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Background During the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and prevent morbidity among healthcare workers.Methods To evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries.Methods We investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch.Results Of the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process.Conclusion The number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.

Summary: Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil’s potential to mitigate LBW-associated risks.

Abstract The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents’ decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents’ decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89–0.99; Model 2: 0.95 0.90–0.997). Critical disease (5.25; 1.09–25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21–14.53; Model 2: 5.47, 1.50–19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14–2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.

Objectives: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). Methods: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. Results: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. Conclusion: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

Abstract Although digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it is subjective. Transperineal ultrasound (TPU) is combined with digital evaluation for accurate assessment of fetal descent and rotation of the advanced part of the fetus. This retrospective study aimed to clarify the impact of introducing TPU on perinatal outcomes at Mie University Hospital. We analyzed singleton pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who used TPU (TPU+ group) and those who did not (TPU− group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased (90.9% vs. 71.6%; P = 0.0017), and the second stage of labor was significantly prolonged in the TPU+ group (148.1 vs. 75.8 min; P

Background/Objective: This study determines whether the use of a portable interface pressure sensor (Palm Q) for robotic surgery could prevent compartment syndrome. Methods: In the present single center, non-trial observational study, patients diagnosed with gynecological diseases between April 2015 and August 2020 treated with laparoscopic or robotic surgery were enrolled. We assessed 256 cases involving surgery performed in the lithotomy position with an operative time >4 h. The Palm Q device was placed preoperatively on both sides of the patients’ lower legs. The pressure was measured every 30 min preoperatively and intraoperatively and adjusted to ≤30 mmHg. If the pressure reached ≥30 mmHg, the operation was stopped, the patient was repositioned, the leg position was released, the pressure was reduced to ≤30 mmHg, and the procedure was resumed. We compared the maximum creatine kinase levels of the Palm Q and non-Palm Q groups. We also analyzed the correlation between the patients’ symptoms postoperatively (shoulder and leg pain) and compartment syndrome. Results: Our data showed that immediate postoperative creatine kinase levels predict compartment syndrome. Propensity score matching of the 256 enrolled patients resulted in 92 cases (46 per group), balanced for age, body mass index, and lifestyle disease. Creatine kinase levels differed significantly between the Palm Q and non-Palm Q groups (p = 0.041). None of the patients in the Palm Q group experienced well-leg compartment syndrome complications. Conclusion: Palm Q can potentially help to prevent perioperative compartment syndrome.

Abstract This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3–4.7) for 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.

Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin–eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

Abstract Background The impact of cumulative dose of cisplatin on gonadal function has not been clarified. We evaluated whether the cumulative cisplatin dose affects the resumption of menses in patients treated with bleomycin, etoposide, and cisplatin (BEP). Main body A case series study of women

A clinical challenge remains in the treatment of hypoxic–ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD + ) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD + -promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia–ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia–ischemia. At different time points after hypoxia–ischemia, hippocampal NAD + , caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia–ischemia reduced NAD + and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD + and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia–ischemia in mice suggesting as a possible novel treatment for neonatal brain injury. Summary Statement Neonatal hypoxia–ischemia reduces nicotinamide adenine dinucleotide (NAD + ) and SIRT6 levels in the injured hippocampus. Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia–ischemia. Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD + and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release. NMN improves early developmental behavior, as well as motor and memory function.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Abstract To investigate the relationships between communicative and critical health literacy (CCHL) and anxiety and depressive symptoms (ADs) in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was conducted and 5466 pregnant women responded in Japan in September 2020. A Kessler 6 scale (K6) score ≥ 10, an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13, and four CCHL groups were analyzed using a logistic regression model and trend test. The proportions of pregnant women with a K6 score ≥ 10 and EPDS score ≥ 13 were 13.5 and 15.4%, respectively. In comparisons with the low CCHL group, the adjusted odds ratio (95% CI) for anxiety symptoms was 0.770 (0.604–0.982) in the high CCHL group, while those for depressive symptoms were 0.777 (0.639–0.946), 0.665 (0.537–0.824), and 0.666 (0.529–0.838) in the lower, higher, and high CCHL groups (all p

Sperm DNA fragmentation (SDF) that occurs during the freezing–thawing of sperm may negatively impact the treatment outcomes of assisted reproductive technologies (ART). In a previous study, we developed a human sperm cryopreservation reagent containing carboxylated poly-L-lysine (CPLL) that reduced SDF after freeze-thawing compared with clinically popular cryopreservation reagents containing human serum albumin. However, it is unclear whether CPLL reduces SDF, as it differed from the constituents of the commercial cryopreservation reagents used for comparison. Therefore, here, we examined whether CPLL reduces the SDF of human sperm and evaluated reactive oxygen species (ROS) levels and lipid peroxidation (LPO), which are the causes of SDF; mitochondrial injury, ROS production; and impaired sperm motility. Furthermore, optimal antioxidants and their concentrations that could further enhance the reduction in SDF were determined for future clinical application in ART and underwent the same functional evaluations. CPLL can reduce SDF via inhibition of intracytoplasmic ROS and LPO. Furthermore, the addition of 0.1 mM resveratrol avoided the enhancement of SDF, which potentially affects mitochondrial and cytoplasmic ROS and LPO. This novel human sperm cryopreservation reagent containing CPLL and resveratrol has the potential to improve treatment outcomes in ART using frozen sperm.

