The November issue of Contemporary OB/GYN is one you do not want to miss.

Volume 65 No 11: The Technology Issue, November 2020

Operation Warp Speed (OWS) officials announced that about 40 million doses of 2 safe and highly effective vaccines for coronavirus disease 2019 (COVID-19) – made by Moderna and Pfizer – could be available for distribution by the end of December, pending FDA approval.

The distribution is enough to vaccinate about 20 million Americans at high risk for COVID-19, Department of Health and Human Services (HHS) Secretary Alex Azar, MD, said in a news briefing on Wednesday.

Both Pfizer and Modera have created messenger RNA (mRNA) vaccine candidates; Pfizers’ showed a 95% efficacy rate in a recent update, whereas Moderna reported meeting its primary end point of efficacy, with 94.5% .

The CDC has moved to facilitate rapid distribution of vaccine to each state, Gen. Gustave Perna, OWS chief operating officer, said in the briefing.

The CDC has collaborated with commercial industry to produce, store, distribute, and administer the vaccine. Perna mentioned McKesson, in addition to Pfizer and Moderna, as partners in distributing the vaccine.

Continue reading this article on Drug Topics.

Articles

Officials with Operation Warp Speed said that COVID-19 vaccine distribution will begin 24 hours after the Food and Drug Administration's (FDA) approval.

Officials expect to see 40 million COVID-19 vaccine doses distributed in December

 revealed that 84% of respondents made available at least one form of emergency contraception, only 18% offer oral ulipristal acetate 30 mg and 29% a copper IUD.

“This study gives us a good picture of ob/gyn practices regarding emergency contraception, in particular about the use of the copper IUD, and highlights areas for improvement,” said principal investigator Daniel Grossman, MD, a professor of ob/gyn and reproductive sciences at the University of California, San Francisco.

The survey targeted fellows and junior fellows of the American College of Obstetricians and Gynecologists (ACOG) between August 2016 and March 2017. The final sample was 1,280 respondents, for a 52.2% response rate.

In total, 80.4% of respondents reported offering patients levonorgestrel 1.5 mg, while 30.5% reported offering combined hormonal contraceptive pills specifically for emergency contraception.

Only 5.4% reported not offering any form of emergency contraception and 11.3% reported not seeing patients for emergency contraception or referring them elsewhere.

The three major reasons for not recommending a copper IUD for emergency contraception were that it was rare for a patient to come to the office seeking emergency contraception (52.4%), lack of patient interest and/or request (33.7%), and that the practice did not stock copper IUDs on site (27.8%).

Expense, inadequate insurance reimbursement, and concern that the IUD acts as an abortifacient were also cited as reasons not to recommend a copper IUD.

Among respondents who reported offering copper IUDs for emergency contraception, only 56.8% reported recommending it for emergency contraception in the past 12 months; 52.3% reported recommending it 10 times or less in the past year and 4.6% reported recommending it 11 times or more in the past year.

Moreover, only 30.3% of practitioners who offered copper IUDs for emergency contraception reported placing one in the prior 12 months, 22.7% reported placing a copper IUD once or twice in the past year, and 7.6% reported placing one three or more times in the past year.

“I was surprised that practices are still lagging behind the evidence that ulipristal acetate and the copper IUD are the two most effective forms of emergency contraception,” Grossman told 

. “I was also surprised that almost a third of ob/gyns still offer combined oral contraceptives for emergency contraception, which are no longer recommended by ACOG.”

The barriers to offering the copper IUD for emergency contraception include the patient lacking information about the option and the physician not stocking the IUD on site. “The former could be addressed by patient education, while the latter could be addressed by training,” Grossman said.

Long-Acting Reversible Contraception (LARC) Program Help Desk

 to assist with both clinical and billing/reimbursement questions.

Grossman said ob/gyns should educate their patients about all of the options for emergency contraception and address the barriers in their practices and communities to offering ulipristal acetate and the copper IUD. “For example, if few pharmacies stock ulipristal acetate, clinicians should consider prescribing the medication in advance because patients may face delays in filling the prescription,” he said. “That way, they will have the medication on hand, if and when they need it.”

