The primary purpose of this prospective cohort study was to determine if treating endometriosis with optimal excision surgery leads to lower rates of repeat surgery as compared to historical rates of repeat surgery by ablation. A secondary outcome was to examine whether the use of hormonal suppression differed before surgery, depending on the stage of endometriosis found at surgery. Optimal excision was defined as completely excising all areas of abnormal peritoneum, wherever found in the pelvis, having looked systematically with near contact laparoscopy. All surgeries were performed by a single surgeon specializing in optimal excision at a tertiary referral center. The rate of repeat surgery after optimal excision surgery for endometriosis was remarkably low (2.5%, 15/620) as compared to historical rates of repeat surgery by ablation. Additionally, the lack of significant evidence between hormonal suppression use and progression of stage of endometriosis provides implicit evidence that hormonal suppression does not prevent progression of the disease. Further controlled studies are needed to verify these findings.

There are currently no effective screening measures to detect early or occult tubo-ovarian cancers resulting in late-stage detection and high mortality. This work explores whether an optical imaging catheter can detect early-stage tubo-ovarian cancers or precursor lesions where they originate in the fallopian tubes. This device collects co-registered optical coherence tomography (OCT) and autofluorescence imaging (AFI). OCT provides three-dimensional assessment of underlying tissue structures; autofluorescence imaging provides functional contrast of endogenous fluorophores. Ex vivo fallopian tubes (n=28; n=7 cancer) are imaged; we present methods for the calculation of and analyze eleven imaging biomarkers related to fluorescence, optical attenuation, and OCT texture for their potential to detect tubo-ovarian cancers and other lesions of interest. We visualize folded plicae, vessel-like structures, tissue layering, hemosiderin deposits, and regions of fibrotic change. High grade serous ovarian carcinoma appears as reduced autofluorescence paired with homogenous OCT and reduced mean optical attenuation. Specimens containing a cancerous lesion demonstrate significant increase in median autofluorescence intensity and decrease in entropy compared specimens with no lesion. Non-cancerous specimens demonstrate an increase in optical attenuation in the fimbriae when compared to the isthmus or ampulla. We conclude that this approach shows promise and merits further investigation of diagnostic potential.

Embryo’s Implantation is a question that we are not in the position to answer in full details. We know that it depends on embryo’s quality and uterine receptivity. It is possible to access uterine cavity before in vitro fertilisation by a variety of tools, however hysteroscopy is the gold standard in evaluation of uterine cavity and potential pathology. The frequencies of unrecognised uterine pathology revealed by hysteroscopy are 18-50% and 40-43% in patients undergoing in vitro fertilisation or after recurrent implantation failure respectively. Data is inconclusive regarding the role of hysteroscopy on pregnancy outcome after in vitro fertilisation. This review aims to evaluate the validity of office hysteroscopy in subfertile population before or after IVF treatment

Harms of combustible cigarette (CC) use in pregnancy for fetal development are well-studied. Less understood is potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (EC). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n=26,394), CC (n=2,216), EC (n=493) were compared on birth outcomes, controlling for background differences. Compared to controls, the EC group had significantly lower birth weight, while CC had reduced birthweight and greater rates of arterial cord pH < 7.1. Compared to EC, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests EC are not safer alternatives to CC, and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average-risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems. The gut microbiota plays a crucial role in in metabolism regulation and immune responses through its interaction with the external environment. This article explores the intricate interplay between intestinal flora and the pathogenesis of PCOS, focusing on the pivotal role of microbial metabolites, specifically short-chain fatty acids (SCFAs). SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria alongside a notable overgrowth of opportunistic microorganisms. An overproduction of acetic acid (AA) and valeric acid (VA) in fecal samples suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (BMI), insulin resistance (IR), and chronic inflammation. This finding points to the potential therapeutic value of maintaining optimal AA levels in the blood. Although serum SCFA levels showed non-significant changes following metformin treatment, the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. This treatment also led to an increase in beneficial gut bacteria and a reduction in opportunistic pathogens, suggesting a restoration of gut microbial balance. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Background Cervical insufficiency, marked by recurrent painless cervix dilation leading to second-trimester pregnancy losses, is traditionally managed through cerclage placement and vaginal progesterone administration. However, a recent experimental approach targeted intra-amniotic inflammation or infection in a selected group of women with cervical dilation over 1 cm, intact membranes, and no uterine contractions in the second or third trimester. Case presentation We report a case of a 21 year old primigravid woman who experienced resolution of mid-trimester cervical insufficiency after the administration of triple antibiotic therapy, as confirmed by ultrasound monitoring. Remarkably, the patient successfully carried the pregnancy to term and delivered a healthy baby. Conclusions This case highlights the potential effectiveness of a novel combination of antibiotics, even in the presence of several high-risk pregnancy conditions, and underscores the possibility of a favorable outcome.

Maternal obesity has been found to be impaired oxidative status in placenta and newborn which can lead to adverse pregnancy outcomes and long-term adverse influence on metabolic programming in the offspring. This study aimed to investigate the role of maternal obesity on maternal and umbilical cord plasma oxidative status and placental oxidative adaptation. Maternal obesity (n=20) defined as pre-pregnancy BMI ≥ 25 kg/m² and maternal lean (n=20) defined as pre-pregnancy BMI < 25 kg/m² were recruited into this study. Both groups were matched by gestational age at delivery. Maternal blood, umbilical cord blood and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress marker (MDA and protein carbonyl) and antioxidant activity (SOD and catalase). Placenta protein expression (SOD2, catalase, UCP2 and Nrf2) was evaluated by western blot analysis. Catalase activity in maternal plasma significantly increased in maternal obesity group (p = 0.0200) with an increased trend in MDA and protein carbonyl levels. Umbilical cord plasma triglyceride, protein carbonyl and catalase activity significantly increased in maternal obesity compared with that in maternal lean (p = 0.0462, 0.0485, and 0.0348, respectively). Although placenta protein expression analysis exhibited significant decreased SOD2 (p = 0.0169) and catalase (p = 0.0067), accompanied by Nrf2 downregulation (p = 0.0453). An increased mitochondrial antioxidant UCP2 expressions was observed (p = 0.0143). Hence, our study provided evidence that maternal obesity is associated with placental and fetal oxidative stress with the parallel increased placental antioxidant UCP2 expression.

Background/Objectives: Douglasectomy is defined as the removal of the pelvic peritoneum of the entire pouch of Douglas. In presumed FIGO Stage I ovarian cancer isolated microscopic cancer cells might disseminate from the ovaries to their neighboring pelvic peritoneum. However, simple hysterectomy with bilateral salpingo-oophorectomy and a staging procedure is the standard of care. This study aims to investigate the safety and feasibility of douglasectomy, compared to random pelvic biopsies, and its on the survival of patients with early ovarian cancer; Methods: We retrospectively analyzed the records of patients with presumed FIGO Stage I ovarian cancer that underwent surgery in the 1st Department of Obstetrics – Gynecology Clinic from 2012 – 2022. Patient characteristics, oncological and follow-up information were collected.; Results: 88 patients were categorized into two groups: Group A (27 patients) with douglasectomy and Group B (61 patients) with random biopsies. There was no statistically significant difference in age, BMI, comorbidities, intraoperative blood loss and ICU admittance between the two groups. On the other hand, patients with en-block hysterectomy-douglasectomy had a statistically significant higher pre-operative CA-125 values, surgery duration, rate of postoperative complications and hospital stay. Concerning survival rates, there was a statistically significant difference in dis-ease-free survival (p=0.033), but no difference was observed in overall survival (p=0.66); Conclu-sions: En-block removal of the pelvic peritoneum of the entire pouch of Douglas with the uterus is a safe and feasible technique during surgery for early ovarian cancer, which leads to improved disease-free survival and local control.

Background and Objectives: The new molecular classification of endometrial cancer continuously changes the management of the disease in every day clinical practice. Lately, FIGO released a new staging system for endometrial cancer, which incorporates molecular sub-stages and subdivides further early-stage disease. The aim of this study is to investigate the differences between the two FIGO staging systems and evaluate the prognostic precision of the new one. Materials and Methods: We retrospectively analyzed the records of patients with endometrial cancer that were fully treated in the 1st Department of Obstetrics-Gynecology, 2012-2023. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcomes were the stage shifts and the survival data. Results: 67 (15.5%) patients had a stage shift and the majority of them concerned early-stage disease and specifically up-shift from 2009 stages IA and IB to 2023 stage IIC. Concerning, survival a better median and 5-year PFS was present in Stage II disease and when compering the prognostic precision of the two FIGO staging systems no significant difference was present. Conclusions: The new 2023 FIGO staging system better distinguishes early-stage endometrial cancer into its prognostic groups and seems to be as precise as the old 2009 FIGO staging system.

