Search Results (590)

Recurrent pregnancy loss (RPL) continues to be a significant challenge in reproductive medicine, particularly in women for whom standard examinations do not reveal a conclusive underlying reason. There is growing evidence that several instances may result from nuanced alterations in the endometrial milieu, particularly with decidualization and maternal–fetal immune tolerance. In recent years, vitamin D has gained recognition for its significance in early pregnancy, serving not only as a regulator of calcium metabolism but also as an active contributor to endometrial and immunological functions. The human endometrium exhibits the vitamin D receptor (VDR) and the enzyme CYP27B1, facilitating the local activation and signaling of vitamin D inside the uterine milieu. Experimental investigations have shown that vitamin D influences many processes critical for effective implantation and placentation, including stromal cell differentiation, cytokine equilibrium, trophoblast invasion, oxidative stress responses, and immune cell communication. Aberrant vitamin D signaling has been associated with heightened inflammatory activity, impaired decidual transformation, altered uterine natural killer cell functionality, and alteration of the Treg/Th17 equilibrium, all of which have been implicated in recurrent pregnancy loss. Concurrently, there is an increasing emphasis on the association between vitamin D and mitochondrial function as well as oxidative stress in decidual and endometrial cells. Interruption of these pathways may influence implantation and early embryonic development by impacting cellular metabolism and immunological control at the maternal–fetal interface. The clinical interest in vitamin D supplementation for women experiencing repeated reproductive failure is increasing; nevertheless, the existing results are conflicting, mostly due to the predominance of research focusing on circulating vitamin D levels rather than localized tissue-specific processes. Our review encapsulates new findings about the function of vitamin D in endometrial biology and reproductive immune regulation, emphasizing its involvement in decidualization, inflammatory signaling, oxidative stress, and maternal–fetal immunological tolerance in recurrent pregnancy loss. The potential ramifications for assisted reproduction and forthcoming tailored therapy techniques are also examined. Full article

Warfarin is a coumarin-derived oral anticoagulant widely used for the prevention and treatment of thromboembolic disorders, particularly in patients with mechanical heart valves. The drug exerts its anticoagulant effect by inhibiting vitamin K epoxide reductase, thereby impairing γ-carboxylation of vitamin K-dependent coagulation factors. Despite its clinical efficacy, warfarin therapy is associated with a narrow therapeutic index, substantial interindividual variability in dose response, numerous drug interactions, and significant hemorrhagic risk. Maternal warfarin therapy during pregnancy is strongly associated with fetal warfarin syndrome (FWS), a characteristic pattern of embryopathy resulting from in utero exposure to the drug. This review summarizes current knowledge regarding the physicochemical properties, pharmacological mechanisms, dose variability, toxicity, and developmental effects associated with warfarin exposure. Evidence from human clinical studies and vertebrate animal models is discussed to elucidate conserved developmental and molecular mechanisms underlying warfarin teratogenicity. The review also examines the signaling pathways disrupted by warfarin exposure, highlighting that its teratogenic effects extend beyond anticoagulation to the disruption of vitamin K-dependent developmental signaling. Inhibition of γ-glutamyl carboxylation, together with alterations in Gas6/TAM, PXR, Ras, and Wnt/β-catenin signaling pathways, impairs skeletal, vascular, and neural development, contributing to the characteristic abnormalities of fetal warfarin syndrome. Collectively, this review integrates clinical, molecular, and experimental findings to provide a comprehensive understanding of warfarin-induced developmental toxicity. Current knowledge is insufficient to fully elucidate the complex mechanisms underlying warfarin-induced embryopathy and fetal toxicity. Further investigations are warranted to identify safer anticoagulant regimens during pregnancy and to inform the development of novel therapeutic strategies that minimize fetal risk while maintaining maternal anticoagulation. Full article

