Publications by authors named "Atsuo Itakura"

116 Publications

Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor.

PLoS One 2021 23;16(4):e0250638. Epub 2021 Apr 23.

Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.

Prostaglandin E2 (PGE2) is known to have important roles in labor, but the detailed mechanism underlying the spontaneous human labor remains unknown. Here, we examined the involvement of prostaglandin biosynthetic enzymes and transporter in the accumulation of PGE2 in amniotic fluid in human labor. PGE2 and its metabolites were abundant in amniotic fluid in deliveries at term in labor (TLB), but not at term not in labor (TNL). In fetal-membrane Transwell assays, levels of PGE2 production in both maternal and fetal compartments were significantly higher in the TLB group than the TNL group. In fetal-membrane, the mRNA level of PTGES3, which encodes cytosolic prostaglandin E synthase (cPGES), was significantly higher in TLB than in TNL, but the mRNA levels of the other PGE2-synthase genes were not affected by labor. Moreover, the mRNA level of PTGS2, which encodes cyclooxygenase-2 (COX-2) in the amnion was significantly higher in TLB than in TNL. Western blot analyses revealed that the levels of COX-1 and COX-2 were comparable between the two groups, however, the level of cPGES was relatively higher in TLB than in TNL. COXs, cPGES, and prostaglandin transporter (SLCO2A1) proteins were all expressed in both chorionic trophoblasts and amniotic epithelium. These findings suggest that COXs, cPGES and SLCO2A1 contribute to PGE2 production from fetal-membrane in labor.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250638PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064594PMC
April 2021

Monitoring drainage flow rate facilitates prompt intervention with re-laparoscopy for postoperative bleeding after laparoscopic gynecologic surgery: A case-control study.

Asian J Endosc Surg 2021 Mar 28. Epub 2021 Mar 28.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Introduction: We aimed to identify the characteristics of cases involving postoperative bleeding after laparoscopic gynecologic surgery, and to clarify the optimal cutoff value of postoperative drainage and vital sign trends for predicting the need for re-laparoscopy.

Methods: Of 6366 patients with gynecologic benign pathologies who underwent laparoscopic surgery at our institution between 2009 and 2018, 13 (0.2%) required re-laparoscopy for postoperative bleeding. After reviewing the perioperative course in the re-laparoscopy group, we examined the postoperative total drainage volume (mL), drainage flow rate (mL/h), and vital sign trends in the re-laparoscopy group (n = 13) and among patients with substantial drainage volume ≥300 mL at 12 hours postoperatively but who did not need re-laparoscopy (observation group, n = 107).

Results: In the re-laparoscopy group, initial laparoscopic surgery included uterine surgery (myomectomy, n = 7; hysterectomy, n = 1), adnexal surgery (n = 3), and uterine plus adnexal surgery (n = 2). Postoperative bleeding sites included the uterine wound (n = 6), adnexal wound (n = 5), umbilical trocar site (n = 1), and mesentery (n = 1). The re-laparoscopy and observation groups did not differ regarding initial surgical characteristics or postoperative vital sign trends. For distinguishing between the re-laparoscopy and observation groups, the drainage flow rate was superior to total drainage volume. Continuous excessive drainage (flow rate >50 mL/h) at 3 hours postoperatively was associated with a remarkably increased risk for re-laparoscopy (odds ratio, 40.07; 95% confidence interval, 5.44 to 1776.41, P < 0.001).

Conclusion: In cases with continuous excessive drainage later than 3 hours postoperatively (flow rate >50 mL/h) should be considered for exploratory re-laparoscopy to enable prompt diagnosis and intervention.
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http://dx.doi.org/10.1111/ases.12936DOI Listing
March 2021

Effect of hypofibrinogenemia on obstetrical disseminated intravascular coagulation in Japan in 2018: a multicenter retrospective cohort study.

Int J Hematol 2021 Mar 12. Epub 2021 Mar 12.

Department of Obstetrics and Gynecology, Hamamatsu Medical Center, Hamamatsu, Japan.

Japanese obstetrical hemorrhage recommendations state that not only pregnant women with an obstetrical disseminated intravascular coagulation (DIC) score ≥ 8 points but also those with fibrinogen levels ≤ 1.5 g/L have a high risk of maternal death and warrant blood transfusion. Our aim was to demonstrate the potential of fibrinogen levels ≤ 1.5 g/L as predictors of a Japanese obstetrical DIC score of ≥ 8. We included 595 participants with blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean delivery. The frequency and volume of red blood cell (RBC), fresh-frozen plasma, platelet concentrate (PC), and fibrinogen administration in women with a DIC score of ≥ 8 and fibrinogen levels of ≤ 1.5 g/L were significantly higher than controls (P < 0.0001). Multivariate analysis demonstrated that a score of ≥ 3 was associated with RBC or fibrinogen administration and a score of ≥ 5 was associated with PC transfusion. Fibrinogen levels ≤ 1.89 g/L and ≤ 2.44 g/L were associated with PC transfusion and fibrinogen administration, respectively. Fibrinogen levels ≤ 1.5 g/L may have similar potential to a DIC score of ≥ 8 points for detecting obstetrical DIC in Japan.
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http://dx.doi.org/10.1007/s12185-021-03119-5DOI Listing
March 2021

Transcriptomic analysis of hormone-sensitive patient-derived endometrial cancer spheroid culture defines Efp as a proliferation modulator.

