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Fertility preservation (FP) for hematological malignancies is difficult because immediate chemotherapy is needed after diagnosis. We report two cases of acute myeloid leukemia (AML) treated with controlled ovarian stimulation (COS) and oocyte cryopreservation using DuoStim after first-line chemotherapy. In Cases 1 and 2, COS and oocyte retrieval (OR) were performed using DuoStim 116 and 51 days after first-line chemotherapy, respectively, and 14 and 6 unfertilized oocytes, respectively, were cryopreserved. Another round of COS and OR was performed using the random-start method 82 days after first-line chemotherapy, and 22 unfertilized oocytes were cryopreserved. DuoStim is useful to maximize OR for patients with a short interval for FP. Many oocytes can be retrieved depending on the timing of recruitment from primary to secondary follicles, although ovarian reserve capacity declines immediately after first-line chemotherapy. Aggressive FP should be performed before allogeneic hematopoietic stem cell transplantation becomes necessary. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of maternal deaths in high-income countries. This study aimed to assess the characteristics of maternal deaths due to CVDs and the quality of care provided to patients, and to identify elements to improve maternal care in Japan. This descriptive study used the maternal death registration data of the Maternal Deaths Exploratory Committee of Japan between 2010 and 2019. Of 445 eligible pregnancy-related maternal deaths, 44 (9.9%) were attributed to CVD. The most frequent cause was aortic dissection (18 patients, 40.9%), followed by peripartum cardiomyopathy (8 patients, 18.2%), and pulmonary hypertension (5 patients, 11.4%). In 31.8% of cases, cardiopulmonary arrest occurred within 30 min after initial symptoms. Frequent symptoms included pain (27.3%) and respiratory symptoms (27.3%), with 61.4% having initial symptoms during the prenatal period. 63.6% of the patients had known risk factors, with age ≥35 years (38.6％), hypertensive disorder (15.9%), and obesity (15.9%) being the most common. Quality of care was assessed as suboptimal in 16 (36.4%) patients. Cardiac risk assessment was insufficient in three patients with preexisting cardiac disease, while 13 patients had symptoms and risk factors warranting intensive monitoring and evaluation. Aortic dissection was the leading cause of maternal death due to CVDs. Obstetrics care providers need to be familiar with cardiac risk factors and clinical warning signs that may lead to impending fatal cardiac events. Timely risk assessment, patient awareness, and a multidisciplinary team approach are key to improving maternal care in Japan. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy.Study Design: We analyzed 35 cases of cerebrovascular diseases related to maternal deaths in Japan those that occurred during pregnancy and reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2018.Results: Cerebrovascular acute disorders occurred at 34.6 ± 6.6 gestational weeks. There were seven intrauterine fetal deaths (IUFD), and eight cases showed neonatal asphyxia with umbilical arterial pH between 6.7 and 7.0 (asphyxia cases, n = 15). In two of eight newborns, brain hypothermia therapy was given, and all survived without neurological sequelae. Maternal dyspnea was significantly related to severe prolonged decelerations of the fetus (p < .05), and asphyxia cases (p < .005). Median time from maternal onset to delivery (OD time) was significantly longer in asphyxia cases than in the non-asphyxia cases (84 vs 29 min, p < .05). OD time over 30 min was significantly related to the antepartum occurrence, cervical dilatation <5 cm (p < .05), onset outside of the hospital (p < .001), and maternal transfer before delivery (p < .001).Conclusion: More than 40% of cases experienced fetal asphyxia, and 20% ended in IUFD in maternal deaths related to cerebrovascular acute disorders. Maternal respiratory support and rapid delivery would be the keys to improve perinatal outcomes in case of cerebrovascular acute disorders during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant. [ABSTRACT FROM AUTHOR]

Objectives: To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women.Methods: A multicenter prospective study was conducted. The subjects included only Japanese pregnant women with viable singleton who requested the first trimester combined (nuchal translucency and maternal serum marker) screening for fetal aneuploidy. Reference values of PAPP-A and total hCG in Japanese population were made and compared with them in Caucasian.Results: Overall 1,751 Japanese pregnant women were analyzed. Median vales of maternal serum concentration in Japanese pregnant women from 11 + 0-13 + 6 weeks' gestation were ranged from 3.01 to 9.51 mIU/mL for PAPP-A and from 70.2 to 58.3 IU/mL for total-hCG, respectively. Regression curve of median maternal serum PAPP-A and total-hCG concentration against gestational days are significantly higher in Japanese comparing with Caucasian. At most distant values, Japanese serum concentration indicated 1.45 MoM for total-hCG and 1.70 MoM for PAPP-A based on Caucasian regression curves.Conclusion: A modification of the equations by specific reference values is necessary for Japanese pregnant women at the risk assessment of chromosomal abnormalities using the first trimester maternal serum marker. [ABSTRACT FROM AUTHOR]

Objective: Hypertensive disorder of pregnancy (HDP) is a major cause of maternal death. The goal of this study was to investigate factors associated with maternal death due to HDP. Study design: HDP-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor and Welfare from 2010 to 2015 were examined. Results: Out of 47 cases of HDP, 30 were identified as the major cause of maternal death. The median maternal age was 34 years (range 24-45) and the mortality in women aged ≥40 years was seven times higher that than in women aged <34 years. The etiologies were intracerebral hemorrhage (n = 22), subarachnoid hemorrhage (n = 3), subcapsular hematoma of the liver (n = 2), peripartum cardiomyopathy (n = 2), and eclampsia (n = 1), and 19 cases were deemed preventable. The most frequent antepartum problems were delays in hospitalization, maternal transfer, and termination of pregnancy. In four cases, diagnosis of HELLP syndrome was too late because laboratory data were not checked, despite the patient reporting epigastric pain or showing elevation of blood pressure (BP). Treatment for lowering of BP was improper in 2/3 intrapartum cases, even though BP was elevated during pregnancy (144 versus 188 mmHg, p < .001). There was inadequate lowering of BP and lack of use of magnesium sulfate in 7/11 postpartum cases (64%), despite aspartate aminotransferase (AST) (p < .005), alanine aminotransferase (ALT) (p < .01), lactate dehydrogenase (LDH) (p < .005), and platelet count (PLT) (p < .01) all significantly worsening after delivery. Conclusion: HDP accounts for 11% of maternal deaths in Japan. Mothers aged ≥40 years are most at risk for HDP-related maternal death. Major concerns for preventabilities were late hospitalization, maternal transportation, and termination of pregnancy for term or near-term HDP. Regular vital checks and prompt lowering of BP were lacked during labor in most cases. HELLP syndrome should be managed at a general hospital with sufficient medical resources. [ABSTRACT FROM AUTHOR]

Objective: The number of stroke-related maternal deaths is increasing in Japan. We investigated methods to reduce maternal death from stroke.Methods: We analyzed stroke-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2014 inclusive.Results: A total of 35 cases were identified. The median maternal age was 35 years (range 22-45) and the incidence of stoke in women ≥40 was seven-fold higher than in <34. Etiologies were pregnancy induced hypertension in 16, subarachnoid hemorrhage in seven, cerebral infarction in three, arteriovenous malformation in two, Moyamoya disease in one, and origin unknown cerebral hemorrhage in six. These cases occurred in antepartum 43%, in postpartum 31%, and in intrapartum 26%. 23 cases were deemed non-preventable and 12 cases preventable. Possible preventable factors occurred antepartum in 23, postpartum in seven, and intrapartum in six. Preventable features included inadequate hypertension control (33%), presenting too late for termination of pregnancy (14%), delayed hospitalization (11%), and delayed maternal transfer (11%).Conclusions: A total of 90% of strokes were hemorrhagic, and older mothers (≥ 40) were most at risk. Most possible preventable factors occurred antepartum, and improved control of hypertension and earlier termination would help to reduce maternal death from stroke. [ABSTRACT FROM AUTHOR]

Objective: Fetoscopic laser photocoagulation of vascular anastomoses (FLP) is the essential choice in twin-twin transfusion syndrome (TTTS). We proposed that the modified sequential selective laser photocoagulation of communicating vessels (modified SQLPCV) to clarify the perinatal outcomes in TTTS.Methods: The modified SQLPCV was designed with the following order: 1, artery-to-artery anastomoses; 2, venous-to-venous anastomoses; 3, artery-to-venous anastomoses from donor to recipient; and 4, artery-to-venous anastomoses from recipient to donor. The perinatal outcomes were present in TTTS patients who underwent the modified SQLPCV.Results: A total of 203 women underwent modified SQLPCV. The mean pregnancy prolongation period was 83 days, and the mean gestational age at delivery was 33 weeks (range 23-40 weeks). There was a significantly lower rate of recipient fetal demise than donor fetal demise (4% vs. 13%; p < .01). The survival rate of zero and one were respectively 6% (13/203) and 19% (39/203). Two survivors were seen in 74% (151/203), and at least one survivor in 94% (190/203). Univariate and multivariate analysis showed that abnormal fetal Doppler measurements in donor were correlated with donor demise after surgery.Conclusions: The modified SQLPCV represents satisfactory outcomes for fetuses complicating with TTTS. [ABSTRACT FROM AUTHOR]

