Search Results (1,288)

Hypoplastic or absent fetal nasal bone (NB) is a significant soft marker in the risk assessment for aneuploidies. This study aimed to evaluate prenatal findings and perinatal outcomes in fetuses with absent or hypoplastic NB managed at our center. This retrospective analysis was conducted at the Department of Obstetrics at the Medical University of Vienna and including all cases with an absent or hypoplastic fetal NB between 2004 and 2022. Clinical data were extracted and analyzed using descriptive statistics. A total of 149 cases were included. Of these, 51% had chromosomal abnormalities, with trisomy 21 present in 30.9%. Malformations were identified in 55% of cases, most commonly congenital heart defects (34.9%) and facial dysmorphism (28.9%). Eighteen fetuses (12.1%) had structural anomalies without genetic disorders. In 32.9% (n = 49), the NB anomaly was isolated. Our findings show that only half of the cases had chromosomal abnormalities, and over half of the pregnancies resulted in live births with generally favorable perinatal outcomes. However, the presence of additional ultrasound abnormalities significantly increased the risk of adverse outcomes. Therefore, detection of a fetal NB anomaly should prompt comprehensive ultrasound evaluation and genetic testing. Full article

Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan with distinct biological functions, dependent on its molecular weight. High-molecular-weight HA (HMWHA) primarily exhibits structural and anti-inflammatory roles, whereas low-(LMWHA) and very low-molecular-weight HAs (vLMWHA) actively participate in tissue regeneration and angiogenesis. This review highlights the pivotal roles of HA across the female reproductive lifespan, emphasizing how molecular weight dictates its therapeutic potential. In gynecology, LMWHA effectively alleviates symptoms of genitourinary syndrome of menopause, restores vaginal architecture, and mitigates complications following pelvic radiotherapy, improving both tissue integrity and patient quality of life. vLMWHA shows promise in enhancing viral clearance and lesion regression in human papillomavirus (HPV) infections. In obstetrics, HMWHA plays crucial roles in implantation, immunotolerance, and embryogenesis and maintains cervical barrier integrity to prevent ascending infections and preterm birth. Moreover, emerging clinical evidence supports oral HMWHA supplementation for reducing pregnancy complications, such as threatened miscarriage, subchorionic hematomas, and preterm delivery. This review underscores the necessity of considering HA’s molecular weight to optimize interventions in gynecological and obstetric care, offering tailored strategies to support women’s health throughout their lives. Full article

Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF patients undergoing in vitro fertilization, stratified by FSHR (follicular stimulating hormone receptor) genotype Asn680Ser with or without GH supplementation. Patients were stratified by FSHR genotype into homozygous Ser/Ser versus Ser/Asn or Asn/Asn groups. Overall, GH co-treatment conferred modest benefits in the unselected RIF cohort, limited to a higher cumulative live birth rate compared to controls and elevated leukemia inhibitory factor (LIF) levels (p < 0.05 both). When stratified by FSHR genotype, the Ser/Ser subgroup exhibited markedly better outcomes with GH. These patients showed a higher (0.5 vs. 0.33, p = 0.003), produced more embryos (2.88 vs. 1.53, p = 0.02), and had a markedly improved cumulative live birth rate—50% with GH versus 13% without—highlighting a clinically meaningful benefit of GH in the Ser/Ser subgroup. No significant benefit was observed in Asn allele carriers. These findings suggest that FSHR genotyping may help optimize treatment selection in RIF patients by identifying those most likely to benefit from GH supplementation. Full article

