Intertwin discordance of aldosterone levels in amniotic fluid with placental anastomoses in monochorionic twins: Insight into the pathophysiology of twin-to-twin transfusion syndrome.

INTRODUCTION: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin-angiotensin-aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF-ALD) levels. In addition, this study also examined the association between AF-ALD and the ALD levels in the umbilical cord blood (UCB-ALD) in monochorionic twins. MATERIAL AND METHODS: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin-to-twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF-ALD levels between the larger and smaller twins were analyzed. RESULTS: The AF-ALD levels showed a strong and significant positive correlation with UCB-ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF-ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). CONCLUSIONS: The AF-ALD levels reflect the UCB-ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS.

Sensitive detection of hemodynamic changes after fetoscopic laser photocoagulation by assessing intraventricular pressure difference in fetuses with twin-to-twin transfusion syndrome.

OBJECTIVES: To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography. METHODS: We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD. RESULTS: Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP. CONCLUSIONS: IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS.

Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

Swim-up method is superior to density gradient centrifugation for preserving sperm DNA integrity during sperm processing.

Purpose: This study aimed to evaluate the effects of swim-up and density gradient centrifugation methods on sperm DNA fragmentation. Methods: Nineteen normozoospermic patient samples with ≥100 × 106 motile sperms were included in this study. Sperm DNA fragmentation, progressive motility, and progressive motile sperm number were measured before and after the swim-up method or density gradient centrifugation. Results: Sperm DNA fragmentation was not statistically different between swim-up-(14.4 ± 2.1%, p = 0.32) and density gradient centrifugation-processed (25.0 ± 3.0%, p = 0.20) and unprocessed semen samples (19.2 ± 1.9%). Sperm DNA fragmentation was significantly lower in swim-up-than in density gradient centrifugation-processed samples (p < 0.05). Sperm progressive motility was significantly higher (p < 0.05) in swim-up-(92.9 ± 1.0%) and density gradient centrifugation-processed (81.3 ± 2.0%) samples, with the former being higher, than in unprocessed semen samples (53.1 ± 3.7%). The recovery rate of progressive motile sperms was significantly lower in swim-up-(9.7 ± 1.4%) than in density gradient centrifugation-processed samples (17.2 ± 1.8%, p < 0.05). Conclusions: The swim-up method is superior to density gradient centrifugation, evidenced by less sperm DNA fragmentation and higher sperm progressive motility. The recovery rate of progressive motile sperms was better after density gradient centrifugation than after swim-up.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Optimal timing to retrieve oocytes for fertility preservation in patients with acute myeloid leukemia: two cases of controlled ovarian stimulation using DuoStim with a literature review.

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.

Different expressions of cardiac biomarkers between different types of acquired right ventricular outflow tract abnormality in monochorionic twins.

OBJECTIVE: To investigate the differences in amniotic fluid cardiac biomarkers and clinical features among types of right ventricular outflow tract (RVOT) abnormality in monochorionic (MC) twins. METHOD: This prospective study included MC twins that underwent laser surgery. Recipient or larger twins (group A) and donor or smaller twins (group B) were assessed and divided into those with a normal right ventricular outflow tract (normal RVOT), functional pulmonary atresia (fPA), or pulmonary stenosis (PS). Amniotic fluid levels of NT-proBNP (afNT-proBNP) and cardiac troponin T (afTnT) were examined during surgery. RESULTS: Of 190 fetuses in group A, there were 14 RVOT abnormality cases (including 7 fPA and 7 PS). No group B fetuses showed RVOT abnormality findings. In group A, later and earlier gestational age at surgery were observed in fPA (25.1 ± 2.8 weeks) and PS groups (17.8 ± 0.9 weeks). All survived PS cases demonstrated progressive pulmonary valve obstruction, not observed in fPA groups. AfNT-proBNP were significantly higher in fPA and PS than in the normal RVOT group (p < 0.05). AfTnT was significantly higher in group A with PS than fPA and normal RVOT groups (p < 0.05). CONCLUSION: Among RVOT abnormality types in group A, amniotic fluid cardiac biomarkers were differently expressed, and clinical features were also differentiated. These findings provide insight into the pathophysiological influence on RVOT in MC twins. CLINICAL TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trial Registry "UMIN-CTR" (http://www.umin.ac.jp/ctr/index-j.htm; trial ID numbers UMIN000024486 and 000037702).

