Search Results (732)

Background: Bilastine is a long-acting, nonsedating antihistamine used to treat allergic conditions. Human pregnancy experience with bilastine remains limited. Objectives: The primary aim was to evaluate the risk of major anomalies following first-trimester bilastine exposure. Secondary endpoints included additional pregnancy outcomes. Methods: This observational, prospective cohort study included women counseled by the Israeli Teratology Information Service regarding first-trimester bilastine exposure between July 2019 and June 2023. Participants were contacted by telephone for follow-up using a structured questionnaire. Pregnancy outcomes were compared with fexofenadine-exposed pregnancies. The data analysis, comparison, and presentation followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guide. Results: Follow-up was obtained for 36 pregnancies with at least first-trimester bilastine exposure. The median daily bilastine dose was 20 mg, with treatment discontinued at a median gestational age of 5 + 6 weeks. First-trimester bilastine exposure was not associated with an increased risk of major anomalies [bilastine: 2/33, 6.1% vs. fexofenadine: 2/27, 7.4%; crude OR 0.81, 95% CI 0.11–6.14]. No pattern of malformations was observed. Rates of live-birth, miscarriage, and pregnancy termination were 91.7%, 5.6%, and 2.8% in the bilastine group, and 72.2%, 19.4%, and 8.3% in the fexofenadine group, respectively. Conclusions: This cohort study, although small, provides preliminary reassurance for counseling regarding inadvertent early pregnancy exposure to bilastine. Larger studies are needed to validate these findings. Full article

Background/Objectives: The role of the endometrial microbiome in reproductive failure remains incompletely understood. This study aimed to describe the composition of the endometrial microbiome in women evaluated for infertility or recurrent miscarriage. Methods: In this single-center descriptive study, endometrial samples were collected from women evaluated for infertility or recurrent miscarriage. Microbiome profiling was performed using 16S rRNA gene next-generation sequencing. Samples were classified as Lactobacillus-dominant when Lactobacillus spp. accounted for ≥90% of the total bacterial community. Alpha diversity was assessed using the Shannon and Simpson indices, while beta diversity was evaluated using Bray–Curtis dissimilarity, principal coordinates analysis (PCoA), PERMANOVA, and PERMDISP. Results: Of the 60 samples, 20 (33.3%) were Lactobacillus-dominant and 40 (66.7%) were non-Lactobacillus-dominant. Across all samples, Firmicutes was the predominant phylum (76.6%). Non-Lactobacillus-dominant samples showed significantly higher alpha diversity than Lactobacillus-dominant samples for both the Shannon and Simpson indices (p = 1.19 × 10⁻⁶ and p = 1.51 × 10⁻⁶, respectively), as well as higher observed taxa richness (p = 0.000017). PCoA based on Bray–Curtis dissimilarity demonstrated clear separation between microbiome profiles, supported by PERMANOVA (pseudo-F = 13.87, R² = 0.193, p = 0.001). PERMDISP showed significantly greater dispersion among non-Lactobacillus-dominant samples (F = 566.94, p < 0.001). Non-Lactobacillus-dominant samples showed greater representation of Enterococcus and Prevotella. Conclusions: In this cohort non-Lactobacillus-dominant communities were more frequent with greater diversity, richness, and compositional heterogeneity than Lactobacillus-dominant communities. These findings highlight the need for larger, standardized studies with appropriate control populations to clarify their clinical significance. Full article