Even though levonorgestrel emergency contraception is available over the counter, “ob/gyns and other women’s health clinicians play an important role in ensuring access to the most effective emergency contraception methods, as well as providing ongoing contraception to those who want it,” Grossman said.

Dr. Grossman reports no relevant financial disclosures.

Castleberry NM, Stark L, Schulkin J, et al. Oral and IUD emergency contraception provision among a national sample of obstetrician-gynecologists. Contraception. Published online September 6, 2020. doi:10.1016/j.contraception.2020.08.013

Less than half of ob/gyns offer their patients the two most effective forms of emergency contraception -- ulipristal acetate and the copper intrauterine device (IUD) -- according to a national survey.

Oral and IUD emergency contraception provision

Journal of Comparative Effectiveness Research

 also found that the risk of prolonged opioid use was significantly greater if comorbidities existed before diagnosis.

Senior author Georgine Lamvu, MN, MPH, a professor of ob/gyn at the University of Central Florida College of Medicine in Orlando, was prompted to undertake the analysis after a colleague remarked to her that he did not believe that women with endometriosis used opioids.

“In my practice, I had seen many women with endometriosis who reported using opioids, so I was curious to find out the actual numbers,” Lamvu told 

Medical and pharmacy claims information on 79,947 women with endometriosis from July 2015 to June 2018 were analyzed from the Symphony Health database.

The date of the first endometriosis diagnosis was deemed the index date and the 1-year period preceding the index data was considered the baseline period.

Women were aged 18 to 49 at the index date and had continuous pharmacy and medical enrollment for at least 1 year before and after their endometriosis diagnosis; in other words, at least one pharmacy claim every 3 months during the study period.

Women with endometriosis who used opioids at baseline were 61% more likely to receive opioids post-diagnosis.

The risk of prolonged opioid supply post-diagnosis was highest among women with a prolonged supply at baseline: relative risk (RR) 21.14, which significantly decreased to 1.32 for patients without a prolonged supply but with at least one comorbidity, 1.37 for pain comorbidities and 1.07 for psychiatric co-morbidities.

“I was surprised to find out how many women with endometriosis actually used opioids beyond 90 days,” Lamvu said. “All the other findings were expected.”

There is limited evidence to indicate that long-term opioid therapy is effective in treating other chronic pain conditions and no research to validate that opioids are efficacious for endometriosis-related pain.

“Nonetheless, the risk of opioid-related adverse events correlates with the dose and duration of opioid use,” Lamvu said. “This can lead to opioid-induced hyperalgesia, which counterproductively amplifies pain.”

In addition, high daily doses and prolonged use of opioids for chronic non-cancer pain can increase the risk of opioid abuse. More definitive is that comorbid psychiatric disorders in patients with chronic pain conditions like low back pain are linked to opioid misuse.

“The high prevalence of psychiatric comorbidities in patients with endometriosis suggests that this population may be vulnerable to opioid misuse,” Lamvu said.

Optimal endometriosis treatment should encompass a patient-centric strategy, according to Lamvu, integrating pharmacologic and surgical options to manage symptoms, in conjunction with therapies to improve health-related quality of life.

“Multi-disciplinary care with adequate management of comorbidities could optimize endometriosis treatment and reduce inappropriate or excessive treatment with opioids,” Lamvu said.

The analysis identifies a group of women who need specific counseling on the risks of long-term opioid use. “However, because we have no research that shows that opioids are effective for endometriosis-related pain, we need more research on this topic,” Lamvu said. “Also, because many women with endometriosis have surgery, post-op opioid use needs to be discussed with caution.”

Lamvu has served as a research consultant for AbbVie.

Lamvu G, Soliman A, Johns B, et al. Impact of pain and nonpain co-morbidities on opioid use in women with endometriosis. J Comp Eff Res. Published online November 3, 2020. doi:10.2217/cer-2020-0181

The risk of opioid use after endometriosis diagnosis is significantly greater in patients who used opioids before diagnosis, according to a retrospective analysis of data from a large health database.

