship between male work-related heat exposure and time to pregnancy (TTP) was investigated. ...
Generally, automobile vehicles discharge specific contaminants into the surrounding environment during operation, which might affect human and reproductive health. Additionally, a more extended period of sitting while driving is linked with the manifestation of heat in the pelvic region, which might also impact the driver’s semen quality. The data on motor traffic pollution, sitting posture duration while driving, and their impact on reproduction was collected by searching various websites. The data on the effects of traffic-related contamination on motorway tollgate workers indicated an alteration in semen quality parameters to some extent compared to control, i.e., nonexposed to traffic-connected pollution. Still, the data on other male reproductive endpoints are scanty. Some data on the impact of traffic-related air pollution (TRAP) on pregnancy outcomes are accessible based on the studies mostly carried out in women residing close to the main road, which suggests the adverse impact of TRAP on pregnancy outcomes. The comprehensive data on drivers with reverence to professional driving i.e., long duration of sitting while driving and reproductive health, is scanty and needs more studies. The available information suggests that vehicular pollution might affect the semen quality and pregnancy outcome to some extent. At the same time, the impact on the other reproductive endpoints of both sexes is inconsistent, and additional data is needed to conclude these aspects of human reproduction. Further, there is a need to adopt better efficient fuel engines to reduce TRAPs or use alternate technology or fuel to petrol/diesel.
... It is well known that elevated temperature in testes plays a malignant role in spermatogenesis and causes infertility both in animal 38,39 and in human beings. 40 Further, testicular hyperthermia is well known to cause oligospermia. In a study by Kim et al., 41 the effect of pectinase-treated ginseng extract (GINST) on heat stress-induced testicular dysfunction was tested in rats. ...
... In reviewing scale items at the data analysis phase, we identified that based on updated evidence regarding lifestyle factors related to male infertility, some items required re-categorization as "decoy" and/or relevant fertility risk factors. Specifically, there is ample recent literature to suggest that poor diet and lack of physical exercise are established risk factors for developing male infertility, while the evidence for "frequent" bicycling and use of a laptop is less conclusive (e.g., Benatta et al., 2020;Durairajanayagam, 2018;Gan et al., 2021;Ilacqua et al., 2018;Jung & Schuppe, 2007;Salas-Huetos et al., 2018). For this study, then, we present two sets of analyses: (a) original scale scores and (b) revised scale scores according to our re-classification of scale items as "decoys" or established risk factors (refer to Supplementary Information for re-classified survey items and justification). ...
There is limited research exploring men’s experiences of infertility, and fewer previous studies have examined what information and support men desire after being diagnosed specifically with male-factor infertility. We conducted a mixed-methods study utilizing a combined sequential, concurrent design (online survey/semi-structured interviews). Survey outcomes (N =12) were analyzed using quantitative data analysis, while qualitative survey data (N = 5) was analyzed by reflexive thematic analysis. Heterosexual men (>18 years), fluent in English, diagnosed solely with male-factor infertility/sub-fertility, who required assisted reproductive treatment within Australia in the past 5 years were recruited online and through fertility clinics Australia-wide. Most men reported that their information and support needs were only somewhat, slightly or not at all met. Preferred information sources on male infertility were a dedicated online resource, app, or fertility doctor/specialist, while support was preferred from fertility specialists and partners. Three themes were identified from the qualitative analysis about men’s experiences and support needs when diagnosed with male infertility (a) Ultimate threat to masculinity; (b) Holistic care, and (c) the power of words. The information-rich data collected provided valuable insights into men’s experiences of male-factor infertility and important considerations to improve recruitment for future research. A diagnosis of male-factor infertility has the potential to be deeply impactful and difficult to navigate for men. Adequate and holistic information, recognition of emotional impacts, proactive offers of support and sensitive language are needed to improve men’s experiences when undergoing assisted reproductive technology.
... [5,6] Considering COVID-19 with fever symptoms, it is clear that the disease causes male infertility. [7,8] Koç et al [9] studied sperm quality and found negative impacts on percentage of total motility, percentage of progressive motility, and normal sperm morphology. Khalili et al [10] found that COVID-19 patients had degenerated seminiferous tubules and germ cells. ...
Background
Coronavirus disease 2019 (COVID-19) is an infectious disease that has many adverse impacts on many systems including reproduction. The direct effects of COVID-19 on urogenital system are still open to argue. This study aimed to compare testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) hormone levels in COVID-19 infected male individuals with infertility suspicion.
Methods
One hundred five control (healthy) and 105 COVID-19 infected males aged between 20 to 54 years old were enrolled in the study. All patients were either diagnosed with primary or secondary infertility suspicion. The COVID-19 infection was diagnosed via reverse-transcription polymerase chain reaction test. Blood samples from patients were analyzed from the control and COVID-19 group to measure serum testosterone, FSH, LH, and E2 levels. Hormone levels were statistically compared between groups with the Independent T test.
Results
In control and COVID-19 patients, no significance was determined for FSH and LH hormone values. Testosterone hormone were significantly decreased and E2 level was statistically increased in COVID-19 patients compared to that in the control group (P < .001).
Conclusion
COVID-19 is a viral disease that affects organ including gonads. COVID-19 infection decreased testosterone levels and increased E2 levels, which leading to disorders in male and female reproductivity.
... 39 A febrile state (>39°C) for more than 3 days induces genital heat stress leading to the affliction of fertility parameters. 24,40 A schematic presentation of the COVID-19 unfavorable effects on male reproduction is presented in Figure 1. ...
As of 2021, roughly 5 million deaths were linked to SARS-CoV-2 infection based on World Health Organization estimates. The pandemic takes its staggering death toll, severely affecting the healthcare systems and leading to detrimental implications globally. While the severe impact on the respiratory system is well-established, the exact effect on male reproduction is still largely uncharted territory. When it comes to gender, men appear more vulnerable compared to women. Increasing evidence suggests that COVID-19 adversely affects spermatogenesis and hormonal balance in diverse ways. Semen parameters seem to be compromised at least temporarily, while long-term worsening needs to be clarified in studies with extended follow-up. For the time being, no data support the adverse effect of COVID-19 vaccines on a male's reproductive health. In the present article, we examine the available literature and briefly discuss the impact of the virus on reproduction and fertility. We further provide a comprehensive overview of the current status of vaccination and its potential effect on male fertility. Ultimately, we address the need for future well-designed large-scale trials before drawing definite conclusions on the exact impact of the virus on a male's fecundity.
... Nghiên cứu của Bujan và cộng sự cho thấy nhiệt độ bìu tăng ảnh hưởng tiêu cực đến sức khỏe sinh sản nam [16]. Nghiên cứu của Jung và cộng sự đã chỉ ra mối tương quan giữa tăng nhiệt độ bìu và giảm chất lượng tinh dịch ở người [17]. ...
Background: Gynostemma pentaphyllum is a precious medicinal herb used in traditional medicines. Male reproductive dysfunction is caused by many factors, including heat stress. This study aimed to investigate the protective effect of Gynostemma pentaphyllum extract on spermatogenesis in heat stress-induced mice. Materials and Methods: Male mice were exposed at 40°C and treated with Gynostemma pentaphyllum extract at doses of 100, 200, and 400 mg/kg. After 5 weeks of treatment, blood samples were collected to determine the concentration of Testosterone in blood plasma. The histological structure of the seminiferous tubules was investigated through HE histological staining. The spermatogenesis progress was assessed using the Johnson scoring system. Results: Heat stress exposed at 40°C for 5 weeks has strongly reduced the concentration of testosterone in blood plasma as well as spermatogenesis in the lumen of the seminiferous tubules of testicular tissue. Heat stress-induced mice treated with oral administration of Gynostemma pentaphyllum extract significantly improved blood testosterone levels. Histological analysis and Johnson scoring show that the Gynostemma pentaphyllum extract significantly improved the spermatogenesis process in stress-induced mice that received the extract. Conclusions: Gynostemma pentaphyllum extract attenuates the impact of heat stress on spermatogenesis in male mice by improving blood testosterone levels and spermatogenesis in the seminiferous tubules. Key words: Gynostemma pentaphyllum, herbs, heat stress, spermatogenesis.
... A 1 • C difference could affect spermatogenesis. Scrotal temperature is increased by the duration of a sedentary posture, professional driving, sitting with portable computers and balancing the computer on one lap, sitting on heated floors, sitting on a heated car seat, tight-fitting underwear, varicocele, fever episodes, and genital heat exposure in a water bath [45]. ...
Purpose:
Male infertility is partially caused by an inappropriate lifestyle and comorbidities. In this study, we analyzed the prevalence of these factors and the effects of lifestyle modifications as part of male preconception care.
Methods:
Four hundred and two male partners of couples seeking conception with abnormal parameters upon the first semen analysis were enrolled. They were advised to modify their inappropriate lifestyle as male preconception care. Afterward, their general and male reproductive health was examined. Semen quality was compared before and after the promotion.
Results:
Smoking, chronic alcohol use, and genital heat stress were found in 22.6%, 47.0%, and 75.1% of patients, respectively. Palpable varicoceles, hypogonadism, obesity (body mass index ≧30 kg/m2), hypertension, zinc deficiency, hyperlipidemia, liver dysfunction, and diabetes mellitus were found in 25.9%, 17.0%, 7.0%, 14.9%, 16.2%, 37.0%, 26.9% and 3.4% of the participants, respectively; 98.8% of the patients had at least one factor. After the promotion, semen parameters and sperm DNA fragmentation were improved significantly. Improvement was found in those with palpable varicocele or hypogonadism but not in those with night work shift, abstinence (>3 days), erectile dysfunction, hypertension, obesity, zinc deficiency, or diabetes mellitus.
Conclusions:
Comorbidities and inappropriate lifestyle choices were common among men with infertility. The promotion of lifestyle modifications as part of male preconception care could improve semen quality without urologic intervention.
