Risk factors for resignation from work during pregnancy among Japanese women: a cross-sectional, multicenter questionnaire survey.

This study was to investigate the employment status of pregnant women in Japan and identify risk factors associated with resigning from work during pregnancy. We conducted a cross-sectional survey with 975 postpartum women in Tokyo and its suburbs, focusing on those who were employed during pregnancy. Women who were employed when they became pregnant were selected and divided into two groups: those who did not resign and those who resigned; the groups were analyzed separately. Multiple logistic regression analyses were performed to examine associations between employment resignation and risk factors. The analysis revealed that 79% continued working, while 8.1% resigned. Risk factors for resignation included non-regular employment (OR: 13.1, 95% CI: 6.6-25.9), fewer employees (OR: 3.4, 95% CI: 1.8-6.4), and shorter employee tenure (OR: 2.4, 95% CI: 1.1-5.2). Non-regular employment status, a smaller number of employees, and shorter employee tenure were identified as risk factors for working women resigning from their job during pregnancy. In work situations and work environments that encourage pregnant women to leave the workforce, developing systems to improve these conditions for pregnant employees may help women to progress in the labor force.

Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

BACKGROUND: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. OBJECTIVE: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. METHODS: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. RESULTS: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. CONCLUSION: Low carnitine level is associated with increased renal excretion during late pregnancy.

A missense variant at the RAC1-PAK1 binding site of RAC1 inactivates downstream signaling in VACTERL association.

RAC1 at 7p22.1 encodes a RAC family small GTPase that regulates actin cytoskeleton organization and intracellular signaling pathways. Pathogenic RAC1 variants result in developmental delay and multiple anomalies. Here, exome sequencing identified a rare de novo RAC1 variant [NM_018890.4:c.118T > C p.(Tyr40His)] in a male patient. Fetal ultrasonography indicated the patient to have multiple anomalies, including persistent left superior vena cava, total anomalous pulmonary venous return, esophageal atresia, scoliosis, and right-hand polydactyly. After birth, craniofacial dysmorphism and esophagobronchial fistula were confirmed and VACTERL association was suspected. One day after birth, the patient died of respiratory failure caused by tracheal aplasia type III. The molecular mechanisms of pathogenic RAC1 variants remain largely unclear; therefore, we biochemically examined the pathophysiological significance of RAC1-p.Tyr40His by focusing on the best characterized downstream effector of RAC1, PAK1, which activates Hedgehog signaling. RAC1-p.Tyr40His interacted minimally with PAK1, and did not enable PAK1 activation. Variants in the RAC1 Switch II region consistently activate downstream signals, whereas the p.Tyr40His variant at the RAC1-PAK1 binding site and adjacent to the Switch I region may deactivate the signals. It is important to accumulate data from individuals with different RAC1 variants to gain a full understanding of their varied clinical presentations.

A Case of a Refractory Bleeding Giant Vaginal Wall Cavernous Hemangioma Successfully Managed with Sclerotherapy.

BACKGROUND Vaginal wall hemangiomas are extremely rare, benign, vascular tumors of the female genitalia. Most cases occur in childhood, but a few cases can be acquired; however, the mechanism of hemangioma formation remains unknown. Most hemangiomas involving female genital organs are small and asymptomatic. However, huge hemangiomas can cause irregular genital bleeding, infertility, and miscarriage. Surgical excision and embolization are the most common treatment options. We reveal that sclerotherapy achieved good outcomes in a patient with an intractable huge vaginal wall hemangioma. CASE REPORT A 71-year-old woman visited a local doctor with concerns of frequent urination. A ring pessary was inserted after a diagnosis of pelvic organ prolapse. However, symptoms did not improve, and the patient consulted another hospital. The previous physician diagnosed vaginal wall tumors and prolapse and performed a colporrhaphy. However, she was referred to our hospital with heavy intraoperative bleeding. Imaging examination revealed a huge hemangioma on the vaginal wall, which was histologically diagnosed as a cavernous hemangioma. Angiography revealed hemorrhage in the right peripheral vaginal artery. Owing to concerns regarding extensive vaginal wall necrosis caused by arterial embolization, sclerotherapy using monoethanolamine oleate was selected. Hemostasis was achieved 1 month after sclerotherapy, and postoperative imaging showed the lesion had shrunk in size. No recurrence of hemangioma was observed 19 months after surgery. CONCLUSIONS We report a case of a large vaginal wall intractable bleeding hemangioma. Sclerotherapy can be a suitable treatment option for large vaginal hemangiomas that are too extensive to be treated using surgery or arterial embolization.

