Risk Factor For Infertility Research Articles

The prevalence and associated risk factors of infertility among type 2 diabetes patients in Qassim region 2022: A cross-sectional study

Background: Diabetes Mellitus has a significant effect on reproductive health, including hypogonadism, hypoactive sexual desire disorder, menstrual dysfunction, and polycystic ovarian syndrome. However, the prevalence and the associations of infertility among type 2 diabetes have not been widely estimated and investigated. Aim: This study aimed to estimate the prevalence of infertility and its associated risk factors among type 2 diabetic patients. Patient and methods: This community-based cross-sectional (prevalence) study was conducted among type 2 diabetic patients in the Qassim Region, Saudi Arabia. A self-administered questionnaire was given to diabetic patients who visited Primary Healthcare Centers. The questionnaire included socio-demographic data (i.e., age, gender, residency, etc.), characteristics of diabetic patients, and a set of questions to assess infertility among patients. Results: Of the 201 type 2 DM patients, 65.7% were males, and 46.8% were aged between 41 to 50 years. Diabetic patients who were smokers constituted 12.4%. A family history of diabetes has been reported by 75.1% and 20.9% reported having difficulties getting pregnant. The prevalence of the patients who had been previously evaluated or treated with infertility was 4.5%. Younger age, being employed, difficulties in getting pregnant, having less than 4 children, and a family history of infertility were the factors that influence patients' infertility. Conclusion: The prevalence of infertility among diabetic type 2 patients is low. Younger patients who were employees, having difficulties getting pregnant, having fewer children, and having a family history of infertility were more likely to exhibit infertility than other diabetic patients. Further investigations are required to determine the associated factors of infertility among patients with type 2 diabetes.

COMMENTARY PART 1: EVALUATING THE ASSOCIATION OF FEMALE OBESITY WITH THE RISK OF LIVE BIRTH FOLLOWING IVF - IMPLICATIONS FOR CLINICAL PRACTICE

Obesity is a well-established risk factor for infertility. Consequentially, women living with obesity may require fertility treatment to support them to conceive. Due to evidence suggesting obesity is also linked with poorer outcomes following in vitro fertilisation (IVF), local commissioning guidelines on assisted conception recommend a BMI of <30kg/m2 before IVF can commence. However, it is currently unclear if these guidelines are evidence based. This commentary aims to critically appraise a recent systematic review by Sermondade, et al., (2019) and expand upon the implications of the findings for clinical practice.

Risk factors for infertility and barriers to treatment in Tanzania: a survey and medical records study.

The burden of infertility is serious for women in high-fertility countries. We sought to identify demographic, behavioral/environmental, and reproductive risk factors for various infertility factors (i.e., ovarian, tubal, uterine/cervical, male/other) among women seeking infertility treatment in central Tanzania; to determine the association between pelvic inflammatory disease (PID) and tubal factor infertility (TFI); and to identify barriers to infertility treatment by women's home regional zone. We conducted a cross-sectional survey of women seeking infertility treatment in Dodoma, Tanzania from January-March 2020. We surveyed 168 participants aged 18-49 years and reviewed their medical records to confirm infertility status and potential risk factors. We estimated prevalence ratios for factors associated with infertility using logistic regression. Treatment barriers were compared by women's regional zone to see if barriers varied geographically. The median age of participants was 32 years (range: 18-48). Infertility factors did not vary greatly by patient demographics, behavioral/environmental, or reproductive risk factors. Approximately 31.48% of women had PID diagnoses. Those with PID had 1.94 (95% CI: 1.30, 2.90) times the prevalence of TFI diagnosis as those with other infertility factors, after adjusting for age, pesticide use, alcohol use, age at sexual debut, prior obstetric events, and family history of infertility. Logistical barriers to treatment, such as time and cost, were more frequently reported than emotional, stigma, or other barriers, regardless of regional zone. PID was strongly associated with TFI after adjustment for confounders. Infertility treatment access due to cost remains a challenge in Tanzania.

