Biomedicines

Research

11 pages, 514 KiB

Open AccessArticle

Findings of Reduced Head Circumference with COVID-19 Infection in the Third Trimester: A Retrospective Cohort Study

by Kristen Lee Moriarty, Kelsey Manfredi, Pascale Carrel, Emma Kryzanski, David A. Schwartz, Lucas Godoy, Chia-Ling Kuo and Andrea Shields

Biomedicines 2025, 13(4), 832; https://doi.org/10.3390/biomedicines13040832 - 31 Mar 2025

Viewed by 365

Abstract

Background: COVID-19 is linked to multiple adverse pregnancy outcomes but with inconsistent evidence associating the disease with fetal growth restriction (FGR) and small for gestational age (SGA). There are limited data on the impact of COVID-19 on neonatal growth measurements, specifically microcephaly [...] Read more.

Background: COVID-19 is linked to multiple adverse pregnancy outcomes but with inconsistent evidence associating the disease with fetal growth restriction (FGR) and small for gestational age (SGA). There are limited data on the impact of COVID-19 on neonatal growth measurements, specifically microcephaly without SGA or low birth weight. We hypothesize that COVID-19 is associated with smaller neonatal head measurements without increasing the risk of small for gestational age. This relationship may be related to the timing of COVID-19 exposure in pregnancy. Methods: An Institutional Review Board (IRB) approved retrospective cohort study enrolled 140 COVID-19-infected and 136 COVID-19-uninfected patients. Inclusion criteria: (a) singleton birth between 28 April 2020 and 31 December 2022; and (b) maternal COVID-19 infection diagnosed via polymerase chain reaction (PCR). Exclusion criteria: Less than 12 years of maternal age, major fetal anomalies, and fetal loss < 15 weeks. The outcomes were a comparison of newborn growth measurements (length, weight, and head circumference (HC) at birth), Ponderal Index (PI), and development of SGA between SARS-CoV-2-infected and uninfected patients. Maternal and neonatal characteristics were descriptively summarized, and multivariate analyses and linear regression models were performed. Baseline maternal demographics did not differ amongst cohorts. Results: Compared to the uninfected cohort, COVID-19 diagnosed in the third trimester was associated with a lower neonatal HC compared to newborns of uninfected patients (β = −0.38 [0.38 SD lower], 95% CI −0.65 to −0.10, p = 0.024). There was no significant difference among cohorts in birth length, weight, or diagnosis of small for gestational age. Conclusions: We found that COVID-19 infection in the third trimester was associated with a lower neonatal head circumference without associated SGA. The cause underlying this association is unknown. Further research to determine the risk of neurotropic fetal infection by SARS-CoV-2, like ZIKA’s effect on the fetal immune system leading to microcephaly, is urgently needed. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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16 pages, 1825 KiB

Open AccessArticle

Antimicrobial Resistance in Maternal Infections During Pregnancy

by Tania Vlad, Anca-Elena Eftenoiu, Adela Voinescu, Silvia Ioana Musuroi, Corina Musuroi, Aurica Elisabeta Moatar, Daliborca Cristina Vlad, Adriana Trandafir, Cristian Sebastian Vlad and Ionut Marcel Cobec

Biomedicines 2025, 13(4), 777; https://doi.org/10.3390/biomedicines13040777 - 22 Mar 2025

Viewed by 554

Abstract

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum [...] Read more.

