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To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation.We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion.The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth.LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.

To evaluate the utility of the risk score in assessing the current status and prognosis of COVID-19 in pregnancy.Seventy-seven cases affected before the Omicron variant epidemic and 50 pregnant cases affected by the Omicron variant were included. The risk score consists of maternal background, current condition, and examination findings. We determined the risk score in the early stages of disease onset.There were no significant differences in the maternal or gestational ages between the groups. The risk score was significantly lower in the After-Group patients (those affected during the Omicron epoch), while 14.3% of the Before-Group patients (those affected during the pre-Delta and Delta epochs), experienced a worsening of disease after the visit to the center, whereas none of the After-Group patients did. The Before Group's frequency of risk score items was higher among the two groups for "fever for ≥48 h," "mild pneumonia image," and "blood tests," whereas "disease onset 14 days after the second vaccination" was increased in After Group. The blood test parameters for platelet count, C-reactive protein, and D-dimer levels were not significantly different between the groups.The risk score system appeared superior in detecting deteriorating cases. There were no cases of post-illness deterioration in the After-Group, suggesting that cases of the Omicron variant in pregnancy may have had a less severe course compared to that of previous variants. However, there was no significant difference between the groups in terms of a specific blood test evaluation, suggesting the need for a combined evaluation of cases affected during pregnancy.

To investigate the association between hypoxic-ischaemic insult timing and brain injury type in infants with severe cerebral palsy (CP).Longitudinal study.Database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy.Infants with severe CP born at ≥34 weeks of gestation.The intrapartum fetal heart rate (FHR) strips were categorised as continuous bradycardia; persistently non-reassuring (NR-NR); reassuring-prolonged deceleration (R-PD); Hon's pattern (R-Hon); persistently reassuring (R-R); and unclassified. The brain magnetic resonance imaging (MRI) scans were categorised based on the predominant site involved: basal ganglia-thalamus (BGT); white matter (WM); watershed (WS); stroke; normal; and unclassified.Manifestations of the brain MRI types and the association between FHR evolution pattern and MRI type were analysed.Among 672 eligible infants, 76% had BGT-dominant injury, 5.4% WM, 1.2% WS, 1.6% stroke, 1.9% normal, and 14% unclassified. Placental abruption and small-for-gestational age were associated with an increased (adjusted odds ratio [aOR] 8.02) and decreased (aOR 0.38) risk of BGT injury, respectively. The majority of infants had BGT injury in most FHR groups (bradycardia, 97%; NR-NR, 75%; R-PD, 90%; R-Hon, 76%; and R-R, 45%). The risk profiles in case of BGT in the NR-NR group were similar to those in the R-PD and R-Hon groups.BGT-dominant brain damage accounted for three-fourths of the cases of CP in term or near-term infants, even in prenatal onset cases. Hypoxic-ischaemic insult has a major impact on CP development during the antenatal period.Basal ganglia-thalamus injury constitutes 76% of severe cerebral palsy cases, predominant even in antenatal-onset cases.

Aim In Japan, the criteria of the latent and active phases of the first stage of labor have not been decided. The Japan Society of Obstetrics and Gynecology (JSOG) Perinatal Committee conducted a study to construct a spontaneous labor curve in order to determine the point of onset of the active phase. Methods The participants were women who had spontaneous deliveries at four health facilities in Japan between September 1, 2011, and September 31, 2019. Spontaneous delivery was defined as the spontaneous onset of labor at term (37 weeks, 0 days to 41 weeks, 6 days) with vaginal delivery of a mature fetus in a cephalic position without uterotonic agents or epidural analgesia. The time points for each "cm" of dilation were collected starting from the time of full dilation retrogradely. The relationship between time since labor onset and cervical dilation was expressed as a curve using a smoothing B-spline. Results A total of 4215 primiparous and 5266 multiparous women were included in this study. The spontaneous labor curve showed that in both primiparous and multiparous women, labor progress was slow until 5 cm cervical dilation, accelerating between 5 and 6 cm dilation, and steadily progressed after 6 cm dilation. Conclusion We propose that the active phase of the first stage of labor be defined as starting at 5 cm dilation of the cervix, and that it be divided into an acceleration phase (5-6 cm dilation) and a maximal phase (>6 cm dilation).

Aim Extended-field concurrent chemoradiation therapy (Ex-CCRT) has been widely used for para-aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. Methods From May 2017 to March 2020, stage IIB-IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography-computed tomography (PET-CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. Results Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB (n = 7) and IIIB (n = 7). The median operating time was 138 min (range, 104-184 min). The median number of harvested PANs was 19 (range, 6-36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. Conclusion Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Obturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension-free direct end-to-end anastomosis. A 36-year-old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.

