Genital Tract Infection Research Articles

INFLUENCE OF UROGENEITRAL INFECTION IN PREGNANT WOMEN ON THE UTERINE – FETOPLACENTARY COMPLEX

As reported by the World Health Organization (WHO), approximately 20 % of pregnant women globally are aff ected by an infection of the lower genital tract. Urogenital infection can result in complications during the onset and progression of pregnancy, as well as the postpartum period. These complications include placental dysfunction, premature birth, low birth weight, premature rupture of the fetal membranes, and postpartum endometritis. A marker of normal placental function is α2-fertility microglobulin (AFMG), the determination of which will refl ect the presence or absence of a uterine- fetoplacental complex violation during urogenital infection in pregnant women.The aim of the study is to reveal the infl uence of urogenital infection on the dysfunction of the uterine – fetoplacental complex in pregnant women.Materials and methods. A total of 75 pregnant women were examined, divided into two groups: the main group (MG) and the comparison group (CG). The MG consisted of 55 pregnant women, of whom 35 underwent local sanitation of the urogenital infection according to the identifi ed pathogen (Subgroup A) and 20 refused this procedure (Subgroup B). The CG consisted of 20 pregnant women without urogenital infection, as determined by bacterioscopic, bacteriological, and polymerase chain reaction (PCR) examinations. All pregnant women underwent determination of AFMG in blood serum via immunoenzymatic methodology. The statistical analysis was conducted using the MedStat software (serial number MS00019). The study was performed in accordance with the provisions of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of PFMU for all women who participated in this study. Statistical processing was performed using the MedStat program (serial number MS00019). The work is a part of the initiative research work of the Department of Obstetrics and Gynecology No. 1 of Poltava State Medical University «Pathogenetic role of endothelial dysfunction and genetic features in pathology during pregnancy and gynecological diseases» (state registration No. 0117U005253, term of implementation 2017-2023).Research results. The results of the study demonstrated that pregnant women with a urogenital infection had a history of chronic pyelonephritis 5.5 times more frequently (p = 0.03) and salpingo- oophoritis 10.2 times more frequently (p < 0.001), which may be a source of latent infection. The most prevalent infectious agents among pregnant women were: The most prevalent microorganisms were Ureaplasma urealyticum (21.4 %), Candida fungi (19.04 %), Gardnerella vaginalis (11.9 %), and Toxoplasma gondii (11.9 %). The level of AFMG in pregnant women with urogenital infection was observed to be 4.3 times lower than in pregnant women with CG (p < 0.001). The remediation of an infection of the lower genital tract during pregnancy has been observed to increase AFMG production by a factor of four (p < 0.001). The level of AFMG in pregnant women of CG was 2.2 times higher than in pregnant womenof Subgroup A (p < 0.004).Conclusions. It was demonstrated that urogenital infection in pregnant women has a considerable impact on the dysfunction of the utero- fetoplacental complex. It was also shown that local sanitation of the lower genital tract in these women, based on the identified pathogen, has a benefi cial eff ect on the placenta’s functioning. However, this approach does not fully address the issue of protein synthesis impairment.

Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model.

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn2+-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis.

Associations of Ureaplasma urealyticum infection with male infertility and intrauterine insemination outcomes.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation (P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.

Genital Tract Infections and Their Correlation with Sociodemographic Features among Infertile Women at a Tertiary Care Center

Genital Tract Infections and Their Correlation with Sociodemographic Features among Infertile Women at a Tertiary Care Center

7800 Real World Incidence Of Urinary Tract Infections (UTI) & Genital Tract Infections (GTI) With SGLT2 Inhibitors Alone Or In Combination With DPP4 Inhibitors In Patients With T2D In India

