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Some monochorionic twin pregnancies need intensive cardiac management even in the absence of twin-to-twin transfusion syndrome after birth. The purpose of this study was to investigate risk factors related to persistent hypotension requiring cardiotonic agent use among monochorionic twin pregnancies without twin-to-twin transfusion syndrome.This was a retrospective study of 316 monochorionic twin pregnancies without twin-to-twin transfusion syndrome (632 babies). All cases were treated in the neonatal intensive care unit. Hypotension was defined as mean arterial blood pressure below the norm for gestational age. Decreased left ventricular ejection fraction was defined as a value60%. Dopamine, dobutamine and phosphodiesterase III inhibitor were used as cardiotonic agents for hypotension persisting even after adequate infusion.Among the 632 cases, 33 (5.2%) needed cardiotonic agents for persistent hypotension. The frequency of persistent hypotension with decreased left ventricular ejection fraction was significantly higher among larger twins (4.4%) than among smaller twins (0.6%, p = 0.0038). In larger twins, multivariate analysis showed that Z-score for cardiothoracic area ratio (odds ratio, 2.31; p 0.001), tricuspid regurgitation (odds ratio, 6.34; p = 0.015) and gestational age at delivery (odds ratio, 0.66; p 0.001) correlated with persistent hypotension. In smaller twins, univariate analysis showed gestational age at delivery, birth weight, Z-score for birth weight and Z-score for cardiothoracic area ratio of the larger twin were related to persistent hypotension. Concentration of brain natriuretic peptide in the umbilical vein in larger and smaller twins were significantly correlated (coefficient of correlation = 0.792, p 0.001).In monochorionic twin pregnancies, attention needs to be given to cardiac size along with amniotic fluid and fetal growth. Both larger and smaller twins carry risks of persistent hypotension after birth. Close observation is needed, especially in cases where the larger twin displays cardiomegaly despite absence of twin-to-twin transfusion syndrome.

Background: There have been no previous reports on the postnatal course, especially long-term outcomes, of fetal hydrothorax patients, including those treated with thoracoamniotic shunting (TAS) using a double-basket catheter.The outcomes of cases from a single center are reported. Methods: Cases of fetal hydrothorax managed at our center between 2005 and 2015 were enrolled retrospectively. TAS was performed if indicated. Long-term outcomes such as cerebral palsy, developmental disabilities, and others were analyzed. Results: Ninety-two cases of fetal hydrothorax were included. The causes were primary chylothorax, transient abnormal myelopoiesis, cardiac disease, pulmonary sequestration, mediastinal neoplasm, and infection. TAS was performed in 36 cases. Early neonatal death occurred in 19 cases. The 28-day survival rates for all cases and for TAS cases were 70% (48/69) and 72% (26/36), respectively. Of the cases that underwent TAS, one was treated with home oxygen therapy, one was diagnosed with cerebral palsy and severe intellectual disability, and five were diagnosed with mild or moderate developmental disabilities. Conclusions: The results showed that the survival rate and long-term outcomes of cases with hydrothorax have improved as TAS has become more prevalent. The reasons for these results need to be elucidated, and efforts are needed to further improve outcomes.

Objective: To elucidate the efficacy and safety of attempting a vaginal birth and to understand the factors that contribute to the increased risk of operative delivery in women aged 40 years or old...

Although amnioinfusion (AI) for repetitive variable deceleration has been reported to reduce the frequency of variable deceleration and cesarean section (CS) rate, CS is sometimes unavoidable even after therapeutic AI. The purpose of this study was to investigate prenatal factors related to the efficacy of therapeutic AI during labor.This retrospective study investigated 80 singleton pregnancies that underwent transcervical therapeutic AI for repetitive variable deceleration during labor. AI was performed with 500 mL of warmed saline through an intrauterine pressure catheter by gravity infusion. Prenatal factors related to emergency CS for fetal distress even after therapeutic AI were investigated.Emergency CS was performed for 12 of the 80 cases due to fetal distress. Z-score for umbilical cord length was significantly smaller in the CS group (-0.68 SD) than in the vaginal delivery group (0.15 SD,Therapeutic AI for repetitive variable deceleration was considered useful, in many cases avoiding emergency CS. Short umbilical cord length (lower Z-score) was related to emergency CS after therapeutic AI for repetitive variable deceleration. Umbilical cord length may offer an important factor for assessing the risk of fetal distress that is difficult to avoid, if methods to accurately determine umbilical cord length can be developed.

Aim Cervical cancer onset initially occurs during youth. Papanicolaou tests performed in early pregnancy can detect cervical cancer; however, Papanicolaou tests during pregnancy have been noted to be inaccurate, reflecting changes associated with pregnancy. Therefore, we assessed the effect of pregnancy on Papanicolaou test results. Methods Of 1351 pregnant women who delivered at Ise Red Cross Hospital between January 2010 and December 2014, 1213 underwent Papanicolaou tests at early pregnancy and post-partum. We compared the Papanicolaou test results. Results The results of the Papanicolaou test were different in 32 patients. Of the 1191 patients negative for intraepithelial lesions or malignancy in early pregnancy, 16 had other cytological abnormalities post-partum. We performed therapeutic conization post-partum in four patients. The Papanicolaou test results in early pregnancy of the four patients were negative for intraepithelial lesions or malignancy in one patient, atypical squamous cells of undetermined significance in one and high-grade squamous intraepithelial lesion in two. Conclusion The results of the Papanicolaou test during pregnancy may not be accurate because of the influence of hormones associated with pregnancy. Taking advantage of the one-month post-partum screening visit can lead to early detection and treatment of cervical cancer in young people.

