Association between adenomyosis and placenta accreta and mediation effect of assisted reproductive technology on the association: A nationwide observational study.

OBJECTIVES: To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association. METHODS: We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach. RESULTS: Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005). CONCLUSION: Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.

Clinical relevance of reversible cerebral vasoconstriction syndrome in pregnant women with posterior reversible encephalopathy syndrome: review of case reports in Japan.

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.

Automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation predicts preterm preeclampsia: a retrospective cohort study.

Our aims were to obtain the gestational-age-specific median of common logarithmic placental growth factor (PlGF) values in the first trimester in women with a singleton pregnancy in order to generate the gestational-age-specific multiple of the median (MoM) of log10PlGF at 9-13 weeks of gestation, to evaluate screening parameters of MoM of log10PlGF at 9-13 weeks of gestation to predict preterm preeclampsia (PE), and to construct an appropriate prediction model for preterm PE using minimum risk factors in multivariable logistic regression analyses in a retrospective sub-cohort study. Preterm PE occurred in 2.9% (20/700), and PE in 5.1% (36/700). Serum PlGF levels were measured using Elecsys PlGF®. MoMs of log10PlGF at 9-13 weeks of gestation in Japanese women with a singleton pregnancy followed a normal distribution. We determined the appropriate cut-off value of MoM of log10PlGF to predict preterm PE at around a10% false-positive rate (0.854). The MoM of log10PlGF < 0.854 yielded sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (95% confidence interval [CI]), and negative likelihood ratio (95% CI) of 55.0%, 91.9%, 17.5%, 98.5%, 6.79 (4.22-10.91), and 0.49 (0.30-0.80), respectively. The combination of MoM of log10PlGF and presence of either chronic hypertension or history of PE/gestational hypertension (GH) yielded sensitivity and specificity of 80.0 and 85.7%, respectively, to predict preterm PE. In conclusion, the automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation may be useful to predict preterm PE.

Uterine cervical conisation and chorioamnionitis: A nationwide observational study.

OBJECTIVE: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). DESIGN: A nationwide observational study. SETTING: Japan. POPULATION: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. METHODS: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. MAIN OUTCOME MEASURES: Clinical CAM. RESULTS: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63-3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20-1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57-3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58-1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. CONCLUSIONS: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation.

Maternal outcomes of placental abruption with intrauterine fetal death and delivery routes: A nationwide observational study.

INTRODUCTION: Placental abruption is a serious complication, especially when accompanied by intrauterine fetal death. The optimal delivery route for placental abruption with intrauterine fetal death for reducing maternal complications is still unclear. In this study we aimed to compare the maternal outcomes between cesarean delivery and vaginal delivery in women with placental abruption with intrauterine fetal death. MATERIAL AND METHODS: Using the Japan Society of Obstetrics and Gynecology nationwide perinatal registry database, we identified pregnant women with placental abruption with intrauterine fetal death between 2013 and 2019. The following women were excluded: those with multiple pregnancies, placenta previa, placenta accreta spectrum, amniotic fluid embolism, or whose delivery route was missing data. The association between delivery routes (cesarean delivery and vaginal delivery) and the maternal outcome was examined using a linear regression model with inverse probability weighting. The primary outcome was the amount of bleeding during delivery. Missing data were imputed using multiple imputation. RESULTS: The number of women with placental abruption with intrauterine fetal death was 1218/1601932 (0.076%). Of 1134 women analyzed, 608 (53.6%) underwent cesarean delivery. Bleeding during delivery (median [interquartile range]) was 1650.00 (950.00-2450.00) (mL) and 1171.00 (500.00-2196.50) (mL) in cesarean and vaginal delivery, respectively. Bleeding during delivery (mL) was significantly greater in cesarean delivery than in vaginal delivery (regression coefficient, 1086.39; 95% confidence interval, 130.96-2041.81; p = 0.026). Maternal death and uterine rupture occurred in four (0.4%) and five (0.4%) women, respectively. The four maternal deaths were noted in the vaginal delivery group. CONCLUSIONS: Bleeding during delivery was significantly greater in cesarean delivery than that in vaginal delivery in women with placental abruption with intrauterine fetal death. However, severe complications, including maternal death and uterine rupture, occurred in vaginal delivery-related cases. The management of women with placental abruption with intrauterine fetal death should be cautious regardless of the delivery route.

