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Item Role of progestogens in women at risk for spontaneous preterm birth: the final word?(Elsevier, 2021-03) Ibrahim, Sherrine A.; Haas, David M.; Obstetrics and Gynecology, School of MedicineItem Equity + Wellness: A Call for More Inclusive Physician Wellness Efforts(MedEdPublish, 2021) Sotto-Santiago, Sylk; Ansari-Winn, Dianne; Neal, Chemen; Ober, Michael; Obstetrics and Gynecology, School of MedicineThe challenges, importance, and state of physician wellness and burnout have been well documented throughout the literature.Research continues to prove the value of tools and interventions while institutions appear to be listening and adapting important practices. However, although the wellness literature encourages a review of organizational challenges, local needs, and individual solutions, organizations may fail to align these efforts along with equity, diversity, inclusion, and belonging (EDIB). A pandemic and recent events in our society heightened awareness about health inequities, structural violence and racism, and demand that we look within our institutions and health systems. It also demands that we speak of wellness and equity together. We cannot engage in conversations about wellness without asking about equity...because equity and inclusion lead to wellness. We simply cannot expect our healthcare workforce, faculty, and physicians of color to be "well" if they are experiencing exclusion and inequality. In this article, we present the concepts of inclusive excellence and leading with wellness in mind while calling for more inclusive physician wellness efforts.Item Progestogens for preventing miscarriage: a network meta-analysis(Wiley, 2021-04) Devall, Adam J.; Papadopoulou, Argyro; Podesek, Marcelina; Haas, David M.; Price, Malcolm J.; Coomarasamy, Arri; Gallos, Ioannis D.; Obstetrics and Gynecology, School of MedicineBACKGROUND: Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage). OBJECTIVES: To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile. SEARCH METHODS: We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens. AUTHORS' CONCLUSIONS: The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage.Item Obesity, Second Stage Duration, and Labor Outcomes in Nulliparous Women(Thieme, 2021-03) Frolova, Antonina I.; Raghuraman, Nandini; Stout, Molly J.; Tuuli, Methodius G.; Macones, George A.; Cahill, Alison G.; Obstetrics and Gynecology, School of MedicineObjective: This study aimed to estimate second stage duration and its effects on labor outcomes in obese versus nonobese nulliparous women. Study design: This was a secondary analysis of a cohort of nulliparous women who presented for labor at term and reached complete cervical dilation. Adjusted relative risks (aRR) were used to estimate the association between obesity and second stage characteristics, composite neonatal morbidity, and composite maternal morbidity. Effect modification of prolonged second stage on the association between obesity and morbidity was assessed by including an interaction term in the regression model. Results: Compared with nonobese, obese women were more likely to have a prolonged second stage (aRR: 1.48, 95% CI: 1.18-1.85 for ≥3 hours; aRR: 1.65, 95% CI: 1.18-2.30 for ≥4 hours). Obesity was associated with a higher rate of second stage cesarean (aRR: 1.78, 95% CI: 1.34-2.34) and cesarean delivery for fetal distress (aRR: 2.67, 95% CI: 1.18-3.58). Obesity was also associated with increased rates of neonatal (aRR: 1.38, 95% CI: 1.05-1.80), but not maternal morbidity (aRR: 1.06, 95% CI: 0.90-1.25). Neonatal morbidity risk was not modified by prolonged second stage. Conclusion: Obesity is associated with increased risk of neonatal morbidity, which is not modified by prolonged second stage of labor.Item Weight gain in early, mid, and late pregnancy and hypertensive disorders of pregnancy(Elsevier, 2020-04) Dude, Annie M.; Kominiarek, Michelle A.; Haas, David M.; Iams, Jay; Mercer, Brian M.; Parry, Samuel; Reddy, Uma M.; Saade, George; Silver, Robert M.; Simhan, Hyagriv; Wapner, Ronald; Wing, Deborah; Grobman, William; Obstetrics and Gynecology, School of MedicineObjective: To examine the relationship of weight change during early, mid, and late pregnancy with the development of a hypertensive disorder of pregnancy (HDP). Study design: These data are from a prospective cohort study of nulliparous women with live singleton pregnancies. "Early" weight change was defined as the difference between self-reported pre-pregnancy weight and weight at the first visit (between 6 and 13 weeks' gestation); "mid" weight change was defined as the weight change between the first and second visits (between 16 and 21 weeks' gestation); "late" weight change was defined as the weight change between the second and third visits (between 22 and 29 weeks' gestation). Weight change in each time period was further characterized as