Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

Appendectomy in the surgical management of women with endometriosis and pelvic pain.

OBJECTIVE: To evaluate the role of appendectomy in surgical excision of endometriosis and to assess complications associated with appendectomy. METHODS: Retrospective study of women undergoing appendectomy for pelvic pain and/or endometriosis during a primary gynecologic procedure. RESULTS: Record review was performed for 609 women who underwent appendectomy between 2013 and 2019 for pelvic pain (6.9%, 42/609), stage I-II endometriosis (63.7%, 388/609), or stage III-IV endometriosis (29.4%, 179/609). Appendiceal endometriosis (AppE) was present in 14.9% (91/609); 2.4% without endometriosis (1/42, reference group), 7.0% with stage I-II endometriosis (27/388, odds ratio [OR] 3.06, 95% confidence interval [CI] 0.41-23.11, P = 0.278), and 35.2% with stage III-IV endometriosis (63/179, OR 22.24, 95% CI 2.99-165.40, P = 0.002). AppE was significantly associated with endometriosis present in other locations (OR 5.27, 95% CI 2.66-10.43, P < 0.001). The predicted probability of identifying AppE ranged from 6% with 0 positive endometriosis sites to 56% when 4 or more sites were identified. There were no complications related to the performance of an appendectomy. CONCLUSION: Women with chronic pelvic pain and/or endometriosis have an increased risk of AppE. Modern appendectomy at the time of gynecologic surgery is safe, with no associated complications in this study. Our findings support the consideration of appendectomy as part of the comprehensive surgical management of endometriosis.

An updated guide to the diagnosis and management of cesarean scar pregnancies.

PURPOSE OF REVIEW: To review the current literature on the diagnosis and management of cesarean scar pregnancies RECENT FINDINGS: The incidence of cesarean scar pregnancies (CSPs) is increasing as a result of the increasing cesarean section rate, improved diagnostic capabilities, and a growing awareness. CSPs are associated with significant morbidity and early diagnosis is key. Diagnosis is best achieved with transvaginal ultrasound. Sonographic diagnostic criteria have been developed over decades and recently endorsed by the Society for Maternal-Fetal Medicine and other professional societies. The current categorization system differentiates CSPs that are endogenic or 'on the scar' from those that are exogenic or 'in the niche'. Following diagnosis, the challenge remains in determining the optimal management as multiple modalities can be considered. Studies have demonstrated the favorable outcomes with combined local and systemic methotrexate, surgical excision through multiple routes, and adjunctive therapies, such as uterine artery embolization or uterine balloons. The current evidence is insufficient to identify a single best treatment course and a combined approach to treatment is often required. SUMMARY: Successful outcomes while minimizing complications can be achieved with a multidisciplinary, collaborative effort. Guidelines for cesarean scar pregnancies will continue to evolve as the published reports grow.

Surgical Excision Versus Ablation for Superficial Endometriosis-Associated Pain: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare surgical excision and ablation of endometriosis for treatment of chronic pelvic pain. DESIGN: Randomized clinical trial with 12-month follow-up (Canadian Task Force classification I). SETTING: Single academic tertiary care hospital. PATIENTS: Women with minimal to mild endometriosis undergoing laparoscopy. INTERVENTIONS: Excision or ablation of superficial endometriosis at the time of robot-assisted laparoscopy. MEASUREMENTS AND MAIN RESULTS: Primary outcome was visual analog scale (VAS) scoring at baseline and 6 and 12 months for menstrual pain, nonmenstrual pain, dyspareunia, and dyschezia. Secondary outcomes included survey results at baseline and 6 and 12 months from the Short Form Health Survey, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and the International Pelvic Pain Assessment. From December 2013 to October 2014, 73 patients were randomized intraoperatively to excision (n = 37) or ablation (n = 36) of endometriosis. Patients were followed at 6 and 12 months to evaluate the above outcomes. After ablation of endometriosis, dyspareunia (VAS scores) improved at 6 months (mean change [MC], -14.07; 95% confidence interval [CI], -25.93 to -2.21; p = .02), but improvement was not maintained at 12 months. Dysmenorrhea improved at 6 months (MC, -26.99; 95% CI, -41.48 to -12.50; p < .001) and 12 months (MC, -24.15; 95% CI, 39.62 to -8.68; p = .003) with ablation. No significant changes were seen in VAS scores after excision at 6 or 12 months. When comparing ablation and excision, the only significant difference was a change in dyspareunia at 6 months (MC, -22.96; 95% CI, -39.06 to -6.86; p = .01). CONCLUSION: Treatment with ablation improved dysmenorrhea at 6 and 12 months and improved dyspareunia at 6 months as compared with preoperative data. However, only dyspareunia demonstrated a significant difference between ablation and excision. Excision and ablation showed similar effectiveness for the treatment of pain associated with superficial endometriosis, with ablation showing more significant individual changes. Careful patient counseling regarding expectations of surgical intervention is vital in the management of endometriosis.

Opioids and Alternatives in Female Chronic Pelvic Pain.