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum infections, when not adequately managed, can significantly impact maternal and neonatal health. Antimicrobial resistance poses an escalating global health threat, with newborns particularly vulnerable. Methods: This study constitutes a retrospective observational analysis, encompassing all microbial strains isolated from pregnant women admitted to the “Pius Brînzeu” Clinical County Emergency Hospital in Timișoara, Romania for various infectious diseases over one year. We analyzed 274 samples from 246 pregnant women, of which 242 were cervical samples, 23 urine cultures, 3 wound secretions, 3 amniotic fluids, 1 peritoneal cavity fluid, 1 sputum, and 1 hemoculture. Results: In cervical samples, Group B Streptococcus (GBS) was the most prevalent, representing 42.46% of the isolates. E. coli was the second most frequent at 30.16%, followed by K. pneumoniae at 11.9%, S. aureus at 8.73%, C. albicans at 2.78%, and other species at 3.97%. A total of 9.63% of cervical GBS isolates exhibited resistance to penicillin, while 23.36% were identified as multi-drug resistant (MDR). Methicillin-resistant S. aureus (MRSA) and MDR S. aureus strains were identified in 50% and 54.54% of the S. aureus-positive cervical samples, respectively. Conclusions: Recognizing the implications of maternal infection or colonization, especially with antimicrobial resistance bacteria, aids in assessing risks during pregnancy. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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18 pages, 8382 KiB

Open AccessArticle

Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes

by Jiuming Fan, Mengyao Zhang, Huailiang Wu, Zehua Ye and Liyan Wang

Biomedicines 2025, 13(2), 498; https://doi.org/10.3390/biomedicines13020498 - 17 Feb 2025

Viewed by 953

Abstract

Background: Elevated estrogen has been found to contribute to the pathological development of endometrial cancer (EC), potentially through alterations in the tumor inflammatory immune microenvironment. However, the exact mechanisms underlying this process remain unclear. Methods: Bioinformatics was used to identify differentially [...] Read more.

Background: Elevated estrogen has been found to contribute to the pathological development of endometrial cancer (EC), potentially through alterations in the tumor inflammatory immune microenvironment. However, the exact mechanisms underlying this process remain unclear. Methods: Bioinformatics was used to identify differentially expressed genes, analyze pathway enrichment, and assess their correlation with immune cell infiltration. Ishikawa cells and ECC-1 cells were stimulated with estradiol (E2) or the selective estrogen receptor modulator Arzoxifene, and qPCR was performed to measure gene expression changes. CCK8 and FACS assays were used to analyze cell cycle alterations, while Western blotting (WB) was used to evaluate apoptosis. Results: ZNF626 and SLK were highly expressed in EC tissues, whereas RFWD3 expression was downregulated. Immune cell infiltration analysis revealed a positive correlation between ZNF626 and M2 macrophages, while SLK was negatively correlated with M1 macrophages, memory B cells, and plasma cells. RFWD3 showed more complex correlations with multiple immune cell phenotypes, including T cells. E2 stimulation resulted in the increased expression of ZNF626 and SLK, while RFWD3 expression decreased. This was accompanied by enhanced cell proliferation and suppressed apoptosis. In contrast, Arzoxifene stimulation produced the opposite effects. Conclusions: Estrogen promotes cell proliferation and inhibits apoptosis by upregulating ZNF626 and SLK, while downregulating RFWD3. Furthermore, estrogen induces a shift in the tumor microenvironment, characterized by a reduction in memory CD4+ T cells and a transition from M1 to M2 macrophage phenotypes, thus facilitating the onset and progression of EC. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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15 pages, 1306 KiB

Open AccessArticle

ECO-SCORE: Development of a New Ultrasound Score for the Study of Cystic and Solid-Cystic Adnexal Masses Based on Imaging Characteristics

by Carmen Rodríguez-Rubio, Sara Vegas-Viedma, Malena del Olmo-Reillo, Paula Quintana-Zapata, Javier Sancho-Sauco, Mª Jesús Pablos-Antona, Juan Luis Alcázar and Irene Pelayo-Delgado

Biomedicines 2025, 13(2), 317; https://doi.org/10.3390/biomedicines13020317 - 29 Jan 2025

Viewed by 793

Abstract

The accurate diagnosis of adnexal masses is a critical challenge in gynecological practice. Current ultrasound-based models, such as the ADNEX model, IOTA Simple Rules, and O-RADS, have demonstrated good diagnostic performance but are limited by the inclusion of demographic factors and solid confounding [...] Read more.

