Search Results (276)

Background/Objectives: Prenatal Exome Sequencing (pES) has revolutionized prenatal diagnosis in fetuses with congenital anomalies. Although its performance is very promising, previous pES studies have mainly focused on diagnostic yield, often without considering the actual impact on ongoing pregnancies. In this study, we aim to (1) assess whether a prenatal molecular diagnosis can reliably predict the clinical features of the unborn child and (2) determine the gestational age (gw) at which ultrasound (US) findings are sufficient to support the pathogenicity of genetic variants detected by pES. Methods: We retrospectively selected 47 cases complicated by US anomalies that underwent Exome Sequencing (ES) and for which complete clinical assessment was available. A blinded reanalysis of ES data was performed, considering only prenatal features. Results: In our cohort, standard ES led to a molecular diagnosis in 43% of cases. The blinded reanalysis revealed that a complete or partial retrospective prenatal diagnosis was achievable in 95% of diagnosed cases. The mean gestational week at which US data would have supported molecular diagnosis was 22 + 5 weeks. The clinical follow-up confirmed a syndromic presentation in 21 out of 23 newborns and in all terminated pregnancies. Conclusions: Our study further confirms that pES is a valuable diagnostic tool for detecting genetic etiology in fetuses with congenital malformations. In most cases, pES results accurately predict the postnatal phenotype. However, the prenatal setting requires specific adjustments and precautions, and a negative pES result cannot be considered reassuring. Full article

Background and Clinical Significance: Carcinosarcomas are highly aggressive tumors with both carcinomatous and sarcomatous components, typically arising from the female genital tract. Primary retroperitoneal carcinosarcomas are extremely rare, and their occurrence during pregnancy presents major clinical and ethical challenges. Case Presentation: We report a case of a 24-year-old primigravida diagnosed with a large encapsulated retroperitoneal mass at 12 weeks of pregnancy, initially presenting with abdominal pain. The patient declined medical advice for pregnancy termination and chose to continue despite oncological risks. A multidisciplinary team planned delayed surgery after delivery. At 34 weeks, a cesarean section resulted in a healthy newborn, but surgical exploration revealed an inoperable, invasive tumor. The patient died two days later from postoperative complications. Autopsy confirmed widespread tumor invasion and lung metastases consistent with primary retroperitoneal carcinosarcoma. Conclusions: This case highlights the challenges of managing aggressive malignancies during pregnancy, emphasizing early diagnosis, multidisciplinary care, and ethical decision-making while respecting patient autonomy. Full article

Background: Gestational guilt is an understudied emotional experience that can affect maternal well-being and prenatal bonding. This study aimed to develop and validate the Pregnancy Guilt Assessment Scale (PGAS) in a sample of Spanish pregnant women, assessing its factorial structure, reliability, and validity. Methods: Four phases were conducted: (1) item generation through focus groups (n = 17) and cognitive interviews (n = 8); (2) expert content validation (n = 3); (3) exploratory factor analysis (EFA) in a pilot sample (n = 85); and (4) confirmatory factor analysis (CFA) and validity testing in an independent sample (n = 171). Additional measures included antenatal depression, prenatal distress, affect, self-esteem, social support, and dispositional guilt. Internal consistency, correlations, and multiple regressions assessed reliability and convergent and incremental validity. Results: The final 16-item PGAS showed a bifactor structure with a general factor and four dimensions: G-LSC (Lack of self-care), G-UEE (Unmet emotional expectations), G-SP (Social pressure), and G-CWR (Conflict with work role). The model demonstrated good fit (χ² = 109.42, df = 88, p = 0.061; CFI = 0.974; TLI = 0.965; RMSEA = 0.069; SRMR = 0.030) and high reliability (α total = 0.96; ω = 0.98; subscales α = 0.90–0.94). PGAS scores correlated positively with dispositional guilt, negative affect, prenatal distress, and antenatal depression. In regressions, G-UEE uniquely predicted depression (β = 0.213, p = 0.002) and G-SP predicted distress (β = 0.303, p < 0.001). Women who had considered pregnancy termination scored higher on guilt (p < 0.001). Conclusions: The PGAS is a reliable and valid instrument for assessing pregnancy-related guilt in Spanish women, with potential relevance for perinatal mental health research and clinical practice, while future studies should evaluate its performance in other cultural settings. Full article

