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Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center. [ABSTRACT FROM AUTHOR]

The aims of this study are to evaluate coagulation and fibrinolytic features using TEG6s® in normal pregnant courses, in the early postpartum period and in cases with postpartum hemorrhage (PPH) caused by uterine atony. We also analyze cases with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) under treatment with unfractionated heparin. The non-pregnant women (n = 13) and healthy pregnant women (at 9–13 weeks of gestation (n = 13), at 27–30 weeks of gestation (n = 14), at 35–38 weeks of gestation (n = 14)) were cross-sectionally studied, while the normal pregnant women at delivery (n = 14) were sequentially investigated. Blood samples from those patients with PPH (n = 15) and DVT and/or PE (n = 11) were also obtained and compared with those of normal women. Significant changes of clot formation parameters were observed in all parameters and, interestingly, fibrinolytic parameter (LY30) was maintained at a low value even within 120 min after placental delivery (median of LY30; 0) and also in cases with uterine atony (median of LY30; 0.1). The parameter that indicates the effectiveness of heparin showed strong correlation (R = 0.788) with activated partial thromboplastin time. Thromboelastography may be less sensitive to fibrinolysis in the conditions of uterine atonic bleeding. [ABSTRACT FROM AUTHOR]

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients' red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the nature of decidual polyp (DP) and to compare DP outcomes treated with cervical cerclage for a shortened cervix with the outcomes of cases treated with cervical cerclage without DP. The medical records of pregnant women who were complicated with cervical polyps were retrospectively reviewed. Cervical cerclage was considered for those cases with a shortened cervical length of under 25 mm and before 25 gestational weeks. We also reviewed pregnant women who had no cervical polyps, and who underwent cervical cerclage during the same study period, and defined them as the control group. A total of 56 pregnant women with cervical polyps were identified. All of the polyps in the 14 cases that had undergone cervical cerclage migrated into the cervical canal. Of the thirty seven cases with cervical polyps that did not necessitate cervical cerclage, eight women delivered preterm and six of these cases were diagnosed as DP. In all of the women studied, polyp migration was observed in 68.6 %. Cervical cerclage was performed significantly earlier in the DP group than in the control group of 46 cases (p < 0.001; 18.4 weeks vs. 21.4 weeks, respectively). Cervical cerclage is effective in DP cases with a shortened cervical length and polypectomy should not be performed during pregnancy because of the risk of miscarriage. [ABSTRACT FROM AUTHOR]

We aimed to investigate the relation between the time intervals of the flow velocity waveform of ductus venosus (DV-FVW) and cardiac cycles. We defined Delta A as the difference in the time measurements between DV-FVW and cardiac cycles on the assumption that the second peak of ductus venosus (D-wave) starts simultaneously with the opening of the mitral valve (MV). As well, we defined Delta B as the difference of the time measurements between DV-FVW and cardiac cycles on the assumption that the D-wave starts simultaneously with the closure of the aortic valve (AV). We then compared Delta A and Delta B in the control and fetal growth restriction (FGR) groups. In the control group of healthy fetuses, Delta A was strikingly shorter than Delta B. On the other hand, in all FGR cases, no difference was observed. The acceleration of the D-wave is suggested to be generated by the opening of the MV under normal fetal hemodynamics, whereas it precedes the opening of the MV in FGR. Our results indicate that the time interval of DV analysis might be a more informative parameter than the analysis of cardiac cycles. [ABSTRACT FROM AUTHOR]

Thrombopoietin receptor agonists (TPO-RAs) are an effective treatment for refractory immune thrombocytopenia (ITP). However, the use of TPO-RAs is limited for ITP in pregnant women due to concerns about fetal toxicity. In this study, we examined the effects of romiplostim, one of the TPO-RAs, on pregnant mice. The mice were injected subcutaneously with romiplostim (1, 5, 10, 30, and 100 μg/kg) on gestational days (GD) 1, 8, and 15. We evaluated maternal and fetal platelet and megakaryocyte counts (MK), fetal weight at birth, placental morphology, and miscarriage rates. Romiplostim increased platelet and MK counts in pregnant mice at all doses and in fetuses at doses above 10 µg/kg. Fetal weight at birth was slightly reduced at a dose of 100 μg/kg, but there were no significant differences in placental weight, spiral artery wall thickness, placental growth factor signal changes, or the rate of resorption at that dosage. The dose of romiplostim used clinically for ITP patients (1–10 μg/kg) did not show any adverse effects on pregnant mice. Although the results of the present study are encouraging, until there are more conclusive data, the use of romiplostim should be evaluated individually in severe, life-threatening cases, and all relevant ethical aspects should be considered. [ABSTRACT FROM AUTHOR]

