Outpatient Use of Monoclonal Antibodies Casirivimab and Imdevimab in Pregnancy for Mild-to-Moderate Coronavirus Disease 2019.

OBJECTIVE: The aim of this study was to report the use casirivimab/imdevimab therapy in pregnant women with moderate coronavirus disease 2019 (COVID-19). STUDY DESIGN: We report 12 cases of unvaccinated pregnant patients with mild-to-moderate COVID-19 treated with casirivimab/imdevimab. RESULTS: Twelve unvaccinated pregnant patients with mild-to-moderate COVID-19 received casirivimab/imdevimab at the dose of 1200/1200 mg by intravenous infusion over 60 minutes. All women were managed outpatient. None experienced severe adverse drug reaction and none progressed to severe disease. CONCLUSION: Casirivimab/imdevimab should be considered for outpatient treatment of unvaccinated pregnant women with mild-to-moderate COVID-19 to decrease the risk of severe disease. KEY POINTS: · Casirivimab/imdevimab is not well studied in pregnant women.. · Casirivimab/imdevimab in pregnant women with mild-to-moderate COVID-19 decreases the risk of severe disease.. · Casirivimab/imdevimab in pregnant women with mild-to-moderate COVID-19 is well tolerated..

Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial.

BACKGROUND: Cesarean scar ectopic pregnancy is a type of ectopic pregnancy in which the fertilized egg is implanted in the muscle or fibrous tissue of the scar after a previous cesarean delivery. The condition can be catastrophic if not managed on time and can lead to significant morbidity and mortality. Several approaches have been studied for the management of cesarean scar ectopic pregnancy in women who opted for termination of pregnancy with no consensus on the best treatment modality reached so far. OBJECTIVE: This study aimed to compare the success rate of hysteroscopic resection vs ultrasound-guided dilation and evacuation for the treatment of cesarean scar ectopic pregnancy. STUDY DESIGN: This was a parallel group, nonblinded, randomized clinical trial conducted at a single center in Italy. Women with singleton gestations at <8 weeks and 6 days of gestation were included in the study. Inclusion criteria were women with a cesarean scar ectopic pregnancy with positive embryonic heart activity who opted for termination of pregnancy. Patients were randomized 1:1 to receive either hysteroscopic resection (ie, intervention group) or ultrasound-guided dilation and evacuation (ie, control group). Both groups received 50 mg/m2 of methotrexate intramuscularly at the time of randomization (day 1) and another dose at day 3. A third dose of methotrexate was planned in case of persistence of positive fetal heart activity at day 5. Participants received either ultrasound-guided dilation and evacuation or hysteroscopic resection from 1 to 5 days after the last dose of methotrexate. Hysteroscopic resection was performed under spinal anesthesia using a 15 Fr bipolar mini-resectoscope. Dilation and evacuation were performed by vacuum aspiration with a Karman cannula, followed by sharp curettage, if necessary, under ultrasound guidance. The primary outcome was the success rate of the treatment protocol, defined as no further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. Resolution of the cesarean scar ectopic pregnancy was evaluated based on decline of beta-hCG and the absence of residual gestational material in the endometrial cavity. Treatment failure was defined as the necessity for further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. A sample size calculation indicated that 54 participants were required to test the hypothesis RESULTS: A total of 54 women were enrolled and randomized. Number of previous cesarean deliveries ranged from 1 to 3. Overall, 10 women received a third dose of methotrexate with 7 of 27 (25.9%) participants in the hysteroscopic resection group and 3 of 27 (11.1%) in the dilation and evacuation group. The success rate was 100% (27/27) in the hysteroscopic resection group and 81.5% (22/27) in the dilation and evacuation group (relative risk, 1.22; 95% confidence interval, 1.01-1.48). Additional procedures were required in 5 cases of the control group, namely 3 hysterectomies, 1 laparotomic uterine segmental resection, and 1 hysteroscopic resection. The length of stay in the hospital was 9.0±2.9 days in the intervention group and 10.0±3.5 days in the control group (mean difference, -1.00 days; 95% confidence interval, -2.71 to 0.71). No cases of admission to intensive care unit or maternal death were reported. CONCLUSION: Hysteroscopic resection was associated with an increased success rate in the treatment of cesarean scar ectopic pregnancy when compared with ultrasound-guided dilation and evacuation.