Abstract Disclosure: A. Gupta: None. N. Singh: None. S. Phatak: None. A.N. Singh: None. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with urinary and genital tract infections (UTI and GTI), as they increase glucose availability in these areas, fostering bacterial growth. A study found a 26% lower occurrence of UTI and GTI in patients using a combination of Dipeptidyl Peptidase-4 inhibitors (DPP4i) and SGLT2i compared to those on SGLT2i alone. (1) The present study assessed whether patients receiving SGLT2i were at increased risk of significant UTIs & GTIs compared with those using a combination of SGLT2i & DPP-4i. A cross-sectional, multicenter, real-world study was conducted that enrolled patients with Type 2 Diabetes Mellitus (T2D) from 15th June to 30th September 2023 across 42 sites in India. The recorded data encompassed demographic information, glycemic parameters, medication use & information on hygiene practices. The sample considered for this analysis is those on SGLT2i & with or without DPPi. [Note – all patients are on other OHAs besides SGLT2i or DPP4i]. Of 10,179 patients, 2,123 were on only SGLT2i (Group A), and 8,052 were on SGLT2i and DPP4i (Group B). Group A showed a significantly higher incidence of UTI (9.09% vs. 6.11%) and GTI (6.64% vs. 5.2%). Elderly patients, especially those aged 60-69 and >70, exhibited higher UTI and GTI rates in Group A. In both genders, the incidence of UTI was higher in Group A (7.93%-males & 10.53%-females) than in Group B (5.41%-males & 7.11%-females). Amongst males, the incidence of GTI was significantly higher in Group A (5.63%) than in Group B (4.12%). In females, no significant difference was noted. Two models were developed to assess the impact of SGLT2i and insulin usage on UTI and GTI likelihood. Propensity score matching addressed confounding variables like age, gender, BMI, and comorbidities. Subsequently, logistic regression analysis focused solely on medication variables. The odds of developing UTI were calculated for various medication possibilities. As against ‘No SGLT2i’, Group A has 2.24 (CI 1.69-2.96) times higher odds of UTI, while Group B has 1.45 (CI 1.15-1.72) times. or GTI, Group A shows 3.18 (CI 2.23-4.53) times higher odds, and Group B has 2.48 (CI 1.90-3.25) times, as against ‘No SGLT2i’. In summary, DPP-4 & SGLT2 inhibitors combination therapy decreases the incidence of UTI & GTI linked to SGLT2i. Reference: (1) Fadini et al. DPP4i moderate the risk of GTI & UTI associated with SGLT2i. Diab Obes Metab. 2018 Mar;20(3):740-744. Presentation: 6/2/2024

Antifungal susceptibility and biofilm production of Candida species- causative agents of female genital tract infections.

Recurrent vulvovaginal candidosis (RVVC) is a chronic infection affecting 8-10% of women worldwide. Biofilm production of the infecting species and reduced sensitivity to antimycotics could contribute to the recurrence of this infection. This study aimed to examine the biofilm production ability and antifungal susceptibility of genital yeast isolates to determine their virulence potential. Matrix-assisted laser desorption in ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to identify 300 Candida species. Using crystal violet method, strains were categorized into non-producers, weak, moderate, and strong biofilm producers (BFP). Antifungal susceptibility testing was performed using commercial Integral System YEASTS Plus test (ISYPT) and broth microdilution method (BMM). MALDI-TOF MS identified 150 Candida albicans, 124 non-albicans Candida (NAC), and 26 Saccharomyces cerevisiae strains. Within 138 (46.0%) BFP, 23 (16.7%) were strong, 44 (31.9%) moderate, and 71 (51.4%) weak. BMM was done for 43 BFP selected isolates with nystatin MIC ˃1.25 μl, fluconazole MIC ˃64 μl, and clotrimazole MIC ˃1.0 μl determined by ISYPT. Compared to all examined isolates, BMM confirmed that: i) C. albicans and NAC BFP showed low sensitivity to fluconazole (12% and 4%, respectively); ii) all BFP showed low sensitivity to nystatin (12.7% C. albicans, 14.5% NAC, and 23.1% S. cerevisiae); iii) clotrimazole in vitro was the most efficient regarding C. albicans and S. cerevisiae strains, but in 4.0% NAC BFP for this antimycotic higher MIC was established. Novel antimycotics or possible combinations of antifungal agents and natural products could be a new treatment option for RVVC.

Intranasal immunization with CPAF combined with cyclic-di-AMP induces a memory CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum.

Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants. To address this need, we produced CPAF in a cell-free protein synthesis platform and adjuvanted it with the TLR9-agonist CpG1826, STING (stimulator of interferon genes) agonist cyclic-di-AMP (CDA), and/or the squalene oil-in-water nanoemulsion, AddaS03. We determined that intranasal immunization with CPAF plus CDA was well tolerated in female mice, induced CD4 T cells that produced IL-17A or IFNγ, significantly reduced bacterial shedding, and shortened the duration of infection in mice intravaginally challenged with Chlamydia muridarum . These data demonstrate the potential for CDA as a mucosal adjuvant for vaccines against Chlamydia genital tract infection.