Our study aimed to analyze the differences in intra-amniotic pressures in patients with polyhydramnios with and without symptoms.We recruited patients with pregnancies in which amnioreduction was performed for polyhydramnios in the Department of Fetal-Maternal Medicine at Nagara Medical Center between April 2017 and August 2018. Amnioreduction was performed for severe polyhydramnios with maternal symptoms [symptomatic group] or polyhydramnios without maternal symptoms [asymptomatic group] such as abdominal distension, dyspnea, or threatened premature labor. We measured the intra-amniotic pressure after every 200 ml volume reduction during the amnioreduction.A total of 27 patients who underwent amnioreduction were classified into symptomatic (66.7%, 18/27) and asymptomatic (33.3%, 9/27) groups. Gestational age, amniotic fluid index at the time of amnioreduction, and the volume of amniotic fluid removed were not significantly different between the symptomatic and asymptomatic groups [median 32.4 weeks vs. 33.1 weeks, median 38.0 cm vs. 39.0 cm, and median 1500 ml vs. 2500 ml, respectively]. However; the intra-amniotic pressure before amnioreduction was significantly higher in the symptomatic group than in the asymptomatic group [median 15.0 mmHg (range, 10-27) vs. 10.0 mmHg (range, 6.0-13); p 0.005]. After amnioreduction, these pressures decreased significantly to median 9.0 mmHg (range, 5.0-13) (p 0.001) in the symptomatic and 7.0 mmHg (range, 4.0-11) (p 0.05) in the asymptomatic group. The median intra-amniotic pressure gradually decreased and reached a plateau during the amnioreductions in both groups.With polyhydramnios, the intra-amniotic pressure was significantly higher in the symptomatic group than in the asymptomatic group. Therefore, uterine pressure tolerance might vary according to the individual. In addition, intra-amniotic pressure monitoring might enhance the safety during amnioreduction procedures to avoid drastic and potentially harmful pressure changes.

We report prophylactic amnioinfusion (AI) for variable decelerations in umbilical cord compression without oligohydramnios as an early sign of deterioration. We performed a transabdominal AI in cases without oligohydramnios using the ultrasonography findings of umbilical cord compression (i.e. sandwich sign [SWS]) and variable decelerations (VD) in a foetal heart rate. Thirteen cases and 21 AIs were analysed. Nine (69%) cases were of a foetal growth restriction and 4 (31%) had umbilical hyper-coiled cords. VD frequency (p .0001), umbilical artery pulsatility index (PI) (p .01) and ductus venous PI (0.66 vs. 0.48; p .05) significantly decreased, and an umbilical venous (UV) flow volume (121 vs. 197 ml/min/kg; p .05) significantly increased after AI. The umbilical artery diastolic blood flow abnormalities and UV pulsation improved. In conclusion, AI improves the umbilical cord compression even without oligohydramnios. The SWS is an important marker of deterioration to severe oligohydramnios and latent foetal damage. IMPACT STATEMENT What is already known on this subject? Antepartum variable decelerations due to umbilical cord compression are significantly associated with the deceleration in labour. In particular, foetal hypoxia leads to other adverse events such as foetal distress, hypoxic-ischemic encephalopathy, and pulmonary arterial hypertension after birth. Amnioinfusion has been shown to be effective in patients who also have oligohydramnios. What do the results of this study add? Amnioinfusion may be effective in the cases with ultrasonography findings of umbilical cord compression (i.e. sandwich sign) and in cases with variable decelerations in foetal heart rate, but without oligohydramnios. What are the implications of these findings for clinical practice and/or further research? Amnioinfusion may be helpful to prevent adverse events including oligohydramnios and anhydroamnios.

Objective: To elucidate the efficacy of continuous amnioinfusion on perinatal outcome in women with preterm premature rupture of membranes (PPROM) at periviable gestational ages.Methods: A database...

Objective: To elucidate the efficacy of induction of labor with metreurynter for women with one previous cesarean delivery. Methods: A database was reviewed to identify women with singleton and vertex pregnancies who underwent trial of labor after one cesarean delivery (TOLAC) at or after 39 weeks of gestation between the years 2010 and 2016. Results: Fifty-one women underwent induction of labor with metreurynter, and 230 women had spontaneous onset of labor pain. Successful TOLAC was observed in 95.2% (219/230) and 74.5% (38/51) of women with spontaneous onset of labor pain and induction, respectively (p

Intra-amniotic, fetal intrathoracic, and intraperitoneal pressures during pregnancy have been previously investigated. However, to our knowledge, changes in these pressures during uterine contractions have not been reported. Herein, we present three cases of polyhydramnios, fetal pleural effusion, and fetal ascites, in which intra-amniotic, fetal intrathoracic, intraperitoneal pressures increased with uterine contractions. These pressure increases may affect the fetal circulation. We suggest that managing potential premature delivery (e.g., with tocolysis) is important in cases with polyhydramnios and excess fluid in fetal body areas, such as the thorax, abdomen, and heart. The results of this preliminary study on intrafetal pressure measurements will be useful in performing fetal and neonatal surgeries in the future.