Chronic pelvic pain is a complex condition with peripheral and central mechanisms of pain. Successful nonsurgical management typically relies on a multimodal approach, with integration of both pharmacologic and nonpharmacologic interventions. This article reviews nonpharmacologic therapies including pelvic floor physical therapy, dietary modifications, psychotherapy, and acupuncture. These interventions are low risk and should be incorporated into treatment for chronic pelvic pain, as they show promise for successful symptom relief in many overlapping chronic pain conditions. Common nonopioid medications for pelvic are also reviewed, including analgesics, hormone modulating agents, antidepressants, and anticonvulsants. Guidelines for cautious and responsible opioid use are also summarized. While data specific to chronic pelvic pain management remain limited, evidence supporting treatment of other chronic pain conditions is reviewed to help guide management.

Physical Well-Being and Route of Benign Hysterectomy.

OBJECTIVES: We sought to determine if there is an association between preoperative risk factors as defined by the American Society of Anesthesiologists (ASA) physical status score and the route of hysterectomy for benign indications. METHODS: In this retrospective cohort study, the American College of Surgeons National Surgical Quality Improvement Project database was used to determine the route of hysterectomy, using Current Procedural Terminology codes, and associated ASA class. The analysis included abdominal, vaginal, total laparoscopic, and laparoscopic assisted vaginal routes of hysterectomy. Routes of hysterectomy were also grouped as either abdominal or minimally invasive for analysis. Multinomial logistic regression was used to model route of hysterectomy as a function of patient covariates, including ASA class, age, race and ethnicity, and body mass index. RESULTS: The analysis included 117,919 patients from the National Surgical Quality Improvement Project database. Patients with ASA classification of III or IV to V had significantly decreased odds of undergoing a minimally invasive approach for hysterectomy (odds ratio [OR], 0.81 [95% confidence interval (CI)], 0.77-0.85; and OR, 0.42 [95% CI, 0.37-0.48], respectively). Secondary outcome analysis revealed that a body mass index of more than 30 kg/m2 was associated with significantly lower odds of undergoing a minimally invasive hysterectomy (OR, 0.87; 95% CI, 0.85-0.89). With respect to race/ethnicity, all non-White groups had decreased odds of undergoing a hysterectomy via a minimally invasive approach. Age 75 years or older was correlated with an increased likelihood of minimally invasive hysterectomy (OR, 1.18; 95% CI, 1.10-1.26). CONCLUSIONS: Patients with increased preoperative risk as defined by a high ASA classification are less likely to undergo a hysterectomy using a minimally invasive route for benign indications.

The Impact of Pregnancy on the Evaluation of Chest Pain and Shortness of Breath in the Emergency Department.

BACKGROUND: Pregnant patients are at an increased risk for severe morbidity and mortality when compared to the general population. Imaging studies have become an integral part of the work-up for patients who present to the emergency department. However, lack of clear guideline has led to confusion regarding the appropriate indications and protocols for examining pregnant patients. OBJECTIVE: To investigate the comparative rates of imaging studies between pregnant and non-pregnant female patients who presented for emergent evaluation of chest pain and shortness of breath. STUDY DESIGN: All reproductive age females presenting to the emergency department at an academic teaching institution with a chief complaint of "chest pain" or "shortness of breath" from 2010 to 2015 were identifi ed. Cohorts were divided based on pregnancy status and chief complaint. Utilization rates of imaging studies were compared between cohorts. RESULTS: Over the study period 4,834 women were included. One hundred and seventy-four were pregnant. Pregnant patients with "chest pain" or "shortness of breath" were signifi cantly more likely to undergo a venous duplex, but less likely to undergo a chest X-ray as compared to non-pregnant patients. There was no difference in the rates of chest computed tomography (CT) imaging or magnetic resonance imaging (MRI) based on pregnancy status in our data set. CONCLUSION: Imaging studies are an integral adjunct for evaluation in patients reporting "chest pain" and "shortness of breath." Pregnancy places patients at an increased risk of severe sequelae requiring prompt diagnosis to prevent harm to the mother and fetus. American College of Obstetrics and Gynecology (ACOG) Committee Opinion 656 clearly states that, with few exceptions, radiography should not be withheld from pregnant patients. This study suggests that pregnant patients are signifi cantly less likely to undergo radiography, which could place them at increased risk for delayed diagnosis and treatment.

The impact of pregnancy on headache evaluation in the emergency department, a retrospective cohort study.

BACKGROUND: Headache is one of the most common emergency department complaints with three million visits annually in the USA. This is further complicated with 30% of those emergency visits being for a hypertensive disorder of pregnancy. There is no currently well-established guideline for diagnostic imaging with a common concern being ionizing radiation exposure in pregnancy. The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. OBJECTIVE: The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. STUDY DESIGN: This retrospective cohort study identified all reproductive age female patients who presented to the emergency department with a chief complaint of "headache." They were then divided into cohorts based on pregnancy status. Rates and types of imaging studies utilized in patient evaluation were then compared. RESULTS: Two thousand seven hundred ninety patients met our criteria for evaluation; 95 were found to be pregnant. Head CTs were ordered significantly less and MRIs were ordered significantly more in the pregnant cohort as compared to the non-pregnant cohort with a P value of <0.0001 and an odds ratio of 4.21 and a P value of 0.0127 and an odds ratio of 0.49, respectively. CONCLUSION: Our data shows a difference in evaluation for pregnant patients as compared to their non-pregnant cohort. CT should not be considered contraindicated in the pregnant population and the amount of ionizing radiation to the fetus is well within the maximum safe dose, particularly with appropriate shielding. The time difference, cost, fetal exposure risk, and availability of CT compared to MRI should be taken into account when establishing a criterion for diagnostic evaluation. This difference validates the need for further research into a well-established guideline for the emergent evaluation of headache in the ED without special bias placed on pregnancy status.