Objectives: The aim of our study was to assess the efficacy and safety of two different labor induction methods in patients after fetal demise beyond 28 weeks, with an unfavorable cervix: misoprostol—prostaglandin E1 analog (PGE1) and dinoprostone—prostaglandin E2 analog (PGE2). Methods: This retrospective single-center cohort study included all labor cases after fetal demise (intrauterine fetal death or termination of pregnancy with feticide) from 28 to 40 weeks of gestation, where labor was induced by either PGE1 or PGE2. The primary outcome was the induction-to-delivery time interval. Secondary outcomes included the proportion of patients who delivered within 24 h, the failed induction rate, the length of labor, pain during induction, the adverse outcome rate, and the post-labor hospital stay. Results: The induction-to-delivery time interval was shorter in the PGE1 group (p = 0.048). There was no statistically significant difference in the proportion of patients who delivered within 24 h (p = 0.651) and failed inductions (p = 0.18) between groups. The duration of labor was longer in the PGE2 group (p = 0.01). Oxytocin augmentation was more common in the PGE2 group (p < 0.001). Pain during induction was greater in women in the PGE1 group (p < 0.001). There were no statistically significant differences in adverse effects between groups. There was no significant difference in induction to delivery interval between the two methods when comparing lower and higher gestational ages (28 to 34 weeks, p = 0.18; 35 to 40 weeks, p = 0.343). Conclusions: Our findings support the use of a PGE1 regimen for third-trimester labor induction after fetal demise, when no contraindications exist. This approach appears to improve the efficiency of induction and may enhance overall patient care by reducing intervention needs. Full article

Background: The standard protocol for early first-trimester termination of pregnancy (TOP) involves administration of mifepristone followed by misoprostol after a 48-h interval. While concurrent administration may improve convenience and access, evidence regarding its effectiveness remains limited. This study aims to compare the efficacy, safety, and acceptability of concurrent oral administration of mifepristone and misoprostol with the 48-h interval regimen for early TOP. Methods: In this randomized controlled trial (ClinicalTrials.gov: NCT03440866), 250 patients with intrauterine pregnancies up to 49 days’ gestation were randomized to receive either concurrent treatment (600 mg mifepristone and 400 mcg misoprostol) or the same medications administered 48 h apart. The primary outcome was complete abortion without additional intervention. Secondary outcomes included adverse events, pain, and patient satisfaction. Follow-up occurred approximately two weeks post-treatment. Data were available for 220 participants. Results: The concurrent group had a significantly lower success rate compared to the control group (68.8% vs. 84.3%, p = 0.007). Continuing pregnancy was more frequent with concurrent administration (13.4% vs. 2.8%, p = 0.004). No significant differences were observed in hemoglobin change, adverse events, or pain scores. Patient satisfaction was higher in the control group (81.1% vs. 63.6%, p = 0.04), though preferences for future abortion methods did not differ between groups. Conclusions: Concurrent administration of mifepristone and misoprostol is less effective and less satisfactory than the standard 48-h regimen, although safety and pain profiles are comparable. It should not replace the interval protocol, and patients choosing concurrent treatment should be counseled about its lower efficacy and higher likelihood of requiring additional intervention. Full article

Background and Clinical Significance: Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is caused by deletion of the distal short arm of chromosome 4. It is characterized by intrauterine growth restriction (IUGR), developmental delay, epilepsy, distinctive facial features, and urinary tract anomalies, particularly renal hypoplasia. However, the histological profile of renal involvement in WHS is rarely documented. Case presentation: We report a case of fetal WHS with renal hypoplasia and histological evidence of oligomeganephronia (OMN). At 21 weeks’ gestation, a prenatal ultrasound revealed oligo/anhydramnios and IUGR. Genetic testing (karyotype and CGH-array) confirmed a de novo 17.92 Mb terminal deletion from 4p16.3 to 4p15.31. The pregnancy was legally terminated at 23 weeks. The autopsy showed characteristic WHS dysmorphisms, growth restriction, and markedly small kidneys. Histology revealed OMN with a thinned renal cortex with reduced glomeruli, mainly hypoplastic, some of which were hypertrophic, and dilated proximal tubules. Scattered medullary tubules were present within the tubulointerstitial compartment, alongside thickened tubular basement membranes highlighted by Collagen IV staining. Conclusions: This case suggests that OMN may be a histological hallmark of renal hypoplasia in WHS, especially in larger 4p deletions. Recognizing this pattern may help with prenatal prognosis and clinical management. Further studies are needed to confirm this association. Full article