Ovarian torsion (OT) is a rare gynaecological emergency that requires a prompt diagnosis for optimal patient management. To determine whether there were any biomarkers suitable for the non-invasive detection of OT, two independent reviewers performed systematic searches of five literature databases following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Full-texts of 24 selected articles were assessed for risk of bias and quality assurance using a modified Newcastle-Ottawa Scale (NOS).  15 articles described studies on animals and all described serum biomarkers comparing results between OT versus a sham operation, a control group or readings before and after OT. Ischaemia modified albumin (IMA), serum D-dimer (s-DD), heat shock protein-70 (hsp-70), Pentraxin-3 (PTX-3) and c-reactive protein (CRP) showed the most promise, each with p-values for the difference between groups achieving ≤0.001. In studies of humans, the biomarkers ranged from 16.4-92.3% sensitivity and 77-100% specificity. The most promising biomarkers for the early prediction of OT in patients included s-DD, interleukin-6 (IL-6), IMA and tumour necrosis factor-alpha (TNF-. IL-6 had the highest sensitivity of any biomarker identified in this review and was raised in all 13 patients with proven OT, with values of ≥10.2pg/ml, indicative of a 16 times higher risk of having OT. Signal peptide, CUB domain and EGF like domain containing 1 (SCUBE1) had a high specificity at 93.3%, second only to s-DD and a positive likelihood ratio (LR)&gt;10. IMA was the only other biomarker that also had a positive LR&gt;10, making it a promising diagnostic biomarker. The studies identified by this systematic literature review each analysed small patient groups but IMA, DD and SCUBE1 nevertheless showed promise as serum biomarkers with a pooled LR&gt;10. However, further well-designed studies are needed to identify and evaluate individual markers, or diagnostic panels to help clinicians manage this important, organ-threatening condition.

Background/Objectives: The use of post-operative drains in gynaecologic oncology procedures is controversial with evidence both supporting and questioning their efficacy. Proponents argue that such drains help detect complications early, reduce abscess formation, and also alleviate post-operative pain. On the other hand, drains are associated with increased risks of incisional hernia, infection, prolonged hospitalization, and postoperative pain. Methods: We conducted a research in the PubMed database and supplemented it with a manual search to retrieve addition-al papers eligible for inclusion. Results: Their use is not always found to improve outcomes, no-tably in surgeries such as a radical hysterectomy with pelvic lymphadenectomy, where they may actually enhance lymphocyst formation and other complications. In cytoreductive surgery for ovarian cancer, negative pressure wound therapy showed some potential benefits, but evidence remained inconclusive due to limited studies. The international guidelines presented in this re-view, suggest avoiding the routine use of drains and promote early removal when their use is necessary. Conclusions: This review aims to present an update on the current knowledge re-garding the role of drainage in gynaecologic oncology and while further good-quality research is required, particularly in high-risk surgical procedures, numerous prospective trials have exten-sively addressed the topic, trying to provide clear suggestions.

Reproductive disorders are a common event in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies of the molecular mechanisms of implantation disorders in thin endometrium, including the study of gene transcriptional activity, have shed light on the identification of potential biological markers of endometrial receptivity. Background/Objectives: to reveal significantly dysregulated selected genes expression between RIF and RPL patients with thin endometrium. Methods: Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and RPL patients (n=19). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Total RNA was purified, reverse-transcribed; gene expression was quantified by RT-PCR. Results: The expression of the IL-15, INFG and HPRT1 genes were significantly decreased in RIF with thin endometrium patients compared to the RPL patients (log2 fold change=0.92, p=0.023 for IL-15, log2 fold change=1.24, p=0.046 for INFG, and log2 fold change=0.579, p=0.046 for HPRT1). There were not significant differences in expression of CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB and HAND2 genes between groups. Conclusions: decreased expression of IL-15, INFG and HPRT1 genes was found in patients with RIF with thin endometrium compared to the endometrium of women with RPL. This has practical significance for clinicians for differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review existing literature, and elucidate its clinicopathological characteristics, including potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 516 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLA. Results: Among the 516 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52-76 years old, and the initial FIGO stages were IC1 (2 cases) and IIIB (1 case). All cases exhibited HRP, pMMR, PD-L1 negativity (CPS&lt;1), and HER2-low expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. MLA frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLA accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. Literature also reports a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Nowadays recurrent implantation failure (RIF) after invitro fertilization is common problem that reproductive specialists usually faced. The phenomenon of thin endometrium in RIF patients has yet not completely understood and properly treated. This study aimed to reveal significantly dysregulated selected genes expression between RIF patients with thin endometrium and fertile women. Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and fertile women (n=14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Endometrial gene expression levels showed differences in RIF samples compared to fertile samples. The significant downregulation was observed for CXCL1 (p=0.005) and C4BPA (p=0.03) genes. There was no statistically significant difference between the RIF groups and the fertile group in the expression of 8 genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL15 and TNC (p&gt;0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for good discrimination of RIF patients from fertile women (AUC 0.806).

Background and Objectives: Proteomics encompasses the exploration of protein composition, regulation, function, and pathways. Its influence spans diverse clinical fields and holds promise in addressing various women’s health conditions, including cancers, osteoporosis, and cardiovascular disorders. However, no comprehensive summary of proteomics and menopausal health exists. Our objective was to summarize proteomic profiles associated with diseases and disorders in peri and postmenopausal women. Materials and Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, Cochrane database, Elsevier, and ScienceDirect until 2022. A total of 253 studies were identified, 41 studies met the inclusion criteria to identify data of interest. These included study design, disease, and proteomics/proteins of significance as described by the authors. Results: The 41 studies, covered diverse areas including bone disorders (10 studies), cardiovascular diseases (5 studies), oncological malignancies (10 studies), and conditions such as obesity, nonalcoholic liver disease, the effects of hormone replacement therapy, and neurological diseases (16 studies). Results of our study indicate that proteomic profiles correlate with heart disease in peri- and postmenopausal women, with distinct sex differences. Furthermore, proteomic profiles significantly differed between women with and without osteoporosis. Additionally, patients with breast, ovarian, and endometrial cancer exhibited notable variations in proteomic profiles compared to those without these conditions. Conclusions: Proteomics has the potential to enhance risk assessment and disease monitoring in peri- and postmenopausal women. By analyzing unique protein profiles, clinicians can identify individuals with heightened susceptibility to specific diseases or those already affected by established conditions. This review suggests that there is sufficient preliminary data for proteomics in peri- and postmenopausal women for early identification of cardiovascular disease, osteoporosis, and cancers, in disease monitoring, and in tailoring individualized therapies. Rigorous validation studies involving large populations are essential before drawing definitive conclusions regarding the clinical applicability of proteomic findings.

Background and Objective: Although possible risk factors associated with maternal postpartum depression (PPD) have been elucidated, it is still unknown how some newborns characteristics could influence the appearance of PPD. Our research aimed to unravel the impact of newborn’s characteristics on PPD. Methods: The study was conducted in the Obstetrics &amp; Gynecology Department, from our University Emergency County Hospital, between August 2019 and April 2021. We included women in the 2 nd day of the postpartum period (n=904), divided into 2 groups: women with PPD (n=236) and control (women without PPD, n=668), by using the Edinburg Postpartum Depression Scale. Characteristic information on newborns (i.e., the months in which they were born, premature delivery, birth weight, or gender) were assessed. Results: Our findings suggest that the winter season (i.e. December and January, p=0.01) births and male newborns (p=0.02) were associated with the appearance of depressive symptoms during postpartum. Conclusions: Therefore, our study showed that women who give birth to male newborns in winter are likely to develop PPD. This should be considered by all public health systems in order to prevent such manifestations in certain groups of women.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Electronic cigarette (ecig) use in pregnancy is common, but potential effects on fetal development are largely unknown. The study goal was to examine the association between ecig exposure and fetal growth. Data were extracted from medical charts in this single site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used ecigs throughout pregnancy and non-ecig user controls. Fetal size measurements from second and third trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for ecig exposed compared to controls. By the third trimester, femur length difference was 28.5 points, with fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal ecig exposure, becoming larger and impacting more parameters with increasing gestation. While additional study is warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following ecig exposure in pregnancy, and suggests that ecigs may not be a “safer” alternative to combustible cigarette smoking in pregnancy.

Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with Strelka2 and GATK4 with Mutect2. Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, CHIT1, CEP170, and CTR9, recurrently altered in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. These observations suggest that IGM may be influenced by non-genetic factors, such as environmental triggers or immune system dysregulation, rather than being primarily a genetic disorder.

Detailed sonographic assessment of the fetal neuroanatomy plays a crucial role in prenatal diagnosis, providing valuable insights into timely well-coordinated fetal brain development and detecting even subtle anomalies that may impact neurodevelopmental outcomes. With recent advancements in artificial intelligence (AI) in general and medical imaging in particular, there has been growing interest in leveraging AI techniques to enhance the accuracy, efficiency, and clinical utility of fetal neurosonography. The paramount objective of this scoping review is to discuss the latest developments in AI applications in this field, focusing on image analysis, automation of measurements, prediction models for neurodevelopmental outcomes, visualization techniques, and integration into clinical routine.