inadequate, adequate, or excessive based on the Institute of Medicine's (IOM's) trimester-specific weekly weight gain goals based on pre-pregnancy body mass index. Multivariable Poisson regression was performed to adjust for potential confounders. Main outcome measure: Development of any hypertensive disorder of pregnancy. Results: Of 8296 women, 1564 (18.9%) developed a HDP. Weight gain in excess of the IOM recommendations during the latter two time periods was significantly associated with HDP. Specifically, trimester-specific excessive weight gain in the mid period (aIRR 1.16, 95% CI 1.01-1.35) as well as in the late period (aIRR = 1.19, 95% CI = 1.02-1.40) was associated with increased risk of developing HDP. The weight gain preceded the onset of clinically apparent disease. Conclusions: Excessive weight gain as early as the early second trimester was associated with increased risks of development of HDP.Item Pten and Dicer1 loss in the mouse uterus causes poorly-differentiated endometrial adenocarcinoma(Springer Nature, 2020-10) Wang, Xiyin; Wendel, Jillian R. H.; Emerson, Robert E.; Broaddus, Russell R.; Creighton, Chad J.; Rusch, Douglas B.; Buechlein, Aaron; DeMayo, Francesco J.; Lydon, John P.; Hawkins, Shannon M.; Obstetrics and Gynecology, School of MedicineEndometrial cancer remains the most common gynecological malignancy in the United States. While the loss of the tumor suppressor, PTEN (phosphatase and tensin homolog), is well studied in endometrial cancer, recent studies suggest that DICER1, the endoribonuclease responsible for miRNA genesis, also plays a significant role in endometrial adenocarcinoma. Conditional uterine deletion of Dicer1 and Pten in mice resulted in poorly differentiated endometrial adenocarcinomas, which expressed Napsin A and HNF1B (hepatocyte nuclear factor 1 homeobox B), markers of clear-cell adenocarcinoma. Adenocarcinomas were hormone-independent. Treatment with progesterone did not mitigate poorly differentiated adenocarcinoma, nor did it affect adnexal metastasis. Transcriptomic analyses of DICER1 deleted uteri or Ishikawa cells revealed unique transcriptomic profiles and global miRNA downregulation. Computational integration of miRNA with mRNA targets revealed deregulated let-7 and miR-16 target genes, similar to published human DICER1-mutant endometrial cancers from TCGA (The Cancer Genome Atlas). Similar to human endometrial cancers, tumors exhibited dysregulation of ephrin-receptor signaling and transforming growth factor-beta signaling pathways. LIM kinase 2 (LIMK2), an essential molecule in p21 signal transduction, was significantly upregulated and represents a novel mechanism for hormone-independent pathogenesis of endometrial adenocarcinoma. This preclinical mouse model represents the first genetically engineered mouse model of poorly differentiated endometrial adenocarcinoma.Item To Flip or Not to Flip: Learning Style Preferences among Millennial Physician Assistant Students(Cureus Inc, 2021-02) Schultz, Katherine; Schaffer, Alicia; Rebman, Rebecca; Shanks, Anthony; Obstetrics and Gynecology, School of MedicineIntroduction: Presenting material in a manner that is most palatable to students is important to improve the learning process. We evaluated the efficacy of different teaching styles including the flipped classroom and assessed the learning style preferences of a cohort of medical learners in a preclinical obstetrics and gynecology course. Methods: We conducted three teaching sessions with 35 physician assistant students. A different teaching style was implemented for each session including a traditional lecture with interactive learning technology augmentation, a flipped classroom, and a hybrid approach incorporating lecture and group work. Students were surveyed using a Likert scale regarding the efficacy of the format, clinical relevance of the material, and their learning preference for future sessions. Results: Students rated the traditional approach as the most effective, most relevant, and most preferred method. Students preferred the flipped classroom least, but they rated it as slightly more effective and relevant than the hybrid approach. Conclusion: The teaching style of various coursework including the preclinical obstetrics and gynecology curriculum may not need to be altered for millennial learners. This study showed the flipped classroom was the least favored teaching style and that there was a marked preference by students for a more traditional didactic lecture.Item Effect of Prophylactic Negative Pressure Wound Therapy vs Standard Wound Dressing on Surgical-Site Infection in Obese Women After Cesarean Delivery(JAMA, 2020-09-22) Tuuli, Methodius G.; Liu, Jingxia; Tita, Alan T.N.; Longo, Sherri; Trudell, Amanda; Carter, Ebony B.; Shanks, Anthony; Woolfolk, Candice; Caughey, Aaron B.; Warren, David K.; Odibo, Anthony O.; Colditz, Graham; Macones, George A.; Harper, Lorie; Obstetrics and