Successful management of a pregnant woman of lower-limb arteriovenous malformation with chronic cardiac failure.

The clinical features of extracranial arteriovenous malformations (AVM) vary from stages I (quiescence) with few symptoms to IV (decompensation) with overt symptoms of cardiac failure. Although the maternal outcomes of pregnant women with extracranial AVM is understudied due to its rarity, previous studies suggested the difficulty in the management of recurrent hemorrhage due to AVM progression during perinatal period; thus, pregnant case of extracranial AVM complicated with cardiac failure were considered challenging. We have reported a woman of stage IV extracranial AVM in the right lower limb with a history of below-the-knee amputation, in which two pregnancies and vaginal deliveries under epidural anesthesia were managed successfully. Cardiac failure did not exacerbate throughout the gestational or postpartum periods. Ulceration gradually worsened, with no massive hemorrhage. It is ideal to assess abnormal vascularity, especially in the lower abdomen, vagina, and epidural and subdural spaces, through magnetic resonance imaging to ensure safe delivery.

Two cases of pregnancy after achieving complete remission of chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (CAEBV) infection characterized by persistent infectious mononucleosis-like symptoms can lead to cardiovascular diseases. We encountered two pregnant women with CAEBV histories complicated with cardiovascular diseases. A 36-year-old woman with a history of myocardial infarction due to CAEBV and coronary artery bypass grafting became pregnant. Her left ventricular ejection fraction (LVEF) decreased, and cesarean section was performed at 36 weeks of gestation. Her LVEF recovered after delivery. A 32-year-old woman with a history of CAEBV and chronic hypertension was diagnosed with mild pulmonary arterial hypertension (PAH) after conception. She strongly desired to continue the pregnancy. She became complicated with severe superimposed preeclampsia at 31 weeks of gestation, and cesarean section was performed. Her PAH did not deteriorate during pregnancy or the postpartum period. Women treated for CAEBV, even with complete remission, require a preconception evaluation focused on the cardiovascular system and careful management of their pregnancy.

Placenta previa with posterior extrauterine adhesion: clinical features and management practice.

BACKGROUND: A diagnostic sign on magnetic resonance imaging, suggestive of posterior extrauterine adhesion (PEUA), was identified in patients with placenta previa. However, the clinical features or surgical outcomes of patients with placenta previa and PEUA are unclear. Our study aimed to investigate the clinical characteristics of placenta previa with PEUA and determine whether an altered management strategy improved surgical outcomes. METHODS: This single institution retrospective study examined patients with placenta previa who underwent cesarean delivery between 2014 and 2019. In June 2017, we recognized that PEUA was associated with increased intraoperative bleeding; thus, we altered the management of patients with placenta previa and PEUA. To assess the relationship between changes in practice and surgical outcomes, a quasi-experimental method was used to examine the difference-in-difference before (pre group) and after (post group) the changes. Surgical management was modified as follows: (i) minimization of uterine exteriorization and adhesion detachment during cesarean delivery and (ii) use of Nelaton catheters for guiding cervical passage during Bakri balloon insertion. To account for patient characteristics, propensity score matching and multivariate regression analyses were performed. RESULTS: The study cohort (n = 141) comprised of 24 patients with placenta previa and PEUA (PEUA group) and 117 non-PEUA patients (control group). The PEUA patients were further categorized into the pre (n = 12) and post groups (n = 12) based on the changes in surgical management. Total placenta previa and posterior placentas were more likely in the PEUA group than in the control group (66.7% versus 42.7% [P = 0.04] and 95.8% versus 63.2% [P < 0.01], respectively). After propensity score matching (n = 72), intraoperative blood loss was significantly higher in the PEUA group (n = 24) than in the control group (n = 48) (1515 mL versus 870 mL, P < 0.01). Multivariate regression analysis revealed that PEUA was a significant risk factor for intraoperative bleeding before changes were implemented in practice (t = 2.46, P = 0.02). Intraoperative blood loss in the post group was successfully reduced, as opposed to in the pre group (1180 mL versus 1827 mL, P = 0.04). CONCLUSIONS: PEUA was associated with total placenta previa, posterior placenta, and increased intraoperative bleeding in patients with placenta previa. Our altered management could reduce the intraoperative blood loss.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Single versus multiple cervical dilation by osmotic dilator before induction of labor for second-trimester abortion.