Uterine Rupture With Placenta Percreta Following Multiple Adenomyomectomies.

Pregnancy following adenomyomectomy is challenging because uterine rupture or placenta accreta spectrum (PAS) is more likely to occur; however, optimal management has not yet been established. We herein present a case of uterine rupture with placenta percreta in a pregnant woman who underwent adenomyomectomy twice before pregnancy. Magnetic resonance imaging (MRI) was performed in the second trimester and imminent uterine rupture concomitant with PAS was suspected. The patient was immediately admitted to hospital for careful management. Although failed tocolysis forced delivery at 29 weeks of gestation, managed hospitalization allowed cesarean hysterectomy to be performed uneventfully. Extensive PAS was proven pathologically in the removed uterus. Pregnancies following multiple adenomyomectomies are considered to be high-risk. Therefore, a sufficient explanation of the risks associated with future pregnancies is needed, particularly following second adenomyomectomy.

Placental Insertion into the Cervix with Cervical Shortening as a Clinical Sign to Suspect Cervico-Isthmic Pregnancy: A Case Report and Literature Review.

The clinical signs of cervico-isthmic pregnancy during pregnancy remain unknown. We herein report a case of cervico-isthmic pregnancy showing placental insertion into the cervix with cervical shortening, with a final diagnosis of placenta increta at the uterine body and cervix. A 33-year-old multiparous woman with a history of cesarean section was referred to our hospital at 7 weeks of gestation with suspected cesarean scar pregnancy. Cervical shortening with a cervical length of 14 mm was noted at 13 weeks of gestation. The placenta is gradually inserted into the cervix. An ultrasonographic examination and magnetic resonance imaging strongly suggested placenta accreta. We planned elective cesarean hysterectomy at 34 weeks of gestation. The pathological diagnosis was cervico-isthmic pregnancy with placenta increta at the uterine body and cervix. In conclusion, placental insertion into the cervix with cervical shortening in the early pregnancy period may be a clinical sign to suspect cervico-isthmic pregnancy.

Exponential increase of the gestational-age-specific incidence of preeclampsia onset (COPE study): a multicenter retrospective cohort study in women with maternal check-ups at <20 weeks of gestation in Japan.

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at <32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at <20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at <32 and <34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R2 values (0.975, 0.976, and 0.964, respectively). There were no "dual peaks" in the prevalence rates of women with SPE/PE, PE, and PE with severe hypertension. In conclusion, the absence of "dual peaks" refutes the previous rationale of EO-PE being defined as PE at <32 weeks of gestation. Further studies to determine an appropriate definition of EO-PE/SPE are needed.

A multicenter prospective study of home blood pressure measurement (HBPM) during pregnancy in Japanese women.

In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

Non-Coding RNAs and Prediction of Preeclampsia in the First Trimester of Pregnancy.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The only fundamental treatment for PE is the termination of pregnancy. Therefore, not only severe maternal complications but also perinatal complications due to immaturity of the infant associated with early delivery are serious issues. The treatment and prevention of preterm onset preeclampsia (POPE) are challenging. In 2017, the ASPRE trial showed that a low oral dose of aspirin administered to POPE high-risk women in early pregnancy reduced POPE by 62%. A prediction algorithm at 11-13 weeks of gestation identifies POPE with 75% sensitivity when the false positive rate is set at 10%. New biomarkers to increase the accuracy of the prediction model for POPE high-risk women in early pregnancy are needed. In this review, we focused on non-coding RNAs (ncRNAs) as potential biomarkers for the prediction of POPE. Highly expressed ncRNAs in the placenta in early pregnancy may play crucial roles in placentation. Furthermore, placenta-specific ncRNAs have been detected in maternal blood. In this review, we summarized ncRNAs that were highly expressed in the primary human placenta in early pregnancy. We also presented highly expressed ncRNAs in the placenta that were associated with or predictive of the development of PE in an expression analysis of maternal blood during the first trimester of pregnancy. These previous studies showed that the chromosome 19 microRNA (miRNA) -derived miRNAs (e.g., miR-517-5p, miR-518b, and miR-520h), the hypoxia-inducible miRNA (miR-210), and long non-coding RNA H19, were not only highly expressed in the early placenta but were also significantly up-regulated in the blood at early gestation in pregnant women who later developed PE. These maternal circulating ncRNAs in early pregnancy are expected to be possible biomarkers for POPE.

