Bridging the Gap: How environmental exposures compromise male fertility and clinical Outlook

Male infertility as a window to health

Introduction Upper gastrointestinal bleeding (UGIB) is a potentially life-threatening gastrointestinal emergency, and effective management depends on early risk stratification. The Glasgow–Blatchford and Rockall scores are commonly used prognostic measures for UGIB, although these scoring systems are relatively difficult to apply in early emergency settings. AIMS65 with five items, albumin, international normalized ratio, mental status, systolic blood pressure, and age (>65 years), showed efficacy in predicting long-term hospitalization and mortality. This study aimed to investigate the usefulness of the prothrombin time-international normalized ratio-to-albumin ratio (PTAR) in the emergency room for early UGIB risk stratification. Methods We retrospectively examined patients who visited a tertiary academic hospital's emergency department (ED) with UGIB as the chief presentation between January 2019 and December 2020. The cutoff values and diagnostic accuracies of the PTAR, Glasgow–Blatchford score, AIMS65 score, pre-endoscopy, and complete Rockall score were analyzed, and the performance of the PTAR was compared with that of other risk stratification methods. In total, 519 patients were enrolled: 163 patients were admitted in the intensive care unit (ICU) and 35 died during admission. Multiple logistic regression analyses confirmed the association of the PTAR with ICU admission and mortality. The adjusted odd ratio (aOR) of the PTAR for ICU admission care was 8.376 (2.722–25.774), and the aOR of the PTAR for mortality was 27.846 (8.701–89.116). Conclusions The PTAR measured in the ED is an independent factor related to ICU admission and mortality in patients with UGIB. Using ED blood laboratory results, which are reported relatively quickly and are easy to acquire and calculate, the PTAR can be used as a risk stratification marker in the early emergency setting.

ABSTRACTBackground:One of the most serious public health issues in India is reproductive tract infections (RTIs), which have a profound effect on the lives of men and women, as well as their families and communities.Objectives:To describe the sociodemographic traits, assess women’s RTI knowledge, and determine which behavioral risk factors are involved in female RTI.Methods:Using a 30-cluster sampling approach, a cross-sectional study design was employed to examine RTIs in 30 villages located in the Haldwani block of the district Nainital.Results:It was shown that just 7.6% of women knew enough about RTIs. Among the 450 women surveyed, the percentage of RTI cases was significantly lower for those who used the barrier method during menstruation (7.7%), had more than three children (25.7%), had a trained person deliver their baby in a hospital (24.1%), used condoms as a family planning method (5.6%), used sanitary pads during menstruation (25.6%), and maintained good personal hygiene (22.4%).Conclusion:The study revealed that the participants’ understanding of RTI was lacking.

Coronary Artery Disease (CAD) remains a leading cause of global mortality, with dyslipidemia recognized as a major modifiable risk factor. This study investigates the relationship between serum lipid parameters and CAD using the Z-Alizadeh Sani clinical dataset comprising 303 patients with 55 clinical, biochemical, and electrocardiographic attributes. Logistic Regression (LR) and Random Forest (RF) models were developed to predict CAD status, supported by a standardized preprocessing pipeline, multi-split train–test evaluation (70/30, 80/20, 90/10), and performance assessment using Accuracy, Precision, Recall, F1-Score, and AUC-ROC. SHapley Additive exPlanations (SHAP) were employed to enhance model interpretability and quantify the contribution of lipid-related and clinical features to individual predictions. The RF model consistently outperformed LR across all split configurations, achieving a maximum AUC of 0.96, while LR attained an AUC of 0.90. SHAP analysis revealed that total cholesterol (CHOL) and low-density lipoprotein (LDL) were strong positive predictors of CAD, whereas high-density lipoprotein (HDL) exhibited a protective effect, in line with established cardiovascular pathophysiology. These findings demonstrate that integrating explainable machine learning with routine clinical lipid profiles can provide accurate and transparent decision support for early CAD risk stratification.

