Original research publications

Maternal-fetal medicine (MFM) specialists are highly trained subspecialists whose expertise lies in managing complex pregnancies. This paper argues against the routine involvement of MFMs in low-risk labor and delivery, focusing on cost inefficiencies, workforce shortages, maternity care deserts, equity concerns, and comparisons to other subspecialists providing primary care. It also highlights the benefits of obstetric hospitalist frameworks and collaborative care models with midwives as sustainable alternatives.

Vulvovaginal pain disorders can manifest with varying symptomology and can take years to diagnose and even longer to treat. Given the nature and location of the pain, these disorders can significantly affect interpersonal relationships and quality of life. Therapy options range from behavioral interventions to medications and minimally invasive procedures, and in rare cases surgery. The following review covers common etiologies of vulvovaginal pain, evaluation strategies, currently used treatments and promising future therapies.

The occiput posterior (OP) foetal position is a global obstetric challenge associated with increased maternal and neonatal complications. Manual rotation and specific maternal positioning (hands-and-knees, lateral position) are potential interventions for managing persistent OP position during labour; however, their comparative effectiveness remains uncertain. This systematic review and network meta-analysis aimed to evaluate the efficacy of these interventions versus standard care. A systematic search of multiple databases was conducted from inception to January 3, 2025 following PRISMA-NMA guidelines. An updated literature search using the same criteria was performed on July 5, 2026 during the final stage of peer review, which yielded no additional studies for inclusion. Randomised controlled trials comparing manual rotation, hands-and-knees position, or lateral position to standard care or each other were included. The primary outcome was spontaneous vaginal delivery. Secondary outcomes included caesarean delivery, severe perineal lacerations, and low Apgar score. Bayesian and frequentist network meta-analysis was performed using MetaInsight software. Fifteen randomised trials involving 2,934 participants were analysed. No intervention demonstrated statistically significant benefits for any primary or secondary outcome. For spontaneous vaginal delivery, the lateral position showed the highest point estimate (OR: 1.97, 95% CrI 0.83 to 4.88), though all credible intervals were wide and crossed the null value. The evidence was characterised by substantial imprecision and methodological limitations, resulting in low to very low certainty for all comparisons. Current evidence does not support the routine use of manual rotation or specific maternal positions for managing persistent OP position. The substantial uncertainty and methodological limitations preclude definitive recommendations. Future high-quality trials with larger sample sizes and standardised protocols are essential. When a baby is positioned with its head facing the mother’s back during labour, delivery can become more difficult. This position increases the chance of needing a caesarean section or other assisted delivery. Healthcare providers sometimes try to turn the baby’s head by hand, or ask the mother to lie on her side or kneel on her hands and knees. These methods are commonly used, but it is not clear whether they actually help.We reviewed 15 trials involving 2,934 women to see if these techniques increase normal vaginal delivery and reduce complications such as caesarean section, severe vaginal tears, or low health scores in babies after birth. Our findings showed that none of these methods made a clear difference. The evidence was not strong enough to say that manual rotation, lying on the side, or hands-and-knees positions are better than standard care. Many studies were small and used different methods, which made it difficult to draw firm conclusions. Because of this uncertainty, we cannot recommend these methods as routine practice. Women should discuss their options with their healthcare provider and make decisions based on their own situation. More research with larger groups and consistent methods is needed.

The choice of treatment for vulvar squamous cell carcinoma involving the perineum is challenging because of its anatomical proximity to the anus. The study aim was to describe treatment patterns, complications, and survival of women with perineal vulvar squamous cell carcinoma. A population-based study at two tertiary referral hospitals during 2012-2020. Demographic and clinical data were retrieved from medical records. Survival and complications were analyzed according to treatment modality. Relative and progression-free survival were calculated by Kaplan-Meier estimates. The cohort comprised 571 women with primary vulvar squamous cell carcinoma, of which 147 (26%) were located at the perineum. Seventy-eight women (78/147; 53%) underwent surgery only with a median resection margin of 5 mm. In 34/147 women (23%), surgery was followed by adjuvant radiotherapy because of lymph node metastasis (74%) and/or insufficient margins (median resection margin 1.6 mm). Primary radiotherapy was delivered to 35/147 women (24%). Treatment-related complications during the first year were recorded in 47% after surgery only, in 79% after adjuvant radiotherapy and in 71% after primary radiotherapy. After a median follow-up of 41 months, disease progression occurred in 3% of women treated with surgery only, in 18% after adjuvant radiotherapy and in 33% after primary radiotherapy. The 2-year progression-free survival was 82% (95% CI, 74-91) after surgery only, 53% (95% CI, 38-73) after adjuvant radiotherapy, and 31% (95% CI, 19-51) after primary radiotherapy. When diagnosed at an early-stage, perineal vulvar squamous cell carcinoma can successfully be treated by primary surgery. The optimal treatment strategy for advanced disease remains uncertain and requires further investigation.

Lipschütz ulcers, also known as non-sexually acquired acute genital ulcers, are rare lesions that primarily affect adolescent and prepubertal females. Their sudden onset, severe pain, and dramatic appearance can be alarming, often mimicking infectious or autoimmune diseases. A 10-year-old girl presented with severe perineal pain, dysuria, and fever following an episode of pharyngotonsillitis. Examination revealed vulvar ulcers. A diagnosis of Lipschütz ulcers associated with pharyngotonsillitis was established. Supportive therapy led to gradual improvement. This case illustrates the diagnostic challenges of acute vulvar ulcers in pediatric patients and highlights the importance of recognizing Lipschütz ulcers to avoid unnecessary treatments. Although rare, Lipschütz ulcers should be considered in the differential diagnosis of acute genital ulcers in children, especially following systemic illness.