The accurate diagnosis of adnexal masses is a critical challenge in gynecological practice. Current ultrasound-based models, such as the ADNEX model, IOTA Simple Rules, and O-RADS, have demonstrated good diagnostic performance but are limited by the inclusion of demographic factors and solid confounding lesions. This study aimed to develop and validate a novel ultrasound score (ECO-SCORE) for cystic and solid-cystic lesions based solely on imaging characteristics to improve diagnostic accuracy and applicability in clinical practice. Methods: We conducted a retrospective study on 330 women diagnosed with adnexal masses, including 251 benign and 79 malignant cases. Ultrasound features were analyzed using logistic regression to identify key predictors of malignancy. A new scoring model was developed, excluding demographic or tumor-marker data. Diagnostic performance metrics, including sensitivity, specificity, AUC, and odds ratios, were calculated and compared to existing models using a testing set (20% of the data). Results: The ECO-SCORE achieved an AUC of 97.08%, outperforming ADNEX model (87.5%), IOTA Simple Rules (85.7%), and O-RADS (87.5%). Sensitivity and specificity were 92.98% and 88.88%, respectively, with an odds ratio of 106. Key predictors included irregular contour, absence of acoustic shadows, vascularization within solid areas, and vascularization of papillae. Conclusions: The ECO-SCORE demonstrated superior diagnostic accuracy compared to established models, highlighting its potential as a reliable tool for assessing adnexal masses using ultrasound features exclusively. Further multicenter validation is needed to confirm its robustness across different clinical settings. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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23 pages, 2147 KiB

Open AccessArticle

Bariatric Surgery as a Molecular Modulator: The Role of FSHR Polymorphisms in Enhancing eNOS Expression and Reproductive Hormone Dynamics in Women with Severe Obesity

by Charalampos Voros, Despoina Mavrogianni, Kyriakos Bananis, Alexios Karakasis, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Raphail Mantzioros, Panagiota Kondili, Menelaos Darlas, Regina Sotiropoulou, Diamantis Athanasiou, Dimitris Mathiopoulos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis

Biomedicines 2025, 13(1), 67; https://doi.org/10.3390/biomedicines13010067 - 30 Dec 2024

Viewed by 750

Abstract

Background/Objectives: Severe obesity (BMI > 40 kg/m²) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism [...] Read more.

Background/Objectives: Severe obesity (BMI > 40 kg/m²) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism groups in women with extreme obesity. Methods: Twenty-nine women with extreme obesity had bariatric surgery. Pre- and post-surgery levels of eNOS and reproductive hormones such as follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and antral follicle count (AFC) were assessed. Patients were divided into three FSHR polymorphism groups (Ser/Ser, Asn/Asn, and Ser/Asn), and results were compared between them. Statistical techniques were used to determine changes and relationships. Results: Bariatric surgery led to substantial increases in eNOS expression across all FSHR polymorphism groups (p < 0.0001), with the Ser/Ser group exhibiting the most variability. Prior to surgery, the Ser/Ser group had substantially higher FSH levels (7.41 ± 0.60 mIU/mL) than the Asn/Asn group (5.20 ± 0.63 mIU/mL, p < 0.001). Following surgery, FSH levels rose in the Ser/Ser group (9.45 ± 0.87 mIU/mL), with significant differences between the Ser/Ser and Ser/Asn groups (mean difference = 0.97, p = 0.019). SHBG levels had a negative connection with eNOS expression after surgery (r = −0.365, p = 0.049). AMH and AFC remained constant throughout polymorphism groups. BMI decreased uniformly, with an average of 15.2 ± 1.8 kg six months after surgery. Conclusions: Bariatric surgery improves vascular health and regulates reproductive hormones, especially in individuals with the Ser/Ser genotype. These findings indicate the possibility of combining genetic testing and bariatric therapies to improve infertility treatment in obese women. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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12 pages, 1713 KiB

