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This corrects the article DOI: 10.1038/srep46220 [ABSTRACT FROM AUTHOR]

The article discusses the result of a study on cerebral palsy and the development of perinatal emergency care systems conducted by the Perinatology Committee of the Japan Society of Obstetrics and Gynecology. The findings suggest that it is important to decreased fetal movements or their loss as initial symptoms. It also highlights the importance of establishing a system to perform emergency surgery through cooperation between anesthetists and neonatologists.

The article discusses the result of studies which examined the causes of maternal death. It analyzes the pathology of atonic bleeding and amniotic fluid embolism to determine ways to prevent maternal death. The findings reveal that fibrinogen level decreases earlier than antithrombin and platelet during atonic bleeding.

Presents a response to a letter to the editor regarding statistical analysis methods used in the peritoneal fluid concentrations of cytokines and ovarian steroids.

Objective: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT).Study Design: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth.Results: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21.Conclusion: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT. [ABSTRACT FROM AUTHOR]

Purpose: Surgery for endometriomas may cause detrimental effects on ovarian reserve. We evaluated the safety of three‐step laparoscopic surgery for endometriomas utilizing dienogest in terms of post‐surgical ovarian reserve. Methods: Twelve women received first look laparoscopy (FLL) with fenestration and drainage. Immediately after the surgery, they took oral dienogest 2 mg for three months; then, they received second look laparoscopy (SLL) with cystectomy. We compared serum AMH levels between women had three‐step management with dienogest, and another twelve women had conventional one‐step surgery without medications. In women had three‐step procedures, the changes in concentration of proinflammatory cytokines and chemokines in peritoneal fluids were evaluated. Results: Serum AMH levels were significantly decreased after three months of dienogest following FLL. AMH levels were also significantly decreased 3‐6 months both after SLL and after one‐step surgery; however, recovery of serum AMH levels at 9‐12 months after surgery was evident in women had three‐step surgery comparing to those of one‐step surgery. Proinflammatory cytokines and chemokines in peritoneal fluids were downregulated at the time of SLL comparing to those of FLL. Conclusions: Three‐step surgery with dienogest may be a beneficial approach to protect ovarian reserve. Dienogest may exert its effects in part by lowering proinflammatory cytokines and chemokines. [ABSTRACT FROM AUTHOR]

Background: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT.Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package.Results: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive.Conclusions: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women. [ABSTRACT FROM AUTHOR]

Dichorionic diamniotic (DCDA) twin pregnancies after single blastocyst embryo transfer have been reported recently, although a blastocyst ovum is generally believed to divide into monochorionic twin pregnancy. We investigated the incidence of DCDA twin pregnancy after single blastocyst embryo transfer and their zygosity. This prospective cohort study included 655 consecutive twin pregnancies that were managed from 2006 to 2014 at our institution. Chorionicity and amnionicity were determined using first-trimester ultrasonography and/or placental pathology. Zygosity was analyzed if the cases were DCDA twins after single blastocyst embryo transfer. Among 655 twin pregnancies, there were 348 DCDA cases, 295 monochorionic diamniotic (MCDA) cases and 12 monochorionic monoamniotic cases. Single blastocyst embryo transfer was performed in 43 cases. Six out of the 43 (14%) cases involved DCDA twin pregnancies and the other 37 cases involved MCDA twin pregnancies. Three DCDA twins born after single blastocyst embryo transfer, wherein frozen embryo transfer (FET) was performed in the natural cycle, were dizygotic, and the other three cases, wherein FET with hormone replacement therapy was performed, were monozygotic. DCDA twin pregnancy occurred in 14% (7% for monozygotic and 7% for dizygotic) of twin pregnancies after single blastocyst embryo transfer cases. [ABSTRACT FROM AUTHOR]