Human early embryogenesis remains unexplored due to limited access to human embryos for research purposes. Meanwhile, the number of natural early pregnancy terminations remains significant, and solving the problem requires a deep understanding of the developmental mechanisms of this period. Although assisted reproductive technologies (ART) utilize up-to-date approaches in culturing human embryos in vitro, characterization of the embryos is still based on visual evaluation and subjective assessment. In addition, embryonic development in animal models, such as rodents and cattle, correlates poorly with human embryonic development. Synthetic embryology presents a promising new approach for studying human embryos involving the creation of embryos without the use of haploid germ cells. Instead, diploid pluripotent stem cells (PSCs) in a given state of pluripotency, which is maintained under conditions of induction and/or inhibition of certain signaling pathways, are used. Synthetic embryo systems (SES) may become a successful alternative model for studying fundamental processes of human early preimplantation embryogenesis, exploring new methods of objective embryo qualification, and personalized approaches in ART. However, the question of whether SES models can be considered as full-fledged mimics of the embryo remains open. This review examines human blastocyst-like structures known as blastoids. It discusses their use as models, as well as the parameters that need to be modified to more accurately simulate the human blastocyst. Full article

Personality traits, decision-making styles, and socio-demographic information help understand the characteristics of women requesting voluntary termination of pregnancy (VTP) and monitor the timing and quality of this service However, our current data do not allow for an in-depth exploration of additional, less evident factors that might influence the decision. The aim was to characterise a sample of women requesting VTP in terms of socio-demographic, personality, and decision-making style variables, and to examine the associations among these factors. We conducted a cross-sectional study administering the General Decision-Making Style (GDMS) test, the Big Five Questionnaire (BFQ) and the Personality Inventory for DSM-5 (PID-5) to women requesting VTP certification. BFQ scores were generally high, especially for “Conscientiousness” and “Openness”. “Agreeableness” and “Openness” scores were lower in women with low vs. high education (diff = −8.2 [−13.9, −2.4] and diff = −7.5 [−15.0, −0.1]); “Extraversion” was higher in employed women. PID-5 scores for “Detachment” and “Psychoticism” were higher in medium vs. high education (diff = 1.6 [0.05, 3.2] and diff = 1.9 [0.1, 3.8]), but not at pathological level; “Negative affect” was lower in women with children (diff = −1.6 [−3.1, −0.2]). GDMS scores were not associated with socio-demographic factors. “Avoidant” and “Spontaneous” styles were negatively associated with “Conscientiousness” and “Emotional Stability”; “Rational” style was positively associated with “Conscientiousness” and “Disinhibition”. High BFQ and low PID-5 scores suggest no personality dysfunction in women undergoing VTP. No predominant decision-making style emerged, but associations between personality traits, decision-making, and socio-demographic factors such as educational level, employment and parity, were observed. Full article

Breast cancer is one of the most common malignancies worldwide, affecting 2.3 million and causing 670,000 deaths in women annually. However, data indicate that the risk of developing breast cancer decreases with pregnancy at a young age, and each subsequent pregnancy further reduces the risk by approximately 10%. One of the characteristics inherent in both the mammary gland epithelium in pregnant women and luminal epithelial adenocarcinomas is the increased expression of NIS—the sodium/iodide symporter, whose defective cytoplasmic forms possess pro-oncogenic properties. Therefore, the analysis of the degree of influence of pregnancy on NIS expression in breast cancer cells is of medical interest. The aim of this study is to conduct a comparative morphological analysis of NIS expression in breast cancer cells according to the number of pregnancies of each patient. This study included 161 patients with triple-negative breast cancer who visited the P.A. Herzen Moscow Oncology Research Institute from 2020 to 2023. Immunohistochemical examination was performed using antibodies to NIS. The gravidity status of women was determined based on provided medical documentation. The degree of NIS expression was assessed using a modified Gainor scale. Statistical analysis was performed using mean and standard deviation (SD) depending on the normality of the distribution (Lilliefors test: p > 0.20); a p-value ≤ 0.05 was considered statistically significant. The degree of correlation between variables was assessed using Kendall’s tau rank correlation coefficient. A weak to moderate negative correlation (τ: −0.369) was found between the number of pregnancies and the degree of NIS expression in triple-negative breast cancer cells. In patients with triple-negative breast cancer, a weak to moderate negative correlation was found between the degree of NIS expression and gravidity status. The discovered phenomenon is likely due to the terminal differentiation of the mammary gland epithelium that occurs during pregnancy. This may potentially indicate the suppression of pro-oncogenic properties of atypical cells developed from the epithelium that has undergone terminal differentiation. Full article