Hidradenoma papilliferum is a benign neoplasm arising in the vulvovaginal region. These lesions are thought to originate from anogenital mammary-like glands and share morphologic and immunohistochemical features with breast tissue. Though rare, malignant transformation of hidradenoma papilliferum into mammary-type carcinoma, typically mammary-type ductal and mammary-type lobular carcinoma, has been documented. However, mammary-type metaplastic carcinoma arising from hidradenoma papilliferum is exceedingly rare. Herein, we describe a case of this entity in a patient presenting with a labial mass. Histologic examination revealed a papillary proliferation consistent with hidradenoma papilliferum, with focal ductal carcinoma in situ (DCIS). Adjacent to this was a biphasic malignant neoplasm composed of a high-grade carcinomatous component and an infiltrating sarcomatoid component with pleomorphic tumor cells. Immunohistochemically, the DCIS and carcinomatous components were positive for CAM5.2, CK7, claudin-4, and GATA-3, while the malignant sarcomatoid component was positive for p63 and GATA-3. Both invasive components demonstrated aberrant cytoplasmic p53 expression. Molecular analysis identified pathogenic mutations in TP53 , PIK3CA , APC , and NF1 . The aforementioned findings mirror those found in metaplastic carcinoma of the breast, and a diagnosis of biphasic tumor analogous to mammary-type metaplastic carcinoma, likely arising from hidradenoma papilliferum, was rendered. This case captures a continuum of disease progression from hidradenoma papilliferum to mammary-type metaplastic carcinoma and not only strengthens the association of mammary-type malignancies of the vulvovaginal region originating from breast-like structures native to this location, but expands on the spectrum of morphologic, immunohistochemical, and molecular features of these lesions.

The worldwide prevalence of vulvar intraepithelial neoplasia is increasing and is characterized by the high risk of recurrence and evolution towards vulvar cancer. Positive margins following surgical excision are the most important criteria of recurrence risk. We conducted a pilot clinical study to assess the fluorescence-based cartography of VIN lesions using methyl aminolevulinate (m-ALA), which is a prodrug of the fluorophore protoporphyrin IX (PpIX). A prospective, single-center, single-arm clinical trial included 17 women with histologically confirmed high-grade vulvar intraepithelial neoplasia (dVIN or vHSIL). Following topical methyl aminolevulinate application, fluorescence-guided examination under 405-nm light was performed. Targeted biopsies from fluorescent and non-fluorescent areas were compared with histopathology to assess concordance and the ability of fluorescence to accurately identify high-grade lesions. Among 34 biopsies, histopathological findings were concordant with fluorescence in 91% of cases. The procedure correctly identified intraepithelial neoplasia areas in 14 patients, yielding a success rate of 82% (95%CI 56-96%). Sensitivity and specificity were 93% (95%CI 68-100%) and 89% (95%CI 67-99%), respectively. The tolerance of the procedure was excellent with no pain and no side effects neither after cream application nor after illumination. This pilot study suggests that fluorescence imaging is a workable technique to mark VIN lesions with m-ALA cream. Further studies are needed to improve the reproducibility and ease of use of this method.

The gut and vaginal microbiomes are both essential to human health, yet they have largely been studied in isolation. Gut microbiota are central to host metabolism, immunity, and the gut-brain axis, while the vaginal microbiome, typically dominated by Lactobacillus species, protects against infection and shapes reproductive outcomes. Although dysbiosis at either site has been linked to systemic disease, the possibility that these communities are interrelated and that the vaginal microbiome could serve as a clinically accessible proxy for systemic microbial states remains underexplored. This represents a clear gap in the literature. In this review, we examine physiological connections between digestive and genitourinary systems, explore how endocrine and immune networks exert dual control across compartments, and analyze correlations between dysbiosis and disease states. We then consider emerging technologies for microbiome analysis and their clinical and translational implications, including the potential for vaginal microbiome profiling to function as a diagnostic surrogate for the gut and as a complementary biomarker platform for prediction of neurologic disease risk. By building a systems-level understanding of the joint immuno-microbial interactome, evaluating advances in computational and omics-based technologies, and situating these tools within emerging healthcare frameworks, we argue that the cervicovaginal-gut microbiota axis is a unique and understudied source for medical discovery.

Peripheral precocious puberty (PPP) is a rare condition in early childhood, particularly among girls under 3 years of age. One cause of PPP is functional ovarian cysts that secrete estrogen at levels sufficient to trigger the development of premature secondary sexual characteristics. Unilateral ovarian agenesis is an uncommon congenital anomaly. The coexistence of both conditions in a single patient is extremely rare and poses unique diagnostic and management challenges. We report the case of a 2-year and 10-month-old girl presenting with concurrent breast development, pubarche, and recurrent vaginal bleeding. Pelvic imaging revealed a cyst in the left ovary and agenesis of the right ovary. Laparoscopy confirmed absence of the right ovary and ipsilateral fallopian tube. Based on clinical, hormonal, and radiologic findings, a diagnosis of PPP due to a functional ovarian cyst was made. Given the rapid progression of symptoms, increase in cyst size, and concern for torsion, a short observation period of three months was followed by ovarian-preserving laparoscopic cystectomy. Histopathology confirmed a benign follicular cyst. Postoperatively, the patient experienced partial regression of pubertal signs and complete resolution of vaginal bleeding. This case highlights the importance of individualized decision-making in managing PPP,especially in the presence of congenital anomalies.