Aim: Ovarian cancer is the leading cause of gynecological cancer deaths worldwide. Treatment methods are listed as surgery, chemotherapy and radiotherapy depending on the stage of the cancer, but developing resistance to chemotherapy increases the need for alternative agents that act on the same pathways. In this study, the effects of rosmarinic acid (RA) and doxorubicin (DX) on the activation of FOXP3, an important tumor suppressor gene, in OVCAR3 cells were examined. Material Method: In the study, human ovarian adenocarcinoma cell line was used. MTT test was applied to determine the effect of rosmarinic acid and doxorubicin on the proliferation of OVCAR3 cells. Expression levels of FOXP3 for cell proliferation and Capase-3 for Apoptosis were determined by qRT-PCR and Western blot analysis. Wound healing model was applied to determine metastasis. The results were evaluated with one-way ANOVA in SPSS 20.0 program as p≤0.05. Results: It was determined that rosmarinic acid alone and in combination with doxorubicin inhibited the proliferation of OVCAR3 cells in a time- and dose-dependent manner for 24, 48 and 72 hours, and caused the cells to die by causing them to undergo apoptosis. It was observed that Caspase-3 expression increased approximately tenfold in OVCAR3 cells, while FOXP3 expression increased only in RA treatment and was downregulated in DX and RA+DX treatments. Coclusion According to the results of our study, it was observed that many steps of the signaling pathways related to proliferation, migration and apoptosis were affected by the combination of RA and DX in OVCAR3 cells. This shows that RA will gain an important place in cancer treatment with more comprehensive studies.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels <2.5 mU/L and normal free T₄ levels. The patients were divided into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were placed in group A, 34 in group B, and 35 in group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

Aim: In our study, the chemotherapeutic drug doxorubicin (Dox) and the natural anticancer property thymoquinone (TQ) were applied to OVCAR3 human ovarian adenocarcinoma cells and human skin keratinocyte cell line HaCat cells, and their cytotoxic effects were investigated through the EGFR/FOXP3 signaling pathway. Materials and Methods: In our study, different doses of thymoquinone and doxorubicin were applied to the cells for 24, 48 and 72 hours and the cytotoxicity level was determined by the MTT method. With Western blot and qRT-PCR analysis, metastasis markers Epidermal growth factor receptor (EGFR) and forkhead box p3 (FOXP3) and apoptosis marker apoptosis inbibitory 5 (API5) genes and their expression levels were examined. Colony counting was performed after DAPI staining and its effect on cell proliferation was determined. An in vitro wound model for metastasis was created and cell migration was evaluated morphologically. All results were analyzed statistically. Results: By the cell viavility test, it was found that cytotoxicity was at the highest level in the TQ and Dox applied group, metastasis was prevented especially in the TQ and Dox combined treatment group, and by qRT-PCR analysis, the activity in the EGFR and FOXP3 pathway decreased the most with TQ and the amount of protein decreased with TQ and Dox. Conclusion: As a result of the study, it was seen that the highest cytotoxic effect and the highest apoptosis induction occurred with TQ treatment. Additionally, it was determined that a significant decrease in EGFR and FOXP3 levels occurred in TQ and Dox applications.

Aim: Ovarian cancer is one of the most frequently diagnosed cancers in women in the world. Recognition of the differences between tumors in cancers and resistance to treatment in patients have made the treatment potential of chemotherapy, radiotherapy and immunotherapy controversial. Especially against drug resistance, laboratories have implemented the drug diversion system by putting old drugs into new forms. In this study, the cytotoxic and apoptotic effects of the combination of doxorubicin (DX) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3) were investigated. Material Method: OVCAR3 cell line was cultured in RPMI medium containing 10% FBS, 1% penicillin/streptomycin. Cell viability and cell growth rate were determined by MTT viability test by combining doxorubicin and thymoquinone. Nucblue immunofluorescent staining was used to determine the mechanism of cell death at different doses of doxorubicin and thymoquinone compounds, qRT-PCR to determine the pathways underlying the apoptotic mechanism, and western blot methods to show protein levels. Result: We found that the combination of DX and TQ reduced the viability of OVCAR3 cells (MTT assay), induced apoptosis (RAF, RAS, Bcl2, Bax by qRT-PCR) and increased RAF, RAS protein levels in TQ and DX-treated cells by western blot analysis. Conclusion: The results obtained revealed for the first time that combining DX and TQ also had cytotoxic/apoptotic and anti-proliferative effects against ovarian adenocarcinoma cells.

Background Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality globally, necessitating focused attention from midwifery professionals. To mitigate severe complications and improve maternal outcomes, regular and effective training in PPH rescue techniques is essential. Aim To assess the efficacy of the combination of case-based learning (CBL) and problem-based learning (PBL) with simulation teaching methods to enhance the technical proficiency of midwifery trainees in managing PPH Methods This quasi-experimental study included 76 trainees who received PPH training at Peking University Third Hospital from March to July 2023; they were divided into two groups: the control group (n = 50), which followed traditional simulation training methods, and the research group (n = 26), which used a combination of CBL-PBL and scenario simulation. After training, all participants completed a questionnaire to evaluate their satisfaction with the training program and to measure improvements in clinical thinking, practical skills, relevant knowledge, team cooperation, and management abilities. Statistical analysis was conducted using unpaired t-tests and chi-square tests to compare the groups. Findings The combination of CBL-PBL with scenario simulation was found to be highly satisfactory compared with the traditional simulation training. This approach significantly enhanced self-assessed skills among midwifery trainees in the research group. Additionally, a majority of trainees expressed a preference for the inclusion of regular simulation exercises and detailed discussions on PPH cases in future training sessions. Conclusion Combining CBL-PBL with simulation practice is a more effective teaching method for PPH management training than traditional methods. Future studies should explore the implementation of regular PPH rescue skill training and its effectiveness in real clinical settings to substantiate these findings.

Oxytocin is recommended as the first-line choice for labor induction in term pregnant women with premature rupture of membranes (PROM); however, it can occasionally lead to failed induction and delivery complications. The primary objective of this study was to compare delivery information and outcomes following the administration of oxytocin infusion or oral low-dose misoprostol solution for labor induction in term PROM women with an unfavorable cervical condition. Methods: A prospective nested case-control study was conducted at a tertiary general hospital in China from March 2020 to February 2024, comparing oxytocin infusion and oral administration of 25ug misoprostol every 2 hours for labor induction in term PROM women with a Bishop score <6. A total of 449 mothers were included, with 282 in the oxytocin group and 167 in the misoprostol group. Results: The rates of vaginal delivery and failed induction were similar between the two groups. The duration of total labor time was shorter in the misoprostol group. There were no significant differences observed regarding the incidence of uterine hyperstimulation, fetal stress, or suspected intrauterine infection between the two groups; however, there was a markedly higher incidence of postpartum hemorrhage (PPH) and severe PPH but lower postpartum urinary retention (PPUR) observed in the oxytocin group. Logistic regression analysis revealed that misoprostol administration demonstrated a negative relationship (aOR: 0.46; 95% CI: 0.21-0 .95) with failed labor induction outcomes, while IVF-ET showed a positive association (aOR:3.12; 95% CI:1.49-6.43). Furthermore, there was a negative correlation identified between misoprostol administration and occurrence of PPH (aOR: 0.49; 95% CI: 0.27-0.85). Conclusions: Oral low-dose misoprostol has demonstrated both safe and superior efficacy to oxytocin infusion for labor induction and may potentially reduce the incidence of failed induction and associated with a decreased risk of PPH were observed in the misoprostol group in term PROM pregnant women with unfavorable cervical condition.

The goal of the study is to assess the potential correlation between maternal Sars-cov-2 infection , detected three months before the second trimester anomaly scan, and fetal iperecogenicity in order to determine whether or not this could be considered a predictive factor for maternal-fetal complications . The study included 48 pregnant women who did not have any clear maternal or fetal problems. These individuals had an anomaly scan in the second trimester, as well as amniocentesis and fetal cariotyping, and then RT-PCR testing on their placental tissue after birth to rule out transplacental transmission. There have been no reports of fetal abnormalities via amniocentesis or fetal cariotyping. The patients experienced a high rate of spontaneous births (83%). Fetal development problems (2%) and premature delivery (4%) were uncommon, although placental swabs revealed a possibility of viral transmission across the placenta itself. To the best of our knowledge, this is the first observational study to show that detecting isolated intestinal hyperechogenicity during an abnormality scan in fetuses of women infected with Sars-Cov-2 in the previous three months does not appear to be a predictor of poor maternal-fetal outcomes, but may be linked to transplacental virus transmission.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

Pregnancy planning and genetic testing (PPGT) has emerged as a tool in reproductive healthcare, offering parents-to-be insight in their risks of having a child with a genetic disorder. This paper reviews the advantages, drawbacks and challenges associated with PPGT, providing some practical guidance for health care professionals. Advantages include identification of genetic risks, a possibility to informed reproductive decision-making, and the potential to reduce the parents-to-be risk for an affected child. Challenges and drawbacks include provision of service, ethical considerations, genetic counselling complexities, and the need to increase public and professional awareness by comprehensive education and accessibility. Practical guidance involves considerations for selecting appropriate candidates, counselling strategies, and how to integrate PPGT into existing healthcare frameworks. By addressing these factors, PPGT can offer an increased reproductive informed choice for the individual and the couple reducing the burden of disease in the family.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment, and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines, and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with the practical expertise in the oncological field. The article also includes two emblematic clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements of tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity.