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

OBJECTIVE: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. STUDY DESIGN: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). RESULTS: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. KEY POINTS: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value <0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5'UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy.

BACKGROUND: The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March-May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions. METHODS: Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March-May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI). RESULTS: Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of - 101.3 (95% CI - 103.5 to - 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of - 19.7 (95% CI - 23.8 to - 15.6; p < 0.0001). CONCLUSION: A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric-gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.

Urinary Incontinence after Planned Cesarean Hysterectomy for Placenta Accreta.

INTRODUCTION: Data regarding the risk of incontinence after cesarean hysterectomy are lacking. We aimed to assess the risk of urinary incontinence in women who underwent planned cesarean hysterectomy for placenta accreta. METHODS: This was a retrospective study of women who underwent planned cesarean hysterectomy for placenta accreta. The primary outcome was the incidence of post-cesarean hysterectomy urinary incontinence, defined as involuntary loss of urine between 3 and 12 months after cesarean hysterectomy. Outcomes were compared in a cohort of women who underwent planned cesarean hysterectomy for placenta accreta with a control group of women who underwent scheduled cesarean section without hysterectomy. RESULTS: Forty-seven singleton gestations who underwent planned cesarean hysterectomy for placenta accrete were included in the study and were compared with 100 controls. Eight cases of bladder injuries were reported, 7 in the planned cesarean hysterectomy group and one in the planned cesarean delivery group. Overall, urinary incontinence was reported in 10 women of the planned cesarean hysterectomy group and in 8 women of the planned cesarean section group (21.3% vs. 8.0%; p = 0.03). CONCLUSION: Planned cesarean hysterectomy for placenta accreta is a risk factor for urinary incontinence.

Use of Negative Pressure Wound Therapy Systems after Radical Vulvectomy for Advanced Vulvar Cancer.

A retrospective cohort study was performed to evaluate the efficacy of negative pressure wound therapy in improving vulvectomy healing. Women who underwent radical vulvectomy with complete inguinofemoral lymphadenectomy for advanced vulvar cancer were divided into two groups according to immediate postoperative care: patients treated with negative pressure wound therapy using the device applied on the site of the wound (including vulva and inguinal region), and patients receiving conventional care. 18 patients were included in the study. 7 (38.9%) women were treated with negative pressure wound therapy immediately after the surgery and were included in the intervention group, and 11 (61.1%) patients were included in the control group. Women who received negative pressure wound therapy had significantly lower length of stay in the hospital (14.2 ± 4.7 versus 17.1 ± 6.1 days, mean difference -6.90 days, 95% confidence interval -11.91 to -1.89), and significantly lower length for wound healing (-31.90 days, 95% confidence interval -43.48 to -20.32). In conclusion, the utilization of the negative wound pressure therapy may contribute to reduce hospitalization after radical vulvectomy for vulvar cancer. Large and well-designed randomized trials with cost effectiveness analyses are needed to confirm these findings.

Early amniotomy after cervical ripening for induction of labor: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE DATA: Timing of artificial rupture of membranes (ie, amniotomy) in induction of labor is controversial, because it has been associated not only with shorter labors, but also with fetal nonreassuring testing, at times necessitating cesarean delivery. The aim of this systematic review and metaanalysis of randomized trials was to evaluate the effectiveness of early amniotomy vs late amniotomy or spontaneous rupture of membranes after cervical ripening. STUDY: The search was conducted with the use of electronic databases from inception of each database through February 2019. Review of articles included the abstracts of all references that were retrieved from the search. STUDY APPRAISAL AND SYNTHESIS METHODS: Selection criteria included randomized clinical trials that compared early amniotomy vs control (ie, late amniotomy or spontaneous rupture of membranes) after cervical ripening with either Foley catheter or prostaglandins at any dose. The primary outcome was the incidence of cesarean delivery. The summary measures were reported as summary relative risk with 95% of confidence interval with the use of the random effects model of DerSimonian and Laird. RESULTS: Four trials that included 1273 women who underwent cervical ripening with either Foley catheter or prostaglandins and then were assigned randomly to either early amniotomy, late amniotomy, or spontaneous rupture of membranes (control subjects) were included in the review. Women who were assigned randomly to early amniotomy had a similar risk of cesarean delivery (31.1% vs 30.9%; relative risk, 1.05; 95% confidence interval, 0.71-1.56) compared with control subjects and had a shorter interval from induction to delivery of approximately 5 hours (mean difference, -4.95 hours; 95% confidence interval, -8.12 to -1.78). Spontaneous vaginal delivery was also reduced in the early amniotomy group, but only 1 of the included trials reported this outcome (67.5% vs 69.1%; relative risk, 0.78; 95% confidence interval, 0.66-0.93). No between-group differences were reported in the other obstetrics or perinatal outcomes. CONCLUSION: After cervical ripening, routine early amniotomy does not increase the risk of cesarean delivery and reduces the interval from induction to delivery.