Primary vaginal carcinoma is rare and far less common than vaginal metastases, which usually originate from neighboring organs. Primary carcinomas are predominantly squamous in type and human papillomavirus (HPV)-associated while primary adenocarcinomas are mostly HPV-independent; as glands are normally absent in the vagina, a congenital or acquired glandular precursor lesion is a prerequisite for their development, although this is not always identified. A variety of rare benign squamous and glandular lesions may also occur at this site. In this article the spectrum of vaginal squamous and glandular neoplasia, precursor and rare non-neoplastic lesions is discussed, with emphasis on recent developments.

DNA polymerase ε (POLE)-mutant endometrial carcinosarcoma (ECS) is a rare clinical lesion. The current study describes the diagnosis and treatment of a woman who presented with yellow vaginal discharge for >2 months; in addition, a literature review was conducted, and the clinical and pathological characteristics, treatment and prognosis of POLE-mutant ECS are discussed. Preoperative endometrial curettage was performed and the patient was diagnosed with poorly differentiated adenocarcinoma. Based on this finding, a total hysterectomy, bilateral adnexectomy and lymph node dissection were performed. A postoperative pathological examination revealed the morphological characteristics of a high-grade carcinosarcoma in the endometrial tumor. The results of immunohistochemical staining showed that the carcinoma was cytokeratin 7-positive (sarcoma, -) and both the carcinoma and sarcoma were vimentin-positive (carcinoma, weak +; sarcoma, +). Additionally, TP53 showed aberrant immunohistochemical overexpression in the carcinoma and sarcoma, and the Ki-67 proliferation index was 80% in carcinosarcoma. Molecular testing revealed a c.1231G>T (p.Val411Leu) mutation in exon 13 of the POLE gene, and mutations in the TP53 gene were detected in exons 5, 6 and 8. Adjuvant therapy was not administered to the patient after surgery, and no recurrence/metastasis was detected during the 18-month follow-up period. These findings indicate that molecular subtyping should be performed routinely in ECS to identify the POLE-mutant subtype and to avoid overtreatment.

Bacterial vaginosis (BV) is the most prevalent vaginal infection among reproductive-age women and is associated with increased susceptibility to gynecological complications. Current antibiotic treatments achieve high initial cure rates but show high rates of recurrence, partly due to their inability to remove persistent biofilms. p Hyph is a novel, non-antibiotic treatment that lowers vaginal pH, promoting Lactobacillus growth and biofilm disruption. To evaluate the immediate and long-term effects of p Hyph on the vaginal microbiome, BV resolution, and symptom reduction. In a randomized, controlled, partially blinded study, 61 women with clinically diagnosed BV were randomized to immediate (IT, n = 35) or delayed (DT, n = 26) treatment. Vaginal swabs were collected before treatment, after 6 days, and during maintenance to Day 70. Microbiome composition was analyzed using a qPCR panel targeting 47 bacterial and 6 fungal species. Compared to controls , p Hyph reduced the abundance of multiple BV-associated species and increased Lactobacillus iners following 6-day treatment (median 8.96 ×10 3 [Q1-Q3: 3.10 ×10 3 -2.72 ×10 4 ] vs. median 9.44 × 10² [Q1-Q3: 0.00-4.29 × 10 ³] normalized qPCR counts, p < 0.05). Additionally, p Hyph reduced BV-related symptoms, particularly fishy odor (p < 0.05). Treatment promoted a shift to CST III microbiome composition, and maintenance dosing was associated with sustained Lactobacillus abundance up to Day 70. p Hyph shows potential as an alternative BV treatment by reducing BV-associated pathogens while promoting lactobacilli. Extended dosing may enhance microbiome stability.

This article reviews recent literature to assess the challenges that define approaches in rectovaginal fistula (RVF) repair. RVFs remain a significant clinical challenge because of their profound impact on patient quality of life and the absence of standardized management strategies. The predominance of small studies and case series limits the ability to determine the most effective repair techniques. Consequently, a synthesis of contemporary evidence is needed to better inform decisions regarding surgical timing, technique selection, and optimization of patient comorbidities. Sphincter-preserving techniques continue to show promise for low- and mid-level fistulas. Fecal diversion may benefit patients with recurrent RVF or prior failed repairs, and the Martius flap remains a mainstay for complex cases, with the Musset technique emerging as a potential alternative. Multidisciplinary teams remain essential for repair success. Postoperative strategies, including negative pressure dressings and hyperbaric oxygen therapy, show potential for improving healing and reducing RVF recurrence. RVF remains a debilitating condition. Optimizing surgical timing, managing comorbid conditions, and tailoring operative and postoperative care through multidisciplinary collaboration are essential to achieving optimal patient outcomes. Further research is needed to clarify long-term functional results and refine emerging repair techniques, especially in those with recurrent RVFs.