Rubinstein–Taybi Syndrome type 1 (RSTS1) is an uncommon autosomal dominant genetic disorder associated with neurodevelopmental impairments and multiple congenital anomalies, with an incidence of 1:100,000–125,000 live births. The syndrome, caused by de novo mutations in the CREBBP gene, is characterized by phenotypic variability, including intellectual disability, facial dysmorphisms, and systemic abnormalities. The current case report describes a 15-year-old Brazilian female diagnosed with RSTS1 through whole-exome sequencing, which identified a de novo heterozygous missense mutation in the CREBBP gene (NM_004380.3; c.4393G > C; p.Gly1465Arg), classified as pathogenic. The patient’s clinical presentation included facial dysmorphisms, skeletal abnormalities, neurodevelopmental delay, psychiatric conditions, and other systemic manifestations. A comprehensive genetic counseling process facilitated the differential diagnosis and management strategies, emphasizing the importance of early and precise diagnosis for improving clinical outcomes. This report contributes to the growing knowledge of the genotype–phenotype correlations in RSTS1, aiding in the understanding and management of this uncommon condition. Full article

Congenital hypothyroidism (CH) is a leading preventable cause of neurocognitive impairment. Its incidence appears to be rising in several countries. We analysed 27 years of newborn-screening data (1997–2023) from the largest Chilean screening centre, covering 3,225,216 newborns (51.1% of national births), to characterise temporal trends and potential drivers of CH incidence. Annual CH incidence was modelled with Prais–Winsten regression to correct for first-order autocorrelation; additional models assessed trends in gestational age, sex, biochemical markers, and aetiological subtypes. We identified 1550 CH cases, giving a mean incidence of 4.9 per 10,000 live births and a significant yearly increase of 0.067 per 10,000 (95 % CI 0.037–0.098; p < 0.001). Mild cases (confirmation TSH < 20 mU/L) rose (+0.89 percentage points per year; p = 0.002). The program’s recall was low (0.05%). Over time, screening and diagnostic TSH values declined, total and free T4 concentrations rose, gestational age at diagnosis fell, and a shift from thyroid ectopy toward hypoplasia emerged; no regional differences were detected. The sustained increase in CH incidence, alongside falling TSH thresholds and growing detection of in situ glands, suggests enhanced recognition of milder disease. Ongoing surveillance should integrate environmental, iodine-nutrition, and genetic factors to clarify the causes of this trend. Full article

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013–2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04–1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis. Full article

Background/Objectives: Niemann-Pick disease Type C (NPC) represents an autosomal recessive disorder with an incidence rate of 1 in 100,000 live births that belongs to the lysosomal storage diseases (LSDs). NPC is characterized by the abnormal accumulation of unesterified cholesterol, in addition to being an autosomal recessive inherited pathology, which belongs to LSDs. It occurs in 95% of cases due to mutations in the NPC1 gene, while 5% of cases are due to mutations in the NPC2 gene. In the cerebral cortex (CC), the disease shows lipid inclusions, increased cholesterol and multiple sphingolipids in neuronal membranes, and protein aggregates such as hyperphosphorylated tau, α-Synuclein, TDP-43, and β-amyloid peptide. Mitochondrial damage and oxidative stress are some alterations at the cellular level in NPC. Therefore, the aim of this work was to determine the gene expression profile in the CC of NPC1 mice in order to identify altered molecular pathways that may be related to the pathophysiology of the disease. Methods: In this study, we performed a microarray analysis of a 22,000-gene chip from the cerebral cortex of an NPC mutant mouse compared to a WT mouse. Subsequently, we performed a bioinformatic analysis in which we found groups of dysregulated genes, and their expression was corroborated by qPCR. Finally, we performed Western blotting to determine the expression of proteins probably dysregulated. Results: We found groups of dysregulated genes in the cerebral cortex of the NPC mouse involved in the ubiquitination, fatty acid metabolism, differentiation and development, and underexpression in genes with mitochondrial functions, which could be involved in intrinsic apoptosis reported in NPC, in addition, we found a generalized deregulation in the cortical circadian rhythm pathway, which could be related to the depressive behavior that has even been reported in NPC patients. Conclusions: Recognizing that there are changes in the expression of genes related to ubiquitination, mitochondrial functions, and cortical circadian rhythm in the NPC mutant mouse lays the basis for targeting treatments to new potential therapeutic targets. Full article

