Search Results (75)

Objective: This retrospective study aims to evaluate the effect of copper intrauterine device (Cu-IUD) use on the adequacy and diagnostic quality of endometrial biopsy specimens in women with abnormal uterine bleeding (AUB). Patients with levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. The study compares the histopathological adequacy of endometrial samples between Cu-IUD users and non-users, highlighting potential interpretation challenges in routine pathological assessment. Methods: The study was conducted on 409 women aged 25–55 who presented with abnormal uterine bleeding (AUB) to the Gynecology and Obstetrics Outpatient Clinic at Kayseri City Hospital between 1 April 2021 and 1 April 2023. The patients were divided into two groups: copper IUD (Cu-IUD) users (n = 215) and non-IUD users (n = 194). Patients using levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. Endometrial biopsies were obtained using the Pipelle curette technique without anesthesia, preserved in 10% formalin, and assessed for pathological classification and diagnostic adequacy. Results: The proportion of unclassifiable pathological categories was significantly higher in copper IUD users (63.93%) compared to non-IUD users (36.05%) (p = 0.013). Additionally, a negative correlation was observed between pathological category and endometrial thickness (r = −0.3147, p < 0.001), suggesting that thinner endometrial lining may reflect atrophic or diagnostically ambiguous tissue patterns. However, no significant association was found between IUD use and endometrial thickness (p = 0.073). Conclusions: The findings indicate that copper IUD use may affect the diagnostic adequacy of endometrial biopsy specimens, likely due to inflammatory or structural changes in the endometrium. These results underline the importance of considering IUD-related alterations when interpreting biopsy findings. Further research is needed to refine diagnostic approaches and better understand the clinical implications of these effects. Full article

Background/Objectives: This study aimed to investigate oncologic and obstetrical outcomes of patients conservatively treated for atypical hyperplasia (AH), endometrial intraepithelial neoplasm (EIN), and early endometrial cancer (EC), as well as factors that influence these outcomes. Methods: This study included 87 women conservatively treated due to AH/EIN and well-differentiated endometrioid EC confined only to the endometrium during past 10 years. Therapy type, course, and duration were registered. The response totherapy after 12 months (remission vs. disease persisting or progressing) was considered as the oncologic outcome. All attempted and achieved pregnancies, along with conception method, gestational week, and delivery type, were recorded. The obstetrical outcomes were classified as adverse (miscarriage) or successful (healthy child). Results: All patients received LNG-IUD along with GnRHa and, if indicated, metformin. Complete remission was achieved in 74.7% of patients. The disease was persisting in 17.2% and progressing in 3.5% of patients, while recurrence was registered in 4.6% of patients. Radical surgery during follow-up was indicated in 15% of patients due to condition deterioration. Pregnancy was attempted by 29.9% of patients, out of which nine succeeded (34.6%). There were two early miscarriages, while the remaining seven pregnancies ended in a term delivery of a healthy child, mostly by planned cesarean section. The only predictor of long-term disease remission was malignancy-free control histological findings. Better therapy response and achieving remission in shorter time were predictors of good obstetrical outcome. Conclusions: This study proved the efficacy and safety of current protocols for AH/EIN/EC conservative treatment and indicated that adequate early (6-month) response totherapy has the most importance for long-term remission and pregnancy achievement. Full article

Background/objectives: Brain cancer remains difficult to treat, with survival statistics stagnant for decades. The resistance of glioblastoma brain tumours can greatly challenge the effectiveness of conventional cancer radiotherapy. However, high dose rate radiotherapy has unique effects that allow for normal tissue sparing whilst maintaining tumour control. The addition of targeted radiosensitisers, such as the chemotherapeutic drug methotrexate (MTX) or the high-Z halogenated pyrimidine drug iododeoxyuridine (IUdR), can improve radiotherapy outcomes. Combining these radiosensitiser agents with ultra-high dose rate (UHDR) synchrotron X-rays can bear synergistic effects to enhance the efficacy of these multi-modal UHDR therapies, providing a means to overcome the radioresistance of brain cancer. Methods: Here, we use controlled in vitro assays following treatment, including a clonogenic assay to determine long-term cell survival and γH2AX immunofluorescent confocal microscopy to quantify double-strand DNA breaks (DSBs). Results: We find significant enhancement for highly synergistic combinations of IUdR+MTX with synchrotron X-rays. Cell survival results demonstrate 5.4 times increased 9L gliosarcoma cell killing when these agents are combined with UHDR synchrotron X-rays compared with conventional X-rays alone at the same 5 Gy dose. The underlying mechanisms are unveiled using γH2AX imaging and reveal significant increases in DSBs and dying cells following exposure to UHDR radiation. Conclusions: Our results demonstrate that highly synergistic combination treatments using UHDR synchrotron radiation can yield significantly improved brain cancer killing compared with conventional radiotherapy. We anticipate that these additive, multi-modal combination therapies will provide options for more targeted and effective use of radiotherapies for the future treatment of brain cancer. Full article