Dysregulation of fibrinolysis and its relationship with blood cellular indices in acute pulmonary embolism

Background/Introduction Myocardial infarction with non-obstructive coronary arteries (MINOCA) still consists an "enigmatic" and heterogenous clinical entity. Takotsubo syndrome (TTS) represents a significant proportion of such cases. Despite its predominance on female sex and its imaging characteristics of the "signature" apical form, it remains hardly distinguishable from MINOCA without the contribution of cardiac magnetic resonance (CMR). On the other hand, INTERTAK score is the only risk model to estimate the probability of TTS, whereas angina characteristics were not used in this model. Considering the guarded prognosis of MINOCA and TTS, an early risk stratification and differential diagnosis could improve therapeutic decisions and prognosis. Purpose The aim of our study was to investigate potential prognostic markers of early diagnosis and risk stratification among patients admitted with a working diagnosis of MINOCA. Methods In a multicenter prospective study, we enrolled 111 patients aged 38-85 years old who fulfilled the diagnostic criteria of MINOCA. All patients received treatment according to the latest guidelines and consensus documents and CMR was performed within 30 days of the acute event. Patients with findings of myocarditis were excluded (n=21) and the remaining population was divided into TTS (n=38) and non-TTS (n=52) groups according to clinical assessment and multimodality imaging results. Non-TTS group included MINOCA patients with ischemic pattern of late-gadolinium enhancement (LGE) and patients with clear CMR representing the "MINOCA of unknown etiology" group. The investigated potential prognostic markers were parameters derived of blood pressure and heart rate variability assessed by 24hr ECG and blood pressure monitoring, as well as clinical parameters used in the most common risk stratification tools used in the setting of ACS, such as TIMI and GRACE scores. Results In our population, female sex (94.7% vs 55.8%, p<0.001), older age (67 ± 10 vs 60 ±12, p=0.003) were more frequent in TTS group. Focusing on angina characteristics, "severe angina" expressed as 2 or more episodes of angina within 24 hours as included in the established TIMI score was significantly more frequent among the TTS compared to the non-TTS patients (54.1% vs 24%, p=0.007). Μultivariate analysis revealed that "severe angina" (OR, 0.153; CI 95%: 0.039 – 0.605, p=0.007) is predictive of TTS independently of age, ECG pattern, peak troponin and even after the inclusion of INTERTAK score in the model. Conclusions In our preliminary analysis, "severe angina" emerged as a potent and independent predictor of TTS diagnosis. Due to lack of availability of CMR, clinical tools as the INTERTAK score are useful in everyday practice. Based on our finding, inspired by the TIMI score, the presence of "severe angina" may strengthen the predictive value of the INTERTAK score when integrated with the latter.

Early dynamic risk stratification with baseline troponin levels and 90-minute ST-segment resolution to predict 30-day cardiovascular mortality in ST-segment elevation myocardial infarction: Analysis from CLopidogrel as Adjunctive ReperfusIon TherapY (CLARITY) - Thrombolysis in Myocardial Infarction (TIMI) 28

Epidemiological observations and work in experimental models in animals have highlighted the link between the nutritional environment in early life and an increased risk for offspring to develop a range of cardiometabolic and reproductive disorders in later life. This framework falls under the “Developmental Origins of Health and Disease” (DOHaD) hypothesis via a process termed developmental programming. Altered maternal nutrition, including undernutrition, overnutrition and specific micronutrient deficiencies during critical early windows of developmental plasticity, results in adaptive processes that confer short-term survival advantages but can lead to lifelong adverse impacts on the health of offspring. These effects are amplified postnatally via an obesogenic diet and sedentary behaviour and can also be passed on to future generations. The mechanistic basis of early-life programming remains largely undefined. However, involvement of epigenetic mechanisms, such as altered DNA methylation, histone modifications and miRNAs, has been implicated in addition to permanent structural changes during organ development. Further, at least in animal models, aberrant developmental programming can be reversed via targeted nutritional supplementation during early life, albeit in a sex-specific manner. A better understanding of early nutritional programming and how disease traits are transmitted across future generations is essential for the development of preventative strategies aimed at addressing the current health crisis around obesity and related metabolic disorders.

