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This study describes the content of TikTok videos related to tubal permanent contraception and evaluates the quality, understandability and actionability of the educational videos on tubal permanent contraception on TikTok by creator type. A TikTok Data webscraper tool was used to download and extract information of the top 500 videos on TikTok videos with hashtags related to tubal permanent contraception. After qualitative descriptive analysis, videos classified as educational were further evaluated using the mDISCERN, PEMAT and GQS scoring systems. Healthcare providers (HCP) created videos with higher mDISCERN scores, with an overall difference in score between the two groups of 1.79 (95% CI 1.36-2.23, p-value<0.001). The four major recurring themes in the content of videos included pregnancy after permanent contraception, access to permanent contraception, types of procedures, and childfree by choice content. Subthemes included experiences with providers including barriers to access and coercion. Healthcare providers (HCP) created higher quality and more understandable videos on permanent contraception, highlighting the importance of HCPs as a source of health information on social media.

Access to information has been identified as a social determinant of health, influencing knowledge, attitudes, and behaviors that can shape health outcomes. Contraceptive information influences how individuals make decisions about accessing contraceptive care and method use, as well as broader reproductive health trajectories. The recent proliferation of contraceptive misinformation has led to increased research and media attention on this topic. Misinformation from all types of information sources must be understood and addressed by the sexual and reproductive health, rights, and justice field to enable people to make informed, autonomous decisions about contraception based on high-quality, high-integrity evidence. This Research Practice Support aims to guide researchers interested in studying contraceptive misinformation. First, we define key terms related to the information environment and ecosystem, including misinformation, disinformation, and other related concepts. Then, we provide actionable recommendations for each stage of the research process for studies focused on contraceptive misinformation, including study design and ethical considerations, data sources and collection, and dissemination. Scholars are encouraged to consider these recommendations to maximize the impact of their research focused on contraceptive misinformation.

The number of reproductive-age solid organ transplantation (SOT) recipients is growing, yet comparative data on contraception use across organ types are limited. We performed a retrospective cohort study of women who underwent first-time liver, kidney, heart, or lung transplantation between the ages of 18 and 45 years from 2015 and 2025 using TriNetX (n = 10 155). Contraception uptake within 2 years was assessed by organ, including patterns of initial contraceptive method and subsequent method changes, and clinical outcomes, including osteoporosis, thromboembolism, and graft rejection, were compared by contraception type. Among 10,155 eligible SOT recipients, 19.9% had documented contraception within 2 years of SOT (heart 27.3%, lung 22.5%, kidney 19.7%, liver 16.8%, P < .001). Combined oral contraception was the most common initial contraception method, followed by depot medroxyprogesterone acetate (DMPA). However, those who started on DMPA were more likely to switch methods. Compared with no contraception, DMPA was associated with increased risk of osteoporosis, hypertension, thrombosis, and graft rejection, whereas estradiol-containing agents were not. Overall, contraception use after SOT was uncommon with very low rates of highly effective options, particularly after liver and kidney transplant. Higher switching and adverse associations with DMPA support early, organ-tailored contraceptive counseling and careful method selection post-SOT.

Prior research has demonstrated that adolescent and adult patients are interested in receiving contraceptive care in the ED. We sought to determine knowledge, attitudes, and behaviors of ED clinicians towards contraceptive care and perceived barriers and challenges to providing contraception. This was cross-sectional online survey of ED physicians and advanced practice providers across 5 Oregon EDs affiliated with a single health system, encompassing academic adult and pediatric, community, and critical access sites. The survey was developed collaboratively by ED and women's health experts and piloted for face validity. Analysis included calculation of counts, means, and percentages, and deductive content analysis of free-text comments. Fifty people (26% of the practice population) responded to the questionnaire: 72% indicated that prescribing contraception was important and 78% felt it was feasible within their current practice; 24% reported being currently engaged in management of contraception in the ED. Only 73% of surveyed clinicians stated they currently offer emergency contraception; over 90% stated they currently provide or are willing to refill or initiate hormonal contraception. Those practicing at the academic sites were more likely to state that they initiate prescription hormonal therapy (28% vs 9%, p < 0.001) or would be willing to do so in the future (72% vs 45%, p < 0.001) and that they were willing to offer injectable hormonal contraception (89% vs 36%, p < 0.001). Most commonly identified barriers were concerns about adequate follow up, time to provide care, and training needs (e.g., medical indications for and contraindications to contraception). Contraception provision was seen as important and feasible by many ED practitioners. Training and systems supports that could help EDs function as a contraceptive safety net for some patients were identified.