Biochem Biophys Res Commun 2021 Apr 26;548:204-210. Epub 2021 Feb 26.

Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan; Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan. Electronic address:

Estrogen-responsive endometrial cancer (EC) is prevalent in uterine cancer. Its precise molecular mechanisms remain to be elucidated partly because of limited availability of estrogen-sensitive EC models recapitulating clinical pathophysiology. We previously established EC patient-derived cancer cell (EC-PDC) spheroid culture with high expression of estrogen receptor α (ERα). Using this EC-PDC, we study the transcriptional regulation and function of estrogen-responsive finger protein (Efp), a prototypic tripartite motif (TRIM) protein that modulates protein degradation and RNA processing. Intense estrogen-dependent EFP mRNA induction and high ERα occupancy to EFP estrogen responsive element (ERE) were observed in EC-PDC. Luciferase reporter gene assay showed that the ERE facilitates EFP transcriptional activity estrogen-dependently. siRNA-mediated Efp silencing in EC-PDC resulted in suppressed spheroid proliferation and altered gene expression profile, featuring downregulation of genes related to cell cycle (e.g., CDK6) and inflammation/immune responses (e.g., IL10RA, IL26, and IL6ST) while unaffected expression of cancer stemness-related markers. Taken together, EC-PDC spheroid culture is a powerful EC tool that enables to dissect Efp-mediated ERα signaling pathways as an estrogen-sensitive EC model. This study provides an insight into alternative EC therapeutic strategies targeting ERα-Efp axis.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.066DOI Listing
April 2021

YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer.

Sci Rep 2021 Feb 18;11(1):4220. Epub 2021 Feb 18.

Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.
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http://dx.doi.org/10.1038/s41598-021-83200-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893073PMC
February 2021

Analysis of severe psychological stressors in women during fertility treatment: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study.

Arch Gynecol Obstet 2021 Jan 1. Epub 2021 Jan 1.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Purpose: To identify risk factors for severe psychological stress in women undergoing fertility treatment.

Methods: This cross-sectional, multi-center study was conducted from August to December 2018. We recruited 1672 subjects who completed an anonymous, self-reported questionnaire regarding fertility treatment, conditions at work and home, and psychological stress using K6 score, which estimates psychological distress during the previous 30 days. We further focused our analysis on 1335 subjects who were working when starting fertility treatment.

Results: Of 1672 women, mean K6 score (range 0-24) was 4.8 ± 4.4, including 103 women (6.2%) with K6 score ≥ 13 (high K6), and classified as probable severe psychological distress. Multivariate logistic regression analysis showed that high K6 was strongly associated with low annual family income of ≤ USD55,700 (JPY6 million) (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.04-3.42), infertility duration of ≥ 2 years (OR 1.87, 95% CI 1.08-3.25), and no experience of childbirth (OR 2.04, 95% CI 1.05-3.97). Focusing on 1335 working women, 266 (19.9%) experienced resignation from work. High K6 was strongly associated with low family income (OR 2.83, 95% CI 1.52-5.28), cessation of professional duties (OR 2.08, 95% CI 1.05-4.14), infertility-related harassment in the workplace (OR 2.07, 95% CI 1.08-3.98), and perceived difficulties to continue working during fertility treatment (OR 2.94, 95% CI 1.15-7.50).

Conclusion: Severe psychological stressors in women during fertility treatment included low family income, long infertility duration, childlessness, infertility-related harassment, and perceived difficulty in working conditions or cessation from work. Establishment of mental health care support systems is urgently required in this population.
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http://dx.doi.org/10.1007/s00404-020-05923-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775729PMC
January 2021

Risk factors for resignation from work after starting infertility treatment among Japanese women: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study.

Occup Environ Med 2020 Dec 3. Epub 2020 Dec 3.

Department of Public Health, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan

Objective: To elucidate the risk factors associated with resignation from work of Japanese women undergoing infertility treatment.

Methods: A total of 1727 female patients who attended a private fertility clinic in Japan participated in the Japan-Female Employment and Mental health in Assisted reproductive technology study. Questions related to demographic, clinical and socioeconomic characteristics were employed in the questionnaire. Out of the 1727 patients, 1075 patients who were working at the time of initiating infertility treatment and felt infertility treatment incompatible with work were included in the analysis. Risk factors for resignation were assessed by using multivariable logistic regression models.

Results: Among 1075 working women who started infertility treatment, 179 (16.7%) subsequently resigned. Multivariable-adjusted ORs for resignation in those with lower educational background and infertility for ≥2 years were 1.58 (95% CI: 1.07 to 2.34) and 1.82 (95% CI: 1.15 to 2.89), respectively. The OR for resignation in non-permanent workers undergoing infertility treatment was 2.65 (95% CI: 1.61 to 4.37). While experiencing harassment in the workplace approached significance, lack of support from the company was significantly associated with resignation after starting infertility treatment, with ORs of 1.71 (95% CI: 0.98 to 2.99) and 1.91 (95% CI: 1.28 to 2.86), respectively.

Conclusion: One-sixth of women resigned after starting infertility treatments. It was found that factors related to education, infertility duration and work environment were significantly associated with resignation. Reducing the physical and psychological burden endured by women, for example, by increasing employer-provided support, is vitally important in balancing infertility treatment with maintenance of work life.
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http://dx.doi.org/10.1136/oemed-2020-106745DOI Listing
December 2020

Analysis of the risk factors and treatment for repeated implantation failure: OPtimization of Thyroid function, IMmunity, and Uterine Milieu (OPTIMUM) treatment strategy.

