Search Results (75)

Background: Outpatient operative hysteroscopy is a minimally invasive procedure widely used for the diagnosis and treatment of intrauterine pathologies, including intrauterine adhesions (IUAs), which significantly affect fertility. Despite its therapeutic potential, the procedure itself may predispose patients to de novo adhesion formation. This review evaluates the effectiveness of anti-adhesion gels, particularly hyaluronic-acid-based formulations, in preventing IUAs and improving reproductive outcomes after outpatient operative hysteroscopy. Materials and Methods: A systematic search was performed in PubMed, CINAHL, Embase, and Web of Science for studies published between January 2020 and May 2025. Inclusion and exclusion criteria were defined using PICO guidelines. Relevant studies were screened and selected by two independent reviewers. Results: Anti-adhesion gels, especially hyaluronic acid and its derivatives, were associated with a lower recurrence of IUAs and improved reproductive outcomes. Combination therapies, such as hyaluronic acid gel with intrauterine devices (IUDs), showed better efficacy than monotherapy. Several studies also reported increased endometrial thickness, higher implantation rates, and improved pregnancy outcomes, although live birth rates remained inconsistent. Conclusions: Hyaluronic-acid-based anti-adhesion gels appear effective in reducing postoperative adhesion formation and enhancing reproductive outcomes in outpatient hysteroscopy. The best results are seen with multimodal preventive strategies. However, heterogeneity across studies highlights the need for standardized, prospective, randomized controlled trials to establish optimal clinical use. Full article

Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). Numerous studies have been carried out to investigate the relationship between GDM and ART. This comprehensive systematic review seeks to identify potential biomarkers for the early diagnosis of GDM in pregnancies conceived through ART. We conducted a PubMed search covering the past five years to identify studies that explore biomarkers associated with the development of GDM in pregnancies conceived through ART. The outcome measures included human chorionic gonadotropin (HCG), the body mass index (BMI), the Follicle Stimulating Hormone to Luteinizing Hormone (FSH/LH) ratio, increased hemoglobin A1c levels, fasting insulin concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol concentrations, low-density lipoprotein/high-density lipoprotein (LDL/HDL), total cholesterol to high-density lipoprotein (TC/HDL), the estradiol/follicle ratio, soluble fms-like tyrosine kinase-1 (sFlt-1), Placental Growth Factor (PLGF), endometrial thickness, and psychological stress. Seventeen studies were included. The identification and development of serum or ultrasound biomarkers for the early detection of GDM in pregnancies conceived through ART pose considerable challenges. These challenges arise from the multifactorial nature of GDM, the methodological variations in ART, and the limited availability of relevant studies. The most promising biomarker identified was the estradiol/follicle ratio. Women with a higher estradiol/follicle ratio exhibited significantly lower rates of GDM. There is a pressing necessity for biomarkers to enable the early detection of GDM in pregnancies conceived through ART. E2 levels, β-hCG, and the E2/F ratio, along with the TC/HDL and LDL/HDL ratios, show potential as reliable biomarkers for identifying GDM. Full article

Background/Objectives: The success of artificial reproductive technologies (ARTs) depends on different factors, such as patient-specific reproductive features, ovarian response to stimulation, oocyte and embryo quality, and endometrial receptivity. This study aimed to evaluate their association with oocyte yield, fertilization, endometrial thickness, and pregnancy outcomes. Methods: A prospective clinical study included 128 women undergoing IVF/ICSI. Baseline hormone levels (E2, P4, FSH, LH, AMH) were assessed prior to stimulation. E2 levels were monitored during stimulation, and P4 was measured on the day of oocyte retrieval. Patients were grouped based on P4 levels (<2 ng/mL vs. ≥2 ng/mL). IVF outcomes and endometrial characteristics were statistically analyzed. Results: Lower P4 levels (<2 ng/mL) on the day of oocyte retrieval were significantly associated with higher fertilization rates (p < 0.003), more fertilized oocytes (p < 0.001), and increased pregnancy rates (p < 0.001). Elevated P4 (≥2 ng/mL) correlated with a higher frequency of thin endometrium (<7 mm, p < 0.007). E2 levels on the hCG trigger day correlated positively with the number of retrieved and mature oocytes and fertilization outcomes (p < 0.05). Patients who achieved pregnancy had lower P4 and BMI, and higher E2, AMH, and endometrial thickness. ROC identified a P4 threshold of 1.99 ng/mL with moderate predictive value. Conclusions: Elevated progesterone levels on the day of oocyte retrieval negatively impact fertilization and pregnancy outcomes, likely due to impaired endometrial receptivity. Combined assessment of P4, E2, AMH, and endometrial thickness may enhance embryo transfer planning and improve IVF success rates. Full article