Background: Non-syndromic orofacial clefts (NSOFCs) are one of the common congenital malformations in Vietnam, with 1.4 per 1000 live births, with notable sex differences in occurrence. This case–control study aims to investigate potential sex-specific interactions of WNT3 and NOG polymorphisms across NSOFC subtypes in a Vietnamese population. Methods: A total of 720 participants were separated into 4 groups with a male/female ratio of 1:1 (160 individuals with cleft lip and palate (NSCLP), 160 with cleft lip only (NSCLO), 160 with cleft palate only (NSCPO), 240 healthy controls). Two single-nucleotide polymorphisms (SNPs), rs3809857 and rs227731, were genotyped by using the StepOnePlus Real-Time PCR System. Results: The most significant findings were found in the male NSCLO group under a recessive model of WNT3 rs3809857 after applying Bonferroni correction, as a five-fold protective factor with OR = 0.18 (95% confidence interval: 0.05–0.64, p = 0.0033). Additionally, the weak or moderate protective association between rs3809857 and male NSCLP was found with p < 0.05 under the dominant model. However, there were no significant findings in the female NSOFC subtypes associated with WNT3. Conversely, NOG rs227731 results showed a weak increased risk in female NSCLO and NSCPO with p < 0.05. Conclusion: this study identified the critical role of WNT3 rs3809857 in reducing NSCLO risk in males. These findings support the potential influence of sex as a modifying factor in the genetic susceptibility to non-syndromic orofacial clefts. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

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

Congenital hypothyroidism (CH) is one of the major preventable causes of intellectual disability. This study evaluates the incidence of CH through a newborn screening (NBS) program in eastern Morocco. A descriptive cross-sectional design was used and heel prick blood samples were collected on blotting paper to measure Thyroid-Stimulating Hormone (TSH) using an immunofluorimetric assay. 4062 newborns were screened (51.3% male, 48.7% female). TSH levels significantly varied by age: newborns sampled before 24 h had a higher median TSH (3.7 µU/mL [0.10–28.90]) compared to those sampled at 24 h or more (2.1 µU/mL [0.10–32.30]; p < 0.001). Using age-specific cut-off values, 18 suspected CH cases were recalled (recall rate: 0.44%). Among the 16 cases who completed confirmatory testing, 4 had transient hyperthyrotropinemia (HTT), characterized by mildly abnormal serum TSH and T4 levels that normalized spontaneously after few months without treatment. Three cases were diagnosed with CH confirmed at birth with markedly elevated serum TSH concentrations and significantly reduced T4 levels. Consequently, the birth prevalence of CH confirmed at birth was 1:1354 live births. The median preanalytical delay was 6 days (IQR: 3–12) and the TSH result turnaround was 8 days (IQR: 5–15), potentially affecting timely intervention. This first report from eastern Morocco confirms the relevance of neonatal screening but highlights delays that must be addressed to enhance early diagnosis and management. Full article

Background/Objectives: Renal transplantation (RT) represents the optimal treatment for end-stage renal disease (ESRD), offering improved quality of life and restored fertility in women post-transplant. While post-transplant pregnancies are possible, they can lead to complications including pre-eclampsia, graft dysfunction, and other adverse outcomes. This study evaluates existing literature to assess pregnancy’s impact on kidney transplantation outcomes, specifically long-term graft function and survival. Methods: We conducted a systematic review of English-language literature from January 2000 to September 2023 across multiple databases, following PRISMA guidelines. We established inclusion criteria focusing on graft function and adverse events. Two independent reviewers performed data extraction, and we assessed risk of bias using the ROBINS-I tool. Results: From 4917 articles, we included 26 studies encompassing 1202 pregnancies in 902 kidney transplant recipients. Mean maternal age was 30.8 years, with an average interval of 52 months between transplant and pregnancy. Pre-pregnancy hypertension occurred in 54.2% of cases, and pre-eclampsia developed in 25.7%. The live birth rate reached 70.5%, while miscarriage, stillbirth, and neonatal death rates were 11.3%, 2.7%, and 2.5%, respectively. We noticed graft dysfunction during pregnancy in 20.2% of cases. Though kidney function often deteriorated temporarily, most patients recovered post-delivery. Discussion: Post-transplant pregnancies remain viable but high-risk, with elevated rates of obstetric complications. Our findings highlight the need for standardized data collection and reporting to better understand and manage pregnancy’s impact on graft outcomes. Conclusions: With appropriate management, pregnancy in kidney transplant recipients is feasible, though it carries elevated risks of obstetric complications. We recommend further multicenter studies with standardized data collection to improve understanding and outcomes. Full article