AIM: In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second-trimester abortion. METHODS: We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12-21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel. RESULTS: The women were categorized into two groups: 191 women had a delivery time of <24 h, whereas 47 had delivery times >24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for <24 h and 2.4 ± 0.87 for >24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of >24 h and the number of used gemeprost. CONCLUSION: Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible.

Systematic review on the needle and suture types for uterine compression sutures: a literature review.

BACKGROUND: This study aimed to identify and review associations between the types of sutures used for uterine compression suture (UCS) and its outcomes in postpartum hemorrhage. METHODS: An electronic search using PubMed and Scopus databases was performed. We included the English articles reported from January 1, 1997, to May 31, 2017, using search words or terms regarding the types of suture and needle used for UCSs. We only included studies describing the sutures in the systematic review. RESULTS: We found 196 studies and included 76 (38.8%) in our analysis. We collected data on maternal outcomes for 924 patients and categorized them. Of the 76 studies, suture sizes 0, 1, and 2 were used in 6, 44, and 32 articles, respectively (some studies used multiple sutures). Of the 45 studies mentioning the needles, curved and straight needles were used in 35 and 10, respectively. The results of our review revealed that about 80% of previous articles used Catgut and Polyglactin 910 sutures. Because no studies that compared the efficacy of different size of sutures were identified, we investigated the differences using the cases reported in previous studies mentioned above. In the first analysis, we compared the uterine preservation rate between size 1 and size 2 sutures. We found no significant difference in uterine preservation rate (92.8%: size 1 vs. 94.2%: size 2, p > 0.05) but found significant difference in transfusion rate (62.4% vs. 79.1%, p < 0.01). With the hypothesis that non-transfusion cases were less severe, we excluded these cases from second analysis. Although our second analysis of only Catgut or Polyglactin showed strong selection bias, we observed that uterine preservation rate was significantly higher in cases with size 2 suture than in those with size 1 suture (86.9% vs. 93.5%, p = 0.033). CONCLUSIONS: Our systematic review showed that approximately 80% of cases were treated by Catgut and Polyglactin 910. Due to the heterogeneity of cases included in this review, it is difficult to estimate which suture is better for UCSs. More robust studies are necessary to enable the identification of the superior suture for performing UCSs.

New dedicated blunt straight needles and sutures for uterine compression sutures: a retrospective study and literature review.

BACKGROUND: We developed a dedicated blunt straight needle with No. 2 polydioxanone sutures (2-Monodiox®) for uterine compression sutures (UCSs) and aimed to assess the outcomes and complication rates of UCSs for postpartum hemorrhage by comparing with commercially available needle and suture types. METHODS: A retrospective analysis was performed between January 2010 and February 2018. During the study period, two types of commercially available sutures and 2-Monodiox® were used. PubMed, MEDLINE, and Scopus databases were searched for English articles published between January 1997 and May 2017 using search terms related to the suture and needle types for UCSs to discuss the dedicated needles and sutures for UCS. RESULTS: The analysis included 47 cases of UCSs for the uterine body with three suture types (No. 0 polydioxanone, 7 cases; No. 1 poliglecaprone 25, 21 cases; and No. 2 polydioxanone, 19 cases). B-Lynch suture using No. 0 sutures was associated with a significantly lower uterine preservation rate than those with Nos. 1 and 2 sutures (42.9% vs. 95.2 and 89.5%, respectively; p < 0.01). A modified Hayman suture technique was performed using 2-Monodiox® sutures, which achieved a similar uterine preservation rate compared with B-Lynch suture using No. 1 poliglecaprone 25 sutures. No patients developed severe complications. The literature review showed that no dedicated sutures have developed for UCSs. Three dedicated needles for UCSs have been developed, and 2-Monodiox® is the first dedicated blunt straight needle for UCSs. CONCLUSION: Our data showed that No. 0 sutures should not be used for B-Lynch suture. The uterine preservation rate is similar for 2-Monodiox® with modified Hayman suture and No. 1 poliglecaprone 25 sutures with B-Lynch suture, without the occurrence of severe complications.

Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis.

Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1. The relationship between arginase, one of the nitric oxide (NO) modulators, and sFlt-1 was examined. First, the pregnant women were divided into 4 groups: group 1, sFlt-1 <6000 pg/ml and arginase activity <110 U/L; group 2, sFlt-1 ≥6000 pg/ml and arginase activity <110 U/L; group 3, sFlt-1 ≥6000 pg/ml and arginase activity ≥110 U/L; and group 4, sFlt-1 <6000 pg/ml and arginase activity ≥110 U/L. Groups 2 and 3 comprised preeclamptic women. The preeclampsia/normotensive ratio increased from groups 1 to 3. Under the higher sFlt-1 condition, lower arginase activity was associated with lower occurrence of preeclampsia. Next, in human umbilical endothelial vein cells (HUVECs), a slightly higher concentration of sFlt-1, as in group 2, reduced arginase expression and arginase activity, and S-(2-boronoethyl)-l-cysteine (BEC; arginase inhibitor) impaired sFlt-1 secretion. In contrast, a higher level of sFlt-1 increased arginase expression and activity in HUVECs, as in group 3. These results showed that arginase controlled sFlt-1 elevation to some extent. In conclusion, our results suggest the existence of a mechanism to maintain the level of sFlt-1. Soluble Flt-1 negatively regulated itself against increasing serum sFlt-1 in preeclampsia. Moreover, this study revealed that arginase inhibitors are a potential treatment option for preeclampsia.

Obstetric outcome in patients with a unicornuate uterus after laparoscopic resection of a rudimentary horn.

AIM: Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. METHODS: Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a 'postlaparoscopic resection of the rudimentary horn' group (study group) and an 'other uterine anomalies' (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. RESULTS: Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (<10th percentile) (0% vs 24.2%; P = .31) and HDP rate (0.0% vs 3.0%; P = 1.0). Three of seven cases with postlaparoscopic resection of the rudimentary horn were able to deliver vaginally without complications. CONCLUSION: Our study shows that the obstetric outcome observed in the study group was similar to that observed in the control group.

A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage.

BACKGROUND: Sheehan's syndrome occurs because of severe postpartum hemorrhage causing ischemic pituitary necrosis. Sheehan's syndrome is a well-known condition that is generally diagnosed several years postpartum. However, acute Sheehan's syndrome is rare, and clinicians have little exposure to it. It can be life-threatening. There have been no reviews of acute Sheehan's syndrome and no reports of successful pregnancies after acute Sheehan's syndrome. We present such a case, and to understand this rare condition, we have reviewed and discussed the literature pertaining to it. An electronic search for acute Sheehan's syndrome in the literature from January 1990 and May 2014 was performed. CASE PRESENTATION: A 27-year-old woman had massive postpartum hemorrhage (approximately 5000 mL) at her first delivery due to atonic bleeding. She was transfused and treated with uterine embolization, which successfully stopped the bleeding. The postpartum period was uncomplicated through day 7 following the hemorrhage. However, on day 8, the patient had sudden onset of seizures and subsequently became comatose. Laboratory results revealed hypothyroidism, hypoglycemia, hypoprolactinemia, and adrenal insufficiency. Thus, the patient was diagnosed with acute Sheehan's syndrome. Following treatment with thyroxine and hydrocortisone, her condition improved, and she was discharged on day 24. Her next pregnancy was established 2 years after her first delivery. She required induction of ovulation for the next conception. The pregnancy, delivery, and postpartum period were uneventful. An electronic search of the literature yielded 21 cases of acute Sheehan's syndrome. Presenting signs varied, including adrenal insufficiency (12 cases), diabetes insipidus (4 cases), hypothyroidism (2 cases), and panhypopituitarism (3 cases), with a median time of presentation after delivery for each of those conditions being 7.9, 4, 18, and 9 days, respectively. Serial changes in magnetic resonance imaging were reported in some cases of acute Sheehan's syndrome. CONCLUSION: Clinicians should be aware of the risk of acute Sheehan's syndrome after a massive postpartum hemorrhage in order to diagnose it accurately and treat it promptly.

