Labor induction at 41+0 gestational weeks or expectant management for the nulliparous woman: The Finnish randomized controlled multicenter trial.

INTRODUCTION: Neonatal and maternal risks increase in term pregnancy as gestational age advances and become increasingly evident post-term. Management practices of late- and post-term pregnancies vary, and the optimal time point for intervention by labor induction is yet to be determined. MATERIAL AND METHODS: This randomized controlled trial of 381 nulliparous women with unripe cervices compared labor induction at 41+0 gestational weeks (early induction) with expectant management and labor induction at 41+5 to 42+1 gestational weeks (expectant management). This multicenter study included all five university hospitals and the largest central hospital in Finland. The study period was 2018-2022. Participants were randomized to either early induction (48.8%, n = 186) or expectant management (51.2%, n = 195) with equal randomization ratios of 1:1. This was a superiority trial, and the primary outcomes were rates of cesarean section (CS) and composite of adverse neonatal outcomes. The trial was registered at the ISRCTN registry (ISRCTN83219789, https://doi.org/10.1186/ISRCTN83219789). RESULTS: The rates of CS (16.7% [n = 31] vs. 24.1% [n = 47], RR 0.7 [95% CI: 0.5-1.0], p = 0.07) and a composite of adverse neonatal outcomes (9.7% [n = 18] vs. 14.4% [n = 28], RR 0.7 [95% CI: 0.4-1.2] p = 0.16) did not significantly differ between the groups, but the operative delivery rate was lower in the early induction group than in the expectant management group (30.6% [n = 57] vs. 45.6% [n = 89], p = 0.003). The rates of hemorrhage ≥1000 mL and neonatal weight ≥4000 g were also lower in the early induction group, as was the vacuum extraction rate in women with vaginal delivery. Of the women with expectant management, 45.6% (n = 89) had spontaneous onset of labor. No perinatal deaths occurred, but one case of eclampsia appeared in the expectant management group. CONCLUSIONS: Offering labor induction to nulliparous women at 41+0 gestational weeks may decrease the probability of operative delivery, postpartum hemorrhage, and neonatal weight ≥4000 g. However, this study was underpowered to affirm the trends of rising rates of CS and adverse neonatal outcomes in the expectant management group. Thus, expectant management could remain an option for some, as one in two women with expectant management had a spontaneous onset of labor.

Delayed umbilical cord clamping in elective and nonelective term Cesarean delivery.

BACKGROUND: Delayed cord clamping (DCC) is recommended for preterm and term neonates, regardless of delivery mode. After impression of increased maternal blood loss following DCC implementation during Cesarean delivery (CD) concerns arose about maternal safety, particularly in term CDs. MATERIALS AND METHODS: We conducted a retrospective cohort study by reviewing birth records from our tertiary hospital in Kuopio, Finland including 914 women with singleton term CD and recorded estimated blood loss. Early cord clamping (ECC) occurred from January 2016 to December 2019, while DCC (30-60 s) from January 2020 to December 2020. We evaluated maternal and neonatal outcomes for ECC vs. DCC and assessed severe postpartum hemorrhage (PPH) (≥1500 ml) and its potential clinical risk factors. RESULTS: In total, 914 women were included (DCC N = 152; ECC N = 762). Estimated mean maternal blood loss showed no significant difference between DCC and ECC groups (697 ml vs. 750 ml, p < 0.96). Severe PPH was less frequent in the DCC group (4.6% vs. 10.5 %, p < 0.024). Neonatal outcomes were similar between groups. Multivariable analysis revealed that women with placenta previa (OR 5.63, p < 0.001), macrosomic neonate (OR 2.75, p < 0.001), and intrapartum infection (OR 2.00, p < 0.057) had an increased risk for severe PPH. Earlier CD was associated with less severe PPH (OR 0.36, p < 0.001). CONCLUSIONS: DCC (30-60 s) during term CD did not increase maternal blood loss in singleton pregnancies and demonstrated no short-term adverse effects on neonates. Our findings support the general practice of DCC during both elective and nonelective term CD.

Oxycodone does not affect placental circulatory physiology during the early first stage of labor-A randomized trial.