Retained products of conception (RPOC) represent a significant cause of morbidity in the post-abortive and postpartum periods, potentially leading to abnormal uterine bleeding, pelvic pain, infections, and intrauterine adhesions. Accurate diagnosis is crucial to avoid unnecessary surgical interventions and to preserve future fertility. Transvaginal ultrasound constitutes the primary imaging modality for identifying RPOC, but the lack of standardized diagnostic criteria complicates clinical decision-making. This narrative review explores the current literature on sonographic findings associated with RPOC, focusing on the diagnostic value of endometrial thickness (ET), the presence of intrauterine echogenic masses, and the use of Color Doppler imaging. Although an ET ≥15 mm is frequently used to suspect RPOC, the variability in cut-off thresholds and limited specificity reduce its diagnostic reliability. The detection of an echogenic intrauterine mass appears to be the most sensitive and specific sonographic feature. Color Doppler assessment, particularly the presence of enhanced myometrial vascularity (EMV) and classification systems like the Gutenberg score, offers further insight by stratifying hemorrhagic risk and guiding therapeutic choices. However, vascular parameters such as peak systolic velocity (PSV) and resistive index (RI) demonstrate a substantial overlap between benign and pathological conditions, limiting their stand-alone utility. The review also addresses the differential diagnosis of RPOC, including blood clots, arteriovenous malformations, placental polyps, gestational trophoblastic disease, and endometrial osseous metaplasia. The role of three-dimensional ultrasound remains limited in clinical practice, offering no significant advantage over two-dimensional imaging. Finally, the timing of follow-up ultrasound after medical treatment with misoprostol is critical: delayed assessment reduces overtreatment by allowing time for spontaneous resolution. In conclusion, despite advances in ultrasound technology, the diagnosis of RPOC remains challenging due to heterogeneity in imaging findings and inter-observer variability. A multimodal approach integrating grayscale and Doppler ultrasound with clinical evaluation is essential for optimal management. Full article

Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed to investigate its role in embryo implantation and maintenance of a pregnancy-supportive environment. We analyzed the protein expression pattern of bcf-hCG in the intrauterine environment during early pregnancy by performing western blotting and immunohistochemistry with a monoclonal anti-bcf-hCG antibody. We performed a cell proliferation assay in the presence of bcf-hCG compared with intact hCG. We conducted an ex vivo study by performing intrauterine injection of bcf-hCG or intact hCG in mice. Endometrial thickness was measured using histological methods, and uterine gene and protein expression were analyzed following intrauterine injection of bcf-hCG. We evaluated the effect of bcf-hCG on embryo implantation in the uterus. bcf-hCG was highly abundant in the placenta and epithelial stromal glands of the uterine endometrium during early pregnancy and significantly induced proliferation of a stromal epithelial cell line. Intrauterine injection of bcf-hCG induced expression of specific genes and proteins, including homeobox A10, for embryo implantation and placental development. Upon embryo transfer, the implantation rate of bcf-hCG-treated embryos was higher than that of control embryos. In conclusion, bcf-hCG plays a role in the proliferation of glandular epithelial cells in the endometrium and placenta during early pregnancy. Therefore, bcf-hCG is an early-phase pregnancy biomarker that maintains the initial phase of pregnancy. Full article

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

Objective: Transvaginal ultrasonography plays a crucial role in contemporary fertility management, offering insights into uterine and endometrial blood flow. Three-dimensional ultrasonography utilizing power Doppler angiography (3D-CPA) allows precise measurement of endometrial volume and vascular parameters, such as the vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI); variables that indirectly assess endometrial receptivity and integrity. Doppler technology allows for the capture of changes in the uterus induced by hormonal-related fluctuations during the menstrual cycle, revealing a significant correlation between endometrial receptivity and vascularity. Age-related changes in endometrial function are implicated in declining fertility, with limited research exploring this aspect. The aim of this study was to investigate the impact of aging on various ultrasound parameters of the uterus, including endometrial vascularity. Methods: A retrospective cross-sectional study of women who attended the Feto-Maternal Centre from January 2022 to December 2023. Each woman whose menstrual cycle was regular underwent 3D ultrasound with power Doppler as part of the routine assessment of the pelvis. Parameters assessed include the VI, FI, and VFI as well as uterine volume, endometrial volume, and endometrial thickness. The women were grouped based on age, and the variables measured in the follicular and luteal phases were compared between the age groups using SPSS version 30 September 2024. Results: A total of 907 women (427 follicular and 480 luteal phase) were studied: 297 (131 follicular and 166 luteal) were 20–29 years old; 471 (240 follicular and 231 luteal) were aged 30–39; and 139 (56 follicular and 83 luteal) were aged 40–49. Uterine volume, endometrial volume, and thickness increased significantly and steadily with age. VI, VFI, and FI decreased significantly with age in the follicular phase, but in the luteal phase there was no statistically significant difference in any of these indices with age. Conclusions: Uterine volume, endometrial thickness, and endometrial volume increased with age, but the vascular indices decreased with age in the follicular but not in the luteal phase. These age-related changes in endometrial vascularity may partly explain the decrease in age-related fertility. Further research is needed to comprehensively explore the complexities of uterine aging and its implications for female fertility. Full article

Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal senescence in the progression of endometrial fibrosis, termed intrauterine adhesions (IUA). IUA have significant negative effects on women’s reproductive health and are associated with infertility. We have generated original gene signatures to identify endometrial stromal senescence in single-cell and bulk RNA-sequencing data. By applying generated gene signatures, we revealed an increased level of stromal senescence during the proliferative phase in the endometrium of patients with IUA. Further comparative analysis of cell–cell communications demonstrated that senescent stromal cells in the IUA endometrium create an immunosuppressive and profibrotic microenvironment through an elevated expression of LGALS9. Endometrial stromal senescence persists during the window of implantation and correlates with impaired embryo receptivity of the IUA endometrium. Therefore, stromal senescence can be regarded as a primary cause of an unresponsive endometrium with decreased receptivity and thickness in IUA patients. A LGALS9 immunotherapy protocol, specifically designed to neutralize LGALS9 immunosuppressive activity of senescent cells, may offer a promising opportunity to restore effective immune clearance of these cells within the IUA stroma. Consequently, an LGALS9-based strategy could emerge as a novel therapeutic avenue in the treatment of IUA. Full article

Background: Ultrasonography is essential for diagnosing endometrial pathologies, such as hyperplasia, polyps, and endometrial cancer. The International Endometrial Tumor Analysis (IETA) group provides guidelines for using ultrasound to assess endometrial thickness, texture, and irregularities, aiding in the diagnosis of these conditions. The aim of this study was to evaluate the utility of various endometrial morphological features, as assessed by gray-scale ultrasound, and endometrial vascular features, as assessed by power Doppler ultrasound, in differentiating benign and malignant endometrial pathologies. A secondary objective was to compare the effectiveness of these ultrasound techniques in assessing myometrial invasion. Methods: A total of 162 women, both pre- and postmenopausal, with or without abnormal vaginal bleeding were enrolled in a prospective study. All participants underwent transvaginal gray-scale and color Doppler ultrasound examinations, conducted by examiners with over 15 years of experience in gynecological ultrasonography. Endometrial morphology and vascularity characteristics were evaluated based on the IETA group criteria, which include parameters such as endometrial uniformity, echogenicity, the three-layer pattern, regularity of the endometrial–myometrial border, Doppler color score, and vascular pattern (single dominant vessel with or without branching, multiple vessels with focal or multifocal origin, scattered vessels, color splashes, and circular flow). Sonographic findings were compared with histopathological results for comprehensive assessment. Results: The mean age of the study population was 56.46 ± 10.84 years, with a range from 36 to 88 years. Approximately 53.08% of the subjects were postmenopausal. The mean endometrial thickness, as measured by transvaginal ultrasonography, was 18.02 ± 10.94 mm with a range of 5 to 64 mm (p = 0.028), and it was found to be a significant predictor of endometrial malignancy. The AUC for the ROC analysis was 0.682 (95% CI: 0.452–0.912), with a cut-off threshold of 26 mm, yielding a sensitivity of 62.5% and a specificity of 89%. Vascularization was absent in 68.4% of patients with polyps. Among the cases with submucosal myomas, 80% exhibited a circular flow pattern. Malignant lesions were identified in 22.84% of the cases. Subjective ultrasound assessment of myometrial invasion, categorized as <50% or ≥50%, corresponded in all cases with the histopathological evaluation, demonstrating the effectiveness of ultrasound in evaluating myometrial invasion in endometrial cancer. Conclusions: In this study, cystic atrophic endometrium was identified as the most prevalent cause of postmenopausal bleeding. The most significant ultrasound parameters for predicting malignancy included heterogeneous endometrial echogenicity, increased endometrial thickness, and the presence of multiple vessels with multifocal origins or scattered vascular patterns. Additionally, color Doppler blood flow mapping was demonstrated to be an effective diagnostic tool for the differential diagnosis of benign intrauterine focal lesions. Full article