The management of women of childbearing age with rheumatoid arthritis: an expert report.

INTRODUCTION: The introduction of biologic therapies and a treat-to-target approach has transformed the management of rheumatoid arthritis (RA), which has led to improved outcomes for women with RA who wish to become pregnant. However, guidelines for the management of reproductive health in female patients with RA are still lacking. AREAS COVERED: A task force (Women of Childbearing Age [WoCBA]-Rheumatoid Arthritis in Japan) comprising 10 experts in the fields of rheumatology, obstetrics and orthopedic surgery developed 10 clinical questions (CQ) related to the management of WoCBA with RA. For each CQ, a systematic literature review was conducted to identify relevant evidence. Based on this evidence, a set of recommendations for each CQ were drafted and evaluated using the modified Delphi method. This article describes the agreed recommendations along with the supporting evidence. EXPERT OPINION: There are many ongoing challenges associated with the provision of reproductive healthcare in WoCBA with RA. It is hoped that the consensus-based recommendations provided here can be implemented in clinical practice in order to increase collaboration between rheumatologists and obstetricians/gynecologists and to improve reproductive health outcomes for WoCBA with RA.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

BACKGROUND: Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. METHODS: Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. RESULTS: Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was âˆ¼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. CONCLUSION: The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

Cervical Cerclage to Prevent Intrauterine Balloon Prolapse.

Intrauterine balloon prolapse sometimes occurs, and the intrauterine balloon must be reinserted. Furthermore, intrauterine balloon tamponade (IBT) failure can necessitate additional invasive procedures. We report a case of cervical cerclage with IBT for placenta previa with a cervical dilation. In our case, emergency cesarean section was performed at 35 + 4 weeks of gestation because of persistent hemorrhage. During the operation, we performed IBT to prevent further postpartum hemorrhage. However, immediately after the operation, uterine cervical dilatation was 6 cm, which resulted in cervical dilation and prolapse of the intrauterine balloon. Therefore, we performed cervical cerclage using absorbable sutures with IBT and blood transfusion. We speculated that the intrauterine balloon might have induced cervical canal ripening during the operation. Our case suggested that cervical cerclage with IBT is a useful method to prevent intrauterine balloon prolapse in cases with cervical dilation.

Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism.

TNNI2 at 11p15.5 encodes troponin I2, fast skeletal type, which is a member of the troponin I gene family and a component of the troponin complex. Distal arthrogryposis (DA) is characterized by congenital limb contractures without primary neurological or muscular effects. DA is inherited in an autosomal dominant fashion and is clinically and genetically heterogeneous. Exome sequencing identified a causative variant in TNNI2 [NM_003282.4:c.532T>C p.(Phe178Leu)] in a Japanese girl with typical DA2b. Interestingly, the familial study using Sanger sequencing suggested a mosaic variant in her healthy father. Subsequent targeted amplicon-based deep sequencing detected the TNNI2 variant with variant allele frequencies of 9.4-17.7% in genomic DNA derived from peripheral blood leukocytes, saliva, hair, and nails in the father. We confirmed a disease-causing variant in TNNI2 in the proband inherited from her asymptomatic father with its somatic variant. Our case demonstrates that careful clinical and genetic evaluation is required in DA.

A nationwide study of obstetric management and outcomes in premature rupture of membrane at term: Report from the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2017-2018.

AIM: This nationwide study aimed to investigate the practical management of term premature rupture of membrane (PROM) and its relationship with maternal and neonatal outcomes. METHODS: We conducted a questionnaire survey of 415 facilities participating in the Japan Perinatal Registry Network of the Japan Society of Obstetrics and Gynecology in 2016. The patients were women expecting vaginal birth after PROM at term without clinical chorioamnionitis. We classified the facilities into three groups based on duration of the expectant management after PROM (within 24, 24, and 48 h). Furthermore, we analyzed the association between perinatal outcomes and management protocol using the Japan Perinatal Registry Network Database 2016. RESULTS: Of 415 facilities, 346 (83.4%) completed and returned the survey. Among 231 facilities with management protocols, an interval of 3 days from PROM to delivery was acceptable in 167 facilities (72.3%). One hundred forty-nine facilities (64.5%) responded that they did not perform mechanical cervical dilation, and 90 (39.0%) used oxytocin as a uterotonic irrespective of cervical maturation. The number of hospitals that had a policy to administer antibiotics to Group B streptococcus-positive patients was 211 (91.3%). Neonatal outcomes at birth and the frequency of cesarean section and postpartum fever did not differ among the three groups. CONCLUSIONS: Most facilities in the Japan Perinatal Registry Network managed women at term to delivery within 3 days after PROM with attention to bacterial infection. Expectant management up to 48 h after PROM did not increase the risk of postpartum fever, compared to labor induction immediately after PROM.