INTRODUCTION: Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory physiology. We hypothesized that maternal intravenous (i.v.) oxycodone has no detrimental effect on utero- and fetoplacental hemodynamics during the early first stage of labor. MATERIAL AND METHODS: Twenty-two parturients requiring pain relief during the first stage of labor were randomized in a double-blinded and placebo-controlled study. By Doppler ultrasonography, both uterine artery (Ut) and umbilical vein (UV) volume blood flows (Q), Ut pulsatility index (PI), and Ut vascular resistance (RUt) were calculated. Blood flow velocity waveforms were obtained between uterine contractions. After baseline measurements, women received oxycodone 0.05 mg/kg or a placebo intravenous. Doppler ultrasonography was repeated up to 120 min after the first drug administration. The second dose of oxycodone 0.05 mg/kg was allowed at 60 min to all parturients with contraction pain ≥5/10. Maternal plasma samples were collected at each study phase and after delivery with umbilical cord plasma samples, to measure oxycodone concentrations. CLINICALTRIALS: gov identifier (NCT no. NCT02573831). RESULTS: At baseline, mean QUt and QUV did not differ significantly between the placebo-first (478 mL/min and 57 mL/min/kg) and the oxycodone-first (561 mL/min and 71 mL/min/kg) groups. In addition, RUt and Ut PI were comparable between the groups. Following oxycodone at 60 min, mean QUt and QUV (714 mL/min and 52 mL/min/kg) were similar to the placebo-first (520 mL/min and 55 mL/min/kg) group. Furthermore, all the measured parameters were comparable to the baseline values. At 60 min after the first study drug administration, all the parturients in the placebo-first group needed intravenous oxycodone 0.05 mg/kg. At 120 min, we found no statistically significant change in any of the measured parameters. No significant correlation was found between maternal oxycodone concentration and QUt or QUV. Furthermore, newborn oxycodone concentration did not correlate with QUV. CONCLUSIONS: Oxycodone did not have any detrimental effect on either utero- or fetoplacental circulatory physiology during the early first stage of labor. Maternal plasma oxycodone did not correlate with utero- and fetoplacental hemodynamics. No correlation was found between newborn oxycodone concentration and fetoplacental hemodynamics.

Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti-D prophylaxis: A retrospective nationwide cohort study.

INTRODUCTION: Targeted routine antenatal anti-D prophylaxis was introduced to the national prophylaxis program in Finland in late 2013. The aim of this study was to assess the incidence, time-points, and risk factors for Rhesus D immunization after the implementation of routine antenatal anti-D prophylaxis, in all women in Finland with antenatal anti-D antibodies detected in 2014-2017. MATERIAL AND METHODS: In a nationwide population-based retrospective cohort study, the incidence, time-points, and risk factors of anti-D immunizations were analyzed. Information on antenatal screening was obtained from the Finnish Red Cross Blood Service database, and obstetric data from hospital records and the Finnish Medical Birth Register. RESULTS: The study included a total of 228 women (197 with complete data for all pregnancies). After the implementation of routine antenatal anti-D prophylaxis, the prevalence of pregnancies with anti-D antibodies decreased from 1.52% in 2014 to 0.88% in 2017, and the corresponding incidence of new immunizations decreased from 0.33% to 0.10%. Time-points for detection of new anti-D antibodies before and after 2014 were the first screening sample at 8-12 weeks of gestation in 52% vs 19%, the second sample at 24-26 weeks in 20% vs 50%, and the third screening at 36 weeks in 28% vs 32%. CONCLUSIONS: The incidence of new anti-D immunizations decreased as expected after the implementation of routine antenatal anti-D prophylaxis. True failures are rare and they mainly occur when the prophylaxis is not given appropriately, suggesting a need for constant education of healthcare professionals on the subject.

The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women: A randomized national multicenter trial.

INTRODUCTION: Our objective was to compare the efficacy of a 200-µg misoprostol vaginal insert vs oral misoprostol regarding the cesarean section rate and the time interval to vaginal delivery in nulliparous women with unfavorable cervix. MATERIAL AND METHODS: In this prospective multicenter trial, 283 nulliparous women at term with Bishop score <6 were randomized to induction of labor with either a misoprostol vaginal insert (n = 140) or oral misoprostol (n = 143). In the oral misoprostol group, a 50-µg dose of oral misoprostol was administered every 4 hours up to three times during the first day; during the second day, the dose was increased to 100-µg every 4 hours up to three times during the first day, if necessary. Primary outcome was the cesarean section rate. Secondary outcomes were the time from induction of labor to vaginal delivery, the rate of other induction methods needed, labor augmentation with oxytocin and/or amniotomy, use of tocolytics and adverse neonatal and maternal events. RESULTS: In the misoprostol vaginal insert group, median time to vaginal delivery was shorter (24.5 hours vs 44.2 hours, P < 0.001), whereas no difference was found in the cesarean section rate (33.8% vs 29.6%, odds ratio [OR] 1.21, 95% confidence interval [CI] 0.66-1.91, P = 0.67). Other induction methods and labor augmentation with oxytocin and/or amniotomy were less frequent in the misoprostol vaginal insert group (OR 0.32, 95% CI 0.18-0.59 and OR 0.56, 95% CI 0.32-0.99, respectively). Need for tocolysis and meconium-stained amniotic fluid were more common in the misoprostol vaginal insert group (OR 3.63, 95% CI 1.12-11.79 and OR 2.38, 95% CI 1.32-4.29, respectively). Maternal and neonatal adverse events did not differ between groups. CONCLUSIONS: Misoprostol vaginal insert proved to shorten the time to vaginal delivery and to reduce the use of other methods of labor induction and augmentation, but it did not reduce the cesarean section rate compared with oral misoprostol. The benefit of more rapid delivery associated with misoprostol vaginal insert should be weighed against the greater risks for uterine hyperstimulation and meconium-stained amniotic fluid.

Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study.

OBJECTIVES: Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. METHODS: We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0-13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. RESULTS: The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7-11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1-60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1-60.6), intermediate onset (delivery between 34+0-36+6 weeks of gestation) to 25.1-fold (95%CI 3.1-79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0-52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1-3.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.5-20.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.4-9.8), of severe preeclampsia 22.2-fold (95%CI 9.9-41.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.0-57.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.1-21.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia. CONCLUSION: The risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia.

Maternal drug or alcohol abuse is associated with decreased head size from mid-pregnancy to childhood.

AIM: Maternal alcohol abuse is poorly recognised and causes developmental problems. This study explored the foetal central nervous systems (CNS), head circumference and psychomotor development of children exposed to drugs or alcohol during pregnancy up to 2.5 years of age. METHODS: We recruited 23 pregnant women referred to Kuopio University Hospital, Finland, by their family doctor because of drug or alcohol abuse, and 22 control mothers. Foetal CNS parameters were measured by three-dimensional ultrasonography at the mean gestational age of 20 weeks and the Griffiths Mental Developmental Scales (GMDS), and anthropometric measurements were carried out at the mean ages of one and 2.5 years. RESULTS: The exposed foetuses had decreased biparietal and occipito-frontal distances and head circumferences, but unchanged cerebellar volume at 20 weeks, and decreased head circumferences and length and height at birth, one and 2.5 years of age. They scored lower than the controls on the GMDS general quotient and the hearing, language and locomotor subscales at 2.5 years of age. CONCLUSION: Maternal alcohol or drug exposure was associated with decreased head size from mid-pregnancy to childhood and reduced development at 2.5 years. Foetal head circumference at mid-pregnancy was a useful indicator of substance abuse affecting the CNS.

Neonatal outcomes after the obstetric near-miss events uterine rupture, abnormally invasive placenta and emergency peripartum hysterectomy - prospective data from the 2009-2011 Finnish NOSS study.

INTRODUCTION: Neonatal outcomes after the maternal obstetric near-miss complications of uterine rupture, abnormally invasive placenta, and emergency peripartum hysterectomy were assessed. MATERIAL AND METHODS: This case-control study was conducted as part of the Nordic Obstetric Surveillance Study (NOSS). Data on 211 newborns from 197 deliveries in which an obstetric near-miss complication was involved, were collected prospectively from April 2009 to August 2011 from all Finnish delivery units via questionnaires. Missing cases were obtained from national health registers and confirmed by the clinics. Control populations consisted of all other children born during the same period of time in the Finnish Medical Birth Register (n = 147 551). RESULTS: The number of stillbirths in this cohort was high [n = 8, 3.8% vs. 0.3% among controls, odds ratio (OR) 12.5, 95% confidence interval (CI) 6.32-24.9]. In addition, there were two neonatal deaths. The majority of cases (n = 8, 80%) were connected to uterine rupture. The risk of severe birth asphyxia diagnosis was increased compared with controls (n = 17, 8.1% vs. 0.1%, OR 137, 95% CI 82.7-226). A low umbilical artery pH (<7.05) was also observed among these neonates (28.8% vs. 1.0%, OR 28.7, 95% CI 21.5-38.2). Post-term pregnancies were relatively common among the uterine rupture cases. Adverse neonatal outcomes in the AIP and emergency peripartum hysterectomy cases were associated with preterm deliveries. CONCLUSIONS: The prospective data collected from clinicians, combined with the information gathered from national health registers, provided valuable insights into rare maternal near-miss cases. These complications also predisposed stillbirth and neonatal death. In this study, 75% of fetal losses were associated with uterine rupture.

Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study.