Background: Pregnancy-related listeriosis typically causes mild, self-limited maternal symptoms but can lead to severe fetal and neonatal outcomes, posing a significant public health concern given its rising incidence. However, data on the epidemiology of this infection and its impact on maternal and neonatal outcomes in China remain scarce and fragmented. Methods: A systematic search was conducted in the following three Chinese-language databases (CNKI, Wanfang, and CBM) and two English-language databases (PubMed and Embase) for studies performed in China from 1 January 2018 to 14 March 2026. Relevant studies published before 2018 were identified from two previous systematic reviews. Information on the epidemiology, clinical manifestations, and outcomes of pregnancy-related listeriosis was extracted. For inclusion in pooled incidence estimates for pregnant women, studies were required to have the number of pregnant women or pregnancies as the denominator; for pooled neonatal case fatality risk estimates, studies were required to report the total number of neonatal listeriosis cases. The methodological quality of each included study was appraised using the Joanna Briggs Institute critical appraisal tool. Heterogeneity among the studies was quantified by the I² statistic. All statistical analyses were performed using STATA version 12 and Microsoft Excel 365 (PROSPERO: CRD420261326136). Results: Of 389 abstracts initially identified, 160 full-text articles were retrieved for detailed evaluation, and 73 studies (including two previous systematic reviews) ultimately met the inclusion criteria. These studies, which were conducted across 19 provinces, provided sufficient data for analysis, encompassing 956 pregnant women and 749 neonates. Pregnancy-related listeriosis showed regional variation, with Beijing (n = 215), Zhejiang (n = 143), and Shaanxi (n = 142) contributing the most cases. The pooled incidence of obstetric listeriosis was 11.57 per 100,000 pregnancies (95% CI, 7.63–15.50; I² = 73%) based on nine studies, and the pooled incidence of neonatal listeriosis was 7.55 per 100,000 live births (95% CI, 4.44–10.67; I² = 60%) based on six studies. Fever (53.7%, 513/956) was the most common symptom among pregnant women, whereas respiratory distress (34.8%, 261/749) predominated in neonates. For empirical therapy, only 6.0% (57/956) of pregnant women received a penicillin-based regimen, whereas 32.5% (311/956) received cephalosporins. Two maternal deaths were recorded, whereas major adverse outcomes (miscarriage, stillbirth, prematurity, or low birth weight) occurred in 58.3% of pregnancies. Among neonates, 27.5% (206/749) received empirical penicillin therapy and 15.6% (117/749) received cephalosporins. The neonatal case fatality rate was 11% (95% CI, 0.06–0.17; I² = 60%). Conclusions: Pregnancy-related listeriosis in China carries a substantial burden, with high rates of adverse fetal and neonatal outcomes. Suboptimal surveillance and inappropriate empirical antibiotic therapy likely contribute to these poor outcomes, highlighting the urgent need for enhanced surveillance, prompt recognition, and appropriate antibiotic use when Listeria infection is suspected. Full article

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy arising from a single-nucleotide transversion (GAG → GTG) at codon six of the HBB gene on chromosome 11, substituting glutamic acid with valine in the β-globin chain and producing hemoglobin S (HbS). Under hypoxic conditions, HbS polymerizes and distorts erythrocytes into the characteristic sickle shape, initiating a cascade of vaso-occlusion, chronic hemolytic anemia, and progressive multi-organ damage that defines the clinical burden of this disease. Although SCD has ancient origins in sub-Saharan Africa, the Indian subcontinent, the Middle East, and the Mediterranean, regions where it conferred heterozygous resistance to malaria, the ease of human migration has long since made it a global health concern, affecting an estimated 300,000–400,000 newborns annually. Advances in molecular and genomic research have deepened our understanding of SCD pathophysiology, revealing the central contributions of hemoglobin polymerization, oxidative stress, endothelial inflammation, and nitric oxide depletion to disease progression. Current management rests on supportive pharmacological interventions, including hydroxyurea, chronic transfusion therapy, L-glutamine, and multimodal pain management, complemented by lifestyle modifications. Curative approaches have advanced substantially: hematopoietic stem cell transplantation (HSCT) remains the established standard of cure, while the regulatory approvals in late 2023 of the CRISPR/Cas9-based exagamglogene autotemcel (Casgevy) and the lentiviral vector-based lovotibeglogene autotemcel (Lyfgenia) represent the most transformative development in the history of SCD therapeutics. This review traces the disease from its ancient origins and molecular characterization through to its clinical manifestations, inheritance patterns, screening strategies, and the full spectrum of current and emerging therapies. Persistent challenges, prohibitive treatment costs, healthcare inequities, the ethical dimensions of genome editing, and the urgent need for long-term safety data, are examined critically, with a view to informing the research and policy agenda that must accompany these remarkable scientific advances. Full article