Vaginal intraepithelial neoplasia (VAIN) is a rare HPV-related condition with heterogeneous behavior and a relevant recurrence risk. Factors associated with severity and recurrence remain incompletely defined. To explore clinical, cytological, virological, and colposcopic features associated with high-grade VAIN and recurrence. This retrospective study included 42 women with histologically confirmed VAIN at a tertiary center between January 2020 and January 2026. All underwent vaginal cytology, high-risk HPV (HR-HPV) genotyping, colposcopy, and biopsy. Histology was classified as VAIN1 or VAIN2-3. Recurrence was defined as a histologically confirmed lesion after treatment and documented disease-free assessment. Associations were assessed using bivariate and exact analyses. VAIN2-3 was diagnosed in 31 women (73.8%). Among HR-HPV-positive women, HPV16-related infection was more frequent in VAIN2-3 than VAIN1 (65.4% vs 18.2%; OR 8.50, 95% CI 1.27-91.56; p = 0.013). Cytology was associated with histological grade ( p = 0.024); all women with HSIL/ASC-H had VAIN2-3, although sensitivity was limited. Over a median follow-up of 24 months, eight women (19.0%) recurred after a median of 11.5 months. HPV16-related infection was more frequent with recurrence (75.0% vs 38.2%; OR 4.85, 95% CI 0.70-54.01; p = 0.112), but the evidence was not definitive. HPV16-only infection showed borderline evidence of association ( p = 0.050), while no clear outcome pattern emerged for multiple-genotype infection. No other significant associations with recurrence were observed. HPV16-related infection was associated with high-grade histology among HR-HPV-positive women, while its prognostic relevance for recurrence remains uncertain. The limited sensitivity of cytology underscores the value of multimodal assessment. These exploratory signals warrant prospective validation.

To compare labor induction characteristics and delivery outcomes among individuals with body mass index < 40 versus ≥ 40 kg/m 2 undergoing induction at term. This secondary analysis utilized data from the vaginal misoprostol arm of a cluster randomized controlled trial comparing vaginal to oral misoprostol for induction. Individuals at ≥ 37 weeks gestation with cervical dilation ≤ 2 cm undergoing induction using a standardized protocol were included. Vaginal misoprostol was given in 25 µg doses every three hours for up to five doses, followed by a standardized oxytocin protocol. We compared labor progression among individuals with BMI < 40 and ≥ 40 kg/m 2 at delivery, including labor duration, misoprostol use, and obstetric and neonatal outcomes. Generalized estimating equations were used to account for clustering and comorbid conditions. Effect sizes were presented as odds ratios and adjusted mean differences with 95% confidence intervals. From May 2021 to September 2022, 1,322 patients received vaginal misoprostol for labor induction at term. Among these, 1,058 (80.0%) had a BMI < 40 kg/m 2 and 264 (20.0%) had a BMI ≥ 40 kg/m 2 . Individuals with severe obesity were more likely to start induction with a closed cervix. After adjustment for clustering, initial cervical dilation, hypertension, and diabetes, inductions in the group with severe obesity had longer total durations (adjusted mean difference 3.5h, 95% CI 1.9-4.8), first stage of labor (adjusted mean difference 2.2h, 95% CI 0.6-3.8), and duration of oxytocin use (adjusted mean difference 2.5, 95% CI 1.1-3.8). Individuals with BMI ≥ 40 kg/m 2 also had lower odds of vaginal delivery (aOR 0.6, 95% CI 0.4-0.8) and required more doses of misoprostol for induction. Severe obesity, defined as BMI ≥ 40 kg/m 2 , is associated with longer time to delivery, increased misoprostol requirement, longer duration of oxytocin use, and lower odds of vaginal delivery compared to individuals with lower BMI. Consideration of alternative labor induction protocols must be balanced with increased comorbidities and overall obstetric morbidity in this group.

To evaluate the association between maternal hemodynamic patterns, cervical stiffness, and fetal Doppler indices with maternal and perinatal delivery outcomes in low-risk term women, and to identify potential clinical predictors. This prospective single-center study was conducted between May and September 2025 at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Singleton pregnancies between 36 and 38 gestational weeks were included. Exclusion criteria were oocyte donation, chronic maternal diseases, pregnancy complications, or fetal anomalies.At recruitment, participants underwent transabdominal ultrasound including estimated fetal weight and fetal and uterine Doppler. Cervical strain elastography was performed using the E-Cervix software (Samsung HERA Z20), and cervical stiffness was assessed using the hardness ratio. Maternal hemodynamic patterns were evaluated using the Ultrasound Cardiac Output Monitor (USCOM). Maternal and neonatal outcomes were recorded at delivery.Associations between maternal hemodynamic patterns, cervical stiffness, fetal Doppler indices, and delivery outcomes were assessed using logistic regression and generalized linear models adjusted for relevant cofounders. A total of 172 women were enrolled. Labor was induced in 55.2%; spontaneous vaginal, operative vaginal, and emergency cesarean deliveries occurred in 68.2%, 11.8%, and 20.0% of cases, respectively. Two hemodynamic profiles were identified: hyperdynamic (high CO, low SVR) and hypodynamic (low CO, high SVR). Birthweight was positively associated with the hyperdynamic profile (β = 85.6, 95% CI 38.7-132.6; p < 0.001) and negatively with the hypodynamic profile (β= -57.2, 95% CI -110- -4.3; p = 0.05). Maternal blood loss was lower in women with a hypodynamic pattern (β= -38.6, 95% CI -73.4- -3.9; p < 0.05). A hyperdynamic pattern increased the odds of unassisted vaginal delivery (aOR 1.33, 95%CI 1.01-1.66; p < 0.05), whereas a higher cervical hardness ratio reduced them (aOR 0.96, 95%CI 0.93-0.99; p < 0,05). Higher cerebroplacental ratio values were positively associated with umbilical cord arterial pH (β = 0.03, 95%CI 0.00-0.06; p = 0.05). In low-risk term pregnancies, integrated assessment of maternal hemodynamics, cervical elastography, and fetal Doppler may improve prediction of delivery outcomes. A hyperdynamic maternal profile was associated with higher birthweight and a greater likelihood ofunassisted vaginal delivery, whereas lower cervical stiffness was associated with increased odds of vaginal delivery.