To evaluate the short- and long-term outcomes among very low birth weight (VLBW) preterm infants after histologic chorioamnionitis (HCA).We performed a retrospective analysis of 5849 single infants (birth weight1500 g) born at a gestational age between 22 + 0 and 33 + 6 weeks. Clinical data were obtained from the Neonatal Research Network Japan between 2003 and 2007. Multivariable logistic regression analyses were performed to assess the effect of HCA on short- and long-term outcome.According to logistic regression analysis, HCA was associated with lower incidence of respiratory distress syndrome (odds ratio [OR] = 0.54; p 0.001), increased chronic lung disease (OR = 1.68; p 0.001) and sepsis (OR = 1.71; p 0.001) and as a short-term outcomes. There was no significant association with intraventricular hemorrhage (OR = 1.11; p = 0.33), periventricular leukomalacia (OR = 1.07; p = .070) and death before discharge (OR = 0.97; p = 0.084). HCA was associated with increased home oxygen therapy (OR = 3.09; p 0.001), but not with cerebral palsy (CP; OR = 0.91; p = 0.63), develop quotient 70 (OR = 1.27; p = 0.17), visual impairment (OR = 1.08; p = 0.77), severe hearing impairment (OR = 1.28; p = 0.62) and death (OR = 0.98; p = 0.91) before three years of age.In this retrospective population-based study in Japan, HCA was not a risk factor for death, neurodevelopmental impairment and CP in VLBW three-year-old preterm infants.

Acute funisitis is characterized by the infiltration of fetal neutrophils from the umbilical vessels into Wharton’s jelly and presents as fetal inflammation. However, no reports about its prenatal diagnosis using ultrasonography have been published. We encountered one case of oligohydramnios at 26 weeks and another case of threatened premature delivery at 27 weeks of gestation with ultrasonographic findings of non-uniform thickening of Wharton’s jelly, a heterogeneous internal echo, and a high echoic line of the umbilical vessel wall. Acute funisitis was diagnosed, and the postpartum histopathological examination revealed severe funisitis in both cases. To our knowledge, this is the first case report of prenatal diagnosis of funisitis determined using ultrasonography. When we find such ultrasonographic features under the circumstances of intrauterine infection, severe funisitis should be included in the differential diagnosis.

To clarify the association between amniotic neutrophil elastase levels and the development of bronchopulmonary dysplasia (BPD).The database between July 2001 and December 2012 was reviewed for women with amniocentesis on admission for amniotic fluid neutrophil elastase levels and with singleton deliveries between 22 + 0 and 31 + 6 weeks of gestation. Following deliveries, placentas were examined for histologic chorioamnionitis. The peripheral blood of the neonates was analyzed for acute phase reactants.Among 294 infants, no, mild, moderate or severe BPD was observed in 126, 89, 40 and 39 infants, respectively. The medians of gestational age on admission, at premature rupture of membranes and at delivery were significantly smaller in BPD (+) when compared with BPD (-) (p 0.001). The median level of amniotic neutrophil elastase on admission was significantly greater in BPD (+) than that in BPD (-). Histologic chorioamnionitis and funisitis were both detected more frequently in BPD (+) patients than in BPD (-) patients. In a logistic regression model, the only variable that affected an increased chance of BPD was the gestational age at delivery (odds ratio, 0.58; 95% confidence interval, 0.36-0.92; p = 0.021).The level of amniotic neutrophil elastase cannot be a definitive risk factor for BPD.

Aim The aim of this study was to clarify the association between fetal heart rate (FHR) tracing interpretation levels in the second stage of labor and poor fetal acid-base balance. Material and Methods The database at one tertiary hospital in Nagoya, Japan, was retrospectively reviewed for women with singleton fetuses in cephalic presentation and vaginal labor at ≥37 + 0 gestational weeks between 1 June 2011 and 30 April 2012. Continuous FHR tracings in the second stage of labor were subdivided into 15-min intervals, each of which we called a window, from the beginning of labor through delivery, and were assessed according to the five-tier classification proposed by the Japan Society of Obstetrics and Gynecology, in which level 1 is normal, level 2 is subnormal, and levels 3–5 are abnormal patterns. Results In total, 777 parturient women were eligible for the study protocol. The numbers of women with maximal levels of 1, 2, 3, 4, and 5 were 3, 77, 341, 349, and 7, respectively. No cases of severe fetal acidosis (pH

To evaluate the effectiveness of antenatal corticosteroids (AC) therapy on outcomes of very low birthweight infants with histologic chorioamnionitis. We performed a retrospective analysis of 10,935 single infants born at a gestational age between 22 + 0 and 33 + 6 weeks and birth weight