Open AccessArticle

Effect of High-Intensity Focused Electromagnetic Technology in the Treatment of Female Stress Urinary Incontinence

by Cheng-Yu Long, Kun-Ling Lin, Jian-Lin Yeh, Chien-Wei Feng and Zi-Xi Loo

Biomedicines 2024, 12(12), 2883; https://doi.org/10.3390/biomedicines12122883 - 18 Dec 2024

Cited by 1 | Viewed by 1905

Abstract

Background: The aim of the study was to assess the effect of high-intensity focused electromagnetic (HIFEM) technology in the treatment of female stress urinary incontinence (SUI). Materials and Methods: 20 women with SUI were delivered a treatment course with HIFEM technology. [...] Read more.

Background: The aim of the study was to assess the effect of high-intensity focused electromagnetic (HIFEM) technology in the treatment of female stress urinary incontinence (SUI). Materials and Methods: 20 women with SUI were delivered a treatment course with HIFEM technology. Patients attended 6 therapies scheduled twice a week. Validated questionnaires were assessed, including the overactive bladder symptoms score (OABSS), urogenital distress inventory-6 (UDI-6), incontinence impact questionnaire-7 (IIQ-7), international consultation on incontinence questionnaire (ICIQ), and valued living questionnaire (VLQ). Some urodynamic parameters, such as maximum flow rate (Qmax), residual urine (RU), and bladder volume at first sensation to void (Vfst). Bladder neck mobility in ultrasound topography was also collected pre- and post-treatment at 1- and 6-month follow-up visits. Results: HIFEM treatment significantly improved SUI symptoms on pad tests from 4.2 ± 5.5 to 0.6 ± 1.3 and patients’ self-assessment in the 6-month follow-up. Additionally, the data from urinary-related questionnaires, including OABSS (5.3 ± 3.9 to 3.9 ± 3.6), UDI-6 (35.7 ± 22.3 to 15.2 ± 10.6), IIQ-7 (33.1 ± 28.7 to 14.3 ± 17.2), and ICIQ (9.4 ± 5.0 to 5.4 ± 3.6), all showed a significant reduction. Then, the analysis of the urodynamic study revealed that only maximum urethral closure pressure (MUCP) (46.4 ± 25.2 to 58.1 ± 21.2) and urethral closure angle (UCA) (705.3 ± 302.3 to 990.0 ± 439.6) significantly increased after the six sessions of HIFEM treatment. The urethral and vaginal topography were performed and found that HIFEM mainly worked on pelvic floor muscles (PFM) and enhanced their function and integrity. Conclusions: The results suggest that HIFEM technology is an efficacious therapy for the treatment of SUI. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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Review

Jump to: Research, Other

15 pages, 234 KiB

Open AccessReview

Metabolomics-Driven Insights into Biomarkers for Poor Ovarian Response: A Narrative Review

by Anastasios Potiris, Sofoklis Stavros, Eleni Alyfanti, Nikolaos Machairiotis, Eirini Drakaki, Athanasios Zikopoulos, Efthalia Moustakli, Charikleia Skentou, Peter Drakakis and Ekaterini Domali

Biomedicines 2025, 13(1), 214; https://doi.org/10.3390/biomedicines13010214 - 16 Jan 2025

Cited by 1 | Viewed by 1003

Abstract

Poor ovarian response (POR) remains a significant challenge in the field of assisted reproductive technology (ART), as the quantity and quality of oocytes retrieved directly influence embryo implantation, clinical pregnancy, and live birth rates. Metabolomics has become a valuable tool for elucidating the [...] Read more.