Abstract Background The aim of the present study was to clarify fetal heart rate (FHR) evolution patterns in infants with cerebral palsy (CP) according to different types of umbilical cord complications. Methods This case–control study included children born: with a birth weight ≥2000 g, at gestational age ≥33 weeks, with disability due to CP, and between 2009 and 2014. Obstetric characteristics and FHR patterns were compared among patients with CP associated with (126 cases) and without (594 controls) umbilical cord complications. Results There were 32 umbilical cord prolapse cases and 94 cases with coexistent antenatal umbilical cord complications. Compared with the control group, the persistent non-reassuring pattern was more frequent in cases with coexistent antenatal umbilical cord complications (p = 0.012). A reassuring FHR pattern was observed on admission, but resulted in prolonged deceleration, especially during the first stage of labor, and was significantly identified in 69% of cases with umbilical cord prolapse and 35% of cases with antenatal cord complications, compared to 17% of control cases (p

Abstract Objective Here, we tested the correlation between maternal placental growth factor (PlGF) and fetal heart rate (FHR) monitoring findings. Methods We included 35 women with single pregnancies from 35 to 42 weeks of gestation who were hospitalized owing to onset of labor. Blood samples were collected at the start of labor. Intrapartum FHR monitoring parameters included total deceleration area, average deceleration area (mean deceleration area per 10 min), and five-tier classification level. Results Of the 35 women, 26 (74%) had vaginal delivery and 9 (26%) had cesarean section. After excluding 2 women who had cesarean section for arrest of labor, we analyzed 26 women who had vaginal delivery (VD group) and 7 who had cesarean section for fetal indications (CSF group). PlGF level was significantly higher in the VD group (157 ± 106 pg/ml) than in the CSF group (74 ± 62 pg/ml) (P = 0.03). There were no significant correlations between PlGF and total (r = -0.07) or average (r = -0.08) deceleration area. There was a significant negative correlation (r = -0.42, P = 0.01) between PlGF and the percentage of level 3 or higher in the five-level classification. Conclusion PlGF was correlated with FHR monitoring findings and might be a promising biomarker of intrapartum fetal function.

Abstract Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 μg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation.

Abstract Purpose To examine the optimal timing of second ovarian stimulation using the dual stimulation method for good ovarian responders with cancer undergoing oocyte retrieval for fertility preservation. Methods A retrospective analysis was conducted using data from 69 patients with cancer who underwent oocyte retrieval for fertility preservation at four Japanese institutions during 2010–2021. Twenty‐two patients underwent two oocyte retrievals for fertility preservation. We studied the relationship between the initial number of oocytes retrieved via dual stimulation and risk of ovarian enlargement as well as the appropriate waiting interval between the end of the first ovarian stimulation and beginning of the second ovarian stimulation. Results The risk of ovarian enlargement was high when the initial number of oocytes retrieved via dual stimulation was ≥5. An 8‐day waiting interval may be more effective for performing a second ovarian stimulation oocyte retrieval in these cases, although the difference was not significant. Conclusions This study provides one policy for effectively managing ovarian enlargement and timing of second ovarian stimulation during oocyte retrieval via the dual stimulation method for patients with cancer undergoing fertility preservation. If more facilities implement this procedure, more oocytes may be obtained in a short period for fertility preservation purposes.

The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system.

Objective To identify independent risk factors for severe COVID-19 in pregnant women and to evaluate the impact of disease severity on preterm birth.Design A case–control study based on data from a nationwide questionnaire-based survey of maternity services in Japan.Setting A questionnaire was mailed to all 2135 delivery institutions in Japan between July and August 2021. A total of 1288 institutions responded (60% of all delivery institutions in Japan). 566 facilities reported having cared for pregnant women with COVID-19, and 722 facilities reported having had no such patients.Participants One thousand and forty-three hospitalised and non-hospitalised pregnant women diagnosed with COVID-19 between July 2020 and 30 June 2021.Primary and secondary outcome measures The primary outcome was progression to severe COVID-19. The secondary outcome was preterm birth due to COVID-19 infection.Results 56 cases (5.4%) were severe, and 987 (94.6%) were non-severe. Multivariable logistic regression analysis showed that gestational age≥24 weeks (adjusted OR (aOR) 6.68, 95% CI 2.8 to 16.0) and maternal age≥32 years (aOR 2.40, 95% CI 1.3 to 4.3) were independently associated with severe cases. Using the Kaplan-Meier method, the probability of continued pregnancy at 14 days after diagnosis for severe cases was 0.57 between 24 and 31 weeks’ gestation and 0.27 between 32 and 36 weeks’ gestation. The probability for non-severe cases was 1.0 between 24 and 31 weeks’ gestation and 0.8 between 32 and 36 weeks’ gestation. Among the patients with COVID-19 in the preterm period, preterm birth due to infection was significantly more common in severe than non-severe cases (48% vs 6%, p< 0.0001).Conclusions Severe COVID-19 in pregnant women was associated with gestational age≥24 weeks and maternal age≥32. The rate of preterm delivery due to the infection was significantly higher in severe COVID-19 cases.