Impact of opioids in women with endometriosis

a BELS-certified medical writer and editor, and an editorial consultant for 

A retrospective study by researchers from Cedars-Sinai Medical Center in Los Angeles of the impact of COVID-19-driven changes in Labor and Delivery (L&D) protocols shows that shortening lengths of stay (LOS) was safe for both mothers and their babies. The results reflect experience with both vaginal and cesarean deliveries early in the pandemic, in comparison with similar periods in 2018 and 2019.

Beginning in March 2020, in response to COVID-19, Cedars-Sinai modified its L&D practices to reduce risk of infection to patients and staff. Among the measures instituted were:

Permitting no visitors during the hospital stay for mothers admitted with or suspected to have COVID-19;

Allowing COVID-19-negative mothers to have only one support person during delivery and no visitors postpartum (after April 20, 2020, a single support person was allowed postpartum for COVID-19-negative mothers);

Advising COVID-19-positive mothers or those undergoing testing for it to be temporarily separated from their newborns after delivery; and

Recommending protective measures, such as isolette care in the room and gloving and masking during handling of the newborn, to COVID-19-positive mothers or those undergoing testing who did not want to be temporarily separated from their newborns after delivery.

During the period of study—January 1, 2020 to April 30, 2020—1,936 deliveries occurred: 1,016 before the changes were made and 920 after. Only two COVID-19 laboratory test-positive cases occurred during the study period, both of which were removed from the LOS analysis.

Postpartum LOS was significantly shorter after implementation of the COVID-19-driven measures. Of the patients treated post-implementation, 48.5% had a one-night stay after vaginal delivery, versus 24.9% in the preimplementation group (

 < .0001). Among those who delivered by cesarean, 40.9% had an LOS of two nights or less postimplementation, versus 11.8% preimplementation (

Reviewing newborn care, the authors found that 49.0% delivered vaginally were discharged home after one night in the post-implementation group versus 24.9% in the preimplementation group (

 < .0001). A similar trend was seen in association with cesarean delivery: 42.5% discharge rate after two nights or less in the post-implementation group vs 12.5% in the preimplementation group (

There were no differences in cesarean delivery rate, induction of labor, or adverse maternal or neonatal outcomes between the two groups. Adjustment for month-to-month variation in length of postpartum hospitalization for mothers and newborns showed no significant differences in neonatal or maternal LOS between January to February and March to April in 2018 and 2019, regardless of mode of delivery.

The American Journal of Obstetrics & Gynecology Maternal-Fetal Medicine

, the authors said that “the reasons for this reduction in postpartum length of stay are likely multifactorial but may be attributed partially to changes to our visitor policy…It is likely that the initial restrictions may have motivated patients and providers toward an earlier discharge.”

The researchers said their study “suggests that it is reassuring that these early discharges were not associated with an increased rate of readmissions or postpartum medical complications,” noting that “future studies are needed to determine what long-term effects the shorter stay might have on other outcomes such as maternal health, bonding, and ongoing breastfeeding.”

Greene NH, Kilpatrick SJ, Wong MS, et al. Impact of labor and delivery unit policy modifications on maternal and neonatal outcomes during the coronavirus disease 2019 pandemic.

The results of this retrospective study reflect experience with both vaginal and cesarean deliveries early in the pandemic, in comparison with similar periods in 2018 and 2019.

L&D discharge profiles in the wake of COVID-19

The study also found limited evidence of tumor shrinkage and disease stabilization in some patients.

The ARTISTRY-1 trial is sponsored by Alkermes plc (Dublin, Ireland), maker of the cytokine ALKS 4230, which is administered intravenously as monotherapy and in combination with pembrolizumab.

“There is a large unmet need in the gynecological cancer space, especially for platinum-resistant ovarian cancer,” said principal investigator Ira Winer, MD, PhD, an associate professor of gynecologic oncology at Wayne State University and Karmanos Cancer Institute in Detroit.