Poor ovarian response (POR) remains a significant challenge in the field of assisted reproductive technology (ART), as the quantity and quality of oocytes retrieved directly influence embryo implantation, clinical pregnancy, and live birth rates. Metabolomics has become a valuable tool for elucidating the molecular mechanisms underlying diminished ovarian reserve (DOR) and POR. This review aims to synthesize findings from metabolomic studies examining metabolite expression patterns in serum and follicular fluid samples from women with POR. A literature search was performed using the Medline/PubMed and Scopus databases, employing keywords related to metabolomics and POR. In total, nine studies met the inclusion criteria for this review. These studies identified several metabolites with differential expression in serum and follicular fluid samples between women with normal ovarian response and those with POR. Although the metabolomic profiles varied significantly among studies, consistent alterations in prostaglandin related metabolites were observed in two of the nine studies reviewed. These findings suggest that, pending further validation, these metabolites may serve as potential biomarkers for ovarian response. Metabolomics has significantly advanced our understanding of the mechanisms underlying ovarian function and holds promise for identifying effective biomarkers that could improve the prediction and management of POR. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

14 pages, 246 KiB

Open AccessReview

Recent Advances in Vaginal Atresia: A Literature Review

by Xijuan Lin, Jia Kang and Lan Zhu

Biomedicines 2025, 13(1), 128; https://doi.org/10.3390/biomedicines13010128 - 8 Jan 2025

Cited by 1 | Viewed by 1240

Abstract

Vaginal atresia is a rare anomaly of the female reproductive tract that significantly impacts women’s reproductive health and quality of life. Although there has been relatively extensive research on the clinical manifestations and differential diagnosis of vaginal atresia, there is a paucity of [...] Read more.

Vaginal atresia is a rare anomaly of the female reproductive tract that significantly impacts women’s reproductive health and quality of life. Although there has been relatively extensive research on the clinical manifestations and differential diagnosis of vaginal atresia, there is a paucity of literature specifically addressing the genetic background, treatment protocols, and psychological status of patients with vaginal atresia, indicating a need for further investigation. In this context, this article systematically reviews the epidemiological characteristics of vaginal atresia and explores its etiology from multiple perspectives, including developmental processes, genetic factors, and environmental factors, emphasizing the importance of genetic susceptibility and environmental interactions in the pathogenesis of the condition. Building upon a summary of the clinical presentations, classification, and diagnostic methods of vaginal atresia, this article provides an overview of current treatment strategies for both partial vaginal atresia and complete vaginal atresia, discusses the psychological status of affected patients, and examines fertility outcomes and sexual function. The aim is to offer insights and recommendations for future research on vaginal atresia, ultimately striving to enhance the quality of life for affected individuals. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

Other

Jump to: Research, Review

15 pages, 492 KiB

Open AccessSystematic Review

Unveiling the Impact of COVID-19 on Ovarian Function and Premature Ovarian Insufficiency: A Systematic Review

by Charalampos Voros, Despoina Mavrogianni, Aspasia Minaoglou, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Dimitris Mathiopoulos, Panagiota Kondili, Menelaos Darlas, Agni Pantou, Sophia Sina, Antonia Athanasiou, Diamantis Athanasiou, Dimitrios Loutradis and Georgios Daskalakis

Biomedicines 2025, 13(2), 407; https://doi.org/10.3390/biomedicines13020407 - 7 Feb 2025

Viewed by 2060

Abstract

Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which [...] Read more.

Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which are enhanced by its entrance into ovarian tissues via ACE2 receptors. The purpose of this comprehensive review was to investigate the molecular pathways that link SARS-CoV-2 infection to POI and analyze their consequences for ovarian reserve and fertility. Methods: We searched databases such as PubMed, Scopus, EMBASE, and Google Scholar for papers published between 2020 and 2024. Eligible studies investigated the effects of SARS-CoV-2 on ovarian function, including the hormonal indicators anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), oocyte quality, and ovarian reserve. The data were compiled into a complete examination of molecules and clinical findings. Increased inflammatory indicators, such as interleukin-6 and NLRP3 inflammasome activation, impaired ovarian homeostasis. Anti-SARS-CoV-2 antibodies in follicular fluid could have impaired oocyte quality. Observational studies showed transitory decreases in AMH and changed FSH levels following infection, with variable effects on antral follicle count and IVF results. Changes in lipid profiles and VEGF expression emphasized the virus’s influence on ovarian angiogenesis and the ovarian microenvironment. Conclusions: SARS-CoV-2 infection impairs ovarian function by causing oxidative stress, inflammation, and hormonal disruption, thereby increasing the incidence of POI. While most alterations are temporary, the long-term reproductive consequences remain unknown. Continuous monitoring and specific treatments are required to reduce the reproductive risks associated with COVID-19. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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11 pages, 2074 KiB