To elucidate the factors that contribute to prolonged pregnancy and promote neonate survival in women with bulging fetal membranes.A database was reviewed to identify women with singleton pregnancies who underwent amniocentesis on admission to determine amniotic fluid neutrophil elastase levels before 26 + 0 weeks gestation between July 2001 and January 2015. Following delivery, the placentas of these patients were examined for histologic chorioamnionitis.Ninety-seven women delivered before 28 weeks gestation, and 117 women delivered at or after 28 weeks gestation. Rescue cerclage performed via the McDonald procedure (adjusted odds ratio [aOR]: 3.78; 95% confidence interval [CI]: 1.35-11.80) was associated with a higher likelihood of reaching at least 28 weeks gestation before delivery, whereas protruding membranes (aOR: 0.38; 95% CI: 0.18-0.78), elevated amniotic neutrophil elastase levels (≥0.15 μg/ml) (aOR, 0.41; 95% CI: 0.20-0.82) and elevated peripheral C-reactive protein levels (≥0.4 mg/dl) (aOR: 0.34; 95% CI: 0.180.65) were associated with a significantly reduced likelihood of reaching this gestational age before delivery. Among women who underwent rescue cerclage, amniorrhexis was associated with a negative prognosis (aOR: 0.18; 95% CI: 0.05-0.51).Intra-amniotic inflammation, protrusion of fetal membranes and amniorrhexis are factors that may prevent pregnancy prolongation. Rescue cerclage improves pregnancy outcomes.

Cervical cancer onset initially occurs during youth. Papanicolaou tests performed in early pregnancy can detect cervical cancer; however, Papanicolaou tests during pregnancy have been noted to be inaccurate, reflecting changes associated with pregnancy. Therefore, we assessed the effect of pregnancy on Papanicolaou test results.Of 1351 pregnant women who delivered at Ise Red Cross Hospital between January 2010 and December 2014, 1213 underwent Papanicolaou tests at early pregnancy and post-partum. We compared the Papanicolaou test results.The results of the Papanicolaou test were different in 32 patients. Of the 1191 patients negative for intraepithelial lesions or malignancy in early pregnancy, 16 had other cytological abnormalities post-partum. We performed therapeutic conization post-partum in four patients. The Papanicolaou test results in early pregnancy of the four patients were negative for intraepithelial lesions or malignancy in one patient, atypical squamous cells of undetermined significance in one and high-grade squamous intraepithelial lesion in two.The results of the Papanicolaou test during pregnancy may not be accurate because of the influence of hormones associated with pregnancy. Taking advantage of the one-month post-partum screening visit can lead to early detection and treatment of cervical cancer in young people.

Objective To assess the neonatal and maternal outcomes of pregnancy complicated by previable preterm premature rupture of membranes (PPROM). Design Retrospective study. Setting Tertiary referral hospital. Sample. Forty-five women having aggressive intervention with antibiotics, amnioinfusion, cerclage and tocolysis. Methods The hospital database between July 2001 and December 2009 was reviewed for women with singleton fetuses and PPROM before 23(+0) weeks of gestation. We analysed maternal and neonatal characteristics. Main outcome measures Neonatal survival without major morbidity. Results Thirty-eight infants were delivered alive and seven were stillborn. Ten infants died in the neonatal intensive care unit and one in the labor ward. Twenty-seven live-born infants survived to discharge from hospital. The survival rate of pregnancies with aggressive management was 60% (27 of 45); that of live-born infants was 71.1% (27 of 38). The median gestational age at PPROM and at delivery were significantly lower in the non-surviving group than the surviving group. Thirty-seven women (82.2%) had an amniotic neutrophil elastase level >0.15 μg/mL. Only four women (8.9%) developed clinical chorioamnionitis. Overall, 90.7% of the women showed histological evidence of chorioamnionitis. Eighty-three per cent of the surviving children had bronchopulmonary dysplasia. Nine infants had serious sequelae at a corrected age of one and a half years. Maternal complications were uncommon. Conclusions An aggressive treatment protocol for women with previable PPROM resulted in a high neonatal survival rate. Neonatal survival was associated with higher gestational age at delivery and with more frequent use of antenatal corticosteroids. The prognosis is still bad in PPROM before 22(+0) weeks of gestation.

Aim: To validate a previously developed prediction model for vaginal birth after cesarean (VBAC) using a Japanese cohort. Methods: We performed a cohort study of all term pregnant women with a vertex position, singleton gestation, and one prior low transverse cesarean delivery attempting a trial of labor between April 1985 and March 2010. Variables necessary for the prediction of successful VBAC were maternal age, pre-pregnancy body mass index, ethnicity, prior vaginal delivery, prior VBAC, and indication for prior cesarean delivery. They were extracted from medical records and put into the formula that calculates an individual woman's predicted VBAC success rate. The predicted rates were then partitioned into deciles and compared with the actual VBAC rates. The predictive ability of the model was assessed with a receiver operating characteristic and the area under the curve (AUC) was determined. Results: Seven hundred and twenty-five women who met the inclusion criteria had complete data available, of which 664 (91.6%) had VBAC. The predicted probability of VBAC, as calculated by the regression equation, was significantly higher in those who had a successful trial of labor (median 80.1%, interquartile range 71.5-88.7) than those who did not (median 69.4%, interquartile range 59.9-78.9, P