Prenatal evaluation of functional pulmonary hypoplasia via fetal magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to retrospectively examine the use of lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images to predict functional pulmonary hypoplasia. METHODS: The subjects of this study were pregnant women who underwent magnetic resonance imaging (MRI). Patients who required nitric oxide inhalation and those who died from respiratory disorders were classified as having functional pulmonary hypoplasia (FPH). All other cases were presented as the control group. We retrospectively analyzed MRI and perinatal data. LLSIR was defined as the ratio of lung signal intensity to liver signal intensity. We examined the relationship between LLSIR and gestational age, compared the LLSIRs in the two groups, and calculated the best cut-off value of the LLSIR to predict FPH. RESULTS: One hundred and ninety-one patients were eligible for this study, and 12 cases were classified as having FPH. In the control group, LLSIR increased with age (r = 0.383, p < 0.001). We used the observed/expected LLSIR (o/e LLSIR), which was the ratio of obtained LLSIR to expected LLSIR calculated by the regression line to correct the effect of gestational age. In the FHP group, o/e LLSIR was significantly lower than in the control group (p < 0.001). A receiver operating characteristic curve analysis showed that cases with o/e LLSIR above 0.85 were less likely to cause FPH. CONCLUSIONS: Low o/e LLSIR might reflect the histological characteristics of hypoplastic lung structures. O/e LLSIR seems to be a useful MRI parameter for screening FPH.

Biochemical effects of intraoperative cell salvage and autotransfusion during cesarean section: A prospective pilot study.

AIM: Intraoperative cell salvage and autotransfusion (ICSA) is a useful technique for women undergoing cesarean sections who are predicted to experience significant bleeding. This method can reduce allogeneic transfusions as well as its associated risks and costs. Amniotic fluid embolism (AFE) is an abnormal maternal response to ICSA similar to the classic systemic inflammatory response syndrome, but its mechanism is not well understood. This study was conducted to investigate the biochemical aspects of AFE. METHODS: A prospective case-controlled pilot study was conducted in a general perinatal hospital in Japan. ICSA was performed using a two-step retransfusion process. Blood samples were collected presurgery, immediately postsurgery, and 24 h after surgery. Changes in sialyl Tn antigen (STN), complement C3 and C4, fibrinogen, and fibrin degradation product and D-dimer, C1 esterase inhibitor, and interleukin-8 (all considered AFE-related markers) activities were compared between patients who underwent cesarean sections with ICSA (ICSA group) versus without ICSA (control group). RESULTS: Fibrinogen levels were significantly lower in the ICSA group than in the control group before surgery but not immediately after or 24 h after surgery. D-dimer was significantly higher immediately after surgery but not 24 h later. STN was significantly lower only before surgery. None of the AFE-related markers showed significant differences between the groups after 24 h. No adverse events were observed in the ICSA group. CONCLUSIONS: There is no clinical evidence that ICSA alters the biochemical statuses of AFE-related markers in a manner that could lead to adverse maternal responses.

iPREFACE score: Integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring.

AIM: Cardiotocography is used worldwide to evaluate fetal well-being during pregnancy and labor. In past guidelines, the management plan was determined based on the assessment of the most severe waveform. There are no guidelines for evaluating the integrated recurrent decelerations; however, we believe their assessment to be essential for predicting the status of the fetus. The objective of this study was to propose an indicator for performing medical interventions during labor by creating a scoring system that reflects integrated recurrent decelerations. METHODS: In this retrospective cohort study, we included data for only full-term single fetus births from vaginal deliveries. The score named the iPREFACE score (integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring) was calculated using cardiotocography findings from continuing 30 min before delivery. We examined the iPREFACE score and fetal acidemia association and calculated the cut-off iPREFACE scores for acidemia using receiver operating characteristic curves. RESULTS: The study included 469 delivery cases. Their iPREFACE scores exhibited a significant negative correlation with the umbilical artery blood pH (correlation coefficient; -0.43). The cut-off iPREFACE scores for the umbilical artery blood with pH <7.20, <7.10 and <7.0 were 44, 46 and 67, respectively (the areas under the curve were 0.776, 0.962 and 0.996, respectively). CONCLUSION: The iPREFACE score may predict fetal acidemia and could be used as an indicator for timely medical interventions during labor. Because assessments using a cardiotocography are quick and easy to perform, the iPREFACE score could be a valuable tool in clinical practice.