Am J Reprod Immunol 2021 05 27;85(5):e13376. Epub 2020 Nov 27.

Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan.

Problem: What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)?

Method Of Study: Infertile women with a history of RIF after more than three embryo transfer (ET) cycles underwent implantation testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25-hydroxyvitamin D , interferon-γ-producing helper T (Th1) cell, IL-4-producing helper T (Th2) cell, thyroid-stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening between April 2017 and August 2018. We treated chronic endometritis with antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus intake, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of the 116 RIF women, 88 women with 133 ET cycles were recruited from a questionnaire-based survey regarding pregnancy outcomes. Fifty-nine consecutive RIF patients without the OPTIMUM treatment strategy were also recruited as a control.

Results: The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3-19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control.

Conclusions: The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.
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http://dx.doi.org/10.1111/aji.13376DOI Listing
May 2021

A Retrospective Multicenter Study on the Usefulness of 50 g Glucose Challenge Test in Gestational Diabetes Mellitus Screening.

JMA J 2020 Apr 6;3(2):125-130. Epub 2020 Apr 6.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Introduction: To clarify the usefulness of glucose challenge test (GCT), the rate of gestational diabetes mellitus (GDM) detection and perinatal outcomes were compared between the groups of random blood glucose level (RBG) and 50 g GCT in this study.

Methods: The first survey was conducted at 255 institutions registered by the Kanto Society of Obstetrics and Gynecology and clinical training institutions in the Kanto Area, followed by a second survey. The included women were broadly classified into the RBG and GCT groups, according to the mid-trimester blood glucose screening method, and the perinatal outcomes of the two groups were retrospectively compared. The primary outcomes were the proportion of infants weighing 3,500 g or more and birth weight ≥90-percentile infants.

Results: The rate of GDM diagnosis was significantly higher in the GCT group (7.6%) than that in the RBG group (4.8%). However, no significant differences were observed in perinatal outcomes, i.e., the proportion of infants weighing 3,500 g or more or birth weight ≥90 percentile.

Conclusions: GCT is not superior for predicting infants weighing 3,500 g or more and birth weight ≥90 percentile, as compared with RBG.
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http://dx.doi.org/10.31662/jmaj.2019-0072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590393PMC
April 2020

Whole exome sequencing of fetal structural anomalies detected by ultrasonography.

J Hum Genet 2021 May 3;66(5):499-507. Epub 2020 Nov 3.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

The objective of this study was to evaluate the efficacy of whole exome sequencing (WES) for the genetic diagnosis of cases presenting with fetal structural anomalies detected by ultrasonography. WES was performed on 19 cases with prenatal structural anomalies. Genomic DNA was extracted from umbilical cords or umbilical blood obtained shortly after birth. WES data were analyzed on prenatal phenotypes alone, and the data were re-analyzed after information regarding the postnatal phenotype was obtained. Based solely on the fetal phenotype, pathogenic, or likely pathogenic, single nucleotide variants were identified in 5 of 19 (26.3%) cases. Moreover, we detected trisomy 21 in two cases by WES-based copy number variation analysis. The overall diagnostic rate was 36.8% (7/19). They were all compatible with respective fetal structural anomalies. By referring to postnatal phenotype information, another candidate variant was identified by a postnatal clinical feature that was not detected in prenatal screening. As detailed phenotyping is desirable for better diagnostic rates in WES analysis, we should be aware that fetal phenotype is a useful, but sometimes limited source of information for comprehensive genetic analysis. It is important to amass more data of genotype-phenotype correlations, especially to appropriately assess the validity of WES in prenatal settings.
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http://dx.doi.org/10.1038/s10038-020-00869-8DOI Listing
May 2021

Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia.

PLoS One 2020 3;15(11):e0241482. Epub 2020 Nov 3.

Department of Obstetrics and Gynecology, School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Around the world, cervical cancer is one of the most common neoplastic diseases among women, and the prognosis of patients in an advanced stage remains poor. To reduce the mortality rate of cervical cancer, early diagnosis and treatment are essential. DNA methylation is an important aspect of gene regulation, and aberrant DNA methylation contributes to carcinogenesis and cancer progression in various cancers. Although 5-methylcytosine (5mC) has been analyzed intensively, the function of 5-hydroxymethylcytosine (5hmC) has not been clarified. The purpose of our study was to identify the molecular biomarkers for early diagnosis of cervical tumors due to epigenetic alterations. To assess the clinical relevance of DNA methylation, we used immunohistochemistry (IHC) to characterize the level of 5hmC in 102 archived human cervical intraepithelial neoplasia (CIN) samples and cervical cancer specimens. The level of 5hmC was significantly decreased between CIN2 and CIN3. The progression of cervical tumors is caused by a reduction of TP53 and RB1 because of HPV infection. We observed that Tp53 and Rb1 were knocked down in mouse embryonic fibroblasts (MEF), a model of normal cells. The level of 5hmC was reduced in Tp53-knockdown cells, and the expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) were induced. In contrast, there was no significant change in Rb1-knockdown cells. Mechanistically, we focused on apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) 3B (A3B) as a cause of 5hmC reduction after TP53 knockdown. In the human cell line HHUA with a wild-type TP53 gene, A3B was induced in TP53-knockdown cells, and A3B knockdown recovered 5hmC levels in TP53-knockdown cells. These data indicate that TP53 suppression leads to 5hmC reduction in part through A3B induction. Moreover, IHC showed that expression levels of A3B in CIN3 were significantly higher than those in both normal epithelium and in CIN2. In conclusion, 5hmC levels are decreased between CIN2 and CIN3 through the TP53-A3B pathway. Since A3B could impair genome stability, 5hmC loss might increase the chances of accumulating mutations and of progressing from CIN3 to cervical cancer. Thus, these epigenetic changes could predict whether CINs are progressing to cancer or disappearing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241482PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608920PMC
December 2020