Background and Objectives: A relationship between endometrial polypectomy and in vitro fertilization (IVF) pregnancy outcomes has been reported; however, only a few studies have compared polyp removal techniques and pregnancy rates. We investigated whether different polypectomy techniques with endometrial curettage and hysteroscopic polypectomy for endometrial polyps affect subsequent pregnancy outcomes. Materials and Methods: Data from 434 patients who had undergone polypectomy for suspected endometrial polyps using transvaginal ultrasonography before embryo transfer in IVF at four institutions between January 2017 and December 2020 were retrospectively analyzed. Overall, there were 157 and 277 patients in the hysteroscopic (mean age: 35.0 years) and curettage (mean age: 37.3 years) groups, respectively. Single-blastocyst transfer cases were selected from both groups and age-matched to unify background factors. Results: In the single-blastocyst transfer cases, 148 (mean age: 35.0 years) and 196 (mean age: 35.9 years) were in the hysteroscopic and curettage groups, respectively, with the 148 cases matched by age. In these cases, the pregnancy rates for the first embryo transfer were 68.2% (odds ratio (OR): 2.14) and 51.4% (OR: 1.06) in the hysteroscopic and curettage groups, respectively; the resulting OR was 2.03. The pregnancy rates after up to the second transfer were 80.4% (OR: 4.10) and 68.2% (OR: 2.14) in the hysteroscopic and curettage groups, respectively, in which the OR was 1.91. The live birth rates were 66.2% (OR: 1.956) and 53.4% (OR: 1.15) in the hysteroscopic and curettage groups, respectively, in which the odds ratio was 1.71. These results show the effectiveness of hysteroscopic endometrial polypectomy compared to polypectomy with endometrial curettage. No significant difference was found regarding the miscarriage rates between the two groups. Conclusions: Hysteroscopic endometrial polypectomy resulted in a higher pregnancy rate in subsequent embryo transfer than polypectomy with endometrial curettage. Therefore, establishing a facility where polypectomy can be performed hysteroscopically is crucial.

Abstract Background Few reports have presented an overall view of pregnant women with coronavirus disease 2019 (COVID-19) across an entire country and throughout the entire gestation period. Furthermore, no such reports are available for Japan. We examined the clinical characteristics and outcomes of pregnant women with COVID‑19 on a national scale in Japan. Methods A nationwide questionnaire-based survey for all 2,185 maternity services in Japan was conducted between July and August 2020. Information regarding maternal characteristics and epidemiological, clinical, treatment, and perinatal outcomes of pregnant women diagnosed with COVID-19 between 16 January and 30 June 2020 were collected. Main outcome measures were incidence of pregnant women with COVID-19 and infant infection, positive rate of the universal screening test for asymptomatic pregnant women, identification of infection route and rates of maternal death, and severe cases. Results Responses from 1,418 institutions were assessed (65% of all delivery institutions in Japan). Seventy-two pregnant women were reported to have been diagnosed with COVID-19. The positive rate of the universal screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic pregnant women was 0.03% (2/7428). The most common route of infection was familial (57%). Fifty-eight pregnant women with COVID-19 were symptomatic, of whom five (8.6%) had a severe infection and one died (a tourist). Severe respiratory symptoms, oxygen administration, and pneumonia were frequently reported in the third trimester and postpartum period compared with in early pregnancy (22.2% vs 2.5% [P = 0.03], 38.9% vs 7.5% [P = 0.01], and 50.0% vs 7.5% [P

Objective: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. Materials and methods: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. Results: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p

Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants’ neuro-developmental prognosis.

BackgroundThe aim of this study was to determine the usefulness of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in predicting the time for pregnancy termination in pregnant women with known preeclampsia (PE) onset.MethodsForty-four pregnant women diagnosed with PE (22 weeks 0 days to 33 weeks 6 days gestation) were included in this study. The levels of sFlt-1 and PlGF, and the sFlt-1/PlGF ratio were compared between the women that delivered in