Autoimmune reactions and subsequent inflammation may underlie spermatogenic dysfunction and endometriosis-related infertility. The aim of this study is to identify disease-specific antigens in immune complexes (ICs) in seminal plasma (SP) and in follicular fluid (FF). Immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, was performed for specimens collected from infertile couples undergoing assisted reproduction. Forty-two male patients consisting of subjects with oligozoospermia (n = 6), asthenozoospermia (n = 8), and normal semen analysis (n = 28). Fifty-eight female patients consisting of subjects with ovarian endometriosis (n = 10) and control women without disease (n = 48). Four disease-specific antigens were identified in subjects with oligozoospermia, while five disease-specific antigens were detected in subjects with asthenozoospermia, some of which are involved in sprematogenesis. Eight antigens were detected only in subjects with endometriosis. Functional characteristics of disease-specific antigens were found to correspond to the pathogenesis of male and female infertility. The formation of ICs may contribute to spermatogenic dysfunction and endometriosis-related infertility via loss of function of the related proteins. Immune complexome analysis is expected to be a valuable tool for the investigation of novel diagnostic methods and treatment strategies for infertility. • We identified the immune complex antigens in seminal plasma and follicular fluid. • Several disease-specific antigens were found in infertile male or female. • Immune complexome analysis may be a new path to biomarker discovery in infertility. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP).Study Design: This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed.Results: A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP.Conclusion: A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group (P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption. [ABSTRACT FROM AUTHOR]

Aim To determine whether three-dimensional saline infusion sonohysterography (3D-SISH) is useful for the detection of endometrial polyps and whether it can accurately identify the site of attachment within the uterine cavity. Methods Sixteen women who underwent preoperative magnetic resonance imaging (MRI), 3D-SISH and subsequent hysteroscopic resection or total hysterectomy and who were surgically diagnosed with endometrial polyps were enrolled. The rate of polyp detection and the accuracy of attachment site within the uterine cavity for each test were examined. Results Endometrial polyps could only be identified in 37.5% of women using MRI, but could be identified in all women using 3D-SISH. The accuracy rate of the attachment site of endometrial polyps was 87.5% on 3D-SISH and 18.8% (in all patients) or 50.0% (in polyp-detected patients) on MRI, indicating a higher accuracy rate using 3D-SISH. Conclusion We demonstrated that 3D-SISH is useful for the detection and localization of endometrial polyps and is likely to become the examination method of first choice for the identification of endometrial polyps. [ABSTRACT FROM AUTHOR]

Aim In order to investigate the current status of prenatal testing for genetic disorders, we conducted a multicenter retrospective questionnaire survey. Methods The questionnaire was sent to 105 facilities with genetic counseling systems. The questionnaire consisted of two parts: (i) the number of prenatal tests conducted for genetic disorders from January 2010 to December 2012, whether the laboratory was combined with the counseling facility or separate, the sampling procedure method, the testing results, and the outcomes of the affected fetus in addition to treatment; and (ii) a survey of personal comments regarding prenatal testing for genetic disorders. Results We received responses from 69 of the 105 facilities (65.7%), and genetic testing was performed at 26 of these facilities. Nucleic acid sequential testing was performed on 45 disorders and 252 cases during a three-year period. There were 67 cases of affected fetuses. Six cases continued pregnancy and were treated. The comment survey highlighted difficulties in locating a laboratory to assess prenatal samples, as well as inadequate counseling and preparation for genetic disorders. Conclusions Our study revealed that a number of prenatal testing for genetic disorders are conducted in Japan; however, it is difficult for counselors to locate a laboratory capable of testing for specific genetic disorders. Inadequate counseling and healthcare providers' lack of knowledge is a current problem. A well-established system of prenatal testing for genetic disorders and the further education of general physicians is required. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL), which is difficult to cure. In Japan, a nationwide HTLV-1 screening test in pregnant women has been recommended since 2011. A 30-year-old woman was diagnosed as being an HTLV-1 carrier in her previous pregnancy. During the current pregnancy, she had persistent fever and cough. Although she had treatment with antibiotics, peripheral white blood cell count remained high, with an abnormal lymphocyte count. Given that she was an HTLV-1 carrier, she was diagnosed with unfavorable chronic ATL (aggressive ATL) at 12 weeks gestation. After pregnancy termination, her ATL status became favorable chronic ATL (indolent ATL). Therefore, watchful waiting was performed until disease progression. This is the first case report of chronic ATL in early pregnancy, in a woman already diagnosed as an HTLV-1 carrier on screening test. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to clarify the association between placenta previa and circulating levels of cell-free pregnancy-associated placenta-specific microRNAs (miRNAs) in maternal plasma. Method: Twenty singleton pregnancies with placenta previa (placenta previa group) and 26 uncomplicated pregnancies (control group) were recruited. Blood sampling was performed at 32 weeks of gestation, and cesarean delivery in all cases of placenta previa was performed at a mean gestational age of 37 weeks. The maternal plasma concentrations of cell-free pregnancy-associated placenta-specific miRNAs (miR-517a and miR-518b) were measured by absolute quantitative real-time reverse transcription-polymerase chain reaction. Results: Plasma concentrations of cell-free miR-517a were significantly higher in the placenta previa group than that in the control group (P = .011), while the plasma concentration of cell-free miR-518b was significantly lower in the placenta previa group than that in the control group (P = .004). Plasma concentrations of cell-free miR-517a in placenta previa were significantly higher in placenta previa with alert bleeding later group than those in placenta previa without alert bleeding group or control group (P = .030 or .047, respectively) and correlated with the volume of hemorrhage at delivery (R and P value: .512 and .025). Conclusion: Plasma concentrations of cell-free miR-517a and miR-518b at 32 weeks of gestation were altered in pregnant women with placenta previa, and the circulating level of cell-free miR-517a in placenta previa may be a predictive marker for the risks of alert bleeding later and massive hemorrhage at delivery. [ABSTRACT FROM AUTHOR]