Efficacy and safety of controlled-release dinoprostone vaginal delivery system (PROPESS) in Japanese pregnant women requiring cervical ripening: Results from a multicenter, randomized, double-blind, placebo-controlled phase III study.

J Obstet Gynaecol Res 2021 Jan 22;47(1):216-225. Epub 2020 Oct 22.

Ferring Pharmaceuticals Co. Ltd., Minato-ku, Tokyo, Japan.

Aim: To evaluate the efficacy and safety of dinoprostone vaginal insert (PROPESS) in pregnant post-term Japanese women requiring cervical ripening.

Methods: This randomized, double-blind, placebo-controlled study included 114 pregnant Japanese women at term (41 weeks of gestation) requiring cervical ripening (baseline Bishop score (BS) ≤ 4). The primary end-point was the proportion of subjects with successful cervical ripening defined as BS ≥ 7 or vaginal delivery in 12 h. The secondary end-points were changes in BS, proportion of women with vaginal delivery, proportion of women receiving mechanical cervical ripening procedure and use of oxytocic drugs.

Results: PROPESS administration for a maximum of 12 h showed significantly higher successful cervical ripening rate (47.4% vs 14.3%, respectively; treatment contrast [TC]: 33.1%; P = 0.0002). The median time from administration to vaginal delivery was significantly shorter in the PROPESS group than in the placebo group (26.18 h vs 33.02 h; OR 2.51; 95% CI [1.60-3.92]; P < 0.0001). In the PROPESS group, the dosage of uterotonic drugs, such as oxytocin, decreased, and the number of patients who used these drugs also decreased.

Conclusion: PROPESS administration for a maximum of 12 h was an effective and well-tolerated treatment for pregnant Japanese women post-term requiring cervical ripening.
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http://dx.doi.org/10.1111/jog.14472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820955PMC
January 2021

Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals.

Reprod Biomed Online 2021 Jan 3;42(1):125-132. Epub 2020 Sep 3.

Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo 116-0023, Japan.

Research Question: What are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles?

Design: A retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum.

Results: The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively).

Conclusions: The highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.
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http://dx.doi.org/10.1016/j.rbmo.2020.09.001DOI Listing
January 2021

Nonsense variants of result in distinct congenital anomalies.

Hum Genome Var 2020 18;7:26. Epub 2020 Sep 18.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Herein, we report two female cases with novel nonsense mutations of at Xq25, encoding stromal antigen 2, a component of the cohesion complex. Exome analysis identified c.3097 C>T, p.(Arg1033*) in Case 1 (a fetus with multiple congenital anomalies) and c.2229 G>A, p.(Trp743*) in Case 2 (a 7-year-old girl with white matter hypoplasia and cleft palate). X inactivation was highly skewed in both cases.
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http://dx.doi.org/10.1038/s41439-020-00114-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501222PMC
September 2020

Effect of thyroxine treatment on pregnancy outcomes in infertile Japanese women with TSH levels between 2.5 μIU/mL and the upper reference limit: a retrospective study.

Endocr J 2021 Feb 1;68(2):171-177. Epub 2020 Oct 1.

Department of Metabolism & Endocrinology, Juntendo University Graduate School, Tokyo 113-8421, Japan.

Recent randomized controlled studies have revealed that levothyroxine (LT4) treatment improves pregnancy outcomes only in infertile women with subclinical hypothyroidism who have thyroid autoantibodies (TAs), but not for those with high TSH levels within the normal range who have TAs. Here, we retrospectively investigated pregnancy outcomes in infertile Japanese women with 2.5 μIU/mL ≤ TSH < upper reference limit (URL). Between 2012 and 2018, 286 patients diagnosed with infertility were followed for more than 1 year at our institution. Among them, we included 106 patients with 2.5 μIU/mL ≤ TSH < URL. We divided these patients into four groups based on the combination of TA positivity and LT4 treatment status to assess the effects of LT4 treatment considering TA positivity on the incidence of pregnancy or miscarriage. In this study, we did not find any significant differences in the rates of pregnancy or miscarriage among the four groups (p = 0.81 and 0.52, respectively). In addition, logistic regression analysis showed that age and history of miscarriage were associated with the incidence of pregnancy, but presence of TAs and LT4 treatment status were not and that no variables examined were associated with the incidence of miscarriage. In summary, we were not able to demonstrate the benefit of LT4 treatment for pregnancy outcomes in Japanese euthyroid infertile women with 2.5 μIU/mL ≤ TSH < URL regardless of TA status in this study.
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http://dx.doi.org/10.1507/endocrj.EJ20-0380DOI Listing
February 2021

Interferon therapy for pregnant patients with essential thrombocythemia in Japan.