Pathogenic variants detected by RNA sequencing in Cornelia de Lange syndrome.

Recent studies suggest that transcript isoforms significantly overlap (approximately 60%) between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Interestingly, 14 cohesion-related genes with variants that cause Cornelia de Lange Syndrome (CdLS) are highly expressed in the brain and LCLs. In this context, we first performed RNA sequencing of LCLs from 22 solved (with pathogenic variants) and 19 unsolved (with no confirmed variants) CdLS cases. Next, an RNA sequencing pipeline was developed using solved cases with two different methods: short variant analysis (for single-nucleotide and indel variants) and aberrant splicing detection analysis. Then, 19 unsolved cases were subsequently applied to our pipeline, and four pathogenic variants in NIPBL (one inframe deletion and three intronic variants) were newly identified. Two of three intronic variants were located at Alu elements in deep-intronic regions, creating cryptic exons. RNA sequencing with LCLs was useful for identifying hidden variants in exome-negative cases.

An infant of 26 weeks gestation with congenital miliary tuberculosis complicated by chronic lung disease requiring CPAP was diagnosed on Day 104 of life: congenital tuberculosis was confirmed by detection of calcified ovaries in his mother.

INTRODUCTION: Early diagnosis of tuberculosis (TB) in infants is important but is commonly missed because the symptoms are often non-specific. CASE PRESENTATION: A Nepalese male infant born at 26 weeks gestation and weighing 1227 g (97th centile) was admitted to the neonatal intensive care unit (NICU) immediately after birth for the management of his prematurity. After extubation on Day 8, his oxygen saturation became unstable and he required nasal continuous positive airway pressure with oxygen for 3 months. On Day 104, further detailed evaluation was required because there was no improvement in his respiratory condition. A computed tomography (CT) scan demonstrated scattered miliary nodules in both lung fields. Acid-fast staining for the mycobacteria and TB polymerase chain reaction (PCR) of the sputum obtained directly by laryngeal aspiration confirmed Mycobacterium tuberculosis. On Day 105, he was therefore transferred to a tertiary care hospital for further intensive care. Pathology findings suggested placental involvement with TB owing to chronic endometrial infection. In addition, a maternal abdominal CT scan demonstrated bilateral calcified lesions in the ovaries. He completed antituberculous chemotherapy and was discharged 3 months later. At 18 months of age there are no sequelae and his development is almost normal. None of the infants or medical personnel who were exposed in the NICU developed secondary TB. CONCLUSION: In neonates with persistent respiratory distress, neonatologists should consider TB infection as a differential diagnosis. ABBREVIATIONS: CLD: chronic lung disease; CRP: C-reactive protein; CT: computed tomography; IGRA: interferon-γ release assay; IVF-ET: in vitro fertilisation-embryo transfer; N-CPAP: nasal continuous positive airway pressure; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PROM: premature rupture of membranes; TB: tuberculosis; WBC: white blood cells.

The retrospective study for effectiveness of cervical cerclage in preventing recurrent preterm birth.

OBJECTIVE: This study aimed to clarify the effectiveness of cervical cerclage in preventing recurrent preterm births. MATERIALS AND METHODS: A retrospective study was conducted using the perinatal registration database of the Japan Society of Obstetrics and Gynecology for the Perinatal Center from 2014 to 2016. The efficacies of history-indicated, ultrasound-indicated, and physical examination-indicated cerclage as preventive treatments for women with a history of preterm birth were evaluated by comparing cerclage and non-cerclage cases. Fisher's exact test was performed to evaluate any significant differences in patient backgrounds. Prior to the evaluation, propensity score matching was performed for history-indicated and ultrasound-indicated cerclage patients. RESULTS: For this study, 6060 multiparous women with a history of preterm birth were reviewed. After excluding 17 patients with unknown indications for cervical cerclage, 6043 patients were included in the study. History-indicated and ultrasound-indicated cerclage did not reduce the risk of preterm birth in subsequent pregnancies for any of the pregnancy periods (p = 0.413, p = 1.000). In contrast, physical examination-indicated cerclage significantly reduced the risk of subsequent preterm births for all pregnancy periods (p < 0.001). CONCLUSION: Subsequent preterm births were effectively prevented only in physical examination-indicated cerclage cases. For history- or ultrasound-indicated cerclage, statistically significant differences in subsequent preterm births were not evident.