Numerous studies in humans and in animal models have demonstrated that exposure to adverse environmental conditions in early life results in long-term structural and functional changes in an organism, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life. Such effects are not limited to the first generation offspring but may be transmitted to a second or a number of subsequent generations, through non-genomic mechanisms. While the transmission of ‘programmed’ effects through the maternal line could occur as a consequence of multiple influences, for example, altered maternal physiology, the inheritance of effects through the male line is more difficult to explain and there is much interest in a potential role for transgenerational epigenetic inheritance. In this review, we will discuss the mechanisms by which induced effects may be transmitted through the paternal lineage, with a particular focus on the role of epigenetic inheritance.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

Background: The reported prevalence of infertility in Pakistan is 21% of which 35% is contributed by male factor. Male infertility has multifactorial etiologies ranging from modifiable to genetic risk factors. Among all the risk factors that may account for male infertility, obesity is one of the emerging public health problems. Therefore, the aim of the study was to determine the association of obesity with infertility in Pakistani men. Methods: We conducted a case control study. Cases were men with impaired semen parameters and controls did not have impaired semen parameters. Results: The final multivariable logistic regression model after adjusting for the effect of other variables revealed that with every 1 kg/m2 increase in BMI the odds of being infertile was 6% higher as compared to being fertile (aOR = 1.06; 95% CI = 1.01, 1.11). Moreover the odds of having education of higher secondary or above was 3 times greater among cases as compared with the controls (OR = 3.10; 95% CI = 1.66, 5.77). Furthermore the odds of having previous medical conditions increasing the risk of infertility was higher among cases as compared with the controls (OR = 3.07; 95% CI = 1.63, 5.79). Conclusion & recommendations: This study indicates that obesity is an important risk factor for male infertility. Moreover our findings also indicate that higher educational status and previous medical conditions are also associated with male infertility. Thus awareness can be raised through treating physicians and public health messages.

Infertility in rural Ghana

Background & objective: Infertility is a problem of public health importance because of its high prevalence and serious social implications on affected couples and families. Although once believed that the problem is solely due to female factor, it is now generally accepted that male factor infertility is equally as important as the female factor. However, it is not known how far the problem is attributed to male factor. The present study is intended to find the prevalence of male infertility among the infertile couples and its determinants in the context of Bangladeshi population.
 Patients & Methods: The present study was a descriptive cross-sectional study conducted on male partners of infertile couples (over a period of three months) visiting the Infertility Clinic of Bangladesh Institute of Research and Development in Endocrine & Metabolism (BIRDEM) General Hospital, Dhaka. Male infertility was defined as the inability of a man to make his partner conceive (because of quantitative and/or quantitative deficiency of his sperm) after 12 months of regular unprotected sexual intercourse. On the basis of semen analysis, male partners were divided into two groups – Infertile Group and Fertile Group and the suspected factors were compared between groups using crosstab analysis to determine the factors responsible for male infertility.
 Result: The present study demonstrated that respondents were generally middle aged (between 30-50 years) with mean age being 35.5 years. Majority (88.5%) was Muslim and belonged to middle class (74.3%). Nearly half (47%) was service-holder and one-third (35.8%) was businessman. About 62% of the male partners were revealed to be infertile on semen analysis [combined prevalence of azoospermia (19%), asthezoospermia (29.2%) oligospermia (12.8%), and teratzoospermia (7.1%)]. Of them nearly one-third (azoospermic ones) was solely responsible for infertility and the rest played contributing role to the overall infertility. The reproductive tract infection (STDs) was reported to be alarmingly high among infertile males (21.4%) than that among their fertile peers (p = 0.002). Smoking, varicocele, overweight or obesity and diabetes also demonstrated their significant presence among infertile males compared to the fertile male group. History of occupational exposure to high temperature, pesticide, trauma to testes, abdominal and urogenital surgery were not associated with male partner fertility.
 Conclusion: From the findings of the present study, it can be concluded that a substantial proportion of infertility can be attributed due to male partner infertility and its significant predictors are reproductive tract infections or sexually transmitted diseases. The second leading causes are varicocel, diabetes and obesity.
 Ibrahim Card Med J 2016; 6 (1&2): 25-32