Open AccessCase Report

Syphilis Infection During Pregnancy: The Possible Effect on the Course of Pregnancy and Fetal Outcomes—A Case Report and Literature Review

by Dovile Kielaite, Saule Januskiene and Virginija Paliulyte

Biomedicines 2025, 13(1), 169; https://doi.org/10.3390/biomedicines13010169 - 13 Jan 2025

Cited by 2 | Viewed by 1728

Abstract

Background/Objectives: A wide range of syphilis-related pregnancy complications are encountered in clinical practice. Active surveillance of the epidemiological situation in different countries and a series of retrospective data analyses allow for a comprehensive assessment of the feasible consequences of syphilis infection during pregnancy. [...] Read more.

Background/Objectives: A wide range of syphilis-related pregnancy complications are encountered in clinical practice. Active surveillance of the epidemiological situation in different countries and a series of retrospective data analyses allow for a comprehensive assessment of the feasible consequences of syphilis infection during pregnancy. The negative effects of infection on reproductive health are also described. Risk-increasing factors (inadequate or late treatment, partner coinfection) and protective factors (timely diagnostics and treatment) are distinguished. The importance of adequate and timely management as well as the accessibility of healthcare and socioeconomic status, which influence health outcomes, are stressed. This article presents a rare case of untreated syphilis infection during pregnancy. The infection was diagnosed during the first antenatal visit; how-ever, treatment was not initiated. At the 33rd week of gestation, the patient was admitted to the hospital because of sparse bloody vaginal discharge. Following sudden fetal hypoxia, an urgent cesarean section was performed at 33 weeks of gestation. A preterm newborn was delivered in critical condition, and congenital syphilis was diagnosed. Methods: We searched the PubMed, Cochrane, and MeSH databases using the key search terms “treponema pallidum”, “sexually transmitted infections”, “pregnancy”, “congenital infection”, “syphilis”, and “congenital syphilis”, as well as their combinations. A total of 28 papers published over a ten-year period were included in the literature review. A clinical case was analyzed. Results: The impact of syphilis on pregnancy is quite evident. Our case showcased one of the most common impacts, i.e., premature birth, of congenital infections with associated bacterial meningitis, respiratory distress syndrome, multiple organ damage, and insufficient weight. Such associations with many adverse pregnancy outcomes as well as congenital syphilis and neonatal defects are often avoidable. Conclusions: Considering the potential consequences of infections, the issue of sexually transmitted diseases remains relevant, and improving diagnostic and treatment opportunities becomes of paramount importance as cases increase. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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9 pages, 969 KiB

Open AccessCase Report

Successful Pregnancy Outcome in a Patient Treated with Pembrolizumab and Exposed to Fluoro-Deoxyglucose (¹⁸F-FDG) PET/CT: Case Report and Review of Literature

by Anna Lucia Mastricci, Felice Sorrentino, Elisa Giansiracusa, Erika Zanzarelli, Graziana Silvana De Lucia, Vincenza Fernanda Fesce, Luigi Nappi and Lorenzo Vasciaveo

Biomedicines 2025, 13(1), 140; https://doi.org/10.3390/biomedicines13010140 - 9 Jan 2025

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Abstract

Background: Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with ¹⁸F-FDG PET/CT, a diagnostic method contraindicated [...] Read more.