Background: Toxoplasmosis is a prevalent zoonotic disease worldwide, affecting approximately one-third of the global human population. Primary infection with Toxoplasma gondii during pregnancy can induce miscarriage or congenital infection, leading to irreversible damage to the foetus. Moreover, reactivation of T. gondii infection in immunosuppressed individuals can result in fatal outcomes. No vaccine exists to prevent human disease caused by this parasite. Thus, a vaccine that could induce complete and lasting protection against human toxoplasmosis is an unmet need. Method: In this work, BALB/cByJ mice were intranasally immunised with a subunit vaccine consisting of T. gondii membrane proteins (TGMP) from the T. gondii Me49 strain plus CpG-oligodeoxynucleotide adjuvant (CpG). Antibody responses were analysed by ELISA, while T-cell responses were evaluated by flow cytometry. The immunogenic proteins present in TGMP were identified by mass spectrometry, and parasite burden was quantified by qPCR. Result: The results showed raised TGMP-specific serum IgG and intestinal IgA antibody levels, and parasite-specific IFN-γ-producing CD4⁺ and CD8⁺ memory T cells. Dense granule proteins (GRA) 2 and 7, surface antigen (SAG)-related sequences 25, 29B, and 34A, microneme protein (MIC) 10, toxofilin, nascent polypeptide-associated complex (NAC) domain-containing protein, and NAC subunit beta were identified as immunogenic proteins. Mice immunised with TGMP+CpG were challenged with T. gondii tachyzoites and showed a significant reduction in the parasitic burden in the peritoneal exudate, spleen, and lungs, compared to mice sham-immunised with CpG alone. Conclusions: Altogether, these results indicate that mucosal immunisation with TGMP plus CpG adjuvant is worth exploring as a vaccination approach to prevent toxoplasmosis. Full article

Background: Hysteroscopic endometrial fundal incision (HEFI) is a novel addition to the standard IVF procedure. This study aimed to evaluate whether different depths of incision during HEFI could affect reproductive outcomes in oocyte recipients. Methods: A prospective analysis was conducted on women who underwent HEFI 1–2 months prior to embryo transfer with donor oocytes. Patients were categorized into three groups based on the depth of incision: U2a (superficial level) U2aa (intermediate level), and U2aaa (deep level). Pregnancy and live birth rates were assessed. Results: A total of 212 women without intrauterine pathology were included. Positive pregnancy rates were 78% in U2a, 76.9% in U2aa, and 77.1% in U2aaa (p = 0.95). Live birth rates were 58.5%, 57.1%, and 56.4%, respectively (p = 0.97). Early and late miscarriage rates and biochemical pregnancies showed no significant differences between the groups. Conclusions: Based on the results obtained, we could speculate that the depth of infiltration during HEFI does not significantly influence reproductive outcomes in oocyte recipients without intrauterine pathology. However, these findings should be interpreted with caution, given the limitations of the study, including its non-randomized design and differences among groups, such as variations in the number of embryos transferred and intraoperative group allocation. Therefore, further randomized clinical trials should be performed to more comprehensively understand the impact of incision depth on reproductive outcomes. Full article

Background/Objectives: Although current research suggests beneficial effects of dietary supplements on female infertility, existing evidence is often inconsistent and of limited certainty. This systematic review and meta-analysis aimed to investigate the effect of dietary supplements on female infertility in terms of endometrial thickness, pregnancy, live birth, and miscarriage compared to placebo (primary objective) and compared to placebo or a no-treatment comparator (secondary objective). Methods: PubMed, Embase, and CENTRAL were searched up to March 2025. Randomized controlled trials assessing the effect of dietary supplements compared to placebo or a no-treatment comparator among infertile women were included. Screening, data extraction, risk of bias, and certainty of evidence assessments were conducted by two independent reviewers. Data was synthesized quantitatively using random effects restricted maximum likelihood models. Results: Twenty placebo-controlled and 20 no-treatment comparator studies were included. Most studies had some concerns in risk of bias. Primary analyses showed an improvement in endometrial thickness following N-acetyl-cysteine supplementation compared to placebo, while no effect was found for supplements on pregnancy-related outcomes. Certainty of evidence of primary analyses was low. Secondary analyses indicated positive differences in endometrial thickness and pregnancy-related outcomes following supplementation with different supplements compared to placebo and no treatment. Conclusions: This review found no high-certainty evidence that dietary supplements improve female infertility outcomes when compared with placebo. Secondary analyses combining placebo and no-treatment comparator studies generated hypotheses for myo-inositol, N-acetyl-cysteine, vitamin D, vitamin E, and ≥3 substance dietary supplements, but these are at higher risk of bias and require confirmation in adequately powered placebo-controlled trials with live birth as the primary outcome. Full article