Winer, who presented study results in November at the 35th annual meeting of the Society for Immunotherapy of Cancer (SITC), said patients with platinum resistant and refractory ovarian cancer “typically do not do well. Newer agents and therapeutic avenues are desperately needed.”

Although checkpoint inhibitors are approved to treat several types of cancer, they have limited success for ovarian cancer to date, according to Winer. “There is only about a 10% to 15% response rate in patients suitable for prototypical immune-oncology (IO) therapy,” he said. “The goal is to improve these outcomes.”

The combination phase of ARTISTRY-1, which comprises a subgroup of 15 ovarian cancer patients, was initiated at Karmanos Cancer Institute roughly 2 years ago. Patients range in age from 48 to 83, with an average age of 74.

Prior to the study, these ovarian cancer patients had received a median of five regimens, ranging from two to 11, and all were previously treated with platinum-based therapy.

Then, during the study period, each patient participated in one or more 21-day therapy cycles, with median treatment duration of roughly 7 weeks.

Each cycle consisted of ALKS 4230 (3 µg/kg) on days 1 through 5 and pembrolizumab (200 mg) on day 1 only.

Changes in tumor microenvironment (TME) were calculated using baseline and on-treatment biopsies.

Among 13 evaluable patients (at least one post-treatment assessment), 9 patients attained disease control or stable disease at first scan and the other 4 experienced disease progression.

Five patients experienced tumor shrinkage for more than 20 weeks, including 3 patients who experienced an objective response: 1 complete response (complete disappearance of cancer), 1 partial response and 1 unconfirmed partial response.

“All 3 of these patients were platinum resistant and negative for BRCA mutations,” Winer told Contemporary 

Unexpectedly, the patient with the complete response was heavily pretreated and has participated in the trial for well over 1 year. “Quality and quantity of life are important in patients with ovarian cancer, as with all disease, and this patient has seen both, despite being on such an intensive regimen,” Winer said.

He said for ovarian cancer, the study responses would be rare from checkpoint inhibitors alone. “In fact, a single checkpoint inhibitor response would be anecdotal,” he said. “We might see one or two patients respond, but not multiple, as we have seen in this small cohort of patients.”

Treatment-related adverse events at the doses tested have generally been transient and manageable, according to Winer, with the majority being grade 1 or grade 2 severity. The cytokine did not show any additive toxicity to that already established with pembrolizumab alone.

“The way ALKS 4230 is designed helps modulate the immune environment and immune cells themselves to make the prototypical checkpoint inhibitor work better,” Winer said. “Our results are one of the reasons we are starting to develop a Phase 2 study. We want to ensure that what are we observing in this smaller group of patients will translate to a larger population.”

Winer reports no relevant financial disclosures.

Heavily pretreated ovarian cancer patients who received a combination therapy of a novel engineered interleukin-2 (IL-2) cytokine plus pembrolizumab achieved an acceptable safety profile, according to a small cohort of an ongoing phase 1/2 trial.

Novel engineered cytokine plus pembrolizumab to treat ovarian cancer

While pregnant patients with ILD have a higher risk of adverse outcomes, termination may not be needed if women are carefully monitored before, during, and after pregnancy. Megan E. B. Clowse, MD, MPH, associate professor of medicine, Division of Rheumatology and Immunology at Duke University and colleagues presented this research at the American College of Rheumatology’s November 2020 Convergence meeting.

Patients with ILD develop scarred lung tissue from inflammation that may result in difficulty breathing. The condition may accompany other autoimmune diseases such as lupus, sarcoidosis, and scleroderma. Avoiding or terminating pregnancy is often recommended to these patients due to limited data on adverse pregnancy outcomes for women with ILD.