Perineal hernia is an infrequent complication of abdominoperineal resection (APR) and, currently, there is no consensus as to the optimal operative technique. Surgical repair can be achieved by either cerclage or the use of mesh or autologous tissue, and it has been reported that the recurrence rate after repair using autologous tissue is 33%. We present two post‐APR cases of severe perineal hernia with pelvic organ prolapse (POP) which did not improve after repair using mesh. We regenerated the pelvic floor using a vertical rectus abdominis myocutaneous (VRAM) flap and performed a concomitant sacrocolpopexy to fix the POP. Drooping of the perineum and pelvic floor was greatly improved, and the patients have not experienced any recurrence for 6 years. This dual procedure has not been previously mentioned in the literature, and we consider this the first report of its kind. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Pelvic organ prolapse (POP) in women is associated with deficiency of elastic fibers, and fibulin-5 is known to be a critical protein in the synthesis of elastin. The purpose of this study is to investigate the related pathway for the synthesis of elastin via fibulin-5 using fibulin-5 knockout mice. Methods: Fibulin-5 knockout mice were generated using the CRISPR/Cas9 system, and vaginal dilatation was used to mimic vaginal delivery. We divided the mice into three groups: Fbln5+/+ mice immediately after dilatation (Fbln5+/+ day0), Fbln5+/+ mice 3 days after dilatation (Fbln5+/+ day3) and Fbln5−/− mice 3 days after dilatation (Fbln5−/− day3). Proteins related to elastogenesis in the vaginal wall were measured by liquid chromatography mass spectrometry (LC-MS/MS) analysis, and differences in the expression of these proteins between the Fbln5−/− mice and the Fbln5+/+ mice were analyzed using western blotting. Results: In the LC-MS/MS analysis, protein tyrosine kinase 7 (PTK7) was not detected in the Fbln5−/− day3 group, although the expression increased by > 1.5 times between the Fbln5+/+ day0 and day3 groups. PTK7 and β-catenin are known to act in the Wnt/β-catenin pathway, and both were upregulated after dilatation in the Fbln5+/+ mice, though not in the Fbln5−/− mice. Conclusion: Our findings suggest that these proteins are involved in elastogenesis via fibulin-5, and the impairment of these proteins might be the underlying cause of POP manifestation. [ABSTRACT FROM AUTHOR]

Aim: Tension‐free vaginal mesh (TVM) surgery using synthetic polypropylene (PP) soft mesh had spread rapidly. However, the frequency of mesh‐related postoperative complications had increased, and PP was banned in April 2019. In Japan, however, transvaginal surgery using polytetrafluoroethylene (PTFE) mesh had been approved. In this study, we evaluated the clinical outcome and quality of life (QOL) of the postoperative course using PP mesh and PTFE mesh (named "ORIHIME™") in a combination surgery for utero‐sacral ligament suspension and anterior vaginal support using anterior TVM. Methods: The vaginal hysterectomy and utero‐sacral ligament colpopexy augmented by anterior vaginal mesh implants using PP mesh and PTFE mesh were performed on patients with stage III to IV cystocele and uterine prolapse. The clinical outcome and QOL changes in their postoperative course were evaluated by comparing 15 cases of PP mesh and 13 cases of PTFE mesh. Results: There was no difference between the PP group and PTFE group in characteristics. No mesh‐related complications occurred during the follow‐up period. With regard to the pelvic organ prolapse quantification (POP‐Q) score, no significant difference was found between the two groups. Comparing the postoperative QOL of both groups, the PTFE group had significantly higher values in two domains than PP group (SF‐12v2 questionnaire). Conclusions: We used the world's first PTFE mesh to compare PP mesh with postoperative POP‐Q and QOL after the same surgery, with the same operator, and at the same institution. The results showed no significant difference between both mesh materials in the short‐term. [ABSTRACT FROM AUTHOR]

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post‐micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post‐micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse. Methods: This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates. Results: This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien–Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3‐month follow‐up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall. Conclusions: These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery. [ABSTRACT FROM AUTHOR]

Since it is extremely difficult to establish an animal model for human chromosomal abnormalities, induced pluripotent stem cells (iPSCs) provide a powerful alternative to study underlying mechanisms of these disorders and identify potential therapeutic interventions. In this study we established iPSCs from a young girl with a hemizygous deletion of Xq27.3-q28 who exhibited global developmental delay and intellectual disability from early in infancy. The deletion site on the X chromosome includes Fragile X Mental Retardation 1 (FMR1), the gene responsible for fragile X syndrome, which likely contributes to the patient's neurodevelopmental abnormalities. The FMR1 gene was expressed in approximately half of the iPSC clones we generated while it was absent in the other half due to the random inactivation of normal and abnormal X chromosomes. The normal or absent expression pattern of the FMR1 gene was not altered when the iPSCs were differentiated into neural progenitor cells (NPCs). Moreover, chromosome reactivating reagents such as 5-aza-2-deoxycytidine, trichostatin A, and UNC0638, were tested in an attempt to reactivate the suppressed FMR1 gene in affected iPSC-NPCs. The affected and control isogenic iPSCs developed in this study are ideal models with which to identify downstream consequences caused by the Xq27.3-q28 deletion and also to provide tools for high-throughput screening to identify compounds potentially improving the well-being of this patient population. [ABSTRACT FROM AUTHOR]

Background: Infants <6 months of age are too young to receive influenza vaccine, despite being at high risk for severe influenza-related complications.Methods: To examine the effectiveness of maternal influenza vaccination in preventing influenza in their infants, we conducted a prospective cohort study of 3441 infants born at participating hospitals before the 2013-2014 influenza season. At the time of recruitment, their mothers completed a questionnaire about influenza vaccination status for the 2013-2014 season. A follow-up survey was conducted after the end of the 2013-2014 season to collect information regarding influenza diagnosis and hospitalization among infants.Results: During the 2013-2014 influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%) were hospitalized with influenza. Maternal influenza vaccination (especially prenatal vaccination) decreased the odds of influenza among infants. The effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%), whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal influenza vaccination was also associated with a decreased odds of influenza-related hospitalization among infants, vaccine effectiveness (73%) did not reach statistical significance, owing to the limited number of infants hospitalized because of influenza.Conclusions: The present findings indicated that pregnant women and postpartum women should receive influenza vaccination to protect their infants. [ABSTRACT FROM AUTHOR]