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27 pages, 2003 KB  
Review
Maternal–Fetal Crosstalk in Cardiovascular Programming: Linking the Intrauterine Environment to Lifelong Disease Risk
by Ning Wu, Hairui Sun, Siyao Zhang, Jiaqi Fan, Tong Yi, Ruimin Liu and Yihua He
J. Cardiovasc. Dev. Dis. 2026, 13(7), 292; https://doi.org/10.3390/jcdd13070292 - 24 Jun 2026
Viewed by 338
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal–fetal crosstalk, mediated largely [...] Read more.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal–fetal crosstalk, mediated largely through placental function, coordinates the transfer of metabolic, endocrine, and immune signals that are essential for normal cardiac and vascular development. Disruptions in maternal physiology—including metabolic disorders, hypertensive conditions, inflammation, and environmental stress—can perturb this communication network and alter the intrauterine milieu. These changes induce persistent modifications in cardiomyocyte growth, endothelial function, and key regulatory pathways, thereby contributing to long-term cardiovascular risk. Emerging studies highlight that cardiovascular programming is governed by interconnected mechanisms involving epigenetic regulation, mitochondrial function, immune signaling, and intercellular communication. This review synthesizes current evidence on how maternal–fetal crosstalk shapes cardiovascular development beyond genetic determinants and provides an integrated framework linking early-life exposures to lifelong cardiovascular health. Full article
(This article belongs to the Special Issue Feature Review Papers in the ‘Genetics’ Section)
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35 pages, 1503 KB  
Review
Placental Pathophysiology in Maternal Psychoactive Substance Use: Biological, Clinical, and Forensic Perspectives
by Oscar Fraile-Martinez, Natalia Rubio-Bedoya, Cielo García-Montero, Diego Liviu Boaru, Patricia de Castro-Martinez, Julia Bujan, Laura López-González, Raul Díaz-Pedrero, Natalio García-Honduvilla, Melchor Álvarez-Mon, Miguel A. Saez, Juan A. De León-Luis, Coral Bravo and Miguel A. Ortega
Cells 2026, 15(12), 1128; https://doi.org/10.3390/cells15121128 - 22 Jun 2026
Viewed by 358
Abstract
Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal–fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross [...] Read more.
Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal–fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross the placental barrier and induce structural and functional alterations. This review synthesizes current evidence on the biological mechanisms, diagnostic approaches, and forensic relevance of psychoactive substances-induced placental pathology. We summarize how different substances disrupt placental vascularization, oxidative balance, epigenetic regulation, and cellular viability, leading to impaired nutrient and oxygen transfer and increasing the risk of adverse outcomes such as intrauterine growth restriction, preterm birth, congenital anomalies, and long-term neurodevelopmental impairment. We further discuss the role of placental tissue in identifying prenatal drug exposure and reconstructing exposure timelines. Beyond its clinical relevance, placental examination provides objective evidence with potential forensic value in cases of suspected maternal substance use, while also informing non-punitive, evidence-based interventions. Overall, integrating placental pathology into reproductive health research and prenatal care offers a multidisciplinary framework to improve maternal–fetal outcomes and guide public health strategies addressing substance use during pregnancy. Full article
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13 pages, 620 KB  
Article
Does the Depth of Hysteroscopic Endometrial Fundal Incision Influence Reproductive Outcomes in Oocyte Recipients? A Prospective Study
by Robert Najdecki, Nikolaos Peitsidis, Ioannis Tsakiridis, Evangelos Papanikolaou, Fotini Chouliara, Georgios Michos, Krzysztof Łuszczyński, Marcin Chlebus, Paweł Kamiński and Monika Szafarowska
J. Clin. Med. 2026, 15(12), 4689; https://doi.org/10.3390/jcm15124689 - 17 Jun 2026
Viewed by 182
Abstract
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 [...] Read more.
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
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19 pages, 936 KB  
Article
Predictive Performance of Oocyte Count for Clinical Pregnancy in GnRH Antagonist IVF Cycles: A Multivariable Analysis of 1171 Fresh Embryo Transfers over a 14-Year Period
by Ömer Osman Eroğlu, Runa Özelçi, Ramazan Erda Pay and Cansın Eroğlu
Medicina 2026, 62(6), 1110; https://doi.org/10.3390/medicina62061110 - 7 Jun 2026
Viewed by 302
Abstract
Background and Objectives: The optimal oocyte yield in gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles remains debated, and data specific to antagonist protocols are limited. This study evaluated the discriminative and independent predictive performance of oocyte count for clinical pregnancy in [...] Read more.