Aim The aim of this study was to clarify the physical and mental burden of the COIVD‐19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress. Methods A web‐based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020. Results A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID‐19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID‐19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID‐19 infection. Conclusions Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.

AIM The purpose of this study was to evaluate the current state and clinical characteristics of spontaneous hemoperitoneum in pregnancy (SHiP) in Japan by performing a comprehensive survey. METHODS We reviewed data on pregnant women who developed SHiP during 2013-2017 (for 5 years), and were admitted to any of the perinatal centers in Japan. The survey assessed maternal background and maternal and neonatal prognosis. We divided the cases into two groups, favorable and poor prognosis groups, and made comparisons between the two groups. RESULTS Of the 407 facilities in Japan, 267 (66%) facilities responded to our survey. Overall, 31 cases of SHiP were registered. Maternal death occurred in one case (3%) due to liver bleeding with an unknown cause. Of 23 cases with a SHiP onset during pregnancy, 12 (53%) had been misdiagnosed as placental abruption. The prognosis for the fetuses included miscarriage or stillbirth in three cases (10%) and asphyxia in 12 cases (42%). There was no significant correlation between the amount of intra-abdominal blood loss and neonatal prognosis based on umbilical artery pH. Incidences of preterm birth

Aim In Japan, the frequency of maternal deaths due to obstetric hemorrhage has been decreasing in the last decade, while that resulting from other causes such as pulmonary thromboembolism (PTE) was consistent. To help reduce maternal deaths due to PTE, we investigated PTE during pregnancy and puerperium and compared the survival and death cases, and aimed to find out life and death factors. Methods This study was a retrospective analysis based on a clinical chart review in 407 maternal and perinatal centers. We compared the survival and death cases of PTE during pregnancy and puerperium from 2013 to 2017. Results In PTE during pregnancy, the survival cases underwent significantly earlier diagnoses than the death cases, and thromboprophylaxis was performed in most of both the survival and death cases of PTE during puerperium according to the existing Japanese guidelines; however, only one fourth of the total cases underwent anticoagulation to prevent venous thromboembolism (VTE). Conclusions Early diagnosis of PTE in suspected cases was associated with better survival during pregnancy.

Objective: Cardiotocography is widely used to assess fetal well‐being during labour. The positive predictive value of current clinical algorithms to identify hypoxia‐ischaemia is poor. In experimental studies, fetal hypotension is the strongest predictor of hypoxic‐ischaemic injury. Cohort studies suggest that deceleration area and deceleration capacity of the fetal heart rate trace correlate with fetal acidaemia, but it is not known if they are indices of fetal arterial hypotension. Design: Prospective, controlled study. Setting: Laboratory. Sample: Near‐term fetal sheep. Methods: 1 min of complete umbilical cord occlusions (UCOs) every 5 min (1:5min, n=6) or every 2.5 min (1:2.5min, n=12) for 4 h or until fetal mean arterial blood pressure fell Main Outcome Measures: Deceleration area and capacity during the UCO series were related to evolving hypotension. Results: The 1:5min group developed only mild metabolic acidaemia, without hypotension. By contrast, 10/12 fetuses in the 1:2.5min group progressively developed severe metabolic acidaemia and hypotension, reaching 16.8±0.9mmHg after 71.2±6.7 UCOs. Deceleration area and capacity remained unchanged throughout the UCO series in the 1:5 min group, but progressively increased in the 1:2.5 min group. The severity of hypotension was closely correlated with both deceleration area (p Conclusions: Both deceleration area and capacity were strongly associated with developing fetal hypotension, supporting their potential to improve identification of fetuses at risk of hypotension leading to hypoxic‐ischaemic injury during labour.

Background Streptococcal toxic shock syndrome is associated with the highest rates of infection-related maternal mortality. We conducted a comparative analysis of background factors and treatment course between patients who survived and those who did not to improve our understanding of the optimal initial treatment approach for this fulminant disease. Methods: A retrospective observational study was conducted based on clinical data collected from two national organizations. Clinical data of patients who died and of those who survived, including background information, clinical course, and treatment administered, were collated. Results: No statistical differences were found between groups for age, parity, season, gestational age, or the patient’s location at the onset of symptoms. After the onset of initial symptoms, survivors were administered antibiotics systematically during their first visit to a clinic (p = 0.006). More survivors had received treatment within 1 hour of onset of fulminant disease (p = 0.069). The number of fetal deaths was significantly higher in the mortality group (p = 0.003), while that of fetal survival was higher in the group of maternal survivors (p = 0.055). Maternal survivors with non-specific initial symptoms received early intervention if there was a family history of group A streptococcal infection or a positive rapid antigen test result. Conclusions Intensive care, including systemic administration of antibiotics, may contribute to maternal survival when administered immediately (within 1 hour) after the onset of fulminant streptococcal toxic shock syndrome. Eliciting a family history of streptococcal infection and conducting a rapid antigen test can identify patients needing early intervention.