Background and Clinical Significance: Lues remains a global health concern despite the well-known nature of its symptoms, the availability of diagnostic methods, and the existence of effective therapy. The recent increase in maternal syphilis has been accompanied by a rise in congenital infections, which are associated with stillbirth, prematurity, neonatal mortality, and severe multisystemic disorder. In newborns, it may present with highly variable clinical manifestations, making timely diagnosis and treatment essential. We report a case of severe early congenital syphilis in a premature newborn with extensive multiorgan involvement; Case Presentation: We present a case of a male infant born at 31 + 6 weeks of gestation to a 26-year-old mother with inadequate antenatal care and no documented screening or treatment for syphilis during pregnancy. Prenatal ultrasound revealed fetal ascites. At birth, the infant presented with severe respiratory failure requiring immediate resuscitation, endotracheal intubation, and intensive care support. Clinical findings included hepatosplenomegaly, generalized edema, ascites, petechial rash, palmoplantar desquamation, severe thrombocytopenia, anemia, coagulopathy, liver dysfunction, and hemorrhagic syndrome. Maternal and neonatal serologic testing confirmed syphilis infection. The clinical course was complicated by pneumonia with prolonged mechanical ventilation, cardiovascular involvement impairing cardiac function, and heart failure. Treatment consisted of intravenous penicillin G, broad-spectrum antimicrobial therapy, antifungal medication, respiratory support, transfusion therapy, cardiovascular management, and intensive multidisciplinary care; Conclusions: This report presents consequences of untreated maternal syphilis and underscores the importance of timely diagnosis, early initiation of penicillin therapy, and close multidisciplinary follow-up to optimize outcomes in neonates. Full article

Background/Objectives: Intrinsic genetic instability and the marked heterogeneity of malignant cell populations represent significant clinical challenges in oncology, often limiting the efficacy of conventional receptor-targeted and antigen-based therapies. To overcome these limitations, [⁶⁴Cu]CuCl₂ has emerged as a particularly promising theranostic agent because it combines PET imaging (β⁺ emission) with therapeutic effects (β⁻ particles and Auger electrons). In particular, Auger electrons, when delivered to the cell nucleus, induce severe DNA damage due to their high linear energy transfer and very short tissue range. This work aimed to deepen existing preclinical knowledge by providing a comprehensive in vitro analysis of the interactions of [⁶⁴Cu]CuCl₂ with various human cancer cell lines—specifically, the breast adenocarcinoma (MDAf-MB-231) and gastric carcinoma (NCI-N87) cell lines—and a healthy control (IMR-90 normal human fetal lung fibroblasts). Methods: We focused on evaluating cellular uptake, subcellular localization, impact on metabolic activity, and induction of apoptosis. Cell lines (MDA-MB-231, NCI-N87, IMR-90) were exposed to increasing activities of [⁶⁴Cu]CuCl₂ (10, 100, and 250 µCi/mL). Uptake was assessed in both nuclear and cytoplasmic compartments after 4 h. Metabolic activity and apoptosis/necrosis were evaluated at 96 and 120 h post-treatment. Results: Tumor cell lines demonstrated significantly higher [⁶⁴Cu]CuCl₂ uptake, particularly at the nuclear level, compared to healthy controls. A marked decrease in metabolic activity and an increase in apoptosis were observed in MDA-MB-231 and NCI-N87 cells (from 50% to 90% and 5% to 60% apoptosis, respectively). In contrast, IMR-90 cells exhibited minimal cytotoxic response (≤20%), suggesting a preferential response in the malignant cell models tested. Conclusions: [⁶⁴Cu]CuCl₂ induced distinct patterns of intracellular accumulation and biological response among the investigated cell models, with cancer cells displaying greater nuclear uptake and apoptotic susceptibility than non-malignant cells. These findings provide a high-resolution radiobiological baseline and microdosimetric validation, supporting the rigorous design of future, dedicated in vivo preclinical investigations to evaluate the translational potential of ionic [⁶⁴Cu]CuCl₂. Full article