We examined factors that inform iron-deficiency screening practices in female athletes, with a focus on the menstrual cycle. Twenty-four National Rugby League athletes attended a 5-week training camp (age 21.6 ± 3.4 years old, body mass: 76.3 ± 12.1 kg, height: 164.9 ± 4.6 cm). Athletes were either naturally cycling (athleteNC; n = 11) or using hormonal contraception (athleteHC; n = 13). Venous blood samples were collected during Phases 1, 2, and 4 of the menstrual cycle in athleteNC for determination of iron status. Three equally spaced, corresponding time points were sampled in athleteHC. Every 48 hr, a capillary blood sample was collected and analyzed for ferritin, hepcidin, creatine kinase, and C-reactive protein. No differences across menstrual phases or groups were evident for ferritin, hepcidin, transferrin or hemoglobin (p > .05). Serum iron (12.9 ± 4.6 μmol/L to 16.9 ± 8.5 μmol/L; p = .045) and transferrin saturation (17.3% ± 7.8% to 22.1% ± 14.5%; p = .041) increased from Phase 1 to Phase 2 in athleteNC only, with no change seen in athleteHC. Ferritin (-16%; p < .001) and hepcidin (-23%; p < .001) declined across the training camp in all athletes. Concentrations of C-reactive protein (p = .039) were consistently higher in athleteHC compared with athleteNC, whereas creatine kinase activity were similar between groups (p = .140). Our findings did not identify clear menstrual cycle phase-related differences in markers of iron status or regulation, suggesting that the influence of cycle phase may be relatively small compared with other sources of variation. Practitioners should be mindful that athletes using hormonal contraceptives may report with greater C-reactive protein concentrations than naturally cycling athletes.

The emergency department (ED) represents a novel venue to initiate contraception, yet little is known about the availability, activities, and outcomes used to assess ED-based contraception programs. This scoping review seeks to identify, describe, and summarize the outcomes used to evaluate these programs in the US. PubMed, CINAHL, Scopus, and MEDLINE identified programs from peer-reviewed and non-peer-reviewed sources. Eligible programs evaluated an intervention aimed at unintended pregnancy prevention in a US ED. Two reviewers independently performed a systematic selection of title, abstract, and full-text before performing data extraction. Percent agreement (PA) assessed reviewer agreement. Characteristics, activities, and outcomes were summarized descriptively. Results reporting followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews. Investigators reviewed 1978 titles (PA = 98.6%); 56 abstracts (PA = 84.4%) and 37 full text sources (PA = 78.4%). Twenty sources underwent data extraction (PA = 90.6%). All programs targeted adolescent females, two included females up to 45 years, and two included males. Implemented activities included pamphlets or videos (n = 5), contraception counseling (n = 4), primary or gynecological care referrals (n = 5), ED initiation of long-acting reversible contraceptives (n = 4), and provision of safe-sex-items (n = 2). Outcomes assessed included pregnancy status three months post-intervention (n = 6), contraception initiation in the ED (n = 2) and post-ED intervention (n = 7), and contraception use at last intercourse (n = 4). Few ED-based programs exist to prevent unintended pregnancy in the US. Existing programs vary in activities and lack standardized outcome measures. Most studies evaluated only short-term outcomes limiting evidence for long-term prevention via contraception initiation within the ED. Continued study in diverse geographic regions with larger sample sizes and standardized long-term outcomes is necessary to better inform effectiveness and scalability.

To describe patterns in contraceptive use and factors influencing contraceptive decision-making during the post-molar beta-hCG monitoring period. This was a mixed methods analysis of patients who received care for molar pregnancy at a regional gestational trophoblastic disease center in the South between March 1996 and February 2025. Associations between demographic factors and contraception use during monitoring were assessed using chi-square and Kruskal-Wallis tests. Semi-structured interviews were conducted from December 2024 to April 2025 until thematic saturation was reached with patients diagnosed since August 2022, to minimize recall bias. Interviews were recorded, transcribed, and analyzed for patterns using NVivo 14. A total of 264 patients were identified for the database. Ten completed a qualitative interview, of whom four did not use contraception during monitoring. Most identified as white (56.4% in database, 70% among those interviewed) and non-Hispanic (85.7%, 70%, respectively). Within the database, 21.6% reported no contraception use during monitoring. The most utilized methods were combined hormonal contraceptives (37.5%), barrier methods (21.6%), and medroxyprogesterone acetate injection (14.8%). Significant differences in method were identified based on age, race, county, and number of live births at molar pregnancy diagnosis. In interviews, participants discussed several key findings related to contraceptive decision-making: (1) familiarity, (2) temporary use, (3) importance of monitoring, (4) side effects, and (5) trying new things. Despite guideline-based recommendations, more than one-fifth of patients did not use contraception during monitoring for molar pregnancy. Qualitative data demonstrate that method selection is uniquely shaped by the importance of beta-hCG monitoring and desire for expeditious return to fertility. One-fifth of patients did not use contraception during molar pregnancy monitoring, highlighting an opportunity for improved contraceptive counseling and alignment with guidelines to reduce the risk of unintended pregnancy and avoid potential confounding of malignant transformation.

To describe patients' decisions to replace or extend use of their 52 mg levonorgestrel (LNG) intrauterine device (IUD) or their 68 mg etonogestrel (ENG) subdermal contraceptive implant beyond the five-year or three-year FDA-approved duration, respectively, through the full known duration of efficacy. We recruited patients presenting for replacement of long-acting reversible contraceptive (LARC) from an obstetrics/gynecology academic clinic to participate in a semi-structured interview regarding their decision to replace or extend use of their LARC. The semi-structured interviews included questions to determine factors that impacted their decision to replace or continue the 52 mg LNG IUD or contraceptive 68 mg ENG implant at five years and three years respectively. We also asked about barriers accessing information regarding the longer duration of efficacy for pregnancy prevention. We interviewed 30 participants with an average age of 32 (range 21-44). Three themes emerged: 1) Central role of information and trust in clinical guidance 2) Physical and experiential factors directly motivate decisions to replace or extend LARC use 3) Desire for more information to make an informed choice. Participants in this study replaced their LARC earlier than the full duration of pregnancy prevention due to changes in symptom and efficacy concerns. The main reasons for extended use of LARC were avoidance of pain with procedures and trust in the clinician. This study highlights the importance of communication improvements from health systems regarding the safety and efficacy of extended use of LARC which may allow patients to make more informed decisions regarding their duration of contraceptive use. Qualitative study examining patients' decisions to replace or extend use of their 52 mg LNG IUD or 68 mg ENG contraceptive implant beyond FDA-approved duration, highlighted the central role of trust in clinical guidance, physical and experiential factors motivate decisions, and desire for more information to make an informed choice.