Study question How does infertility affect women in Ethiopia, and can rehabilitation service providers mitigate its impact? Summary answer Introducing rehabilitation services for women with infertility in Ethiopia could mitigate the frequent adverse psychosocial consequences and maintain women’s integration into family and community structures. What is known already Infertility is a disease that generates a disability as an impairment of function. Globally, millions of people are affected, and women bear the brunt of its consequences. In Ethiopia, infertility can cause significant distress and burden for women who are unable to meet societal expectations of motherhood. Despite this impact, no previous research has been conducted in Ethiopia to explore the role of rehabilitation services in providing support for these women. Study design, size, duration We followed a sequential mixed methods design that consisted of three parts: The national prevalence of infertility in Ethiopia was first determined using data from the 2016 Ethiopian Demographic and Health Survey (DHS); using Interpretive Phenomenology, the lived experiences of Ethiopian women living with infertility was explored; and finally, an Interpretive Description approach was applied to evaluate the role of rehabilitation services in assisting women with infertility. Data were collected between 2022 and 2023. Participants/materials, setting, methods For the first part, we performed secondary data analysis from 15,683 women in Ethiopia through the 2016 Ethiopian DHS. The data were analyzed using two approaches to infertility – the demographic and current duration. In the second part, 13 women undergoing treatment at a fertility center were interviewed. In the third part, 14 rehabilitation, medical, and policy service providers were purposefully selected from diverse institutions across three different geographical locations in Ethiopia. Main results and the role of chance Using the demographic definition, the overall prevalence of infertility was 7.6% (95% CI 6.6-8.8), with a prevalence of primary and secondary infertility of 1.4% (95% CI 1.0-1.9) and 8.7% (95% CI 7.5-10.1), respectively. The current duration approach resulted in a prevalence of overall infertility of 24.1% (95% CI 18.8-34.0) at 12-months, 13.4% (95% CI 10.1-18.6) at 24-months, and 8.8% (95% CI 6.5- 12.3) at 36-months. Thus, the demographic definition resulted in a lower estimate compared to the current duration approach which could be more appropriate for the early detection and management of infertility in Ethiopia. According to participants, infertility had far-reaching consequences that substantially affected women’s psychological, socio-cultural, and spiritual lives. Despite this, women developed various coping mechanisms and resilience. Women had minimal access to psychosocial and financial support and no access to rehabilitation services. Finally, interviewees recognized the potential of rehabilitation services to maximize the day-to-day functioning and overall well-being of women with infertility. Limitations, reasons for caution Using demographic proxies to determine exposure to pregnancy can make estimation unreliable. The fertility center only treated married couples; hence, single, separated, or divorced women were not included. Results are context-specific and cannot be extrapolated to all infertility cases in Ethiopia or elsewhere. Wider implications of the findings This is the first study to explore infertility in Ethiopia from a rehabilitation perspective. Based on the prevalence and impact, infertility in Ethiopia represents a major public health issue. Strengthening policies, integrating rehabilitation services into fertility care, and recognizing infertility as a disabling condition are crucial steps toward addressing infertility. Trial registration number not applicable

What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant? Overweight and obesity are associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count. Higher BMI is associated with impaired semen parameters, while increasing waist circumference (WC) is also associated with impaired semen parameters in infertile men. Data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study were utilized. The LIFE study is a population-based prospective cohort of 501 couples attempting to conceive in two geographic areas (Texas and Michigan, USA) recruited in 2005-2009. Couples were recruited from four counties in Michigan and 12 counties in Texas to ensure a range of environmental exposures and lifestyle characteristics. In person interviews were conducted to ascertain demographic, health and reproductive histories followed by anthropometric assessment. We categorized BMI (kg/m(2)) as <25.0 (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and ≥35 (obese, class II) for analysis. Data were available for analysis in 468 men (93% participation), with a mean ± SD age of 31.8 ± 4.8 years, BMI of 29.8 ± 5.6 kg/m(2) and WC of 100.8 ± 14.2 cm. The majority of the cohort (82%) was overweight or obese with 58% reporting physical activity <1 time/week. The median sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having oligospermia (<15 M/ml). When examining semen parameters, ejaculate volume showed a linear decline with increasing BMI and WC (P < 0.01). Similarly, the total sperm count showed a negative linear association with WC (P < 0.01). No significant relationship was seen between body size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or DNA fragmentation index. The percentage of men with abnormal volume, concentration and total sperm increased with increasing body size (P < 0.05). No relationship between physical activity and semen parameters was identified. Our cohort was largely overweight and sedentary, which may result in limited external validity, i.e. generalizability. The lack of physical activity did preclude examination of exercise more frequently than once per week, thus our ability to examine more active individuals is limited. Body size (as measured by BMI or WC) is negatively associated with semen parameters with little influence of physical activity. Our findings are the first showing a relationship between WC and semen parameters in a sample of men without known infertility. Given the worldwide obesity epidemic, further study of the role of weight loss to improve semen parameters is warranted. Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.

Cryptorchidism: incidence, risk factors, and potential role of environment; an update.