... This finding might imply the possibility of higher success rate in infertility treatment during winter and fall. In some studies, investigators reported no statistically significant seasonal changes in sperm morphology (22,23). ...
Background: Effect of seasonal variations in human fertility has been intensively researched; some studies acknowledge influences of seasonal changes on natural conception while others cannot confirm them. The aim of this study was to assess the presence of a possible Seasonal pattern in the functional parameters of Semen samples.Materials and Methods: This study was carried out on 335 Semen samples that were collected and analyzed according to the average highest temperature of the Normo-spermic men between January 2019 and December 2 014 at the Fertility Center in Al- Sadr medical city. Najaf Iraq.Results: ALL Semen Parameters displayed trends opposite to average highest temperature variations. Semen volume, sperm concentration sperm motility and normal sperm morphology were significantly lower (p<0.05) in summer than other seasons of the red year: Semen volume sperm concentra and normal sperm morphology was found to be statistically significantly higher in the winter (p<0.05). The percentage of sperm motility was a significantly (p<0.05) is higher in spring The highest values of Semen volume sperm concentration and sperm morphology was recorded in January and February, while a higher sperm motility was found during the march any of the year.Conclusion: We observed that was significant effect of season on the semen parameters. Highest environment temperature may be a determining factor for the seasonal variations in semen quality.
... Jung A et al also concluded that the fertility parameters of professionals with exposure to high temperatures and professional drivers with long periods of sitting in vehicles were found to be impaired. [16] It was also observed in this study that the presence of past medical history like diabetes mellitus and hypertension was strongly associated with the subjects with abnormal semen parameters. However, the association of specific diseases with semen abnormality could not be analyzed due to the small sample size. ...
Background: Infertility is a global problem. Male factors are estimated to be the cause of up to 50% of infertility cases. A variety of identifiable and reversible etiological factors are involved in male factor infertility. This study aimed to compare the risk factors in men who have abnormal semen parameters with those with normal parameters. Methodology: This was a case-control study. The male partners of the infertile couples presenting for infertility evaluation were advised for semen analysis and based on the report they were divided into control (normal parameters) and case (abnormal parameters) groups. A detailed interview of each subject was conducted focusing on risk factors causing different semen parameter abnormalities and the risk factors in both groups were compared. Results: There were 50 subjects in each group. The mean age was 31.02 ± 5.183 years and the mean BMI was 24.824 ± 2.438 kg/m2. The mean duration of infertility for those in the case group was significantly higher (p-value 0.006). Mean sperm concentration and sperm motility were 33.492 ± 30.306 million/ml and 38.1% ± 18.893 respectively. 40 subjects had oligozoospermia and 36 had asthenozoospermia. Age (OR1.464), the habit of cigarette smoking (OR 37.946), and the presence of past medical conditions (0R 534.82) were significantly associated with abnormal semen parameters. Service-holder men were significantly less likely to develop semen abnormalities (OR 0.087). Conclusion: Age, cigarette smoking, and presence of past medical history are associated with abnormal semen parameters thus contributing to male factor infertility. Key words: male infertility, risk factors, oligozoospermia, asthenozoospermia.
... As far as radiation is concerned, it should be noted that radiation therapy, used in cancer treatment, has a negative impact on the quality of semen [119]. Another element that disrupts normal semen production are high temperatures and overheating of testicles, which may occur during long car rides, stays in the sauna, wearing uncomfortable underwear, or due to a sedentary lifestyle [120]. In their long-term study performed in the Chinese population, Zhou et al. showed that both too high and too low ambient temperatures have an effect on the quality of semen, with the optimum temperature quoted at 13 degrees Celsius [121]. ...
Infertility is a problem that affects millions of couples around the world. It is known as a disease of couples, not individuals, which makes diagnosis difficult and treatment unclear. Male infertility can have many causes, from mechanical ones to abnormal spermatogenesis or spermiogenesis. Semen quality is determined by a number of factors, including those dependent on men themselves, with the number of infertile men growing every year. These include, e.g., diet, physical activity, sleep quality, stress, among many others. As these factors co-exist with insulin resistance, which is a disease closely related to lifestyle, it has been singled out in the study due to its role in affecting semen quality. In order to examine connections between lifestyle, insulin resistance, and semen quality, a review of literature published from 1989 to 2020 in the following databases PubMed/Medline, EMBASE (Elsevier), Scopus, Web of Science, and Google Scholar was performed. Hence, semen quality, environment, and insulin resistance are interrelated, thus it is difficult to indicate which aspect is the cause and which is the effect in a particular relationship and the nature of possible correlations. Since the influence of lifestyle on semen quality has been extensively studied, it is recommended that more thorough research be done on the relationship between insulin resistance and semen quality, comparing the semen quality of men with and without insulin resistance.
... In vitro experiments showed that the treatment of human peripheral blood mononuclear macrophages with SARS-CoV spike protein (S protein) could lead to the activation of the mononuclear macrophages and induce the secretion of cytokines and chemokines such as IL-6 and IL-8 [133]. This activation may be another important reason for severe orchitis caused by SARS-CoV, in addition to the decreased sperm motility caused by vasculitis and fever and the direct entry of SARS-CoV through ACE2 receptors expressed by Leydig cells [134,135]. ...
The mononuclear phagocytic system (MPS) is the primary innate immune cell group in male reproductive tissues, maintaining the balance of pro-inflammatory and immune tolerance. This article aims to outline the role of mononuclear macrophages in the immune balance of the testes and epididymis, and to understand the inner immune regulation mechanism. A review of pertinent publications was performed using the PubMed and Google Scholar databases on all articles published prior to January 2021. Search terms were based on the following keywords: ‘MPS’, ‘mononuclear phagocytes’, ‘testes’, ‘epididymis’, ‘macrophage’, ‘Mφ’, ‘dendritic cell’, ‘DC’, ‘TLR’, ‘immune’, ‘inflammation’, and ‘polarization’. Additionally, reference lists of primary and review articles were reviewed for other publications of relevance. This review concluded that MPS exhibits a precise balance in the male reproductive system. In the testes, MPS cells are mainly suppressed subtypes (M2 and cDC2) under physiological conditions, which maintain the local immune tolerance. Under pathological conditions, MPS cells will transform into M1 and cDC1, producing various cytokines, and will activate T cell specific immunity as defense to foreign pathogens or self-antigens. In the epididymis, MPS cells vary in the different segments, which express immune tolerance in the caput and pro-inflammatory condition in the cauda. Collectively, MPS is the control point for maintaining the immune tolerance of the testes and epididymis as well as for eliminating pathogens.
... Esto evidencia la influencia de la COVID-19 en las hormonas sexuales masculinas y alerta sobre la necesidad de la evaluación de la función gonadal en pacientes recuperados de la infección por SARS-CoV-2, especialmente aquellos en edad reproductiva. (35) Por otra parte, se reconoce que la fiebre puede alterar la espermatogénesis y disminuir la fertilidad masculina, (36) lo que lleva a suponer que por la COVID-19, en la que este síntoma está presente en la mayoría de los pacientes, se pudiera afectar la función testicular por esta vía. Sobre la base de estos argumentos y de todo lo previamente comentado, se asume que es posible que los efectos reproductivos a causa de la infección pudieran estar presentes, no obstante, hasta el momento, no han sido reportados. ...
Introducción:
La pandemia desatada a partir de la rápida expansión del coronavirus SARS-CoV-2 y su alta contagiosidad y la letalidad de la enfermedad COVID-19, que de él resulta, ha tenido un profundo impacto en todas las esferas de la existencia humana, entre ellas, las relacionadas con la salud sexual y reproductiva.
Objetivo:
Identificar los efectos de la COVID-19 en la salud sexual y reproductiva en tiempos de pandemia.
Métodos:
Se revisaron las bases de datos electrónicas, Google Scholar, Pubmed central, LILACS, BIREME, SciELO Regional, a las cuales se accedieron por medio del buscador web de Google, y se revisó, además, el portal de Infomed. Se identificaron 94 fuentes bibliográficas, de las cuales se excluyeron 45.
Conclusiones:
Los datos sobre el impacto de la COVID-19 en la salud sexual y reproductiva son escasos y aún existen cuestionamientos no esclarecidos en su totalidad. La evidencia sobre la transmisión por semen o heces es contradictoria y no parece transmitirse por las secreciones vaginales, pero la saliva o la intimidad sexual pueden ser fuente de contagio, por lo que se recomienda la necesidad de mantener una conducta sexual responsable. Existe una posibilidad teórica de daño testicular y posible infertilidad después de la infección por SARS-COV-2, para lo cual se necesitan más estudios. La información sobre su posible efecto en el aparato reproductor femenino es insuficiente.
... Although the etiology behind the reduced sperm parameters is not completely clear, several possible factors have been suggested as causes. Some studies found that an elevated BMI can impair spermatogenesis by causing an increase in scrotal temperature 30,31 , thus leading to impaired semen quality 32 . Other studies also reported that obesity is associated with increased oxidative stress 33,34 , an ROS content most likely higher than the usual metabolic rates required to maintain normal biological processes and an increased level of stress in the local testicular environment. ...
... This finding might imply the possibility of higher success rate in infertility treatment during winter and fall. In some studies, investigators reported no statistically significant seasonal changes in sperm morphology (22,23). ...
Background: Effect of seasonal variations in human fertility has been intensively researched; some studies acknowledge influences of seasonal changes on natural conception while others cannot confirm them. The aim of this study was to assess the presence of a possible Seasonal pattern in the functional parameters of Semen samples.
Purpose of review
The increasing rate of obesity is having an adverse impact on male reproduction.
Recent findings
The negative effect of reactive oxygen species on male reproductive tissues and the age of onset of obesity are new areas of research on male infertility.