The role of microsomal placental leucine aminopeptidase (microsomal P-LAP) in the decreased pressor responsiveness to angiotensin II (A-II) in pregnancy was studied. Appreciable amounts of microsomal P-LAP activity were found in rat placenta. The similar dose to the endogenous activity, of human microsomal P-LAP exogenously administered to rats, resulted in significant decrease in the response to A-II. Bestatin, an inhibitor of the microsomal leucine aminopeptidase administered to pregnant rats, enhanced the A-II response. Therefore our present study suggests such refractoriness in response to A-II in pregnancy is due to increased inactivation by the microsomal P-LAP. It was also suggested that prostaglandins were not involved in such refractoriness by the experiments with indomethacin.

We investigated the effects of estradiol and progesterone on placental aminopeptidase A and leucine aminopeptidase activities in pregnant rats. Estradiol (0.5, 1.0 and 2 mg/day) plus progesterone (5, 10 and 20 mg/day) was given for five days starting from the 16th day. Changes in both enzyme activities in the serum, placental cytosol and microsome caused by the steroids were analyzed. Aminopeptidase A activities in all three compartments and leucine aminopeptidase activities in the serum and cytosol were stimulated by estradiol (1.0 mg/day) plus progesterone (10 mg/day). Since we previously found that the placental aminopeptidases degrade peptide hormones, our present study suggests that steroids effect the metabolism of peptide hormones of fetal and/or maternal origin.

Chorioamnionitis (CAM) is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The diagnosis of acute histologic CAM requires delivery and examination of the placenta. Although numbers of markers have been reported to predict histologic CAM before birth, it is unknown whether the levels of neutrophil elastase and lactate dehydrogenase (LDH) in amniotic fluid are associated with histologic CAM.Sixty women at gestational age of 16-35 weeks underwent transabdominal amniocentesis within 48 hr before delivery. Amniotic fluid was analyzed for white blood cell count, glucose level, LDH level, and neutrophil elastase level. The levels of neutrophil elastase were measured by latex immunoassay. Following delivery, tissue samples were obtained from umbilical cord, chorionic plate, and placental membranes. Histologic CAM was diagnosed based on Blanc's criteria.Receiver-operator characteristic curve analysis showed that the amniotic fluid neutrophil elastase had the best screening efficiency in predicting histologic CAM. Using amniotic fluid cut-off levels of 0.15 microg/ml for neutrophil elastase and 250 IU/l for LDH, the sensitivity, specificity, and positive and negative predictive values for predicting histologic CAM were 88.9% versus 84.1%, 73.3% versus 66.7%, 90.9% versus 88.1%, and 68.8% versus 58.8%, respectively.Amniotic neutrophil elastase and LDH are useful markers in predicting histologic CAM.

BACKGROUND: To create a more effective selection standard for early embryos, we developed a new grading system consisting of conventional morphological evaluation in combination with analysis of blastomere nuclei. METHODS: A total of 744 embryos used during 459 cycles of embryo transfer on day 2 and blastocyst transfer were subjected to retrospective analysis. The overall implantation rate was 15.5% (115/744). Morphological evaluation of the embryos was performed on day 2 by referring to both the size of blastomere and fragmentation (conventional method) and the nucleic features of the blastomeres-either multinucleated or anucleic (nuclei counting method). The implantation rate for every transferred embryo and blastocyst was examined. RESULTS: Although a high implantation rate was observed with the highest quality embryos as judged by either the conventional method (24.1%; 57/237) or the nuclei counting method (26.1%; 104/399), the nuclei counting method predicted implantation rate better than the conventional method. The embryos that were considered to be high quality according to the conventional method, but low quality according to the nuclei counting method, had a limited implantation success rate of 6.3% (4/66). Also, after blastocyst transfer, implantation occurred most often when high quality embryos evaluated by the nuclei counting method were used (25.5%; 25/98), while the blastocysts from low quality embryos seldom implanted (3.2%; 2/63). CONCLUSIONS: When choosing which embryo to transfer, the normality of blastomere nuclei may be a more important index of quality than standard fragmentation features and/or blastomere uniformity analysis. When choosing among embryos, if nucleic status is identical, then embryos with the least fragmentation should be chosen. Moreover, in blastocyst transfer, a blastocyst whose nuclei were judged normal on day 2 should be selected on day 5 over any other blastocysts.

hCG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunits. The alpha-subunit has two N-glycosylation sites at Asn52 and Asn78. To obtain more information on the relationship between the structure and function of the alpha-subunit, we introduced a novel N-glycosylation site in the N-terminal region by mutating Asp3 and Gln5 into Asn and Thr, respectively. Glycosylation mutants were expressed alone or with hCGbeta-subunit in Chinese hamster ovary cells. New N-linked oligosaccharides were efficiently added to the wild-type and mutant alpha-subunits lacking N-glycan at Asn52 (alpha deltaAsn1), Asn78 (alpha deltaAsn2), and both (alpha deltaAsn(1 + 2)). The new sugar chain did not affect secretion and assembly except that 1) it increased the intracellular degradation of alpha deltaAsn(1 + 2), and 2) it augmented the assembly of alpha deltaAsn1 with hCGbeta-subunit. Amino acid changes generated the attachment of O-glycosylation in free alpha-subunit but not in assembled form. These data indicate that the newly introduced N-glycosylation consensus sequence is functional, and that the N-terminal region of the alpha-subunit is flexible and can be modified without affecting the intracellular function. Furthermore, amino acid sequences in the N-terminus are involved in the O-glycosylation in free alpha-subunit.