Background/Objectives: Despite well-documented chemical and physical hazards in healthcare settings, existing reviews of occupational reproductive risks have largely focused on single-agent risk estimation and have rarely translated occupational hygiene evidence into clinical decision-making frameworks for reproductive counseling and surveillance. This narrative review synthesizes evidence across multiple occupational exposure categories—antineoplastic agents, high-level disinfectants (HLDs), sterilants, and work-organization factors—and proposes an integrated, clinically operational framework for preconception counseling, pregnancy-sensitive risk stratification, exposure-control verification, and reproductive health surveillance among women healthcare workers. Methods: A structured narrative literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Embase from database inception through January 2025 and updated in March 2026. The review was guided by a Population–Exposure–Comparison–Outcome (PECO) framework and structured using Search–Appraisal–Synthesis–Analysis (SALSA) principles and the Scale for the Assessment of Narrative Review Articles (SANRA). Evidence quality was summarized using a modified hierarchy-of-evidence classification provided as a reader aid. This narrative review employed structured transparency tools but does not claim the methodological status of a systematic review. Quantitative meta-analytic pooling was not performed owing to substantial heterogeneity across study designs, exposure assessment methods, and outcome definitions; findings were synthesized narratively by exposure category. Results: The strongest and most consistent evidence was identified for occupational exposure to antineoplastic agents, which has been associated with spontaneous abortion, stillbirth, congenital abnormalities, impaired fecundability, and selected cancer-related concerns. HLDs and sterilants represent exposure categories warranting precautionary attention, with some evidence suggesting possible adverse effects on fecundability and early pregnancy maintenance; however, findings are considerably more heterogeneous, context-dependent, and reliant on self-reported exposure assessment than those for antineoplastic agents. Broader workplace factors, including shift work, prolonged working hours, physical workload, and mixed exposures, may further contribute to reproductive risk. The synthesis supports task-specific occupational history taking, exposure-control verification, and pregnancy-sensitive risk stratification. Conclusions: This review provides a multi-exposure, clinically operational framework that bridges occupational hygiene evidence with reproductive healthcare delivery, offering practical decision-support tools for clinicians managing women healthcare workers during preconception, pregnancy, and lactation. The framework includes structured occupational history-taking questions, a clinical decision pathway with evidence-tier classification, and a prevention matrix linking exposure sources to workplace controls and clinical actions. Integrating task-specific occupational history taking into routine reproductive care may improve detection of preventable workplace risks and support timely accommodation, while clinicians should calibrate recommendation strength to the underlying evidence quality for each exposure category. Full article

Background and Clinical Significance: Placental site trophoblastic tumour (PSTT) is a malignant tumour of the implantation site intermediate trophoblasts. It has historically been described using terms such as atypical chorioepithelioma, atypical choriocarcinoma, syncytioma, and chorioepitheliosis. It belongs to one of the heterogeneous spectrums of gestational trophoblastic disease. It accounts for about 0.25 to 5% of all gestational trophoblastic neoplasia. The typical clinical presentation is alternating menorrhagia and amenorrhea, mildly elevated β-hCG, and radiological findings of a uterine mass. Case Presentation: A 32-year-old woman presented with a history of intermittent menorrhagia and amenorrhea, with a persistent mildly raised β-hCG level. Ultrasonography showed a hypoechoic lesion on the right side of the posterior wall of the uterus. She was diagnosed with a missed miscarriage, and an evacuation of the products of conception was performed. Histologically, the tissue fragments comprised cords and sheets of atypical intermediate trophoblast cells, with characteristic features of myometrial smooth muscle infiltration, vascular invasion, and vascular wall replaced by the neoplastic cells. Immunohistochemically, these cells are positive for β-hCG and GATA3, while negative for P63. Conclusions: PSTT is a rare form of gestational trophoblastic neoplasia. Early recognition of PSTT is essential because its clinical presentation may mimic benign pregnancy-related conditions, and diagnosis relies heavily on histopathological and immunohistochemical evaluation. Full article