Pregnancy outcomes in women with different doses of corticosteroid supplementation during labor and delivery.

AIM: The aim of this study was to report the pregnancy outcomes of women who received different doses of corticosteroid supplementation during labor and delivery. METHODS: We conducted a retrospective review of 102 pregnant women who received oral corticosteroid therapy, delivered at Osaka University Hospital, and were administered intravenous corticosteroid supplementation during labor and delivery. From January 2008 to May 2012, 47 women were administered a high dose of corticosteroids (HD group). From June 2012 to December 2016, 55 women were given a low dose of corticosteroids (LD group). RESULTS: There were no significant differences in the patient characteristics between the two groups. The most frequent disease was systemic lupus erythematosus (30/102; 29.4%). Most women used prednisolone for more than 1 year (91/102; 89.2%) and at a dose of more than 5 mg/day (88/102; 86.3%). The total intravenous dose of hydrocortisone during labor and delivery ± standard deviation was 233.5 ± 129.4 mg (HD group) and 143.4 ± 38.1 mg (LD group), exhibiting a significantly larger dose in the HD group. No patients suffered an adrenal deficiency and there were no significant differences in the hemodynamics. There were three cases of puerperal endometritis, two patients with hyperglycemia, and one wound infection in the HD group, whereas one case of puerperal endometritis in the LD group. There were no significant differences in the neonatal outcomes. CONCLUSION: Pregnancy outcomes did not differ between the high and low doses of corticosteroid supplementation during labor and delivery.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Functional assessment of hyperoxia-induced lung injury after preterm birth in the rabbit.

The objective of this study was to document early neonatal (7 days) pulmonary outcome in the rabbit model for preterm birth and hyperoxia-induced lung injury. Preterm pups were delivered at 28 days (term = 31 days; early saccular phase of lung development) by cesarean section, housed in an incubator, and gavage fed for 7 days. Pups were divided into the following groups: 1) normoxia (21% O2; normoxia group) and 2) and hyperoxia (>95% O2; hyperoxia group). Controls were pups born at term who were housed in normoxic conditions (control group). Outcome measures were survival, pulmonary function tests using the whole body plethysmograph and forced oscillation technique, and lung morphometry. There was a significant difference in survival of preterm pups whether they were exposed to normoxia (83.3%) or hyperoxia (55.9%). Hyperoxic exposure was associated with increased tissue damping and elasticity and decreased static compliance compared with normoxic controls (P < 0.01). Morphometry revealed an increased linear intercept and increased mean wall transection length, which translates to larger alveoli with septal thickening in hyperoxia compared with normoxia (P < 0.01). In conclusion, the current experimental hyperoxic conditions to which preterm pups are exposed induce the typical clinical features of bronchopulmonary dysplasia. This model will be used to study novel preventive or therapeutic interventions.

Three-dimensional sonography in the differential diagnosis of interstitial, angular, and intrauterine pregnancies in a septate uterus.

Interstitial, angular, and cornual pregnancies and intrauterine pregnancies in an anomalous uterus are separate entities, and the impact of each condition on obstetric outcomes is completely different. However, there is considerable confusion in understanding and managing the natural course of each condition due to a lack of uniform terminology. The single most important factor for differentiating these types of pregnancies is to make an early diagnosis. The differences between interstitial, angular, and cornual pregnancies on 2-dimensional (2D) sonography are subtle. Although magnetic resonance imaging can be used to differentiate these conditions, it is not preferred as the initial assessment tool because of its limited availability and cost-effectiveness. Three-dimensional (3D) sonography has the advantage of providing views of the uterus that cannot be obtained with conventional 2D sonography. We describe 3 cases of interstitial, angular, and intrauterine pregnancies in a septate uterus that were clearly differentiated by 3D sonography. We demonstrate the differences in diagnostic imaging findings and emphasize the importance of 3D sonography in differentiating these entities.

Maternal carbon dioxide level during labor and its possible effect on fetal cerebral oxygenation: mini review.