To analyze the effects of treatments with GH and cyclic estrogen/progesterone (E/P) replacement on bone mineralization in patients with Turner's syndrome (TS), bone mineral density (BMD) was measured longitudinally. BMDs of the whole body and the lumbar spine in 16 adult female patients with TS (17-38 year old; 0-20 years by length of E/P treatment) were assessed using dual energy X-ray absorptiometry one to 5 times over a treatment period of up to 7 years maximum. GH treatment was performed in 9 cases (GH group), but not in the remaining 7 (non-GH group). E/P replacement therapy was initiated in all patients after they finished GH administration. The BMDs of both the whole body and the lumbar spine in the patients with TS were significantly less than those in age-matched normal subjects, and did not improve with E/P treatment. Although there were no differences in final body height and age at the beginning of E/P administration between the GH and non-GH groups, whole body BMD in the GH group was significantly lower than that in the non-GH group. These results indicate that GH administration in childhood and adolescence and E/P treatment in adulthood did not increase bone mineralization in the TS patients. Therefore, we can conclude that the optimal protocol of hormonal replacement therapy with GH and E/P during childhood and adolescence should be established as soon as possible.

To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA). We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis. In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32–0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41–1.99)], development quotient

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit but differ in their hormone-specific beta-subunits. Both subunits have five and six disulfide bonds, respectively, which consist of cystine knot structure. It is evident from numerous studies that the structure of beta-subunits is rigid, whereas that of alpha-subunit is flexible and can be molded by a beta-subunit. Previously, we reported that secreted forms of a mutants where either cysteine residue in the disulfide bond 7-31 or 59-87 was converted to alanine contained a disulfide-linked homodimer in addition to a monomer. To study whether the hCGbeta-subunit affects the conformations of alpha mutants, alpha-subunits lacking either the 7-31 or 59-87 disulfide bond were expressed with wild-type (WT) hCGbeta in Chinese hamster ovary cells, and homodimer formation and glycosylation of dimerized alpha-subunit were assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-alpha or -hCGbeta serum, digestion with endoglycosidase-H or -F, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a non-reducing condition. Our data showed that a homodimer was not observed in the half-Cys mutants except one, where cysteine at position 7 was converted to alanine, in the presence of beta-subunit. This finding indicated that hCGbeta-subunit rescued the a half-Cys mutants from the formation of intermolecular disulfide-linked homodimer by preferentially combining with the alpha mutants. In both free WT and all mutants treated with endoglycosidase-H, no or faint bands were recognized as the same migration as seen in endoglycosidase-F treatment. Even in the endoglycosidase-H sensitive cases, the amount of sensitive alpha-subunits was less than 5% of total alpha-subunits. In contrast to free alpha-subunits, distinct endoglycosidase-H sensitive bands were seen in both WT and mutants, although the ratio was various. We concluded that hCGbeta-subunit affects the folding and glycosylation of the alpha-subunit mutants.

A case of ovarian carcinoma with thrombopoietin production is reported. A 49-year-old Japanese woman had serous cystadenocarcinoma of the right ovary with peritoneal spread. The platelet count was elevated to 432 × 10 9 /L. Enzyme-linked immunosorbent assay of the serum demonstrated remarkably high levels of thrombopoietin (2.96 fmol/ml). Immunohistochemical examination using an antibody specific for thrombopoietin revealed positive staining in the carcinoma cells, confirming thrombopoietin production.

Septic shock during pregnancy is very rare but has high mortality. We report a case of septic shock in a pregnant woman with ileus, showing that severe ileus in a pregnant woman could be attributed to life-threatening septic shock and that we should give special attention to a nosocomial infection.

We evaluated the effect of GnRH on the serum hCG level in gestational trophoblastic disease (GTD). Five patients with GTD were studied. Three patients had hydatidiform mole (two complete and one partial mole) and two had choriocarcinoma. Blood samples were collected immediately before and 30, 60min after the 100μg GnRH iv injection, followed by hCG assay. Only one case of choriocarcinoma demonstrated an hCG increase after intravenous administration of GnRH (positive GnRH test). In that case, the hCG level dropped to the normal range after eight cycles of chemotherapy but the GnRH test was still positive, suggesting the existence of viable cancer cells. Since the GnRH test became negative, no increase in hCG has been observed, indicating that the patient achieved complete remission. Although a positive GnRH test is not common in GTD, GnRH test before treatment might be useful to find a positive case where the test can be repeated to determine complete remission and the time when the chemotherapy may be discontinued.

Periventricular leukomalacia (PVL) is an important cause of cerebral palsy in preterm infants [1]. Although obstetric risk factors for PVL include maternal infection, meconium-stained amniotic flui...

Objective To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC). Design Case–control study. Setting Eleven tertiary referral hospitals in central Japan. Population A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation. Methods Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer). Main outcome measure The incidence of placenta accreta. Results No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P

Objective: To analyze the effects of gonadotropin and ovarian steroid hormones on the gene expression of c-mos in mouse oocytes. Methods: The changes of c-mos messenger RNA (mRNA) levels in oocytes were examined after the administration of pregnant mare's serum gonadotropin (PMSG) in vivo, or after incubation with estrogen and/or progesterone in vitro. Five IU PMSG was injected intraperitoneally to female immature mice, and human chorionic gonadotropin was also injected intraperitoneally 48 hours after the PMSG injection, with or without mating with male mice. The oocytes were collected from follicles or oviducts at 24, 30, 36, 42, 48, 60, 72, and 84 hours after the injection. The RNAs were extracted from 5 oocytes at each time point, and a reverse-transcription polymerase chain reaction using specific primers to c-mos DNA was performed to measure the relative amount of c-mos mRNA. Results: The c-mos mRNA in oocytes at 36 hours after the injection was 2.7 times higher than that at 24 hours. The c-mos mRNA level gradually decreased thereafter, and after ovulation the level was only 1/10 of the peak level. When the oocytes that were retrieved 24 hours after PMSG injection were incubated with 800 ng/ml estradiol 17-β or 600 ng/ml progesterone for 120 minutes, the c-mos gene expression was significantly suppressed or stimulated, respectively, in comparison with the absence of these substances. Conclusion: Although the regulatory mechanism of c-mos gene expression in oocytes is still unclear because the result obtained from the in vitro study, that estrogen suppressed the c-mos gene expression directly, was inconsistent with the result of the in vivo study, that increases of both c-mos mRNA and estrogen occurred simultaneously with PMSG stimulation in the early phase of preovulatory oocytes, our present study revealed that gonadotropin and steroid hormones might affect c-mos gene expression in mouse oocytes indirectly and/or directly.

Cystic teratoma in the greater omentum remains one of gynecology's rarest entities. A 28-year-old woman presented with a goose-egg-sized mass in the right lower quadrant. At laparotomy, the mass proved to be a cystic teratoma of the greater omentum. To our knowledge, this report documents the first case where an omental pedicle was torsioned.

The human chorionic gonadotropin β-subunit (hCGβ) is a glycoprotein in which 12 cysteine residues pair to form six intramolecular disulfide bonds. In order to elucidate the effect of each disulfide bond on glycosylation of the molecule, we analysed structures of asparagine-linked oligosaccharides of various recombinant hCGβ produced in Chinese hamster ovary (CHO) cells: wild-type hCGβ (βWT) and mutants in which any one of the six intramolecular disulfide bonds had been disrupted by site-directed mutagenesis. SDS-PAGE analysis of βWT and these mutants before and after digestion with endoglycosidase F and H revealed structural changes in the oligosaccharide moieties of some mutants. In addition, structural analysis of oligosaccharides obtained from metabolically labeled βWT and a mutant showed that the mutant contained additional high mannose type oligosaccharides. These results suggest that elimination of a specific disulfide bond, resulting in a change in the protein conformation, disturbs the normal assembly of the mature complex type oligosaccharides in the hCGβ molecule. Abbreviations: hCGβ, human chorionic gonadotropin β-subunit; βWT, wild type hCGβ; CHO, Chinese hamster ovary; Endo-H, endoglycosidase H; Endo-F, endoglycosidase F

The aim of this study was to clarify the association between fetal heart rate (FHR) tracing interpretation levels in the second stage of labor and poor fetal acid-base balance.The database at one tertiary hospital in Nagoya, Japan, was retrospectively reviewed for women with singleton fetuses in cephalic presentation and vaginal labor at ≥37 + 0 gestational weeks between 1 June 2011 and 30 April 2012. Continuous FHR tracings in the second stage of labor were subdivided into 15-min intervals, each of which we called a window, from the beginning of labor through delivery, and were assessed according to the five-tier classification proposed by the Japan Society of Obstetrics and Gynecology, in which level 1 is normal, level 2 is subnormal, and levels 3-5 are abnormal patterns.In total, 777 parturient women were eligible for the study protocol. The numbers of women with maximal levels of 1, 2, 3, 4, and 5 were 3, 77, 341, 349, and 7, respectively. No cases of severe fetal acidosis (pH7.0 or base excess-12 mmol/L) were recorded when the maximal levels were below 3. Both the pH and base excess of the umbilical artery decreased with higher levels of FHR tracings interpretation (P0.001). Both the summations of level-4 windows and level-3 and level-4 windows were significantly higher in women with severe fetal acidosis than in women without (P0.001), indicating that the duration of abnormal levels is associated with severe fetal acidosis.Both the degree and duration of FHR tracing abnormalities correlate with severe fetal acidosis.