Background and Objectives: The optimal oocyte yield in gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles remains debated, and data specific to antagonist protocols are limited. This study evaluated the discriminative and independent predictive performance of oocyte count for clinical pregnancy in GnRH antagonist IVF cycles. Materials and Methods: This retrospective cohort included 1171 women undergoing their first GnRH antagonist IVF cycle with fresh embryo transfer at a single tertiary center (September 2007–December 2021). The primary outcome was an institutional composite pregnancy outcome (sustained β-hCG positivity with subsequent ongoing intrauterine pregnancy or live birth; biochemical and ectopic pregnancies were negative). Patients were grouped by oocytes retrieved (1–5, 6–10, 11–15, ≥16). Performance was assessed with logistic regression, ROC with 2000-iteration bootstrap, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and restricted cubic spline. Predefined subgroup analyses by age, regimen, and antral follicle count tertile were performed. Results: A positive outcome occurred in 430 patients (36.7%). After adjustment, oocyte count was not an independent predictor (adjusted odds ratio 0.999, 95% CI 0.979–1.020; p = 0.96). The full model (AUC 0.564, 95% CI 0.529–0.598) did not outperform oocyte count alone (AUC 0.532; bootstrap p = 0.11). IDI (0.011) and NRI (0.135) were statistically detectable but clinically trivial. Spline regression showed no non-linearity (p = 0.47). Findings were consistent across subgroups, and the narrow confidence interval excluded per-oocyte effects ≥1.10. Conclusions: In GnRH antagonist IVF cycles, oocyte count showed weak discriminatory performance and was not independently associated with fresh-cycle pregnancy. Oocyte yield should be interpreted alongside—rather than as a substitute for—established parameters such as age and ovarian reserve. The principal clinical value of a higher oocyte response may lie in cumulative rather than fresh-cycle success. Live-birth outcomes were not available, and the source institution was permanently closed in 2025; these limitations define the boundary of inference. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
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27 pages, 3338 KB  
Review
Maternal–Fetal Implications of Herpes Virus Infection: An Updated Review
by Stefany Silva Pereira, Beatriz Bussi Rosolen, Talita Almeida Durães, Marcela Fermoselle de Vita Silva, Giovanna Alves de Britto, Camila Silva Belo, Thamy Cristina Campos, Gustavo Yano Callado, Susana Cristina Aidé Viviani Fialho, Antonio Braga and Edward Araujo Júnior
Diagnostics 2026, 16(8), 1147; https://doi.org/10.3390/diagnostics16081147 - 13 Apr 2026
Viewed by 1405
Abstract
Herpes simplex virus (HSV) infection is highly prevalent worldwide and poses important risks during pregnancy due to the potential for vertical transmission and severe neonatal disease. HSV-1 is traditionally associated with orofacial lesions and HSV-2 with genital infection; however, HSV-1 has emerged as [...] Read more.
Herpes simplex virus (HSV) infection is highly prevalent worldwide and poses important risks during pregnancy due to the potential for vertical transmission and severe neonatal disease. HSV-1 is traditionally associated with orofacial lesions and HSV-2 with genital infection; however, HSV-1 has emerged as a significant cause of genital and neonatal herpes. Physiological immunomodulation during pregnancy may facilitate viral reactivation and replication. Vertical transmission may occur intrauterinely, intrapartum, or postnatally, with approximately 85% of neonatal infections acquired during delivery through contact with infected genital secretions. The risk is highest when primary maternal infection occurs in the third trimester, before adequate transplacental transfer of protective antibodies. Neonatal infection may present as disease limited to the skin, eyes, and mouth; central nervous system involvement; or disseminated multiorgan disease, the latter associated with high morbidity and mortality. Maternal infection ranges from asymptomatic viral shedding to painful vesiculoulcerative lesions and, rarely, disseminated disease. Because asymptomatic shedding is common, diagnosis relies on laboratory confirmation using polymerase chain reaction (PCR) or viral culture, with type-specific serology aiding in distinguishing primary from recurrent infection. Management aims to reduce symptoms, viral shedding, recurrences near delivery, and vertical transmission. Acyclovir and valacyclovir are safe and effective in pregnancy. Suppressive therapy from 36 weeks’ gestation reduces recurrences and viral shedding at delivery and decreases the need for cesarean delivery, which is recommended when active lesions or prodromal symptoms are present at labor. Neonatal herpes requires prompt recognition and intravenous acyclovir therapy to reduce mortality and neurological sequelae. Preventive strategies include counseling, behavioral risk reduction, suppressive antiviral therapy, and avoidance of neonatal exposure to active lesions. Full article
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7 pages, 1695 KB  
Case Report
Hepatic Ectopic Pregnancy: A Diagnostic Challenge Highlighted by Multimodal Imaging
by Puja Punukollu, Lindsey Grater, Claudia Szlek, Rebecca Joseph, John Lue, James Maher and Lawrence Devoe
J. Clin. Med. 2026, 15(6), 2388; https://doi.org/10.3390/jcm15062388 - 20 Mar 2026
Viewed by 840
Abstract
Background: Ectopic pregnancy occurs in about 1–2% of all pregnancies, with 95% implanting in the fallopian tubes. Hepatic implantation is one of the rarest and most dangerous forms of abdominal ectopic pregnancy. Its diagnosis is often delayed because of nonspecific symptoms, and it [...] Read more.