Risk Factors and Clinical Patterns of Infertility in Couples: A Hospital-based Cross-sectional Study in Southern Khyber Pakhtunkhwa, Pakistan

Infertility is ranked as the fifth-leading cause of disability in the world's population under 60 years old, according to the World Health Organization, affecting an estimated 80 million people worldwide. This reproductive health disorder can be caused by various factors, including structural, biological, and congenital issues, as well as acquired and environmental variables. To investigate the prevalence and potential risk factors of infertility, a hospital-based cross-sectional study was conducted in district Kohat, Pakistan, from January to May 2021. A total of 120 infertile couples were recruited from the outpatient center at Liaquat Memorial Hospital, and their medical files were reviewed, followed by face-to-face interviews with both partners of each couple. Of the participants, 47.5% were suffering from primary infertility, while 52.5% were affected by secondary infertility. Female infertility was the most common form of infertility, affecting 49.16% of couples, followed by male infertility (15.83%), couples with both partners facing infertility issues (8.33%), and unspecified infertility (26.66%). The most frequent causes of male and female infertility were erection issues (48.27%) and hormonal imbalances (40.57%), respectively. Additionally, 46.34% of couples reported stress and anxiety, and 14.16% had a history of assisted reproductive technology. Furthermore, 18.3% of couples had a family history of infertility, with 77.27% of those affected being infertile females. Infertile couples were also assessed based on potential risk factors, including age difference, age at menarche, occupation, smoking, and BMI. These findings may aid in identifying the factors contributing to infertility among the population.

Observational Cross-Sectional Study on Mediterranean Diet and Sperm Parameters

Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40–50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059–0.133; p < 0.00)]. Therefore, adhering to the MD with at least a MEDAS score of 6.26 increases the probability of normozoospermia. Moreover, subjects who had a MEDAS value lower than 6.25 had an Odds Ratio of 6.28 (CI = 3.967–9.945) for having at least one altered sperm parameter compared to those who were more adherent to the MD. In conclusion, our findings show that a higher adherence to the MD is associated with better semen parameters, in particular in relation to sperm count, sperm concentration, typical sperm morphology, and sperm progressive motility.

Awareness of risk factors associated with tubal infertility among female youth corps members in Benin City, Nigeria

Infertility is the inability to achieve pregnancy within one year of regular unprotected coital exposures. It is a common gynecological problem in our environment. The cause of infertility could be of female origin, male origin, a combination of both, or idiopathic. It can be primary when there is no previous pregnancy, or secondary infertility when there is an inability to conceive after a previous conception. In secondary infertility, a tubal factor is the most typical cause globally. In a review of factors associated with tubal factor infertility in a tertiary hospital in southern Nigeria, the tubal aspect constituted 13.5%. It was due to previous post-abortion sepsis, puerperal sepsis, and Pelvic Inflammatory Disease (PID). Awareness of infertility risk factors is an essential first step to safeguard future fertility; however, several studies demonstrated poor knowledge of tubal infertility and its risk factors, especially among infertile couples and couples attending gynecology clinics. This study assesses the knowledge of female youth corps members in Benin City, Edo State, on tubal factor infertility, its risk factors, and management. A cross-sectional analytical study was conducted among female youth corps members in Benin City using a multi-stage sampling technique. A self-administered questionnaire was used for data collection. The data was entered and analyzed using Statistical Package for Social Sciences (SPSS) Version 25.0 (IBM SPSS V 25.0, Chicago, IL, USA) and presented using tables. From this study, there is good knowledge of the burden of tubal infertility and treatment implications (50.4%). However, the knowledge of tubal infertility (34.3%) and its risk factors (27.0%) was poor. Age, marriage, and the medical profession are associated with sound knowledge of the burden of tubal infertility (p=0.02). However, only the medical profession is independently associated with good knowledge of tubal infertility (AOR=2.963, p=0.006, CI=1.370-6.411). There is generally poor knowledge of tubal infertility among females of reproductive age, who are at higher risk of pelvic inflammatory disease being the most typical risk factor for tubal infertility. This calls for more health awareness programs for the youth to help safeguard their future fertility.

Epidemiology of female infertility in Sonepat district of Haryana: a community based cross-sectional study

Background: Infertility is a global reproductive health problem and the prevalence rate increased by 0.37% per year for females. There are many such risk factors which are avoidable. Thus the purpose of the study is to identify and quantify the burden of infertility and associated risk factors for infertility. Methods: This observational community based cross-sectional study was conducted among 444 reproductive age group (18-49 years) women residing in district Sonepat, from August 2021 to May 2022. Simple random sampling technique was used to select the study subjects. The categorical data were analyzed statistically using Chi-Square test and Odds ratio with 95% confidence interval. Continuous variables were analyzed using independent t-test. Results: Out of 444 study population majority of women were fertile (88.7%), while 6.3% of women were secondary infertile and 5% women were primary infertile. Most women were aged between 30-39 years. The difference of occurrence of infertility in relation to time since marriage, male age at marriage, number of family members, thyroid, PCOD, tuberculosis and height were statistically significant. Conclusions: Almost all the factors came out to be responsible for infertility were modifiable. Awareness generation and provision of infertility care services at primary health care facilities will be of use in addressing infertility in Haryana.

Clomiphene Citrate in the Management of Infertility in Oligospermic Obese Men with Hypogonadism: Retrospective Pilot Study.

Background and Objectives: Obesity is a significant risk factor for hypogonadism and infertility that is further associated with reduced semen quality. The aim of this study is to evaluate the effect of clomiphene citrate (CC), prescribed for treating infertility, on serum testosterone and semen parameters, particularly in oligospermic obese hypogonadal men. Materials and Methods: A retrospective analysis of data related to men (n = 53) who underwent CC treatment for infertility and hypogonadism (testosterone < 300 ng/dL) was performed. Patients with obesity (BMI ≥ 30 kg/m2) and sperm concentration ≤ 15 × 106/mL were included for analysis. Results: The overall results showed that, in oligospermic obese men (n = 31), treatment with CC significantly improved baseline sperm concentration (4.5 ± 6.8 × 106/mL vs. 11.4 ± 15.5 × 106/mL, p < 0.05) and motility (31.5% ± 21.5% vs. 42.6% ± 14.7%, p < 0.05). Furthermore, subsequent examination of oligospermic hypogonadal obese men treated with CC (n = 13) revealed substantial improvements in baseline serum testosterone levels (193.8 ± 59.3 ng/dL vs. 332.7 ± 114.8 ng/dL, p < 0.05) along with an increase in sperm concentration, total motility, and normal morphology. Conclusions: The results of this retrospective study suggest that CC treatment not only improves chances of fertility outcomes by substantially improving semen parameters but also increases total serum testosterone levels in oligospermic obese men without any supplemental and expensive testosterone replacement therapy.

Investigation of the Relationship between HIWI3 rs11703684 (C&gt;T) Polymorphism and Idiopathic Azoospermia/Oligozoospermia in the Kurdish Population of Kermanshah

Background &amp; Objective: Genetic factors play a major role in the development of male idiopathic infertility. Because of the multi-genetic base of this disease, not all genetic factors have been investigated. PIWI genes have been reported to be involved in the regulation of piRNAs in spermatogenesis. Our study assessed the association between HIWI3 rs11703684 (C&gt;T) gene polymorphism with the risk of male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah.&#x0D; Materials &amp; Methods: In this case-control investigation, we included two hundred individuals consisting of 100 men with idiopathic azoospermia/oligozoospermia and 100 fertile men as the control group. To determine genotypes of HIWI3 C&gt;T polymorphism, we used the Tetra Arms-PCR technique and significant values were considered as p&lt;0.05.&#x0D; Results: Our findings did not show a statistically significant difference in the genotype frequency of the recessive model (P = 0.118; OR = 0.158; CI, 0.019–1.339), dominant (P = 0.169; OR = 0.625; CI, 0.341–1.144) and co-dominant (P = 0.527; OR = 0.778; CI, 0.417–1.450). In addition, the results described a negative difference in allelic frequency of HIWI3 (rs11703684 C&gt;T) in men with idiopathic azoospermia/oligozoospermia and control group (P = 0.288; OR = 0.749; CI, 0.463–1.212).&#x0D; Conclusion: The current study does not indicate the probability effect of HIWI3 rs11703684 (C&gt;T) gene polymorphism on the male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah. The critical role of PIWI genes in spermatogenesis and as a candidate risk factor for male infertility remained unknown.

Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.

Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans.

FRI083 Identifying Determinants Of Change In Physical Activity In Women With Obesity And Infertility Following The Obesity-Fertility Program

Abstract Disclosure: M. Gélinas: None. M. Belan: None. F. Jean-Denis: None. M. Pesant: None. M. Langlois: None. B. Carranza-Mamane: None. J. Baillargeon: Grant Recipient; Self; Ferring Pharmaceuticals. INTRODUCTION: Obesity is common among women of childbearing age and a risk factor for infertility. The Obesity-Fertility (OF) lifestyle program is an intervention that supports healthy lifestyle habits in women with infertility during the preconception period. Such support, that includes practice of physical activity (PA), is recommended for the management of obesity, and could improve fertility in individuals with obesity. However, there is a large variability in individual response in low-intensity lifestyle interventions. It is therefore important to determine whether there is a typical profile of women with obesity and infertility who benefit more from such program. OBJECTIVE: To determine the baseline characteristics associated with a change in sedentary time in hours per week (ST), the intensity level in leisure PA in METs, and the distance in meters walked during the 6-minute walk test (6MWT) after 6 months of participation in the OF lifestyle program. The 6MWT is associated to the functional capacity in populations with obesity. METHODS: Data from 85 participants enrolled in a randomized controlled trial and who had a research visit after 6 ± 1 months of follow-up were analyzed using univariate and multiple linear regressions (intervention, IG = 42; control, CG = 43). Participants in the CG received standard fertility care, while those in the IG received the OF program alone, which combines individual meetings with a kinesiologist and a nutritionist, and group sessions. Participants were assessed at baseline and after 6 months for outcomes, other lifestyle, anthropometry, weight loss readiness tool, quality of life, and the socio-economical status. RESULTS: After 6 months, women of the IG significantly improved their PA (+0.87 METs, p &amp;lt;0.001), ST (-6.74 hours/week, p &amp;lt;0001), and 6MWT (+23.8 m, p &amp;lt;0.001). The only independent baseline determinants of these changes were a lower baseline level of PA for an increase in PA (p=0.032); a higher baseline ST for a decrease in ST (p=0.002); and a lower baseline distance at the 6MWT for an increase in 6MWT distance (p&amp;lt;0.001). Regarding the CG, the 6-month changes in these outcomes were not significant (PA: +0.21, p=0.34; ST: -0.13, p=0.95; 6MWT: +7.3, p=0.26). The determinants of such changes were the same than in the IG, except for the baseline BMI ≥40 kg/m², which was an additional independent determinant of increase in ST, and baseline 6MWT was not associated with change in 6MWT. CONCLUSION: Less active women with lower functional capacity at baseline appear to benefit more from the OF lifestyle program. Based on the literature, psychosocial factors (motivation, self-efficacy, social support, etc.) were expected to be associated with changes in PA outcomes, but it is likely that our sample did not provide enough power to identify these relationships, or the tools we used were not enough sensitive for assess these characteristics. Presentation: Friday, June 16, 2023

Garcinia Mangostana Pericarp Extract Protection on Reproductive Function of Obese-Diabetic Rats Model

Background: Type 2 diabetes mellitus (T2DM) in obese has been considered a risk factor for male infertility. Garcinia mangostana pericarp extract (GMPE) is known to have anti-hyperglycemic, anti-diabetic, and anti-inflammatory effects. This study aimed to evaluate the effect of GMPE therapy on reproductive function in obese T2DM rats by examining testosterone level, testicular histopathological features, and hs-CRP level.Methods: Thirty-six male Wistar rats, aged 2-3 months, were randomly divided into 6 groups and treated with a standard diet (NC), high-fat diet (HFD) with GMPE 200 mg/kgBW (obese GMPE control/OGC200), HFD with 45 mg/kgBW STZ-NA (obese-diabetic control/ODC), obese-diabetic rats with GMPE 100 (DG100); 200 (DG200); and 400 mg/kgBW (DG400). STZ-NA was administered after 8 weeks of HFD treatment and followed by GMPE for 8 weeks after T2DM was confirmed. The level of hs-CRP and testosterone were measured in the serum using an enzyme-linked immunosorbent assay. Testicular histopathological examination was measured after 8 weeks of treatment by using Modified Jonhson Score (MJS) with HE staining.Results: ODC rats significantly showed increased hs-CRP level compared to NC (8.76±0.27 vs 0.30±0.07 ng/mL, P&lt;0.001) and reduced testosterone level and MJS compared to NC (73.69±2.22 vs170.14±1.34 ng/dL, 4.57±0.93 vs 9.87±0.16 MJS, respectively, P&lt;0.001). Testosterone and hs-CRP levels showed a negative and significant correlation (r=-0.974 and P&lt;0.001). On the treatment group, GMPE significantly reduced hs-CRP and increased testosterone levels in a dose-dependent manner.Conclusion: GMPE effectively protects reproductive function in obese DM rats by increasing testosterone levels and advanced spermatogenesis, as well as decreasing hs-CRP level.

Retracted: Examination on Risk Factors of Infertility Caused by EMT and Their Correlation with VEGF, TNF-α, IL-6, IL-10, and IL-17.

[This retracts the article DOI: 10.1155/2022/4421418.].

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age

BackgroundThis study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association.MethodsThis study is a population-based case–control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package “mediation”.ResultsThe survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01–0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%.ConclusionThese results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Analysis of copy number variation in AZF region of Y chromosome in patients with spermatogenic failure

To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.

Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice

Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.