Summary
This review highlights how obesity impairs male reproduction through complex mechanisms, including metabolic syndrome, lipotoxicity, sexual dysfunction, hormonal and adipokine alterations as well as epigenetic changes, and how new management strategies may improve the reproductive health of men throughout life.
Testicular cancer (TC) leads to infertility through a multifactorial pattern including intrinsic testicular damage, systemic effects, endocrine disruption, possible autoimmune effects, and possible congenital abnormalities in the maturation of the testis. Additionally, the long-term impact of treatment modalities on fertility and hormonal profile is related to patient’s age, as well as the type and intensity of the oncological treatment. Moreover, the treatment protocols for TC have several associated gonadotoxic and sexual dysfunction risks and may lead to decreased fertility and subsequent negative impact on patients’ quality of life. Sperm cryopreservation is the mainstay of the fertility preservation in TC patients and should be advised to all patients in reproductive age before cancer treatment. Clinicians should be aware of the treatment consequences and the different therapeutic options. In this chapter, we will go through the details of the most relevant mechanisms that link TC with male infertility.
Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce high-quality semen following varicocele treatment. Advising varicocelectomy prior to sperm retrieval in a reproductive program is still debated. This study reviewed the impact of varicocele repair on male infertility using several factors. A literature search was conducted using Scopus, PubMed, Embase, the Wiley Online Library, and Cochrane databases. Sperm concentration, sperm progression, overall sperm motility, sperm morphology, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were also compared. Outcomes were compared between those who received treatment for varicocele and those who did not. The data from the pooled analysis were presented as standardized mean difference (SMD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I ² . Additionally, we conducted analyses for publication bias, sensitivity, and subgroup analysis as appropriate. Nine studies were included after screening relevant literature. Statistical analysis revealed a significant improvement in sperm concentration (SMD: 1.81, 95% CI: 0.84–2.77, P < 0.001), progressive sperm motility (SMD: 4.28, 95% CI: 2.34–6.22, P < 0.001), and sperm morphology (SMD: 3.59, 95% CI: 2.27–4.92, P < 0.001). Total sperm motility showed no significant difference following varicocele repair (SMD: 0.81, 95% CI: −0.61–2.22, P = 0.26). No significant differences were seen in serum FSH (SMD: 0.01, 95% CI: −0.16–0.19, P = 0.87) and LH (SMD: 0.19, 95% CI: −0.01–0.40, P = 0.07) levels as well. This study supports varicocele repair in infertile men with clinical varicocele, as reflected by the improvement in sperm parameters after varicocelectomy compared with no treatment. There were no significant improvements in serum FSH and LH levels.
Introduction. Current evidence suggests that management of any grade of varicocele can improve male fertility. However, diagnosis of grade 1 varicocele in infertile men without the use of scrotal Doppler ultrasound may cause overtreatment.
Objective. To study the comparability and accuracy of the visual palpatory examination method with the scrotal Doppler ultrasound data for the diagnosis of varicocele.
Material & methods. Between November 2005 to January 2022, 2871 patients diagnosed with varicocele and infertility who underwent microsurgical varicocelectomy by inguinal access were examined at RSSPMCU. The average age of the patients was 30.16 ± 0.09 (18 – 60) years. Of the 2871 patients, 2592 (90.3%) were diagnosed by physical examination, and 279 (9.7%) patients underwent additional scrotal Dopper ultrasound.
Results. After Doppler scrotal imaging was introduced into practice, the proportion of patients with bilateral varicocele increased from 32.2% to 61.6% (p < 0.01). The proportion of patients with right-sided varicocele also increased significantly. Experienced physicians during physical examination of infertility patients did not diagnose grade 1 varicocele in 4.3%.
Conclusions. The implementation of scrotal Doppler ultrasound for the diagnosis of male infertility improved the detection of grade 1 varicocele and bilateral varicocele. In turn, this contributed to earlier elimination of the male factor of infertility in this contingent of patients.
Balneoterapi: Dünyada ve Türkiye’deki Durum Nalan SEZGİN Balneoterapide Su ve Gazların Özellikleri Esra TOPÇU Balneoterapinin Vücut Sistemleri Üzerine Etkisi Şahide Eda ARTUÇ Balneoterapi Etki Mekanizmaları Gizem KILINÇ KAMACI Balneoterapi Yöntemleri Uğur ERTEM Balneoterapı Kontraendıkasyonları ve Endikasyonları Merve KARAKAŞ Balneoterapi Yan Etkileri Mazlum Serdar AKALTUN Döne CANSU Romatolojik Hastalıkların ve Kas İskelet Sistemi Hastalıklarının Tedavisinde Balneoterapi Fatih BAYGUTALP Obezite Rehabilitasyonunda Balneoterapi Gülseren DEMİR KARAKILIÇ Nörolojik Hastalıklarda Balneoterapi Ezgi AKYILDIZ TEZCAN Türkiye’deki Balneoterapi Uygulama Merkezleri ve Özellikleri Bengü TÜREMENOĞULLARI Hidroterapinin Vücut Sistemlerine Etkisi Yunus Emre DOĞAN Rehabilitasyon Havuzu İçin Gerekli Özellikler Hatice CEYLAN Su İçi Değerlendirme Yöntemleri Elif TEKİN Hidroterapi Uygulama ve Egzersiz Yöntemleri Ayşe GÜLEÇ Ümmü Habibe SARI Su İçi Duyu Bütünleme Tedavisi Vildan ÖZTÜRK GÜLTEKİN Hidroterapi Endikasyonları ve Kontrendikasyonları Gülşah ÇELİK Sağlık Turizminde Balneoterapi ve Hidroterapi Musa POLAT
Although many transgender and gender-diverse (TGD) people express a desire to become parents, providing quality counseling that encompasses patients' short-term and long-term fertility options often represents a challenge for health care professionals. Fertility care (from preservation to restoration or assisted reproduction or both) has a low uptake in the TGD population, with barriers including financial cost, concerns regarding health care professionals’ biases, and patient misconceptions or lack of awareness of fertility outcomes. Fertility care is particularly important for the TGD population, because gender-affirming hormone therapy can negatively affect fertility. Despite this importance, existing guidelines and research on this subject are limited. This article summarizes the currently available fertility care options for TGD patients and provides our clinical opinion on their best provision. We highlight that it is essential for health care professionals to provide TGD patients with holistic counseling to facilitate informed decision making about their reproductive health before initiating gender-affirming therapy. Fertility counseling should outline the options available for the patient, keeping their needs and preferences at the center of the conversation while advising on the associated risks and financial costs.
Background
Due to global warming seasonal heat stress is an increasing problem in temperate zones. Heat stress not only decreases fertility in females, but can also be detrimental to male fertility.
Objectives
We studied the effects of natural summer heat stress during spermatogenesis in Holstein bulls on semen quality parameters and on fertilization performance in vitro and possible intergenerational transmission of effects on the next male generation.
Materials and Methods
Semen samples from young Holstein breeding bulls, referred to as F0 founders during this study, were collected during summer (F0 “summer” semen) and the following winter (F0 “winter” semen). Parameters such as ejaculate volume, sperm density, motility, thermoresistance, and in vitro blastocyst rates from these F0 semen samples were determined. In addition, after generation of offspring by artificial insemination, semen samples from F1 male offspring were collected and tested for the same quality and performance parameters to capture intergenerational effects. F1 bulls were raised together under identical conditions and semen was collected at about 1 year after birth.
Results
The data showed that in vitro blastocyst rates of F0 “summer” semen samples were lower compared with “winter” semen, whereas blastocyst rates of F1 semen samples did not show significant differences. However, whereas F0 semen samples did not indicate significantly different quality parameters we found that motility of F1 semen samples showed significant differences with higher values when collected from bulls generated with F0 “winter” semen.
Discussion and Conclusion
From our data, we conclude that (i) natural summer heat stress during spermatogenesis can affect in vitro fertility parameters and (ii) the observed effects on sperm motility of F1 semen samples suggest intergenerational paternal transmission.
ZUSAMMENFASSUNG
Chronisch-entzündliche Systemerkrankungen wie die rheumatoide Arthritis und die zu ihrer Behandlung eingesetzten Pharmaka können die reproduktive Gesundheit des Mannes beeinträchtigen. Mögliche Angriffspunkte sind endokrine Regulationsmechanismen der Hypothalamus-Hypophysen-Gonadenachse, Spermatogenese, Nebenhodenfunktion und Spermienausreifung sowie Erektionsfähigkeit und Samentransport. Ausprägung und Reversibilität der Störungen hängen vom Alter bei Erstmanifestation, der Dauer und dem Schweregrad der Grunderkrankung ab. Unter den zur Immunsuppression eingesetzten Medikamenten ist insbesondere die Gonadotoxizität von Cyclophosphamid zu beachten, auch Sulfasalazin und Sirolimus beeinträchtigen die Ejakulatqualität. Für zahlreiche weitere synthetische und biologische DMARD wird der Evidenzgrad verfügbarer Studien als gering eingestuft bzw. liegen noch keine Daten vor. Bei Kinderwunsch ist eine frühzeitige interdisziplinäre Paar-Betreuung zu empfehlen. Hierzu gehört eine umfassende andrologische Diagnostik, um die Ursachen bzw. Kofaktoren einer Fertilitätsstörung identifizieren und den möglichen Einfluss von Grunderkrankung und Therapiemaßnahmen einordnen zu können. Besteht das Risiko eines Verlustes der Zeugungsfähigkeit, muss auf die Möglichkeit der Kryokonservierung von Spermien hingewiesen werden.