Probiotics including Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis may prevent recurrent spontaneous preterm delivery.

AIM: A large cohort study of Japanese women reported that the rate of recurrent spontaneous preterm delivery (sPTD) in the next pregnancy was 22.3%; therefore, it is important to prevent recurrent sPTD. The present study investigated the rate of recurrent sPTD in pregnant women treated with probiotics. METHODS: This was a retrospective study. Fifty-one pregnant women with a history of sPTD and who had been taking probiotics before 14 weeks of gestation were selected. The rate of sPTD in the next pregnancy among 255 pregnant women with a history of sPTD who had not taken probiotics was compared with that in the probiotics group. RESULTS: The rate of recurrent sPTD was 9.8% (5/51), which was lower than previously reported values. Furthermore, the rate of recurrent sPTD was significantly lower in the probiotics group (9.8%) than in the nonprobiotics group (31.0% [79/255]; p = 0.002). CONCLUSIONS: Probiotics may reduce the rate of recurrent sPTD.

Two families with TET3-related disorder showing neurodevelopmental delay with craniofacial dysmorphisms.

TET3 at 2p13.1 encodes tet methylcytosine dioxygenase 3, a demethylation enzyme that converts 5-methylcytosine to 5-hydroxymethylcytosine. Beck et al. reported that patients with TET3 abnormalities in either an autosomal dominant or recessive inheritance fashion clinically showed global developmental delay, intellectual disability, and dysmorphisms. In this study, exome sequencing identified both mono- and biallelic TET3 variants in two families: a de novo variant NM_001287491.1:c.3028 A > G:p.(Asn1010Asp), and compound heterozygous variants NM_001287491.1:c.[2077 C > T];[2896 T > G],p.[Gln693*];[Cys966Gly]. Despite the different inheritance modes, the affected individuals showed similar phenotypic features. Including these three patients, only 14 affected individuals have been reported to date. The accumulation of data regarding individuals with TET3-related disorder is necessary to describe their clinical spectrum.

Retrospective study of the recurrence risk of preterm birth in Japan.

BACKGROUND: A history of preterm birth is a risk factor for preterm birth in a future pregnancy, and there are some reports of prevention methods, such as the administration of progesterone. However, the rate of recurrence of preterm birth in Japan has not been clarified, and there is no data for judging whether these preventive methods are effective. OBJECTIVE: To clarify the risk of recurrence of preterm birth and preterm prelabor rupture of membranes (pPROM) in Japan. MATERIALS AND METHODS: A retrospective study was conducted using the perinatal registration database of the Japan Obstetrics and Gynecology Society for the Perinatal Center from 2014 to 2016. There were 704,418 subjects, of which 190,990 were excluded those with unknown maternal information, those under the age of 20 years, those with perinatal disease related to preterm birth, and first-time mothers. RESULTS: Logistic model unavailable and multivariate analysis were performed. An analysis of the preterm birth history indicated the risk of preterm birth in the current pregnancy, and the odds ratio for preterm birth recurrence once, twice, and three times or more was 3.3, 6.6, and 7.8, respectively. As a secondary analysis, we analyzed whether the history of pPROM is a risk factor of recurrence of pPROM and found a significant association with an odds ratio of 3.4. CONCLUSION: Having a preterm birth history increases the risk of recurrence of preterm birth, and the risk of recurrent preterm birth increases as the number of preterm births increases. Although this report is intended for high-risk pregnancies wherein the rate of preterm birth is high, as previously reported, our data indicate that in Japan, preterm birth is a risk factor of recurrent preterm birth.

Chronic active Epstein-Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. CASE PRESENTATION: A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/µL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/µL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein-Barr virus (EBV) DNA level of 8.9 × 105 copies/µg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient's condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. CONCLUSIONS: sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.