Background/Objectives: To assess the effectiveness of the levonorgestrel-releasing intrauterine device (LNG-IUD) compared to hysteroscopic resection for managing women with symptomatic cesarean scar defects (CSDs). Methods: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of four electronic databases was conducted to identify studies comparing LNG-IUD with hysteroscopic management for symptomatic CSDs. Studies reporting outcomes of bleeding and spotting days and effectiveness rates were included. Quality assessment was performed using the ROBINS-I and RoB-2 tools. Results: Three studies involving 344 patients met the inclusion criteria. At 6 months, LNG-IUD use significantly reduced total bleeding days (MD −4.13; 95% CI: −5.17 to −3.09; p < 0.00001) and spotting days (MD 1.90; 95% CI: 0.43 to 3.37; p = 0.01) compared to hysteroscopic treatment. By 12 months, LNG-IUD demonstrated superior effectiveness (OR 3.46; 95% CI: 1.53 to 7.80; p = 0.003), with fewer total bleeding days (MD −5.69; 95% CI: −6.55 to −4.83; p < 0.00001) and spotting days (MD 3.09; 95% CI: 1.49 to 4.69; p = 0.0002). Approximately 50% of LNG-IUD users experienced amenorrhea within 1 year. Conclusions: LNG-IUD offers a minimally invasive and effective alternative to hysteroscopic resection for women with symptomatic CSD and no desire for future pregnancies. Its role should be considered in clinical practice, but further research is needed to validate these findings and define its long-term benefits and limitations. Full article

Background and Clinical Significance: This study presents a case of a 43-year-old female with a long history of infertility, treated for uterine leiomyoma and endometrial hyperplasia, over a total observation period of 42 months. Case Presentation: Levonorgestrel intrauterine device (LNG-IUD) therapy, as a first and subsequent line of treatment, was introduced. The patient also received medroxyprogesterone acetate oral treatment. Finally, she underwent surgery for an ovarian tumor that appeared to be an ovarian adenocarcinoma concurrent with endometrial cancer. After the removal of the reproductive organ, the patient was diagnosed with synchronous low-grade endometrioid adenocarcinoma in the endometrium and a concurrent grade 2 (G2) endometrioid adenocarcinoma in the left ovary. Conclusions: The prognosis and further management largely depend on whether these are two individual neoplasms or one metastatic tumor. Considering the young age of the patients, an early disease stage, a low grade of both cancers, and favorable prognosis, most synchronous endometrial and ovarian cancers are identified as two independent primary tumors. The diagnosis of a multi-focal neoplasm is important, as in patients with endometrial cancer and ovarian metastasis, the 5-year survival rate is 30–40%, whereas in the case of individual neoplasms, it is 75–80%. Full article

Fungi produce dormant structures that are responsible for protection during adverse environmental conditions and dispersal (disease spread). Ustilago maydis, a basidiomycete plant pathogen, is a model for understanding the molecular mechanisms of teliospore dormancy and germination. Dormant teliospores store components required for germination including mRNAs which may be stored as dsRNAs. RNA helicases are conserved enzymes that function to modulate, bind, and unwind RNA duplexes, and can displace other proteins. We hypothesize that RNA helicases function during teliospore dormancy to stabilize and/or modulate stored mRNAs. We identified the U. maydis udbp3 and uded1 as encoding RNA helicases of interest as they are upregulated in the dormant teliospore and decrease during germination. Experimental results suggest that udbp3 may function as a negative regulator of osmotic stress-responsive genes and that uded1 modulates stress response by repressing translation. The altered expression of uded1 also results in slow growth, polarized growth, and the formation of dsRNA. Together, the data support a role for both helicases modulating gene expression, in response to stress, leading to teliospore dormancy and also modulating responses for teliospore germination. Increasing our molecular understanding of these processes will aid in developing novel strategies to mitigate disease spread. Full article