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-age women. Women with PCOS are at higher risk of pregnancy complications including gestational diabetes (GDM). The prevalence of PCOS and GDM varies according to the diagnostic criteria used. The mechanism for the occurrence of GDM in women with PCOS is still unclear. Materials &amp; Methods- A systematic search of the electronic database was done using keywords like PCOS, and GDM to include studies between April 2008 and March 2023 where uniform diagnostic criteria were used. Studies were excluded with high-risk of bias after the assessment of bias, and meta-analysis was done with relative risks and confidence intervals. Results &amp; Discussion-Out of 1896 search results, 95 were selected for full-text. The quality of the studies was scrutinized and a total of 28 studies were included as they fulfilled the inclusion criteria. The incidence of GDM in women with PCOS was found to be 10.55 % (2.9- 54.9%) from pooled data involving 1,280,245. The prevalence of PCOS in women diagnosed with GDM was found from pooled data of 36,351 women in retrospective studies to be 2.47% (1.5- 50.1%). Selection predominantly included cohort studies, most commonly from China. The meta-analysis reported the risk of GDM is higher in women with PCOS than in those without PCOS (HR: 1.59, 95% CI: 1.27–1.91, p &lt; 0.001). Family history of diabetes, ethnicity, pre-pregnancy BMI, insulin resistance, gestational weight gain, use of assisted reproductive techniques, and multifetal gestation were the risk factors for GDM in women with PCOS. Conclusion- The prevalence of GDM in patients with PCOS is high, but the causality is complex. The newer predictive models are promising in clarifying the causative relationships, yet use various parameters at different cut-offs. There is a need for the development of universally acceptable parameters for the early prediction of GDM in women with PCOS.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence, but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here we review the scientific evidence showing how the menstrual cycle meets these criteria and should therefore be treated as a vital sign. Using key words and controlled vocabulary terms, we carried out multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, can cyclically impact health conditions, and its associations with long-term post-menopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplementary materials include patient handouts on menstrual cycle tracking, and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.

Low fertility is a critical social problem worldwide, and infertility has a prevalence of 15%. This cross-sectional study aimed to understand the factors affecting the usage and satisfaction of Korean medicine (KM) in subfertile women. An online survey was conducted from November 3 to November 8, 2021. The survey collected basic information, KM treatment experience, and satisfaction from women who experienced poor pregnancy. The t-test and chi-square test (χ2-test) were used to determine the overall characteristics of the subjects and factors affecting the utilization and satisfaction of KM treatment. Of the total of 29,465 people, 4,922 read the survey email, and 601 responded. After excluding 51 insincere respondents, 550 respondents were included in the final analysis. Of these, 43.1% had experience with conventional treatment, and 15.6% had received KM treatment. Integrative subfertility treatment was significantly more common (24.9%) than KM treatment alone (10.2%) (P=0.00). Women with no childbirth experience (P=0.01) and those with a master’s degree (P=0.01) were more willing to participate in the ‘KM Support Project for Subfertility’. Our findings suggest that subfertile patients prefer integrated medical treatment over KM alone. Further studies are needed to assess the status of integrative medicine treatment, satisfaction with each KM intervention, factors for low satisfaction, and patient requirements.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 65 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2, and altered expression of growth factor receptors and microRNAs. These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

(1) Background: Acute myocardial infarction in pregnancy (pAMI) is a rare event, often caused by non-classical factors rather than atherosclerosis. The management of such a complicationrequires a multidisciplinary team and it is important to bring together the specialities involved to ensure that these teams are coordinated and ready to respond. The management of pAMI poses unique challenges as it requires considering both maternal and fetal well-being. (2) Methods: We present the case of a 36-week pregnant woman who presented with antero-lateral ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock. To ensure comprehensive decision-making, an emergency Pregnancy Heart Team meeting was convened, comprising interventional cardi-ologists, gynecologists, and anesthesiologists. The team prioritized interventional treatment for pAMI, according to ESC guidelines, and opted for primary percutaneous coronary intervention (PCI) due to the unstable maternal condition.; (3) Results: The patient underwent primary PCI as the chosen intervention for pAMI. A rapid response gynecology team closely monitored the procedure and was prepared to intervene in case of irreversible hemodynamic compromise leading to cardiac arrest. An emergency caesarean section was deemed necessary if cardiac ac-tivity was not restored within 4 minutes.; (4) Conclusions: Managing pAMI requires a multidis-ciplinary approach that balances the maternal and fetal well-being. In this particular case, the Pregnancy Heart Team decided to prioritize interventional treatment with primary PCI due to the unstable maternal condition. The presence of a closely monitored gynecology team ensured prompt action in case of complications.

Third and fourth-degree anal sphincter injuries are among the most severe traumas women can experience during childbirth, often leading to lifelong continence issues. Despite extensive research, current repair techniques are often inadequate, failing to provide long-term solutions. Women with previous severe injuries face a higher risk of recurrence in subsequent deliveries, making caesarean sections a safer option in many cases. The existing WHO classification system is outdated, as it doesn't account for injuries to muscles like the levator ani, which are crucial for continence. Effective repairs require skilled surgeons and often involve more than just fixing the sphincter. Smaller hospitals may not have the necessary expertise and resources for these complex repairs. Delaying repairs to allow specialists to perform them can be just as effective as immediate repairs. Comprehensive care that includes thorough anatomical knowledge and surgical skill is essential. As maternal age increases and birth rates decline, it's crucial for specialized centers to handle severe perineal injuries to ensure the best outcomes and long-term care for patients.

Minimal/mild endometriosis (MME) is independently associated with reduced fecundity rates. In this review article, we discuss the role of laparoscopic surgery in enhancing fertility outcomes of patients with MME. Laparoscopic management of MME enhances fecundity and increases chances of spontaneous conception in appropriately selected cases. However, laparoscopy cannot be routinely recommended in asymptomatic patients with the sole purpose of diagnosing and treating potentially present MME. Equally, based on existing evidence, laparoscopic management of MME cannot be routinely recommended prior to in-vitro fertilisation (IVF) attempts, as robust evidence of benefit is lacking. As an overlap between unexplained infertility and MME cases likely exists, the development of reliable, widely available, non-invasive tests for the diagnosis of MME may revolutionize the management of cases currently classified as unexplained infertility. In a disease as diverse as endometriosis, management decisions should be based on a multitude of factors. Future studies should focus on reporting outcomes of interventions for MME on fertility and obstetric outcomes, clearly differentiating between disease stages and phenotypes.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

Introduction: In Part I of this three-part series we report a retrospective, population-based cohort study assessing rates of adverse events (AEs) in pregnancy after COVID-19 vaccines compared to the same AEs after influenza vaccines and after all other vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and prevention (CDC) and the U.S. Food and Drug Administration (FDA). The CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024, for adverse events (AEs) involving pregnancy complications following COVID-19 vaccination. The time-period included 412 months for all vaccines except COVID-19 vaccines, having been used for only 40 of the 412 months (December 1, 2020, to April 26, 2024). Proportional reporting ratios (PRR) by time compared AEs after COVID-19 vaccination to those after influenza vaccination, and after all other vaccine products administered to pregnant women. In cases in which the PRR was not applicable, Chi-square analysis and Fisher’s exact tests were used according to CDC/FDA guidance. CDC/FDA stipulate a safety concern if a PRR is ≥ 2 or if a Chi-square is ≥ 4. Results: The CDC/FDA’s safety signals were breached for all 37 AEs following COVID-19 vaccination in pregnancy: miscarriage, fetal chromosomal abnormality, fetal malformation, cervical insufficiency, premature rupture of membranes, premature labor, premature delivery, placental calcification, placental infarction, placental thrombosis, placenta accreta, placental abruption, placental insufficiency, placental disorder, fetal maternal hemorrhage, fetal growth restriction, reduced amniotic fluid volume, preeclampsia, fetal heart rate abnormality, fetal cardiac disorder, fetal vascular mal-perfusion, fetal arrhythmia, fetal distress, fetal biophysical profile abnormal, hemorrhage in pregnancy, fetal cardiac arrest, fetal death (stillbirth), premature infant death, neonatal asphyxia, neonatal dyspnea, neonatal infection, neonatal hemorrhage, insufficient breast milk, neonatal pneumonia, neonatal respiratory distress, neonatal respiratory distress syndrome, and neonatal seizure. All p values were ≤ 0.001 with the majority being <0.000001. Summary statistics for the deviation from the CDC/FDA safety signals mean (n, range) are as follows: PRR 69.3 (46, 5.37 - 499); z statistic 9.64 (46, 3.29 - 27.0); and Chi-square was 74.7 (26, 28.9 - 148). Conclusions: We found unacceptably high breaches in safety signals for 37 AEs after COVID-19 vaccination in pregnant women. An immediate global moratorium on COVID-19 vaccination during pregnancy is warranted. The United States government, medical organizations, hospitals, and pharmaceutical companies have misled and/or deceived the public regarding the safety of COVID-19 vaccination in pregnancy. Promotion of these products must be immediately halted.