Background: Ectopic pregnancy occurs in about 1–2% of all pregnancies, with 95% implanting in the fallopian tubes. Hepatic implantation is one of the rarest and most dangerous forms of abdominal ectopic pregnancy. Its diagnosis is often delayed because of nonspecific symptoms, and it is also often difficult for routine ultrasound imaging to visualize ectopic pregnancy sites that are not in the pelvis. Since this type of pregnancy carries a risk of severe hemorrhage, early identification is crucial. Case: A 30-year-old woman, gravida 3 para 2, presented with a serum β-hCG of 66,408 mIU/mL, but no intrauterine pregnancy was detected on ultrasound imaging. At an outside facility, a laparoscopy was performed, which also failed to show a pelvic ectopic pregnancy. The patient then received her first dose of methotrexate and was subsequently transferred to a tertiary care center for further evaluation. MRI and liver ultrasound showed a 2.3 cm subcapsular lesion in segment 5 of the liver that was suspicious for a hepatic ectopic pregnancy. However, these imaging studies could not exclude a gestational trophoblastic disease or hepatic neoplasm. A dilation and curettage revealed no trophoblastic tissue. The patient next received two additional doses of methotrexate on hospital days 4 and 7 due to an inadequate decline in interval β-hCG; β-hCG levels declined gradually but steadily over several months until they became undetectable and indicated a successful medical treatment of her hepatic ectopic pregnancy. Conclusions: This case highlights the complex diagnostic and treatment challenges presented by a hepatic ectopic pregnancy. Multimodal imaging, serial monitoring of β-hCG levels, and the engagement of a multidisciplinary team were essential factors in achieving a safe, nonsurgical, and successful resolution of this condition. When a pregnancy of unknown location is suspected, extended imaging studies are critical tools for patient evaluation after initial imaging studies and laparoscopy are inconclusive. Full article
(This article belongs to the Special Issue Recent Advancements in Nuclear Medicine and Radiology: 2nd Edition)
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26 pages, 946 KB  
Review
Umbilical Cord Biomarkers of Nutritional and Metabolic Status in Neonates with Intrauterine Growth Restriction
by Ioana Hermina Toth, Manuela Marina Pantea, Ileana Enatescu, Angelica Teodora Filimon, Flavia Yasmina Kali and Oana Belei
J. Clin. Med. 2026, 15(3), 1043; https://doi.org/10.3390/jcm15031043 - 28 Jan 2026
Cited by 1 | Viewed by 1147
Abstract
Background: Intrauterine Growth Restriction (IUGR) is associated with a distinct neonatal metabolic profile, attributable to chronic intrauterine nutritional deprivation and suboptimal placental nutrient exchange. Upon delivery, IUGR neonates typically present with depleted nutrient stores, dysregulated endocrine activity, and a spectrum of micronutrient deficiencies, [...] Read more.