Abstract We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p

Abstract Background Although spinal schwannomas generally grow very slowly, it has been reported that these clinical growths and their associated neurological symptoms accelerate during pregnancy. Because these cases are rare, surgical intervention for this tumor during pregnancy poses a significant challenge. The change of pregnancy-related hormones, such as estrogen and progesterone, is considered to have an effect on the clinical symptoms of spinal tumors. Expressions of the receptors for estrogen and progesterone in orbital and vestibular schwannomas have been reported; however, those expressions in spinal schwannomas have not been examined. Case presentation A 36-year-old woman at 8 weeks' gestation suffered from developing neck pain and neurological symptoms in the right upper extremity. Magnetic resonance imaging (MRI) confirmed the presence of a cervical intradural extramedullary tumor. Under general anesthesia, using intraoperative neurophysiological monitoring of motor-evoked potentials (MEPs), spinal tumor resection following a hemi-laminoplasty was performed in a prone position at 12 weeks gestation. The pathological diagnosis following surgery was spinal schwannoma. Her neurological symptoms were significantly improved after surgery and she delivered a healthy baby in her 40th week of pregnancy. At a 12-month follow-up, no abnormalities were observed during medical examinations of both mother and child. An immunohistochemical study identified the expression of estrogen receptors, but not progesterone receptors, in the spinal schwannoma. Conclusions A cervical spinal schwannoma was successfully removed under general anesthesia at 12 weeks gestation by coordination between orthopaedic, obstetric and anesthesia teams. For the first time, an immunohistochemical analysis showed that the expression of estrogen receptors was identified in spinal schwannoma cells, suggesting the possibility that these hormone receptors in spinal schwannoma might contribute to the worsening of neurological symptoms during pregnancy.

Abstract Objective This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. Methods The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. Results A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06–2.81) and during the night shift (OR 2.29, 95% CI 1.30–4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97–2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70–2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47–3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76–4.84). Conclusion Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015–2019 as the pre-pandemic and 2020–2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We screened maternal CMV antibodies (the Denka assay) in Japan, from 2017 to 2019, using a revised IgM cutoff (≥4.00 index). Participants were tested for IgG and IgM antibodies, and for IgG avidity if IgM levels exceeded the cutoff. We compared these with corresponding results from 2013 to 2017 based on the original cutoff (≥1.21) and recalculated using the revised cutoff. Newborn urine CMV DNA tests were performed for women with low avidity (≤35.0%). Among 12,832 women screened in 2017–2019, 127 (1.0%) had IgM above the revised cutoff. Thirty-five exhibited low avidity, and seven infants developed cCMV. Of 19,435 women screened in 2013–2017, 184 (1.0%) had IgM above the revised cutoff, 67 had low avidity, and 1 had cCMV. The 2017–2019 results were not significantly different from the 2013–2017 results. The revised IgM cutoff improves maternal screening in identifying primary infection and newborn cCMV; however, further study related to other assays than Denka is required.

Background: This study aimed to evaluate the effectiveness of pelvic and para-aortic lymphadenectomy in patients with advanced epithelial ovarian cancer following neoadjuvant chemotherapy. Methods: This single-center retrospective study analyzed patients with advanced epithelial ovarian cancer who underwent interval debulking surgery between December 2008 and March 2020. Patients’ clinical and pathological data were obtained from medical records. Statistical analyses were performed using the Fisher’s exact and Mann–Whitney U test. Results: Overall, 33 and 22 patients were included in the lymphadenectomy and no-lymphadenectomy groups, respectively. The lymphadenectomy group had longer operative time and higher rates of intraoperative blood loss and lymph cysts than the no-lymphadenectomy group (p < 0.0001). The median progression-free survival (PFS) was longer in the lymphadenectomy group than in the no-lymphadenectomy group (37.0 vs. 20.0 months, p = 0.038). Among patients with enlarged lymph nodes before chemotherapy, the median PFS was longer in the lymphadenectomy group than in the no-lymphadenectomy group (36.0 vs. 15.0 months, p = 0.013). Multivariate analysis of all patients revealed that residual tumor status (p = 0.002) and histology (p = 0.009) were associated with PFS. Additionally, multivariate analysis of patients with enlarged lymph nodes before chemotherapy showed that lymphadenectomy (p = 0.017) and histology (p = 0.021) were associated with PFS. Conclusions: Systematic lymphadenectomy was associated with complications; however, PFS was significantly prolonged in patients with enlarged lymph nodes in the lymphadenectomy group. Therefore, lymphadenectomy has the potential to improve prognosis in patients with ovarian cancer and enlarged lymph nodes.

Abstract Purpose In vitro maturation (IVM) of human oocytes offers an invaluable opportunity for infertility treatment. However, in vitro matured oocytes often show lower developmental abilities than their in vivo counterparts, and molecular mechanisms underlying successful maturation remain unclear. In this study, we investigated gene expression profiles of in vitro matured oocytes at the single‐cell level to gain mechanistic insight into IVM of human oocytes. Methods Human oocytes were retrieved by follicular puncture and in vitro matured. In total, 19 oocytes from 11 patients were collected and subjected to single‐cell RNA‐seq analyses. Results Global gene expression profiles were similar among oocytes at the same maturation stage, while a small number of oocytes showed distinct transcriptomes from those at the corresponding maturation stage. Differential gene expression analysis identified hundreds of transcripts that dynamically altered their expression during IVM, and we revealed molecular pathways and upstream regulators that may govern oocyte maturation. Furthermore, oocytes that were delayed in their maturation showed distinct transcriptomes. Finally, we identified genes whose transcripts were enriched in each stage of oocyte maturation. Conclusions Our work uncovers transcriptomic changes during human oocyte IVM and the differential gene expression profile of each oocyte.