Global pattern of persistent human papillomavirus infection in female genital tract: An update system review and meta-analysis

Global pattern of persistent human papillomavirus infection in female genital tract: An update system review and meta-analysis

Vulvovaginal candidiasis clinical signs, and distribution of Candida species

Background: Vulvovaginal candidiasis is a global issue of concern due to its association with economic costs, sexually transmitted infections, and ascending genital tract infection. The aim of this study was to determine clinical signs and species distribution of Candida species causing vulvovaginal candidiasis. Methods: A cross-sectional study was conducted from December to June 2021-2024 among 400 women attending Obstetrics and Gynecology outpatient clinics in Sana'a City. The study involved collecting vaginal swabs from each participant and analyzing them in a microbiology laboratory. The swabs were used to identify yeast cells, fungal culturing, and germ tube formation tests. The study also used the VITEK II system to confirm species identification, with the VITEK® 2 YST ID identification card being used to identify Candida species. Results: A study of 400 women found that 91.8% were infected with Candida albicans, while 8.2% were infected with other non-Candida albicans. The majority were aged 26-35, with secondary education being the most common. Most were married, with 1-3 pregnancies. The most common sign distribution was vaginal discharge with a 99.5% prevalence. Dysuria was the lowest, with a 65.0% prevalence. Candida species were most frequently isolated, with Candida albicans being the most common. Candida tropicalis was found in 1 out of 6 women, while Candida dubliniensis, Candida famata, Candida glabrata, and Candida lusitaniae were found in 1 out of 6 women. Conclusions: The high prevalence rate of vulvovaginal candidiasis and observation of a low prevalence rate of nonalbicans Candida species in the present study substantiate the importance of conducting continuous epidemiological surveys to measure changes in species distribution from C. albicans to non-albicans Candida species in Yemen.

Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin. This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss. The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104. Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.

Optimization of Ethoxzolamide Analogs with Improved Pharmacokinetic Properties for In Vivo Efficacy against Neisseria gonorrhoeae.

Drug-resistant gonorrhea is caused by the bacterial pathogen Neisseria gonorrhoeae, for which there is no recommended oral treatment. We have demonstrated that the FDA-approved human carbonic anhydrase inhibitor ethoxzolamide potently inhibits N. gonorrhoeae; however, is not effective at reducing N. gonorrhoeae bioburden in a mouse model. Thus, we sought to optimize the pharmacokinetic properties of the ethoxzolamide scaffold. These efforts resulted in analogs with improved activity against N. gonorrhoeae, increased metabolic stability in mouse liver microsomes, and improved Caco-2 permeability compared to ethoxzolamide. Improvement in these properties resulted in increased plasma exposure in vivo after oral dosing. Top compounds were investigated for in vivo efficacy in a vaginal mouse model of gonococcal genital tract infection, and they significantly decreased the gonococcal burden compared to vehicle and ethoxzolamide controls. Altogether, results from this study provide evidence that ethoxzolamide-based compounds have the potential to be effective oral therapeutics against gonococcal infection.

Bacillus coagulans LMG S-24828 Impairs Candida Virulence and Protects Vaginal Epithelial Cells against Candida Infection In Vitro.

Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women of reproductive age at least once during their lifetime, with 5-8% developing the recurrent form (RVVC). The disease is triggered by the overgrowth of Candida on the vaginal mucosa. Here, in order to establish its probiotic potential in the context of VVC, we evaluated the anti-fungal effects of the spore-producing Bacillus coagulans LMG S-24828 against C. albicans and C. parapsilosis as well as its beneficial effects in counteracting Candida vaginal infection in vitro. Our results show that both live B. coagulans and its Cell-Free Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, live B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells, showed co-aggregation capacity, and exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

Mild coronavirus disease 2019: Results of a multicentric prospective study on severe acute respiratory syndrome coronavirus 2 presence in semen fractions and cells and its effects on semen parameters.

Severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function. To investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters. Prospective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined. 11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics. 11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.

Immunity to Sexually Transmitted Bacterial Infections of the Female Genital Tract: Toward Effective Vaccines.

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including antibiotic treatments, are limited by the often-asymptomatic nature of these infections, the need for repetitive and continual screening of sexually active persons, antibiotic resistance for gonorrhea, and shortages of penicillin for syphilis. While vaccines exist for viral STIs like human papillomavirus (HPV) and hepatitis B virus (HBV), there are no vaccines available for bacterial STIs. This review examines the immune responses in the female genital tract to these bacterial pathogens and the implications for developing effective vaccines against bacterial STIs.

Gender Differences in the Clinical Profile of Sodium-Glucose Cotransporter-2 Inhibitor-Related Urinary Tract Infections.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a novel class of oral antidiabetic agents with proven cardiovascular and mortality benefits. By promoting glucosuria, SGLT2Is increase the risk of genital and urinary tract infections (UTIs), which remain uncomplicated in most cases. Comparative studies detailing the gender differences in the clinical profile of SGLT2I-related UTIs (SUTIs) are lacking. Hence, this study was designed to investigate the gender-related differences in the clinical profile of SUTIs. Methodology This prospective study enrolled 100 consecutive diabetes mellitus patients with UTI symptoms who were on SGLT2Is. In addition to collecting clinical details, patients were subjected to the following investigations: complete blood counts, urea, creatine, liver function, lipid components, urine analysis, urine culture, and ultrasonography. Results Females (n = 80) outnumbered males (n = 20). Although females were younger than males (53.68 ± 10.26 vs. 63.30 ± 10.75 years, p = 0.003), body mass index (29.84 ± 7.22 vs. 24.62 ± 3.10 kg/m2, p = 0.008) and waist circumference (103.01 ± 14.49 vs. 93.75 ± 4.50 cm, p = 0.109) were higher in females. About 22.5% of females had undergone hysterectomy. The mean duration of diabetes mellitus was longer in males (10.64 ± 6.74 vs. 7.78 ± 4.75 years), whereas the median duration of SGLT2I use (4 (interquartile range (IQR) = 1-12) vs. 3 (IQR = 2-4) months) and mean HbA1c levels were not different between the two groups. A greater proportion of males were complicated by retinopathy (55% vs. 15%) and proteinuria (65% vs. 17.5%), while neuropathy (85% vs. 71.25%) rates were similar. Overall, 35% of males had complicated UTIs (renal abscess, pyelonephritis, prostatic abscess) compared to only 3.75% of females (p = 0.001). Conclusions The majority of SUTIs are uncomplicated in females whereas in males one-third are complicated infections. Although females with SUTI had a higher prevalence of obesity and dyslipidemia, males had a longer duration of diabetes mellitus and higher retinopathy prevalence. Extreme caution should be exercised in patients at risk for SUTI before prescribing SGLT2I.

Effectiveness of vaginal probiotics Lactobacillus crispatus chen-01 in women with high-risk HPV infection: a prospective controlled pilot study.

Female genital tract infection with high-risk human papilloma virus (HR-HPV) has the risk of developing into cervical cancer, and there is still a lack of effective therapeutic strategies. Probiotic intervention is considered as a potential intervention for HR-HPV, while exploration into living probiotic preparations for specific diseases remains limited and insufficient. This prospective controlled pilot study was conducted to observe the effect of intravaginal transplantation of a vaginal isolated natural probiotic strain, Lactobacillus crispatus chen-01, on the clearance of high-risk HPV infection. 100 women with high-risk HPV infection were enrolled and randomly divided into placebo group and probiotic treatment group, which received intravaginal transplantation of L. crispatus chen-01. Cervical exfoliated cells were collected 6 months later for detecting DNA load, typing of HPV, and cytological analysis. Our results showed that vaginal transplantation with L. crispatus chen-01 significantly reduced viral load of HPV, ameliorated HPV clearance rate, and improved vaginal inflammation state without causing obvious adverse reactions. Analysis of 16S rRNA sequencing revealed that L. crispatus chen-01 could effectively reconstitute the vaginal microbiota in women with high-risk HPV, which might be one of the underlying mechanisms of the beneficial effect of L. crispatus chen-01 transplantation. Our results suggested that vaginal transplantation of L. crispatus chen-01 might be a promising treatment for patients with high-risk HPV infection.