Background: Intrauterine Growth Restriction (IUGR) is associated with a distinct neonatal metabolic profile, attributable to chronic intrauterine nutritional deprivation and suboptimal placental nutrient exchange. Upon delivery, IUGR neonates typically present with depleted nutrient stores, dysregulated endocrine activity, and a spectrum of micronutrient deficiencies, factors that collectively compromise metabolic homeostasis and significantly influence subsequent health trajectories. Methods: This narrative review systematically synthesizes the current body of evidence from clinical, biochemical, and translational investigations pertaining to the micronutrient status and pivotal endocrine markers in neonates affected by intrauterine growth restriction. The collected findings were integrated to elucidate metabolic adaptation mechanisms, immediate clinical ramifications, and the potential pathways linking neonatal biochemical patterns to long-term metabolic programming. Results: IUGR neonates consistently exhibit reduced cord-blood concentrations of essential micronutrients, including vitamin D, iron (Fe), zinc (Zn), magnesium (Mg), folate (vitamin B9), and cobalamin (vitamin B12), reflecting compromised placental nutrient transfer and limited fetal reserves. Concomitantly, endocrine alterations—most notably reduced insulin (INS) and C-peptide (C-pep) levels—indicate suppressed pancreatic β-cell activity and a prevailing hypoanabolic adaptive state. In parallel, disturbances in mineral metabolism, characterized by lower calcium (Ca) concentrations and increased alkaline phosphatase (ALP) activity, suggest impaired bone mineralization during the critical phase of early postnatal adaptation. Collectively, these biochemical patterns increase vulnerability to early clinical complications such as neonatal hypoglycemia and bone demineralization, disrupt early growth trajectories, and are associated with an elevated long-term risk of insulin resistance and adverse cardiometabolic programming. Conclusions: IUGR neonates consistently demonstrate a synergistic interplay of micronutrient deficiencies and adaptive endocrine responses, profoundly impacting immediate postnatal metabolic stability and predisposing them to long-term health challenges. Therefore, early biochemical screening, followed by tailored nutritional and hormonal interventions, may assist restore metabolic balance, promote growth and decrease long term risk for metabolic diseases. Full article
(This article belongs to the Special Issue Risk Factors in Neonatal Intensive Care)
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14 pages, 1242 KB  
Article
Specific IgE/IgG in Umbilical Cord Blood and Maternal Blood in Mothers with Eosinophilia
by Diana Mitkova Hristova, Martin Vladimirov, Bozhidar Karamishev, Anatoli Kolev, Daria Koleva, Liliya Koleva, Victoria Spasova, Svetlana Shumarova and Vesela Karamisheva
Allergies 2026, 6(1), 2; https://doi.org/10.3390/allergies6010002 - 19 Jan 2026
Viewed by 1474
Abstract
Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human [...] Read more.
Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ2, p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns. Full article
(This article belongs to the Section Physiopathology)
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31 pages, 992 KB  
Systematic Review
Tubal Stump Ectopic Pregnancy After IVF-ET in Patients Who Underwent Salpingectomy or Adnexectomy: A Qualitative Systematic Review
by Massimo Criscione, Giorgio Maria Baldini, Elisa Sanna, Laura Saderi, Giovanni Sotgiu, Mario Palumbo, Marco Petrillo and Giampiero Capobianco
Medicina 2026, 62(1), 83; https://doi.org/10.3390/medicina62010083 - 31 Dec 2025
Viewed by 2554
Abstract
Background and Objectives: Ectopic pregnancy (EP) is a life-threatening medical and surgical condition. Tubal stump EPs and heterotopic pregnancies can occur after in vitro fertilization-embryo transfer (IVF-ET), even after salpingectomy. The purpose of this study is to investigate the risk factors, diagnosis, and [...] Read more.