Objectives: This study aimed to compare the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and fibrosis-5 index (FIB-5) between women with threatened miscarriage and healthy pregnant controls, and to evaluate their discriminative performance. Methods: This single-center retrospective case–control study included 100 women with threatened miscarriage and 100 gestational-age-matched healthy pregnant controls within the first 12 weeks of gestation. Demographic, obstetric, ultrasonographic, and laboratory data were retrieved from electronic records. APRI, FIB-4, and FIB-5 were calculated from routine laboratory parameters. Group comparisons, binary logistic regression, and ROC analyses were performed. Results: AST, ALT, ALP, APRI, and FIB-4 were higher, while hemoglobin, platelet count, albumin, and FIB-5 were lower in the threatened miscarriage group (all p < 0.001). APRI (OR = 6.937), FIB-4 (OR = 89.114), and FIB-5 (OR = 0.766) were independently associated with case status. FIB-4 showed the highest discriminative performance (AUC = 0.929), followed by APRI (AUC = 0.903) and FIB-5 (AUC = 0.761). Conclusions: APRI and particularly FIB-4 showed good apparent discrimination between women with threatened miscarriage and healthy controls in this retrospective dataset. However, these indices should be interpreted as exploratory laboratory-derived markers rather than disease-specific biomarkers until validated in prospective multicenter studies. Full article

Background: Precision medicine aims to improve early, individualized risk stratification using biologically relevant biomarkers. In early pregnancy, markers reflecting placental function remain limited. Kisspeptin, a placentally derived peptide that rises during normal gestation, has emerged as a potential indicator of pregnancy viability. Objectives: We aimed to evaluate evidence on maternal serum kisspeptin levels and placental KISS1/KISS1R expression in early pregnancy loss, and to assess its potential relevance as a precision biomarker within personalized pharmacy and individualized monitoring frameworks. Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar (up to 2025) was conducted according to the PRISMA 2020 guidelines. Studies assessing circulating kisspeptin and/or placental expression in early pregnancy loss versus viable pregnancies were included. A formal meta-analysis was not performed due to substantial heterogeneity in study design, biological material, assay methods, gestational age, and outcome reporting formats. Under these conditions, quantitative pooling was considered methodologically inappropriate; therefore, qualitative synthesis was performed. Results: Six studies met the inclusion criteria. Most reported significantly lower maternal serum kisspeptin levels in early pregnancy loss, with good discriminatory accuracy. Immunohistochemical analyses showed reduced placental and choriodecidual KISS1/KISS1R expression in miscarriage and recurrent pregnancy loss, indicating disrupted local signaling. Concordant systemic and tissue findings suggest that circulating kisspeptin reflects placental dysfunction. Conclusions: Kisspeptin appears to be a promising precision biomarker for monitoring early pregnancy viability and supporting individualized pharmaceutical care. Standardized assays and large prospective studies are needed before routine clinical implementation. Full article

Early mammalian embryos are highly sensitive to environmental, metabolic, hormonal, and genomic stress, yet embryo assessment during In Vitro Fertilization (IVF) relies largely on morphology and ploidy for embryo assessment, but these tests incompletely predict miscarriage. We present a transcriptomics based framework to classify and quantify lineage-specific stress in early embryos by benchmarking human preimplantation embryos against dose-, time-, and quality-dependent stress programs defined in Embryonic and placental Trophoblast Stem Cells (ESCs, TSCs) from the implanting blastocyst. Human embryos and stressed ESCs and TSCs are screened using transcriptomic markers from eleven biologically distinct stress Gene Ontology (GO) groups that define functional stress states and enable quantification of pathway presence and upregulation, pathway activity, and downstream outcomes. This framework determines whether the Integrated Stress Response (ISR), once initiated, resolves to enable the Developmentally Associated Stress Response (DASR). High-throughput screening (HTS) titrates stress to define increasingly risky yet biologically equivalent doses for levels of diminished stem cell growth across mechanistically diverse stressors. Then bulk RNA seq derives lineage specific transcriptomic markers putatively respond to common levels of diminished growth and that distinguish weak vs. strong stress and resolved vs. unresolved ISR. These stem cell transcriptomic signatures are applied to bulk RNA seq data from IVF embryos graded for morphology or adhesion, enabling quantitative inference of stress burden, lineage vulnerability, and developmental trajectory. Full article