Background: We analyzed both early and late (persistent) phases of each cytomegalovirus (CMV) antibody in mothers with primary CMV infection during pregnancy and subsequent congenital CMV infection for a long period from late pregnancy to after delivery using our stored serum samples. Methods: We used stored serum samples obtained during pregnancy to after delivery from mothers with CMV immunoglobulin (Ig) G seroconversion and subsequent infant congenital CMV infection. CMV antibodies, including CMV IgG titer, IgM titer, and IgG avidity, were assessed using the Denka IgG assay, Denka IgM assay Ver.1 and Ver.2, and Enzygnost IgG assay and Denka IgG avidity assay, respectively. We analyzed the dynamics of each CMV antibody for a long period from late pregnancy to after delivery and correlations of each antibody, calculating Pearson’s correlation coefficients (R2). Results: We used 67 serum samples obtained from 12 included participants between 2013 and 2018. CMV IgG increased until 61 weeks and did not change significantly after. CMV IgM decreased until 52 weeks and did not change significantly after that in both assays. CMV IgG avidity increased until 64 weeks and did not change significantly after that in both assays. In CMV IgM, a strong positive correlation was found (R2 = 0.9326) between the two different IgM assays. Serum results of the late phase (after 60 weeks) were subsumed into the area of high CMV IgG avidity and low CMV IgM titer, which probably was equivalent to the persistent IgM. Conclusions: CMV antibodies in mothers during the late phase of primary infection were in high IgG avidity and low IgM titer, which probably was equivalent to the persistent IgM.

Background: There are no detailed reports in the literature on maternal cytomegalovirus antibody screening for universal newborn hearing screening (UNHS) referral patients. We examined maternal cytomegalovirus antibody screening results and estimated the incidence of maternal primary cytomegalovirus infection among UNHS referral patients. Methods: During September 2013–March 2021, fresh urine samples were collected in the first week after birth from 98 neonates with UNHS referral results at 15 obstetrical institutions in Mie, Japan (the first hearing screening). We performed a real-time polymerase chain reaction analysis to detect cytomegalovirus DNA in the samples. Infants with ≥200 copies/mL of cytomegalovirus DNA were diagnosed with congenital cytomegalovirus (cCMV) infection. A second hearing screening was performed, and patients with positive results were sent to the otorhinolaryngologists for further examinations of congenital hearing loss. We calculated incidence rates (%) with 95% confidence intervals (CIs) for cCMV infection among patients with UNHS referral results and maternal primary cytomegalovirus infection among patients who underwent maternal cytomegalovirus antibody screening. Results: Among the 98 neonates with UNHS referral results (the first hearing screening), 5 were diagnosed with cCMV infection (incidence rate: 5.1%; 95% CI: 0.8–9.5). All five patients with cCMV had positive second hearing screening results and were sent to their otorhinolaryngologists. All five were diagnosed with congenital hearing loss, and four were diagnosed with congenital hearing loss secondary to cCMV infection. The remaining patient with cCMV infection was diagnosed with congenital hearing loss unrelated to cCMV infection. Of the 98 patients, 60 underwent maternal cytomegalovirus antibody screening. Among the 60 patients, six had maternal primary cytomegalovirus infection during pregnancy (incidence rate: 10.0%; 95% CI: 2.4–17.6). Of the six patients, four were positive for cytomegalovirus immunoglobulin (CMV Ig) G and IgM antibodies in maternal blood with low CMV IgG antibody avidity results during early pregnancy, while the remaining two had maternal CMV IgG antibody seroconversion during pregnancy. Conclusions: This is the first study to examine the maternal primary cytomegalovirus infection incidence rate in patients with UNHS referral results (the first hearing screening). We identified a 10-fold higher risk in this population (10.0%) than in the general population (0.98%).

Objective: The goal of the study was to clarify the risk factors for pregnancy complicated with Eisenmenger syndrome (ES). Materials and methods: A retrospective study was performed in 15 patients with ES who were managed throughout pregnancy at one institution from 1982 to 2013. Cases associated with congenital heart diseases other than atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) were excluded. Results: The congenital heart diseases in ES included ASD (n = 3), VSD (n = 9), and PDA (n = 3). Ten women chose termination and 5 continued with their pregnancies. In the 5 continuation cases (PDA 1, VSD 4), worsening of cyanosis, exertional fatigue and dyspnea appeared between 25 and 30 weeks gestation and cesarean section was performed at 30 (28–33) weeks. LVEF, PaO2, and SpO2 decreased and heart rate increased significantly from before pregnancy to 25–30 weeks gestation. From before to during the pregnancy, there were no significant changes in mean PABP or pulmonary vascular resistance (PVR) in four cases with data (582–592, 885 to 868, 1280 to 1291, 1476–1522 dyn × s/cm2). PVR at conception had a negative relationship with delivery weeks. NYHA classes before, during and 1 year after pregnancy were II, III and II. In one recent case, epoprostenol and tadalafil were administered during pregnancy. Conclusions: Pregnancy with ES has a high risk due to hypooxygenation, cyanosis, and cardiac failure, which can appear as common complications as early as the 2nd trimester. Early interventions with meticulous care are required for these complications during pregnancy and delivery. Keywords: Cardiac failure, Cyanosis, Eisenmenger syndrome, Pregnancy