Bleeding-related outcomes of low-risk total placenta previa are equivalent to those of partial/marginal placenta previa.

OBJECTIVE: To clarify whether "low-risk total PP" patients bleed more than partial/marginal PP patients. MATERIALS AND METHODS: The retrospective cohort study was performed involving patients with PP between April 2006 and December 2018. The placental position was determined by ultrasound. From medical charts, the backgrounds as well as obstetric and neonatal outcomes of PP patients were retrieved. RESULTS: This study included 349 patients with PP, which was classified into three types according to the distance between the placenta and internal ostium: total (n = 174), partial (n = 52), and marginal (n = 123) PP. In total PP patients, three factors (prior CS, anterior placenta, and placental lacunae on ultrasound) significantly increased blood loss at CS, the need for hysterectomy, homologous transfusion (≥10 U), and ICU admission. No significant difference was observed in bleeding-related poor outcomes (rate of blood loss ≥2000 mL, amount of homologous transfusion, need for hysterectomy, and ICU admission) between total PP patients without all three factors: "low-risk total PP patients" and partial/marginal PP patients (19.8 vs. 17.1%; p = 0.604, 3.7 vs. 1.1%; p = 0.330, 1.2 vs. 1.1%; p = 1.000, and 1.2 vs. 1.1%; p = 1.000, respectively). CONCLUSION: Prior CS, anterior placenta, and placental lacunae on ultrasound were risk factors for a bleeding-related poor outcome in total PP patients. Total PP patients without these three factors showed the same bleeding-related poor outcome as partial/marginal PP patients.

Hemostatic effect of combined procedures for placenta previa: cervix-holding, intrauterine balloon, and uterine compression suture.

OBJECTIVES: Various procedures have been introduced to achieve hemostasis for postpartum hemorrhage (PPH) in placenta previa (PP). This study attempted to clarify the effectiveness of the combined use of three hemostatic procedures: Matsubara-Takahashi cervix-holding (MT-holding), intrauterine balloon (IUB), and uterine compression suture (UCS). STUDY DESIGN: This was a historical cohort study on the hemostatic effect of combined procedures for patients with placenta previa (PP) undergoing cesarean section between April 2006 and December 2018. Until 2011 (2006-2011), we used MT-holding alone, whereas since 2012 we have also been using IUB and UCS: MT-holding alone was used in the former period whereas three procedures (MT-holding, IUB, UCS, and their combinations) have been used in the latter period. Perinatal outcomes were compared between 2006-2011 (before group) and 2012-2018 (after group). RESULTS: Of 416 patients with PP, excluding 273 patients with cesarean hysterectomy or no hemostatic procedure, the remaining 143 patients were analyzed. In the after group, intraoperative blood loss, the percentage of patients with postoperative blood loss ≥ 500 ml, and incidence of autologous blood transfusion were significantly lower than in the before group. Multivariate analysis showed that postoperative blood loss ≥ 500 ml decreased in the after group (adjusted OR: 0.3, 95%CI: 0.1-0.8, compared with the before group). CONCLUSION: PPH decreased after introducing the combination of hemostatic procedures in patients with PP. Further studies are needed to determine the best combination and optimal indication for combining hemostatic procedures for PP.

Long-term outcome of fetus with ameliorated cystic hygroma.