Group B Streptococcus (GBS) colonization during pregnancy is associated with adverse outcomes. The associations between GBS colonization status and clinical parameters measured at different antenatal time points, and whether these differ by maternal age, remain unclear. This study aimed to explore age-stratified associations between GBS colonization and clinical parameters. A retrospective case-control study was conducted at a single center. Cases were GBS-positive women ( n = 110), and controls were GBS-negative women ( n = 155) selected from the same cohort and matched on key characteristics. Participants were stratified by maternal age (<35 [GBS-positive: n = 90; GBS-negative: n = 96] vs. ≥35 years [GBS-positive: n = 20; GBS-negative: n = 59]). GBS colonization was determined by standard culture of vaginal and perianal swabs at 35-37 weeks. Oral glucose tolerance test (OGTT) was performed at 24-28 weeks. Hemoglobin (Hb) levels and other biomarkers were compared between cases and controls within each age group. Among women aged < 35 years, GBS colonization was not associated with second-trimester OGTT results but was associated with lower third-trimester hemoglobin levels (116.98 ± 9.89 g/L vs. 120.49 ± 10.19 g/L in controls, p < 0.05) and a statistically significant but clinically negligible earlier gestational age at delivery (39.11 ± 1.05 vs. 39.41 ± 0.98 weeks, p = 0.04). In women aged ≥ 35 years, GBS colonization was associated with significantly higher fasting and 2-hour OGTT glucose levels ( p < 0.05) and a higher second-trimester neutrophil percentage (76.27% ± 5.43% vs. 73.90% ± 4.08%, p = 0.04) compared to controls. The 1-hour OGTT value showed a non-significant trend ( p = 0.06). No significant differences were observed in birth weight, infant sex, or mode of delivery. This exploratory study suggests that maternal age may modify the associations between late-pregnancy GBS colonization status and clinical parameters measured earlier in gestation. The observed patterns highlight the potential importance of considering maternal age when evaluating prenatal laboratory findings in GBS-colonized women and generate hypotheses for future research. However, given the study's retrospective design and the small sample size in subgroups, these findings should be interpreted with caution as hypothesis-generating rather than as evidence to guide clinical practice.

To observe the changes in the vaginal microbiota and cervical immune microenvironment following focused ultrasound treatment of cervical squamous intraepithelial lesions, with clinical efficacy assessed for contextual validation. The case group comprised 50 patients with cervical squamous intraepithelial lesions who underwent focused ultrasound treatment and completed longitudinal collection of cervical secretions at pretreatment, 1-2 weeks, and (14 ± 2) weeks post-treatment. According to the treatment response at (14 ± 2) weeks, the case group was further classified into cure (histopathologically confirmed absence of SIL, or normal cytology and colposcopy) and improvement (decreased SIL level on histopathology or cytology with corresponding colposcopy) subgroups. These patients were compared with 17 healthy individuals (the control group). Changes in the levels of DEFB1, IFN-γ, IL-1β, IL-8, IL-10, SIgA, SLPI, and the Th1/Th2 ratio were measured in cervical secretions. Meanwhile, vaginal microbiota was examined in both groups at baseline and (14 ± 2) weeks post-treatment. (1) Following focused ultrasound treatment, levels of DEFB1, IL-1β, IL-8, SIgA, and SLPI in cervical secretions were significantly decreased at (14 ± 2) weeks post-treatment in the cure group compared with pretreatment levels ( p < 0.05). (2) Compared with pretreatment levels in the cure group, vaginal microbiota indicators-including pH, Nugent score, bacterial diversity, bacterial density, and Lactobacillus abundance-were significantly normalized at (14 ± 2) weeks post-treatment ( p < 0.05). Focused ultrasound treatment may contribute to regression of cervical squamous intraepithelial lesions and may be associated with restoration of vaginal microbiota and cervical immune microenvironment.

Uterus didelphys with vaginal insertion of ureter with ipsilateral renal agenesis is a rare congenital anomaly of the female urogenital development. In this case, we present a 45-year-old-woman with uterus didelphys, longitudinal vaginal septum, and right renal malformations. A remanent of the right ureter inserted into the vaginal fornix alongside an absent ipsilateral kidney was discovered during preoperative MR imaging. Few cases of vaginal insertion of the ureter with uterus didelphys have been reported in the literature. Due to the rarity and anatomical complexity of uterus didelphys, alongside typical asymptomatic presentation, precise pre-operative imaging is integral for successful obstetric and gynecological surgical planning and execution.

Pelvic floor disorders, including urinary incontinence and pelvic organ prolapse (POP), substantially affect women's quality of life, yet epidemiological data from many countries remain limited. This review presents the first nationwide population-based data on pelvic floor disorder symptoms among women in Armenia and identifies factors associated with symptom burden. A nationwide cross-sectional online survey was conducted using the validated Armenian version of the Pelvic Floor Bother Questionnaire. A total of 1503 women were included (mean age: 50.5 ± 11.6 years). Stress urinary incontinence was reported by 69.9%, urgency urinary incontinence by 51.0%, POP symptoms by 16.4%, and urinary urgency by 45.8%. Increasing age, higher BMI, vaginal delivery, previous hysterectomy, and prior pelvic floor surgery were independently associated with greater symptom burden. Vaginal delivery was the strongest independent predictor of POP symptoms, while hysterectomy and previous pelvic floor surgery were also independently associated with prolapse symptoms. Hysterectomy was associated with lower odds of urgency urinary incontinence. Pelvic floor disorders are highly prevalent among women in Armenia. These findings provide the first nationwide population-based epidemiological data from Armenia and highlight the need for increased awareness, prevention, and improved access to specialized pelvic floor care.