Background and Objectives: Ectopic pregnancy (EP) is a life-threatening medical and surgical condition. Tubal stump EPs and heterotopic pregnancies can occur after in vitro fertilization-embryo transfer (IVF-ET), even after salpingectomy. The purpose of this study is to investigate the risk factors, diagnosis, and treatment of tubal stump EPs after IVF-ET in patients with prior salpingectomy or adnexectomy. We also aim to evaluate the intrauterine pregnancy (IUP) outcome in cases of heterotopic pregnancy in this population. Materials and Methods: This systematic review (PROSPERO CRD42023352959) followed PRISMA guidelines. A literature search of MEDLINE®, Scopus, Web of Science, and clinicaltrials.gov was conducted on 30 April 2024. We included studies on tubal stump EP after IVF-ET in patients with previous salpingectomy or adnexectomy and created a qualitative summary. Results: We included 40 studies reporting on 57 patients (58 EP episodes). Most patients (69.0%) had prior bilateral salpingectomy. Tubal rupture occurred in 69.6% of cases, with 69.0% of these cases reporting hemoperitoneum. Abdominal pain was the most frequent symptom (71.7%). Heterotopic pregnancy occurred in 60.0% of cases (82.7% singletons). The IUP outcome was delivery in 81.9% of cases, with 95.5% of singletons delivering at term, compared with 40.0% of twins. The surgical approach (laparoscopy vs. laparotomy) did not change the IUP outcome. Tubal stump excision (74.1%) was the most common treatment. Overall, the certainty of the evidence was judged as moderate to very low according to the GRADE-CERQual approach, mainly due to small sample sizes, observational designs, and heterogeneity among studies. Conclusions: This review, the first on this topic, provides key data for counselling patients with a tubal stump heterotopic pregnancy. Despite its rarity, close follow-up until 8–10 weeks is recommended for IVF-ET patients with positive β-hCG, monitoring for abdominal pain. Successful management (expectant, medical, or surgical) should be guided by β-hCG levels and ultrasound findings (e.g., absence of heartbeat). Medical treatment shows encouraging obstetric outcomes and warrants further research. Full article
(This article belongs to the Special Issue Advances in Laparoscopic Surgery)
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13 pages, 947 KB  
Article
Intrauterine Administration of PBMC Modulated with IFN-τ Before Embryo Transfer Improves Clinical Outcomes of IVF Patients—A Randomized Control Trial
by Margarita Ruseva, Dimitar Parvanov, Rumiana Ganeva, Maria Handzhiyska, Jinahn Safir, Stefka Nikolova, Teodora Tihomirova, Dimitar Metodiev, Georgi Stamenov and Savina Hadjidekova
Biomedicines 2026, 14(1), 61; https://doi.org/10.3390/biomedicines14010061 - 26 Dec 2025
Viewed by 659
Abstract
Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was [...] Read more.
Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was conducted at Nadezhda Women’s Health Hospital (Approval No.: 6/28022023). The study was registered at ClinicalTrials.gov (NCT05775198). Randomization was computer-generated with allocation concealed via sealed envelopes. Participants and statisticians were blinded to group assignment; clinicians were not. Women aged 21–50 undergoing frozen–thawed embryo transfer with euploid embryos were included. Exclusion criteria included uterine anomalies, autoimmune, oncologic conditions, infections, or use of immunosuppressants. Participants (n = 340) were randomized 1:1 to receive either intrauterine infusion of autologous PBMCs activated in vitro with IFN-τ or standard IVF care without PBMC treatment. PBMCs were cultured with recombinant IFN-τ, washed, and infused 24 h prior to single euploid blastocyst transfer. A total of 14 patients were excluded from analysis because of early dropout, leaving 326 (n = 167; n = 159) patients for modified intention-to-treat analysis. Primary outcomes included implantation rate (elevated urinary or blood hCG), clinical pregnancy (fetal heartbeat at 6–8 weeks), and live birth rates. Miscarriage rate and safety were secondary objectives. Patients were followed up until 6 weeks post pregnancy resolution. Results: In the intervention group, 38.3% of patients achieved implantation, compared to 27.7% in the controls (OR 1.6, 95% CI: 1.0–2.6, p = 0.04). Live birth rates were also significantly higher in the IFN-τ-modulated PBMC group (28.7% vs. 17.6%, OR 1.9, 95% CI: 1.1–3.2; p = 0.02). While the clinical pregnancy rate was higher, it did not reach statistical significance (34.7% vs. 25.8%, p = 0.08). There was no difference between the groups in terms of miscarriage (p = 0.4). No serious adverse events were reported after treatment, during pregnancy or in the postnatal period. Conclusions: Intrauterine treatment with IFN-τ-activated PBMCs before ET significantly improves implantation and live birth rates in IVF patients. Full article
(This article belongs to the Special Issue Advances in Medically Assisted Reproduction)
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17 pages, 4675 KB  
Article
Maternal Exposure to 2,4-Di-tert-butylphenol During Pregnancy in a Mouse Model Leads to Abnormal Development of the Urinary System in Offspring
by Yuanyan Jiang, Ningli Ye, Minghui Yu, Haixin Ju, Chunyan Wang, Hengmin Wang, Jiaojiao Liu, Qian Shen and Hong Xu
Toxics 2025, 13(11), 991; https://doi.org/10.3390/toxics13110991 - 18 Nov 2025
Viewed by 1079
Abstract
The occurrence of congenital anomalies of the kidney and urinary tract (CAKUT) is influenced by intrauterine environmental factors, and maternal exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may affect the kidney development of offspring. 2,4-Di-tert-butylphenol (2,4-DTBP) is a high-production volume chemical classified as [...] Read more.