Int J Hematol 2021 Jan 23;113(1):106-111. Epub 2020 Sep 23.

Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongou, Bunkyoku, Tokyo, 113-8421, Japan.

Essential thrombocythemia (ET) mainly affects the elderly, but can also develop in women of childbearing age. The risk of miscarriage and other complications during pregnancy in ET patients are reported to be higher than that compared to the general population. Therefore, management of pregnancy in ET patients requires special considerations. Several groups recommend interferon (IFN) therapy for ET patients with high-risk pregnancies, but currently no guidelines are available in Japan. We report the outcomes of nine ET patients with ten consecutive high-risk pregnancies. All patients were successfully managed with IFN-α during their pregnancies. All patients also received aspirin and switched to unfractionated heparin around 36 weeks of gestation. As for the seven pregnancies in which IFN-α was started after detection of pregnancy, median platelet counts decreased from 910 to 573 × 10/L after 2 months of IFN-α therapy, and median platelet counts at the time of delivery for all ten pregnancies was 361 × 10/L. All patients gave birth to healthy children. IFN-α was well tolerated, safe, and effective as a cytoreductive therapy for all patients. Although evidence is limited and the use of IFN is not approved in Japan, we suggest considering IFN therapy for high-risk ET pregnancies.
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http://dx.doi.org/10.1007/s12185-020-03001-wDOI Listing
January 2021

Respiratory Distress Syndrome in Infants Delivered via Cesarean from Mothers with Preterm Premature Rupture of Membranes: A Propensity Score Analysis.

J Pregnancy 2020 31;2020:5658327. Epub 2020 Jul 31.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.

Objective: This study aimed to clarify the effects of cesarean delivery on neonatal respiratory morbidity when women had preterm premature rupture of membranes.

Methods: This retrospective study included women with preterm premature rupture of membranes who delivered from 23 weeks to 33 weeks of gestation between January 2009 and December 2014. Neonatal outcomes were compared between infants delivered by cesarean section and those delivered vaginally. The primary outcome was respiratory distress syndrome (RDS). Neonatal intubation and mechanical ventilation periods were secondary outcomes. Propensity score matching was used to compare outcomes between cesarean and vaginal delivery cases.

Results: There were 101 cesarean deliveries and 89 vaginal deliveries. A comparison of the presence or absence of neonatal complications based on the delivery type indicated a higher occurrence of RDS with cesarean deliveries ( = 0.025). The intubation and mechanical ventilation periods were not significantly longer in neonates delivered via cesarean section.

Conclusions: Cesarean delivery is a risk factor for neonatal RDS in women with preterm premature rupture of membranes. Trials identifying long-term neonatal prognoses are needed to further develop optimal management strategies in such cases.
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http://dx.doi.org/10.1155/2020/5658327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415122PMC
September 2020

Comparison of the labor curves with and without combined spinal-epidural analgesia in nulliparous women- a retrospective study.

BMC Pregnancy Childbirth 2020 Aug 15;20(1):467. Epub 2020 Aug 15.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Neuraxial labor analgesia is known to increase the rate of instrumental delivery and prolong the second stage of labor; however, there is no standard method to evaluate the progress of labor under analgesia. Friedman curve is considered the gold standard for evaluating the progress of labor. However, it included not only neuraxial labor analgesia but also labor without analgesia. Thus we compared the labor curves of primiparous women undergoing labor with and without neuraxial labor analgesia, to understand the progress of labor in both groups and to arrive at a standard curve to monitor the progress of labor under neuraxial analgesia.

Methods: Primiparous women with cephalic singleton pregnancies who delivered at term from 2016 to 2017 were included. Two hundred patients who opted for combined spinal-epidural (CSE) labor analgesia were included in the CSE group and 200 patients who did not undergo CSE were included in the non-CSE group. In all, 400 cases were examined retrospectively. The evaluation parameters were cervical dilation and fetal station, and we calculated the average value per hour to plot the labor curves.

Results: The labor curve of the non-CSE group was significantly different from the Friedman curve. In the CSE group, the time from 4 cm dilation of the cervix to full dilation was 15 h; in addition, the speed of cervical dilation was different from that in the non-CSE group. The progress of labor in the CSE group was faster than that in the non-CSE group during the latent phase; however, the progress in the CSE group was slower than that in the non-CSE group during the active phase.

Conclusions: Neuraxial labor analgesia results in early cervical dilation and descent of the fetal head; thus, appropriate advance planning to manage the delivery may be essential.
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http://dx.doi.org/10.1186/s12884-020-03161-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429797PMC
August 2020

Antepartum eclampsia with reversible cerebral vasoconstriction and posterior reversible encephalopathy syndromes.

J Obstet Gynaecol Res 2020 Oct 10;46(10):2147-2152. Epub 2020 Aug 10.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

A 39-year-old pregnant woman was experienced thunderclap headache due to reversible cerebral vasoconstriction syndrome (RCVS) as a prodromal symptom. Two days after, she was brought to our hospital after an eclamptic seizure at 35 weeks of gestation. After management with magnesium sulphate, a cesarean delivery was performed, and passed without eclamptic seizure recurrence with calcium channel blocker (CCB) administration for hypertension and prophylaxis of another seizure. Antepartum eclampsia is sometimes complicated by headache as a prodromal symptom. Cerebrovascular diseases in the perinatal period include eclampsia, RCVS and posterior reversible encephalopathy syndrome, which have potentially overlapping pathologies. Here, we first report a case of overlapping those three diseases in the antepartum period. Our best literature review showed that antepartum RCVS is severe and has complications besides thunderclap headache, and there is a case report which CCB administration was shown to be effective in the treatment of antepartum RCVS. If thunderclap headache is recognized, prediction of eclampsia and getting better course of RCVS with CCB administration may be possible.
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http://dx.doi.org/10.1111/jog.14410DOI Listing
October 2020

Maternal risk score for the prediction of fetal inflammatory response syndrome after preterm premature rupture of membranes.