O-304 Is there any association between thyroid-stimulating hormone (TSH) levels and semen parameters? A retrospective study in a European fertility clinic

Abstract Study question Is there any association between TSH levels and semen parameters considering age, body mass index (BMI), and life style? Summary answer In line with the results of logistic regression, normal TSH values increase the probability of having a higher sperm count. What is known already To date, association between TSH levels, semen parameters and other hormones have not been thoroughly investigated in European andrology labs. However, while andrology guidelines do not support a systematic evaluation of thyroid function, some studies reported that men in infertility clinics have higher risks of presenting thyroid disorders than in the general population. Study design, size, duration Both partners investigated for sterility are routinely checked for TSH in the work up of our clinic. We examined for 2021 – 2023 all 347 male patients (infertile/fertile) with complete records of demographic data, semen analysis and hormone analysis. Patients suffering from azoospermia, genital tract infections, hormonal supplementation or heavy medical treatments (radiotherapy, chemotherapy), as well as those receiving iodine supplements or drugs that could potentially affect testicular or thyroid physiology, were excluded. Participants/materials, setting, methods Age, BMI, smoking and detailed alcohol intake were recorded. A blood sample was taken from each patient in connection with the sperm collection to measure TSH, FSH, LH, prolactin and testosterone levels. Spearman’s correlation coefficients were used to determine correlations among hormones. Statistical analyses were performed using semen parameters as dichotomized using WHO reference values. Men above the reference values for count, concentration and motility were used as comparison subjects in multivariate logistic regression. Main results and the role of chance The analysis explored relationships between age, BMI, smoking, alcohol consumption and semen parameters with TSH hormone levels. The mean age of the participants was 35.8 ±7.43 years and BMI was 27.2 ±4.54 kgm-2. Of all participants, 37% reported being smokers, alcohol consumption was 3% regularly, 35% occasionally, 44% rarely, 18% none. Considering a TSH level (0.4-4 mIU/l) as normal, the prevalence of thyroid dysfunction in the cohort was 0.9% (TSH &amp;lt;0.4) and 1.1% (TSH &amp;gt;4) implying that most patients had normal TSH levels. In this cohort, TSH levels were not found to be significantly affected by age, BMI, smoking or alcohol consumption despite being known as putative confounding factors influencing TSH levels. Among the various hormones evaluated, only one significant positive correlation was found between TSH and Prolactin (r = 0.199, p = 0.0001), while a trend towards a negative correlation between TSH and LH (r=-0.101, p = 0.073) was suggested. Multivariate logistic regression analysis showed, not surprisingly, that age was a factor influencing sperm count, sperm concentration as well as total and progressive sperm motility. Logistic regression also showed that when TSH values were within the normal range, sperm counts were significantly higher (OR:1.302, P = 0.043; CI95%:1.009-1.681). Limitations, reasons for caution Sperm morphology and viability were not recorded. Evaluation of thyroxine (T4) and triiodothyronine (T3) levels could be useful. The crucial role of iodine and the complex relationship between iodine and selenium status (which depends on geographical location) in affecting thyroid function should be taken into account in future studies. Wider implications of the findings Male patients with abnormal TSH levels are not very common in this region. Normal TSH level is associated with a higher sperm count. TSH assessment in infertile couples should be routine in both partners, given the recorded worldwide increase in thyroid dysfunction and iodine deficiency. Trial registration number not applicable

Association between hospital procedure volume, socioeconomic status, comorbidities, and adverse events related to surgical abortion: a nationwide population-based cohort study