This qualitative study explored how gender power dynamics shape the decisions of girls and young women in Sagamu Local Government Area (Ogun State) and Benin City (Edo State), Nigeria, regarding romantic relationships, sexual activity, contraceptive use and pregnancy prevention. Semi-structured interviews were conducted with 14 participants (7 pregnant young mothers and 7 sexually active non-mothers), recruited through criterion-based and snowball sampling. Thematic analysis revealed that financial dependence, emotional attachment and the need for companionship were key motivations for relationships. Although awareness of modern contraception was common, its use was limited by misconceptions, fear of side effects, male partner resistance and constrained negotiation ability. Gender power imbalances, exacerbated by age and economic disparities, fundamentally undermined reproductive autonomy. Nonetheless, glimpses of sexual and reproductive agency were evident in the active assertion of sexual desire and in the varied strategies participants employed to negotiate contraceptive use. Findings indicate that addressing adolescent pregnancy in Nigeria requires moving beyond contraceptive knowledge dissemination. Interventions must be gender-sensitive, empower girls and young women to negotiate sexual and reproductive decisions, and address underlying structural inequalities to strengthen relational autonomy.

Women's reproductive rights are intensely debated, with abortion laws in the United States constantly changing. However, the long-term economic consequences of abortion remain largely unknown due to a lack of robust research in this area. Drawing on lifespan career theory, we theorize that pregnancy during the early-career period represents a pivotal inflection point. It initiates divergent reproductive pathways with lasting, path-dependent effects on women's economic trajectories. We conceptualize abortion as a distinct and constrained early-career event that may be associated with career development in ways that differ meaningfully from both parenthood and nonpregnancy. Using national longitudinal data from 6,218 participants in the United States (1979-2020), we examine how having an abortion, compared with becoming a parent or not experiencing pregnancy at all, is related to women's long-term economic trajectories. Results show that women who had an abortion, and those who did not become pregnant, earned significantly more over a 30-year period than those who became mothers by an estimated $398,000 ($495,000 in 2025 dollars) and $448,000 ($556,000 in 2025 dollars), respectively. These findings extend lifespan career theory by conceptualizing reproductive decisions during one's early career as critical but understudied career-defining events that are associated with women's economic mobility. The results also suggest several potential policy implications: Protecting access to contraception and abortion, and providing mothers with structural family support mechanisms such a job-protected paid parental leave and subsidized childcare, may help women achieve sustained economic stability and career advancement. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Couple agreement on contraception is widely treated as a marker of programme success, yet whether such agreement has kept pace with rising contraceptive use in sub-Saharan Africa is largely unknown. We analysed three rounds of the Nigeria Demographic and Health Survey Couples' Recode (2013, 2018, 2024; 23,547 couples) using design-weighted descriptive, trend, and multivariable logistic analyses. We defined practice concordance from partners' independently reported current method status and decomposed it into five mutually exclusive categories. A qualitative study of 42 Ogun State couples illustrated the mechanism behind the pattern. National practice concordance fell from 81.6% to 73.5% (and from 70.0% to 46.4% in Ogun State) even as women's modern use (9.7% to 16.1%), spousal communication (33.0% to 42.1%), and Unmet need (16.1% to 21.3%) rose. Concordance was overwhelmingly shared non-use (69.5% in 2024); genuine mutual active use remained near 4%; and wife-only discordance nearly doubled (7.5% to 14.0%), which supplied most of the offsetting rise in discordance as shared non-use contracted. An inverse socioeconomic gradient and a north-south gradient persisted after adjustment, and spousal communication was negatively associated with concordance (odds ratio 0.83, 95% CI 0.76-0.91). Rising, increasingly female-led contraceptive practice is associated at the population level with falling couple concordance, a pattern consistent with an incomplete gender transition rather than programme failure.

Pelvic venous disorders disproportionately affect women, but women-centered reporting in intervention studies remains unclear. We performed a source-checked, cross-sectional bibliographic analysis of 42 PubMed-indexed original human studies identified from a reconciled 290-record search pool. Prespecified domains covered reproductive context, pelvic and sexual symptoms, patient-reported outcomes, function, and procedural outcomes. Thirty-four studies included only women (81.0%). Pregnancy history, parity, postpartum status, and menopausal/hormonal status were reported in 31 (73.8%), 26 (61.9%), 5 (11.9%), and 6 (14.3%) studies, respectively. Dyspareunia and vulvar varices were reported in 27 (64.3%) and 19 (45.2%). PROM/QoL and return-to-function/work outcomes were reported in 7 (16.7%) and 3 (7.1%), whereas symptom improvement and reintervention were reported in 35 (83.3%) and 28 (66.7%). Later studies more often reported dyspareunia and PROM/QoL, but reproductive and hormonal reporting did not improve uniformly. Despite the predominance of women-only studies, women-centered reporting remains inconsistent.