The occurrence of congenital anomalies of the kidney and urinary tract (CAKUT) is influenced by intrauterine environmental factors, and maternal exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may affect the kidney development of offspring. 2,4-Di-tert-butylphenol (2,4-DTBP) is a high-production volume chemical classified as an EDC, which has been detected in humans and has been found to increase mortality and malformation rates in zebrafish embryos. Its effects on mammalian development are still unknown. In this study, a maternal mouse model exposed to 2,4-DTBP throughout pregnancy was established by gavage. The overall conditions of the maternal mice and their offspring were observed, and the concentrations of 2,4-DTBP in maternal serum and offspring tissues were measured using liquid chromatography–tandem mass spectrometry. Exposure to 2,4-DTBP of 75 µg/g·day during pregnancy markedly reduced the early pregnancy rate in mice to 41.75% (95% CI: 33.53–49.97%; n = 139), compared to 82.29% (95% CI: 74.18–90.39%; n = 85) in the controls (p < 0.0001), with a relative risk (RR) of 0.51 (95% CI: 0.41–0.63). 2,4-DTBP could accumulate in maternal mice and be transferred to embryos and internal organs of the offspring, and is associated with the elevated risk of CAKUT in the offspring, primarily manifesting as hydronephrosis/ureteral dilation. The CAKUT rate of DTBP-75 group is 33.59% (95% CI: 17.62–49.56%; N = 9, n = 56), compared to 11.85% (95% CI: 2.43–21.28%; N = 9, n = 67) in the controls (p = 0.02), RR = 2.53 (95% CI: 1.18–5.42). These findings enhance the understanding of the health risks posed by 2,4-DTBP and provide a theoretical basis for environmental monitoring in public health. Full article
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26 pages, 1617 KB  
Systematic Review
Uterine Artery Pulsatility Index in Singleton Pregnancies Conceived via Assisted Reproductive Technology Versus Spontaneous Conception: A Systematic Review and Meta-Analysis
by Antonios Siargkas, Ioannis Tsakiridis, Areti Faka, Dimitra Kappou, Ioannis Papastefanou and Themistoklis Dagklis
Diagnostics 2025, 15(17), 2192; https://doi.org/10.3390/diagnostics15172192 - 29 Aug 2025
Viewed by 1703
Abstract
Background/Objectives: Uterine artery pulsatility index (UtA-PI) is a key biomarker of placental function, but its clinical interpretation in assisted reproductive technology (ART) pregnancies is uncertain. This meta-analysis aimed to assess trimester- and method-specific UtA-PI differences between ART and spontaneous conceptions (SC) and to [...] Read more.