J Obstet Gynaecol Res 2020 Oct 2;46(10):2019-2026. Epub 2020 Aug 2.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.

Aim: Preterm premature rupture of membranes (PPROM) is common in preterm births. Fetal inflammatory response syndrome (FIRS) is present in nearly 50% of PPROM cases. We created a risk score to predict FIRS using maternal factors after PPROM.

Methods: We conducted a retrospective study of singleton pregnancies complicated by PPROM that resulted in delivery at 23-35 weeks of gestation. Antepartum maternal factors and umbilical cord blood interleukin-6 (IL-6) data were analyzed. FIRS was defined as IL-6 > 11 pg/mL.

Results: Umbilical cord blood IL-6 and maternal blood data within 24 h before parturition were available for 158 cases; 66 were diagnosed with FIRS (41.8%; median IL-6, 57.55 pg/mL). We created a risk score (FIRS score) comprising expected delivery weeks (≤30 weeks), maternal C-reactive protein (≥1.2 mg/dL), maternal white blood cell count (≥13 000/μL), corticosteroid use (none) and PROM latency period (≥3 days) from the multivariate logistic regression model predicting FIRS. Receiver operating characteristic curve analysis of the score produced the following results: area under the curve, 0.82; 95% CI, 0.76-0.89; cut-off value, 7.5; sensitivity, 89%; specificity, 63%; positive predictive value, 63% and negative predictive value, 89%. The probability of FIRS according to the categories of the FIRS score was 11% for those with a score of 0-7, 50% for a score of 8-15, and 88% for a score of 16-22.

Conclusion: The devised maternal risk score could predict FIRS and be helpful to decide the delivery timing for the cases of PPROM.
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http://dx.doi.org/10.1111/jog.14414DOI Listing
October 2020

Pure 9p duplication syndrome with aplasia of the middle phalanges of the fifth fingers.

Eur J Med Genet 2020 Oct 18;63(10):104005. Epub 2020 Jul 18.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

9p duplication syndrome is a common congenital anomaly syndrome with specific facial features, mental and developmental retardations, and characteristic fingers. Pure 9p duplication without other chromosomal structural variations is very rare. It has recently been reported that cases with partial 9p duplication including SMARCA2 have phenotypes overlapping with Coffin-Siris syndrome (CSS). Herein, we present a family with pure 9p duplication syndrome in which phenotypes partially characteristic of CSS were identified. In one of two siblings, X-ray examination revealed hypoplasia of the distal phalanges of the fifth fingers, aplasia of the middle phalanges of the fifth fingers, and aplasia of the distal phalanges of the second to fifth toes. In pure 9p duplication together with our one affected case, 9 out of 14 cases (64.3%), excluding cases whose clinical data were unavailable, presented the absence or hypoplasia of the middle phalanges of fingers or toes. Interestingly, there are no reports on CSS with aplasia or hypoplasia of the middle phalanx. Therefore, this family might suggest that the aplasia or hypoplasia of the middle phalanges of the fifth fingers or toes is a distinct finding that can distinguish between pure 9p duplication and CSS.
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http://dx.doi.org/10.1016/j.ejmg.2020.104005DOI Listing
October 2020

Retraction Note to: Nonsense variants in STAG2 result in distinct sex-dependent phenotypes.

J Hum Genet 2020 09;65(9):811

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s10038-020-0782-2DOI Listing
September 2020

Modified permeable cryoprotectant-free vitrification method for three or fewer ejaculated spermatozoa from cryptozoospermic men and 7-year follow-up study of 14 children born from this method.

Hum Reprod 2020 05;35(5):1019-1028

Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.

Study Question: What technique can be used to successfully cryopreserve three or fewer ejaculated spermatozoa from cryptozoospermic men and is the physical and cognitive development of children born after this technique normal?

Summary Answer: The modified cryopreservation method for three or fewer human spermatozoa from cryptozoospermic men showed a recovery rate above 95% and a survival rate just under 90%, and the physical and cognitive abilities of the children born after ICSI were comparable to those born after natural conception.

What Is Known Already: Clinical outcomes of ICSI using cryptozoospermic men's ejaculated spermatozoa are considered to be inferior to that using testicular spermatozoa from microsurgical testicular sperm extraction (Micro-TESE), possibly because the DNA fragmentation rate is higher in ejaculated spermatozoa than in testicular spermatozoa from Micro-TESE.

Study Design, Size, Duration: Evaluation of the efficiency of cryopreservation of three or fewer spermatozoa was conducted retrospectively at St. Mother Clinic. The physical and cognitive development of children born after this method was studied between 2011 and 2018.