Impact of the ACOG guideline regarding low-dose aspirin for prevention of superimposed preeclampsia in women with chronic hypertension.

BACKGROUND: Patients with chronic hypertension are at increased risk for superimposed preeclampsia. The 2016 American College of Obstetricians and Gynecologists guideline recommended initiating 81 mg of daily aspirin for all pregnant women with chronic hypertension to prevent superimposed preeclampsia. OBJECTIVE: (1) To evaluate the rates of implementation of the 2016 American College of Obstetricians and Gynecologists guideline over time; and (2) to evaluate the effectiveness of aspirin for the prevention of superimposed preeclampsia and other adverse maternal and neonatal outcomes in women with chronic hypertension before and after this guideline. STUDY DESIGN: This is a retrospective study of women with chronic hypertension who delivered at Thomas Jefferson University Hospital from January 2014 through June 2018. This cohort of women with chronic hypertension was divided into 2 groups, before and after the American College of Obstetricians and Gynecologists recommendation published in September 2016. Daily 81 mg of aspirin was initiated between 12 and 16 weeks. We excluded multiple gestations and incomplete records. The primary outcome was incidence of superimposed preeclampsia, and secondary outcomes were incidence of superimposed preeclampsia with or without severe features, small for gestational age, and preterm birth <37 weeks. Subgroup analysis based on risk stratification was evaluated in women with chronic hypertension requiring antihypertensive medication, history of preeclampsia, and pregestational diabetes. RESULTS: We identified 457 pregnant women with chronic hypertension, 203 in the post-American College of Obstetricians and Gynecologists group and 254 in the pre-American College of Obstetricians and Gynecologists group. Aspirin 81 mg was offered to 142 (70%) in the post-American College of Obstetricians and Gynecologists group and 18 (7.0%) in the pre-American College of Obstetricians and Gynecologists group. Maternal demographics were not significantly different. The overall incidence of superimposed preeclampsia was not significantly different: 87 (34.3%) vs 72 (35.5%), P=.79, in the pre- and post-American College of Obstetricians and Gynecologists guideline groups, respectively. Superimposed preeclampsia with severe features significantly increased: 32 (12.6%) vs 9 (4.4%), P<.01, whereas superimposed preeclampsia without severe features significantly decreased: 55 (21.7%) vs 63 (31.0%), P=.03. There were no significant differences in small for gestational age neonates or preterm birth <37 weeks incidences between groups. There were no significant differences in the subgroup analysis based on the severity of chronic hypertension requiring antihypertensive medication, history of preeclampsia, or pregestational diabetes. CONCLUSION: After the adoption of the American College of Obstetricians and Gynecologists guidelines in 70% of the cohort, superimposed preeclampsia, small for gestational age, and preterm birth were not significantly decreased after implementation of aspirin 81 mg initiated between 12 and 16 weeks of gestation.

Delayed versus immediate pushing in the second stage of labor in women with neuraxial analgesia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials was to evaluate the effect of delayed versus immediate pushing in the second stage of labor on mode of delivery and other outcomes in women with neuraxial analgesia. DATA SOURCES: The research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and the Cochrane Library as electronic databases, from the inception of each database to August 2019. No restrictions for language or geographic location were applied. STUDY ELIGIBILITY CRITERIA: Selection criteria included only randomized controlled trials in pregnant women randomized to either delayed or immediate pushing during the second stage of labor. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was mode of delivery. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals using the random effects model of DerSimonian and Laird. An I2 (Higgins I2) value of greater than 0% was used to identify heterogeneity. RESULTS: Twelve randomized controlled trials, including 5445 women with neuraxial analgesia randomized to delayed versus immediate pushing during the second stage of labor, were included in the meta-analysis. Of the 5445 women included in the meta-analysis, 2754 were randomized to the delayed pushing group and 2691 to the immediate pushing group. No significant difference between delayed and immediate pushing was found for spontaneous vaginal delivery (80.9% versus 78.3%; relative risk, 1.05; 95% confidence interval, 1.00-1.10; 12 randomized controlled trials, 5540 women), operative vaginal delivery (12.8% versus 14.6%; relative risk, 0.89; 95% confidence interval, 0.75-1.08; 11 randomized controlled trials, 5395 women), and cesarean delivery (6.9% versus 7.9%; relative risk, 0.89; 95% confidence interval, 0.73-1.07; 11 randomized controlled trials; 5395 women). Women randomized to the delayed pushing group had a significantly shorter length of active pushing (mean difference, -27.54 minutes; 95% confidence interval, -43.04 to -12.04; 7 randomized controlled trials, 4737 women) at the expense of a significantly longer overall duration of the second stage of labor (mean difference, 46.17 minutes; 95% confidence interval, 32.63-59.71; 8 studies; 4890 women). The incidence of chorioamnionitis (9.1% versus 6.6%; relative risk, 1.37, 95% confidence interval, 1.04-1.81; 1 randomized controlled trial, 2404 women) and low umbilical cord pH (2.7% versus 1.3%; relative risk, 2.00; 95% confidence interval, 1.30-3.07; 5 randomized controlled trials, 4549 women) were significantly higher in the delayed pushing group. CONCLUSION: In women with spontaneous or induced labor at term with neuraxial analgesia, delayed pushing in the second stage does not affect the mode of delivery, although it reduces the time of active pushing at the expense of a longer second stage. This prolongation of labor was associated with a higher incidence of chorioamnionitis and low umbilical cord pH. Based on these findings, delayed pushing cannot be routinely advocated for the management of the second stage.

Physical examination-indicated cerclage in twin pregnancy: a randomized controlled trial.

BACKGROUND: Women with twin pregnancies and a dilated cervix in the second trimester are at increased risk of pregnancy loss and early preterm birth; there is currently no proven therapy to prevent preterm birth in this group of women. OBJECTIVE: This study aimed to determine whether physical examination-indicated cerclage reduces the incidence of preterm birth in women with a diagnosis of twin pregnancies and asymptomatic cervical dilation before 24 weeks of gestation. STUDY DESIGN: Multicenter, parallel group, open-label, randomized controlled trial of women with twin pregnancies and asymptomatic cervical dilation of 1 to 5 cm between 16 weeks 0/7 days of gestation and 23 weeks 6/7 days of gestation were enrolled from July 2015 to July 2019 in 8 centers. Eligible women were randomized in a 1:1 ratio into either cerclage or no cerclage groups. We excluded women with monochorionic-monoamniotic twin pregnancy, selective fetal growth restriction, twin-twin transfusion syndrome, major fetal malformation, known genetic anomaly, placenta previa, signs of labor, or clinical chorioamnionitis. The primary outcome was the incidence of preterm birth at <34 weeks of gestation. Secondary outcomes were preterm births at <32, <28, and <24 weeks of gestation, interval from diagnosis to delivery, and perinatal mortality. Data were analyzed by intention-to-treat methods. RESULTS: After an interim analysis was performed, the Data and Safety Monitoring Board recommended stopping the trial because of a significant decrease in perinatal mortality in the cerclage group. We randomized 34 women, with 4 women being excluded because of expired informed consent. A total of 17 women were randomized to physical examination-indicated cerclage and 13 women to no cerclage. Whereas 4 women randomized to cerclage did not receive the surgical procedure, no women in the no cerclage group received cerclage. Maternal demographics were not significantly different. All women in the cerclage group also received indomethacin and antibiotics. When comparing the cerclage group vs the no cerclage group, the incidence of preterm birth was significantly decreased as follows: preterm birth at <34 weeks of gestation, 12 of 17 women (70%) vs 13 of 13 women (100%) (risk ratio, 0.71; 95% confidence interval, 0.52-0.96); preterm birth at <32 weeks of gestation, 11 of 17 women (64.7%) vs 13 of 13 women (100%) (risk ratio, 0.65; 95% confidence interval, 0.46-0.92); preterm birth at <28 weeks of gestation, 7 of 17 women (41%) vs 11 of 13 women (84%) (risk ratio, 0.49; 95% confidence interval, 0.26-0.89); and preterm birth at <24 weeks of gestation, 5 of 17 women (30%) vs 11 of 13 women (84%) (risk ratio, 0.35; 95% confidence interval, 0.16-0.75). The mean gestational age at delivery was 29.05±1.7 vs 22.5±3.9 weeks (P<.01), respectively; the mean interval from diagnosis of cervical dilation to delivery was 8.3±5.8 vs 2.9±3.0 weeks (P=.02), respectively. Perinatal mortality was also significantly reduced in the cerclage group compared with the no cerclage group as follows: 6 of 34 women (17.6%) vs 20 of 26 women (77%) (risk ratio, 0.22; 95% confidence interval, 0.1-0.5), respectively. CONCLUSION: In women with twin pregnancies and asymptomatic cervical dilation before 24 weeks of gestation, a combination of physical examination-indicated cerclage, indomethacin, and antibiotics significantly decreased preterm birth at all evaluated gestational ages. Most importantly, cerclage in this population was associated with a 50% decrease in early preterm birth at <28 weeks of gestation and with a 78% decrease in perinatal mortality.

First-trimester screening based on cell-free DNA vs combined screening: A randomized clinical trial on women's experience.

OBJECTIVE: To compare women's experience of first-trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell-free DNA (cfDNA) analysis. METHODS: This was single-center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first-trimester risk assessment based on FTCS, or to a policy of first-trimester risk assessment based on ultrasound findings and cfDNA. FTCS included ultrasound evaluation with crown-rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP-A and free beta hCG). In this group, invasive diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first-trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, invasive diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre-test and post-test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post-test reassurance, defined as mean score of reassurance post-test questionnaire. The effect of the assigned screening test on the mean of each outcome was quantified as mean difference (MD) with 95% confidence interval (CI). RESULTS: Forty women with singleton gestations were enrolled in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre-test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post-test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfaction and lower mean anxiety score as assessed in the STAI pre-test questionnaire. CONCLUSIONS: First-trimester risk assessment for fetal aneuploidy with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal reassurance and better maternal satisfaction compared to the standard first-trimester combined screening with nuchal translucency, and biochemistry. TRIAL REGISTRATION: Clinicaltrials.gov NCT04077060.

In-bag manual versus uncontained power morcellation for laparoscopic myomectomy.

BACKGROUND: Uterine leiomyomas, also referred to as myomas or fibroids, are benign tumours arising from the smooth muscle cells of the myometrium. They are the most common pelvic tumour in women. The estimated rate of leiomyosarcoma, found during surgery for presumed benign leiomyomas, is about 0.51 per 1000 procedures, or approximately 1 in 2000. Treatment options for symptomatic uterine leiomyomas include medical, surgical, and radiologically-guided interventions. Laparoscopic myomectomy is the gold standard surgical approach for women who want offspring, or otherwise wish to retain their uterus. A limitation of laparoscopy is the inability to remove large specimens from the abdominal cavity through the laparoscope. To overcome this challenge, the morcellation approach was developed, during which larger specimens are broken into smaller pieces in order to remove them from the abdominal cavity via the port site. However, intracorporeal power morcellation may lead to scattering of benign tissues, with the risk of spreading leiomyoma or endometriosis. In cases of unsuspected malignancy, power morcellation can cause unintentional dissemination of malignant cells, and lead to a poorer prognosis by upstaging the occult cancer. A strategy to optimise women's safety is to morcellate the specimens inside a bag. In-bag morcellation may avoid the dissemination of tissue fragments. OBJECTIVES: To evaluate the effectiveness and safety of protected in-bag extracorporeal manual morcellation during laparoscopic myomectomy compared to intra-abdominal uncontained power morcellation. SEARCH METHODS: On 1 July 2019, we searched; the Cochrane Gynaecology and Fertility Group Specialized Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, PubMed, Google Scholar, and two trials registers. We reviewed the reference lists of all retrieved full-text articles, and contacted experts in the field for additional and ongoing trials. SELECTION CRITERIA: We included all randomised controlled trials comparing in-bag extracorporeal manual morcellation versus intracorporeal uncontained power morcellation during laparoscopic myomectomy in premenopausal women. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Two review authors independently reviewed the eligibility of trials, extracted data, and evaluated the risk of bias. Data were checked for accuracy. The summary measures were reported as risk ratios (RR) or mean differences (MD) with 95% confidence interval (CI). The outcomes of interest were a composite of intraoperative and postoperative complications, operative times, ease of morcellation, length of hospital stay, postoperative pain, conversion to laparotomy, and postoperative diagnosis of leiomyosarcoma. Results for the five main outcomes follow. MAIN RESULTS: We included two trials, enrolling 176 premenopausal women with fibroids, who underwent laparoscopic myomectomy. The experimental group received in-bag manual morcellation, during which each enucleated myoma was placed into a specimen retrieval bag, and manually morcellated with scalpel or scissors. In the control group, intracorporeal uncontained power morcellation was used to reduce the size of the myomas. No intraoperative complications, including accidental morcellation of the liver, conversion to laparotomy, endoscopic bag disruption, bowel injury, bleeding, accidental injury to any viscus or vessel, were reported in either group in either trial. We found very low-quality evidence of inconclusive results for total operative time (MD 9.93 minutes, 95% CI -1.35 to 21.20; 2 studies, 176 participants; I² = 35%), and ease of morcellation (MD -0.73 points, 95% CI -1.64 to 0.18; 1 study, 104 participants). The morcellation operative time was a little longer for the in-bag manual morcellation group, however the quality of the evidence was very low (MD 2.59 minutes, 95% CI 0.45 to 4.72; 2 studies, 176 participants; I² = 0%). There were no postoperative diagnoses of leiomyosarcoma made in either group in either trial. We are very uncertain of any of these results. We downgraded the quality of the evidence due to indirectness and imprecision, because of limited sites in high-income settings and countries, small sample sizes, wide confidence intervals, and few events. AUTHORS' CONCLUSIONS: There are limited data on the effectiveness and safety of in-bag morcellation at the time of laparoscopic myomectomy compared to uncontained power morcellation. We were unable to determine the effects of in-bag morcellation on intraoperative complications as no events were reported in either group. We are uncertain if in-bag morcellation improves total operative time or ease of morcellation compared to control. Regarding morcellation operative time, the quality of the evidence was also very low and we cannot be certain of the effect of in-bag morcellation compared to uncontained morcellation. No cases of postoperative diagnosis of leiomyosarcoma occurred in either group. We found only two trials comparing in-bag extracorporeal manual morcellation to intracorporeal uncontained power morcellation at the time of laparoscopic myomectomy. Both trials had morcellation operative time as primary outcome and were not powered for uncommon outcomes such as intraoperative complications, and postoperative diagnosis of leiomyosarcoma. Large, well-planned and executed trials are needed.

Variations in sleep associated with different types of hormonal contraceptives.

Progesterone and some of its metabolites are neuroactive steroids that affect sleep by increasing melatonin secretion and stimulating GABA-A receptors. The effect of progestogens in hormonal contraceptives on sleep has not been thoroughly investigated. This observational study assessed possible associations in sleep changes induced by estrogen-progestogens in contraceptives in 108 women between the ages of 20 and 50 years. We assessed mean nightly sleep time with a 31-day sleep diary, and subjective sleep quality with the five subjective subscores of the Pittsburgh Sleep Quality Index (PSQI). Included women were of childbearing age, healthy, sexually active and had been using a hormonal contraceptive method (pill, intrauterine system (IUS), subcutaneous implant, vaginal ring) for at least six months. Results were compared to a matched control group that did not use hormonal contraceptives. The longest mean nightly sleep time, compared to control (450 min), occurred in women who used progestogen-only oral contraception (510 min), followed by IUS delivery of levonorgestrel 13.5 mg (480 min) and oral ethinylestradiol 0.02/0.03 mg plus gestodene 0.075 mg (475 min). Global subjective sleep quality was influenced most by the administration of etonorgestrel 0.120 mg/ethinylestradiol 0.015 mg via the vaginal route. Our results show that low-doses of progestins affect various aspects of sleep, and that this is influenced by the route of administration.

Ulipristal acetate in symptomatic uterine fibroids. A real-world experience in a multicentric Italian study.

Surgery is the most frequent treatment in women with symptomatic uterine fibroids. A new medical approach with ulipristal acetate (UPA) has been suggested. The aim of this study was to provide data on effectiveness and safety of UPA in premenopausal women with symptomatic uterine fibroids. This was a multicenter retrospective cohort study. Data on all consecutive premenopausal women with symptomatic uterine fibroids referred to three Italian centers were included in a dedicated merged database. Women aged 18-55 years, who received pharmacologic therapy with UPA 5 mg orally once a day, were included in the study. The primary outcome was the percentage of women who underwent surgery after UPA treatment. One hundred and forty-two premenopausal women with uterine fibroids were included in this study. The mean age was 43.2 years. Eighty-one (57.0%) of 142 women treated with UPA had only medical treatment and did not undergo surgery. Surgical treatment occurred in 70, 23, 32, and 8% of the women who received one course, two courses, three courses, or four courses, of UPA treatment, respectively. The incidence of side effects was 10.6%. The effectiveness and safety of repeated UPA treatment courses in reducing number of women requiring surgery is confirmed by real-world data.

Clinical management of coronavirus disease 2019 (COVID-19) in pregnancy: recommendations of WAPM-World Association of Perinatal Medicine.

These guidelines follow the mission of the World Association of Perinatal Medicine, which brings together groups and individuals throughout the world with the goal of improving outcomes of maternal, fetal and neonatal (perinatal) patients. Guidelines for auditing, evaluation, and clinical care in perinatal medicine enable physicians diagnose, treat and follow-up of COVID-19-exposed pregnant women. These guidelines are based on quality evidence in the peer review literature as well as the experience of perinatal expert throughout the world. Physicians are advised to apply these guidelines to the local realities which they face. We plan to update these guidelines as new evidence become available.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

First trimester detection of fetal open spina bifida using BS/BSOB ratio.

BACKGROUND: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect. OBJECTIVE: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound. METHODS: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves. RESULTS: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649. CONCLUSION: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida.

Effect of music on labor and delivery in nulliparous singleton pregnancies: a randomized clinical trial.

BACKGROUND: Women's experience of pain during labor varies greatly, and pain control is a major concern for obstetricians. Several methods have been studied for pain management for women in labor, including drug and non-drug interventions. OBJECTIVE: To test the hypothesis that in nulliparous women with singleton pregnancies at term, listening to music would reduce the pain level during labor. METHODS: Parallel group non-blinded randomized clinical trial conducted at a single center in Italy. Nulliparous women in spontaneous labor with singleton pregnancies and vertex presentation admitted in labor and delivery room between 37 0/7 and 42 0/7 weeks of gestation for active phase of labor were eligible, and were randomized in a 1:1 ratio to receive music during labor or no music during labor. Music in labor was defined listening to music from the randomization until the delivery of the baby. The primary endpoint was the pain level during the active phase of labor, recorded using the visual analogue scale (VAS) for pain, ranging from 0 (no pain) to 10 (unbearable pain). The effect of music use during labor on each outcome was quantified as the mean difference (MD) with 95% confidence interval (CI). RESULTS: During the study period, 30 women agree to take part in the study, underwent randomization, and were enrolled and followed up. 15 women were randomized in the music group, and 15 in the control group. No patients were lost to follow up for the primary outcome. Pain level during the active phase of labor was scored 8.8 ± 0.9 in the music group, and 9.8 ± 0.3 in the control group (MD - 1.00 point, 95% CI - 1.48 to - 0.52; P < 0.01). Music during labor and delivery was also associated with a decreased pain at 1 h postpartum (MD - 2.40 points, 95% CI - 4.30 to - 0.50), and decreased anxiety level during active phase of labor (MD - 19.90 points, 95% CI - 38.72 to - 1.08), second stage of labor (MD - 49.40 points, 95% CI - 69.44 to - 29.36), and at 1 h postpartum (MD - 27.00 points, 95% CI - 47.37 to - 6.63). CONCLUSION: In nulliparous women with singleton pregnancies at term, listening to music reduces the pain level, and the anxiety level during labor. TRIAL REGISTRATION: Clinicaltrials.gov NCT03779386.