A nationwide questionnaire survey about community-acquired infection of coronavirus disease 2019 (COVID-19) was conducted in July 2020 to identify the characteristics of and measures taken by Japanese medical facilities providing maternity services. A case-control study was conducted by including medical facilities with (Cases) and without (Control) community-acquired infection of COVID-19. Responses from 711 hospitals and 707 private clinics were assessed (72% of all hospital and 59% all private clinics provided maternity service in Japan). Seventy-five COVID-19-positive pregnant women were treated in 52 facilities. Community-acquired infection was reported in 4.1% of the facilities. Of these, 95% occurred in the hospital. Nine patients developed a community-acquired infection in the maternity ward or obstetric department. Variables that associated with community-acquired infection of COVID-19 (adjusted odds ratio [95% confidence interval]) were found to be state of emergency prefecture (4.93 [2.17-11.16]), PCR test for SARS-CoV-2 on admission (2.88 [1.59-5.24]), and facility that cannot treat COVID-19 positive patients (0.34 [0.14-0.82]). In conclusion, community-acquired infection is likely to occur in large hospitals that treat a higher number of patients than private clinics do, regardless of the preventive measures used.

Severe neonatal gastrointestinal diseases such as necrotizing enterocolitis or spontaneous intestinal perforation are potentially lethal conditions which predominantly occur in preterm infants. Cytomegalovirus (CMV), which is known to cause congenital and acquired infections in the newborns, has also been implicated in such severe gastrointestinal diseases in premature infants. However, the pathogenic role of CMV and effect of antiviral therapy in severe gastrointestinal disease in premature neonates is currently unclear. We present an infant, born at 26-weeks' gestation, presented with progressive dyspepsia and abdominal distention after the closure of the symptomatic patent ductus arteriosus at the day of life (DOL) 4, requiring the emergent surgery for ileal perforation at the DOL8. After the surgery, abdominal symptoms persisted and the second emergent surgery was performed for the recurrent ileal perforation at DOL17. Even then the abdominal symptoms prolonged and pathological examination in the affected intestine at the second surgery showed CMV inclusion body. Immunoreactivity for CMV antigen was detected in the specimen at the first surgery on DOL8. Blood and urinary CMV-DNA were detected at DOL28. CMV-DNA was also detected in the dried umbilical cord which was obtained within a week from birth. A 6-week course of intravenous ganciclovir (12 mg/kg/day) was started at DOL34 and then symptoms resolved along with decreasing blood CMV-DNA. Pathological findings characteristic of CMV were not detected in the resection specimen at the ileostomy closure at DOL94. These observations indicate that anti-CMV therapy may be beneficial for some premature infants with severe CMV-associated gastrointestinal diseases and warrants further studies focusing on pathogenic role, diagnosis, treatment and prevention of this underrecognized etiology of severe gastrointestinal diseases particularly in premature neonates.

Background and Objectives: Vasopressors are used for treating maternal hypotension. However, the appropriate administration method and effects on newborns have not been reported. We evaluated maternal blood pressure fluctuation and neonatal findings in patients who received continuous vasopressor administration during elective cesarean sections and those who received bolus vasopressor administration upon onset of hypotension. Materials and Methods: We retrospectively analyzed the data of 220 patients scheduled for elective cesarean delivery under spinal anesthesia at Mie University Hospital between April 2017 and March 2021. The patients were classified according to the method of vasopressor administration. Maternal information, intraoperative maternal blood pressure fluctuation, and neonatal findings were examined. A multiple regression analysis was performed for the administration of postpartum neonatal respiratory support using maternal background information and other variables related to blood pressure changes as independent variables. Results: The Continuous group and the Bolus group were composed of 98 and 122 patients, respectively. No difference was observed in maternal background information between the groups. Significant changes were noted in several blood pressure parameters between both groups. As for neonatal parameters, newborns of Bolus group patients had lower pO2, 1 min and 5 min Apgar scores, and required more respiratory support than those of Continuous group patients. In the multiple regression analysis, the groups and maternal post-anesthesia diastolic blood pressure variability were considered explanatory variables. Conclusions: Maternal hypotension and the need for neonatal respiratory support associated with anesthesia administration in elective cesarean section may be improved by continuous vasopressor administration upon induction of combined spinal–epidural anesthesia.