Participants/materials, Setting, Methods: This study included 28 cryptozoospermic men who had three or fewer morphologically normal and motile spermatozoa in their ejaculate after centrifugation and who preferred using cryopreserved spermatozoa to Micro-TESE. Control subjects were 31 cryptozoospermic patients using fresh spermatozoa from their ejaculates and 20 non-obstructive azoospermic patients with fewer than 10 spermatozoa obtained by TESE and vitrified. Clinical outcomes among three groups, vitrified spermatozoa from the ejaculate, fresh spermatozoa from the ejaculate and vitrified spermatozoa from the testis, were statistically analysed. For the 7-year follow up study of the 14 children born after ICSI using the ejaculated vitrified spermatozoa, the Japanese government-issued Boshi Kenko Techo (Mother-Child Handbook) and Kinder Infant Development Scale (KIDS scale) were used to determine whether their physical and cognitive development was comparable to that of naturally conceived children.

Main Results And The Role Of Chance: Recovery and survival rates were 97.8% (510/521) and 87.1% (444/510) for vitrified spermatozoa from the ejaculate and 92.7% (152/164) and 60.5% (92/152) for vitrified spermatozoa from the testis. Clinical pregnancies (%), miscarriages (%) and live birth rates (%), respectively, among the three groups were as follows: vitrified spermatozoa from the ejaculate: 15(25.0), 2(13.3), 13(21.7); fresh spermatozoa from the ejaculate: 26(24.3), 5(19.2), 20(18.7); and vitrified spermatozoa from the testis: 3(16.7), 0(0.0), 3(16.7). Among the groups, there were no statistically significant differences except for the sperm survival rate and the oocyte fertilisation rate, which were lower for vitrified spermatozoa from the testis compared with vitrified spermatozoa from the ejaculate. The 7-year follow-up study showed that the physical and cognitive development of 14 children born after ICSI using vitrified ejaculated spermatozoa from the ejaculate was comparable to that of naturally conceived children.

Limitations, Reasons For Cautions: The maximum number of spermatozoa to which this method can be applied successfully is about 10. When the number of aspirated spermatozoa is over 10, some of them change direction after colliding with each other inside the aspiration pipette and reach the mineral oil, and once this happens, they cannot be expelled out of the pipette. Even though we did not find evidence of DNA fragmentation, further studies with larger participant numbers and longer time periods are necessary.

Wider Implications Of The Findings: This technique is very useful for the cryopreservation of very small numbers of testicular spermatozoa (fewer than 10) in order to avoid or reduce Micro-TESE interventions.

Study Funding/competing Interest(s): No external funding was received to undertake this study. There are no competing interests.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa072DOI Listing
May 2020

Laparoscopic Removal of Modified Vertical Uterine Compression Sutures due to Postoperative Focal Pain.

Surg J (N Y) 2020 Apr 31;6(2):e67-e70. Epub 2020 Mar 31.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Previously we reported laparoscopic removal of compression sutures due to uterine ischemia and related pain, which has two of the difficult aspects: (1) maneuvering the curved needle to perform compression suturing in the narrow surgical field, and (2) distinguishing between the threads of the cesarean section wound sutures versus the vertical compression sutures during removal, as the threads are the same white color. We performed vertical compression sutures for intrapartum hemorrhage with total placental previa, and modified both the needle type and the color of the thread used for uterine compression sutures during cesarean section. After the operation, we performed successful laparoscopic removal of compression sutures for postoperative focal pain. Changing the needle type and color helped to perform operations. The present case supports the concept that the laparoscopic removal of uterine compression suturing is useful for controlling pain in cases where general analgesics are ineffective.
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http://dx.doi.org/10.1055/s-0040-1708865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108947PMC
April 2020

Use of sound-elicited fetal heart rate accelerations to assess fetal hearing in the second and third trimester.

Int J Pediatr Otorhinolaryngol 2020 Jun 13;133:110001. Epub 2020 Mar 13.

Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo, Japan. Electronic address:

Objectives: We previously reported that fetal heart rate (FHR) accelerations could be obtained after fetal sound stimulation. We examined FHR accelerations during 20-37 weeks gestational age (GA) in order to assess the optimal time for the test.

Methods: The fetus was stimulated from the maternal abdomen with pure tone 2000 Hz, 90 dB, 5 s. Changes in the FHR before and after the sound stimulation were measured by a cardiotocometer.

Results: Compared with the positive rate of FHR accelerations at 20-21 weeks GA, significant increases were recognized in 26-27, 28 to 29, 30 to 31, and 34-35 weeks GA. Comparing the positive rate of FHR accelerations between the minimal and moderate variability of FHR baseline, no significant differences were observed at 20-27 weeks GA. On the other hand, at 28-37 weeks GA, the positive rate to detect FHR accelerations due to sound stimulation was 100% in moderate FHR baseline variability.

Conclusion: Considering development of human fetal hearing, the method should be performed between 28 and 37 weeks GA and during moderate FHR variability corresponding to active sleep conditions. The method developed in the present study may provide a promising tool for evaluating the fetal hearing.
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http://dx.doi.org/10.1016/j.ijporl.2020.110001DOI Listing
June 2020

Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production.

Sci Rep 2020 03 18;10(1):4962. Epub 2020 Mar 18.

Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While β-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust downregulation of cell cycle-related genes 1 day after parturition, and the reupregulation of serotonin metabolism-related genes at postpartum day 7. Serotonin synthesis was activated only in lactating females, accompanied by increased β-cell mass. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.
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http://dx.doi.org/10.1038/s41598-020-61850-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080838PMC
March 2020

Dual-specificity phosphatase 6 plays a critical role in the maintenance of a cancer stem-like cell phenotype in human endometrial cancer.