The best treatment for recurrent granulosa cell tumor(GCT)is considered to be surgical resection, because the effects of chemotherapy or radiation on GCT are obscure. The common site of recurrence is the pelvic cavity, including the surface of the liver and intestine as tumor-dissemination-patterns. Between June 1988 and June 2011, we treated 15 patients with GCT at our hospital. The median follow-up time was 56(22-286)months. Ten patients were stage I, 3 were stage II, and 2 were stage III. No patients had residual lesions at the primary surgery area. Six patients have recurred, and the median disease free survival(DFS)was 85(15-128)months. Six patients had relapses in the pelvic cavity, 2 in the retroperitneal lymph nodes, and 1 in the upper abdomen. Two patients relapsed more than twice; however, the rapid detection of recurrence and surgical resection have kept all patients alive. Thirteen patients have no evidence of disease(NED), 2 are alive with disease(AWD), and no one has died of the disease(DOD). We suggest that maximal debulking surgery to achieve complete cytoreduction of recurrent GCT is the most important treatment for prolonging survival.

To study how clinical factors such as embryo quality, cell stage of embryo at cryopreservation, and synchronization of developmental stages between embryo and endometrium at thawing affect the implantation rate after cryopreserved-thawed embryo transfer (ET), these factors were examined in 106 cryopreserved-thawed ETs including 204 embryos.In 86 embryos graded as high quality before transfer by morphological evaluation, 31 implantations were successful, while the other, low-quality embryos did not implant at all. High-quality embryos received less cryoinjury during cryopreservation compared to the injuries sustained by embryos in moderate and poor quality. When cyopreservation was performed at the 1-, 2-, and 3-day cell stages, pregnancies were similiarly achieved among most of the embryos at all cell stages. At thawed ETs in natural ovulation cycles, there were some differences among the developmental stages between thawed embryo and endometrium that received the thawed transferred embryos. Although the transfer timelag ranged a day or more, asynchronism of endometrium growth to the cell stage did not reduce pregnancy rates.These results indicated that embryo quality evaluated morphologically was the most important clinical factor for successful implantation of cryopreserved-thawed ET.

The mutations (Trp8 --Arg and Ile15 --Thr) in the human LHbeta -subunit caused by nucleotide point mutations in the LHbeta gene were reported in women with immunologically anomalous LH and menstrual disorders. To estimate the effects of the mutations on LH bioactivity in vitro and in vivo, we constructed a LHbeta gene containing this nucleotide mutation in each site or in both sites by site- directed mutagenesis and analyzed the bioactivities of the mutant LH expressed in Chinese hamster ovary cells. Although no alterations were noted in the receptor-binding activity of LH due to the mutations, the LHs containing the mutations at Trp8 --Arg and at both sites in the beta-subunit showed a higher biopotency of progesterone production in vitro. The clearance rate from the circulation was faster in vivo in all mutant LHs, which were induced primarily by the mutation at Trp8 --Arg. However, the mutations did not affect the ability of LH to induce ovulation in vivo. These results indicate that LH consisting of the mutant beta-subunit exhibits hyperbioactivity on steroidogenesis and has a short turnover rate. This may affect the endocrine pathway among women with the mutant LH and lead to menstrual disorders.

To clarify whether apoptosis is involved in endometriosis, we obtained eutopic endometrial tissues along with endometriotic tissues from the uterus (adenomyosis) (n = 12) and from the ovary (n = 12) from patients undergoing gynaecological surgery. Apoptosis-induced DNA fragmentation was detected by the TdT-mediated dUTP-biotin nick-end labelling method, and immunostaining with a monoclonal antibody against the Fas, Le(y) or B-cell leukaemia/lymphoma-2 (bcl-2) was also performed using the same tissue section. Analysis showed that apoptosis was occurring in all the samples of ovarian endometriotic tissue but in only two of the 12 adenomyotic and in five of the 24 eutopic endometrial tissue samples. In none of these cases was apoptosis correlated with phases of the menstrual cycle. The expression of bcl-2 in the eutopic endometrial and adenomyotic tissues was limited to the proliferative phase, and was observed in only one of the 12 cases of ovarian endometriosis. Fas and Ley were expressed randomly across a wide range in both the eutopic and ectopic endometrial tissues. These results suggest that the features of ovarian endometriosis are different from those of adenomyosis and eutopic endometrium in terms of the involvement of apoptosis. In addition, the regulatory mechanism involved in ovarian endometriosis may differ from that in other endometrial cells.

To analyze direct effects of estrogen on gene expressions of inhibin subunits in vitro, the mRNA levels of inhibin alpha- and beta A-subunits were measured in rat granulosa cells cultured with FSH or estradiol. Through the culture process of the granulosa cells with serum-free medium, both the alpha- and beta A subunit mRNAs decreased, and were partially increased again by adding FSH to the culture medium. To examine whether these FSH effects are mediated via estrogen production, estradiol or tamoxifen was added to the cultured granulosa cells. After 36-h culture with estradiol, the inhibin alpha-subunit decreased but the inhibin beta A-subunit increased, in a dose-responsive manner. Tamoxifen showed completely opposite effects to estradiol, and a combination of estradiol and tamoxifen resulted in similar levels of inhibin-alpha and -beta A mRNAs to the control. These results indicate that estrogen would by a certain pathway affect gene expressions of the inhibin subunits in the rat granulosa cells, and may regulate the production of inhibin and activin through the paracrine system.