Randomized controlled trial comparing operative times between standard and robot-assisted laparoscopic hysterectomy.

OBJECTIVE: To compare the operative time between robot-assisted laparoscopic hysterectomies and standard laparoscopic hysterectomies. METHODS: A prospective, randomized controlled trial enrolled women aged 18-80 years attending Penn State Hershey Medical Center between April 23 and October 20, 2014 to undergo hysterectomy. Participants were randomized using a random number generator to undergo either robot-assisted or standard laparoscopic hysterectomy. The primary outcome was the total operative time (surgeon incision to surgeon stop, including robot docking time, if applicable). Intention-to-treat analyses were performed and the operative time was compared between the two treatments for non-inferiority, defined as a difference in operative time of no longer than 15 minutes. RESULTS: There were 72 patients randomized to each treatment arm. The mean operative time was 73.9 minutes (median 67.0 minutes; interquartile range 59.0-83.0 minutes) in the robot-assisted hysterectomy group and 74.9 minutes (median 65.5 minutes; interquartile range 57.0-90.5 minutes) in the standard laparoscopic hysterectomy group. The upper bound of the 95% confidence interval of the difference in operative time was 6.6 minutes, below the 15-minute measure of non-inferiority. CONCLUSION: When performed by a surgeon experienced in both techniques, the operative time for robot-assisted laparoscopic hysterectomy was non-inferior to that achieved with standard laparoscopic hysterectomy. CLINICALTRIALS.GOV: NCT02118974.

Combined hormonal contraception use in reproductive-age women with contraindications to estrogen use.

BACKGROUND: The Centers for Disease Control and Prevention's US Medical Eligibility Criteria for Contraceptive Use recommends that combined hormonal contraceptives (ie, birth control pills, contraceptive patch, vaginal ring) should be avoided in women with specific medical conditions because of the increased risk of cardiovascular events associated with estrogen use. Whether women with category 3 (theoretical or proven risk usually outweigh the advantages) or category 4 (unacceptable health risk) contraindications are appropriately avoiding estrogen-containing combined hormonal contraceptives is unknown. OBJECTIVE: We describe the prevalence of combined hormonal contraceptive use among a sample of reproductive-age women with medical contraindications to estrogen use. Our hypothesis was that women with categories 3 and 4 contraindications would use estrogen-containing contraception less often than women without medical contraindications. We also explored whether inappropriate estrogen-containing contraceptive use is related to contraceptive provider characteristics. STUDY DESIGN: Data are from the baseline survey of the MyNewOptions study, which included privately insured women residing in Pennsylvania aged 18-40 years, who were sexually active and not intending pregnancy in the next year. Women were surveyed about their medical conditions, contraceptive use, and characteristics of their contraceptive provider. Women were considered to have a contraindication to combined hormonal contraceptives if they reported a category 3 or category 4 contraindication: hypertension, smokers older than age 35 years, a history of venous thromboembolism, diabetes with complications, coronary artery disease, systemic lupus erythematosus with antiphospholipid antibodies, breast cancer, or migraine headaches with aura. χ(2) tests for general association were used to compare combined hormonal contraceptives use, contraceptive health provider characteristics, and sociodemographic data in women with and without contraindications to estrogen use. RESULTS: The MyNewOptions baseline study sample included 987 adult women who were mostly young (46% were 18-25 years), white (94%), employed (70%), and married or cohabiting (54%). Thirteen percent (n = 130) of the sample had a medical contraindication to estrogen-containing contraceptive use: migraine with aura (81%) was the most common contraindication, followed by smokers older than age 35 years (7%), hypertension (11%), history of venous thromboembolism (4%), and diabetes with complications (2%). High use of combined hormonal contraceptives was reported among the women with medical contraindications to estrogen at 39% (n = 51). This was not statistically different from women without a medical contraindication (47%, P = .1). Among the 130 women with a contraindication, whether they did or did not use an estrogen-containing contraceptive did not vary by education level, income, or weight category. With respect to their contraceptive prescribers, there were no differences in prescriber specialty, provider type, or clinic type comparing women using and not using an estrogen-containing contraceptive. CONCLUSION: Among this study sample of reproductive-age women, there was a high rate of combined hormonal contraceptive use in women with a medical contraindication to estrogen use. These women may be at an increased risk for cardiovascular events. Processes need to be improved to ensure that women with medical contraindications to estrogen-containing contraception are being offered the safest and most effective methods, including long-acting reversible contraceptives, such as intrauterine devices and the contraceptive implant.