About 30–60% of men with impaired fertility suffer from idiopathic infertility for which there are no rational therapeutic approaches. Nevertheless, numerous pharmaceuticals and procedures have been and are still being used, often over long periods of time and frequently in combination or in sequence, which are summarized as empirical therapy. Here, the postulate of evidence-based medicine for randomized controlled trials proves to be particularly important, and it is according to these strict standards that the various therapeutic procedures are critically evaluated in this chapter. While results in individual studies are often promising, further evaluation in meta-analyses is usually less clear. In summary, none of these drugs or procedures is evidence-based and fail to be recommended in guidelines for male infertility.
The male gonads, the testes, fulfill two essential functions. They are the site of spermatogenesis. The male gametes, the sperm, are produced here. As important is their second function as an endocrine gland that synthesizes androgens. Androgens are necessary for the formation of the typical male phenotype. The male gonad develops during the embryonic phase when the SRY gene is expressed in sex differentiation and a testosterone signal occurs.
Testicular tissue is divided into two main compartments: the seminiferous tubules, which are surrounded by peristaltically active peritubular cells, and house the germinal epithelium where the germ cells differentiate through meiosis into haploidization to finally form spermatozoa. The second compartment consists of the interstitium, containing the Leydig cells, which synthesize steroids and produce androgens. In immunological terms, the further differentiated germ cells are protected by the blood–testis barrier, which is formed by the Sertoli cells. The Sertoli cells also provide the niche of spermatogonial stem cells which are unipotent adult stem cells and drive spermatogenesis lifelong after puberty onset. The complex processes of germ cell maturation are regulated by numerous factors, including cytokines, transcriptional and growth factors, but especially by endocrine, paracrine, and autocrine signals.
The endocrine function is part of the hypothalamic-pituitary-gonadal axis. Numerous hormones and receptors act along this axis in a balanced feedback mechanism. Primarily, the system is driven by kisspeptin and pulsatile GnRH controlling the secretion of the pituitary gonadotropins LH and FSH, which in turn induce effects on the testes. LH stimulates the production of testosterone, whilst FSH acts on Sertoli cells and provokes an inhibin response. Testosterone, which is present in the testes in much higher concentrations than in the serum, and inhibin in turn regulate gonadotropin secretion in negative feedback, resulting in an endocrine control loop along the hypothalamic-pituitary-gonadal axis. FSH and androgen action are essential for quantitatively and qualitatively complete spermatogenesis.
Testosterone and its various metabolites, especially dihydrotestosterone and estradiol, are necessary for the normal male development of numerous target organs, including bone metabolism, muscles, hair and beard growth, vocal register, fat distribution, and certain brain functions.
Disorders of testicular function can have various causes, such as genetic or disease-related. Such disorders lead to prenatal disorders of sex differentiation and postnatally to further pathological consequences such as infertility or hypogonadism, which are associated with numerous specifically male diseases.
The ever-increasing number of chemicals to which humans are exposed, together with a recognition that some of them are potentially harmful to the male reproductive system, have driven the development of male reproductive toxicology. This was given a boost in 1992 when a 50% decline in sperm counts over the preceding 50 years was reported (Carlsen et al., Br Med J 305:609–613, 1992), stimulating a huge amount of research into adverse effects on the male reproductive system. Somewhat contentious at the time, the claim has nevertheless been supported by similar, subsequent research (Levine et al., Hum Reprod Update 23:646–659, 2017) that was specifically designed to avoid the problems with the earlier study. Even so, no clear cause for the decline has yet been established. In general, adverse effects on the reproductive system have been found experimentally with a wide range of chemicals but relatively rarely under conditions comparable to human exposure. Population-wide monitoring bears this out with only very small effects on reproductive parameters detectable. The nematocide dibromochloropropane is the classic example of an industrial compound that affects the male reproductive system but there is little evidence that many other toxic agents (e.g. metals, complex organochlorine compounds, alcohol, electromagnetic radiation, heat) have comparable effects at normal exposure and adult susceptibility levels. Certain other agents, particularly smoking and ionising radiation, only show limited heritable effects under certain (usually chronic) exposures. The principal risk to sperm production is from anti-cancer therapies, although the available (albeit limited) evidence indicates no heritable effects, perhaps because the exposures are high dose and acute or sub-chronic. Nevertheless, there is considerable concern that unknown factors in the environment, possibly with endocrine disrupting characteristics, are capable of inducing a range of effects sometimes now grouped together as testicular dysgenesis syndrome. Although there is abundant experimental and environmental evidence that a wide range of specific toxins, especially endocrine-disrupting compounds, can induce such effects, epidemiological evidence in humans is mixed (Rodprasert et al., Front Endocrinol 12:706532, 2021). Consequently, the current legislative framework for regulating exposures that could harm the male reproductive system, has not substantively altered in recent years: with the one exception that guidelines have been introduced for the testing of endocrine disruptors. This is also because the roots of male reproductive toxicity in humans are still only poorly understood. Exciting developments over the last decade however, may be pointing the way towards a better understanding of the mechanisms involved.
Sperm quality can be easily influenced by living environmental and occupational factors. This study aimed to discover potential semen quality related living environmental and occupational factors, expand knowledge of risk factors for semen quality, strengthen men's awareness of protecting their own fertility and assist the clinicians to judge the patient’s fertility. 465 men without obese or underweight (18.5 < BMI < 28.5 kg/m²), long-term medical history and history of drug use, were recruited between June 2020 to July 2021, they are in reproductive age (25 < age < 45 years). We have collected their semen analysis results and clinical information. Logistic regression was applied to evaluate the association of semen quality with different factors. We found that living environment close to high voltage line (283.4 × 10⁶/ml vs 219.8 × 10⁶/ml, Cohen d = 0.116, P = 0.030) and substation (309.1 × 10⁶/ml vs 222.4 × 10⁶/ml, Cohen d = 0.085, P = 0.015) will influence sperm count. Experienced decoration in the past 6 months was a significant factor to sperm count (194.2 × 10⁶/ml vs 261.0 × 10⁶/ml, Cohen d = 0.120, P = 0.025). Living close to chemical plant will affect semen PH (7.5 vs 7.2, Cohen d = 0.181, P = 0.001). Domicile close to a power distribution room will affect progressive sperm motility (37.0% vs 34.0%, F = 4.773, Cohen d = 0.033, P = 0.030). Using computers will affect both progressive motility sperm (36.0% vs 28.1%, t = 2.762, Cohen d = 0.033, P = 0.006) and sperm total motility (57.0% vs 41.0%, Cohen d = 0.178, P = 0.009). After adjust for potential confounding factors (age and BMI), our regression model reveals that living close to high voltage line is a risk factor for sperm concentration (Adjusted OR 4.03, 95% CI 1.15–14.18, R² = 0.048, P = 0.030), living close to Chemical plants is a protective factor for sperm concentration (Adjusted OR 0.15, 95% CI 0.05–0.46, R² = 0.048, P = 0.001) and total sperm count (Adjusted OR 0.36, 95% CI 0.13–0.99, R² = 0.026, P = 0.049). Time spends on computer will affect sperm total motility (Adjusted OR 2.29, 95% CI 1.11–4.73, R² = 0.041, P = 0.025). Sum up, our results suggested that computer using, living and working surroundings (voltage line, substation and chemical plants, transformer room), and housing decoration may association with low semen quality. Suggesting that some easily ignored factors may affect male reproductive ability. Couples trying to become pregnant should try to avoid exposure to associated risk factors. The specific mechanism of risk factors affecting male reproductive ability remains to be elucidated.
Background: One of the most important factors in the development of infertility is oxidative damagewhich is mentioned by free radicals. N-acetylcysteine (NAC) is an antioxidant compound that is able to recover free radicals preventing tissue damage as well as protecting the sperm. This study aimed to summarize the data from the clinical trials in relation to the effects of NAC on oxidative stress parameters, sperm count, motility, and morphology of the sperms in the infertile men. Materials and Methods: By searching in the scientific databases of PubMed, Google Scholar, Science Direct, Scopus, and Web of Science using the N-Acetyl-L-cysteine, NAC, Infertility, Sterility, Sub-fertility keywords, articles released between in 1990-2018 were extracted. Only clinical trials were studied and other types including cross-sectional, prospective, retrospective, overview, etc were excluded. Therefore, the inclusion criteria for this study were considered N-acetylcysteine supplementation. Result: NAC, as part of glutathione plays a role in restoring reserves and increasing antioxidant activity and due to its sulfidryl group it has the ability to clear free radicals by reacting with reactive oxygen species. On the other hand, increasing the production of active oxygen species due to the imbalance between peroxide and antioxidant substances on the sperm plasma membrane could have a negative effect on sperm performance. Conclusion: In most studies, the positive effects of NAC supplementation on sperm parameters, antioxidant capacity, and antioxidant enzymes have been proven, but due to the shortage of studies, more trials are needed.