Fetal growth restriction as the initial finding of preeclampsia is a clinical predictor of maternal and neonatal prognoses: a single-center retrospective study.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder specific to pregnancy that can cause severe maternal-neonatal complications. The International Society for the Study of Hypertension in Pregnancy revised the PE criteria in 2018; a PE diagnosis can be established in the absence of proteinuria when organ or uteroplacental dysfunction occurs. The initial findings of PE (IFsPE) at the first diagnosis can vary considerably across patients. However, the impacts of different IFsPE on patient prognoses have not been reported. Thus, we investigate the predictors of pregnancy complications and adverse pregnancy outcomes based on IFsPE according to the new criteria. METHODS: This retrospective study included 3729 women who delivered at our hospital between 2015 and 2019. All women were reclassified based on the new PE criteria and divided into three groups based on the IFsPE: Classification 1 (C-1), proteinuria (classical criteria); Classification 2 (C-2), damage to other maternal organs; and Classification 3 (C-3), uteroplacental dysfunction. Pregnancy complications and adverse pregnancy outcomes were assessed and compared among the three groups. RESULTS: In total, 104 women with PE were included. Of those, 42 (40.4%), 28 (26.9%), and 34 (32.7%) were assigned to C-1, C-2, and C-3 groups, respectively. No significant differences in maternal characteristics were detected among the three groups, except for gestational age at PE diagnosis (C-1, 35.5 ± 3.0 weeks; C-2, 35.2 ± 3.6 weeks; C-3, 31.6 ± 4.6 weeks, p <  0.01). The rates of premature birth at < 37 weeks of gestation, fetal growth restriction (FGR), and neonatal acidosis were significantly higher in the C-3 group compared to the C-1 and C-2 groups. Additionally, the composite adverse pregnancy outcomes of the C-3 group compared with C-1 and C-2 represented a significantly higher number of patients. CONCLUSIONS: PE patients with uteroplacental dysfunction as IFsPE had the most unfavorable prognoses for premature birth, FGR, acidosis, and composite adverse pregnancy outcomes.

"Step-by-Step" Minimally Invasive Hemostatic Technique Using Intrauterine Double-Balloon Tamponade Combined with Uterine Isthmus Vertical Compression Suture for the Control of Placenta Accreta and Severe Atonic Hemorrhage during a Cesarean Section.

A sudden onset of postpartum hemorrhage (PPH) during a cesarean delivery requires urgent hemostasis procedures, such as the B-Lynch, Hayman, or double-vertical compression sutures, when bimanual compression, uterotonic agent administration, and intrauterine balloon tamponade had failed to achieve sufficient hemostasis. However, after invasive hemostatic procedures, postoperative complications, including subsequent synechiae and infection followed by ischemia, have been reported to occur even in successful cases. To avoid these complications, we devised and performed a minimally invasive combined technique based on a "step-by-step" minimally invasive hemostatic protocol for a case of placenta accreta and severe atonic hemorrhage during a cesarean delivery. A nullipara woman with a history of systemic lupus erythematosus and treatment with prednisolone and tacrolimus underwent a cesarean section because of a nonreassuring fetal status. Severe atonic hemorrhage and placenta accreta were observed which did not respond to bimanual compression and uterotonics. Because severe uterine atony and continuous bleeding from the placental attachment area were observed even with intrauterine balloon tamponade, vertical compression sutures were placed in the uterine isthmus. However, severe uterine atony and atonic bleeding from the uterine corpus persisted; thus, a second balloon was inserted into the uterine corpus. Hemostasis was accomplished with a combination of isthmus vertical compression sutures and double balloons which is a less-invasive approach than existing compression techniques. No complications related to these procedures were observed. This step-by-step minimally invasive hemostatic technique has the potential to control PPH with less complications, especially in immunocompromised patients.

Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor.

Prostaglandin E2 (PGE2) is known to have important roles in labor, but the detailed mechanism underlying the spontaneous human labor remains unknown. Here, we examined the involvement of prostaglandin biosynthetic enzymes and transporter in the accumulation of PGE2 in amniotic fluid in human labor. PGE2 and its metabolites were abundant in amniotic fluid in deliveries at term in labor (TLB), but not at term not in labor (TNL). In fetal-membrane Transwell assays, levels of PGE2 production in both maternal and fetal compartments were significantly higher in the TLB group than the TNL group. In fetal-membrane, the mRNA level of PTGES3, which encodes cytosolic prostaglandin E synthase (cPGES), was significantly higher in TLB than in TNL, but the mRNA levels of the other PGE2-synthase genes were not affected by labor. Moreover, the mRNA level of PTGS2, which encodes cyclooxygenase-2 (COX-2) in the amnion was significantly higher in TLB than in TNL. Western blot analyses revealed that the levels of COX-1 and COX-2 were comparable between the two groups, however, the level of cPGES was relatively higher in TLB than in TNL. COXs, cPGES, and prostaglandin transporter (SLCO2A1) proteins were all expressed in both chorionic trophoblasts and amniotic epithelium. These findings suggest that COXs, cPGES and SLCO2A1 contribute to PGE2 production from fetal-membrane in labor.