Female infertility is an escalating global health challenge. Utilizing data from the Global Burden of Disease Study 2021, this study analyzed the spatiotemporal distribution of female infertility (1990-2021) and projected trends through 2050. We evaluated prevalence, disability-adjusted life years (DALYs), and age-standardized rates across 204 countries, stratified by Socio-demographic Index (SDI). Temporal trends were quantified using Estimated Annual Percentage Change (EAPC), and future burdens were forecasted via Bayesian Age-Period-Cohort models. Global female infertility cases surged by 84.4%, rising from 59.69 million in 1990 to 110.09 million in 2021, with the age-standardized prevalence rate (ASPR) trending upward (EAPC=0.70). While High-middle and Middle SDI regions bore the largest absolute burden-driven by persistent infections and metabolic risks-High SDI regions exhibited the steepest increase (EAPC=1.43). This rapid rise in developed nations aligns with delayed childbearing, evidenced by a peak prevalence shift to the 40-44 age group, contrasting with the global peak at 35-39 years. Projections indicate a continued ascent in burden across all cohorts through 2050. The global burden of female infertility is rising and spatially distinct. Transitioning economies face high baseline rates, yet developed nations show the fastest growth, demanding urgent action. Strategies must be tailored to regional drivers: prioritizing infection control and metabolic health in middle-income settings, and fertility support policies in high-income regions.

This study translates and validates an Assamese version of the Infertility Stigma Instrument-Female (ISI-F) among women seeking Medically Assisted Reproduction (MAR) in Assam, India. The translated ISI-F was administered among 188 Assamese-speaking women in two healthcare facilities. Exploratory factor analysis (EFA), reliability assessment, and confirmatory factor analysis (CFA) were carried out. Convergent validity was examined using Spearman correlations between ISI-F and the Fertility Quality of Life (FertiQOL) subscales. EFA yielded a refined 15-item scale with four factors: Social Withdrawal, Perceived Social Pressure, Experienced Stigma, and Avoidant Coping, explaining 44.36% of the variance. The scale had acceptable reliability (Cronbach's α = 0.728; McDonald's ω = 0.911). CFA demonstrated a better fit to the four-factor Assamese model (RMSEA = 0.051; CFI = 0.92; TLI = 0.90) than the original ISI-F structure. ISI-F scores were significantly and negatively correlated with FertiQOL domains, supporting the convergent validity. Mean stigma score (44.6 ± 9.11) indicated moderate perceived infertility stigma. The Assamese version of the ISI-F is a reliable and culturally appropriate tool for measuring infertility stigma among MAR treatment seekers in Assam, India. The revised factor structure reflects context-specific distinctions between social pressure, experienced stigma, and coping responses.

Female infertility is a common reproductive disorder influenced by metabolic dysfunction. The glycolipid metabolism 7 factors (GLM7) is a composite metabolic index integrating age, BMI, glucose, insulin, and lipid profiles. This study aimed to examine its association with female infertility in a nationally representative population. Data from 1,405 female participants aged 18-45 years from the 2013-2018 cycles of the National Health and Nutrition Examination Survey were analyzed. We used survey-weighted logistic regression models and restricted cubic splines to assess the association between GLM7 and infertility. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy. A total of 167 participants (11.9%) reported infertility. After full adjustment, higher GLM7 levels were independently associated with increased odds of infertility (odds ratio (OR) = 1.401, 95% CI: 1.028-1.909, p = 0.034). A positive linear association was observed, with a potential plateau effect at GLM7 ≈ 6.98. GLM7 showed modest discriminative ability (AUC = 0.596, 95%CI: 0.552-0.639). GLM7 was positively associated with female infertility. As a multidimensional metabolic indicator, GLM7 may provide complementary information for reproductive health research. However, its modest discriminative performance suggests limited value as a standalone screening tool, warranting further validation in longitudinal and clinical studies.

Female infertility is multifactorial, with adiposity and regional fat distribution hypothesized as contributors, though evidence using detailed fat measures is limited. This study aims to examine the association between fat distribution indicators and female infertility in a nationally representative sample. This retrospective cross-sectional study analyzed NHANES 2013-2018 data from 2,531 women aged 20-45. Infertility was defined by self-reported difficulty conceiving ≥ 12 months or seeking fertility care. Exposures included body mass index (BMI) and DXA-based measures: total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral fat/total fat (VPF), subcutaneous fat/total fat (SPF), and visceral fat/subcutaneous fat ratio (VSR). Multivariable logistic regression was used to assess associations, and sensitivity analyses were performed to evaluate robustness. In multivariable-adjusted models, TPF, APF, AGR, and BMI were modestly associated with higher odds of infertility (TPF: OR = 1.02, 95%CI: 1.00-1.05; APF: OR = 1.03, 95%CI: 1.01-1.04; AGR: OR = 1.02, 95%CI: 1.01-1.03; BMI: OR = 1.02, 95%CI: 1.01-1.04). Smooth curve fitting suggested a generally monotonic positive pattern for these associations. Associations were broadly similar across subgroups, although some subgroup interactions were observed. In this analysis, TPF, APF, AGR, and BMI showed modest associations with infertility, which should not be interpreted causally. Although associations were generally consistent across subgroups, subgroup-specific heterogeneity cannot be excluded.

Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored. Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function. Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.

In polyendocrine metabolic ovarian syndrome (PMOS), conventional Rotterdam phenotypes may not adequately capture the multidimensional hormonal and metabolic heterogeneity of the disorder. To identify clinically meaningful PMOS subtypes using a data-driven clustering approach among infertile South Indian women. A cross-sectional study was conducted among 196 infertile women diagnosed with PMOS (Rotterdam criteria) at a fertility centre in South India. Unsupervised k-means clustering was performed and cluster stability was assessed using Jaccard bootstrapping. Three subtypes were identified: gonadotrophin predominant, body mass index (BMI) predominant, and intermediate. The gonadotrophin predominant cluster exhibited intermediate BMI with higher LH and FSH concentrations and the highest LH/FSH ratio. The BMI predominant cluster demonstrated the highest BMI with a relatively low LH/FSH ratio, while the intermediate cluster showed lean-to-normal BMI with the lowest LH, FSH, and LH/FSH ratio. Significant differences were observed between clusters in systolic and diastolic blood pressure and endometrial thickness. No significant between-cluster differences were found for anti-Müllerian hormone, estradiol, prolactin, thyroid-stimulating hormone and haemoglobin A1c. Data-driven clustering using BMI, LH, and FSH identified three PMOS subtypes, demonstrating heterogeneity beyond the conventional Rotterdam phenotypic classification. The identified subtypes enhance understanding of clinical heterogeneity of PMOS and provide a basis for potential application in personalized patient management.

A receptive endometrium is essential for successful embryo implantation, yet its dynamic cellular and molecular features remain poorly understood due to limitations in current in vitro models. We aimed to establish a three-dimensional (3-D) coculture endometrial model mimicking physiological conditions, characterizing its response to varied culture conditions using receptivity-associated gene expression profiling. Epithelial Ishikawa or RL95-2 cells were layered above stromal cells (St-T1b) separated by Matrigel and cultured in different media [such as growth factor-reduced, serum-containing standard, and cytokine- and epidermal growth factor (EGF)-supplemented] or exposed to hormonal stimuli [estradiol (E2), progesterone (P4), and cAMP] over a 10-day differentiation period. Our model effectively recapitulates the layered structure of the endometrium, as confirmed by scanning electron microscopy and immunofluorescence. Transcriptional analysis of fertility-associated markers revealed media- and cell line-dependent alterations of key receptivity markers. In standard media, gene expression alterations occurred for hairy/enhancer-of-split related with YRPW motif protein 1 ( HEY1 ) in both, but for HEY2 solely in the Ishikawa model and endothelin receptor type B ( EDNRB ) only in the RL95-2 model, cytokine-supplemented media for leukemia inhibitory factor ( LIF ) and transgelin ( TAGLN ) in both models, whereas heparanase ( HPSE ) only in RL95-2 models and dipeptidylpeptidase 4 ( DPP4 ) and HEY1 only in Ishikawa models. Notably, the long-term hormonal treatment triggered a transcriptomic signature, especially in the RL95-2 model, which closely correlates to the clinically determined one at the window of implantation (WOI). We conclude that our in vitro model reflects the phenotypic and transcriptional dynamics of the in vivo endometrium and responds distinctly to external stimuli. It serves as a robust platform to study endometrial receptivity mechanisms and holds potential for future applications in infertility and implantation research. NEW & NOTEWORTHY A receptive endometrium is essential for successful embryo implantation, yet its dynamic cellular and molecular features remain poorly understood. Here, we establish and characterize a three-dimensional (3-D) model of the endometrium combining epithelial and stromal cell lines. The model reflects the phenotypic and transcriptional dynamics of the in vivo endometrium and responds distinctly to external stimuli, serving as a robust platform to study endometrial receptivity mechanisms.

Intrauterine adhesion (IUA) significantly contributes to female infertility, primarily characterized by abnormal fibrotic remodeling of the endometrium. The intricate interplay among various cellular components within the endometrial microenvironment plays a pivotal role in IUA pathophysiology. Among these implicated factors, the vitamin D receptor (VDR) has emerged as a potential regulator of fibrotic processes; however, its specific role and underlying mechanisms in IUA remain inadequately understood. This study aimed to investigate the role of VDR in IUA pathogenesis and its impact on endometrial macrophage behavior. To investigate VDR's role in IUA, we conducted a comprehensive analysis of clinical endometrial samples from patients diagnosed with IUA. Complementary to this, we performed in vitro experiments using bone marrow-derived macrophages (BMDMs) obtained from both wild-type (WT) and VDR conditionnal knockout (VDR-cKO) mice. Furthermore, in vivo studies were carried out using an IUA mouse model alongside VDR-cKO mice to assess the physiological relevance of our findings. Our investigation revealed a marked reduction in VDR expression within endometrial macrophages from IUA patients. In vitro assessments indicated that VDR deficiency led to enhanced pro-inflammatory M1 polarization, evidenced by increased level of iNOS and decreased CD206 in BMDMs. Mechanistically, VDR conditional knockout was found to induce cuproptosis, characterized by downregulation of ATP7B and upregulation of DLAT. Additionally, we demonstrated that VDR transcriptionally activates ATP7B expression, with luciferase reporter assays confirming VDR's direct binding to the ATP7B promoter. In vivo experiments further established that macrophage-specific VDR knockout intensified endometrial fibrosis, heightened M1 polarization, and increased cuproptosis in the IUA mouse model, while administration of a VDR agonist effectively reversed these phenotypic alterations. Our findings reveal a novel mechanistic pathway by which macrophage-specific VDR deficiency exacerbates IUA pathogenesis through dysregulation of the ATP7B-cuproptosis axis and promotion of profibrotic M1-like macrophage polarization. These insights suggest that VDR agonism may represent a promising therapeutic approach for the prevention and treatment of IUA, warranting further investigation into its clinical applicability.