Background: Conventional remediation techniques involving male fertility include hormonal therapy, in vitro fertilization and surgery. However, the use of natural products continues to be a popular option. Emerging new products that have not been well investigated is the use of Mucuna pruriens seed powder. Aim: This study aimed at determining the efficacy and safety of Mucuna pruriens (MP) seed powder on the male fertility using normal animal models. Methodology: Four groups of seven (7) male Sprague-Dawley rats were used. Groups comprised Control (distilled water), Low dose (500 mg/kg b.wt MP), Medium dose (1000 mg/kg b.wt MP) and high dose (2000 mg/kg b.wt MP). Test groups were administered aqueous crude extract of MP by gavage over 90 days. Upon sacrifice, the following assays were performed: FSH, testosterone, oestrogen, PSA, semen analyses, histology of reproductive organs, and general haematological and biochemical analyses. Results: FSH increased, whilst oestrogen decreased, across groups: however, it was not statistically significant between groups. Although testosterone increases were not statistically significant, increases were dose-dependant. Sperm count increased significantly between the Control and Medium dose groups (p
Male infertility is a commonly encountered pathology that is estimated to be a contributory factor in approximately 50% of couples seeking recourse to assisted reproductive technologies. Upon clinical presentation, such males are commonly subjected to conventional diagnostic andrological practices that rely on descriptive criteria to define their fertility based on the number of morphologically normal, motile spermatozoa encountered within their ejaculate. Despite the virtual ubiquitous adoption of such diagnostic practices, they are not without their limitations and accordingly, there is now increasing awareness of the importance of assessing sperm quality in order to more accurately predict a male’s fertility status. This realization raises the important question of which characteristics signify a high-quality, fertilization competent sperm cell. In this review, we reflect on recent advances in our mechanistic understanding of sperm biology and function, which are contributing to a growing armory of innovative approaches to diagnose and treat male infertility. In particular we review progress toward the implementation of precision medicine; the robust clinical adoption of which in the setting of fertility, currently lags well behind that of other fields of medicine. Despite this, research shows that the application of advanced technology platforms such as whole exome sequencing and proteomic analyses hold considerable promise in optimizing outcomes for the management of male infertility by uncovering and expanding our inventory of candidate infertility biomarkers, as well as those associated with recurrent pregnancy loss. Similarly, the development of advanced imaging technologies in tandem with machine learning artificial intelligence are poised to disrupt the fertility care paradigm by advancing our understanding of the molecular and biological causes of infertility to provide novel avenues for future diagnostics and treatments.
Die ständig wachsende Zahl von Chemikalien, denen der Mensch ausgesetzt ist, und die Erkenntnis, dass einige von ihnen potenziell schädlich für das männliche Fortpflanzungssystem sind, haben die Entwicklung der männlichen Reproduktionstoxikologie vorangetrieben. Diese Entwicklung erhielt 1992 Auftrieb, als über einen Rückgang der Spermienzahl um 50 % in den vorangegangenen 50 Jahren berichtet wurde (Carlsen et al. 1992, Evidence for decreasing quality of semen during past 50 years. Br Med J 305:609–613), was einen enormen Forschungsaufwand für die Erforschung schädlicher Auswirkungen auf das männliche Fortpflanzungssystem auslöste. Die damals umstrittene Behauptung wurde jedoch durch ähnliche, spätere Untersuchungen (Levine et al. 2017, Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update 23:646–659) gestützt, die speziell darauf ausgerichtet waren, die Probleme der früheren Studie zu vermeiden. Dennoch konnte bisher keine eindeutige Ursache für den Rückgang festgestellt werden. Im Allgemeinen wurden bei einer Vielzahl von Chemikalien experimentell schädliche Auswirkungen auf das Fortpflanzungssystem festgestellt, jedoch relativ selten unter Bedingungen, die mit der Exposition des Menschen vergleichbar sind. Die bevölkerungsweite Überwachung bestätigt dies, wobei nur sehr geringe Auswirkungen auf die Fortpflanzungsparameter feststellbar sind. Das Nematozid Dibromchlorpropan ist das klassische Beispiel für eine industrielle Verbindung, die sich auf das männliche Fortpflanzungssystem auswirkt, aber es gibt kaum Hinweise darauf, dass viele andere toxische Stoffe (z. B. Metalle, komplexe chlororganische Verbindungen, Alkohol, elektromagnetische Strahlung, Wärme) bei normaler Exposition und Empfindlichkeit von Erwachsenen vergleichbare Auswirkungen haben. Bestimmte andere Agenzien, insbesondere Rauchen und ionisierende Strahlung, zeigen nur begrenzte vererbbare Auswirkungen bei bestimmten (meist chronischen) Expositionen. Das größte Risiko für die Spermienproduktion geht von Krebstherapien aus, obwohl die verfügbaren (wenn auch begrenzten) Nachweise darauf hindeuten, dass es keine vererbbaren Auswirkungen gibt, vielleicht weil die Exposition hoch dosiert und akut oder subchronisch ist. Dennoch besteht große Besorgnis darüber, dass unbekannte Faktoren in der Umwelt, die möglicherweise endokrin wirksame Eigenschaften haben, eine Reihe von Wirkungen hervorrufen können, die heute manchmal unter dem Begriff testikuläres Dysgenesiesyndrom zusammengefasst werden. Obwohl es zahlreiche experimentelle und umweltbezogene Beweise dafür gibt, dass eine breite Palette spezifischer Toxine, insbesondere endokrin wirksame Verbindungen, derartige Wirkungen hervorrufen können, stehen vergleichbare Beweise beim Menschen noch aus. Infolgedessen hat sich der derzeitige Rechtsrahmen für die Regulierung von Expositionen, die das männliche Fortpflanzungssystem schädigen könnten, in den letzten Jahren nicht wesentlich geändert, mit der einzigen Ausnahme, dass Leitlinien für die Prüfung von endokrin wirksamen Stoffen eingeführt wurden.¬ Dies liegt auch daran, dass die Ursachen der männlichen Fortpflanzungstoxizität beim Menschen noch immer nur unzureichend bekannt sind. Die aufregenden Entwicklungen des letzten Jahrzehnts könnten jedoch den Weg zu einem besseren Verständnis der beteiligten Mechanismen weisen.
Genital tucking is a behavioural practice facilitating gender expression by genitalia concealment. Genital tucking can be achieved by either pushing the testicles into the inguinal canal and/or securing the scrotum and penis between the legs towards the buttocks. Genital tucking has a negative impact on spermatogenesis, and therefore can result in a suboptimal sample and impaired sperm parameters. Fertility cryopreservation is recommended prior to hormone therapy or elective surgery, and therefore, the practice of genital tucking prior to fertility preservation could result in lesser quality and fewer samples being stored for future use. This case study presents a transwoman, aged 20–30, displaying severe oligoasthenoteratozoospermia derived from genital tucking. The case discusses how the cessation of genital tucking resulted in improved semen parameters, and therefore improved the quality and quantity of samples stored for future use. Fundamentally, the case highlights the necessity for health professionals to broaden their understanding and awareness of genital tucking, the impact it has on fertility, and how to better advise patients prior to fertility cryopreservation.
The objective of this study is to ascertain the effects of polyesther sling scrotal cover on sperm production in healthy Indonesian men. This prospective study consisted of 2 phases, i.e., a control phase and treatment phase trial. Ten normal healthy volunteers used polyester sling scrotal cover all day and night for 24 weeks. Semen was analyzed at a 3-week interval, and clinical chemistry and hematology were monitored at a 12-week interval. The results showed that within 24 weeks sperm concentration, percentage of normal sperm morphology, and sperm velocity decreased to below normal range in all subjects. We concluded that polyester sling scrotal cover can suppress sperm production to oligospermia in Indonesian men. Not a single subject achieved azoospermia, as compared with in Egypt study that showed 100% azoospermia in 14 men. © 1995 Faculty of Medicine, Universitas Indonesia. All rights reserved.
We evaluated the effect fit of underwear had on sperm production in two healthy adult males in their early thirties. The subjects alternated from wearing tight fitting bikini type briefs to loose fitting boxer type briefs in an ABAB withdrawal design. Conditions lasted three months and were alternated twice resulting in a one year study. The initial condition for each subject was randomly determined with the laboratory technologist blind to the conditions. Four semen parameters were analyzed in this study: sperm density, total number of sperm, total number of motile sperm, and total number of motile sperm per hour of abstinence. The results showed the semen parameters gradually decreased in tight conditions and gradually increased during loose conditions. Although preliminary, the results support the commonly held but undocumented belief that the fit of men's underwear can influence sperm production.
We studied the use of a testicular hypothermia device worn daily for at least 16 weeks in 64 men with subfertile semen and elevated testicular temperature, who had had an infertile marriage for 2 or more years in which the wife was judged fertile. Improvement in 1 or more semen parameters was seen in 42 patients (65.6 per cent). Semen analysis was converted into the motile oval index, a numerical value representing the count, motility and normal morphology. The motile oval index helps to predict pregnancy outcome. Of 21 patients with pre-treatment motile oval indexes greater than 4.8 million per ml. 11 (52.4 per cent) produced pregnancy. Patients with lower starting indexes did not fare as well. Of 20 patients who met the criteria, and who wore the device for less than 2 weeks or not at all and had no other treatment 1 (5.0 per cent) produced pregnancy. Mean hypothermia time to date of missed menses was 4.2 months. Six patients with nonobstructive azoospermia showed no semen change with the testicular hypothermia device.
The female germ line (germ cell lineage, Keimbahn) is provided with only one proliferation wave, the oogenic, whereas male gametogenesis involves two successive waves: prespermatogenic, which corresponds to the female proliferation wave, and spermatogenesis, which is responsible for the immense number of male gametes produced in mature testes. Both male proliferation systems are linked by the transitional or T prospermatogonia. Using the reverse percentage of labelled metaphases method, it has been shown that the first differences between female and male germ cells can be identified by the end of the first wave, when oogonia and multiplying or M prospermatogonia are proliferating. This prenatal first wave of proliferation of male germ cells was also demonstrated in man and ceases around the 22nd week of pregnancy. Spermatogenesis involves a stock of stem cells (stem spermatogonia), a flexibly reacting pool of undifferentiated spermatogonia and several generations of differentiating spermatogonia, which proliferate almost exponentially. Furthermore, it consists of spermatocytes and haploid spermatids transforming into spermatozoa. The oocytes pass through the preleptotene stage, synthesizing DNA, and thereafter traverse the meiotic prophase up to the diplotene stage. In mammals they act as ‘pre-embryos’ in a similar but to a lesser degree than oocytes of amphibia and insects. The maternal chromosomes are largely responsible for the development of the embryo, the paternal genome for the development of the extra-embryonic tissue. The synthesis of transgenic animals is a powerful weapon in the armoury of geneticists, as has recently been demonstrated: a 14 kb genomic DNA fragment (Sry) is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
A large body of research confirms the vulnerable nature of spermatogenesis to relatively small increases in testicular temperature. Other physical properties of electromagnetic and ultrasound waves have additive or synergistic effects to those of heat and allow disruption of spermatogenic processes at minimal temperature elevations. In addition there is a rebound in sperm count following heat-induced suppression of spermatogenesis. These findings suggest the theoretical viability of testicular heating as a reversible method of male contraception in humans. However before heating techniques can be used for male fertility control several questions remain to be investigated. The lowest effective doses and the lowest frequency of application of each method of testicular heating necessary for inducing and maintaining a reliable infertile state must be established. It must be determined whether long-term exposure leads to permanent damage or compromise of testicular elements or functions and whether exposure to simple heat electromagnetic waves or ultrasound induces significant changes in the biological constituents of human semen. Also unclear is the exact mutagenic potential of thermal agents on the human gonads. Another research question is whether scrotal warm sensory input rises during testicular heating to a level that is sufficient to alter body core temperature. Rapidly advancing knowledge of biologic constituents of human semen and the increasingly available detection methods of these constituents will enhance research in these areas. It is through such research that the safety efficacy and applicability of thermal manipulation of spermatogenesis as a method of male contraception will be established or refuted.
