Impact of the COVID-19 pandemic on pathological autopsy practices in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.

Successful Management of Complicated Uterine Displacement Caused by Unilateral Incarceration of the Bicornuate Uterus.

Uterine incarceration is a serious complication of pregnancy, in which the gravid uterus becomes trapped in the posterior pelvis. When labor occurs, delivery does not progress, and the uterus may rupture. Therefore, preoperative diagnosis of uterine incarceration is important, and a caesarian section is indispensable except when the polarity of the uterus can be successfully restored. We report the case of a 35-year-old primipara with a complication of a bicornuate uterus who became pregnant after in vitro fertilization and embryo transfer. No abnormality was observed on regular checkups until the second trimester. At 28 weeks' gestation, the uterine cervix revealed marked dislocation, and, at 31 weeks, magnetic resonance imaging (MRI) revealed uterine cervix elongation and left horn incarceration. At 37 weeks' gestation, an elective cesarean section was performed. On laparotomy, the uterus was found to be markedly dislocated, and distended blood vessels were observed on the surface. Ultrasound examination was performed directly on the uterine wall to decide the incision site. After delivery of the baby, manual repositioning of the uterus revealed the unique concurrent clockwise rotation and retro-vertical deflection. Thus, we concluded that incarceration accompanied by a bicornuate uterus can cause complicated uterine displacement, and preoperative MRI and intraoperative ultrasound examination are useful for managing this condition.

Assisted reproductive technology in Japan: A summary report for 2016 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

PURPOSE: The Japan Society of Obstetrics and Gynecology started an online cycle-based assisted reproductive technology (ART) registry system in 2007. This report presents the characteristics and treatment outcomes of ART registered for the cycles practiced during 2016. METHODS: Cycle-specific information for all ART cycles implemented in participating ART facilities were collected. A descriptive analysis was conducted for the registry database of 2016. RESULTS: In total, 447 790 treatment cycles and 54 110 neonates (one in 18.1 neonates born in Japan) were reported in 2016. The mean patients' age was 38.1 years (SD = 4.5). Among the egg retrieval cycles, 104 575 of 251 399 (41.6%) were freeze-all cycles without fresh embryo transfers (ET), while fresh ET was performed in 64 497 cycles (58.4%). A total of 187 132 frozen-thawed ET cycles were reported, resulting in 62 432 pregnancies and 44 484 neonates born. Single ET was selected for 81.0% of fresh transfers and 82.7% of frozen cycles, resulting in singleton pregnancy/live birth rates of 97.0%/96.4% and 96.7%/96.4%, respectively. CONCLUSION: The total ART cycles and subsequent live births continued to increase in 2016. Single ET was performed more than 80%, and ET has shifted from using fresh embryos to frozen ones.

Assisted reproductive technology in Japan: a summary report for 2015 by The Ethics Committee of The Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) implemented an assisted reproductive technology (ART) registry system in 1986. Here are reported the characteristics and treatment outcomes of ART cycles that were registered in 2015. Methods: JSOG has requested all participating ART facilities to register cycle-specific information for all ART cycles since 2007. A descriptive analysis was performed by using the registry database for 2015. Results: In total, 424 151 cycles and 51 001 neonates (1 in 19.7 neonates born in Japan) were registered in 2015. The patients' mean age was 38.2 years (standard deviation = 4.5). Among the fresh cycles, 94 158 of 244 718 (38.5%) egg retrieval cycles were cycles with freeze-all embryos or oocytes, while fresh embryo transfer (ET) was performed in 70 254 cycles, signaling a decrease from 2014. There were 169 898 frozen-thawed ET cycles, resulting in 56 355 pregnancies and 40 599 neonates. Single ET was performed at a rate of 79.7% for fresh and 81.8% for frozen cycles and the singleton pregnancy/live birth rates were 96.9%/96.5% and 96.8%/96.4% for the respective cycles. Conclusion: The total ART cycles and live births resulting from ART has been increasing in Japan. Single ET was performed at a rate of almost 80% and ET cycles have shifted from fresh to frozen cycles.

Assisted reproductive technology in Japan: a summary report of 1992-2014 by the Ethics Committee, Japan Society of Obstetrics and Gynecology.