Objectives Human heat shock protein 70 (HSP70) has been reported to enhance Toll-like receptor 4-mediated pelvic inflammation and growth of endometriotic cells. However, information on tissue expression of HSP70 before and after treatment with estrogen suppressing agent is scanty. Here, we investigated tissue expression HSP70 in the eutopic/ectopic endometria of gonadotropin-releasing hormone agonist (GnRHa)-treated and -non-treated women with endometriosis. Study design Biopsy specimens were collected from peritoneal lesions, cyst walls, and corresponding endometria of 20 women with peritoneal endometriosis, 35 women with ovarian endometrioma, and 15 control women during laparoscopy. Fifteen women with ovarian endometrioma were treated with GnRHa for a variable period of 4–6 months before laparoscopy. The immunoexpressions of HSP70 and CD68-positive macrophages (Mφ) in endometria, peritoneal lesions, and cyst walls were examined by immunohistochemistry. The immunoreactivity of HSP70 in tissues was analyzed by quantitative-histogram (Q-H) score. Results Tissue expression of HSP70 was found to be the highest in the menstrual phase than in other phases of the menstrual cycle. A significantly higher immunoreactivity of HSP70 was found in the eutopic endometria of women with peritoneal and ovarian endometriosis than in controls and in opaque red lesions than in other peritoneal lesions. A significant correlation between Q-H scores of HSP70 and CD68-positive Mφ numbers was found in the endometria derived from women with peritoneal endometriosis ( r = 0.481) and in ovarian endometrioma ( r = 0.560) but not in control women. The Q-H scores of HSP70 expression were significantly lower in cyst walls, coexisting peritoneal lesions and corresponding endometria of women with ovarian endometrioma after GnRHa treatment comparing to similar tissues derived from women without GnRHa treatment. Conclusion These results suggest that as a marker of tissue stress reaction, immunoexpression of HSP70 was highly increased in pathological lesions and endometria of women with endometriosis and had a significant correlation with tissue inflammatory reaction. The higher tissue expression of HSP70 can be effectively suppressed after GnRHa treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study aimed to identify a set of endometrioid endometrial carcinoma EEC-associated microRNAs (miRNAs) in tissue and plasma, and evaluate their clinical significance. Methods: A set of EEC-associated miRNAs in tissue and plasma was identified by next-generation sequencing (NGS), which could enable in-depth characterization of the global repertoire of miRNAs. Results: NGS identified 11 candidate EEC-associated miRNAs. Quantitative reverse-transcriptase PCR identified 8 EEC-associated miRNAs in tissue (upregulated: miR-499, miR-135b, miR-205, downregulated: miR-10b, miR-195, miR-30a-5p, miR-30a-3p and miR-21). Expression of hsa-miR-499 in International Federation of Gynecology and Obstetrics (FIGO) Stage IA and Grade 1 tissues was significantly lower than in others (FIGO Stage IB or more advanced, and Grade 2 or 3). By receiver operating characteristic (ROC) curve analysis, compared with single EEC-associated miRNA, two miRNA signatures (miR135b/miR195 and miR135b/miR30a-3p) could distinguish between EEC and normal endometrial tissue samples yielding a high area under the curve (AUC) of 0.9835 [95% confidence interval (CI): 0.9677–1.0], and 0.9898 (95% CI: 0.9677–1.0), respectively. As possible non-invasive markers for EEC, four EEC-associated miRNAs (increased level: miR-135b and miR-205, decreased-level: miR-30a-3p and miR-21) in plasma were identified. Circulating levels of three EEC-associated miRNAs (miR-135b, miR-205 and miR-30a-3p) in plasma were significantly decreased after hysterectomy. ROC curves analysis revealed that miR-135b and miR-205 levels in plasma yielded AUCs of 0.9722 (95% CI: 0.913–1.0) and 1.0 (95% CI: 1.0–1.0), respectively. Conclusion: Measurement of tissue and plasma EEC-associated miRNAs may be useful for early detection, diagnostic, and follow-up tests for EEC. [Copyright &y& Elsevier]