During pregnancy, and especially during labor, the maternal carbon dioxide level declines considerably. Maternal carbon dioxide levels show a close relation with fetal carbon dioxide levels. The latter affects fetal cerebral oxygenation by regulating cerebral blood flow and shifting the oxyhemoglobin dissociation curve. In addition, maternal hypocapnia appears to impair placental oxygen transfer. Thus, maternal hyperventilation may interfere with optimal fetal cerebral oxygenation. Here, we provide a brief overview of the literature relevant to this issue.

Normalisation of angiogenic imbalance after intra-uterine transfusion for mirror syndrome caused by parvovirus B19.

We report a case of mirror syndrome caused by parvovirus B19, which resolved after intra-uterine transfusion. Mirror syndrome is a rare condition characterised by a triad of foetal hydrops, generalized maternal oedema and placentomegaly. Although the mechanism underlying the onset of this syndrome is unknown, it probably shares a common pathophysiologic origin with pre-eclampsia. Our patient showed increased circulating levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and decreased levels of placental growth factor (PlGF), which have also been reported in pre-eclampsia. The sFlt-1/PlGF ratio decreased immediately after intra-uterine transfusion, followed by resolution of both maternal and foetal symptoms. This suggests that the sFlt-1/PlGF ratio may help to predict the post-treatment course of mirror syndrome.

Stinging abdominal pain at 32 gestational weeks with prior classical uterine incision: Careful assessment or emergency cesarean delivery?

The risk of uterine rupture in subsequent pregnancy is 1%-12% in patients with prior classical uterine incision. Management of mild/moderate abdominal pain without an obvious abnormal finding before 36 weeks is challenging owing to fetal immaturity.

Hypertensive Disorders of Pregnancy in Relation to Coffee and Tea Consumption: The Japan Environment and Children's Study.

BACKGROUND: The association between coffee/tea intake and hypertensive disorders of pregnancy (HDP) remains unclear. This study aimed to investigate the association of caffeine, coffee, and tea intake during pregnancy with the risk of HDP. METHODS: We assessed this association in 85,533 singleton pregnant women with live births in the Japan Environment and Children's Study, a prospective cohort in Japan that included women from early pregnancy onward. Caffeinated and decaffeinated coffee and tea (green, oolong, and black) consumption during pregnancy was assessed using a validated food frequency questionnaire conducted at mid-pregnancy, and caffeine intake was calculated based on coffee and tea consumption. Multivariable logistic regression was used to assess the association with the risk of HDP. RESULTS: HDP developed in 2222 women (2.6%). Caffeine intake was weakly associated with increased risk of HDP; the multivariable odds ratio of HDP for the highest versus the lowest quartile was 1.26 (95% confidence interval: 1.11, 1.43). Coffee drinkers of two or more cups per day showed a decreased risk compared with non-drinkers (multivariable odds ratio 0.79; 0.62, 0.99) even after adjustment for total caffeine intake. Tea consumption was not associated with the risk of HDP. CONCLUSIONS: Our study suggests that higher caffeine intake may increase HDP risk, while coffee drinkers had a lower risk. Further high-quality studies are needed to replicate these findings, and to elucidate if other substances in coffee may be protective against HDP.

Antenatal diagnosis of placenta accreta spectrum after in vitro fertilization-embryo transfer: a systematic review and meta-analysis.

Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011-2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34-7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42-6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12-10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle.

Complement activation by an angiogenic imbalance leads to systemic vascular endothelial dysfunction: A new proposal for the pathophysiology of preeclampsia.

The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This study aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complement factor H (CFH) in endothelial cells, resulting in complement activation and systemic vascular endothelial dysfunction. Viability of human umbilical vein endothelial cells (HUVECs) was assessed upon CFH knockdown by targeted-siRNA, and were incubated with complement factors. HUVECs were also treated with placental growth factor (PlGF) and/or soluble fms-like tyrosine kinase 1 (sFlt1), and CFH expression and secretion were measured. These cells were evaluated by cell viability assay and cell surface complement activation was quantified by immunocytochemical assessment of C5b-9 deposition. HUVECs transfected with CFH-siRNA had significantly lower viability than that of control cells. Moreover, the expression and secretion of CFH were significantly increased upon PlGF treatment compared with PlGF + sFlt1 combo. HUVECs treated with PlGF had less C5b-9 deposition and higher viability than HUVECs treated with PlGF + sFlt1. In summary, CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.