Aim: The Japan Society of Obstetrics and Gynecology implemented a registry report system for the clinical practice of assisted reproductive technology in 1986. The aggregated results from 1992 to 2014 are reported herein. Methods and Results: The total number of registered treatments was 393 745 cycles, of which 66 550 were pregnancy cycles and 46 008 were cycles with a live birth. Compared to the number of registered treatments in 2008, when the cycle-based registry was newly introduced, there was a 2.07-fold increase in the total number of treatments and a 2.25-fold increase in the number of cycles with a live birth. As the average age of patients who receive assisted reproductive technology has become markedly higher year by year, the most common age of those patients who received assisted reproductive technology in 2014 was 40 years. Conclusion: The total numbers of both assisted reproductive technology treatments and assisted reproductive technology live births are likely to be higher in the future. In addition, the trend toward aging patients seems to be continuing into the future.

Diversity of progesterone action on lipopolysaccharide-induced expression changes in cultured human cervical fibroblasts according to inflammation and treatment timing.

PROBLEM: The effectiveness of progesterone (P4) treatment for preventing preterm births is unclear. Its effects on the uterine cervix were tested using cultured human uterine cervical fibroblasts (UCFs). METHOD OF STUDY: UCFs were incubated with lipopolysaccharide (LPS) in the presence or absence of P4 under various conditions. mRNA was subjected to PCR arrays and real-time RT-PCR to assess IL-6, IL-8, IL-1beta, PTGS2, MMP-1, and CXCL10 expression. RESULTS: When exposed to a high-LPS concentration (2.0 µg/mL), expression of these genes was not suppressed by simultaneous P4 (1.0 µmol/L) treatment, but it was significantly inhibited when P4 was administered 1 hour prior to LPS, with the exception of the chemokines IL-8 and CXCL10. Expression of all genes was restricted by P4 under low-level LPS (0.2 µg/mL) stimulation, especially when administered prior to LPS treatment. CONCLUSION: These data suggest that early or prophylactic P4 administration is an effective and important measure for reducing preterm birth risk.

Career satisfaction level, mental distress, and gender differences in working conditions among Japanese obstetricians and gynecologists.

AIM: Career satisfaction level, degree of mental distress associated with certain work-related factors, and demographics were examined for the first time in obstetricians and gynecologists in Japan. MATERIAL AND METHODS: Associations between the score on Kessler 6 screening scale, or the job satisfaction level, and the scores on the job content questionnaire, Social Support Questionnaire (SSQ), working conditions and demographics were examined in 1301 members of the Japan Society of Obstetrics and Gynecology. RESULTS: 8.4% of respondents were speculated to suffer from depression or anxiety disorder. Multivariate linear regression analysis identified a heavier workload, less personal control, lower satisfaction on the SSQ, and longer working hours as being independent risk factors for mental distress. CONCLUSION: Careful monitoring of the mental state is necessary for obstetricians and gynecologists with lower incomes, heavier workloads, lower degrees of personal control, and lower satisfaction scores on the SSQ.

Risk perception of pregnancy promotes disapproval of gestational surrogacy: analysis of a nationally representative opinion survey in Japan.

BACKGROUND: To clarify the relationship between the general attitude towards gestational surrogacy and risk perception about pregnancy and infertility treatment. MATERIALS AND METHODS: This study analysed the data of nationally representative cross-sectional surveys from 2007 concerning assisted reproductive technologies. The participants represented the general Japanese population. We used this data to carry out multivariate analysis. The main outcome measures were adjusted odds ratios and 95% confidence intervals from logistic regression models for factors including the effect of pregnancy risk perception on the attitude toward gestational surrogacy. RESULTS: In this survey, 3412 participants responded (response rate of 68.2%). With regard to the attitude towards gestational surrogacy, 54.0% of the respondents approved of it, and 29.7% stated that they were undecided. The perception of a high level of risk concerning ectopic pregnancy, threatened miscarriage or premature birth, and pregnancy-induced hypertension influenced the participants' attitudes towards gestational surrogacy. Moreover, this perception of risk also contributed to a disapproval of the technique. CONCLUSION: Our findings suggest that a person who understands the risks associated with pregnancy might clearly express their disapproval of gestational surrogacy.

Recovery from peripartum cardiomyopathy in a Japanese woman after administration of bromocriptine as a new treatment option.

Peripartum cardiomyopathy (PPCM) is a form of heart failure that occurs in women within 1 month before delivery and 5 months after delivery. The outcome of PPCM is variable but improves significantly when appropriate medication is administered in the acute phase; furthermore, the outcome does not worsen even after discontinuation of therapy in the chronic phase. The symptoms and signs of PPCM are similar to those of idiopathic dilated cardiomyopathy. The medical management of patients with PPCM is similar to that for other other forms of heart failure. Recent experimental data implicate a casual role of prolactin in the development of PPCM. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a Japanese woman with acute PPCM treated with bromocriptine as a therapeutic option. Following treatment, the serum prolactin levels dropped swiftly. Concurrently, LV function improved, and heart failure symptoms decreased, accompanied by a decrease in the BNP level.