Objectives: To assess the concordance of the preoperative application of the #Enzian classification (#ENZIANi) with the postoperative result (#ENZIANs) using surgical findings as the reference standard. Methods: This retrospective study included 282 consecutive patients with deep endometriosis undergoing surgical treatment. Preoperative assessment with transvaginal sonography and magnetic resonance imaging was compared with postoperative assessment. Concordance and diagnostic test evaluation were calculated. Results: The highest concordance was observed in the F (abdominal wall endometriosis) with k Cohen of 0.837, following the values for pelvic locations, with 0.795 for T left, 0.791 for T right, 0.776 for F (adenomyosis), 0.766 for C (rectum), and 0.75 and 0.72 for O right k and O left, respectively. The highest sensitivity was demonstrated for the P compartment *(98%), T compartment (both sides 97%), and A, B, C (94%- 96%), corresponding with deep endometriosis. Conclusions: Preoperative assessment using TVS/TAS+MRI with the ENZIANi score correlates well with the ENZIANs postoperative score and demonstrates good concordance in the detection and localization of deep endometriosis, thereby minimizing false negative results and ensuring accurate preoperative staging. The ENZIAN classification is well-suited to surgeons&#39; needs and benefits from continuous development. Future improvements, such as adding the expanded C module, may be considered in the next edition.

The Mediterranean Diet, characterized by high intake of plant foods and unsaturated fats, has been suggested to improve assisted reproductive technology (ART) outcomes. This literature review aimed to summarize the evidence from observational studies on the associations between preconception Mediterranean Diet and ART outcomes. PubMed/MEDLINE, Embase, ScienceDirect, and Google Scholar databases were searched to identify relevant studies. Seven observational studies (n=2,321 women on ART) were included. Adherence to the Mediterranean Diet was assessed by food frequency questionnaires with 6-195 items. Three studies found that higher Mediterranean Diet scores improved Clinical Pregnancy or Live Birth rates, while two studies showed a positive effect on ART eggs and embryos. However, two studies reported no significant associations with ultimate ART success, and four studies found no effects on oocyte and embryo number or quality. Evidence for the effects of greater adherence to the Mediterranean Diet on ART outcomes is limited but promising. Additional rigorous research is needed to clarify and weigh the degree of association between the Mediterranean Diet and ART success.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p&lt;0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Pregnancy-related morbidity and mortality remains high across the United States and the majority of deaths are preventable. Misdiagnosis and delay in diagnosis are thought to be contributors to preventable harm. These diagnostic errors in obstetrics are understudied. We present selected research methods to ascertain rates of and harm associated with diagnostic errors, the challenges in investigating them, and present future steps toward achieving diagnostic excellence in obstetrics.

Conclusions: The quantitative method provides a large-scale overview of the biometry measurements of an entire practice. Image audits can then be focused on sonographers whose measurements are outliers, avoiding the time, complexity, and expense of auditing those whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative review.

Abstract: (1) Background: to find out how COVID-19 infection during pregnancy affects the outcome of the pregnancy; (2) Methods: 166 SARS-CoV-2-positive pregnant women formed the study group. 128 SARS-CoV-2-negative pregnant women formed the control group. Anatomopathological study of the placenta was performed in all cases; (3) Results: Placental insufficiency appeared in 38 patients (22.9%) of the study group and in 17 patients (13.2%) in the control group (p=0.016). Villitis appeared in 50 patients (30.1%) of the study group and in 16 (12.6%) in the control group (p=0.000). 166 COVID-19 positive patients were further subdivided, into those with anatomopathological affection of the placenta, and those without. When gestational age between patients with placental insufficiency and those without it are compared, a difference of 4.38 days is obtained (p=0.0393). If we compare neonatal weight between patients with placental insufficiency and those without it, a difference of 406.4 grams is obtained (p=0.0000). When gestational age between patients with villitis and those with-out it are compared, a difference of 3.2 days is found (p=0.0919). When neonatal weight between patients with villitis and those without it are compared, a difference of 242.2 grams is obtained (p=0.0018). (4) Conclusions: COVID-19 infection during pregnancy may produce lower fetal weight and shorter gestational length.

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process disrupted in preeclampsia, characterized by elevated vascular resistance, re-duced utero-placental blood flow and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries isolated from both pregnant and non-pregnant women were precontracted with the thromboxane analogue U46619, and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated using specific inhibitors for ni-tric oxide synthase (L-NAME+LNNA at 10-4 M) and guanylate cyclase (ODQ at 10-5 M). Results showed PP13 induced vasodilation in uterine arteries but not in subcutaneous arteries. Ad-ditionally, PP13 counteract U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on activa-tion of the Nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine ar-teries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest PP13 may be a promising candidate for improving utero-placental blood flow in condi-tions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia.

Understanding and preventing the “great obstetrical syndromes” has been the focus of pregnancy research for decades. The combined global impact from these syndromes on maternal and perinatal morbidity and mortality is compounded by increased long-term risk of adverse health effects following pregnancy. Accumulating evidence indicates that conditions such as pre-eclampsia, fetal growth restriction, spontaneous preterm labour, and stillbirth, are syndromes with etiologic heterogeneity that share common pathophysiologic pathways involving placental dysfunction. Recently, the importance of the interaction between fetal and maternal genomes has been extended to include the epigenetic impact of pre-existing maternal pathophysiology on placental development and highlights the importance of nutritional and environmental factors in altered placentation. Validated first-trimester screening algorithms for preeclampsia can identify high-risk women and prophylactic treatment with low-dose aspirin can be initiated. High-risk women can be monitored during the second trimester using clinical assessment, ultrasound, and biochemical markers, that are able to predict complications prior to the development of clinical signs and symptoms. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care. This approach has the potential to significantly reduce pregnancy complications, maternal and perinatal morbidity and mortality, adverse health outcomes later in life, and health-care costs.

Tertiary lymphoid structures (TLSs) have become the focus of antitumor immunity. However, the prognostic significance of TLSs in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unelucidated. This retrospective study examined the prognostic value of TLSs in tumor tissues obtained during PDS and IDS. Pathological specimens were collected from patients with EOC who underwent PDS or IDS between 2017 and 2020 at the National Cancer Center Hospital East. The correlation of tumor-infiltrating lymphocyte frequency, TLS presence, and PD-L1 expression with progression-free survival (PFS) and overall survival (OS) and the correlation between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS in patients who underwent PDS but not in patients who underwent IDS. No correlation was identified between TLS and PFS in patients with PDS or with IDS. However, TLS was positively correlated with PD-L1 positivity. The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive correlation between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

BackgroundIntracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasound (US) and MRI. Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of two cases of prenatal ICH.Cases presentationThe first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530g.ConclusionFetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

Postpartum haemorrhage remains a significant contributor to maternal mortality and morbidity worldwide, particularly in low- and middle-income countries. PPH continues to pose challenges in both developed and developing nations despite being preventable. This review examines the current state of knowledge regarding PPH within the context of Vietnam, a country with its unique healthcare landscape. This review identifies critical areas for improvement and future research directions based on a comprehensive literature analysis, including epidemiological insights, risk factors, prevention strategies, and management approaches. Discrepancies in PPH definitions and prevalence rates across regions highlight the need for tailored interventions and policies. Understanding the specific challenges and opportunities related to PPH in Vietnam is crucial for informing evidence-based interventions and policies to improve maternal health outcomes. This review contributes to the broader global effort to reduce maternal mortality by addressing gaps in knowledge and proposing strategies to enhance PPH prevention and management in Vietnam.