Alterations of intrascrotal temperature markedly affect spermatogenesis and sperm counts. In euspermic subjects, scrotal exposure for 30 minutes to a 150-watt electric light bulb resulted in reversal of the scrotal-rectal temperature ratio by a mean of 2.9 C. Such treatment on 14 consecutive days caused depression of spermatogenesis followed by rebounds to temporarily high sperm counts. Application of an ice bag to the scrotum for a mean of about 30 minutes cooled the testicular environment by a mean of 6.9 C. Such cold treatment on 14 consecutive days, beginning not less than 12 days following cessation of exposure to heat, stimulated spermatogenesis without initial inhibition, nearly trebling the mean pretreatment count. Oligospermic subjects responded to both heating and cooling faster and to a relatively greater degree, but less predictably, than did euspermics. The greatest increase in spermatogenesis followed sequential application of heat and cold, which suggested possible therapeusis in oligospermia.
This study had the purpose of exploring the possible association between the work exposures of professional drivers and their reproductive health, by studying a group of 201 taxi drivers in the city of Rome. Data on work and reproductive history were collected by interviews. Biological markers examined in 72 subjects included salivary testosterone levels, sperm quality (i.e., sperm concentration, sperm morphology, and motility), and fertility experience, including time to pregnancy. Their spermatologic profile was compared with that of a control group of 50 healthy subjects of similar age and smoking habits. The results showed that taxi drivers, compared to the controls, had a significantly lower prevalence of normal sperm forms (45.8% vs. 64.0%); this was particularly true for those with a longer time on this job. This result was confirmed by a multivariate analysis in which confounders such as age, smoking, and alcohol consumption were controlled. The other sperm parameters did not differ in the study and the control groups. Among the life-style factors, we found smoking to be associated with poorer sperm morphology. Moderate alcohol consumption was associated with a better seminologic profile, while the pattern in respect to coffee intake was inconclusive. Subjects with poor semen quality also more frequently exhibited longer time to pregnancy of their partner. The results suggest that prolonged urban automobile driving might be a risk factors for sperm quality, and particularly for sperm morphology, but the finding needs further confirmation. © 1996 Wiley-Liss, Inc.
Alterations of intrascrotal temperature markedly affect spermatogenesis and sperm counts. In euspermic subjects, scrotal exposure for 30 minutes to a 150-watt electric light bulb resulted in reversal of the scrotal-rectal temperature ratio by a mean of 2.9 C. Such treatment on 14 consecutive days caused depression of spermatogenesis followed by rebounds to temporarily high sperm counts. Application of an ice bag to the scrotum for a mean of about 30 minutes cooled the testicular environment by a mean of 6.9 C. Such cold treatment on 14 consecutive days, beginning not less than 12 days following cessation of exposure to heat, stimulated spermatogenesis without initial inhibition, nearly trebling the mean pretreatment count. Oligospermic subjects responded to both heating and cooling faster and to a relatively greater degree, but less predictably, than did euspermics. The greatest increase in spermatogenesis followed sequential application of heat and cold, which suggested possible therapeusis in oligospermia.
It is well established that heat is associated with reduced sperm production, but the role of physiological variation in temperature has never been scrutinized in humans. We studied diurnal scrotal temperature and markers of male fertility in a population of couples planning their first pregnancy. Sixty men from a cohort of couples who were planning their first pregnancy were included and scrotal skin temperature was monitored during 3 days using a portable data recorder. Working hours and working postures were recorded daily in a questionnaire. Each man provided a fresh semen sample and the couples were followed for six menstrual cycles or until a clinical pregnancy was recognized. The median value of scrotal skin temperature was 33.3 °C in the daytime and 34.8 °C at night. In periods of sedentary work, the median temperature was on average 0.7 °C higher (SE=0.2 °C). In addition, scrotal temperature was higher in the daytime, in summer, and in leisure time compared with working hours. Median sperm concentration among men with more than 75% of their daytime readings above 35 °C was 33.4 × 106/mL, compared with 91.8 × 106/mL for men with less than half of their readings above 35 °C (difference 58.4; 95% CI: 25.9–77.8 × 106/mL). It is concluded that a sedentary position is a significant source of increased scrotal skin temperature, and even moderate and physiological elevation in scrotal skin temperature is associated with a substantially reduced sperm concentration. Sedentary work should be considered as an important potential confounder for reduced sperm count in epidemiological research.
Background and Objective. Fever of ≥39°C for ≥3 days can lead to severely impaired semen quality and even azoospermia. Among spermatogenic cells, pachytene spermatocytes and spermatids are particularly sensitive to temperature. Because of the nature of a spermatogenic cycle, impairment of semen quality becomes obvious after a latent period of several weeks. The changes are usually reversible within a few months. Therefore, a careful history with regard to fever episodes during preceding 3 months is mandatory for interpretation of semen analysis.
Patients/Methods. Five patients are reported who desired a child and had experienced high fever of ≥39°C for ≥3 days. The results of semen analyses are presented in relation to fever episodes.
Results. Sperm concentration declined to 0,4–7% and fast progressive motility to 0–23% 3–6 weeks after the fever episodes and returned to base line levels within 4–6 months. In patients without semen analysis before the fever episode, semen quality remarkably improved thereafter.
Conclusions. Investigating patients for a history of fever during the 3 months preceding fertility work-up avoids unreasonable treatment recommendations based on transient impairment of semen quality.
The aim of this study was to estimate whether male welding has an impact on couple fecundability (the probability of conceiving in a menstrual cycle). A sample of Danish couples without previous reproductive experience was recruited nationwide by postal letters to members of the union of metal workers and three other trade unions. Among 430 included couples, 201 males were metal workers and 130 were welders. The couples were followed for a maximum of six menstrual cycles from termination of birth control until a clinical pregnancy was detected. Compared with nonwelding metal workers the fecundability odds ratio (OR) of male exposure to welding was 0.86 (95% confidence interval [CI] 0.58-1.28). An interaction between male smoking and welding was found; within smokers the OR for welding was 0.40 (95% CI 0.17-0.95) and within nonsmokers it was 1.22 (95% CI 0.74-1.99). Previous welding exposure was negatively related to fecundability among smokers (OR 0.84 per year with mild steel welding, OR 0.76 per year with stainless steel welding). No significant results were found when comparing with an external group of nonmetal workers. Decreased fecundability among smoking welders attributable to both current and previous welding exposure is possible, but these findings were the results of subanalyses that were not part of the a priori hypothesis.
Objective:
To determine whether there is an association between abnormal semen parameters and occupational exposures to organic solvents, metals, and pesticides.
Design:
Case-control study using three case groups based on different cutoff values for semen parameters and one standard reference group.
Setting:
University Hospital Utrecht and University Hospital Rotterdam, the Netherlands.
Patient(s):
Male partners of couples having their first consultation at the two infertility clinics (n = 899).
Intervention(s):
Men provided at least one semen sample. Occupational exposure was assessed with use of job-specific questionnaires, a job exposure matrix, and measurements of metals and metabolites of solvents in urine.
Main outcome measure(s):
Standard clinical semen analyses were used to define case groups and controls.
Result(s):
An association between aromatic solvents and reduced semen quality was demonstrated, irrespective of the exposure assessment method used. The associations were stronger if the case definition was based on stricter cutoff values for semen parameters. Risk estimates were higher if the analysis was restricted to primary infertile men. Exposure to other pollutants at the workplace was not associated with impaired semen quality.
Conclusion(s):
The findings indicated an association between aromatic solvent exposure and impaired semen parameters.
The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls.
Abdominal testes of adult, naturally unilaterally cryptorchid boars were subjected to continuous artificial cooling for 5, 15, 25, or 45 days. This treatment initiated development of the spermatogenic epithelium. After a cooling period of 45 days there was complete differentiation in many seminiferous tubules. The results indicate that the spermatogenic arrest in abdominally located testes is not due to an inborn defect in the testis, but is caused by the maintenance of the testis at the abdominal temperature.
The effect of long-term driving upon spermiogenesis was investigated in 2984 patients, including 281 professional drivers. The incidence of pathospermia was significantly increased among the 281 occupational drivers as compared to other professionals. The ratio of severe pathospermia was increased in proportion to the number of years of driving. The deterioration of spermiogenesis was mild among car drivers, but was severe in agricultural-industrial hard machinery and farm equipment drivers. There was a higher incidence of impaired fertility in drivers as compared to other professionals. The possible factors influencing these results are discussed.