Candida species, normally part of the healthy human flora, can cause severe opportunistic infections when their population increases. This risk is even greater in immunocompromised individuals. Women using intrauterine contraceptive devices (IUDs) are at higher risk for IUD-associated vulvovaginal candidiasis (VVC) because the device provides a surface for biofilm formation. This biofilm formation allows the normal flora to become opportunistic pathogens, leading to symptoms of VVC such as hemorrhage, pelvic pain, inflammation, itching and discharge. VVC is often linked to IUD use, requiring the prompt removal of these devices for effective treatment. This study evaluated the activity of the arginine-rich peptide “protamine” against Candida albicans, Candida tropicalis and Candida krusei isolated from IUD users who had signs of VVC. The antimicrobial activity was measured using the agar disk diffusion and microbroth dilution methods to determine the minimum inhibitory concentration (MIC). The MIC values of protamine against C. albicans, C. tropicalis and C. krusei are 32 μg mL⁻¹, 64 μg mL⁻¹ and 256 μg mL⁻¹, respectively. The determined MIC of protamine was used for a biofilm inhibition assay by crystal violet staining. Protamine inhibited the biofilm formation of the VVC isolates, and its mechanisms were studied through scanning electron microscopy (SEM) and a reactive oxygen species (ROS) assay. The disruption of cell membranes and the induction of oxidative stress appear to be key mechanisms underlying its anti-candidal effects. The results from an in vitro assay support the potential use of protamine as an antibiofilm agent to coat IUDs in the future for protective purposes. Full article

Intrauterine devices (IUDs) are highly effective long-acting contraceptives. However, pain associated with insertion deters some women and impacts satisfaction. This systematic review critically evaluates the effectiveness of local anesthetics, misoprostol, nonsteroidal anti-inflammatory drugs (NSAIDs), and conscious sedation for managing pain associated with IUD insertion. A comprehensive database search including PubMed, Web of Science, Google Scholar, ClinicalTrials.gov, and ProQuest was conducted from inception to July 2023 for randomized controlled trials (RCTs). RCTs assessing interventions for IUD insertion pain were included. Case reports, non-randomized studies, and non-English papers were excluded. Two independent reviewers extracted data on pain outcomes and adverse effects. The risk of bias was assessed using Cochrane tools. Thirty-nine RCTs (n = 12,345 women) met the inclusion criteria. Topical lidocaine effectively reduced pain on consistent findings across multiple high-quality RCTs. Misoprostol pretreatment facilitated easier insertions through cervical ripening. However, evidence for NSAIDs was inconclusive, with some RCTs finding no additional benefits versus placebo. Results also remained unclear for nitrous oxide conscious sedation due to variability in protocols. Nulliparity predicted higher reported pain consistently. Lidocaine and misoprostol show promise for minimizing IUD insertion pain and difficulty. Further optimization is required to standardize conscious sedation and fully evaluate NSAIDs. Improving pain management may increase favorable experiences and uptake of this reliable method. Full article

The Spodoptera frugiperda Sf9 insect cell line is used in the baculovirus expression vector system for the development of various viral vaccines and some gene therapy products. Early studies indicated that Sf9 cells produced a reverse transcriptase (RT) activity that was detected using a sensitive PCR-enhanced reverse transcriptase (PERT) assay. Since RT is generally associated with retrovirus particles, we undertook the investigation of the physical properties and infectious nature of the extracellular RT activity that was constitutively expressed from Sf9 cells or induced after the chemical treatment of the cells with drugs known to activate endogenous retroviruses. A density gradient analysis indicated that the peak RT activity corresponded to a low buoyant density of about 1.08 g/mL. Ultracentrifugation and size filtration of cell-free Sf9 supernatant indicated that different particle sizes were associated with the RT activity. This was confirmed by transmission electron microscopy and cryoEM, which revealed a diversity in particle size and type, including viral-like and extracellular vesicles. The treatment of Sf9 cells with 5-iodo-2′-deoxyuridine (IUdR) induced a 33-fold higher RT activity with a similar low buoyant density compared to untreated cells. Infectivity studies using various target cells (human A204, A549, MRC-5, and Raji, and African green monkey Vero cells) inoculated with cell-free supernatant from untreated and IUdR-treated Sf9 cells showed the absence of a replicating retrovirus by PERT-testing of cell-free supernatant during the 30 day-culturing period. Additionally, there was no evidence of virus entry by whole genome analysis of inoculated MRC-5 cells using high-throughput sequencing. This is the first study to identify extracellular retroviral-like particles in Spodoptera. Full article