Background/Objectives Bowel endometriosis (BE) is defined as the presence of endometrial-like tissue in the muscular layer of the bowel wall. When BE does not cause severe obstruction to fecal transit, not leading to (sub)occlusive symptoms, the decision to operate becomes challenging as intestinal surgery is associated with higher complication rates and long-term bowel dysfunction. The aim of this cross-sectional study is to evaluate the quality of life (QoL) in patients with BE undergoing medical therapy or expectant management, investigating the impact of characteristics of BE nodules on QoL and intestinal function. Methods A retrospective cross-sectional analysis was conducted on 580 patients with BE who did not undergo surgery but were treated conservatively by medical therapy or expectant management between January 2017 and August 2022. The diagnosis of BE was done by transvaginal ultrasound and confirmed at double contrast barium enema. After at least one year of follow-up, QoL and intestinal function of patients were evaluated by the Endometriosis Health Profile-5 (EHP-5) questionnaire and Bowel Endometriosis Symptom score (BENS), whereas pain symptoms were assessed by the Visual Analogic Scale (VAS 0-10). Statistical analysis was performed to investigate possible associations between QoL and characteristics of bowel nodules (dimension, location, and evidence of stenosis) as well as type and length of eventual medical therapy. Results Patients with BE had a satisfying overall QoL with a mean EHP-5 score of 105.42 ± 99.98 points and VAS lower than 3 for all pain domains; additionally, they did not show a significant impartment of bowel function with mean BENS score of 4.89 ± 5.28 points. Notably, patients under medical therapy had a better QoL than patients without therapy (p

This review article delves into the multifaceted nature of primary ovarian insufficiency (POI), a condition marked by diminished ovarian function before age 40, underscoring the complexity of its aetiology encompassing genetic, autoimmune, infectious, and environmental factors. A significant focus is placed on the potential role of single-gene mutations, such as those in FMR1, BMP15, and GDF9, in the pathogenesis of POI, highlighting the intricate interplay between genetics and ovarian health. The article also explores innovative therapeutic avenues, including the activation of dormant follicles in vitro, offering hope for fertility restoration in affected individuals. Despite the prevalence of traditional treatments, such as Chinese medicine and hormone therapy, in China, these approaches often need to meet therapeutic needs, underscoring the urgency for advanced research and tailored treatment strategies. The discovery of a pituitary tumour-associated POI case further complicates the diagnostic landscape, suggesting a broader diagnostic lens and more in-depth research to unravel the complex underpinnings of POI and enhance patient care.

Previous studies show that women with a history of high-grade CIN have a greater risk of subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue and they show mixed results. This study aimed to investigate the incidence of high-grade or worse VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease, illustrate treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent laparoscopic hysterectomy for high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and diagnosis of high-grade VaIN was 18 months. Results: High grade or worse VaIN was found in 8 patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized for CIN3 showed an 8-fold greater risk than women hysterectomized for benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized for benign disease. The risk of developing VaIN is greater in women with viral persistence Conclusion. All these elements suggest that it is the history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered a risk factor for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of HR-HPV infection in female population has led to the discovery of several cases of double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate high risk (HR) HPV infections in women with double cervix within the National Cervical Cancer Screening program of the Lazio Region (Italy). From June 2021 to March 2024 a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervixes and analyzed separately. Twenty-seven women with double cervix were identified (0.019%): 20 women were tested as negative for both cervices, while the remaining four (namely A, B, C and D) resulted positive. By genotyping, the following results were obtained: A) both samples showed genotype 31; B) one cervix was negative while the other showed genotype 58. C) one cervix was positive for HPV 18 and 31 while for 18, 31 and 33 in the other. D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition, where the presence HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

Adenomyosis, a benign gynecological condition characterized by the infiltration of endometrial tissue into the myometrium, poses significant challenges to women's reproductive health. Recently, the landscape of adenomyosis diagnosis transformed significantly, thanks to advancements in imaging technologies such as transvaginal ultrasound and magnetic resonance imaging. This lead to a noticeable shift in the demographic profile of patients diagnosed with adenomyosis, including younger women of reproductive age who frequently present with a diverse array of symptoms. Approximately 20% of women are affected by adenomyosis. Adenomyosis manifests with various subtypes, distinct epidemiological profiles, symptomatology, and treatment responses, necessitating tailored approaches for optimal management. Despite its clinical significance, adenomyosis remains understudied, resulting in a significant disparity in research and literature compared to other gynecological conditions. The severity of adenomyosis is compounded when coexisting with endometriosis, particularly deep infiltrating endometriosis (DIE), leading to exacerbated fertility issues and severe symptomatology. The wide range of symptoms, including adverse pregnancy outcomes such as pre-eclampsia, highlights its wider impact and emphasizes the need for increased awareness of the condition. Furthermore, Adenomyosis is frequently associated with treatment failure in endometriosis, contributing to dienogest resistance, elevated discontinuation rates, and persistent pain post endometriosis surgery. Additionally, the lack of specific treatments tailored to adenomyosis poses a considerable challenge in clinical management.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Objective: To analyse the association between maternal risk factors such as age, body mass index (BMI) and cigarette smoking, with perinatal outcomes. Materials and Methods: This a retrospective analysis from prospectively collected data performed at Hospital Universitario de Torrejón (Madrid, Spain), between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. Association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small for gestational age (SGA) or fetal growth restricted (FGR) neonates and type of delivery according to maternal age, BMI, and cigarrete smoking was studied. Logistic mixed models were used to analyze the data. Results: 1921 patients were included in the analysis. Women of 40 years old had a significantly higher risk of having GDM (Odds Ratio (OR) 1.61, 95% Confidence Interval (CI) 1.08 to 2.36), and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI &lt;18 had an increased rate of birth SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women in the childbearing age. Pregnancy in SLE patients poses unique challenges due to the po-tential impact on maternal and fetal outcomes. We provide an overview of the management of SLE during pregnancy, including pre-conception risk stratification and counselling, treatment, and disease activity monitoring. These assessments are critical to minimize maternal and fetal adverse events in SLE pregnant patients. Disease flares, preeclampsia, antiphospholipid syn-drome complications, and maternal mortality are the major risks for a woman with SLE during gestation. Timely treatment of SLE relapse, differentiation of preeclampsia from lupus nephritis, and tailored management for antiphospholipid syndrome are essential for a successful pregnan-cy. Fetal outcomes include neonatal lupus (NL), preterm birth, cesarean delivery, fetal growth re-striction (FGR), and small for gestational age (SGA) infants. We focused on NL, linked to mater-nal anti-Ro/SS-A and anti-La/SS-B antibodies, which can lead to various manifestations, partic-ularly cardiac abnormalities in newborns. While there is a common consensus regarding the pre-ventive effect of hydroxychloroquine, the role of echocardiographic monitoring and fluorinated steroid treatment is still debated. Finally, close postpartum monitoring and counseling for sub-sequent pregnancies are crucial aspects of care.

Background/Objectives: Forceps delivery is a crucial obstetrical technique that has been increasingly underutilized in favor of cesarean delivery, despite numerous complications related to cesarean section. The major concerns in assisted vaginal birth (AVB) are the safety and long-term consequences. Thus, we aimed to investigate the neurodevelopmental outcome of children born with forceps delivery up to the age of seven. Methods: A prospective descriptive study was conducted from January 2011 to December 2016 among 49 women from our department in the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The study included women with term singleton cephalic pregnancies. Descriptive statistics were calculated for the baseline demographic and clinical features, whereas the logistic regression analysis was used to explore the association between various perinatal parameters and neurological status of newborns. The Sarnat and Sarnat classification was used to evaluate neurological status of newborns, while long-term neurodevelopmental outcome was assesed with Griffiths Mental Development Scale and additional questions based on the neurologist's clinical practice and experience. Results: Pathological neurological status of the newborn was found in 16.3%, with pathological ultrasound of CNS in 3%. A statistically significant association was observed with Apgar score, odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, this was unlikely to be related to the mode of delivery. Long-term adverse neurological outcome was seen in three cases, which accounts for 6.4%. These included mild disorders, such as delayed milestone, speech delay and motor clumsiness. Conclusion: The present study highlights the safety of forceps delivery regarding children's neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). A targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented an expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference.