Background and Clinical Significance: Fetus papyraceus is a term describing fetal findings associated with miscarriage, wherein the fetus is not expelled, remains in the uterine cavity, and is compressed by neighboring structures, with an inability for fetal resorption due to advanced pregnancy. Case Presentation: Herein, we present the case of a 33-year-old primigravida with two previous presentations to our institution due to emotional stress without evidence of physical abuse, the last one being at the 14th week of pregnancy. The latest presentation was with complaints of intermittent lower abdominal pain and an outpatient gynecology consultation describing fetal demise, with fetal parameters corresponding to demise in the 15th to 16th week of gestation. Pregnancy termination was performed with the specimen sent for pathology, revealing fragmented placental parts, which, on section, were firm, with greyish areas and notable calcification, fragments of an umbilical cord appeared normal, and a significantly compressed fetus, which was flattened in the anteroposterior aspect with significant compressive deformation of the limbs—fetus papyraceus characteristics. Histology of the placental fragments revealed fibrin thrombi in large blood vessels, intense fibrosis of the villi with focal fibrin extravasation, and focal necrosis and inflammation, as well as extensive calcium deposits. Conclusions: Fetus papyraceus is a rare complication of intrauterine demise and fetal compression, which can vary in its degree of presenting severity and requires the co-occurrence of specific conditions. The condition is rarely associated with singleton pregnancies. Full article

Background and Clinical Significance: Spina bifida in the cervical region is closely associated with Chiari malformation, which is an amalgamation of terminology for separate conditions with similar pathophysiological mechanisms and progression from one another. Chiari malformations are associated with varying degrees of dilation of the foramen magnum or lack of fusion of the occipital bone with syringomyelia, herniation of the cerebellum, occipitocele and occipitomyelocele; Case Presentation: A previously healthy 23-year-old primigravida presented to our institution due to fetal demise in the third lunar month, established on routine outpatient maternal consultation. Point-of-care ultrasound revealed an amniotic sac measuring 3 cm in diameter and containing a single fetus, without cardiac function. Due to these, the patient was scheduled for pregnancy termination, during which the cervix was noted to be spontaneously dilated and abrasion accomplished complete evacuation of the amniotic sac, without its rupture. Upon sectioning of the amniotic sac, a fetus, measuring 2.5 cm in length, was noted, with a significant cuffing of the occipital and cervical paraspinal region. Histology revealed fetal structures with an adequate maturation index for its gestational age, but it presented with a pronounced meningoencephalomyelocele in the cervical and thoracic regions, characterized by the complete absence of vertebral arches and spinous processes from the atlanto-occipital to the sacral region; Conclusions: In the present case, not only is a significant and complex form of Chiari type III reported, but the condition is also associated with spina bifida aperta in all spinal regions, leading to meningoencephalomyelocele, incompatible with life. Full article

Background and Clinical Significance: The occurrence of acute myeloid leukemia (AML) in pregnancy represents a diagnostic and management challenge in the attempt to balance and achieve both maternal and fetal wellbeing. Pregnancy-specific manifestations mimic the initial symptoms of leukemia and may lead to a delay in diagnosis, especially during the first trimester of pregnancy. Decision-making strategies involve the patient and couples counseling with a multidisciplinary team of hematologists, obstetricians, neonatologists and psychologists. Maternal outcome depends on the disease subtype, progression and response to medication. Fetal outcome depends on other potential pregnancy complications, possible teratogenicity, gestational age at delivery and sometimes iatrogenic prematurity. Case Presentation: We present the case of a 38-year-old multiparous patient with a late first trimester, with an AML diagnosis presenting with hyperemesis gravidarum-like symptoms. Genetic testing revealed the presence of an Fms-like tyrosine kinase 3-internal tandem duplication mutation (FLT3-ITD). Following that, a repeatedly refused termination of pregnancy and rapid disease progression with azacitidine therapy was initiated. Elective cesarean delivery was performed at 34 weeks of gestation due to progressive leukocytosis, which persisted postpartum, requiring the use of first-, second-, and eventually third-line chemotherapy. Fetal outcome was favorable at 3 months postpartum. Conclusions: Cases of AML in pregnancy require a tailored approach according to guidelines, but also patient/couple preferences, while the choice of chemotherapy is limited considering its potential teratogenic effects. This is a case with a misleading first presentation and a challenging therapeutic choice due to its genetic subtype and maternal treatment postponement. Full article