Objectives: The downregulation of anti-adhesive regulatory proteins and upregulation of adhesive genes are critical for the receptive endometrium. This study was designed to determine whether switching between the anti-adhesive podocalyxin (PDX) and adhesive HOXA10 receptivity modulator occurs in the endometrium of women with recurrent implantation failure (RIF). Methods: Twenty-four patients with RIF who could not conceive for three or more cycles despite good-quality embryo transfer constituted the study group. Twenty-four patients with unexplained infertility (UEI) matched for age, BMI, and infertility duration were included in the control group. Twenty women scheduled to undergo intrauterine device (IUD) placement for birth control were included in the comparative group. Endometrial tissue was collected from patients with RIF and UEI during egg retrieval after ovarian stimulation using the GnRH antagonist protocol. In the fertile group, endometrial tissues were collected during IUD insertion. HOXA10 mRNA expression was analyzed by qRT-PCR and PDX protein expression was analyzed by ELISA. The relative expression of endometrial HOXA10 mRNA was calculated using the 2^−ΔΔCt equation. Results: The relative expression of HOXA10 mRNA in the RIF group was significantly lower than that in the UEI group (p < 0.001). HOXA10 mRNA expression in the fertile group was significantly higher than that in the RIF group and was similar to that in the UEI group. PDX expression in the RIF group was significantly higher than that in the UEI group (p < 0.001). PDX expression in the fertile group was significantly lower than in the RIF and UEI groups. A negative correlation was detected between the anti-adhesive PDX protein and adhesive HOXA10 (r = −0.797, p < 0.001). Although there was a positive correlation between endometrial thickness recorded on the day of hCG administration and HOXA10 (r = 0.590, p < 0.01), endometrial thickness was negatively correlated with PDX (r = −0.529, p < 0.01). Conclusions: The failed physiological downregulation of the anti-adhesive PDX protein in patients with RIF prevented the upregulation of adhesive HOXA10 mRNA. Full article

Background/Objective: Indwelling intrauterine contraceptive devices (IUDs) have surfaces that facilitate the attachment of Candida spp., creating a suitable environment for biofilm formation. Due to this, vulvovaginal candidiasis (VVC) is frequently linked to IUD usage, necessitating the prompt removal of these devices for effective treatment. In this study, we evaluated the susceptibility of antimicrobial peptides in vitro against biofilm forming, Amphotericin B (MIC50 > 2 mg L⁻¹) resistant Candida krusei and Candida tropicalis isolated from IUD users who had signs of vaginal candidiasis (hemorrhage, pelvic pain, inflammation, itching, and vaginal discharge). Three antimicrobial peptides, namely, epinecidin-1 (epi-1) and its two variants, namely, variant-1 (Var-1) and variant-2 (Var-2), which were reported to have enhanced antibacterial activity were tested against IUD isolates (C. krusei and C. tropicalis) with pathogenic form of Candida albicans as control. Variants of epi-1, namely, Var-1 and Var-2 were created by substituting lysine in the place of histidine and alanine. Methods: The antimicrobial activity was measured using the microbroth dilution method to determine the minimum inhibitory concentration (MIC) of peptides against C. albicans, C. krusei and C. tropicalis. The MIC of each peptide was used for biofilm assay by Crystal violet staining, Scanning Electron Microscopy, and Reactive Oxygen Species (ROS) assay. To find the possible mechanism of anti-biofilm activity by the peptides, their ability to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2 were determined through PatchDock. Results: The MIC values of peptides: epi-1, var-1 and var-2 against C. albicans are 128 μg mL⁻¹, 64 μg mL⁻¹ and 32 μg mL⁻¹, C. tropicalis are 256 μg mL⁻¹, 64 μg mL^−1, and 32 μg mL⁻¹ and C. krusei are 128 µg mL⁻¹, 128 µg mL⁻¹ and 64 µg mL⁻¹, respectively. Both the variants outperformed epi-1. Specifically for tested Candida spp., var-1 showed two- to four-fold enhancements and var-2 showed two- to eight-fold enhancements compared to epi-1. Electron microscopy confirmed that the mechanism of action involves pore formation thus inducing reactive oxygen species in Candida spp. cell membrane. Computational analysis showed that the peptides have a high tendency to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2, thereby preventing biofilm formation. Conclusions: The in vitro evidence supports the potential use of epi-1 and its variants to be used as an anti-biofilm agent to coat IUDs in the future for therapeutic purposes. Full article