Key points The majority of intrapartum decelerations are widely believed to be mediated by the baroreflex secondary to brief umbilical cord occlusions (UCOs) but this remains unproven. We examined the responses to brief-UCOs in fetal sheep and compared these to a phenylephrine-stimulated baroreflex in a separate cohort. A further cohort was instrumented with near-infrared spectroscopy to measure cerebral oxygenation during UCO. The first 3-4 s of the brief-UCOs were consistent with a baroreflex, and associated with a minor fall in FHR. Thereafter, the remainder of the FHR decelerations were highly consistent with the peripheral chemoreflex. The baroreflex is not sufficient to produce deep, rapid decelerations characteristic of variable decelerations and it is therefore likely a minor contributor to intrapartum decelerations. Abstract Fetal heart rate (FHR) monitoring is widely used to assess fetal wellbeing during labour, yet the physiology underlying FHR patterns remains incompletely understood. The baroreflex is widely believed to mediate brief intrapartum decelerations, but evidence supporting this theory is lacking. We therefore investigated the physiological changes in near-term fetal sheep during brief repeated umbilical cord occlusions (brief-UCOs, n = 15). We compared this to separate cohorts that underwent a phenylephrine challenge to stimulate the baroreflex (n = 9) or were instrumented with near-infrared spectroscopy and underwent prolonged 15-min complete UCO (n = 9). The first 3-4 s of brief-UCOs were associated with hypertension (p = 0.000), a fall in FHR by 9.7-16.9 bpm (p = 0.002). The FHR/MAP relationship during this time was consistent with that observed during a phenylephrine-induced baroreflex. At 4-5 s, the FHR/MAP relationship began to deviate from the phenylephrine baroreflex curve as FHR fell independently of MAP until its nadir in association with intense peripheral vasoconstriction (p = 0.000). During prolonged-UCO, cerebral oxygenation remained steady until 4 s after the start of prolonged-UCO, and then began to fall (p = 0.000). FHR and cerebral oxygenation then fell in parallel until the FHR nadir. In conclusion, the baroreflex has a minor role in mediating the first 3-4 s of FHR decelerations during complete UCO, but thereafter the peripheral chemoreflex is the dominant mediator. Overall, the baroreflex is neither necessary nor sufficient to produce deep, rapid decelerations characteristic of variable decelerations; it is therefore likely to be a minor contributor to intrapartum decelerations. This article is protected by copyright. All rights reserved.

Aim To clarify whether the incidence of umbilical cord prolapse (UCP) at delivery is related to the cervical ripening balloon (CRB). Methods A postal questionnaire study was conducted in 2018 in institutions providing maternity services across Japan. Questions on the number of deliveries, labor inductions, used CRB and cases of UCP in 2017 were included. Because a similar questionnaire survey was conducted in 2012, the incidence of UCP and frequency of the use of CRB were compared. Results A total of 1354 answers were assessed (57% of all delivery institutions). The total number of deliveries was 490 279. Of these, 78% were transvaginal; 74 cases of UCP were reported (0.015%), while 13 cases were reported from obstetric facilities never using CRB (0.008%). The incidence of UCP (odds ratio [95% confidence interval]) was 0.036% in the intracervical type (4.3 [1.6-11.3]), 0.091% in the disk-type (11.0 [4.2-29.0]) and 0.067% in the ball-type (8.1 [2.8-22.8]). Frequencies of the use of CRB were 7.3% and 6.6% in the 2012 and 2018 surveys, respectively. The use of the intracervical type increased from 2.8% in the 2012 survey to 3.5% in the 2018 survey, while that of the disk-type and ball-type declined. However, the incidence of UCP was not different between the two surveys regardless of the use of cervical ripening balloons (0.014% vs 0.015% with CRB, 0.005% vs 0.008% without CRB). Conclusion Although the frequency of CRB use significantly declined, the incidence of UCP did not significantly reduce in the last 5 years.