Celocentesis represents a novel form of invasive pregnancy test that allows the genetic material of the embryo to be tested during the embryonic stage at 6–9 weeks of gestation. The purpose of this narrative review is to present the latest available literature on celocentesis, including its biological basis, technical aspects, diagnostic performance, safety profile, clinical applications, and future perspectives. Available evidence from selected studies conducted in highly specialized centers suggests that the diagnosis of monogenic diseases by celocentesis can achieve high accuracy, with reported success rates ranging from 93% to 99% when combined with molecular testing and selective fetal cell isolation. Similarly, a high level of concordance with conventional prenatal and postnatal diagnostic methods has been reported. The pregnancy loss associated with celocentesis appears to be low and comparable to baseline early pregnancy loss, although current evidence is derived primarily from observational studies and limited clinical series. One of the main benefits of celocentesis is the capability to perform prenatal diagnosis at an early stage of pregnancy, which facilitates more informed decisions about treatment options, minimizes parental anxiety, and allows earlier intervention when required. Moreover, experimental evidence suggests that celocentesis may provide a future platform for intrauterine therapeutic approaches, including stem cells and gene-based therapies, although these applications remain investigational. Despite these promising findings, celocentesis should currently be considered an experimental procedure, as its use remains largely confined to specialized centers and further multicenter studies are required to establish its safety, reproducibility, and broader clinical utility. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

Advances in fetal diagnosis and molecular medicine have opened new opportunities for in utero molecular-targeted drug therapy, shifting fetal treatment from purely procedural interventions toward pharmacologic strategies that address disease mechanisms before irreversible organ damage occurs. In this review, we highlight recent advances in in utero drug therapy, focusing on molecular-targeted approaches with emerging clinical or trial-level evidence. Early clinical experience and ongoing trials have demonstrated the feasibility of achieving therapeutically relevant fetal drug exposure, although the strength of evidence varies considerably across therapeutic classes. However, significant challenges remain, including optimization of fetal drug delivery, characterization of fetal pharmacokinetics and pharmacodynamics, long-term safety assessment, and ethical considerations. The current evidence base ranges from single case reports to ongoing Phase 3 clinical trials, underscoring both the promise of prenatal molecular therapeutics and the need for further prospective evaluation. Continued integration of fetal imaging, genomics, ethics and pharmacology will be essential to advance safe and effective prenatal precision therapies. Full article

Toxoplasmosis remains one of the most common parasitic infections affecting humans, with significant implications for pregnancy and fetal health. Maternal primary infection during gestation can result in transplacental transmission of Toxoplasma gondii, leading to a wide spectrum of congenital disease. The risk of vertical transmission increases with gestational age, whereas disease severity is inversely related—early infections causing severe neurological and ocular damage, and late infections often resulting in subclinical forms. Advances in serological testing, including IgG avidity assays and molecular diagnostics such as PCR on amniotic fluid, have improved early detection and management. Prenatal treatment with spiramycin or pyrimethamine–sulfadiazine–folinic acid combinations has been associated with reduced transmission and less severe fetal disease in several studies, although the magnitude of benefit remains debated. Long-term follow-up is essential, as late-onset manifestations, particularly chorioretinitis and neurodevelopmental impairment, are common. This narrative review was based on a comprehensive literature search of major medical databases and summarizes current knowledge on the epidemiology, pathophysiology, diagnosis, treatment, and outcomes of toxoplasmosis in pregnancy. Particular emphasis is placed on high-prevalence countries, where greater parasite genetic diversity, distinct epidemiological patterns, and a higher burden of congenital disease pose unique clinical and public health challenges. Despite progress in understanding parasite biology, pathogenesis, and treatment efficacy, congenital toxoplasmosis continues to be underdiagnosed and underreported, especially in low-resource settings. Ongoing challenges include optimizing screening strategies, ensuring access to standardized therapies, and strengthening surveillance systems. Full article