OBJECTIVE: Outcome after intrauterine transfusions due to severe hemolytic disease of the fetus and newborn. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All women treated with intrauterine transfusions for hemolytic disease of the fetus and newborn in Finland in 2003-2012. POPULATION: 339 intrauterine transfusions, performed in 104 pregnancies of 84 women. METHODS: Information on antenatal screening of red cell antibodies and red cell units issued for intrauterine transfusion was obtained from the Finnish Red Cross Blood Service database, and obstetric and neonatal data from hospital records. MAIN OUTCOME MEASURES: Procedure-related complications, perinatal mortality, neonatal morbidity. RESULTS: Overall survival was 94.2% (95% confidence interval 89.7-98.7). There were four fetal and two neonatal deaths. Procedure-related fetal loss rate was 1.2% (95% confidence interval 0.04-2.4) per procedure and 3.8% (95% confidence interval 0.1-7.5) per pregnancy. Of the four procedure-related losses, three were due to technically difficult intrauterine transfusions causing infection and preterm birth. Of the live born infants, 19% (95% confidence interval 11.3-26.7) were born before 32 weeks' gestation. The incidence of severe neonatal morbidity (respiratory distress syndrome, severe cerebral injury, sepsis) was 22.2% (95% confidence interval 13.4-30.2). Poor outcome (death, severe neonatal morbidity) was negatively associated with gestational age at first transfusion (p = 0.001) and at birth (p = 0.00006). Follow-up of the infants was too incomplete to assess the neurodevelopmental outcome. CONCLUSIONS: Although overall survival is comparable with previous studies, our concern is procedure-related infections and preterm births. Close collaboration between the university hospitals is needed to ensure timely treatment, operator skills and systematic follow-up of the children.

A highly reproducible xenograft model for human ovarian carcinoma and application of MRI and ultrasound in longitudinal follow-up.

OBJECTIVE: Typically, human ovarian cancer is widely disseminated at the time of diagnosis and shows extremely poor prognosis. Experimental animal models that mimic human ovarian cancer are often incomplete when compared to the full spectrum of the human disease with regard to its histological hallmarks such as the spread of carcinoma, its ability to seed the peritoneal cavity and formation of ascites. We have established and characterized a new animal model for human ovarian cancer in nude mouse. METHODS: A new cell line SKOV-3m was injected intraperitoneally in nude mice. Mice were divided in two groups A and B, which received 1 x 10(7) and 2 x 10(7) cells, respectively. Histology, immunohistochemistry, magnetic resonance imaging and ultrasound were used to analyze tumors. RESULTS: All mice had tumors within 18 days and histologically they resembled poorly differentiated human cystadenocarcinomas with bloody ascites. Mean survival of the mice was 42+/-14 and 21+/-2 days in groups A and B, respectively. Magnetic resonance imaging and ultrasound were used to confirm the presence of tumors and to monitor their growth without sacrificing the animals. CONCLUSION: This new xenograft model accompanied by noninvasive imaging is highly reproducible and likely to be very useful in testing new treatment strategies for ovarian cancer.

Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis.

BACKGROUND: For clinically relevant proangiogenic therapy, it would be essential that the growth of the whole vascular tree is promoted. Vascular endothelial growth factor (VEGF) is well known to induce angiogenesis, but its capability to promote growth of larger vessels is controversial. We hypothesized that blood flow remodels vascular growth during VEGF gene therapy and may contribute to the growth of large vessels. METHODS AND RESULTS: Adenoviral (Ad) VEGF or LacZ control gene transfer was performed in rabbit hindlimb semimembranous muscles with or without ligation of the profound femoral artery (PFA). Contrast-enhanced ultrasound and dynamic susceptibility contrast MRI demonstrated dramatic 23- to 27-fold increases in perfusion index and a strong decrease in peripheral resistance 6 days after AdVEGF gene transfer in normal muscles. Enlargement by 20-fold, increased pericyte coverage, and decreased alkaline phosphatase and dipeptidyl peptidase IV activities suggested the transformation of capillaries toward an arterial phenotype. Increase in muscle perfusion was attenuated, and blood vessel growth was more variable, showing more sprouting angiogenesis and formation of blood lacunae after AdVEGF gene transfer in muscles with ligated PFA than in normal muscles. Three-dimensional ultrasound reconstructions and histology showed that the whole vascular tree, including large arteries and veins, was enlarged manifold by AdVEGF. Blood flow was normalized and enlarged collaterals persisted in operated limbs 14 days after AdVEGF treatment. CONCLUSIONS: This study shows that (1) blood flow modulates vessel growth during VEGF gene therapy and (2) VEGF overexpression promotes growth of arteries and veins and induces capillary arterialization leading to supraphysiological blood flow in target muscles.