Background/Objectives: Uterine artery pulsatility index (UtA-PI) is a key biomarker of placental function, but its clinical interpretation in assisted reproductive technology (ART) pregnancies is uncertain. This meta-analysis aimed to assess trimester- and method-specific UtA-PI differences between ART and spontaneous conceptions (SC) and to examine associated risks for preeclampsia (PE) and small-for-gestational-age (SGA) neonates to contextualize its findings. Methods: A systematic search of MEDLINE, Scopus, and the Cochrane Library was conducted through 25 June 2025. We included observational studies comparing UtA-PI and perinatal outcomes in singleton ART versus SC pregnancies. The primary outcome was the standardized mean difference (SMD) in first (until the 13+6 gestational week) and second trimester (14+0–23+6 gestational weeks) UtA-PI measurements; secondary outcomes were PE and SGA rates. Analyses were stratified by ART modalities. Random-effects models were used, and study quality was evaluated using the Newcastle–Ottawa Scale and risk of bias with QUIPS tool (INPLASY registration: INPLASY202560104). Results: Thirteen cohort studies were included. Overall, ART pregnancies had significantly lower UtA-PI values than SC in both the first (SMD = −0.28; 95% CI: −0.53 to −0.03) and second trimesters (SMD = −0.20; 95% CI: −0.36 to −0.04). These reductions were driven by oocyte donation (first-trimester SMD = −0.70; 95% CI: −1.21 to −0.18; second-trimester SMD = −0.46; 95% CI: −0.65 to −0.26) and artificial cycle frozen embryo transfers (ET) (first-trimester SMD = −0.69; 95% CI: −1.00 to −0.39). These lower UtA-PI values typically suggest better placental perfusion and a lower risk of placental related complications. However, ART pregnancies had an elevated overall risk for PE (risk ratio [RR] = 2.32; 95% CI: 1.72 to 3.12), with the highest risk in oocyte donation (RR = 6.11; 95% CI: 3.35 to 11.17) and artificial cycle frozen ET (RR = 3.45; 95% CI: 1.51 to 7.90). Conclusions: ART pregnancies, particularly from oocyte donation and artificial cycle frozen ET, show lower UtA-PI values despite a significantly elevated risk for PE. This finding suggests that mechanisms other than placental perfusion contribute to PE development. Clinically, the ART method is an independent risk factor for PE, and UtA-PI interpretation should be adjusted accordingly. Further research is crucial to elucidate the underlying pathophysiology. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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14 pages, 3178 KB  
Article
The Role of β-Core Fragment hCG in Embryo Implantation and Early Pregnancy
by Ji Soo Ryu, Nu Ri Yang, Yu Ha Shim, Yu Jin Kim, Won Jae Kwag, Jin Dong Chang and Jae Ho Lee
Int. J. Mol. Sci. 2025, 26(16), 7974; https://doi.org/10.3390/ijms26167974 - 18 Aug 2025
Cited by 2 | Viewed by 4586
Abstract
Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed [...] Read more.
Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed to investigate its role in embryo implantation and maintenance of a pregnancy-supportive environment. We analyzed the protein expression pattern of bcf-hCG in the intrauterine environment during early pregnancy by performing western blotting and immunohistochemistry with a monoclonal anti-bcf-hCG antibody. We performed a cell proliferation assay in the presence of bcf-hCG compared with intact hCG. We conducted an ex vivo study by performing intrauterine injection of bcf-hCG or intact hCG in mice. Endometrial thickness was measured using histological methods, and uterine gene and protein expression were analyzed following intrauterine injection of bcf-hCG. We evaluated the effect of bcf-hCG on embryo implantation in the uterus. bcf-hCG was highly abundant in the placenta and epithelial stromal glands of the uterine endometrium during early pregnancy and significantly induced proliferation of a stromal epithelial cell line. Intrauterine injection of bcf-hCG induced expression of specific genes and proteins, including homeobox A10, for embryo implantation and placental development. Upon embryo transfer, the implantation rate of bcf-hCG-treated embryos was higher than that of control embryos. In conclusion, bcf-hCG plays a role in the proliferation of glandular epithelial cells in the endometrium and placenta during early pregnancy. Therefore, bcf-hCG is an early-phase pregnancy biomarker that maintains the initial phase of pregnancy. Full article
(This article belongs to the Special Issue Reproductive Endocrinology Research)
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23 pages, 1017 KB  
Article
The Impact of Oral Health and Dental Care on Pregnancy: A Cross-Sectional Study Among Women of Reproductive Age
by Paulina Adamska, Hanna Sobczak-Zagalska, Zuzanna Gromek, Barbara Wojciechowska, Paulina Doroszkiewicz, Marek Chmielewski, Dominika Cichońska, Adam Zedler and Andrea Pilloni
J. Clin. Med. 2025, 14(14), 5153; https://doi.org/10.3390/jcm14145153 - 20 Jul 2025
Cited by 7 | Viewed by 10004
Abstract
Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related [...] Read more.
Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related to the mother, such as smoking, alcohol drinking, drug use, malnutrition, or certain diseases. It is imperative to educate women of reproductive age (15–49) about the basic factors influencing embryonic development, such as oral health, diet, medicine intake, and harmful habits. Even though most women are aware of the negative impact of harmful habits on the fetus, still too little attention is paid to oral health in pregnant women. Poor oral health may influence the well-being of the future mother, as well as of the child. Therefore, women of reproductive age and those who are pregnant must have adequate knowledge on this subject. The aim of this study was to assess the knowledge of Polish women of reproductive age (15–49) regarding oral health during pregnancy, including the impact of dental treatment, oral hygiene, and maternal oral conditions on pregnancy outcomes and the health of the newborn. Materials and Methods: This was a cross-sectional study of 508 women, in the reproductive age, whose age ranged from 18 to 49 years old. The surveys were conducted from April 2020 to November 2020. The questionnaire was originally developed based on the available literature and consisted of seven sections: basic information, general health and habits, pregnancy status and dental care, knowledge of treatment options during pregnancy, oral health status and its association with the risk of preterm birth, prematurity and the child’s oral health, and breastfeeding and oral development. Results: After excluding incomplete questionnaires, a total of 499 questionnaires were included in the analysis. Women participating in the study had a fairly good understanding of the impact of oral health on the fetus and the role of breastfeeding in the development of the stomatognathic system (from 50% to 70% correct answers). However, even though most respondents had completed higher education (344/68.94%), their knowledge of oral health, preterm birth, and low birth weight was very limited (including the impact of inflammation on the intrauterine development of the child or bacteria and transfer across the placenta). In these sections, the percentage of correct answers ranged from less than 20% to 50%. When analyzing knowledge by age, education, number of births, and place of residence, the highest levels of knowledge were observed among respondents with higher education, particularly those aged 27–32. Conclusions: Respondents had a fairly good understanding of the general impact of oral health during pregnancy and recognition of the importance of breastfeeding for infants. However, their knowledge about the impact of bacteria and inflammation in the mother’s oral cavity on prematurity and low birth weight was limited. Therefore, educating women of reproductive age and pregnant women on this topic is essential, as it may help reduce the adverse consequences of prematurity. Full article
(This article belongs to the Special Issue Oral Health and Dental Care: Current Advances and Future Options)
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10 pages, 1443 KB  
Article
Anti-Adhesive Podocalyxin Expression Is Disrupted in Recurrent Implantation Failure
by Mustafa Tas
Diagnostics 2025, 15(1), 100; https://doi.org/10.3390/diagnostics15010100 - 3 Jan 2025
Cited by 1 | Viewed by 1585
Abstract
Objectives: The downregulation of anti-adhesive regulatory proteins and upregulation of adhesive genes are critical for the receptive endometrium. This study was designed to determine whether switching between the anti-adhesive podocalyxin (PDX) and adhesive HOXA10 receptivity modulator occurs in the endometrium of women with [...] Read more.
Objectives: The downregulation of anti-adhesive regulatory proteins and upregulation of adhesive genes are critical for the receptive endometrium. This study was designed to determine whether switching between the anti-adhesive podocalyxin (PDX) and adhesive HOXA10 receptivity modulator occurs in the endometrium of women with recurrent implantation failure (RIF). Methods: Twenty-four patients with RIF who could not conceive for three or more cycles despite good-quality embryo transfer constituted the study group. Twenty-four patients with unexplained infertility (UEI) matched for age, BMI, and infertility duration were included in the control group. Twenty women scheduled to undergo intrauterine device (IUD) placement for birth control were included in the comparative group. Endometrial tissue was collected from patients with RIF and UEI during egg retrieval after ovarian stimulation using the GnRH antagonist protocol. In the fertile group, endometrial tissues were collected during IUD insertion. HOXA10 mRNA expression was analyzed by qRT-PCR and PDX protein expression was analyzed by ELISA. The relative expression of endometrial HOXA10 mRNA was calculated using the 2−ΔΔCt equation. Results: The relative expression of HOXA10 mRNA in the RIF group was significantly lower than that in the UEI group (p < 0.001). HOXA10 mRNA expression in the fertile group was significantly higher than that in the RIF group and was similar to that in the UEI group. PDX expression in the RIF group was significantly higher than that in the UEI group (p < 0.001). PDX expression in the fertile group was significantly lower than in the RIF and UEI groups. A negative correlation was detected between the anti-adhesive PDX protein and adhesive HOXA10 (r = −0.797, p < 0.001). Although there was a positive correlation between endometrial thickness recorded on the day of hCG administration and HOXA10 (r = 0.590, p < 0.01), endometrial thickness was negatively correlated with PDX (r = −0.529, p < 0.01). Conclusions: The failed physiological downregulation of the anti-adhesive PDX protein in patients with RIF prevented the upregulation of adhesive HOXA10 mRNA. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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