To conduct the study, Clowse and colleagues used Duke University Health System medical records to study retrospective data on pregnant patients with ILD secondary to autoimmune disease from January 1996 to July 2019. The research team classified pregnancies according to ILD severity based on forced vital capacity and diffusion capacity for carbon monoxide, and set cut off values for mild, moderate, and severe lung disease. To date, this is the largest cohort ever studied to improve pregnancy recommendations for women with ILD.

Ninety-four pregnancies were examined among 67 women, with 5 being twin pregnancies. Eighty-three percent of women identified as Black, and the average maternal age was 32.1. Clowse and colleagues defined adverse outcomes that included neonatal death, fetal death, small for gestational age, preterm delivery, and preeclampsia, according to the PROMISSE-APO and PROMISSE-APO SEVERE standard scores.

Sarcoidosis was diagnosed in 69% of pregnant patients, while 31% had an ILD- associated connective tissue disease. Eleven percent of pregnant patients were classified as having severe ILD, 25% moderate, 50% mild, and 14% normal. The severe ILD group only consisted of pregnant patients with ILD-associated connective tissue disease, while sarcoidosis was present in 89% of normal pregnancies. Seven pregnant patients had been taking mycophenolate during conception, which is documented as causing major birth defects and pregnancy loss.

The results of the study revealed 70% of pregnancies resulted in live birth, and none of the women died. ICU care only was required for 2.1% of patients during or immediately following delivery. Ten percent of pregnancies were terminated, and 15% of pregnant patients were diagnosed with pre-eclampsia.

The study found that pregnant patients with severe ILD had more adverse outcomes. Increased fluid volume in the lungs around the time of delivery resulted in 4.2% of patients with ILD to experience significant shortness of breath, and one patient developed heart failure postpartum. One patient required intubation for asthma during mid-pregnancy, while 8 pregnancies required oxygen delivered to the patient during delivery.

that the most significant aspect of the study is the change in pregnancy recommendations for pregnant patients with autoimmune-related ILD. “Historically, we have been nervous about women with chronic lung disease and pregnancy, but the data from this study demonstrates that these pregnancies went remarkably well. There are certainly risks, but our patients do better than previously anticipated. These patients really can have healthy pregnancies if we work with them.”

She added that treatments for patients with lupus, sarcoidosis, and a range of other rheumatological diseases are different. “Many of the study patients with sarcoidosis were not taking immunosuppressant medication during pregnancies, but patients with rheumatic disease like lupus continued their anti-rheumatic medications throughout pregnancy to control their diseases. There are multiple safe medications available to treat lupus and ILD during pregnancy, so patients do not need to stop their medicine,” she said. She also noted that an updated guideline publication is available from the 

“It is important that we come up with a good plan for these patients that involves careful monitoring,” Clowse told 

. “We also still need more data in the form of larger, prospective, multicentered studies that can tell us how these patients do in pregnancy and how we can manage them best.”

Safe pregnancy is possible for women with interstitial lung disease. November 2020. 

https://www.eurekalert.org/pub_releases/2020-11/acor-spi110520.php

Pregnant women with autoimmune-related interstitial lung disease (ILD) can have safe pregnancy outcomes if closely monitored by a multidisciplinary team of physicians.

Women with interstitial lung disease can have safe pregnancies

The guideline, which was formulated by an American Association of Gynecologic Laparoscopists (AAGL) Task Force of U.S. and Canadian gynecologic surgeons, incorporates the five canonical components of every ERAS protocol: preoperative patient education and optimization; multimodal, narcotic-sparing analgesia; nausea, surgical site infection (SSI) and venous thromboembolism (VTE) prophylaxis; maintenance of euvolemia; and liberalization of activity.

When it comes to improving quality and outcomes, it is not enough to ‘simply do a good job in the operating room,’ said senior author Rebecca Stone, MD, an associate professor of gynecologic oncology at Johns Hopkins School of Medicine.