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review. Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases of ICI exposure during pregnancy. Observations: Two patients were identified at our institution, both treated with ICIs for advanced melanoma. One patient received pembrolizumab during early pregnancy, with the final dose administered five days after conception, and subsequently gave birth to a healthy term infant without complications. The second patient conceived while receiving adjuvant nivolumab and experienced a miscarriage at 13 weeks of gestation. Neither patient experienced immune-related toxicity during pregnancy, and both remained without evidence of disease at follow-up. The literature review identified 21 reported pregnancies with ICI exposure and variable outcomes. Most resulted in live births (85.7%), though preterm delivery occurred in approximately 50% of cases, often due to maternal or fetal indications. Additional reported outcomes included miscarriage, neonatal death, fetal growth restriction, preeclampsia, and rare immune-related neonatal effects. Congenital anomalies were reported in a small number of cases. Conclusions and Relevance: These findings suggest that, while many pregnancies exposed to ICIs result in live births, there may be an increased risk of adverse maternal and fetal outcomes. However, causality cannot be established due to the limited quality and quantity of available data. These findings underscore the importance of effective contraception during ICI therapy and careful multidisciplinary counseling when exposure occurs during pregnancy. Full article

Recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder with important genetic, endocrine, immune, and metabolic determinants. Growing evidence links vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms to pregnancy complications, including RPL. A narrative review was conducted via a literature search in major databases: PubMed, EMBASE, Scopus, and Web of Science from January 2010 to January 2026, which synthesized observational studies on maternal 25-hydroxyvitamin D [25(OH)D] status and/or VDR polymorphisms in RPL, with predefined eligibility criteria and qualitative risk-of-bias assessment. Most studies focused on FokI (rs2228570) and the 3′ regulatory block BsmI/ApaI/TaqI. FokI is the most extensively studied VDR variant in RPL and showed the most consistent directional association compared with other variants, particularly in Asian and Middle Eastern populations, though the effect varied by study design, ancestry, and covariate adjustment. Contrary to that, investigations of BsmI/ApaI/TaqI loci were not consistent due to ancestry-specific linkage disequilibrium (LD). Genotype and vitamin D interaction effects were scarcely studied, with stratified analyses indicating a more significant genotype effect under vitamin D deficiency. From clinical practice perspectives, VDR polymorphisms may explain why some patients with RPL have a poor response to standard vitamin D supplementation. Women with the FokI f allele polymorphism associated with lower VDR activity require higher vitamin D dosing or earlier immunomodulatory support to achieve adequate endometrial receptivity. VDR variation, particularly FokI, may contribute to RPL susceptibility within an endocrine–immune–metabolic framework. Clinical translation will require standardized RPL definitions, concurrent 25(OH)D assessment, robust control for confounders, and analytical models that account for gene–environment interactions. Full article

Background: Micro- and nano-plastics (MNPs) are pervasive environmental contaminants that accumulate in various tissues, including the placenta. Experimental and clinical studies suggest potential cytotoxic, oxidative, and inflammatory effects that may lead to placental dysfunction and adverse obstetric outcomes. However, high-quality evidence on the clinical relevance of MNPs exposure during pregnancy remains scarce, underscoring the need for systematic evaluation of their impact on maternal and fetal health. Methods: The databases PubMed, ScienceDirect, CENTRAL, Embase, MDPI and Google Scholar were searched for studies published up to September 2025 investigating the relationship between MNPs and obstetric outcomes. Results: Twelve studies were included in this review, with half employing an observational design in human subjects and the other half using experimental studies in murine models. Although the available evidence is limited, there are studies reporting the association between MNPs exposure and premature birth, low birth weight, intrauterine growth restriction, and miscarriage. The most prevalent polymer detected was polyethylene, and the most commonly used MNPs detection techniques were Raman microspectroscopy, digital microscopy, Fourier Transform Infrared, and Pyrolysis gas chromatography-mass spectrometry. Conclusions: This systematic review summarizes current limited insights on the potential effects of MNPs on obstetric outcomes, highlighting possible associations with low gestational age, low birth weight, intrauterine growth restriction, and miscarriage. Findings do not allow causal inference due to heterogeneity in study design, exposure assessment, contamination control, and analytical methodologies. Full article