AIM We previously reported that female babies born small developed cardiovascular risks in middle age. The present study was conducted using the same cohort to examine the relationship between physique at 6 years and the metabolic disease risk in middle age. METHODS Data collected from 721 women aged 41-69 years who underwent a medical examination at a single institution between 2007 and 2008 were retrospectively examined. We collected data from medical examinations and a questionnaire on physique (thin, normal, and fat) at 6 years. The relationship between birthweight and physique at 6 years was investigated. RESULTS Among females who were born small (

To predict the prognosis of infants with congenital heart disease, accurate prenatal diagnosis of structural abnormality and heart failure are both necessary. The aim of this study was to investigate whether cardiovascular profile (CVP) and biophysical profile (BP) scores are useful for predicting prognosis in infants with congenital heart defect (CHD).A retrospective review of singletons prenatally diagnosed with CHD at a tertiary pediatric cardiac center between 2011 and 2015 was undertaken.A total of 202 patients with CHD were analyzed. Perinatal and infant deaths occurred in 16 (7.9%) and 10 cases (5.0%), respectively. Infants with the last CVP score ≤ 5 had 18.7-fold higher perinatal mortality than those with a last CVP score 5 (P 0.01). Infants with a last BP score ≤ 6 had 18.7-fold higher perinatal mortality than those with a last BP score 6 (P 0.01). Infants with a CVP score decrease in utero had 4.5-fold higher infant mortality than those with an increase or no change (P 0.01). Multivariate analysis showed that single-ventricle physiology, pre-term birth at37 weeks of gestation, last CVP score ≤ 5, and last BP score ≤ 6 were independent predictors of perinatal mortality. Single-ventricle physiology and a CVP score decrease were independent predictors of infant mortality.CVP and BP scores are useful for predicting perinatal prognosis in infants with CHD. A CVP score decrease in utero is associated with infant mortality, suggesting that serial CVP score assessment may be useful for management planning.

AIM We sought to examine the safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG-IUS insertion in women with cardiovascular disease. METHODS We prospectively followed women with a cardiovascular disease in whom a 52-mg LNG-IUS was inserted between 2009 and 2015. The primary outcome was the frequency of cardiovascular and gynecologic side effects due to the LNG-IUS over the year after LNG-IUS insertion. The secondary outcomes were the changes in menstrual blood loss and biomarkers, e.g., white blood cell count and the levels of C-reactive protein, hemoglobin and brain natriuretic peptide. We also evaluated the 24-month continuation rate of LNG-IUS. RESULTS A total of 34 women were prospectively followed-up, including two women with pulmonary hypertension. No cardiovascular side effects were identified during the 1 year after LNG-IUS insertion, other than one case of mild vasovagal reaction at insertion. Neither the white blood cell count nor the C-reactive protein value increased after LNG-IUS insertion. The menstrual blood loss was decreased in most subjects and the median hemoglobin levels increased significantly within 1 year after insertion (P

A 52-year-old woman presented to our hospital complaining of genital bleeding and was found to have a 50-mm vaginal tumor that involved the bladder, rectum, and small bowel and extended to the left pelvic side wall. Her history included a bilateral salpingo-oophorectomy and a total abdominal hysterectomy for fibroids and endometriosis. She had been prescribed estrogen replacement therapy (1.25 mg/day) following the second surgery and continued it for 8 years. The pathology of the vaginal biopsy showed endometrioid adenocarcinoma. Total pelvic exenteration was recommended for complete resection, but she chose chemotherapy (paclitaxel 175 mg/m2 and carboplatin AUC:6). Clinical complete remission was obtained for 11 years. She had a recurrence 11 years later. She was again found to have a 5-cm vaginal tumor. Surgical excision with upper vaginectomy was performed. The tumor was resected without invasion of the bladder, rectum and small bowel. Histologic examination of the specimen confirmed clear cell carcinoma with endometriosis. Chemotherapy may be the first-line treatment that can preclude aggressive surgery for malignant transformation of extragonadal endometriosis. However, combined chemotherapy and surgery is necessary for this disease.

Aim To investigate the influence of reproductive medicine in maternal death cases in Japan. Methods This retrospective study investigated the incidence of maternal deaths related to reproductive medicine in Japan from 2013 to 2015, and the relationship between fertility treatment and maternal death. Results Fifteen out of 134 women (11.2%) involved in this study who underwent treatment for infertility died. Four experienced pregnancy with severe maternal complications (26.6%). The complications were active systemic lupus erythematosus, exacerbated depression, uncontrolled arrhythmia and uncontrolled type 2 diabetes mellitus. At least three of these four died due to these complications. Conclusion The maternal death rate of women who have undergone fertility treatment is similar to the birth rate due to assisted reproductive technology in Japan. Some maternal death cases involve severe uncontrolled complications. Therefore, medical histories should be evaluated before fertility treatment.

Posterior urethral valve (PUV) rarely causes bladder rupture. We experienced hydronephrosis due to ureteral obstruction after the natural repair of a ruptured bladder in a fetus with PUV. Fetal ascites and oligohydramnios were diagnosed at 26 weeks' gestational age. While we followed up with ultrasonography, we regularly removed the fetal ascites via abdominal puncture, injecting warm saline instead of amniotic fluid. At 35 weeks' gestational age, the infant was diagnosed with severe bilateral hydronephrosis, absent of ascites and oligohydramnios. Therefore, a Caesarean section was performed. After birth, the infant was diagnosed with hydronephrosis due to ureteral obstruction after the natural repair of a ruptured bladder associated with PUV. Thus, a ruptured bladder in a fetus with PUV that has naturally repaired should be closely monitored via ultrasonography for hydronephrosis due to ureteral obstruction.

Aim To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed. Methods Cases of uterine rupture recorded for a period of 5 years were included. Results There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30-32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases. Conclusion This survey revealed the current incidence of uterine rupture in Japan.

AIM To clarify the perinatal outcomes in pregnancy complicated with intracranial arteriovenous malformation (i-AVM). METHODS A retrospective study was performed in 36 pregnancies complicated by i-AVM from 1981 to 2013 at one institution. RESULTS In total, 6 women miscarried, and 30 had live births. The median (range) gestational age at delivery was 38 (24-40) weeks; 11 cases experienced initial i-AVM rupture during pregnancy (first, second and third trimester: 18%, 64% and 18%, respectively). At onset, 4 cases had a Glasgow Coma Scale ≤10, 10 cases needed emergency maternal transport, 4 underwent neurosurgery with the fetus in utero and 4 had termination of pregnancy in the second trimester for emergent treatment for i-AVM. Two cases delivered vaginally. Another 25 cases had already been diagnosed as i-AVM at conception. Of these, as an indication for epidural birth, 18 cases had either residual lesion of i-AVM or neurological symptoms, although 18 cases had received treatments of i-AVM before conception. Without rupture of i-AVM and worsening of symptoms, 15 cases succeeded in epidural birth. One case was delivered by cesarean section for residual i-AVM with indication of treatment. Another case who had refused treatment of i-AVM experienced rupture of i-AVM 1 year after delivery. CONCLUSION Most of the cases with residual i-AVM lesion and neurological symptoms could deliver vaginally without worsening of symptoms. However, pregnancy with i-AVM can be complicated by rupture of i-AVM. In cases with a residual lesion with indication of treatment and rupture of i-AVM during pregnancy, meticulous care is required during pregnancy and after delivery.

AIM The study identifies the relevant obstetric factors associated with fetal heart rate (FHR) monitoring for cerebral palsy (CP) in pregnant women with hypertensive disorders of pregnancy (HDP). METHODS The subjects were neonates with CP (birth weight ≥ 2000 g, gestational age ≥ 33 weeks) who were approved for compensation for CP by the Operating Organization of the Japan Obstetric Compensation System between 2009 and 2012. After selection of women with antepartum HDP, obstetric characteristics associated with FHR monitoring were analyzed. RESULTS The subjects included 33 neonates with CP whose mothers suffered from HDP during pregnancy and 450 neonates whose mothers did not develop HDP. The rates of placental abruption (48.5% vs. 20%; P < 0.001) and light-for-gestational age (12.1% vs. 2.2%; P = 0.011) were significantly higher in women with HDP than in those without HDP. Regarding FHR pattern analysis, fetal bradycardia was observed on admission to hospital in 94% of women with placental abruption. In women without placental abruption, FHR was likely to indicate a favorable pattern on admission, but became worse with the progression of labor. CONCLUSION This is first study to clinically demonstrate FHR patterns in CP cases in association with HDP. Although antepartum CP is undetectable, pregnant women with HDP should be placed under strict observation and management to minimize fetal hypoxic conditions during labor.

Aim We designed a safety and dose-finding trial of tadalafil administered for fetal growth restriction (FGR). Methods Three cases were initially commenced on 10 mg/day and monitored for major adverse events. Should a major adverse event be observed in one or more of the three cases, an examination into its relation with tadalafil would be conducted by a safety evaluation committee. If one or more of these new cases exhibited the same adverse event, the trial would be stopped completely. If there were no harmful side-effects, the trial would be extended to three cases at 20 mg/day, and the protocol would continue as in the 10-mg/day dose. The 40-mg/day dosage was tried in six cases as the dosage was considered to be high. Results The study population consisted of pregnant women with FGR. Maternal adverse events in all doses were recorded as least one grade 1 adverse events, as tadalafil was considered acceptable from the viewpoint of the mothers. However, a dose of 40 mg/day increased the number of grade 1 adverse events. The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord. Neonatal adverse events showed no correlation to tadalafil dose, but were found more frequently in preterm births and, therefore, were correlated to infant prematurity. Conclusion This safety and dose-finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR.

For severe pre-eclampsia (PE) with fetal growth restriction (FGR), the only effective treatment is early delivery of the placenta. Clinicians are often forced to end the pregnancy because of maternal indications. We report a case of severe PE with FGR in which the PE was temporarily improved and pregnancy successfully prolonged with tadalafil, a phosphodiesterase 5 inhibitor. A 35-year-old primigravid woman presented at 27 3/7 weeks of gestation with severe PE and FGR. After commencing tadalafil administration, biochemical and angiogenic markers improved. Thereafter, hypertension and proteinuria temporarily improved. Importantly, the pregnancy was prolonged by 14 days after the initiation of tadalafil administration. Tadalafil may be a novel treatment for severe PE with FGR to prolong pregnancy.

Aim This study was conducted to examine whether babies born small develop cardiovascular problems in later life. Methods Data were examined retrospectively for 1241 city dwellers (men 521, women 720) aged 40–69 years who received a medical examination at a single institution. Blood tests, physical measurements, and a questionnaire survey regarding birth weight (small, medium, large), medication history and lifestyle (alcohol consumption, smoking, exercise) was administered. We selected 28 persons (12 men and 16 women) from and studied the rate of conformity between the participants’ memory (small, medium, large) and the actual birth weight recorded in their maternal and child health handbook ( 3500 g). Results Participants’ recall of their birth weight correlated well with the weight recorded in the maternal notebook (r = 0.73; P < 0.025). Low-density lipoprotein (P < 0.05), and total cholesterol (P < 0.01) levels in men, and systolic (P < 0.05) and diastolic (P < 0.05) blood pressure in women were significantly inversely related to birth weight when controlling for age, body mass index, medication, and lifestyle. The percentage of women born small, medium, and large taking antidiabetic agents was 17.8%, 2.9% and 0% (P < 0.05), respectively. Conclusion A low birth weight was associated with high low-density lipoprotein and total cholesterol levels in men, and hypertension and diabetes mellitus in women aged 40–69.

Pregnancy with pulmonary arterial hypertension (PAH) has a significantly high risk of maternal death and women with PAH are basically advised to avoid pregnancy. Recently, several reports have described pregnant women with PAH who were treated with pulmonary vasodilators during pregnancy and delivered safely. However, the efficacy of this treatment during pregnancy is still not clear. Here we report on the short-term outcomes of three primiparous women with PAH who were prescribed pulmonary vasodilator therapy during their pregnancies. All women delivered preterm due to cardiac and/or obstetric reasons and were discharged without any complication. Pulmonary vasodilator therapy can be used safely during the pregnancies of PAH patients and may contribute to improved maternal and fetal prognoses.

We describe a case fetal ventricular tachycardia secondary to long QT syndrome successfully treated with maternal intravenous magnesium.

Aim The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes. Methods We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group). The conventional management for FGR was performed according to guidelines for obstetric practice in Japan. Results Both birthweight and fetal growth velocity from enrollment to birth were significantly higher in the tadalafil group than in the conventional management group. The cesarean delivery rate was approximately twofold higher in the conventional management group than in the tadalafil group. Importantly, cesarean section due to non-reassuring fetal status was performed in seven pregnant women in the conventional management group (58.3%) but in none in the tadalafil group (P < 0.05, chi-squared test). Conclusions Tadalafil may improve perinatal outcome in FGR by modulating fetal growth through maintenance or improvement of fetal well-being.

BACKGROUND The Japan Association of Obstetricians and Gynecologists (JAOG) recommends transfusion with a fresh-frozen plasma (FFP):red blood cell (RBC) ratio of 1 or more in postpartum hemorrhage. However, no global consensus exists concerning this, and little is known regarding the impact of FFP:RBC ratio on maternal mortality. This study evaluates the efficacy of transfusion with FFP:RBC ratio of 1 or more for amniotic fluid embolism (AFE) with coagulopathy. STUDY DESIGN AND METHODS The Maternal Death Exploratory Committee, established by the JAOG, conducted this retrospective nationwide case–control study in Japan. Women with AFE and coagulopathy were included in the study and were stratified into survival and death groups. Obstetric variables and therapy methods (hysterectomy, uterine artery embolism, and transfusion with FFP:RBC ratio ≥ 1) were compared between the survival and death groups. RESULTS A total of 54 women had AFE and coagulopathy (death group, n = 22; survival group, n = 32). Only nine (40.9%) women in the death group were transfused with FFP:RBC ratio of 1 or more, whereas 29 (90.6%) women in the survival group were transfused with FFP:RBC ratio of 1 or more. FFP:RBC ratio of 1 or more was found to be associated with better survival rate (adjusted odds ratio, 28.32; 95% confidence interval, 4.26-188.37). No difference was found in obstetric variables, hysterectomy, and uterine artery embolism between survival and death groups. CONCLUSION Transfusion with FFP:RBC ratio of 1 or more is associated with higher survival rate in women with AFE with coagulopathy.

To make recommendations for saving mothers' lives, issues related to maternal deaths including diseases, causes, treatments, and hospital and regional systems are analyzed by the Maternal Death Exploratory Committee in Japan. In this report, we present ten clinical important recommendations based on the analysis of maternal deaths between 2010 and 2014 in Japan.

Introduction Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. Material and methods This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. Results IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2–18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. Conclusions IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.

Clusters of negatively charged liposomes encapsulated with glucose oxidase were prepared in the presence of Ca2+ and used to catalyze the oxidation of glucose in an external loop airlift bubble column. The clusters exhibited higher catalytic activity compared to nonclustered glucose oxidase-containing liposomes (GOLs) when the liposome membranes were incorporated with cholesterol. The clusters were structurally altered in shear flow to give sufficient interfacial area accessible to glucose. The reactivity of GOL clusters could be modulated on the basis of lipid composition of the membranes which affected the mode of interaction among liposomes through Ca2+. Part of GOL clusters could be separated from the reaction mixture by centrifugation, which would be advantageous for reusing liposomal catalysts. The liposome clusters can be the platforms to regulate the catalytic performance of glucose oxidase in the airlift.

Amniotic fluid embolism (AFE) causes consumption coagulopathy, which requires a massive transfusion to save the mother's life. The preparation of such a massive transfusion is too time-consuming in extremely emergent clinical settings and occasionally leads to devastating side effects such as transfusion-associated acute lung injury. C1 esterase inhibitor (C1INH) is a protein with the ability to inhibit complement, coagulation and kinin pathways. The C1INH concentration in AFE patients is low, and it has been speculated that the administration of C1INH concentrate could have a striking and beneficial effect on AFE patients in critical condition by ameliorating their perturbed coagulation system. We report the case of a 32-year-old Japanese AFE patient in whom deteriorated vital signs and coagulopathy recovered within minutes after an injection of C1INH concentrate. C1INH concentrate can quickly revive the deteriorated vital signs and the atonic uterus that stem from AFE and may reduce the total amount of transfusion.

Perinatal care in Japan has progressed rapidly in recent decades, remarkably reducing maternal, perinatal and neonatal mortality rates. This is attributable not only to the sustained efforts and dedication of past obstetricians and midwives, but also to the collective results achieved by the Japan Society of Obstetrics and Gynecology and healthcare administration, including research on advanced medical care, education, medical care improvements and establishing perinatal care centers. Although the maternal mortality rate was in steady decline until 2007 (3.1/100 000 births), it repeatedly fluctuated thereafter, plateauing at 3.4 per 100 000 births in 2013 and 2.7 per 100 000 births in 2014. Thus, the Perinatology Committee has analyzed the current situation of maternal deaths and has proposed countermeasures to reduce such death. The items deliberated upon by related subcommittees in 2015 are presented herein. The addition of indications for ‘fibrinogen concentrate’, ‘eptacog alfa’ and approval of the PGE2 vaginal tablet for cervical ripening were discussed in the subcommittee for unapproved drug review. Thus, a request for approval for health insurance coverage was submitted to the ‘Evaluation committee on unapproved or off-label drugs with high medical needs’ of the Ministry of Health, Labour and Welfare. Maternal and late-maternal deaths from suicide during the 10 years from 2005 to 2014 in Tokyo's 23 wards were jointly examined with the Tokyo Medical Examiner's Office. The suicide rate in the 23 wards is very high, at 8.7 per 100 000 births. Thus, the subcommittee for the reduction of maternal death discussed countermeasures for the eradication of maternal death and maternal suicide and the revision of death certificates.

Aim Cesarean section is commonly selected in pregnancy with Moyamoya disease. We consider vaginal delivery with epidural anesthesia a viable alternative in such cases. Methods Mode of delivery and outcomes were examined in 27 pregnancies in 19 women with Moyamoya disease treated at the Department of Perinatology, National Cardiovascular Center, Japan, from 1983 to 2013. Of these 27 pregnancies, 20 were delivered vaginally with epidural anesthesia. The cerebral circulation, mode of delivery, maternal outcome (presence of symptoms due to Moyamoya disease intrapartum) and neonatal outcome (gestational week, birthweight, Apgar score at 5 min and pH of umbilical artery) were investigated. Results The cerebral circulation was judged to be good in all pregnancies. No symptoms due to Moyamoya disease intrapartum were seen in the vaginal delivery cases. Conclusion Our findings indicate that vaginal delivery is viable in pregnancy with Moyamoya disease and that unnecessary cesarean section may be avoided. These findings are limited by the retrospective nature of the study.

Aim The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally. Material and Methods A nationwide study of pregnancy-related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O–D time), and obstetric data were recorded. Results Thirty-eight cases of pregnancy-associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre-eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre-eclampsia, HELLP syndrome and O–D time >3 h were significantly associated with maternal mortality. Conclusion Early diagnosis may prevent maternal death, even in severe cases of pregnancy-related ICH. However, maternal–fetal care centers do not always have full-time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.

Objective To describe the safety and efficacy of thoracoamniotic shunting for fetal pleural effusion using a doublebasket catheter with a very small diameter (1.47mm). Method In this 2-year multicenter, prospective single-arm clinical studyregistered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN00001095); shunting was performed between 18w0d and 33w6d of gestation with this catheter in cases of fetal pleural effusions reaccumulating after thoracocentesis. The primary endpoint measures were maternal and fetal adverse effects and survival in the neonatal period. Results A total of 24 cases were included, of which 17 had hydrops (71%). The median gestational ages at shunting and delivery were 27.4 and 34.8weeks, respectively. There were no fetal deaths, lung injuries, or severe maternal complications. Preterm rupture of the membranes occurred in 7/24 (29%) cases at a median of 62days after the shunting. Preterm rupture of the membranes within 28days of the procedure occurred in 1/24 (4%) cases. Catheter displacement towards the fetal thoracic cavity occurred in 4/42 (10%) cases. The overall survival rate was 79% (19/24), whereas it was 71% (12/17) in the cases with hydrops. Conclusion Drainage of fetal pleural effusions with a double-basket shunt is safe and effective, and the shunt could be an alternative device. © 2012 John Wiley & Sons, Ltd.

The Maternal Death Exploratory Committee in Japan analyzed 313 maternal deaths that occurred in the country between January 1, 2010 and March 31, 2017. The details of the Committee have been described previously.1 The study was approved by the ethics board of the National Cerebral and Cardiovascular Center (Osaka, Japan) and the Japan Association of Obstetricians and Gynecologists. This investigation was conducted according to the principles expressed in the Declaration of Helsinki. Informed consent was not obtained from patients or their families, because the study was based on the analysis of institutional forms, and the patient records/information was anonymized. This article is protected by copyright. All rights reserved.

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

Aim: To clarify the cause of maternal deaths, an autopsy is essential. However, there has been no systemic analysis of maternal death in Japan based on autopsy cases. Material & Methods: Maternal death reports were retrieved from a large amount of registered autopsy data on maternal death in the series of ‘Annual of pathological autopsy cases in Japan’. These files contain 468 015 autopsy records from 1989 to 2004. We collected 193 cases of maternal death due to direct obstetric causes. We recorded all the data into Excel files. Then we analyzed the causes of death and classified them into 11 categories. Results: The causes of maternal death were as follows: amniotic fluid embolism (AFE), 24.3%; disseminated intravascular coagulation (DIC) related to pregnancy-induced hypertension, 21.2%; pulmonary thromboembolism, 13.0%; injury to the birth canal, 11.4%; medical and surgical complications, 9.8%; and atonic bleeding or DIC of unknown cause, 8.3%. A discrepancy between the clinical diagnosis and pathological diagnosis was frequently observed in cases of AFE, septic DIC and injury to the birth canal. AFE diagnosed by autopsy was often clinically diagnosed as atonic bleeding or DIC of unknown cause before death. Half of the cases of AFE diagnosed by autopsy were associated with DIC. Conclusion: We found that AFE, DIC related to pregnancy-induced hypertension, pulmonary thromboembolism and injury to the birth canal were the major causes of maternal death in Japan. AFE had various clinical features such as uterine atony and DIC in addition to pulmonary cardiac collapse.