Operative vaginal delivery (OVD) is an important alternative to cesarean section, but the relative outcomes of vacuum, forceps, and sequential vacuum + forceps approaches remain uncertain. Moreover, predictors of instrument choice are incompletely understood. This study aimed to compare maternal, intrapartum, and neonatal outcomes across OVD modalities and to integrate conventional statistics with machine learning to identify key predictive factors. We retrospectively analyzed 967 singleton deliveries at a tertiary center: vacuum ( n = 208), forceps ( n = 706), and sequential vacuum + forceps ( n = 53). Maternal characteristics, intrapartum variables, and neonatal outcomes were compared using ANOVA and chi-square tests. A Random Forest classifier was trained to rank predictors of delivery mode, with performance assessed by accuracy, AUC, and Cohen's κ. Forceps deliveries were more frequent among younger, primiparous women, while vacuum was used in older, higher-parity mothers with better base excess (BE). Vacuum + forceps deliveries had the longest decision-to-delivery interval (26.9 vs. 17.7 and 16.8 min, p < 0.001), highest rates of severe perineal laceration (73.6% vs. 34.1% and 47.5%, p < 0.001), and poorest neonatal outcomes, including lower Apgar scores and higher cephalohematoma, hyperbilirubinemia, and transfer rates. Random Forest achieved 73.7% accuracy (AUC 0.758) and identified second-stage duration, decision-to-delivery time, lactate, and BE as top predictors, some not significant in univariate tests. Vacuum and forceps each have distinct maternal and neonatal risk profiles, while sequential vacuum + forceps delivery confers the greatest morbidity, largely reflecting case complexity. Traditional statistics and machine learning offer complementary insights, highlighting both established and novel predictors. Integrating these approaches may support individualized decision-making and improve OVD outcomes.

Inflammatory response to Gardnerella during bacterial vaginosis (BV) is linked to complications including preterm birth and infection susceptibility. Platforms for local antibiotic and probiotic co-delivery have recently emerged to promote user adherence and avoid recurrence. This study designed a novel 3D cell assembly for controlled response evaluation to co-delivery platforms. Vaginal bilayer model was configured with 3.0 μm pore inserts in 24-well plates, with confluent vaginal epithelial cells (VK2 E6/E7) in apical chamber and peripheral mononuclear cells (PBMCs) in basal chamber. PEO (rapid-dissolving) and PEO:PLGA (sustained-release) nanofibers were loaded with 7.5 mg metronidazole and 5x10 7 CFU L.crispatus, and added to apical chamber. After 24-h Gardnerella treatment followed by 72-h nanofiber treatment, IL-8 and TNF-α levels were measured. Probiotic-loaded nanofibers elicited weak inflammatory response compared to Gardnerella or L. crispatus exposure. TNF-α was lower with sustained L. crispatus recovery compared to burst release (without metronidazole). IL-8 was comparable between rapid vs. sustained release. Metronidazole elicited transient Gardnerella decrease while L. crispatus inhibited longer term. Burst release yielded greater Gardnerella inhibition than sustained release, while L. crispatus recovery was relatively unaffected. Nanofibers had no cytotoxicity on VK2 cells or PBMCs. A 3D cell assembly model was established for controlled response evaluation to dual-agent nanofibers targeting BV, furthering the goal of more refined in vitro new approach methodologies (NAMs) for FRT research.

Objective To evaluate the association between uterine synechiae and obstetric outcomes and to identify factors associated with their presence in a retrospective observational cohort. This retrospective observational cohort study included 120 pregnant women, comprising 60 women with uterine synechiae and 60 without synechiae. Demographic characteristics, obstetric history, and pregnancy outcomes were compared between groups. Ultrasonographic characteristics, including synechiae thickness, were recorded. Multivariable logistic regression analysis was performed to identify factors independently associated with uterine synechiae. Maternal age was similar between groups; however, gravidity and parity were significantly higher in women with uterine synechiae ( p < 0.05). Prior curettage was significantly more frequent in the uterine synechiae group than in the control group (50.0% vs. 20.0%, p = 0.001). Gestational age at delivery was significantly lower in the synechiae group compared with controls (36.45 ± 3.57 vs. 37.95 ± 1.90 weeks, p = 0.036). Among pregnancies that reached delivery, normal spontaneous vaginal delivery was more frequent in women with synechiae, whereas cesarean section rates were comparable. Malpresentation did not differ significantly between groups. In multivariable analysis, previous curettage (OR: 3.84, 95% CI: 1.36-7.76, p = 0.001) and prior vaginal delivery (OR: 2.58, 95% CI: 1.02-6.50, p = 0.039) were independently associated with the presence of uterine synechiae. Pregnancies with ultrasonographically detected uterine synechiae were characterized by a higher prevalence of previous uterine curettage and a lower mean gestational age at delivery compared with matched controls. Although preterm birth rates were similar between groups, these findings suggest a possible association between uterine synechiae and certain pregnancy characteristics. Further prospective studies are needed to clarify their clinical significance.