Background: This study compared outcomes of pregnant females with and without COVID-19 and their fetuses/newborns. Methods: This is a retrospective study from 2020 to 2023 utilizing the United States Collaborative Network of the TriNetX Database. We compared the outcomes of pregnant females with COVID-19 and pregnant females without COVID-19. Maternal outcomes evaluated were death, intubation, intensive care unit (ICU) admission, and premature rupture of membranes (PROM) within 9 months of the diagnosis of pregnancy. Fetal outcomes included preterm birth and intrauterine death (IUD). A subgroup analysis of outcomes was performed based on the mother’s vaccine status. Results: The risks of maternal death (RR = 1.97), maternal intubation (RR = 3.33), and maternal (ICU) admission (RR = 1.76) were significantly higher in pregnant females with COVID-19. For the neonate, there was a higher risk of preterm birth (RR = 1.12). When the confounders were eliminated with propensity matching, there was still an increase in maternal intubation (RR = 3.24) and maternal ICU admission (RR = 1.60). For the neonate/fetus, there was a decreased risk of PROM (RR = 0.83) and IUD (RR = 0.74) for the fetuses of the mothers with COVID-19. For the subgroup analysis, the mother was at an increased risk of ICU admission (RR = 0.04) when unvaccinated. Conclusions: There is an increased risk of poor outcomes for pregnant women infected with COVID-19; however, fetal outcomes are generally favorable. When unvaccinated, there was an increased risk of ICU admission for the mother. Full article

Background/Objectives: Endometriosis is a chronic condition that affects 6–10% of women of reproductive age, with pain and infertility being its primary symptoms. The most common aspects of pain are overall pelvic pain, dysmenorrhea, and dyspareunia. Our aim was to compare the available medical treatments for endometriosis-related pain. Methods: A systematic search was conducted in three medical databases to assess available drug options for pain management. Randomized controlled trials (RCTs) investigating various medical treatments for endometriosis-related pain on different pain scales were included. Results were presented as p-scores and, in cases of placebo controls, as mean differences (MD) with 95% confidence intervals (CI). From the available data, a network meta-analysis was carried out. Results: The search yielded 1314 records, of which 45 were eligible for data extraction. Eight networks were created, and a total of 16 treatments were analyzed. The highest p-score, meaning greatest pain relief (p-score: 0.618), for the treatment of dysmenorrhea was achieved using gonadotropin-releasing hormone (GnRH) agonists for 3 months on a scale of 0–100. Additionally, a p-score of 0.649 was attained following a 6-month treatment with GnRH agonists combined with hormonal contraceptives (CHCs). In the case of dyspareunia on a scale of 0–100 following 3 months of treatment, CHCs (p-score: 0.805) were the most effective, and CHCs combined with aromatase inhibitors (p-score: 0.677) were the best treatment option following 6 months of treatment. In the case of overall pelvic pain, CHCs (p-score: 0.751) yielded the highest p-score on a scale of 0–100 following 3 months of treatment, and progestins combined with aromatase inhibitors (p-score: 0.873) following 6 months of treatment. Progestins (p-score: 0.901) were most effective in cases of overall pelvic pain on a scale of 0–3 following 3 months of treatment. Conclusions: Our network meta-analysis showed that in cases of dysmenorrhea, GnRH agonists supplemented with CHCs reduced pain the most following 3 months of treatment. Regarding dyspareunia CHCs were most effective, and in the case of overall pelvic pain, CHCs or progestins combined with aromatase inhibitors yielded the most desirable results. Full article

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications. Full article

This article introduces a case of pelvic actinomycosis, which is easily confused with an ovarian malignant tumor. These images are from a 52-year-old woman who was admitted to hospital with difficulty defecating. Colonoscopy and biopsy indicated inflammatory changes within the intestinal tract, but the anti-inflammatory treatment was not effective. Later, she was readmitted due to abdominal pain and emaciation, and laboratory findings revealed mild anemia and inflammation. Various tumor markers are normal. CT suggested inflammatory lesions in the sigmoid colon and upper rectum. PET-CT considered a high metabolic mass originating from the mesentery. Ultrasound scan revealed a mixed-echo mass adjacent to the right side of the uterus, poorly demarcated from the rectum and right ovary, suggesting a neoplastic lesion. A biopsy of the right ovarian mass indicated suppurative inflammation, with negative antacid staining and microscopic observation of yellowish sulfur granules, suggestive of Actinomyces infection. Following a 12-month treatment regimen involving the removal of an intrauterine device and administration of penicillin, the patient’s condition markedly improved. Pelvic actinomycosis is usually characterized by abdominal pain accompanied by an abdominal mass, which is often related to an intrauterine device (IUD), and is very difficult to distinguish from pelvic tumors and tuberculosis, so it is necessary for doctors to understand its clinical and imaging features. Full article