OBJECTIVE: Cystic hygroma often ameliorates or disappears with pregnancy progression. Fetuses/neonates with amelioration, when without chromosomal or major structural abnormality, generally show a favorable outcome at birth. The present study was aimed to clarify the short/long-term outcomes of fetuses/neonates with the amelioration of cystic hygroma during pregnancy. MATERIAL AND METHODS: This was a retrospective observational study. We focused on fetuses with cystic hygroma managed in our institute between January 2006 and June 2019. The infants were followed by pediatricians (neonatologist, pediatric cardiologist, and pediatric neurologist) and pediatric outcomes were retrieved from the medical records up to 3 years old. RESULTS: One hundred and seven fetuses with cystic hygroma were included. Of the 107, cystic hygromas ameliorated in 31 fetuses (31/107: 29%). Of the 31, there were 26 livebirths. Half (n = 13) of the 26 fetuses had a good outcome, whereas the remaining half (n = 13) had abnormalities. Various abnormalities were detected in their infancies. A nuchal thickness (diameter of hygroma) of ≥5 mm was significantly correlated with abnormalities (P = 0.047). CONCLUSION: Physicians should pay attention to fetuses/neonates with ameliorated cystic hygroma. Of those, special attention should be paid to fetuses/neonates with a nuchal thickness at diagnosis ≥5 mm.

Expectant management of retained products of conception following abortion: A retrospective cohort study.

OBJECTIVE: To clarify the natural history of retained products of conception (RPOC) following abortion at less than 22 weeks of gestation, and those who show major bleeding during course observation. STUDY DESIGN: We retrospectively reviewed 640 patients who had spontaneous or artificial abortion at less than 22 weeks of gestation between January 2011 and August 2019 in our institute. Of those, patients with RPOC were included. The maternal background, RPOC characteristics, and subsequent complications including additional interventions were reviewed. RESULTS: Fifty-four patients with RPOC were included. The incidence of RPOC was 6.7 %. The median (interquartile range: IQR) RPOC length was 29 (20-38) mm. RPOC hypervascularity was observed in 26 (48 %) patients. The median (IQR) periods of RPOC flow disappearance and RPOC disappearance on ultrasound from abortive treatment were 50 (28-76) and 84 (50-111) days, respectively. Of the 54, 44 patients were selected for expectant management. Of the 44, 34 (77 %) patients were observed without intervention (recovery group); the other 10 (23 %) patients required additional interventions associated with subsequent bleeding (intervention group). Compared with the recovery group, heavy bleeding (> 500 mL) at abortion (6/10: 60 %) and RPOC hypervascularity (8/10: 80 %) were more frequently observed in the intervention group. CONCLUSION: Expectant management was successful in almost 80 % of patients with RPOC following abortion. The additional interventions were required in patients with heavy bleeding at abortion and RPOC hypervascularity.

Cerebral Aneurysm Rupture during Pregnancy Resulting in Subdural Hematoma without Subarachnoid Hemorrhage.

Subarachnoid hemorrhage is typically present in cerebral aneurysm rupture, whereas acute subdural hematoma without subarachnoid hemorrhage is rare. We herein report a case of cerebral aneurysm rupture during pregnancy resulting in acute subdural hematoma without subarachnoid hemorrhage. A 37-year-old gravida 4 para 3 pregnant woman was admitted for threatened preterm labor at 294/7 weeks of gestation. At 296/7 weeks of gestation (day -14), she developed mild left eye pain, which disappeared within one day. At 316/7 weeks of gestation (day 0), she developed the sudden onset of severe headache and nausea. A neurological examination revealed no abnormal findings, and analgesics ameliorated her headache. At 321/7 weeks of gestation (day 2), after consultations with neurosurgeons, magnetic resonance imaging showed acute subdural hematoma without subarachnoid hemorrhage. Further examinations revealed a cerebral aneurysm. Emergent clipping surgery was performed with the fetus in utero in consideration of the immaturity of the fetus and stable maternal/fetal general conditions. At 356/7 weeks of gestation (day 28), her headache of unknown cause recurred. Considering the maturity of the fetus, the patient underwent cesarean section with good maternal and neonatal outcomes. The absence of subarachnoid hemorrhage does not eliminate cerebral aneurysm rupture.