Obesity May Impairs Mice Testicular Structure by STAT3/CYP19A1/Testosterone

Obesity is an increasing serious global public health issue and a risk factor for male infertility. Aromatase expression level is elevated in obese men, and this high level is as-sociated with diminished serum testosterone levels. We explored the underlying mechanism of infertility in obese men. Genome-wide association study datasets were used to predict the causal relationship between obesity and male infertility. An obese male mouse model was generated by feeding mice a high-fat diet while control model was generated by feeding mice a normal chow diet. Serum indicators including free fatty acids, insulin, Follicle-stimulating hormone, and testosterone were measured using ELISA, and impaired fertility in mice was demonstrated using immunohistochemistry. The expression levels of STAT3 and CYP19A1 were measured by RT-qPCR and western blotting, respectively. Simultaneous bioinformatics analysis of publicly available data was performed using the R programming language and JASPAR database. Obesity might lead to male infertility from a genomic perspective. Obese mice displayed reduced serum testosterone and follicle stimulating hormone levels along with structural abnormalities, ectopic lipid deposition, and chronic inflammation in the testes. Upregulation of STAT3/CYP19A1 expression in obese mice was linked to reduced serum testosterone levels and impaired fertility. Our observation may support the hypothesis that since the elevation of STAT3 expression in obesity, the promoted expressed CYP19A1 could increase a shift from testosterone to estrogens. The persistently elevated level of estrogen will further stimulate STAT3, which may constitute a positive feedback loop. These findings provide new insights into the mechanisms of obesity-mediated male fertility impairment.

Analysis of the factors influencing male infertility of reproductive age in Jinan.

The World Health Organization (WHO) defines infertility as a person failing to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. Infertility includes female infertility and male infertility. The aim of this paper is to study the etiology of infertility and related influencing factors in men of reproductive age in Jinan. In this study, 172 male infertile patients who attended the Department of Assisted Reproduction of Shandong Provincial Maternal and Child Health Hospital in Shandong, China and the Infertility Clinic of Jinan Central Hospital in Shandong, China from August 2021 to April 2022 are selected as the study population (infertility group). A convenience sampling method is used to select 257 men from couples attending the Obstetrics Department of Qilu Hospital in Shandong, China, the Obstetrics Department of the Second Hospital of Shandong University in Shandong, China, and the Obstetrics Department of Maternal and Child Health Hospital in Shandong, China from October 2021 to February 2022 as the study subjects (control group). A self-designed questionnaire is used to conduct the survey, which includes basic personal information, lifestyle information, marital and family-related information, and one-way and multi-way logistic regression analyses are performed. The average age of the case group and the control group are 34.03±5.13 years old and 33.61±8.18 years old; the average height is 175.80±5.91 cm and 176.78±5.25 cm; the average weight is 80.28±14.70 kg and 83.09±45.36 kg. The differences in age, height, and weight between the case group and the control group are not statistically significant by t-test. Moderate oligospermia is the predominant cause of infertility in men of reproductive age in Jinan. A multifactorial logistic regression analysis yields that academic qualifications (OR=2.518, 95% CI: 1.023 to 6.196), coffee consumption (OR=7.692, 95% CI: 1.623 to 36.460), living in a room that had been renovated within a period of time (OR=2.769, 95% CI: 1.104 to 6.949), stress level (OR=47.280, 95% CI: 23.656-94.494), quality of sexual life (OR=3.352, 95% CI: 1.331-8.442), and duration of couple separation (OR=3.851, 95% CI: 1.094-13.557) are the main risk factors for infertility in men of reproductive age in Jinan. In this study, a total of 6 risk factors are screened for male infertility in Jinan in the reproductive age, including high academic qualifications, coffee consumption, living in a room that has finished renovation within 3 months, high stress, poor quality of sexual life, and long spousal separation. Three factors can be controlled, avoided, or reduced through personal actions; the factors are coffee consumption, living in a room that has finished renovation within 3 months, and high stress, all of which may reduce the level of male reproductive health.

Endometrial receptivity in women of advanced age: an underrated factor in infertility.

Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility. The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field. The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded. In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity. Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age has been shown to have a negative impact on endometrial functioning. This information can provide recommendations for future research focusing on molecular mechanisms of age-related cellular senescence, cellular composition, and transcriptomic changes in relation to endometrial aging. Additionally, further prospective research is needed to explore newly emerging therapeutic options, such as the senolytic agents that can target endometrial aging without affecting decidualization. Moreover, clinical trial protocols, focusing on oocyte donation cycles, would be beneficial in understanding the direct clinical implications of endometrial aging on pregnancy outcomes.

Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.

Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility. We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval. 24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress. Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.