Abstract Background Peripartum cardiomyopathy is a life-threatening condition that occurs during the peripartum period in previously healthy women. Cardiovascular magnetic resonance (CMR) T1 mapping permits sensitive detection of tissue edema and fibrosis, and it may be useful in identifying altered myocardial tissue characteristics in peripartum cardiomyopathy. However, left ventricular (LV) volumes and mass increase considerably even in normal pregnancy, and it is not known whether altered tissue characteristics can be found in normal pregnancy. The aim of this study was to investigate whether the LV remodeling observed in normal pregnancy is associated with altered tissue characteristics determined by CMR. Methods Twelve normal pregnant women and 15 non pregnant women underwent cine CMR and myocardial T1 measurement at 1.5 T. Pregnant women were scanned three times, in the 2nd and 3rd trimesters of pregnancy and at 1 month postpartum. LV volumes, LV mass (LVM), and global longitudinal strain (GLS) were analyzed by cine CMR. Native myocardial T1 was determined using modified Look-Locker inversion recovery (MOLLI) images. Results LV end-diastolic volume (EDV) was significantly greater in the 3rd trimester (126 ± 22 mL) than in non-pregnant women (108 ± 14 mL, p

Objective: We studied the effect and safety of epidural anesthesia during labor in pregnant women with cardiovascular disease. Materials and methods: In the pregnant women with cardiovascular disease, we compared maternal outcome and suppressive effect on blood pressure retrospectively between the epidural group (anesthetized epidurally during labor) and the no-epidural group (not anesthetized epidurally during labor). Results: A total of 277 patients were included in the analyses. Cardiovascular events decreased significantly in epidural group (P

Abstract Background Malignancy during pregnancy has become a significant cause of maternal death in developed countries, likely due to both an older pregnant population, and increases of cervical cancer in younger women. Our aim is to investigate the clinical aspects of malignancy during pregnancy in Japan and to use this information to identify opportunities for earlier detection and treatment. Methods We provided a questionnaire to 1508 secondary or tertiary care hospitals in Japan. We reviewed the clinical characteristics of cases with malignancy during pregnancy for the period of January to December, 2008. From the 760 institutions which responded, we obtained clinical information for 227 unique cases. The questionnaire provided clinical information, including disease site, pregnancy outcome and how the disease was detected. Results The most common type of malignancy was cervical cancer (n = 162, 71.4%) followed by ovarian (n = 16, 7.0%) and breast cancer (n = 15, 6.6%). Leukemia (n = 7, 3.1%), colon cancer (n = 5, 2.2%), gastric cancer (n = 5, 2.2%), malignant lymphoma (n = 4, 1.8%), thyroid cancer (n = 3, 1.3%), brain cancer (n = 3, 1.3%), endometrial cancer (n = 2, 0.9%), and head and neck cancer (n = 2, 0.9%) accounted for the remaining cases. Overall, gynecological malignancies accounted for 79.3% (95% confidence interval 74.0–84.6) of pregnancy associated malignancies diagnosed in the present study. The majority of cervical cancers, 149 (92.0%) of 162, were diagnosed by a Pap (Papanicolaou) smear during early gestation. Ten (62.5%) of the ovarian cancer cases were diagnosed by ultrasonography during a prenatal checkup or at the time of initial pregnancy diagnosis. Out of 14 breast cancers, only one (7.1%) was diagnosed by screening breast exam. Conclusions From this study, we reaffirm the clear and significant benefits of prenatal checkups starting at an early gestational age for the detection of gynecological cancers during pregnancy. Conversely, breast cancer detection during pregnancy was poor, suggesting new strategies for early identification of this disease are required.

Ovarian dermoid cysts (ODCs) are the most common benign tumors in young women, but autoimmune hemolytic anemia (AIHA) induced by ODC is rare. We report the first case of ODC-associated AIHA with improvement after laparoscopic oophorocystectomy. An 18-year-old nulliparous woman was diagnosed with a left ODC that was 7 cm in diameter. Preoperative blood tests showed macrocytic anemia, reticulocytosis, high serum lactate dehydrogenase activity, hyperbilirubinemia, and low haptoglobin. Direct and indirect Coombs tests were positive. We diagnosed AIHA. Prednisolone therapy did not result in improvement, so it seemed that AIHA was being induced by the ODC. After laparoscopic oophorocystectomy, the patient's condition improved without blood transfusion. Resection of ODC should be performed first for ODC-associated AIHA; laparoscopic surgery may be superior to laparotomy from the standpoint of hemorrhage given the underlying anemia.

Post-partum obstetric haemorrhage is a leading cause of mortality among Japanese women, generally treated with haemostatic measures followed by supplementary transfusion. Commonly used in the setting of severe trauma, massive transfusion protocols (MTPs), preparations of red blood cell concentrate (RBC) and fresh frozen plasma (FFP) with additional supplements, have proved effective in decreasing patient mortality following major obstetric bleeding events. Although promising, the optimal configuration of RBC and FFP utilized for obstetric bleeding needs to be verified. Here, we conducted a systematic literature review to define the optimal ratio of RBC to FFP for transfusion therapy during instances of obstetric bleeding. Our analysis extracted four retrospective, observational studies, all demonstrating that an FFP/RBC ratio of ≥1 was associated with improved patient outcomes following obstetric haemorrhage. We therefore conclude that, from the standpoint of haemostatic resuscitation, an FFP/RBC ratio of ≥1 is a necessary condition for optimal clinical management during MTP administration in the field of obstetrics. Hence, we further propose an optimized MTP strategy to be utilized in the setting of severe obstetric bleeding.