Objective: To clarify the necessity for and problems related to autopsy for determining the cause of maternal death in Japan.Methods: Women who died during pregnancy or within a year after delivery were analyzed by the Maternal Death Exploratory Committee between 2012 and 2015 in Japan. Maternal deaths were analyzed to verify the requirement of autopsy in cases in which autopsy was performed and the need for autopsy in cases in which it was not performed.Results: Among the 49 cases performed autopsy, the final diagnosis was compatible with the clinical course in 24 cases, while the autopsy diagnosis was incompatible with the clinical course in 13 cases. In two cases, the final diagnosis was based on the clinical course, but an autopsy could exclude other possible causes. In three cases, no exact cause of maternal death was identified after autopsy. On the other hand, in cases without an autopsy, the final diagnosis was made using ante-mortem operating findings and surgical specimens in twenty-one cases. Though, thirty-one cases were estimated diagnosis based on post-mortem imaging or ante-mortem examinations, the exact original cause of death was not determined in 25 cases, and the cause of death could not be identified in eight cases without autopsy.Conclusion: Because in most cases the autopsy provides an exact cause of death, the necessity of autopsies should be more widely accepted in Japan. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the rate of coagulopathy progression in amniotic fluid embolism (AFE), using the level of fibrinogen.Methods: We examined all cases of maternal death (46 cases) related to AFE between 2010 and 2013 in Japan (total number of deliveries: 4,291,459). Fibrinogen, blood loss from AFE onset to fibrinogen measurement, and time from onset to fibrinogen measurement were investigated. The correlations of fibrinogen with time from onset to fibrinogen measurement and blood loss at fibrinogen measurement were analyzed.Results: Fibrinogen was undetectable (less than 50 mg/dL) in 14 cases (93%) and 65 mg/dL in one case (7%). All the cases involving not less than 1000 mL of blood loss or within 60 min from onset to fibrinogen measurement demonstrated low levels of fibrinogen.Conclusions: Coagulopathy in AFE was not directly proportional to bleeding. Furthermore, coagulopathy in AFE developed in a remarkably short length of time. If AFE is suspected, fibrinogen level should be measured rapidly for favoring a more AFE to decrease the risk of death from AFE. And, rapid treatment of coagulopathy can help reduce mortality from AFE. [ABSTRACT FROM AUTHOR]

Objective. Fetal swallowing and gastric emptying contribute importantly to amniotic fluid (AF) homeostasis and fetal gastrointestinal development. We speculated that fetal gastric emptying must be functional early in gestation to prevent rapid increases in AF. We sought to determine the human fetal ontogenic pattern of gastric emptying. Study design. Gastric emptying of eighty normal fetuses at 12–39 weeks was studied. Real-time ultrasound of the fetal stomach was continuously recorded for 1 hour. The gastric area ratio (GAR) was defined as the gastric area divided by the abdominal transverse area. The delta GAR was defined as the change between the maximum and the minimum gastric area ratio x 100 (expressed as percent). A change of the fetal gastric area more than the 10th percentile of the delta GAR at 36–39 weeks was used to define gastric emptying. Results. The 10th, 50th and 90th percentile of delta GAR at 36–39 weeks' was 5.2, 6.5 and 8.7%, respectively. Fetal gastric emptying was detected as early as 12 5/7 weeks of gestation. The proportion of fetuses demonstrating gastric emptying (?>?10th percentile delta GAR) increased with gestational age: 4/33 (12.1%) 12–23 weeks, 3/9 (33.3%) at 24–27 weeks, 8/11 (72.7%) at 28–31 weeks, 12/14 (85.7%) at 32–35 weeks, and 11/13 (84.6%) at 36–39 weeks. Conclusions. Fetal gastric emptying occurs by the beginning of the second trimester, contributing to AF regulation. The increased frequency of gastric emptying in late gestation is likely secondary to increased swallowing, altered fetal behavioral state or endogenous production of gastrointestinal motility factors. [ABSTRACT FROM AUTHOR]