Prenatal diagnosis of placenta accreta and percreta with ultrasonography, color Doppler, and magnetic resonance imaging.

BACKGROUND: The risk of placenta previa and accreta is increased in females with previous cesarean deliveries, and there has been an increasing number of these operations. CASES: We present 2 cases with previous cesarean and placenta previa in the following pregnancy. One patient had placenta accreta and the other, placenta percreta. In both cases, prenatal diagnosis was based on ultrasonography, where features such as loss of the hypoechoic retroplacental zone and irregular uterine serosa were found in grayscale ultrasonography. In color Doppler imaging, in both cases, increased vascularity between myometrium and placenta, as well as intraplacental lacunae, were seen. Thinning of the uterine wall, found in magnetic resonance imaging, contributed to the diagnosis of placenta percreta. CONCLUSION: Prenatal diagnosis of placenta accreta is of importance because it reduces fetal and maternal morbidity as appropriate preoperative and perioperative procedures are possible.

Adenoviral catheter-mediated intramyocardial gene transfer using the mature form of vascular endothelial growth factor-D induces transmural angiogenesis in porcine heart.

BACKGROUND: It is unclear what is the most efficient vector and growth factor for induction of therapeutic vascular growth in the heart. Furthermore, the histological nature of angiogenesis and potential side effects caused by different vascular endothelial growth factors (VEGFs) in myocardium have not been documented. METHODS AND RESULTS: Adenoviruses (Ad) at 2 doses (2x10(11) and 2x10(12) viral particles) or naked plasmids (1 mg) encoding LacZ control, VEGF-A165, or the mature, soluble form of VEGF-D (VEGF-D(DeltaNDeltaC)) were injected intramyocardially with the NOGA catheter system into domestic pigs. AdVEGF-D(DeltaNDeltaC) gene transfer (GT) induced a dose-dependent myocardial protein production, as measured by ELISA, resulting in an efficient angiogenic effect 6 days after the injections. Also, AdVEGF-A165 produced high gene transfer efficacy, as demonstrated with immunohistochemistry, leading to prominent angiogenesis effects. Despite the catheter-mediated approach, angiogenesis induced by both AdVEGFs was transmural, with maximal effects in the epicardium. Histologically, strongly enlarged alpha-smooth muscle actin-positive microvessels involving abundant cell proliferation were found in the transduced regions, whereas microvessel density did not change. Myocardial contrast echocardiography and microspheres showed marked increases in perfusion in the transduced areas. VEGF-D(DeltaNDeltaC) but not matrix-bound VEGF-A165 was detected in plasma after adenoviral GT. A modified Miles assay demonstrated myocardial edema resulting in pericardial effusion with the higher AdVEGF doses. All effects returned to baseline by 3 weeks. Naked plasmid-mediated GT did not induce detectable protein production or vascular effects. CONCLUSIONS: Like AdVEGF-A165, AdVEGF-D(DeltaNDeltaC) GT using the NOGA system produces efficient transmural angiogenesis and increases myocardial perfusion. AdVEGF-D(DeltaNDeltaC) could be useful for the induction of therapeutic vascular growth in the heart.

Kinetics of a US contrast agent in benign and malignant adnexal tumors.

PURPOSE: To evaluate the effects of a microbubble contrast agent on the power Doppler ultrasonographic (US) examination of adnexal tumors, with a special focus on the timing of the transit of the microbubble bolus. MATERIALS AND METHODS: Seventy patients who were suspected of having ovarian tumors were examined preoperatively with contrast material-enhanced US. Images obtained during a 5-minute examination were stored digitally, and the behavior of the contrast agent was evaluated objectively with measurement of the time-dependent image intensity at the region of interest with a computer program. A time-intensity curve in each case was derived and analyzed. The Mann-Whitney U test was used to compare intensity changes and tumor parameters in benign and malignant adnexal tumors. RESULTS: Both the baseline and maximum power Doppler intensities, as well as the absolute and relative (percent) rise in intensity, were significantly higher (P <.001) in malignant as compared with benign tumors. The arrival time was shorter (17.5 vs 22.5 seconds; P =.005) and the duration of contrast agent effect was longer (190.4 vs 103.6 seconds; P <.001) in malignant tumors than they were in benign tumors. The area under the time-intensity curve was significantly greater in malignant tumors compared with that in benign tumors (P <.001). CONCLUSION: After microbubble contrast agent injection, malignant and benign adnexal lesions behave differently in degree, onset, and duration of Doppler US enhancement.