Spontaneous pregnancy loss is the most common pregnancy complication; 15–25% of clinically confirmed pregnancies end in miscarriage, and when early, undetected pregnancy losses are included, the miscarriage rate can reach as high as 30–60% of all pregnancies. Women who lose their babies in the early stages of pregnancy often experience this as a bereavement. However, in Lithuania, 95.2% of women who had experienced a miscarriage and participated in the study did not receive any psychological support; only 4% of those surveyed stated that they did not need it. However, both in Lithuania and abroad, there is still a lack of research on women’s emotional state following a spontaneous pregnancy loss and the impact of interventions on it. Research question: What experiences emerge in the thematic analysis of women who have experienced a spontaneous miscarriage? A qualitative study was conducted using the inductive thematic analysis method. The study participants underwent a 10-session group art therapy programme. After each art therapy session, the study participants reflected on their experiences related to their miscarriage by analyzing the drawings they had created. Verbal data from the reflections were recorded, then transcribed and analysed according to identified themes. The research participants were four women who had experienced a spontaneous pregnancy loss. The study analyses the reflections of three women who participated in all sessions. The thematic analysis revealed four themes characterising the women’s core experiences of spontaneous pregnancy loss: defensiveness, the grieving process, a complicated relationship with oneself and others, and awareness and finding meaning. Full article

Background/Objectives: Septate uterus is the most prevalent uterine malformation and is commonly associated with impaired reproductive outcomes. Hysteroscopic metroplasty is the gold standard treatment, but surgical management of complex septate uteri with associated cervical and vaginal anomalies remains challenging. This study aimed to evaluate surgical and reproductive outcomes following a standardized minimally invasive hysteroscopic approach using a 15 Fr bipolar mini-resectoscope across different subtypes. Methods: This retrospective single-center, single-surgeon study included women who underwent hysteroscopic correction of partial and complete septate uterus, with or without cervical and/or vaginal anomalies, between January 2021 and January 2025 at the Digital Hysteroscopic Clinic CLASS Hysteroscopy, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy. Preoperative assessment included three-dimensional transvaginal ultrasound and diagnostic hysteroscopy. All procedures were performed using a standardized hysteroscopic technique with a 15 Fr bipolar mini-resectoscope. Surgical outcomes included operative time and the need for second-step surgery. Reproductive outcomes included clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). Results: A total of 154 patients were included, comprising 70 partial and 84 complete septate uteri; 52.4% of complete septa were associated with cervical and/or vaginal anomalies. Median operative time was 18.0 min for partial septa and 31.0 min for complete septa (p < 0.01), and a second surgical step was required in only 5/84 complete septa (5.9%) and in none of the partial septa. Reproductive outcomes were analyzed in a subgroup of 70 patients who attempted conception. After metroplasty, CPR increased from 35.7% to 84.3% (p < 0.01), LBR per pregnancy increased from 16.0% to 78.0% (p < 0.01), and MR per pregnancy decreased from 84.0% to 10.2% (p < 0.01). Postoperative reproductive outcomes appeared comparable between partial and complete septa and according to the presence of associated anomalies. Conclusions: A standardized hysteroscopic technique using a 15 Fr bipolar mini-resectoscope is feasible and effective for treating septate uterus, including complex cases associated with cervical and/or vaginal anomalies. Favorable reproductive outcomes can be achieved regardless of anomaly complexity when accurate preoperative diagnosis and a structured surgical approach are applied. Full article