Uterine leiomyosarcoma (uLMS) is a rare, aggressive uterine malignancy that usually metastasizes hematogenously, whereas gastrointestinal involvement is uncommon. A 69-year-old woman with uLMS treated by hysterectomy and adjuvant chemotherapy developed metachronous lung, sigmoid colon, gallbladder, and abdominal wall metastases. After treatment of these metastases, periodical surveillance endoscopy revealed a 15-mm subepithelial lesion with a shallow central depression in the lower gastric body. Endoscopic ultrasonography showed a well-defined submucosal lesion without muscularis propria invasion, and biopsy confirmed metastatic leiomyosarcoma. Endoscopic submucosal dissection (ESD) was performed, achieving en bloc resection without adverse events. This rare metachronous combination of gastric, colonic, and gallbladder metastases highlights that incidental gastric metastasis may occur during prolonged disease courses and suggests that ESD may be a useful minimally invasive option for local control of small gastric metastases.

To compare dydrogesterone versus levonorgestrel-releasing intrauterine system (LNG-IUS) for abnormal uterine bleeding (AUB) management with long-term follow-up and etiology-stratified analysis. This single-center retrospective cohort study analyzed reproductive-aged women with International Federation of Gynecology and Obstetrics (FIGO)-classified AUB receiving dydrogesterone ( n = 131) or LNG-IUS ( n = 118). Propensity score matching balanced baseline covariates between groups ( n = 104 pairs). Primary outcomes were bleeding control rates (composite: hemoglobin increase ≥ 1.5 g/dL, ≥ 50% Pictorial Blood Loss Assessment Chart [PBAC] reduction, no rescue interventions) at 3 and 12 months. Secondary outcomes included 24-month recurrence and adverse events (AEs). LNG-IUS demonstrated superior 3-month bleeding control versus dydrogesterone (82.7% vs. 65.4%; relative risk [RR] 1.26, 95% confidence interval [CI] 1.08-1.48; p = 0.002). At 12 months, bleeding control rates were comparable between groups (78.8% vs. 72.1%; RR 1.09, 95% CI 0.96-1.24; p = 0.17). LNG-IUS significantly reduced 24-month recurrence risk (hazard ratio [HR] 0.48, 95% CI 0.32-0.72; p < 0.001), particularly for structural AUB (HR 0.39, 95% CI 0.24-0.64). Subgroup analysis revealed LNG-IUS superiority in adenomyosis at 12 months (88.2% vs. 60.0%; RR 1.47, 95% CI 1.24-1.74; p < 0.001) but comparable efficacy in nonstructural AUB (76.6% vs. 72.9%; RR 0.95, 95% CI 0.78-1.16; p = 0.63). Dydrogesterone exhibited higher systemic AEs (28.2% vs. 13.6%; p = 0.003), while LNG-IUS had device-related events including expulsion (5.1%). LNG-IUS offers superior short-term bleeding control and sustained long-term recurrence prevention, especially for structural AUB. Dydrogesterone effectively manages nonstructural etiologies but carries higher systemic adverse event rates. Treatment selection should be etiology-guided, balancing immediate symptom control versus recurrence prevention and individualized safety considerations.

Uterine peristalsis, which originates from sub-endometrial zone of myometrium, is observed at ultrasonography as a wave-like activity of endometrium. Increased uterine peristalsis is suggested to be related to decreased pregnancy rates in both fresh and frozen embryo transfer cycles. The aim of this study is to compare the effects of two different frozen embryo transfer preparation protocols on the frequency of uterine peristalsis and to evaluate the effect of peristalsis on pregnancy rates. In this observational cohort study, 3-min transvaginal ultrasound videos were recorded one hour before embryo transfer in frozen embryo transfer cycles prepared by either artificial hormone treatment or aromatase inhibitor stimulation. Peristalsis frequency was assessed by reviewing videos at triple speed. Consequent pregnancy outcomes were also analyzed. During the study period of four months, a total of 147 patients with 99 artificial hormone treatments and 48 aromatase inhibitor-stimulated frozen embryo transfer cycles were included. The absence of uterine peristalsis was observed in 27.1% of the aromatase inhibitor-stimulated patients and 23.2% of the artificial hormone-treated patients ( p = 0.68). Among those with peristalsis, the frequency was similar between groups (0.95 ± 0.59 and 0.98 ± 0.68 for the aromatase inhibitor-stimulated and artificial hormone treatment protocols, respectively; p = 0.97). Peristalsis presence or frequency was not associated with pregnancy or live birth rates. In this study, uterine peristalsis frequency at frozen embryo transfer cycles did not differ between endometrial preparation protocols and showed no significant association with pregnancy outcomes. Further randomized studies are warranted. Uterine peristalsis prior to embryo transfer does not differ between artificial hormone treatment and aromatase inhibitor-stimulated frozen embryo transfer cycles.Neither pregnancy rates nor live birth rates were affected by the frequency of uterine peristalsis.Routine assessment of uterine contractility may not be necessary in standard frozen embryo transfer practice.