Background: Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with ¹⁸F-FDG PET/CT, a diagnostic method contraindicated during pregnancy. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are innovative therapies for relapsed HL (rHL) with significant efficacy. However, ICIs can impair immune tolerance, potentially increasing immune-related adverse events. The PD-1/PD-L1 pathway, targeted by pembrolizumab, plays a critical role in maternal–fetal immune adaptation, raising concerns about its safety during pregnancy. Case Report: We report the case of a 36-year-old woman diagnosed with rHL who unknowingly became pregnant during treatment with pembrolizumab and ¹⁸F-FDG PET/CT scans. The pregnancy was diagnosed at 24 weeks, after five cycles of pembrolizumab during the first two trimesters and an ¹⁸F-FDG PET/CT scan in the first trimester. Following multidisciplinary counseling, the pregnancy was closely monitored, culminating in the delivery of a healthy male infant at 37.5 weeks. Conclusions: This case highlights a favorable maternal–fetal outcome despite exposure to pembrolizumab and ¹⁸F-FDG PET/CT during pregnancy. Given the limited data on such exposures, case reports like this are essential for improving counseling and management strategies. Further research and registries are crucial to provide robust evidence for clinical decision-making in these complex scenarios. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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22 pages, 754 KiB

Open AccessSystematic Review

Nitrate–Nitrite–Nitric Oxide Pathway, Oxidative Stress, and Fertility Outcomes in Morbidly Obese Women Following Bariatric Surgery: A Systematic Review

by Charalampos Voros, Despoina Mavrogianni, Aspasia Minaoglou, Alexios Karakasis, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Raphail Mantzioros, Panagiota Kondili, Menelaos Darlas, Regina Sotiropoulou, Diamantis Athanasiou, Dimitrios Loutradis and Georgios Daskalakis

Biomedicines 2025, 13(1), 64; https://doi.org/10.3390/biomedicines13010064 - 30 Dec 2024

Viewed by 1141

Abstract

Obesity reduces nitric oxide (NO) production due to endothelial nitric oxide synthase (eNOS) dysfunction, resulting in oxidative stress, mitochondrial dysfunction, and chronic inflammation. These factors have a negative impact on reproductive health, including oocyte quality, endometrial receptivity, and embryo implantation. When oxidative stress [...] Read more.

Obesity reduces nitric oxide (NO) production due to endothelial nitric oxide synthase (eNOS) dysfunction, resulting in oxidative stress, mitochondrial dysfunction, and chronic inflammation. These factors have a negative impact on reproductive health, including oocyte quality, endometrial receptivity, and embryo implantation. When oxidative stress affects eNOS function, the nitrate–nitrite–nitric oxide (NO₃-NO₂-NO) pathway provides an alternate route for NO production. Bariatric surgery has been found to restore NO production, reduce oxidative stress, and improve fertility in morbidly obese women. This review investigates the molecular mechanisms by which bariatric surgery affects eNOS activity, the NO₃-NO₂-NO pathway, and oxidative stress reduction, with an emphasis on intracellular activities including mitochondrial biogenesis and NO production. A systematic review employing PRISMA criteria included articles published between 2000 and 2024 from PubMed, Scopus, and Embase that investigated NO₃-NO₂ pathways, oxidative stress markers, hormonal alterations, and reproductive outcomes in morbidly obese women following bariatric surgery. After evaluating 1542 studies, 11 were selected for the final analysis. Results showed a 45% increase in NO₃-NO₂ levels (p < 0.001), a 35% reduction in oxidative stress indicators (p < 0.01), a 60% increase in pregnancy rates, and a 50% increase in spontaneous ovulation rates following surgery. These benefits were connected to improved mitochondrial function and endometrial receptivity as a result of reduced oxidative stress and inflammation. The NO₃-NO₂-NO route is critical in compensating for lower NO generation under oxidative stress and hypoxia, and bariatric surgery significantly improves this pathway to optimize blood flow, mitochondrial function, and reproductive results. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology)

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