Resting oxygen consumption in patients with twin pregnancy.

OBJECTIVE: This study examined the resting oxygen consumption in patients with a twin pregnancy and compared the results with those of singleton pregnancies. METHODS: In 15 patients with a twin and 26 patients with a singleton pregnancy, the resting oxygen consumption was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The average resting oxygen consumption in patients with a twin pregnancy was 231+/-25 ml/min, significantly higher than that in patients with a singleton pregnancy (209+/-24 ml/min, P<0.05). CONCLUSION: Our results indicate an estimated increase in metabolic rate in patients during the third trimester of a twin pregnancy compared with those with a singleton pregnancy.

Plasma adenosine concentrations increase in women with hyperemesis gravidarum.

BACKGROUND: Adenosine is an important metabolic modulator and its concentrations are affected by sympathetic nerve stimulation and cytokine production. Since hyperemesis gravidarum is characterized by overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha, plasma adenosine concentrations may be altered. The present study evaluated plasma adenosine concentrations and their relation with norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum. METHODS: Plasma concentrations of adenosine, norepinephrine, and TNF-alpha were measured in 34 healthy nonpregnant women, and 34 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. The relationships between plasma adenosine, and norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum were evaluated. RESULTS: Mean plasma adenosine, norepinephrine, and TNF-alpha concentrations were significantly increased in women with hyperemesis gravidarum compared to those in nonpregnant and normal pregnant women (p<0.05). The increase in plasma adenosine concentrations correlated with the increase of norepinephrine and TNF-alpha in hyperemesis gravidarum (r=0.50, p<0.05 and r=0.43, p<0.05, respectively). CONCLUSIONS: Adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, so the increase in plasma adenosine in hyperemesis gravidarum might serve to counteract further progression of hyperemesis gravidarum.

Plasma adenosine concentrations increase in women with hyperemesis gravidarum.

BACKGROUND: Adenosine is an important metabolic modulator and adenosine concentrations are affected by sympathetic nerve stimulation and cytokine production. Since hyperemesis gravidarum is characterized by overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha, plasma adenosine concentrations may be altered. The present study evaluated plasma adenosine concentrations and their relation with norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum. METHODS: Plasma concentrations of adenosine, norepinephrine, and TNF-alpha were measured in 34 healthy nonpregnant women, and 34 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. The relationships between plasma adenosine, and norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum were evaluated. RESULTS: Mean plasma adenosine, norepinephrine, and TNF-alpha concentrations were significantly increased in women with hyperemesis gravidarum compared to those in nonpregnant and normal pregnant women (p<0.05). The increase in plasma adenosine concentrations correlated with the increase of norepinephrine and TNF-alpha in hyperemesis gravidarum (r=0.50, p<0.05 and r=0.43, p<0.05, respectively). CONCLUSIONS: Adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, so the increase in plasma adenosine in hyperemesis gravidarum might serve to counteract further progression of hyperemesis gravidarum.

Intrauterine therapy for the acutely enlarging fetal cystic hygroma.

Enlarged fetal cystic hygroma is known to cause life-threatening complications such as fetal hydrops and neonatal respiratory difficulty. A 28-year-old Japanese woman, gravida 0, presented with fetal cystic hygroma at 23 weeks of gestation. There were no other structural malformations or hydrops detected by ultrasonographic examination. In addition, the karyotype was diagnosed as normal through amniotic fluid analysis. The cystic lesion showed acute enlargement and intrauterine sclerotherapy using OK-432 was performed at 26 weeks. The size of the cyst initially decreased, which was followed by a gradual increase. A viable 3,098 g male infant was delivered by cesarean section at 37 weeks without any other complications. The infant had no clinical difficulty during the neonatal period and later underwent a surgical removal of the remaining cystic lesion. Cases of fetal cystic hygroma showing acute enlargement without other complications are considered good candidates for intrauterine therapy to prevent subsequent complications.

Fetal plasma prostaglandin F(2alpha) and cortisol responses to high-dose endotoxin administration in fetal goats.