Intrauterine adhesion (IUA) is a leading cause of female infertility with suboptimal clinical treatment outcomes. Puerarin (PUE) exhibits potent anti-fibrotic activity. Herein, we fabricated a PUE-loaded peptide hydrogel (PUE-Gel) and investigated its physicochemical properties, biocompatibility, and therapeutic efficacy against IUA, as well as the underlying mechanism. PUE-Gel exhibited excellent biocompatibility, injectability, sustained drug release, and biodegradability. In an in vivo IUA model, PUE-Gel significantly restored injured endometrial morphology, increased gland and blood vessel numbers, and attenuated fibrosis in IUA rats. It also restored the expression of estrogen/progesterone receptors and integrin ανβ3 to improve endometrial receptivity, along with a markedly enhanced pregnancy rate. Transcriptomic and mechanistic studies suggested that the injury-activated Wnt/β-catenin signaling pathway may contribute to endometrial fibrosis. Collectively, PUE-Gel acts as both a physical anti-adhesion barrier and a localized sustained drug delivery system, effectively alleviating IUA potentially through modulation of the Wnt/β-catenin pathway to promote endometrial regeneration, angiogenesis, and fertility recovery. This work provides a bioactive hydrogel biomaterial and a promising potential strategy for IUA and endometrial damage-induced infertility.

High-risk human papillomavirus-independent, p53-wild-type vulvar intraepithelial neoplasia (HPVi(p53wt) VIN) is a squamous cell carcinoma precursor lesion with altered squamous maturation but minimal to no cytologic atypia. Use of p16 and p53 immunohistochemical stains is strongly encouraged for accurate subclassification of VIN lesions due to the potential for overlapping morphologic features. Additionally, there are a number of benign and inflammatory mimics of HPVi(p53wt) VIN. For lesions that cannot be definitively classified as either neoplastic or inflammatory/reactive/benign, descriptive diagnoses or "vulvar aberrant maturation" are appropriate.

Vulvar adenocarcinoma of mammary gland type (AMGT) is a rare, locally aggressive neoplasm of anogenital mammary-like glands that mimics the histologic and immunophenotypic features of breast carcinoma. Fewer than 60 cases have been described in the literature since the first documented case in 1936. The extreme rarity and resemblance to breast carcinoma complicate diagnosis and treatment. This report presents a case of AMGT in a 61-year-old woman who presented with a palpable, subcutaneous lesion of the lateral mons pubis and labia minora. Initial biopsy identified the lesion as metastatic carcinoma, but immunohistochemical (IHC) analysis and PET/CT indicated a vulvar adenocarcinoma with local nodal metastasis. Aggressive management with radical vulvectomy and bilateral inguinofemoral lymphadenectomy with thorough specimen evaluation by surgical pathology led to the final diagnosis of AMGT TNM stage pT1bpN2cM0 and vulvar FIGO Stage IIIC. IHC staining identified the tumor as ER, PR, and 3+ HER2 positive. Breast cancer treatment guidelines informed the ultimate systemic therapy regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab. Maintenance therapy with trastuzumab and anastrozole was utilized. The patient remained in remission from AMGT 24 months following completion of chemotherapy. While the diagnosis of AMGT poses a unique challenge, IHC staining and imaging to rule out metastatic carcinoma can support the ultimate diagnosis. The sustained remission in this case supports the extrapolation of treatment from vulvar and breast cancer guidelines. Additionally, this case suggests the utility of hormone receptor- and HER2-targeted therapies for systemic treatment.

Angiomyofibroblastoma is a rare, benign mesenchymal tumor of the vulvovaginal region, often misdiagnosed due to its nonspecific clinical presentation. Accurate diagnosis and appropriate surgical management are essential to achieve optimal oncological and aesthetic outcomes. This reports presents the case of a 28-year-old woman with a two-year history of a slowly enlarging, painless mass of the left labium majus. Clinical and ultrasonographic evaluation suggested a benign lesion. The patient underwent surgical excision via an interlabial sulcus approach, selected to ensure adequate exposure and optimal cosmetic outcome. Histopathological examination revealed a well-circumscribed mesenchymal tumor composed of spindle and oval stromal cells arranged around numerous thin-walled vessels, without atypia or mitotic activity. Immunohistochemistry showed positivity for desmin, estrogen receptors, and progesterone receptors, with negative staining for CD34 and S100 protein, confirming the diagnosis of angiomyofibroblastoma. The postoperative course was complicated by hematoma and edema, which resolved with conservative management. At one month, a favorable cosmetic outcome had been achieved, and no evidence of recurrence was observed at five-month follow-up. Angiomyofibroblastoma should be considered in the differential diagnosis of vulvar masses. Complete local excision is curative in most cases. In large tumors, careful surgical planning with reconstructive techniques is essential to achieve both oncological safety and satisfactory cosmetic results. Long-term follow-up is recommended despite the benign nature of the disease.

Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare SMARCB1-deficient mesenchymal neoplasm of adult women that can mimic malignant vulvar sarcomas, particularly epithelioid sarcoma. Although loss of SMARCB1/INI1 expression is a defining feature, the comprehensive genomic landscape of MELTVR remains poorly characterized. We report two cases of MELTVR and performed integrated histopathologic, immunophenotypic, and molecular analyses, including whole-exome sequencing (WES) with copy number assessment and targeted RNA-based fusion testing using the Archer FusionPlex Sarcoma panel. Histologically, both tumors consisted of relatively uniform epithelioid to short spindle cells in solid nests and cords within focal myxoid stroma, with complete loss of INI1 and positivity for smooth muscle markers and focal ER/EMA expression. Genomic profiling demonstrated a quiet molecular background in both cases, with low tumor mutation burden (0.45 and 1.03 mut/Mb) and no pathogenic SNVs/indels in major cancer-associated genes. One case showed a focal homozygous deletion of the SMARCB1 locus at 22q11.2, whereas the other case exhibited INI1 loss without detectable SMARCB1 mutation or copy number loss, suggesting heterogeneous mechanisms of inactivation. CDKN2A copy number remained neutral in both tumors. No canonical sarcoma-associated gene rearrangements, including EWSR1, FUS, PLAG1, or NR4A3, were identified. Together with a review of previously reported cases, these findings support MELTVR as an SMARCB1-inactivated neoplasm with low genomic complexity and highlight the diagnostic value of NGS-based profiling in excluding malignant mimics and preventing overtreatment.

This study aimed to investigate the efficacy of focused ultrasound (FU) for vulvar lichen simplex chronicus (VLSC) and its effect on Cyclin D1 and cyclin-dependent kinase 4 (CDK4) expression. 102 skin samples from reproductive-age patients with VLSC were included; all patients received FU treatment and formed the post-treatment group. 50 normal vulvar skin samples served as controls. Clinical efficacy and Vulvar Quality of Life Index (VQLI) were evaluated at 6 months post-treatment. Immunohistochemistry was performed to detect Cyclin D1 and CDK4 expression, quantified by mean optical density (MOD). The total clinical efficacy rate was 95.1%, and post-treatment VQLI scores were significantly decreased. Both the MOD values and prickle to basal layer MOD ratios of Cyclin D1 and CDK4 were significantly higher in the VLSC group than in the control and post-treatment groups, with no significant differences between the control and post-treatment groups. FU effectively alleviates the clinical symptoms of VLSC, an effect associated with the downregulation of abnormally high Cyclin D1 and CDK4 expression and the restoration of their normal distribution pattern in lesional tissues.

Acute vulvar ulcers have been reported following gene-based COVID-19 vaccinations, though causality remains uncertain. This study aims to examine the association between vaccination and ulcer occurrence. This observational study analyzed vulvar ulcer cases reported to the Vaccine Adverse Event Reporting System (VAERS) from January 2002 to February 2022. Risk was estimated by comparing VAERS-reported ulcer cases with vaccine recipient data from the COVID Data Tracker. Causality was assessed using the Bradford Hill criteria. From 2021 to 2022, the proportion of vulvar ulcers among reported adverse events exceeded the upper control limits for the first time since 2002. Most cases (134/137, 97.8%) were linked to COVID-19 vaccines. Ad26.COV2.S had the highest relative risk (2.72 vs. BNT162b2; 95% CI: 1.17-6.30). For two-dose vaccines, the second dose posed a higher risk (dose 2 vs. dose 1: RR 3.52; 95% CI: 2.06-6.02 for BNT162b2; RR 2.40; 95% CI: 1.82-3.18 for mRNA-1273). Ulcers appeared a median of 2 days post-vaccination (IQR: 1.25-2.75) and resolved after a median of 12 days (IQR: 7-18). Adolescent females aged 12-17 years had the highest risk (RR vs. age 25-39: 4.01; 95% CI: 2.67-6.05), with a 46.0-fold increased risk (95% CI: 11.2-188.9) compared to age-matched females who received HPV vaccines. Vulvar ulcers were closely associated with COVID-19 vaccination, especially in adolescent females. While findings suggest a potential link, further research is warranted to determine causality.