Our purpose was to examine the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), either singly (10 μg/kg) or with 17β-estradiol (E2, 100 μg/kg), on the growth of endometriosis in a mouse endometriosis model by employing histo-morphometrical analysis as well as expression of arylhydrocarbon receptor (AhR) and estrogen receptor (ER). Epithelial height, stromal thickness, and proliferative activity of the endometriotic lesions were significantly increased by E2 in ovariectomized mice, whereas co-administered TCDD significantly reduced these effects. TCDD alone did not affect the proliferative activity but rather reduced the epithelial height and stromal thickness. ER expression in the luminal epithelium was decreased by E2 compared with ovariectomy alone, while TCDD significantly increased it. On the other hand, stromal ER expression was significantly increased by ovariectomy and decreased by E2, though TCDD did not further enhance this expression. These results indicate that a short-term exposure to TCDD failed to increase the growth of endometriotic lesion and the direct effect of TCDD probably depends on a cell-specific interaction with ovarian steroids mediated by their own receptors. These initial findings in intact tissue of mouse endometriosis may suggest critical roles of steroid hormones in the pathogenesis of endometriosis in relation to endocrine disruptors. [Copyright &y& Elsevier]

: ObjectiveTo investigate the possible involvement of hepatocyte growth factor (HGF) in the cellular changes of pelvic mesothelium and the association of these changes with macrophage (Mφ) infiltration and the different stages of pelvic endometriosis.: DesignControlled clinical study using intact tissue.: SettingNagasaki University School of Medicine, Nagasaki, Japan.: Patient(s)Biopsy specimens from 25 red lesions, 20 black lesions of pelvic endometriosis and their adjacent peritoneum were excised either en bloc or separately during laparoscopy.: Intervention(s)Hepatocyte growth factor and activated macrophage-marker CD68 were immunolocalized using respective antibodies, and were quantitated by a computer analyzed quantitative-histogram (Q-H) score and light microscopy, respectively.: Main outcome measure(s)The possible immunoreaction of HGF near the endometriotic lesions and their adjacent peritoneal mesothelium was examined. The association between immunostaining of HGF and macrophage infiltration around these cells was also investigated.: Result(s)A fraction of biopsy specimens of pelvic peritoneum revealed histologically proven change from normal flat to cuboidal or columnar cell types. In cuboidal cells or flat cells of mesothelium adjacent to red lesions, the immunoreaction of HGF, as expressed by the Q-H scores, was found to be significantly higher than in corresponding cells adjacent to black lesions. The flat or cuboidal cells of pelvic mesothelium surrounding the red lesions also demonstrated greater macrophage infiltration than the cells surrounding black lesions. The Q-H scores of HGF in the cuboidal or columnar cells surrounding the red lesions showed a statistically significant correlation with the accumulation of macrophage in the cells; no similar correlation was demonstrated for black lesions.: Conclusion(s)Adjacent peritoneum of pelvic endometriotic lesions may manifest an inflammatory response. Hepatocyte growth factor might be involved in the cellular changes found in the peritoneal mesothelium of women with pelvic endometriosis. [Copyright &y& Elsevier]