BackgroundLimited evidence exists on the influence of hospital procedure volume, socioeconomic status, and comorbidities on surgical abortion outcomes. ObjectiveOur study aimed to assess the association between hospital procedure volume, individual and neighborhood deprivation, comorbidities, and abortion-related adverse events. Study DesignA nationwide population-based cohort study of all women hospitalized for surgical abortion was conducted from January 1, 2018, to December 31, 2019 in France. Annual hospital procedure volume was categorized into four levels based on spline function visualization: very low (<80), low ([80-300[), high ([300-650[), and very high-volume (≥650) centers. The primary outcome was the occurrence of at least one surgical-related adverse event, including hemorrhage, retained products of conception, genital tract and pelvic infection, transfusion, fistulas and neighboring lesions, local hematoma, failure of abortion, admission to an intensive care unit or death. These events were monitored during the index stay and during a subsequent hospitalization up to 90 days. The secondary outcome encompassed general adverse events not directly linked to surgery. ResultsOf the 112,842 hospital stays, 4,951 (4.39%) had surgical-related adverse events and 256 (0.23%) had general adverse events. The multivariate analysis showed a volume-outcome relationship, with lower rates of surgical-related adverse events in very high-volume (2.25%, aOR=0.34, 95%CI [0.29-0.39], p<0.001), high-volume (4.24%, aOR=0.61, 95%CI [0.55-0.69], p<0.001), and low-volume (4.69%, aOR=0.81, 95%CI [0.75-0.88], p<0.001) when compared to very low-volume centers (6.65%). Individual socioeconomic status (aOR=1.69, 95%CI [1.47-1.94], p<0.001), neighborhood deprivation (aOR=1.31, 95% CI [1.22-1.39], p<0.001), and comorbidities (aOR=1.79, 95%CI [1.35-2.38], p<0.001) were associated with surgical-related adverse events. Conversely, the multivariate analysis of general adverse events did not reveal any volume-outcome relationship. ConclusionThe presence of a volume-outcome relationship underscores the need for enhanced safety standards in low-volume centers to ensure equity in women's safety during surgical abortions. However, our findings also highlight the complexity of this safety concern which involves multiple other factors including socioeconomic status and comorbidities that policymakers must consider.

Leukocytospermia and/or Bacteriospermia: Impact on Male Infertility.

Infertility is a globally underestimated public health concern affecting almost 190 million people, i.e., about 17.5% of people during their lifetime, while the prevalence of male factor infertility is about 7%. Among numerous other causes, the prevalence of male genital tract infections reportedly ranges between 10% and 35%. Leukocytospermia is found in 30% of infertile men and up to 20% in fertile men. Bacterial infections cause an inflammatory response attracting leukocytes, which produce reactive oxygen species (ROS) and release cytokines, both of which can cause damage to sperm, rendering them dysfunctional. Although leukocytospermia and bacteriospermia are both clinical conditions that can negatively affect male fertility, there is still debate about their impact on assisted reproduction outcomes and management. According to World Health Organization (WHO) guidelines, leukocytes should be determined by means of the Endtz test or with monoclonal antibodies against CD15, CD68 or CD22. The cut-off value proposed by the WHO is 1 × 106 peroxidase-positive cells/mL. For bacteria, Gram staining and semen culture are regarded as the "gold standard", while modern techniques such as PCR and next-generation sequencing (NGS) are allowing clinicians to detect a wider range of pathogens. Whereas the WHO manual does not specify a specific value as a cut-off for bacterial contamination, several studies consider semen samples with more than 103 colony-forming units (cfu)/mL as bacteriospermic. The pathogenic mechanisms leading to sperm dysfunction include direct interaction of bacteria with the male germ cells, bacterial release of spermatotoxic substances, induction of pro-inflammatory cytokines and ROS, all of which lead to oxidative stress. Clinically, bacterial infections, including "silent" infections, are treatable, with antibiotics being the treatment of choice. Yet, non-steroidal antiphlogistics or antioxidants should also be considered to alleviate inflammatory lesions and improve semen quality. In an assisted reproduction set up, sperm separation techniques significantly reduce the bacterial load in the semen. Nonetheless, contamination of the semen sample with skin commensals should be prevented by applying relevant hygiene techniques. In patients where leukocytospermia is detected, the causes (e.g. infection, inflammation, varicocele, smoking, etc.) of the leukocyte infiltration have to be identified and addressed with antibiotics, anti-inflammatories or antioxidants in cases where high oxidative stress levels are detected. However, no specific strategy is available for the management of leukocytospermia. Therefore, the relationship between bacteriospermia and leukocytospermia as well as their specific impact on functional sperm parameters and reproductive outcome variables such as fertilization or clinical pregnancy must be further investigated. The aim of this narrative review is to provide an update on the current knowledge on leukocytospermia and bacteriospermia and their impact on male fertility.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.