Low placental growth factor levels and high soluble endoglin levels at 26-31 weeks of gestation precede light placenta with and without relatively heavy infant, respectively: A retrospective cohort study.

AIM: Our aim was to examine whether serum levels of placental growth factor (PlGF) and soluble endoglin (sEng) at 19-25 and 26-31 weeks of gestation were associated with the occurrence of the 9-block categorization of placenta weight (PW) and fetal/placenta ratio (F/P ratio). METHODS: We performed a retrospective cohort study in 1391 women with singleton pregnancy. Serum levels of PlGF and sEng were measured by enzyme immunosorbent assay. A light placenta was defined as PW ZS < -1.28 SD. Based on the PW (light, normal, and heavy) and F/P ratio (relatively heavy, balanced growth, and relatively small), 9-block categorization were performed. Multivariable logistic regression analyses were performed. RESULTS: Low PlGF at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block A (light placenta and relatively heavy infant), after adjusting for prepregnancy body mass index and serum levels of sEng. High sEng at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block D (light placenta and balanced growth of infant), after adjusting for past history of either preeclampsia or gestational hypertension, high pulsatility index of uterine artery flow velocity waveforms in the second trimester, and serum level of PlGF. CONCLUSIONS: Low PlGF levels at 26-31 weeks of gestation may precede a light placenta and relatively heavy infant (Block A), and high sEng levels at 26-31 weeks of gestation may precede a light placenta and balanced growth of infant (Block D).

Extravillous trophoblast invasion accelerated by WNT3A, 5A, and 10B via CD44.

INTRODUCTION: Appropriate extravillous trophoblast (EVT) invasion is essential for successful pregnancy. Previously, we showed that EVTs express CD44, which accelerated EVT invasion. However, its regulation mechanism via CD44 remains unknown. Our hypothesis was that WNT signaling enhanced EVT invasion via CD44. To test this hypothesis, we investigated the effects of WNT ligands on CD44 expression and EVT invasion using EVT cell lines and isolated primary EVTs. METHODS: We used EVT cell lines (HTR8/SVneo and HChEpC1b) and isolated primary EVTs, extracted from first-trimester trophoblasts. The cells were supplemented with WNT3A, 5A, and 10B. We examined cell invasion and the expressions of CD44 and matrix metalloproteinase (MMP) 9. Next, to clarify the pathway of WNT10B in EVTs, we knock-downed WNT10B using siRNA and activated or inhibited the WNT canonical pathway using an activator (lithium chloride) or inhibitor (FH535, XAV939) with WNT10B addition. RESULTS: WNT3A, 5A, and 10B accelerated the invasion in the EVT lines and isolated primary EVTs. The expressions of CD44 and MMP9 were also upregulated by WNT ligands. WNT10B knockdown significantly inhibited EVT invasion concomitantly with CD44 expression. The WNT canonical pathway activator upregulated CD44 expression and its inhibitor downregulated it with WNT10B addition. CONCLUSIONS: The present study is the first to show the possibility that WNT3A, WNT5A, and WNT10B exist upstream of CD44 in EVTs. Among them, WNT10B may be a novel accelerator of EVT invasion. WNT signaling mediated by multiple WNT ligands may contribute to EVT invasion.

Prognosis and Prognostic Factors of Patients with Emergent Cerclage: A Japanese Single-Center Study.