This study is based on a questionnaire which focused on the possible association between life-style factors and male fertility in a group of 252 men attending our laboratory in connection with a fertility investigation. Their answers were correlated to sperm quality. No association could be documented between sperm quality and smoking habits, coffee drinking, a moderate alcohol intake, exposure to heat (sauna, hot baths, type of underwear, sedentary activities), or physical activities in their leisure time. In contrast, the reported average ejaculation frequency was significantly positively correlated to the motility of the sperm (% progressive), and inversely related to the proportion of sperm with abnormal morphology and semen volume. This indicates that the life style of the subject has little if any impact on semen quality, at least within the limits recorded in the present study.
The contraceptive effect of a polyester sling applied to the scrotum was studied in 14 men. The suspensor was worn for 12 months. Follow-up investigations comprised periodic check of semen character, testicular size, rectal-testicular temperature difference, serum reproductive hormones and testicular biopsy. The electrostatic potentials generated by friction between the polyester suspensor and the scrotal skin were determined. Female partners used contraceptives until the men became azoospermic. After 12 months, the suspensor was abandoned and the aforementioned investigations were performed again. In the suspensor-wearing period, all men became azoospermic after a mean of 139.6 +/- 20.8 sd days, with decrease in both testicular volume (P less than 0.05) and rectal-testicular temperature difference (P less than 0.001). Serum reproductive hormones showed no significant change (P greater than 0.05). Seminiferous tubules revealed degenerative changes. No pregnancy occurred during this period. The polyester suspensor generated electrostatic potentials (mean 366.4 +/- 30.5 sd volt/cm2 by day and 158.3 +/- 13.6 sd volt/cm2 by night). In the suspensor-release period, the sperm concentration returned to the pre-test level in a mean period of 156.6 +/- 14.8 sd days. Likewise, the testicular volume and rectal-testicular temperature difference were normalized. The 5 couples, who had planned to become pregnant, conceived. The azoospermic effect of the polyester sling seems to be due to two mechanisms: 1) the creation of an electrostatic field across the intrascrotal structures, and 2) disordered thermoregulation. To conclude, fertile men can be rendered azoospermic by wearing the polyester sling. It is a safe, reversible, acceptable and inexpensive method of contraception in men.
Several studies suggest that welding is detrimental to the male reproductive system. Welding fume and radiant heat are of interest as possible causal factors. This study investigates semen quality and sex hormone concentrations among 17 manual metal arc alloyed steel welders with a moderate exposure to radiant heat (globe temperature ranging from 31.1 degrees to 44.8 degrees C), but without substantial exposure to welding fume toxicants. During exposure to heat the skin temperature in the groin increased on average by 1.4 degrees C (SE +/- 0.72 degrees C). Sperm count and motile sperm count were non-significantly reduced among welders in comparison with two different reference groups. Within the group of welders the proportion of sperm with normal shape declined significantly after six weeks of exposure to heat and increased after a break in exposure. Sperm count and sperm concentration had the same pattern of intraindividual change in relation to exposure to radiant heat, but the changes were not statistically significant. No consistent changes in concentrations of sex hormones were found. The welders investigated were more exposed to radiant heat than welders in general. The results suggest that the study group of welders experienced a reversible decrease in semen quality, most likely caused by a moderate exposure to radiant heat (about five hours a day through several weeks). It remains to be established if even lower levels of exposure to radiant heat in the general population of welders has any impact on semen quality and fertility.
The female germ line (germ cell lineage, Keimbahn) is provided with only one proliferation wave, the oogenic, whereas male gametogenesis involves two successive waves: prespermatogenic, which corresponds to the female proliferation wave, and spermatogenesis, which is responsible for the immense number of male gametes produced in mature testes. Both male proliferation systems are linked by the transitional or T prospermatogonia. Using the reverse percentage of labelled metaphases method, it has been shown that the first differences between female and male germ cells can be identified by the end of the first wave, when oogonia and multiplying or M prospermatogonia are proliferating. This prenatal first wave of proliferation of male germ cells was also demonstrated in man and ceases around the 22nd week of pregnancy. Spermatogenesis involves a stock of stem cells (stem spermatogonia), a flexibly reacting pool of undifferentiated spermatogonia and several generations of differentiating spermatogonia, which proliferate almost exponentially. Furthermore, it consists of spermatocytes and haploid spermatids transforming into spermatozoa. The oocytes pass through the preleptotene stage, synthesizing DNA, and thereafter traverse the meiotic prophase up to the diplotene stage. In mammals they act as 'pre-embryos' in a similar but to a lesser degree than oocytes of amphibia and insects. The maternal chromosomes are largely responsible for the development of the embryo, the paternal genome for the development of the extra-embryonic tissue. The synthesis of transgenic animals is a powerful weapon in the armoury of geneticists, as has recently been demonstrated: a 14 kb genomic DNA fragment (Sry) is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
The Testicular Hypothermia Device (THD) was conceived to test the theory that an intrinsic defect in testicular thermoregulation causes elevation of intrascrotal temperature and results in subfertile semen (Zorgniotti et al., 1980, 1986). When it was found that lowering temperature about 2.0°C by a prototype THD resulted in semen improvement and pregnancy in the wives of infertile men, the therapeutic potential was realized. The THD is a cotton scrotal covering which lowers temperature by controlled evaporation of water from its surface (Figure 1).
The application of a new, miniaturized portable digital data recorder "Thermoport" (Institute for Reproductive Medicine, Münster, West Germany) for continuous determination of scrotal temperatures revealed great variations of scrotal temperature during 24 hours in normal men. Maximum temperatures approached body core temperatures. Mean scrotal temperatures of 10 normal men rose during sauna from 32.72 +/- 0.23 degrees C to 37.53 +/- 0.38 degrees C. During treadmill running, scrotal temperatures increased by more than 2.5 degrees C. Minimal scrotal temperatures were increased in some men with varicocele compared with normal fertile men indicating impaired cooling mechanisms. The continuous temperature measurements facilitate assessment of temperature dynamics. The miniaturized design of the Thermoport makes it suitable for routine use in outpatients of infertility clinics, in occupational medicine for evaluation of heat hazards, and for investigations of body temperatures under various experimental conditions.
The authors used intrascrotal deep body (intratesticular) temperature measurement in an attempt to make the diagnosis of varicoceles more objective. Two hundred five male patients complaining of infertility were classified into three groups: group A consisted of 84 patients with varicocele; group B of 66 patients without varicocele; and group C of 55 patients after varicocelectomy. The bilateral intrascrotal temperatures were recorded in the supine position and then monitored continuously in the standing position. The maximum temperatures in both positions were compared between each group. The mean temperature of the varicocele group was higher than that of the other two groups in the standing position. The authors studied the difference in temperature (delta T) due to postural change from supine to standing. The mean delta T of the left testis was +0.78 degrees C in the varicocele group, whereas it was approximately -0.5 degrees C in the other two groups. The authors conclude that deep body temperature provides a practical index of the intrascrotal temperature and is useful as one of the objective, clinical criteria for the diagnosis of varicocele.
A possible mechanism of varicocele-induced infertility is believed to be elevation of testicular temperature. Sensitive needle thermistors were used to measure directly intratesticular and bilateral scrotal surface temperatures simultaneously in anesthetized infertile men with varicocele and control subjects. We found that intratesticular temperature is elevated significantly in humans with varicocele. In addition, we have shown that scrotal skin surface temperature is elevated in men with varicocele. Furthermore, we demonstrate that unilateral varicocele is associated with bilateral elevation of scrotal surface temperature. These findings confirm the results of animal studies revealing elevation of intratesticular temperature associated with varicocele and suggest bilateral elevation in unilateral varicocele.
Decreased sperm count and motility were observed in men after induction of local testicular hyperthermia by raising the testicles into the inguinal canal during the day in adult volunteers. A similar technique in which the testicles were better maintained in the inguinal canal resulted in more marked suppression of spermatogenesis. As assessed by the total motile sperm count, the mean inhibitory effect of hyperthermia was at least 97% after 2 months using this technique. This effect of 'artificial cryptorchidism' may be of practical interest in the manipulation of male fertility.
A comparison of semen parameters from 25 workers at a reinforced plastic production plant and from 46 age-matched male fertility patients was carried out. For a period of more than three months before the semen analyses, the 25 workers had been exposed to styrene and acetone in concentrations exceeding the Danish threshold limit values. Serum concentrations of follicle stimulating and luteinizing hormones, semen sample volume, and concentration of sperm showed no differences between the two groups. Significant differences between the two groups were found in the percentage of live sperm, immotile sperm, and normal sperm. The reinforced plastic plant workers showed, in terms of semen quality, better values in the percentages of live sperm and immotile sperm, whereas they had a reduced percentage of normally shaped sperm. It was found that the reinforced-plastic workers had increased percentages of the amorphous and the pyriform sperm head shapes as compared to the fertility clientele. In sperm midpiece and sperm tail defects, the two groups showed similar values. From the data it could be concluded that work with production of reinforced plastic might result in an increase in the number of abnormal sperm heads.
Fifty-six males from infertile couples were categorised into two different groups and their semen quality examined. Patients in which there was no evidence of interference with normal testicular thermoregulation either during the day or the night were classified as 'cool workers' and 'cool sleepers' (Group I, n = 26). In the other group (II), 'warm workers'/'warm sleepers' (n = 30), there was evidence for scrotal insulation. The number of good moving spermatozoa per ejaculate as well as this number per ml was greater in 'cool workers'/'cool sleepers' than in 'warm workers'/'warm sleepers' (p less than 0.001). These results emphasize the need for comprehensive patient history when evaluating infertility problems. Similarly, living habits may play a role in human male infertility and treatment.
PIP
A large body of research confirms the vulnerable nature of spermatogenesis to relatively small increases in testicular temperature. Other physical properties of electromagnetic and ultrasound waves have additive or synergistic effects to those of heat and allow disruption of spermatogenic processes at minimal temperature elevations. In addition, there is a rebound in sperm count following heat-induced suppression of spermatogenesis. These findings suggest the theoretical viability of testicular heating as a reversible method of male contraception in humans. However, before heating techniques can be used for male fertility control, several questions remain to be investigated. The lowest effective doses and the lowest frequency of application of each method of testicular heating necessary for inducing and maintaining a reliable infertile state must be established. It must be determined whether long-term exposure leads to permanent damage or compromise of testicular elements or functions, and whether exposure to simple heat, electromagnetic waves, or ultrasound induces significant changes in the biological constituents of human semen. Also unclear is the exact mutagenic potential of thermal agents on the human gonads. Another research question is whether scrotal warm sensory input rises during testicular heating to a level that is sufficient to alter body core temperature. Rapidly advancing knowledge of biologic constituents of human semen and the increasingly available detection methods of these constituents will enhance research in these areas. It is through such research that the safety, efficacy, and applicability of thermal manipulation of spermatogenesis as a method of male contraception will be established or refuted.
The purpose of this study was to investigate whether men employed in the metal industry have sperm of poorer quality than men in other types of work. A postal questionnaire was sent to men employed in the metal industry, certain other types of nonmetal industries, and other types of employment in which the factors suspected to influence sperm quality were not present. By means of this questionnaire survey, it was hoped to define the possible influences of the work environment on sperm quality. Out of the total of 3,119 men included in the investigation, 2,517 (81%) filled out the questionnaire satisfactorily. Semen analysis was performed for all 3,119 men. There was a greater risk for poor sperm quality among welders than among men not employed in welding. The risk for poor sperm quality was increased for those welders who worked with stainless steel. Welding in general, and specifically with stainless steel, is connected with a risk of reduced sperm quality.
Disturbances in semen quality can be induced by exogenous factors including trivial illnesses like throat infection and viral infection with fever. Hansen's disease presents with problems such as long term dependence on drugs, hyperthermia, haemolysis and anxiety due to social stigma. In the present study the semen quality of patients with tuberculoid-type leprosy was studied during and after withdrawal of therapy. Patients generally had low sperm counts and spermatozoal motility was low with a greater number of abnormal forms compared with control subjects. Patients did not show a circannual variation in their sperm count as was observed in controls. The patients were oligozoospermic during their first year of medication, showing improvement in subsequent years.
Evidence to support the contention that avoidance of testicular hyperthermia (due to hot baths and/or tight clothing) will improve fertility is, in the main, anecdotal. Semen samples derived from 128 infertile men were analyzed before and after a 3-month conservative treatment regimen. Six seminal characteristics were studied. Clinical evaluation included normal bath temperature, types of underwear worn, and past history of hernia repair, orchiopexy, or varicocelectomy. The patients were divided into three groups (A to C) according to sperm density and then subclassified on the basis of progressive motility status. The results show that a significant, or approaching significant, improvement in seminal characteristics occurs in certain groups of oligospermic individuals with pretreatment progressive motility of less than 40%. In clinical trials, it should be recognized that any improvement in seminal quality following pharmacologic or surgical intervention may include a contribution from conservative treatment.
Intratesticular and scrotal skin temperatures were measured in 34 men undergoing scrotal or inguinal surgical procedures under general anesthesia. Scrotal temperatures were measured before and after a dry scrotal shave. Intratesticular temperature was measured under direct vision with a needle thermistor. Linear regression analysis revealed a strong correlation between intratesticular and scrotal skin temperatures. In addition, simple scrotal shaving significantly decreased scrotal skin temperature. These observations suggest that scrotal skin temperature measurements may be useful to detect elevations of intratesticular temperature and scrotal shaving may be a useful adjunct for testicular cooling.
We studied the use of a testicular hypothermia device worn daily for at least 16 weeks in 64 men with subfertile semen and elevated testicular temperature, who had had an infertile marriage for 2 or more years in which the wife was judged fertile. Improvement in 1 or more semen parameters was seen in 42 patients (65.6 per cent). Semen analysis was converted into the motile oval index, a numerical value representing the count, motility and normal morphology. The motile oval index helps to predict pregnancy outcome. Of 21 patients with pre-treatment motile oval indexes greater than 4.8 million per ml. 11 (52.4 per cent) produced pregnancy. Patients with lower starting indexes did not fare as well. Of 20 patients who met the criteria, and who wore the device for less than 2 weeks or not at all and had no other treatment 1 (5.0 per cent) produced pregnancy. Mean hypothermia time to date of missed menses was 4.2 months. Six patients with nonobstructive azoospermia showed no semen change with the testicular hypothermia device.
Indirect methods for measuring testicular temperatures probably give valid results. A change in position from supine to standing resulted in a drop of 0.6° C. in intrascrotal temperature. There was no difference in right versus left intrascrotal temperatures except in standing varicocele subjects, in whom the left intrascrotal temperature was significantly higher (0.3° C.). There was a significantly higher intrascrotal temperature (0.6-0.8° C.) in infertile subjects with varicocele than in a control group. Temperature comparisons between infertile subjects without varicocele and a control group did not yield significant results. A distribution curve of intrascrotal temperatures in infertile subjects without varicocele was bimodal, suggesting the presence of a nonhomogeneous population within this group. There was a relationship between decreased testicular size and deranged morphology and increased intrascrotal temperatures in the subjects studied. Tympanic membrane temperatures appeared to be higher in variococele patients than in a control group.
Changes in the seminiferous epithelium of the rat testis occurring within 24 hr after exposure to 43° C for 15 min were investigated using a quantitative technique. The earliest cytochemical or morphological changes were detected in the pachytene spermatocytes in stages IX to XII, the diakinetic and dividing spermatocytes in stages XIII and XIV and the young spermatids at stage I of spermatogenesis within 1 hr after exposure. The spermatocytes showed changes in the cytoplasm and the spermatids, in the nucleus.
The number of abnormal spermatocytes increased progressively with time after the exposure and the damage was detectable in more stages at later time intervals. Within 4 hr after exposure, the damage could also be detected in pachytene spermatocytes at stages VII and VIII, as well as through all the stages up to XIV. The pachytene, diakinetic and dividing spermatocytes from stages IX to XIV were essentially absent 24 hr after the exposure, and those at stages VII and VIII showed a drastic reduction in count. Similarly, a progressive increase in the number of abnormal spermatids was noted, associated with an intensification of the morphological changes in the nucleus characterized by typical ring formation pyknosis and chromatolysis. The sequence of degenerative changes varied considerably between spermatids and spermatocytes—the former showing the earliest changes in the nucleus, and the latter in the cytoplasm.
These findings extend and confirm earlier observations on the specific susceptibility of testicular germinal cells to heat. The pachytene, dia-kinetic and dividing spermatocytes at stages IX to XIV and the young step-1 spermatids are most susceptible to heat under the described experimental conditions.
In order to determine the influence of intrascrotal hyperthermia on testicular function, studies were carried out on human males with the following results:
• 1.1. The mean scrotal-rectal temperature differential (S-R differential) of 36 normal men in the supine position at room temperature was 2.38°C. Changes in posture affected this gradient to some extent. Age apparently had no effect.
• 2.2. The mean S-R differential of 1.75° C. in 21 euspermic individuals, 1.93° C. in 37 oligospermics, and 2.0° C. in 8 men with varicoceles must await interpretation pending the accumulation of sufficient data to warrant statistical evaluation.
• 3.3. Infraclavicular immersion of 8 euspermic subjects in hot baths (38 to 43° C.) resulted in a shift of the median S-R differential from −1.6° C. to +1.2° C., i.e., an inversion of the S-R ratio from 36.1:37.7 to 40.5:39.3, or from 0.96 to 1.03.
• 4.4. In 6 euspermic individuals wearing insulating underwear almost constantly for about 6 weeks, and in a seventh subject who wore the insulating clothing for approximately 14 weeks, the sperm count began to decrease at about the third week after the start of insulation, reaching its lowest point between the fifth to the ninth week. With one exception, the men remained oligospermic for 3 to 8 weeks after omitting insulation and then gradually returned to their characteristic preinsulation sperm output. This was reached, at the latest, by the twelfth postinsulation week in all subjects. No effect on volume of semen was observed. Nor was there any change in the morphology of spermatozoa, with the single exception of the subject who wore the insulation for as long as 14 weeks. A lowering of the mean S-R temperature differential by 1° C. accompanied the suppression of spermatogenesis.
• 5.5. In 20 oligospermic individuals, application of wet heat (43 to 45° C.) to the scrotum for half an hour on 6 alternate days resulted in a decrease in sperm count within 11 to 112 days. In 9 of the men, the drop was followed later by a rebound to levels higher than had prevailed prior to treatment. The wives of 6 of the men conceived within 5 months of start of therapy. All pregnancies were normal.
Modification of spermatogenesis by induced intrascrotal hyperthermia may have practical application not only as a means of controlling fertility, but also as a therapeutic tool in certain cases of oligospermia. These studies are being continued with the aim of elucidating the exact mechanism whereby heat effects such changes in testicular function.
Six men with infertile marriages associated with poor semen and raised testicular temperature were treated by an experimental appliance which exploits evaporation to obtain normal testicular temperatures. This was worn with little discomfort for as long as 24 h a day and for periods as long as 20 weeks. Three wives became pregnant while their husbands were on treatment. Semen analysis at the time of the missed menses showed improvements in all three men. In two patients who did not achieve a pregnancy, semen improvements were also seen after 12 weeks. The improvements in semen quality cannot be attributed to any agency other than the hypothermia; this strengthens the theory that raised temperature plays a role in male infertility. Scrotal hypothermia seems to be a suitable treatment in men with varicocele, varicocelectomy failure, and idiopathic infertility where intrascrotal temperature is raised.