Intrauterine inflammation/infection has been associated with prenatal mortality and morbidity. However, few studies have been performed to investigate how the fetus responds to intrauterine inflammation/infection in utero. In the present study, fetal plasma prostaglandin (PG) F(2alpha) and cortisol responses to high-dose fetal endotoxin administration were evaluated in late gestation goats (n=8). After 160 microg/kg of fetal weight of endotoxin (Escherichia coli, O111:B4 lipopolysaccharide) administration via the fetal jugular vein over a 5-min period, fetal plasma PGF(2alpha) and cortisol levels, fetal blood gases and pH were measured periodically. After endotoxin administration, fetal plasma cortisol levels significantly increased to 9.5+/-0.8 ng/mL and 9.3+/-0.7 ng/mL after 1 and 3h, respectively (p<0.05) and plasma PGF(2alpha) levels did not change throughout the study. These results suggest that absent PGF(2alpha) and attenuated cortisol responses to high-dose fetal endotoxin administration, relative to the adult, may be a self-protective mechanism that diminishes premature delivery and fetal asphyxia.

Effects of maternal oxygen supplementation on fetal oxygenation and lipid peroxidation following a single umbilical cord occlusion in fetal goats.

Maternal oxygen supplementation is commonly performed to improve fetal oxygenation and acid-base balance during fetal asphyxia. The efficiency of this treatment is controversial, which may be associated with the production of oxygen free radicals and lipid peroxidation. However, only a few studies have been performed to evaluate these issues. To clarify them, we investigated the effects of maternal oxygen supplementation on fetal oxygenation and lipid peroxidation following fetal asphyxia in late gestation goats. We measured fetal blood gases, pH and plasma malondialdehyde (MDA), one of the endproducts of lipid peroxidation, before, during and after fetal asphyxia with and without maternal oxygenation in late gestation goats. Fetal asphyxia was induced by a single total umbilical cord occlusion of 3 minutes' duration, and maternal oxygenation was initiated at 20 min before the cord occlusion and terminated at 20 min after the release of cord occlusion. Maternal oxygen supplementation resulted in a significant increase in fetal PaO(2) before and after the cord occlusion (p<0.05). During the cord occlusion, the extents of hypoxia and acidemia were not changed by maternal oxygen supplementation. Fetal plasma MDA levels before maternal oxygen supplementation averaged 0.80+/-0.04 micromol/L, significantly increased after the initiation of maternal oxygen supplementation (1.11+/-0.07 micromol/L), and further increased following fetal asphyxia (1.28+/-0.06 micromol/L), and after the release of the cord occlusion (1.58+/-0.7 micromol/L)(p<0.05). These values were significantly higher than those in fetuses without oxygenation. We conclude that maternal oxygen supplementation increased fetal oxygenation but caused a concomitant increase in lipid peroxidation in the fetus.

Basal metabolic rate in hyperemesis gravidarum: comparison to normal pregnancy and response to treatment.

OBJECTIVE: The aim of the study was to measure resting minute ventilation and oxygen consumption in patients with hyperemesis gravidarum before and after treatment and to compare the results with those of normal pregnant women. STUDY DESIGN: Baseline evaluation was performed with the use of an open-circuit ventilatory system in 17 hospitalized patients with hyperemesis gravidarum and was repeated 1 week after treatment. Thirty-seven normal pregnant women served as control subjects. RESULTS: Resting minute ventilation and oxygen consumption were decreased by 20% and 15% (P <.001), respectively, in patients with hyperemesis compared with control subjects. The decrease occurred despite a measurable increase of free thyroxine compared with normal pregnancy. Treatment resulted in a 10% increase in oxygen consumption in those patients with increased thyroid stimulation, but not otherwise. CONCLUSION: Resting oxygen consumption is reduced significantly in patients with hyperemesis gravidarum that is consistent with a state of partial starvation rather than increased in parallel with increases of thyroid axis activity.

Relation between plasma endothelin-1 levels and T helper-1:T helper-2 immunity in women with twin pregnancies.

The aim of this study was to investigate the relationship between plasma ET-1 levels and T helper-1 (Th1):Th2 immunity in women with twin pregnancies. The percentage of Th1 and Th2 cells and the Th1:Th2 cell ratios in peripheral blood from 13 normal singleton pregnant women and 13 patients with twin pregnancies at 29-34 weeks' gestation were calculated using flow cytometry. The plasma ET-1 was also determined using a modified radioimmunoassay. The plasma ET-1 concentrations and the cell ratios of Th1:Th2 in twin pregnancies were significantly lower than those in singleton pregnancies. A positive correlation was found between plasma ET-1 levels and the ratios of Th1:Th2 cells in the whole subjects. Our results indicate that decreased ET-1 levels are associated with Th1:Th2 immunity in twin pregnancies.

Increased plasma adenosine concentrations and the severity of preeclampsia.