Objectives: To assess if the instillation of plasma rich growth factors (PRGFs) improves endometrial thickness (EMT) in frozen embryo cycles performed under hormone treatment where the endometrium was very thin (≤5 mm). Methods: First, a randomized controlled trial (RCT) was performed comparing women only receiving an increase in estrogen therapy (n = 9) and women receiving both the increase in estrogen therapy and three instillations of PRGF (n = 13). The second part of the study consisted of a prospective observational follow-up of the patients included in the RCT (for 1–3 months in the study group, and for 1–6 months in the control group). Results: In the RCT, there was an increase in EMT in both the PRGF and control groups. However, the increase was significantly higher in the PRGF group (1.30 ± 0.67 mm) compared to the control group (0.58 ± 0.51 mm). In the PRGF group, 23% achieved an EMT of 7 mm compared to 0% in the control group. There were 2 pregnancies in the PRGF group resulting from the 3 transfers performed in that group. No transfer was carried out in the control group. There was a significant increase in EMT 1–3 months after the PRGF cycle. The live birth rate per transfer was 20% in the cycles following the PRGF cycles, whereas it was 30% per starting woman. For women in the control group who later underwent PRGF, the LBR was 57.1%. Conclusions: PRGF instillation in cases of very thin endometrium increases EMT moderately. It is suggested that the beneficial effect of PRGF may persist for 1–3 cycles after instillation. Full article

Background and Objectives: The current study was designed as a prospective laboratory investigation to evaluate the histopathological effects and VEGF (vascular endothelial growth factor) expression in uterine tissue following treatment with a combination of methylprednisolone and hyaluronic acid in a rat model of experimentally induced Asherman Syndrome. Materials and Methods: Twenty-six female Sprague-Dawley rats were used. Trichloroacetic acid was applied to the right uterine horns of all the groups to induce adhesion formation. First, we induced the Asherman model in two rats (Group 1). The remaining rats were divided into the following three groups: Group 2 received intrauterine hyaluronic acid treatment, Group 3 received oral methylprednisolone treatment, and Group 4 received both treatments. Inflammation, gland count, and fibrosis levels were assessed histopathologically. VEGF levels were analyzed immunohistochemically. Results: Hyaluronic acid treatment increased the uterine lumen diameter and vascularization. Methylprednisolone treatment increased the gland count and uterine wall thickness while decreasing the inflammation and fibrosis scores. Combined treatment provided a statistically significant advantage over single treatments. In particular, the combined treatment group exhibited significantly lower fibrosis (p = 0.184) and inflammation scores (p = 0.071), as well as higher gland counts (p = 0.849) and VEGF expression (p = 0.114), compared to the groups receiving only methylprednisolone or hyaluronic acid. These differences indicate that the synergistic effect of the two agents results in more effective endometrial healing than when either treatment is applied alone. Conclusions: Methylprednisolone treatment significantly prevented adhesion formation and reduced the inflammation and fibrosis scores compared to hyaluronic acid treatment alone. The combined treatment adds to the effects of the hyaluronic acid treatment alone and provides better healing. Full article

This case report presents the therapeutic effects of herbal medicine modified Sihogyeji-tang monotherapy for suspected nonatypical endometrial hyperplasia (EH), documented through transabdominal ultrasonography monitoring and clinical symptom assessment. A 38-year-old woman presented with hypomenorrhea and ovulation-related pain, headache, body aches, and nausea since April 2023. The patient was clinically assessed as having nonatypical EH based on the ultrasound findings and clinical symptoms. She was treated with modified Sihogyeji-tang twice daily from 3 June 2023 to 29 December 2023. Treatment outcomes were evaluated using regular transabdominal ultrasonography measurements of endometrial thickness and changes in menstrual patterns, including cycle length and blood volume. Menstrual symptoms showed notable improvements: severe ovulation pain decreased from NRS 7–8 to 0, menstrual volume increased from 2 to 3 medium pads to 4 to 5 large pads per day during peak flow, and menstrual duration normalized from 4 to 6 days. Symptoms associated with ovulation and menstruation, headache, chills, and nausea resolved. At the 3-month follow-up visit after 7 months of herbal medicine treatment, endometrial thickness measured during the secretory phase had normalized to 1.40 cm (normal range: 0.7–1.4 cm). The coexisting uterine myoma remained stable throughout the treatment and follow-up. No adverse events were reported during the entire course of treatment. This case demonstrated that modified Sihogyeji-tang alone may effectively improve suspected nonatypical EH and its associated symptoms. Improvement was objectively assessed using ultrasound measurements and was sustained over a 9-month follow-up. Full article

Objective: This study investigated the effects of a supraphysiological dose of testosterone on uterine morphology and the regulation of the leukaemia inhibitory factor (LIF) signalling pathway during endometrial receptivity. Methods: In this study, 30 adult female Sprague–Dawley rats were divided into treatment and control groups. The treatment groups received subcutaneous injections of 1 mg/kg/day of testosterone from gestational day 1 to day 3, either testosterone alone or in combination with inhibitors (anastrozole, finasteride, or both). A control group of six untreated rats was maintained for comparison. Rats were euthanised on the evening of gestational day 4 to examine uterine morphological changes, gene expression and the distribution of proteins associated with the LIF signalling pathway (LIF, LIFR, JAK1 and STAT3) and MUC1 by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. Results: The results of this study showed that the thickness of the endometrium and myometrium, as well as the number of glands, markedly decreased in all testosterone-treated rats. In addition, the mRNA levels of LIF, LIFR, JAK1 and STAT3 were significantly downregulated in response to supraphysiological testosterone treatment, while the mRNA of MUC1 was significantly upregulated. The IHC results were consistent with the mRNA data and confirmed the changes in protein distribution in all treatment groups. Conclusions: A supraphysiological dose of testosterone may impair endometrial receptivity through dysregulation of the LIF signalling pathway, potentially affecting fertility. Full article

Abdominal wall endometriosis (AWE) is a clinical disorder with unknown pathogenesis with an incidence between 0.03% and 1% in women affected by cutaneous/scar endometriosis. We investigated the pathological, molecular cytogenetic and cell proliferation features of a primary AWE developed in rectus abdominis muscle in a patient without co-existing pelvic endometriosis. An investigational model of cultured stromal cells was additionally established. Histologically, the lesion revealed areas of endometrial-like glands surrounded by a thick stromal layer in addition to numerous disseminated foci composed exclusively of stromal cells. Beyond the strong expression of Estrogen (ER) and Progesterone receptors (PRs), consistent immunolabeling for several mesenchymal stromal/stem cell antigens and oncoproteins was revealed in both the endometrioma as well as in the cultured stromal cells. The Fluorescence in situ hybridization (FISH) analysis of the endometrioma demonstrated a structural alteration of the c-MYC protooncogene, with a mean of three gene copies in 3% to 5% of both glandular and stromal cells. The FISH assay applied on the cultured cells showed c-MYC gene amplification, with an average number of more than six gene copies in 18% to 25% of the cellular nuclei. Altogether, these results markedly highlight the pathological and molecular features of idiopathic AWE essential for histo-pathogenetic categorization. Full article

Background and Objectives: Autologous platelet-rich plasma (PRP) transfusions are a relatively new treatment method used in different fields of medicine, including the field of reproductive medicine. One of the applications of these concentrated platelet infusions is the treatment of endometrial receptivity, which is a key factor for embryo implantation. There are implications that PRP infusions can lead to increased endometrial thickness, endometrial receptivity, and significantly elevated clinical pregnancy rates. Our objective is to briefly understand what PRP is and to, through a narrative review, summarize the findings from studies focused on evaluating the benefits of PRP infusions to treat thin endometrium with the goal of achieving better endometrial receptivity. Materials and Methods: Reference data was searched using Medline, PubMed, and EMBASE to identify reports from 2015 to 2024. The combination of search words used was “PRP” and “platelet-rich plasma” with “thin endometrium”, “endometrial receptivity”, “endometrial thickness”, and “endometrial implantation”. Obtained articles were screened, and suited studies (randomized controlled trials, case reports, case series, pilot studies, and reviews) were included in the present review. Reports not available in the English language were eliminated from the current review. Results: The results from most of the reviewed studies showed a positive effect of autologous PRP infusions on increasing endometrial thickness, enhancing endometrial receptivity, and elevating clinical pregnancy rates. The majority of the evaluated findings revealed endometrial thickness > 7 mm (increased endometrial thickness was observed in each evaluated study) following the PRP treatment. More than 50% of the evaluated studies resulted in enhanced endometrial thickness, increased endometrial receptivity, and an elevated pregnancy rate after the PRP application. Conclusions: Autologous PRP infusions for treating endometrium are a relatively new method that has shown promising results. Its major strengths are availability and proper application, which eliminates possible immunological reactions or disease transmission. The main drawbacks are not enough data on safety (i.e., its effect on endometriosis) and the lack of uniformity in the PRP preparation, which would provide optimal standardized quality and quantity of the PRP product and, thus, optimal treatment results. Full article