Objectives: With the development of artificial intelligence technology in medicine, an intelligent deep learning-based embryo scoring system (iDAScore) has been developed on full-time lapse sequences of embryos. It automatically ranks embryos according to the likelihood of achieving a fetal heartbeat with no manual input from embryologists. To ensure its performance, external validation studies should be performed at multiple clinics. Methods: A total of 6291 single vitrified–thawed blastocyst transfer cycles from 2018 to 2021 at the Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed by the iDAScore model. Patients with two or more blastocysts transferred and blastocysts that were not cultured in a time-lapse incubator were excluded. Blastocysts were divided into four comparably sized groups by first sorting their iDAScore values in ascending order and then compared with the clinical, perinatal, and neonatal outcomes. Results: Our results showed that clinical pregnancy, miscarriage, and live birth significantly correlated with iDAScore (p < 0.001). For perinatal and neonatal outcomes, no significant difference was shown in four iDAScore groups, except sex ratio. Uni- and multivariable logistic regressions showed that iDAScore was significantly positively correlated with live birth rate (p < 0.05). Conclusions: In conclusion, the objective ranking can prioritize embryos reliably and rapidly for transfer, which could allow embryologists more time for processes requiring hands-on procedures. Full article

Background and aim: The death of a woman while pregnant or within 42 days of delivery, regardless of the cause of death, or even up to one year after the end of the pregnancy, due to causes related to or aggravated by pregnancy remains a critical public health problem globally and in Colombia. While the country shows a general decreasing trend (preliminary Maternal Mortality Ratio 38.6/100,000 live births in 2023), significant regional disparities persist. Understanding precise underlying causes, especially in high-complexity referral centers, is vital. This study describes the sociodemographic and anatomopathological characteristics associated with autopsy-verified maternal mortality cases at a Level-4 hospital in southwestern Colombia (2000–2023). Methodology: A descriptive observational retrospective study analyzed 42 maternal mortality cases verified by clinical autopsy (2000–2023) at the Pathology Department of Universidad del Valle, a Level-4 referral center in Cali, Colombia. Cases met the WHO definition. Data on sociodemographic, clinical, and pathological characteristics were retrospectively extracted from clinical records and autopsy reports. Results: The analysis of 42 autopsies (2000–2023) showed that 85.7% were early maternal deaths. Indirect causes predominated (57.1%, n = 24) over direct (42.9%, n = 18). Septic shock was the main indirect cause (65.2% of indirect), often from endemic infections. Hypovolemic shock due to PPH was the main direct cause (50% of direct). A high proportion were from subsidized/uninsured schemes (65.7%) and had a migratory history (20%). Discussion and conclusions: This study highlights the value of autopsy in revealing maternal mortality etiologies, showing a predominance of indirect/infectious causes and endemic diseases often missed clinically, despite PPH remaining the main direct cause. Findings reaffirm the strong link between maternal death and social/economic inequity, access barriers, and regional/migratory vulnerabilities. Effectively reducing maternal mortality necessitates rigorous clinical management, regionalized public health strategies addressing inequities, and integrating pathological data for targeted surveillance. Full article