Introduction: Upper urinary tract infections (UUTIs) are among the most common serious infections during pregnancy and may be associated with maternal and fetal complications. The increasing prevalence of multidrug-resistant pathogens has led to the use of broader-spectrum antibiotics, including meropenem. However, data regarding the safety and efficacy of meropenem in pregnant women remain limited. The aim of this study was to evaluate the indications, efficacy, and safety of meropenem treatment in pregnant women with UUTIs and its impact on maternal and fetal outcomes. Methods: We conducted a retrospective study over a 12-year period including pregnant women hospitalized with UUTIs who received meropenem. The control group consisted of pregnant women with UUTIs who were treated with ceftriaxone during the same period. Results: Pregnant women treated with meropenem were more frequently diagnosed in the third trimester of pregnancy (p = 0.01) and were more often multiparous (p = 0.006). Sepsis and septic shock occurred significantly more frequently in the study group (p < 0.01), and multivariate analysis identified them as the main indications for meropenem administration (OR 10.54, 95% CI 3.30–33.70 for sepsis; OR 3.28, 95% CI 1.01–10.62 for septic shock). Patients in the study group had a higher rate of transfer to the obstetrics clinic (p = 0.032), a longer duration of antibiotic therapy (p = 0.031), and a longer hospital stay (p < 0.01). No maternal deaths were reported in either group. The rate of adverse pregnancy outcomes was similar between the two groups, except for the Apgar score, which was lower in the meropenem group (p = 0.007). Escherichia coli and Klebsiella pneumoniae were the most frequently isolated pathogens in both groups. Conclusions: Meropenem therapy in pregnant women with UUTIs was mainly indicated in cases of sepsis and septic shock and was associated with favorable maternal clinical evolution, even in patients with severe infections. The rate of adverse pregnancy outcomes was similar between the two groups, although a lower Apgar score was observed in the meropenem group; the severity of illness in the meropenem group should be considered when interpreting the lower Apgar scores. Further prospective multicenter studies are needed to better evaluate the safety and clinical effectiveness of meropenem during pregnancy. Full article

Sickle Cell Disease (SCD) is a pervasive monogenic disorder characterized by chronic hemolytic anemia, unpredictable vaso-occlusive crises, and progressive multi-organ damage, representing a significant global health burden. Driven by a point mutation in the β-globin gene, the resulting abnormal Hemoglobin S (HbS) polymerizes under deoxygenated conditions, leading to erythrocyte sickling and systemic endothelial dysfunction. While supportive therapies such as hydroxyurea and transfusions manage symptoms, the mandate for definitive curative therapies is urgent. Historically, allogeneic hematopoietic stem cell transplantation (HSCT) utilizing matched sibling donors (MSD) has been the sole curative option, offering high survival rates but constrained by limited donor availability and the risk of graft-versus-host disease (GVHD). Consequently, alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical donors, have expanded patient access, particularly with the integration of post-transplant cyclophosphamide (PTCy) to mitigate alloreactivity. Concurrently, the advent of autologous gene therapy, encompassing lentiviral gene addition (Lyfgenia) and CRISPR-Cas9 gene editing (Casgevy) offers a revolutionary donor-independent approach that eliminates GVHD risk. Lyfgenia employs a lentiviral vector to introduce an anti-sickling βT87Q hemoglobin variant into autologous hematopoietic stem cells, while Casgevy employs CRISPR-Cas9 to disrupt the erythroid-specific enhancer of the BCL11A transcription factor, derepressing γ-globin expression and elevating fetal hemoglobin. This review synthesizes the pathophysiological mechanisms of SCD, evaluates the clinical outcomes and limitations of both allogeneic HSCT and autologous gene therapies, and outlines the clinical decision-making paradigms and future innovations required to achieve equitable global access to these transformative treatments. Full article

Perinatal lymphangiomas are rare benign congenital malformations of the lymphatic system, whose potential for rapid growth and local invasiveness may pose significant risks to fetal well-being. This report presents a case of a large fetal lymphangioma diagnosed prenatally during a second-trimester ultrasound examination. The lesion was initially asymptomatic but subsequently progressed, resulting in ascites and pericardial effusion. In light of progressive fetal deterioration, prenatal sclerotherapy was performed using ultrasound-guided transabdominal administration of bleomycin. Despite the technical success of this procedure, the neonate developed severe cardiorespiratory failure and died shortly after delivery. This case highlights both the potential benefits and limitations of prenatal intervention in severe lymphatic malformations. This study also includes a concise review of current perinatal and postnatal management strategies. Despite advances in prenatal imaging and therapy, further studies are needed to optimize treatment and improve neonatal outcomes. Full article

Cell replacement therapy is a promising investigational approach for Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD. 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