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 toxoplasmosis cases among patients receiving biologics (including CAR T-Cell Therapies) or small molecules for diverse autoimmune, oncologic and transplant conditions. These cases were reported from 18 countries, including the United States and several European countries. Most patients developed severe disease. Fifty percent (23/46) presented with cerebral toxoplasmosis, 33% (15/46) with ocular toxoplasmosis, 7% (3/46) with lymphadenopathy, 4% (2/46) with disseminated disease, 2% (1/46) with both cerebral and ocular disease, 2% (1/46) with pneumonic toxoplasmosis, and 2% (1/46) with severe fetal congenital toxoplasmosis. Among those were also four cases with fatal outcomes due to toxoplasmosis and eight cases with permanent ocular or neurological deficits. In addition, there was a case of fetal congenital toxoplasmosis that occurred despite maternal discontinuation of adalimumab five months before conception, resulting in elective pregnancy termination due to severe fetal cerebral disease. Overall, 44% (20/46) of cases were due to reactivation of chronic latent Toxoplasma infections and 39% (18/46) due to acute primary infections; 17% did not report this information. One case of disseminated acute toxoplasmosis was also identified after eating wild boar sausages, and two cases of severe acute ocular toxoplasmosis after eating undercooked venison meat, and undercooked unspecified type of meat respectively, while on small molecules or biologics. Details on the clinical presentations, management and clinical outcomes of these cases were reported. Recommendations for the management of toxoplasmosis in patients with targeted immunotherapies were also provided. Health care providers should consider toxoplasmosis in patients on biologics or small molecules who present with compatible clinical syndromes. Prompt diagnosis and treatment can be lifesaving. Full article

Background: Foetal structural abnormalities can be detected in approximately 3% of all pregnancies and frequently remain without a genetic diagnosis. This study aims to apply an integrated approach with the final goal of providing a molecular diagnosis in the challenging Italian setting of early termination of pregnancy. Methods: In a cohort of 86 foetuses, post-mortem dysmorphological examination, radiological assessments, and molecular autopsy through Whole-Exome Sequencing—WES—analysis were performed. Results: Forty-two foetuses were phenotypically classified as presenting a single major malformation (i.e., central nervous system, skeletal, urogenital, or cardiac anomalies, or fluid accumulation), while 44 foetuses presented multiple malformations and/or dysmorphic features. Overall, WES provided a diagnostic yield of 26.7%; additionally, seven Variants of Uncertain Significance (VUS) potentially liked to the foetal phenotype were identified. The highest detection rate was achieved for foetuses presenting a single major urogenital (50%) or skeletal (42.9%) malformation, followed by foetuses presenting multiple malformations (27.3%). Peculiar results of particular interest were (1) the identification of two splicing variants (within the INPPL1 and RHOA genes), functionally characterised through minigene assay, which contributed to evaluate their pathogenicity, and (2) the identification of a novel de novo missense ZNF292 variant (NM_015021.3:c.6325A>C p.(Ser2109Arg)) in a foetus affected by corpus callosum hypoplasia. The ZNF292 gene is associated with the Intellectual developmental disorder, autosomal dominant 64 and this finding represents the first report of prenatally detected anomalies of the central nervous system in a foetus carrying a ZNF292 variant. Conclusions: This study underlines the diagnostic utility of an integrated approach to achieve a precise genetic diagnosis for structural foetal abnormalities, thus providing families with precise recurrence risk estimations and detailed options about future pregnancies. Additionally, a systematic implementation of this strategy could be crucial to better characterise new variants and discover new genes involved in embryonic and foetal development. Full article

Background and Clinical Significance: Binder syndrome or maxillonasal dysplasia is a rare developmental disorder affecting the anterior maxilla and nasal complex, characterized by midfacial hypoplasia, a flattened nasal bridge, and increased nasofrontal angle. Case Presentation: We present a case series of seven fetuses diagnosed with Binder phenotype through targeted ultrasound examination at our prenatal diagnosis center during the SARS-CoV-2 pandemic, between September 2021 and July 2023, including the first case described in the literature before 14 weeks. The median gestational age at diagnosis was 21 weeks. Ultrasound features included flattened fetal facial profile, increased nasofrontal angle (>143°), verticalized nasal bones and widened maxillary alveolar arch. Five cases presented as isolated anomalies, while two showed associated findings including growth restriction and polyhydramnios. Invasive prenatal diagnosis was offered in all cases, with three patients consenting to amniocentesis, all revealing normal karyotype and chromosomal microarray. Pregnancy outcomes varied: three patients opted for termination of pregnancy, one case resulted in intrauterine fetal demise, one delivered prematurely with confirmed postnatal phenotype, and two continued pregnancy with normal delivery. Conclusions: This relatively high case frequency within a short timeframe suggests that Binder syndrome, while rare, may not be as uncommon as previously reported. Accurate ultrasound diagnosis combined with comprehensive genetic counseling enables appropriate pregnancy management and optimal perinatal outcomes. Full article