OBJECTIVE:The relevance between time-series fetal heart rate (FHR) pattern changes during labor and outcomes such as arterial blood gas data at delivery has not been studied. Using 3-tier and 5-tier classification systems, we studied the relationship between time-series FHR pattern changes before delivery and umbilical artery blood gas data at delivery. METHODS:The subjects were 1,909 low-risk women with vaginal delivery (age: 29.1 ± 4.4 years, parity: 1.7 ± 0.8). FHR patterns were classified by a skilled obstetrician based on each 10 min-segment of the last 60 min before delivery from continuous CTG records in an obstetric clinic. RESULTS:The relationship between each 10 min-segment FHR pattern classification from 60 minutes before delivery and umbilical artery blood pH and base excess (BE) values at delivery changed with time. In the 3-tier classification, mean pH of Category I group in each 10 min-segment was significantly higher than that of Category II group. For Category I groups in each 10-minute segment, its number decreased and its average pH increased as the delivery time approached. In the 5-tier classification, there was the same tendency. About each level group in 10 min-segment, the higher the level, the lower the blood gas values, and mean pH of higher level groups decreased as the delivery time approached. CONCLUSIONS:The relationship between classifications and outcomes was clear at any time from 60 min before delivery in 3- and 5-tier classifications, and the 5-tier classification was more relevant.

A 27-year-old pregnant woman who was positive for anti-cytomegalovirus (CMV) antibodies gave birth to a congenitally CMV-infected neonate at 40 weeks of gestation. According to strain-specific serological analysis, which is able to determine the two types of CMV glycoprotein H (gH), the mother possessed anti-gH(To) antibodies only, but the neonate possessed anti-gH(AD) and anti-gH(To) antibodies at 4 weeks after birth. As the anti-gH(To) IgG was decreased in the neonate at 8 months post-delivery, these antibodies are thought to have been transferred from the mother as maternal antibodies. The anti-gH(AD) IgG level was maintained in the child even after 8 months post-delivery. Congenital infection with a CMV gH(AD) type strain was confirmed by strain-specific real-time PCR using a urine specimen from the child. On the other hand, anti-gH(AD) IgG was not detected even after 8 months post-delivery in a maternal specimen. The mother only produced antibodies against the CMV strain identified as the primary infection, which is characteristic of original antigenic sin. Keywords: Cytomegalovirus, Congenital infection, Glycoprotein H, Original antigenic sin

Sudden unexpected death in epilepsy (SUDEP) is defined as the sudden death of a patient with epilepsy in the absence of an anatomic or toxicologic cause. Whether pregnancy is a risk factor for SUDEP is unclear. Using data submitted to the Japan Association of Obstetricians and Gynecologists (JAOG), which has been collating information regarding all maternal deaths in Japan since 2000, this study evaluated maternal mortality data from 2010 to 2019 to evaluate the current circumstances of maternal death related to SUDEP in Japan. Six women died due to SUDEP during this period; the maternal mortality rate related to SUDEP was 0.066/100,000 individuals. Two women each died during the second trimester, third trimester, and postpartum period. Four and two women were receiving monotherapy and no therapy with anti-epileptic drugs, respectively. The duration of epilepsy was ≤15 years in three women, >15 years in one woman, and unknown in two women. This study furthers our understanding of the prevalence of maternal deaths due to SUDEP in Japan. Further studies are needed to confirm whether pregnancy is a risk factor for SUDEP.

In human sperm cryopreservation, test yolk buffer and human serum albumin have been used as permeating macromolecular-weight cryoprotectants. In clinical reproductive medicine, human serum albumin is frequently used because of low risks of zoonoses and allergic reactions. However, the risk of allogeneic infectious diseases exists, and the supply may be unstable because human serum albumin is derived from human blood. Therefore, the development of xeno-free human sperm cryopreservative reagents that could overcome the aforementioned problems is warranted. We succeeded in developing a new xeno-free and defined sperm cryopreservation reagent containing glycerol, carboxylated poly-l-lysine, and raffinose. The cryopreservation reagent was not significantly different in terms of sperm motility, viability, and DNA fragmentation and was comparable in performance to a commercial cryopreservation reagent containing human serum albumin. Moreover, the addition of saccharides was essential for its long-term storage. These results may help elucidate the unknown function of macromolecular-weight permeating cryoprotective agents.

The PROPESS, a controlled-release dinoprostone vaginal delivery system, is a pharmacological cervical ripening intervention and promotes cervical change causing uterine contraction. During insertion of the PROPESS, uterine hyperstimulation could occur and result in fetal heart rate (FHR) abnormality. We report a case of uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS in a pregnant woman. Postural change, oxygenation, fluid infusion, and the immediate PROPESS removal were ineffective to address the adverse event, so we administered nitroglycerin for acute uterine relaxation. The nitroglycerin resulted in uterine relaxation, and the FHR abnormality was resolved immediately, thereby preventing an emergency cesarean section. Therefore, nitroglycerin could be considered an effective option for uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS.