Vilaprisan 2 mg given daily significantly induced amenorrhea, controlled bleeding and decreased uterine fibroids (UF) size in women with heavy menstrual bleeding (HMB) associated with UF, compared to placebo, according to data from the phase 2b randomized controlled randomized ASTEROID 2 trial.

Study results, which were published in the 

European Journal of Obstetrics & Gynecology and Reproductive Biology

Vilaprisan is an investigational selective progesterone receptor modulator(SPRM) and emerging medical treatment being developed by Bayer HealthCare Pharmaceuticals for UF that targets the progesterone receptor expressed on UF tissue to inhibit cell proliferation and induce apoptosis, thus resulting in reduced UF volume.

The study recruited women (mean age 42.5 years), beginning in June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL among the 155 women who completed the initial 12-weeks of therapy.

The primary endpoint compared the efficacy of vilaprisan to placebo at 12 weeks, defined as the absence of bleeding/spotting recorded in a bleeding diary. Participants also documented menstrual blood loss per sanitary product.

The three largest UF were identified during screening and documented at each ultrasound.

Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9% of women receiving vilaprisan versus 0.0 % with placebo (

In addition, the predefined HMB response of <80 mL and >50 % reduction from baseline during the last 28 days of treatment was attained by 95.7 % of women treated with vilaprisan.

Secondary endpoints of the study compared the efficacy of vilaprisan to ulipristal acetate, also a SPRM, which was approved in Europe in 2012 and Canada in 2013 for treating UF, but with some reports of serious liver injury.

Overall, 55.4% of women treated with ulipristal acetate 5 mg noticed an absence of bleeding/spotting and 86.5% achieved the predefined HMB response.

Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF, as measured by magnetic resonance imaging (MRI), by 29.9 % and 23.8 %, respectively, in contrast to an increase of 6.3 % in the placebo group.

No safety concerns were noted for any of the treatments.

Results essentially mirror those of the phase 2b ASTEROID 1 trial.

The authors noted that most pivotal trials investigating UF treatment typically use either ultrasound or MRI to measure UF volume, whereas ASTEROID 2 uses both modalities. “The observed differences between the two methods indicate that studies using only ultrasound should be interpreted with caution and highlight MRI as a more precise method in the diagnosis and assessment of women with UF,” they wrote.

Study data indicates that treatment with vilaprisan can achieve higher efficacy at a lower dose than ulipristal acetate, perhaps due to optimization of the molecular structure of vilaprisan, which was developed to maximize specificity for the progesterone receptor, while eliminating structural elements that could induce undesirable liver effects.

Unlike other compounds containing structural motifs known to impact liver function, vilaprisan has a metabolic elimination pathway involving CYP3A, which should result in a favorable hepatic safety profile.

Gemzell-Danielsson K, Heikinheimo O, Zatik J, et al. Efficacy and safety of vilaprisan in women with uterine fibroids: data from the phase 2b randomized controlled trial ASTEROID 2. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:7-14. doi:1016/j.ejogrb.2020.05.043

Articles

Study results, which were published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, also found the drug well tolerated.

Treatment with vilaprisan for uterine fibroids shows positive outcomes in study

CEUS also provides a test of choice in patients with a contraindication to MRI.

Said principal investigator Chris DeMauro, MD, chief of body imaging and director of ultrasound at Christiana Care Health Services in Newark, Delaware, “CEUS is an exciting and relatively new exam in the United States, and I am constantly thinking of new ways to use this technology.”

As a trained radiologist in body imaging, Dr. DeMauro performs and interprets both pelvic ultrasound (US) and MRI exams for the evaluation of UF.

“While discussing the benefits of CEUS with some of my training residents and reviewing an MRI of the pelvis for fibroids, I developed a hypothesis that a CEUS of the pelvis should perform similarly to MRI in identifying fibroids,” Dr. DeMauro told 

Below are CEUS and MR images of the same patient. Both images depict avid enhancement of the uterine myometrium and a single fibroid without enhancement.

Dr. DeMauro noted there is tremendous overlap in these two exams, with the primary difference being contrast enhancement previously not available for US. “The biggest challenge was optimizing the scanning protocol for CEUS,” he said. “After discussions with experts in the field of CEUS, we quickly developed a robust protocol that was easy to follow and to replicate.”

The study consisted of 26 premenopausal women (mean age 43.6 years) with a UF who underwent both a transabdominal CEUS and MRI exam at Christiana Care Health Services between March 2018 and July 2019.

The CEUS exam is performed transabdominally and the uterus is evaluated after the intravenous injection of US contrast (microbubbles).“These microbubbles resonate when under the US beam, thus allowing the visualization of vascularity of the uterus and fibroids, similar to a contrast-enhanced MRI,” Dr. DeMauro said.

For the study, the mean uterus size was 13.0 cm, with a mean time of 6.7 days between the two exams, but 12 patients had both exams on the same day.

A total of 126 fibroids (≥1 cm) were identified in the 26 patients, of which 91.3% (n = 115) were identified by both modalities, whereas 7.1% (n = 9) were identified by MRI only and 1.6% (n = 2) by CEUS only.

The study found a high correlation between the two modalities for the number of fibroids identified per patient (r = 0.97; 

There were also no significant differences between the two imaging techniques in fibroid number, size, location and enhancement for each patient.

Dr. DeMauro is not surprised by the study’s findings. “With my experience in both CEUS and MRI, I expected CEUS to perform well,” he said.

Dr. DeMauro believes CEUS of the pelvis “is a terrific alternative to MRI to identify/characterize fibroids and assess enhancement prior to uterine artery embolization (UAE) or myomectomy. In some scenarios, this may be the study of choice for the ordering clinician.”

CEUS is ideal for patients not only with a contraindication to MRI, but for those who may have an allergy to the contrast, kidney dysfunction or claustrophobia, according to Dr. DeMauro.

“Furthermore, CEUS is very well tolerated by patients and is a fraction of the cost of MRI,” he said. “In fact, many of the study patients commented on how CEUS was much more tolerable than MRI.”

Dr. DeMauro has begun a cost-effectiveness analysis of CEUS pelvis versus MRI pelvis.

Dr. DeMauro reports no relevant financial disclosures.

Chhabra P, Daugherty R, LeNoir AM, et al. Comparison of contrast-enhanced ultrasound versus magnetic resonance imaging in the detection and characterization of uterine leiomyomas. J Ultrasound Med. Published online September 15, 2020. doi:10.1002/jum.15495

A prospective observational study in the Journal of Ultrasound in Medicine has concluded that for pretreatment evaluation of uterine fibroids (UF), transabdominal contrast-enhanced ultrasound (CEUS) represents a viable alternative to traditional contrast-enhanced magnetic resonance imaging (MRI).

Ultrasound vs. MRI to detect uterine leiomyomas

A research team led by Queen Mary University of London discovered pollution particles, including metals, in the placentas of 15 women.

"Our study for the first time shows that inhaled carbon particulate matter in air pollution travels in the bloodstream and is taken up by important cells in the placenta. We hope that this information will encourage policymakers to reduce road traffic emissions in this post-lock down period,” said lead author Professor Jonathan Grigg from Queen Mary University in a recent press release.

Research has shown a connection between maternal exposure to high pollution levels and adverse obstetrical outcomes, such as low birth weight and preterm birth, but the insight was limited as to the ways the association occurred in the body. To gain further insight, the research team sought to investigate the presence of air pollution-derived particulate matter (PM) in tissue-resident phagocytes.

Fifteen placentas were donated from 15 healthy women who had recently given birth at The Royal London Hospital. Researchers determined pollution exposure in 13 of the women, all of whom had exposure above the annual mean World Health Organization’s limit for particulate matter. The placental cells were examined using a variety of techniques, including light, electron microscopy, magnetic analyses and energy dispersive X-ray spectroscopy.

Researchers found black particles that closely resembled air pollution-derived PM in an average of 1% of cells in all 15 placentas.

Although most of the particles were carbon-based, they also found trace amounts of metals associated with vehicle-emitted air pollution from fossil fuel combustion and brake wear, such as phosphorus, calcium, iron and chromium, titanium, zinc and cerium.

These findings are important for all expecting mothers and ob/gyns, especially in urban communities around the world.

Panel discussion: Impacts of climate change on women's health

In this panel discussion, Senior Editor Angie DeRosa sat down Drs. Bekkar, DeNicola, Pandipati and Abel to discuss findings from a recent study on the association with air pollution and heat exposure with adverse obstetrical outcomes, such as preterm birth and stillbirth.

“Association of Air Pollution and Heat Exposure with Preterm Birth, Low Birth Weight, and Stillbirth in the U.S.: A Systematic Review,

 about the role of climate change in obstetrics.

First evidence that air pollution particles and metals are reaching the placenta. News release. Queen Mary University of London. EurekaAlert! September 23, 2020. Accessed October 22, 2020. 

https://www.eurekalert.org/pub_releases/2020-09/qmuo-fet092320.php

Liu N, Miyashita L, Maher B, McPhail G, et al. Evidence for the presence of air pollution nanoparticles in placental tissue cells. Sci Total Environ. Published online September 12, 2020. 

https://www.sciencedirect.com/science/article/abs/pii/S0048969720357648

New research suggests that air pollutant particles and metals are reaching the placenta. 

Evidence suggests environmental pollutants cross placenta

Data on COVID-19 during pregnancy, as reported by the CDC, in collaboration with state, local, and territorial health departments and external partners.

The data below is a reflection of data collected weekly by the Centers for Disease Control and Prevention (CDC). The cases reported are only confirmed cases with laboratory evidence of SARS-CoV-2 infection.

Here’s the latest data, updated on October 23:

Pregnant women with COVID-19, United States

Data is updated weekly based on data collected by the Centers for Disease Control and Prevention (CDC). The cases reported are only confirmed cases with laboratory evidence of SARS-CoV-2 infection. CDC’s case numbers are validated through a confirmation process with each jurisdiction.

Currently, there are 56 U.S.-affiliated jurisdictions reporting cases of COVID-19, including 50 states, District of Columbia, Guam, New York City, the Northern Marina Islands, Puerto Rico, and the U.S. Virgin Islands.

 and additional information from the CDC’s 

Data on COVID-19 during pregnancy, as reported by the CDC, in collaboration with state, local, and territorial health departments and external partners.



COVID-19 Pregnancy Data in the United States: October 23 Update

The impact of extended newborn screening programs on inherited metabolic diseases

The Womxn's Health Collaborative with Dr. Michal Elovitz

October is Pregnancy and Infant Loss Awareness Month

Infectious complications after massive blood loss from gynecologic laparotomy

It was a very busy week for the Contemporary OB/GYN team. 

What you missed this week on Contemporary OB/GYN 

investigated the association between epidural analgesia for vaginal delivery and the risk of autism spectrum disorders in children.

The retrospective longitudinal birth cohort study collected data from electronic medical records from a population-based clinical birth cohort. In total, 147,895 singleton children were delivered vaginally between January 1, 2008, and December 31, 2015, in a single integrated health care system.

Researchers followed up with the children from age of 1 year until the first date of the following occurrences: clinical diagnosis of an autism spectrum disorder; last data of health plan enrollment; death; or the study end date on December 31, 2018.

Among the cohort of 147,895 children (74,425 boys [50.3%]; mean [SD] gestational age at delivery, 38.9 [1.5] weeks, 74.2% were exposed to maternal LEA (109,719). Researchers observed fever during labor in 11.9% of mothers in the LEA group and 510 of 38,176 mothers (1.3%) in the non-LEA group.

Researchers found autism spectrum disorders in 1.9% of children (2,039) in the LEA group and 1.3% (485) in the non-LEA group. After adjusting for several factors, such as birth year, medical center, maternal age at delivery, parity, race/ethnicity, educational level, household income, history of comorbidity, diabetes during pregnancy, smoking during pregnancy, preeclampsia or eclampsia, prepregnancy body mass index, gestational weight gain, gestational age at delivery, and birth weight, the HR associated with LEA vs non-LEA exposure was 1.37 (95% CI, 1.23-1.53).

The study suggests that maternal LEA may be associated with increased risk of autism spectrum disorder risk in children. The authors note, however, that this does not appear to be directly associated with epidural-related maternal fever.

This article was originally published on 

Qiu C, Lin J, Shi J, et al. Association between epidural analgesia during labor and risk of autism spectrum disorders in offspring. 

. October 12, 2020. Epub ahead of print. doi:10.1001/jamapediatrics.2020.3231

Although the safety of labor epidural analgesia (LEA) for neonates is well-documented, the long-term health effects on offspring are not. 

Epidurals during delivery may increase autism risk

The investigators ran that initiative within the context of a multicenter learning collaborative that was focused on reducing the unnecessary use of antibiotics. 

The strategies for improvement addressed the gaps seen in the core elements of antibiotic stewardship programs. Outcomes measured included the antibiotic use rate and the percentage of infants who were discharged without any exposure to antibiotics.

At the baseline of the quality initiative, the antibiotic use rate was 27.6% and it decreased to 15.5%, which was a 43% reduction in antibiotic use. The reduction was additionally maintained for >18 months. 

The investigators said that changes that had the biggest effect on this decrease included a 36-hour hard stop for antibiotics, a novel guideline for early-onset sepsis evaluation among infants <35 weeks, implementing a sepsis risk calculator, and adopting a 36-hour rule-out period for sepsis evaluation. 

During the quality initiative, the percent of infants who were discharged from the hospital without any exposure to antibiotics increased from 15.8% to 35.1%. 

Additionally, the perfect of infants ≥ 36 weeks who underwent an evaluation for early-onset sepsis decreased by 42.3% and among infants < 35 weeks, it went down by 26%.

The researchers involved in the quality initiative concluded that it had led to a significant reduction in both antibiotic use and exposure in their neonatal intensive care unit. 

They also believe that the comprehensive approach to the quality initiative could be useful to other teams that have a focus on improvement.

Over the past decade, efforts to reduce unnecessary antibiotic use in the neonatal intensive care unit (NICU) have increased. A new report delivered results of a comprehensive quality improvement run in a level 4 NICU with the goal of decreasing antibiotic use by 20%

Reducing antibiotic exposure in the NICU

The WHC is a response to the recent creation of a pregnancy think tank and years of fighting for equality.

The Womxn's Health Collaborative with Dr. Michal Elovitz 

 and get additional information about the WHC 

Podcasts

Senior Editor Angie DeRosa interviews Dr. Michal Elovitz, executive director of the recently formed Womxn’s Health Collaborative (WHC), a group whose mission is to empower women from diverse backgrounds to succeed and become leaders in science and health in the field of women’s health.

S2E5: The Womxn's Health Collaborative with Dr. Michal Elovitz

"Vaginal Dilators 101: Basic suggestions for the health care professional,"

 which will be published in the November issue of 

Poll

This week's poll focuses on vaginal dilation for treatment of various sexual concerns. 

Do you recommend vaginal dilation to patients?

Most fetal anomalies are not determined prenatally. Fluid buildup in fetuses, known as nonimmune Hydrops fetalis (NIHF), is no exception and can often be lethal. 

used exome sequencing to analyze 127 fetuses with unexplained cases of NIHF and identified a gene variant in approximately one-third of the cases.

Researchers evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of the following conditions: fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions.

In 29% of the cases (37), researchers identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnosis); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others.

Overall, 68% of cases (25 of 37) with diagnostic variants were autosomal dominant, of which 12% were inherited and 88% were de novo. Ten of 37 (27%) were autosomal recessive, of which 95% were inherited and 5% were de novo. One was inherited X-linked recessive, and 1 was of uncertain inheritance.

Additionally, researchers identified potentially diagnostic variants in 12 additional cases.

Ob/gyns know that NIHF is often fatal and has several genetic causes. Exome sequencing is a rapid DNA sequencing technique that may be used to provide more in-depth information than current genetic testing methods.

The researchers were funded by the National Institutes of Health (NIH). Lead investigator Teresa Sparks, MD, of the University of California, San Francisco, is supported by a Women’s Reproductive Health Research grant from NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. Additional support was provided by the National Human Genome Research Institute.

Sparks T, Lianoglou B, Adami R, et al. Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. 

. Published online October 7, 2020. doi: 10.1056/NEJMoa2023643

Science Update: DNA sequencing technique helpful for identifying genetic causes of fetal fluid buildup, NIH-funded study suggests. News release. National Institute of Child Health and Human Development. October 9, 2020.

A new study in The New England Journal of Medicine used exome sequencing to analyze 127 fetuses with unexplained cases of nonimmune Hydrops fetalis.

Epidurals during delivery may increase autism risk

Reducing antibiotic exposure in the NICU

S2E5: The Womxn's Health Collaborative with Dr. Michal Elovitz

Do you recommend vaginal dilation to patients?

DNA sequencing technique may help prenatally detect NIHF