Detection of locoregional lymph node (LN) metastases is a critical prognostic factor in gynecologic squamous cell carcinoma (SCC). Contrast-enhanced computed tomography (CT) is limited by insufficient specificity, potentially leading to overtreatment. We evaluated gallium-68 fibroblast activation protein inhibitor ( 68 Ga-FAPI-04) positron-emission tomography (PET)/CT for the detection of locoregional LN metastases in this setting, using CT as comparator. In this retrospective single-center study, 68 Ga-FAPI-04 PET/CT scans of 15 patients with gynecologic SCC (nine cervical, six vulvar carcinomas; mean age 56.3 years, range=38-86 years) were analyzed. PET/CT and CT were read independently by two blinded readers. Histopathology and/or clinical and radiological follow-up (12-18 months) served as the reference standard. Diagnostic performance was calculated on a patient-based level; maximum standardized uptake values (SUV max ) were compared using Welch's t -test and the Mann-Whitney U -test. Histopathological confirmation was available in 12 patients; three were classified by follow-up. LN metastases were confirmed in five patients. 68 Ga-FAPI-04 PET/CT achieved a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 100%. CT achieved a sensitivity and NPV of 100% but produced false-positive findings in three patients (specificity=70%, PPV=62.5%, accuracy=80%), caused by tattoo-associated lymphadenopathy, sarcoidosis and reactive nodal enlargement, none of which showed pathological tracer uptake. Metastatic LNs exhibited higher SUV max (mean 23.2±6.0) than nodes false-positive on CT (mean 4.5±4.6; p =0.004 and p =0.036). Primary tumors were visualized in all patients undergoing initial staging; peritoneal nodules down to 7 mm were detected. In this small cohort, 68 Ga-FAPI-04 PET/CT showed a higher observed specificity than contrast-enhanced CT for the detection of locoregional LN metastases in gynecologic SCC, with no false-negative cases observed.

Negative or focal p16 expression may occur in cervical squamous cell carcinomas (SCCs) associated with high-risk or low-risk human papillomavirus (HPV), as well as in HPV-independent SCCs. However, this phenomenon is uncommon, and its pathologic and molecular characteristics remain poorly defined. In this single-institution study, we identified 11 cases (11/201 [5.5%]) with negative or focal p16 expression, including 4 (2.0%) associated with high-risk HPV, 6 (3.0%) HPV-independent, and 1 (0.5%) associated with low-risk HPV. Among the 4 high-risk HPV-associated SCCs with complete loss of p16 expression, 3 showed complete loss of the methylthioadenosine phosphorylase (MTAP). Notably, MTAP loss was also observed in 2 p16-negative high-grade squamous intraepithelial lesions (HSILs), suggesting that p16/MTAP codeletion may occur at both precursor and invasive stages. In contrast, all 6 HPV-independent SCCs retained MTAP expression. Two HPV-independent SCCs were associated with precursor lesions: 1 resembled verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), while the other was analogous to HSIL. Consistent with high-risk HPV infection, all 4 HPV-associated SCCs demonstrated partial or complete loss of RB1 expression. In comparison, only 2 of 6 HPV-independent SCCs showed partial RB1 loss, likely through HPV-independent mechanisms. A wild-type p53 immunostaining pattern was observed in all cases except 1 HPV-independent SCC (case 7), which exhibited a null pattern and harbored a TP53 nonsense mutation (c.430C>T; p.Gln144Ter). p16 promoter methylation was detected in case 9 (HPV-independent SCC). Somatic TERT promoter mutations were identified in 2 of 4 (50%) HPV-associated SCCs, including c.-131C>T, c.-148C>T, and c.-150C>T. Among HPV-independent SCCs, 4 of 6 cases (66.7%) harbored pathogenic TERT promoter mutations, including c.-138C>T (n=1) and c.-124C>T (n=3). No PIK3CA hotspot mutations were detected in p16-negative, high-risk HPV-associated SCCs. In contrast, 2 HPV-independent SCCs harbored PIK3CA hotspot mutations (p.E545K and p.H1047R), supporting a role for PI3K-AKT-mTOR signaling in this setting. Because nondiffuse p16 expression can occur in both HPV-associated (high-risk and low-risk HPV) and HPV-independent cervical SCCs, which may have different clinical outcomes, awareness of this phenomenon is important when interpreting negative p16 immunostaining. Although data are limited, routine assessment of both p16 immunohistochemistry and HPV status, or correlation with prior liquid-based HPV test results when available, is recommended.

Vulvar high-grade squamous intraepithelial lesion (HSIL) is an HPV-associated premalignant lesion requiring prompt management. Its occurrence in primary lymphedema is rarely described. We report a 37-year-old woman with childhood-onset primary lymphedema who presented after 31 years of clinical quiescence with recurrent right lower-extremity and genital lymphedema presenting with vulvar swelling, erythema, follicular lesions, and persistent lymphorrhea. Indocyanine green (ICG) lymphography confirmed recurrent combined genital and lower-extremity lymphedema. Lymphaticovenular anastomosis (LVA) and abnormal perineal tissue excision were performed during the same operative session at different sites. Histopathology unexpectedly demonstrated multifocal vulvar HSIL with lymphangiectatic change. Immunohistochemistry showed p16 and Ki-67 overexpression, wild-type p53, D2-40 positivity, and CD34 negativity. HPV genotyping detected HPV16 and HPV42. Lymphorrhea decreased substantially, and leg volume decreased by 9.5%. Chronic genital lymphedema can obscure premalignant disease; morphologically abnormal or persistent vulvar lesions warrant histopathological assessment. LVA may reduce lymphorrhea and edema but cannot replace definitive oncologic treatment.