Background: This study assesses the effects of the ‘Radiant’ image enhancement technique on fetal nuchal translucency (NT) measurements during first trimester sonographic ex-ams. Methods: A retrospective analysis of 263 ultrasound images of first trimester midsagittal sections was conducted. NT measurements were obtained using a semi-automatic tool. Statistical methods were applied to compare NT measurements with and without ‘Radi-ant’ enhancement. An in-vitro setup with predefined line distances provided additional data. Results: Incremental increases in NT measurements were observed with varying levels of ‘Radiant’ application: An average increase of 0.19 mm with ‘Radiant min’, 0.24 mm with ‘Radiant mid’ and 0.30 mm with ‘Radiant max.’ The in-vitro results supported these findings, showing consistent effects on line thickness and measurement accuracy, with the smallest mean deviation occurring at the ‘Radiant mid’ setting. Conclusions: ‘Radiant’ image enhancement leads to significant increases in NT measure-ments. To avoid systematic biases in clinical assessments, it is advisable to disable ‘Radi-ant’ during NT measurement procedures. Further studies are necessary to corroborate these findings and to consider updates to the NT reference tables based on this technology.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Introduction: Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Materials and methods: Fetal biometric data, and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Results: Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β=0.39, p

Objective: The goal of this review is to provide a succinct, yet comprehensive, guide to the an-tepartum management of multiple gestations. Methods: This narrative review on twins and multiple gestation provides a concise guide for providers with this ever-growing patient population. PubMED was utilized for literature search. Each reference was evaluated and graded for quality of evidence by US Preventative Services Task Force and Cochrane Review guidelines. Screening, surveillance, and management strategies are delineated succinctly and organized by type of multiple gestation being managed from the lowest risk dichorionic twin pair to the increasingly escalating risks of twins and higher order multiples sharing a placenta and/or amniotic sac. Results: The incidence of twin pregnancies has grown over the past several years, due in large part to delayed reproductive timing and surge in assisted reproductive technologies. Twin pregnancies are associated with higher morbidity for both gravidas and offspring, warranting evidence-based approach in counseling and management. Conclusions: We note the important differences among multiples in chorionicity and amnionicity, in the importance of close surveillance and early delivery. Graded clinical pearls and evi-dence-based recommendations are presented to guide obstetric providers.

Objectives: The purpose of this study is to determine the association between umbilical venous blood flow (UVBF) to placental pulsatility index (PPI) ratio and gestational age (GA) in women undergoing prenatal assessments and adverse pregnancy outcome (APO) screening Methods: Between January and December 2022, sonographic examinations were conducted to assess the fetal umbilical cord insertion site in singleton fetuses, and hemodynamic indices of the umbilical artery, umbilical vein, and uterine artery were computed. Through regression analysis, we derived the optimal regression equation to elucidate the UVBF/PPI ratio parameters based on GA. Results: Among 492 singleton fetuses between 21+0 and 40+6 weeks of gestation in the final study. The average fetal UVBF/PPI ratio was 180.45±119.32. Correlation analysis revealed a positive relationship between the UVBF/PPI ratio and GA(p = .000). Using regression analysis, the best-fit regression equation was the linear function model, which explains the value of UVBF/PPI ratio parameters based on GA. Lower UVBF/PPI ratio revealed a positive relationship in the low birth weight fetuses (p=0.021) and higher preterm delivery rate (p=0.034). Cerebroplacental ratio (CPR) showed a high correlation with the UVBF/PPI ratio (r=0.471, p=0.000). Conclusions: The findings of our analyses revealed that contribute to our understanding of fetal hemodynamics and highlight the potential of UVBF/PPI ratio as a predictive marker for adverse pregnancy outcomes, such as preterm birth, low birth weight, or potential fetal hypoxemia. It might be useful for prenatal counseling and clinical purposes.

Objective: This study aims to examine CA-125 and miRNAs as biomarkers in endometriosis pathophysiology and their potential roles in clinical diagnostics and prognostics. Methods:We reviewed a variety of studies, including cross-sectional, case-control, and prospective designs, examining a broad spectrum of patient demographics, clinical features, and biomarker (CA-125 and miRNA) expression levels. Results: CA-125 has been reaffirmed as a valuable biomarker in diagnosing and monitoring endometriosis, with its utility enhanced when used alongside other markers. MiRNAs have emerged as promising molecular regulators, offering new avenues for non-invasive diagnostics and a deeper understanding of the disease's pathophysiology. The integration of these biomarkers presents a potential shift towards more personalized and effective diagnostic and therapeutic strategies. Conclusion: Endometriosis presents a significant challenge in women's health, requiring innovative approaches for its management. The convergence of CA-125 and miRNA research represents a promising advance, potentially leading to more accurate diagnostics and personalized treatment. Future research should focus on standardizing methodologies, expanding study cohorts, and integrating findings into clinical practice to fully harness the potential of these biomarkers.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLNs assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is at stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: we described a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary to evolve through future IDEAL stage 2b (multi-center studies) and stage 3 (randomized controlled trials) studies.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which ranges from 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. Improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Cellular aging is considered as one of the main factors leading to female infertility. The process called “inflammaging”, which was proposed by C. Franceschi in 2014 is characterized by chronic asymptomatic inflammation state resulting to whole body aging and age-associated diseases. In this work the inflammaging model was developed; markers expression associated with SASP (senescence associated secretory phenotype) and cell aging were verified in endometrial cells; the correlation analysis with the known inflammaging markers was done; as well as the age dynamic of markers expression in the groups of young reproductive age and late reproductive age was evaluated. For the first time, the comparative study of the expression of the key signalling molecules involved in the mechanisms of the aging was carried out: IL-6, IL-8, IL-1a, MMP3, SIRT1,6, TERF-1, CALR in endometrial cells in the age aspect and under the influence of the genotoxic stress. The SASP phenotype characterizing the phenomenon of inflammaging can be significantly expanded by the including of the studied molecules - SIRT-1, SIRT-6, TERF, CALR, that we demonstrated for the first time. These signalling molecules may be new therapeutic targets for the age-associated female reproductive system diseases treatment.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Objective: The aim of our study was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Results: There was a statistically significant age difference between the two study periods, both by the average age of patients and by age group. The mean difference was 32 years before the pan-demic and 35 years during the pandemic (p-value >0.05). The majority of patients presenting for investigations before and during the pandemic were in the 30-39-year-old age group (31.95%, respectively; 34.2% (p-value = 0.003). The biggest patient loss ratio identified by age group was in the 50–59 years: 14,53% in the pre-pandemic period and 9,1% in the pandemic period. In the pan-demic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the prepandemic period, with an increase in more severe lesions in the pandemic period, has a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusion: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervicorrhagia as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

Background: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women´s diet and glucose tolerance test (GTT) results. Objective: To evaluate the relationship between previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-hours, 75g-GTT). Shortly after diagnosis, participants answered a validated food frequency questionnaire to assess food consumption in the last 6 months. Mann-Whitney´s test was used to compare the dietary intake of participants with one (group 1) versus two-three (group 2) abnormal GTT values. Results: Participant characteristics were similar. There were no significant differences between groups in median intake of total calories, carbohydrates, lipids and proteins. Participants in group 1 had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p= 0.049), vitamin D (40.6 vs. 40.4 mcg/day p= 0.049) and vitamin C (180.0 vs. 151.0 mg/day p= 0.008) than those in group 2. Conclusion: Results suggest a possible association between consumption of fiber and some antioxidant micronutrients and GDM severity at the time of diagnosis.

(1) Background: BRCA mutation and homologous recombination deficiency (HRD) are used to administrate PARP inhibitors (PARPi) maintenance therapy. It is known that PARPi efficacy is related to platinum sensitivity and that the latter can be demonstrated from the CA-125 elimination rate constant (KELIM). This study aims to investigate if KELIM can be another tool in the identification of patients that could be benefit from PARPi therapy.; (2) Methods: Retrospective analysis of patients with high-grade serous advanced ovarian cancer that underwent cytoreduction and was further tested for HRD status. The HRD status was tested either by myChoice HRD CDx assay or by RediScore assay. KELIM score was measured in both neoadjuvant and adjuvant settings with the online tool biomarker-kinetics.org.; (3) Results: Thirty-nine patients had available data for estimating both HRD status and KELIM score. When assuming KELIM as a binary index test with the value 1 as the cut-off point, the sensitivity was 0.86, 95% CI (0.64-0.97), and the specificity 0.83, 95% CI (0.59-0.96). On the other hand, when assuming KELIM as a continuous index test, the AUC was 81% and the optimal threshold, using the Youden index, was identified as 1.03 with a sensitivity of 85.7% and a specificity of 83.3%; (4) Conclusions: KELIM score seems to be a new, cheaper and faster tool to identify patients that can benefit from PARPi maintenance therapy.

Gestational diabetes mellitus (GDM) is a hyperglycemia state that is typically diagnosed by an oral glucose tolerance test (OGTT), which is unpleasant, time-consuming, poorly reproducible, and tardy. The machine learning (ML) predictive models that have been proposed to improve GDM diagnosis are usually based on instrumental methods that take hours to get a result. Near-infrared (NIR) spectroscopy, a simple, fast and low-cost analytical technique has never been assessed for the prediction of GDM. This study aims to develop ML predictive models for GDM based on NIR spectroscopy, and to evaluate their potential as early detection or alternative screening tools according to their predictive power and time of analysis. Serum samples from the first (before GDM diagnosis) and the second (at the time of GDM diagnosis) trimester of pregnancy were analyzed by NIR spectroscopy. Four spectral ranges were considered, and 80 pretreatments were tested for each. NIR data-based models were built with single- and multi-block ML techniques. Every model was subjected to double cross-validation. The best first and second trimester models got areas under the receiver operating characteristic curve of 0.5768 ± 0.0635 and 0.8836 ± 0.0259, respectively. This is the first study reporting NIR spectroscopy-based methods for the prediction of GDM. The developed methods allow to predict GDM from 10 µL of serum in only 32 minutes. They are simple and fast, and have a great potential to be applied in clinical practice, especially as alternative screening tools to the OGTT at the time of GDM diagnosis.

Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Background: The management of gestational diabetes mellitus (GDM) focuses on dietary interventions, physical activity, and pharmacological therapy. Strategies that enhance adherence to the diet could play a pivotal role in managing this population. Objective: To compare the effectiveness of outpatient nutritional guidance supplemented by digital media with exclusively standard outpatient nutritional guidance in pregnant women with GDM. Methods: This was a randomized, patient-blinded clinical trial conducted at the Diabetes and Pregnancy outpatient clinic from February 2021 to January 2023. Pregnant women with GDM were randomly allocated into two groups: the Control Group (CG) received exclusively outpatient nutritional guidance, and the Intervention Group (IG) received outpatient nutritional guidance along with reminders via WhatsApp. Dietary intake (calories, carbohydrates, lipids, proteins, and fibers) was evaluated using 24-hour dietary recalls (24HR). Glycemic control and the need for pharmacological treatment were also assessed. Mann-Whitney tests were applied to numerical variables, and Fisher's exact test or Chi-square tests were used for categorical variables. Results: 81 women were included, 34 allocated to the CG, and 47 to the IG. Patients were followed for a period of 4 to 8 weeks. Few differences were observed in glycemic control between the two groups over the follow-up period. There were no statistical differences in pharmacological therapy (p=0.498); 188 24HR were conducted in the CG and 290 in the IG. A statistically significant increase in lipid intake was observed in the IG over the follow-up period compared to the CG (p

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Artificial intelligence (AI) is experiencing advances and integration in all medical specializations, and this creates excitement but also concerns. This narrative review aims at a critical assessment of the state of the art of AI in the field of endometriosis and adenomyosis. By enabling automation, AI may speed up some routine tasks, decreasing gynecologists’ risk of burnout, as well as enabling them to spend more time interacting with their patients, increasing their efficiency and patients’ perception of being taken care of. Surgery may also benefit from AI, especially through its integration with robotic surgery systems. This may improve the detection of anatomical structures and enhance surgical outcomes by combining intra-operative findings with pre-operative imaging. Not only, AI promises to improve the quality of care by facilitating clinical research and through the introduction of decision support tools that can enhance diagnostic assessment and predict treatment effectiveness and side effects, as well as reproductive prognosis and cancer risk. However, concerns exist regarding the fact that good quality data used in tool development and compliance with data sharing guidelines are crucial. Also, professionals are worried AI may render certain specialists obsolete. This said, AI is more likely to become a well-liked team member rather than a usurper.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

RNA extraction from human cumulus cells (CCs) is considered challenging due to low cell’s pop-ulation and small cell. The successful gene expression analysis from cumulus cells ultimately de-pends on an excellent concentration of Ribonucleic acid (RNA) yield by an appropriate technique. Our study aims to consolidate appropriate cumulus cell collection method, preparation and ex-traction techniques to ensure a good yield of RNA for better gene expression analysis. From the results obtained, the optimal strategy found involved mechanical denudation without an enzy-matic process, followed by the use of RNA stabilizer prior to RNA extraction. Subsequently, uti-lizing a smaller homogenizer, preferably manual pressure control with filter (Bio-Masher III®) is paramount for a pure and homogenize sample. Subsequently, during RNA extraction, the use of RNeasy micro kit and RNA carriers is recommended. These sample collection, preparation, and extraction techniques yielded an excellent-quality RNA concentration and successful gene expres-sion analysis. We also conducted a systematic review to consolidate our findings with current evidence of RNA extraction technique. Our results added a value as a current strategy for opti-mizing RNA extraction in CCs for experimental studies. Thus, our findings can contribute to for-mulating a better strategy for optimizing the RNA extraction in CCs for transcriptomic studies.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly in gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5,397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

Peritoneal fluid is an ovarian exudate from the growing follicle or corpus luteum. Therefore, the free concentrations of estrogens and progesterone are always much higher than in plasma, especially after ovulation. The peritoneum is not vascularised, and peritoneal implants and the superficial portion of deep endometriosis are likely influenced mainly by peritoneal fluid. Follicular phase progesterone concentrations are as high as during the luteal phase in plasma. This explains that most peritoneal implants are rarely proliferative and out of phase with the endometrium. From some 5 mm of depth onwards, endometriosis is rather influenced by plasma hormone concentra-tions, and the deeper parts can be proliferative as the endometrium. Because of these progesterone concentrations, progesterone resistance has to be postulated, permitting endometriosis lesions to initiate and develop. This opens the discussion of whether endometriosis is similar to the basal endometrium. These peritoneal fluid concentrations are important to understand the natural history and medical therapy of endometriosis. Most medical therapies decrease ovarian function and affect peritoneal fluid steroid hormone concentrations. It is suggested that the efficacy of medical therapy for endometriosis-associated pain is a consequence of the decreased estrogen concentrations in the peritoneal cavity and that the local effect of progestins may not be determinant for pain relief. If this is true, a history of endometriosis should not be considered a contraindication for hormone re-placement therapy.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

(1) Background: Although diagnostic criteria for massive hemorrhage with organ dysfunction such as disseminated intravascular coagulation associated with delivery have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with ≥2,000 g of blood loss, among 13,368 deliveries from nine national perinatal centers in Japan between 2020 and 2023 was obtained. Twenty-three patients had fibrinogen levels &lt;170 mg/dl, which is the initiation of coagulation system failure per our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. If the FDP–fibrinogen/3–60 (mg/dl) value is positive, this indicates hematuria; otherwise, the case is non-hematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: The borderline criterion dividing the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery was obtained using artificial intelligence, and this method seemed to be useful.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

Dysmenorrhea symptoms are frequent and often self-treated using non-prescription medicines. To further characterize women with dysmenorrhea using a combination of hyoscine butylbromide and paracetamol (PLUS) for self-management of their complaints, we performed a secondary analysis of a published pharmacy-based patient survey. 314 women (mean age 32.3 years) with dysmenorrhea reported a pain and cramps intensity of 7.45 ± 2.13 on a 0-10 Likert scale, which was reduced to 2.86 ± 1.81 upon treatment. Associated impairments of work/daily chores, leisure activities, and sleep were improved by 64.6%, 62.2% and 70.4%, respectively. The onset of symptom relief was within 60 min in 84.7%. Tolerability was rated as very good or good by 97.2%. These findings confirm the efficacy and tolerability data on PLUS from randomized controlled trials in a larger group of women conducting self-management of their dysmenorrhea.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Background: Perinatal exposure to pollutants could lead to side-effects in mothers and children, since this is a period of high vulnerability. Sparse and contradictory data are available on the impact of pollutants on breast milk. Objective: The present study consists of a scoping to review the recent research on the persistent presence of organic pollutants (POPs) and heavy metals in breast milk. Design: We performed a scoping review using two online databases to identify articles published from 1995 to 2023 on pollutants in breast milk, using the PRISMA Checklist. Results: A total of 54 articles were found relevant. POPs were present in breast milk in higher concentrations the longer the lactation period. In 3-year-old children, the presence of POPs correlated with the duration of breastfeeding. Estimated dietary exposure to Polychlorinated Biphenyls (PCBs) during pregnancy was positively associated with plasma concentrations in 3-year-old children, but not in pregnant women, suggesting transplacental transfer of these substances. Indeed, plasma concentrations were approximately 40% higher in children compared to pregnant women. In China, a clinical study assessed the risks of POPs in breastfed infants under 6 months of age. POPs decreased over time. Dichloro-Diphenyl-Trichloroethane (DDT) was present in infants living in coastal areas. Hexachlorobenzene (HCB) was the pollutant of greatest concern. Parity is a major determinant of POP levels in breast milk, as are heavy metals. Carcinogenic PAHs were found to a greater extent in obese mothers than in mothers with a normal body mass index. Discussion: POPs and heavy metals could be found in infant formula as well as maternal milk. furthers studies are needed to compare the concentrations between the two milks. Conclusions: Breastfeeding is the only food recommended by the WHO for optimal infant growth. It would seem advisable to pursue risk reduction policies to protect mothers and infants from contaminants in breast milk.

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. Conclusion: In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at

Viruses are the most common congenital infections and an important cause of fetal malformations, morbidity, and mortality. The effects of these infections, which are transmitted in-utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (where the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, parvovirus B-19, rubella, varicella and zika. There are currently very few efficacious antiviral agents licensed for use in pregnancy and therefore for most of these infections, prevention by means of immunisation (where there is a vaccine), administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss the current understanding of some of the congenital infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.