At the 2018 annual AAGL meeting, only a third of attendees surveyed at the inaugural Enhanced Recovery After MIS Surgery (ERAmiS) Panel Session reported using a formal ERAS pathway for perioperative management of patients undergoing minimally invasive endoscopic and vaginal surgery, according to Stone. “This was attributed in part to the lack of formalized ERAS guidelines dedicated to MIGS,” she told 

Several guideline recommendations may be new to clinicians, including a “pathway to surgery” that minimizes missed opportunities to treat the most relevant and common medical comorbidities, such as obstructive sleep apnea, anemia, and diabetes. “The goal is to ensure that the patient is as well prepared as possible, in order to maximize their resilience to the physiological stress of surgery,” Stone said. “The surgeon and patient should partner in tackling risks related to functional status, chronic health and acute physiological deterioration.”

Gabapentinoids (pregabalin and gabapentin) have long been part of enhanced recovery multimodal, narcotic-sparing medication bundles. “However, recent FDA warnings about respiratory depression from gabapentinoids, with particular increased risk in narcotic-naïve older patients and/or those with obstructive sleep apnea, led us to recommend against their routine use in the prevention/treatment of surgical pain,” Stone said.

Intravenous first-generation cephalosporins, most commonly cefazolin, are the preferred prophylactic antibiotics for hysterectomy. “But emerging data indicate that SSI rates are higher when beta-lactam alternatives like clindamycin plus gentamycin are used, so their use should be restricted to those patients with a history of bonafide immunoglobulin E (IgE)-mediated penicillin hypersensitivity reactions, including urticaria, not just rash; angioedema; and anaphylaxis,” Stone said.

Conversion to chlorhexidine gluconate (CHG) for perioperative vaginal preparation also is recommended.

“There is a lot of controversy over the need for extended VTE prophylaxis following MIGS for cancer,” Stone said. “This has resulted in huge practice variation in the prescribing of extended thromboprophylaxis for MIGS, which is inconsistent with the overall ERAS mission of evidence-based care standardization.”

The new guideline modifies the historic Caprini scoring system for VTE risk assessment and prescribing of extended thromboprophylaxis, based on clinical risk factors like cancer stage, grade and extent of lymphadenectomy that now align with the VTE incidence observed during the past 10 years of MIGS in over 10,000 women with gynecologic cancer.

“In general, the guideline provides a real opportunity for us to intensify the known benefits of MIGS, including decreased pain, complications and recovery time,” Stone said. “Another advantage of protocolized perioperative care is reducing clinically inappropriate variability in care. This is important for cost containment and eradicating health inequalities.”

Moreover, the guideline facilitates shared care, encourages multidisciplinary communication and action in general, which is especially critical during the COVID-19 pandemic.

Stone reports no relevant financial disclosures.

Stone R, Carey E, Fader A, et al. Enhanced recovery and surgical optimization protocol for minimally invasive gynecologic surgery: an AAGL white paper. JMIG. Published online August 19, 2020. doi:org/10.1016/j.jmig.2020.08.006.

The first Enhanced Recovery After Surgery (ERAS) guideline for standardizing and optimizing perioperative care for women undergoing minimally invasive gynecologic surgery (MIGS) has been published in The Journal of Minimally Invasive Gynecology.

First enhanced recovery after surgery guideline for minimally invasive gynecologic surgery

You can expect a variety of topics to be covered this week on 

Although peer surgical coaching bolsters surgical education and promotes continuous professional development throughout a surgeon’s career, the reality is that few surgeons apply coaching theory or operationalize the concept of coaching.

What to look for this week on Contemporary OB/GYN

This week on Contemporary OB/GYN: November 23 to November 27

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 November 19:

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.

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: November 19 Update

View the slideshow from our sister publication, 

From vitamin D to calcium supplements and beta-blockers for bone loss density prevention, this slideshow from Rheumatology Network breaks it all down.

Volume 65 No 11: The Technology Issue, November 2020

Women with interstitial lung disease can have safe pregnancies

First enhanced recovery after surgery guideline for minimally invasive gynecologic surgery

This week on Contemporary OB/GYN: November 23 to November 27

COVID-19 Pregnancy Data in the United States: November 19 Update

Key women’s health and osteoporosis studies you should know about