OBJECTIVE: To investigate the relationship between changes in plasma adenosine and the severity of preeclampsia, and norepinephrine and tumor necrosis factor-alpha concentrations. METHODS: Plasma concentrations of adenosine, norepinephrine, and tumor necrosis factor-alpha relating to the pathogenesis of preeclampsia were measured in women with mild (n = 21) and severe (n = 21) preeclampsia and normal pregnancies (n = 21), matched for age, gestational age, and parity, in the third trimester of pregnancy. We then evaluated the relationships among plasma adenosine, norepinephrine, tumor necrosis factor-alpha concentrations, and the severity of preeclampsia. RESULTS: Mean plasma adenosine, norepinephrine, and tumor necrosis factor-alpha concentrations were significantly higher in women with mild and severe preeclampsia than in normal control subjects (P <.05). In women with preeclampsia, plasma adenosine concentrations increased according to the severity of preeclampsia (0.60 +/- 0.03 micromol/L and 0.72 +/- 0.03 micromol/L, respectively, versus 0.41 +/- 0.03 micromol/L for normal subjects), which correlated with increases of norepinephrine and tumor necrosis factor-alpha concentrations (r =.58, P <.05; r =.49, P <.05, respectively). In preeclampsia, norepinephrine concentration also correlated with maternal blood pressure (r =.50, P <.05). CONCLUSION: Adenosine is an established suppressor of the effects of norepinephrine and tumor necrosis factor-alpha. The increased plasma concentrations of adenosine in preeclampsia might serve to counteract further progression of the complication.

The T-helper 1/T-helper 2 balance in peripheral blood of women with hyperemesis gravidarum.

OBJECTIVE: The purpose of this study was to evaluate the T-helper 1/T-helper 2 balance and its relation with pregnancy-related hormones in hyperemesis gravidarum. STUDY DESIGN: The T-helper 1/T-helper 2 ratio and plasma progesterone and estrogen levels were examined in the peripheral blood of 22 women with hyperemesis gravidarum and normal pregnancies. The proportion of CD4-positive cells that expressed intracellular cytokines (interferon gamma and interleukin-4) were analyzed by blood flow cytometry. The ratio of interferon gamma-secreting cells to interleukin-4-secreting cells was taken as the T-helper 1/T-helper 2 ratio. RESULTS: In hyperemesis gravidarum, the proportions of interleukin-4-secreting cells increased, and the T-helper 1/T-helper 2 ratio averaged 8.4 +/- 0.9, which was significantly lower than in normal pregnancy (11.6 +/- 1.1, P <.05). The changes in the T-helper 1/T-helper 2 ratio in hyperemesis gravidarum were accompanied by the elevation of progesterone and estrogen levels. CONCLUSION: A further shift of the T-helper 1/T-helper 2 balance to the T-helper 2 dominance in hyperemesis gravidarum may be related to the increase of progesterone and estrogen levels.

Relationship between adenosine deaminase activity and cytokine-secreting T cells in normal pregnancy.

OBJECTIVE: To evaluate the relationship between plasma adenosine deaminase activity and the proportion of cytokine-secreting T cells as causes of changes in adenosine deaminase activity in normal pregnancy. METHODS: Plasma adenosine deaminase activity and the proportions of cytokine-secreting T cells were measured in the peripheral blood of 26 nonpregnant and normal pregnant women in the third trimester. The proportion of CD4-positive T cells secreting interferon-gamma derived from T helper 1 cells, and interleukin-4 derived from T helper 2 cells, were analyzed by flow cytometry. The ratio of interferon-gamma-secreting cells to interleukin-4-secreting cells was taken as the T helper 1/T helper 2 ratio. RESULTS: Mean plasma adenosine deaminase activity in normal pregnant women, averaged, was significantly lower than that in nonpregnant women (10.3 +/- 0.6 U/L versus 13.8 +/- 0.5 U/L, P <.05). In normal pregnant women, the proportion of interferon-gamma-secreting cells was significantly lower than that in nonpregnant women (20.5% +/- 1.0% versus 24.7% +/- 1.2%, P <.05), but the proportion of interleukin-4-secreting cells did not differ from that of nonpregnant women. Consequently, the T helper 1/T helper 2 ratios were significantly decreased during normal pregnancy. A significant correlation was found between adenosine deaminase activity and the proportion of interferon-gamma-secreting cells (r =.54, P <.05). CONCLUSION: Decreased plasma adenosine deaminase activity in normal pregnant women may be in part associated with changes in the immunological status, especially the decrease of the proportion of interferon-gamma-secreting cells.