Int J Cancer 2020 10 26;147(7):1987-1999. Epub 2020 Mar 26.

Department of Obstetrics and Gynecology, School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The prognosis of patients with high-grade or advanced-stage endometrial cancer remains poor. As cancer stem-like cells (CSCs) are thought to be associated with endometrial cancers, it is essential to investigate the molecular mechanisms that regulate endometrial CSCs. Dual-specificity phosphatase 6 (DUSP6) functions as a negative-feedback regulator of MAPK-ERK1/2 signaling, but its role in endometrial cancer remains unknown. We investigated whether DUSP6 is involved in cancer cell stemness using endometrial cancer cell lines and specimens from endometrial cancer patients. DUSP6 induced the expression of CSC-related genes including ALDH1, Nanog, SOX2 and Oct4A, increased the population of cells in the G0/G1 phase, and promoted sphere formation ability. DUSP6 knockdown resulted in reduced cell invasion and metastasis, whereas DUSP6 overexpression inhibited apoptosis under serum-free conditions. Moreover, DUSP6 decreased phosphorylated ERK1/2 and increased phosphorylated Akt levels, which potentially induces CSC features. In patients with endometrial cancers, DUSP6 expression was determined using immunohistochemistry, and based on the results, the patients were dichotomized into high- and low-DUSP6-expression groups. Progression-free survival and overall survival were significantly shorter in the high-DUSP6-expression group. These results suggest that DUSP6 has potential value as a biomarker of CSCs and as a target of therapies designed to eliminate CSCs in endometrial cancer.
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http://dx.doi.org/10.1002/ijc.32965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496376PMC
October 2020

Retrospective study of the recurrence risk of preterm birth in Japan.

J Matern Fetal Neonatal Med 2020 Feb 18:1-5. Epub 2020 Feb 18.

Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan.

A history of preterm birth is a risk factor for preterm birth in a future pregnancy, and there are some reports of prevention methods, such as the administration of progesterone. However, the rate of recurrence of preterm birth in Japan has not been clarified, and there is no data for judging whether these preventive methods are effective. To clarify the risk of recurrence of preterm birth and preterm prelabor rupture of membranes (pPROM) in Japan. A retrospective study was conducted using the perinatal registration database of the Japan Obstetrics and Gynecology Society for the Perinatal Center from 2014 to 2016. There were 704,418 subjects, of which 190,990 were excluded those with unknown maternal information, those under the age of 20 years, those with perinatal disease related to preterm birth, and first-time mothers. Logistic model unavailable and multivariate analysis were performed. An analysis of the preterm birth history indicated the risk of preterm birth in the current pregnancy, and the odds ratio for preterm birth recurrence once, twice, and three times or more was 3.3, 6.6, and 7.8, respectively. As a secondary analysis, we analyzed whether the history of pPROM is a risk factor of recurrence of pPROM and found a significant association with an odds ratio of 3.4. Having a preterm birth history increases the risk of recurrence of preterm birth, and the risk of recurrent preterm birth increases as the number of preterm births increases. Although this report is intended for high-risk pregnancies wherein the rate of preterm birth is high, as previously reported, our data indicate that in Japan, preterm birth is a risk factor of recurrent preterm birth.
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http://dx.doi.org/10.1080/14767058.2020.1727435DOI Listing
February 2020

Assessment of extravasation on ruptured uterine artery pseudoaneurysm using contrast-enhanced ultrasonography during uterine balloon tamponade.

J Int Med Res 2020 Apr 20;48(4):300060519893166. Epub 2019 Dec 20.

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Objective: Contrast-enhanced ultrasonography (CEU) has been used in critical trauma situations to visualize extravasation; however, its use is limited in the field of obstetrics. Cases of ruptured uterine artery pseudoaneurysm (UAP) were analyzed to clarify the efficacy to CEU during uterine balloon tamponade.

Methods: Cases of ruptured UAP diagnosed at a teaching university hospital from January 2015 to December 2017 were retrospectively analyzed. UAP was diagnosed using color Doppler ultrasonography. Extravasation was identified using computed tomography and double checked using CEU with an intravenously administered contrast agent (Sonazoid; Daiichi Sankyo Company, Ltd., Tokyo, Japan) and an ultrasound instrument (HI VISION Preirus; Hitachi Aloka Medical, Ltd., Tokyo, Japan). A balloon was then inserted into the uterine cavity and inflated at the point of bleeding until extravasation ceased.

Results: Three patients exhibited ruptured UAP during the study period. Bleeding points were successfully identified using CEU in all cases, and hemostasis was achieved using uterine balloon tamponade. Obliteration of UAP was confirmed using magnetic resonance imaging, and no patients developed recurrent UAP or any complications.

Conclusion: CEU can be used at the bedside to promptly diagnose ruptured UAP. Moreover, it precisely facilitates balloon compression at the point of bleeding.
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http://dx.doi.org/10.1177/0300060519893166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645375PMC
April 2020

Hereditary angioedema with deep vein thrombosis and pulmonary thromboembolism during pregnancy.

Taiwan J Obstet Gynecol 2019 Nov;58(6):895-896

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.

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http://dx.doi.org/10.1016/j.tjog.2019.04.003DOI Listing
November 2019