OBJECTIVES: The aims of this study were to clarify the following: (1) how often does prolonged pregnancy ≥34 weeks occur in patients with emergent cerclage without progesterone and (2) the risk factors preventing such pregnancy continuation. MATERIALS AND METHODS: This retrospective observational study was performed using medical records of patients for whom emergent cerclage had been performed between April 2006 and December 2018 in our institute. RESULTS: Emergent cerclage was performed in 123 patients (median age: 34, interquartile range: 31-36). Primiparous patients numbered 44 (36%). A history of spontaneous preterm birth (SPTB) was present in 30 (24%). The median presurgical cervical length (CL) was 16 (8-21) mm at surgery. Of the 123, 20 (16%) were delivered at 33 + 6 weeks or less (<34 weeks). We conducted logistic regression analysis of the risk factors of SPTBs <34 weeks after cerclage. Three risk factors were identified that increased the risk of SPTB <34 weeks: presurgical CL 0 mm (odds ratio (OR): 5.30; 95% confidence interval (CI): 1.58-17.7), a history of SPTB (OR: 4.65; 95% CI: 1.38-15.7), and the presence of sludge (OR: 4.14; 95% CI: 1.20-14.3). CONCLUSION: Three risk factors predicted SPTB <34 weeks after emergency cerclage without progesterone administration: unmeasurable CL (CL 0 mm), a history of SPTB, and the presence of sludge on ultrasound. SPTB <34 weeks occurred after emergency cerclage in 16% of patients, being comparable with the recent data with progesterone.

Usefulness of dynamic computed tomography for diagnosing and evaluating uterine artery pseudoaneurysms in women with late post-partum hemorrhage not complicated by retained products of conception.

AIM: We examined whether critical conditions, which were defined as having hemoglobin (Hb) less than 7.0 g/dL, shock index ≥1.0, or need for transfusion, were associated with the presence of extravasation (EV) on dynamic computed tomography (CT) in women with late post-partum hemorrhage (PPH). METHODS: Forty post-partum women with late PPH without evident retained products of conception performed dynamic CT. Two radiologists retrospectively evaluated dynamic CT, and determined the presence or absence of EV and a sac-like structure within the uterine cavity with enhancement. RESULTS: Ultrasound images were available in 34/40 patients. Color Doppler flow in uterine cavity was evaluated in 33/34 (97%), and all women showed abnormal flow. Of 40 patients, dynamic CT revealed EV in 8 (20%), and a sac-like structure in 30 (75%). Thus, we diagnosed these 38 (95%) as having uterine artery pseudoaneurysm (UAP). Uterine artery embolization was performed in 36/38 diagnosed as having UAP, and in 2/2 patients with an unknown cause of hemorrhage. The incidence rates of critical conditions were significantly increased in PPH women with than without EV on dynamic CT: Hb <7.0 g/dL (62.5 vs 0%, [P < 0.001]), shock index ≥1.0 (50 vs 9.4% [P = 0.020]), and need for transfusion (37.5 vs 0% [P = 0.006]). Abnormal color Doppler flows were observed in all patients with either EV and sac on dynamic CT. CONCLUSION: Dynamic CT was useful for diagnosing UAP, and for evaluating critical conditions, in women with late PPH not complicated by retained products of conception.

Perinatal outcome of pregnancy after adenomyomectomy: summary of 10 cases with a brief literature review.

Objectives: The purpose of this study was the perinatal outcomes of patients who became pregnant after adenomyomectomy.Study design: The retrospective cohort study was performed involving pregnant women with a history of adenomyomectomy between 1 January 2011 and 31 December 2018. At 24-26 weeks, the patients were admitted even without symptoms or signs. When regular uterine contractions were observed, tocolysis was performed.Results: Ten patients were included. Elective and emergent cesarean section (CS) was performed in seven and three patients, respectively. Emergent CS was performed due to onset of labor (tocolytic failure) at 28, 24, and 32 weeks. Although no patients suffered uterine rupture, myometrial thinning was observed at the site corresponding to that of adenomyomectomy in three patients. Of these three patients, two required emergent CS due to tocolytic failure with cervical length (CL) shortening. In contrast, CLs were stable in the other seven patients with elective CS.Conclusions: Three patients after adenomyomectomy showed preterm delivery, and three had a very thin uterus to the extent that the fetus could be observed through the uterine wall. A short CL should be paid special attention in pregnant women with a history of adenomyomectomy.