Taohe Chengqi Decoction (THCQD), a classical formula from Shang Han Lun, is traditionally used to clear heat, purge accumulation, activate blood circulation, and dispel blood stasis in lower-jiao blood accumulation and gynecological stasis-heat disorders. Acute pelvic inflammatory disease (APID) frequently affects the upper female reproductive tract during reproductive age, and its acute-stage uterine injury is closely linked to inflammatory imbalance, oxidative stress, and local tissue damage. Therefore, evaluating THCQD in an experimental model of APID-related uterine inflammatory injury may provide evidence for its potential relevance to gynecological inflammatory injury. To evaluate the effects of THCQD in a mechanical-chemical injury-induced rat model of APID-related local uterine inflammatory injury and to explore its possible association with inflammatory responses, oxidative stress, and JNK/p38 MAPK-NF-κB-apoptosis-related signaling. A rat model was generated using endometrial mechanical injury together with intrauterine injection of phenol mucilage. Pharmacodynamic effects and potential mechanisms were assessed by biochemical assays, ELISA, histopathology, UPLC-MS/MS profiling, network pharmacology, transcriptomics, molecular docking, Western blotting, RT-qPCR, and immunohistochemistry. Cell-based validation was performed using LPS-stimulated primary rat uterine endometrial epithelial cells, H-THCQD-containing serum, and JNK/p38 MAPK inhibitors. THCQD improved inflammatory activation, redox imbalance, peripheral blood inflammatory cell abnormalities, and uterine pathological injury. Integrated analyses and experimental validation supported the possible involvement of JNK/p38 MAPK-NF-κB-apoptosis-related signaling in THCQD intervention. THCQD alleviated APID-related local uterine inflammatory injury, and this effect may be associated with the involvement of JNK/p38 MAPK-NF-κB-apoptosis-related signaling. These findings provide experimental evidence for the effects of THCQD on APID-related uterine inflammatory injury and support further mechanistic research on classical formulas in gynecological inflammatory injury.

Diethylstilbestrol (DES) is a potent synthetic estrogen implicated in endometrial carcinogenesis through estrogen receptor (ER)-dependent mechanisms. However, the temporal relationship between DES exposure, estrogen receptor alpha (ERα) expression, and histopathological progression of endometrial lesions remains incompletely defined in vivo. An experimental in vivo study was conducted using 32 eight-week-old female mice randomly assigned to eight groups, including two untreated controls and six DES-treated groups with varying exposure and observation durations. DES was administered at 1000 µg according to predefined schedules. Uterine tissues were examined histopathologically using HE staining, and ERα expression was evaluated by immunohistochemistry using the modified Remmele Immunoreactive Score. Statistical analyses included one-way ANOVA with Tukey post hoc testing, Kruskal-Wallis and Mann-Whitney U tests, and path analysis to assess mechanistic relationships. ERα expression differed significantly among groups, with the highest expression observed in mice receiving prolonged DES exposure followed by extended observation. Histopathological evaluation demonstrated a clear progression from normal endometrium in control groups to higher-grade lesions in DES-treated groups, with severe (Grade 3) changes predominating in high exposure cohorts. Path analysis revealed a significant association between DES exposure and ERα expression, as well as a positive effect of ERα on EC development. DES promotes endometrial carcinogenesis through ERα dependent mechanisms in vivo. Increased ERα expression parallels histopathological progression, and mechanistic analysis confirms ERα as a key mediator linking synthetic estrogen exposure to tumor development. These findings underscore the central role of estrogen signaling in DES-induced EC.

Women with congenital uterine anomalies (CUA) are at increased risk for spontaneous preterm birth (sPTB). Cervical length surveillance is commonly used to identify cervical shortening as a predictor of sPTB. However, evidence supporting its predictive value in women with CUA remains limited. This study aims to evaluate the effectiveness of cervical length surveillance in predicting sPTB in women with CUA. This retrospective observational study included women with CUA diagnosed on imaging who attended the preterm birth prevention clinic between 2020 and 2024. Singleton pregnancies without additional risk factors for sPTB were included. Cervical length was measured by transvaginal ultrasound between 16 and 24 weeks of gestation. The primary outcome was sPTB before 37 weeks' gestation. Logistic regression analysis and receiver operating characteristic (ROC) curve analyses were performed to assess the association between cervical length and sPTB and its predictive value. Of 502 women referred to the preterm birth prevention clinic, 49 had CUA as their only risk factor for preterm birth. Five women (10.2%) experienced sPTB, and all had normal cervical length measurements. Cervical shortening (<25 mm) was identified in only one woman (2.0%), who subsequently delivered at term following cervical cerclage insertion. The prevalence of sPTB was highest among women with a unicornuate uterus (33.3%), followed by those with a septate uterus (11.1%) and a bicornuate uterus (9.1%). Logistic regression analysis demonstrated no association between cervical length and sPTB (OR 0.97, 95% CI 0.78-1.19; p = 0.75). ROC curve analysis showed poor predictive performance (AUC 0.57, 95% CI 0.31-0.84). While cervical length surveillance showed limited predictive value of sPTB in this cohort, the low incidence of cervical shortening precludes definitive conclusions. Larger prospective studies are required to clarify the role of cervical length surveillance in this high-risk group. Some women are born with a uterus that has a different shape from usual. This is called a congenital uterine anomaly (CUA). Women with congenital uterine anomalies may have a higher chance of giving birth early, before 37 weeks of pregnancy. To help identify those at risk of early birth, many hospitals monitor the length of the cervix during pregnancy. A cervix that shortens more than expected may indicate an increased risk of early birth. We studied 49 pregnant women with congenital uterine anomalies who attended a specialist clinic for preventing early birth (preterm birth prevention clinic). Cervical length was measured between 16 and 24 weeks of pregnancy using transvaginal ultrasound scans. Five of the 49 women (10.2%) gave birth before 37 weeks of gestation. However, all five had normal cervical length measurements during pregnancy. Only one woman in the study developed a short cervix, and after receiving treatment, she gave birth at full term. These findings suggest that measuring cervical length may not always identify women with CUA who will give birth early. Because a short cervix was uncommon in our study, research involving larger numbers of women is needed to understand whether cervical length monitoring is useful for predicting early birth in this group.