Gynecology, School of MedicineImportance: Obesity increases the risk of both cesarean delivery and surgical-site infection. Despite widespread use, it is unclear whether prophylactic negative pressure wound therapy reduces surgical-site infection after cesarean delivery in obese women. Objective: To evaluate whether prophylactic negative pressure wound therapy, initiated immediately after cesarean delivery, lowers the risk of surgical-site infections compared with standard wound dressing in obese women. Design, setting, and participants: Multicenter randomized trial conducted from February 8, 2017, through November 13, 2019, at 4 academic and 2 community hospitals across the United States. Obese women undergoing planned or unplanned cesarean delivery were eligible. The study was terminated after 1624 of 2850 participants were recruited when a planned interim analysis showed increased adverse events in the negative pressure group and futility for the primary outcome. Final follow-up was December 18, 2019. Interventions: Participants were randomly assigned to either undergo prophylactic negative pressure wound therapy, with application of the negative pressure device immediately after repair of the surgical incision (n = 816), or receive standard wound dressing (n = 808). Main outcomes and measures: The primary outcome was superficial or deep surgical-site infection according to the Centers for Disease Control and Prevention definitions. Secondary outcomes included other wound complications, composite of surgical-site infections and other wound complications, and adverse skin reactions. Results: Of the 1624 women randomized (mean age, 30.4 years, mean body mass index, 39.5), 1608 (99%) completed the study: 806 in the negative pressure group (median duration of negative pressure, 4 days) and 802 in the standard dressing group. Superficial or deep surgical-site infection was diagnosed in 29 participants (3.6%) in the negative pressure group and 27 (3.4%) in the standard dressing group (difference, 0.36%; 95% CI, -1.46% to 2.19%, P = .70). Of 30 prespecified secondary end points, 25 showed no significant differences, including other wound complications (2.6% vs 3.1%; difference, -0.53%; 95% CI, -1.93% to 0.88%; P = .46) and composite of surgical-site infections and other wound complications (6.5% vs 6.7%; difference, -0.27%; 95% CI, -2.71% to 2.25%; P = .83). Adverse skin reactions were significantly more frequent in the negative pressure group (7.0% vs 0.6%; difference, 6.95%; 95% CI, 1.86% to 12.03%; P < .001). Conclusions and relevance: Among obese women undergoing cesarean delivery, prophylactic negative pressure wound therapy, compared with standard wound dressing, did not significantly reduce the risk of surgical-site infection. These findings do not support routine use of prophylactic negative pressure wound therapy in obese women after cesarean delivery.Item To Flip or Not to Flip: Learning Style Preferences among Millennial Physician Assistant Students(Cureus, 2021-02-21) Schultz, Katherine; Schaffer, Alicia; Rebman, Rebecca; Shanks, Anthony; Obstetrics and Gynecology, School of MedicineIntroduction: Presenting material in a manner that is most palatable to students is important to improve the learning process. We evaluated the efficacy of different teaching styles including the flipped classroom and assessed the learning style preferences of a cohort of medical learners in a preclinical obstetrics and gynecology course. Methods: We conducted three teaching sessions with 35 physician assistant students. A different teaching style was implemented for each session including a traditional lecture with interactive learning technology augmentation, a flipped classroom, and a hybrid approach incorporating lecture and group work. Students were surveyed using a Likert scale regarding the efficacy of the format, clinical relevance of the material, and their learning preference for future sessions. Results: Students rated the traditional approach as the most effective, most relevant, and most preferred method. Students preferred the flipped classroom least, but they rated it as slightly more effective and relevant than the hybrid approach. Conclusion: The teaching style of various coursework including the preclinical obstetrics and gynecology curriculum may not need to be altered for millennial learners. This study showed the flipped classroom was the least favored teaching style and that there was a marked preference by students for a more traditional didactic lecture.Item Contraceptive Method Choices in Women With and Without Opioid Use Who Have Infants in the Neonatal Intensive Care Unit and Nursery(Mary Ann Liebert, Inc., 2020-09-24) Radwan, Alia; Ray, Bobbie Nicole; Haas, David M.; Obstetrics and Gynecology, School of MedicineObjective: The aim of this study was to examine whether a history of opioid use predicts tier 1 contraceptive use or plan to use in women with infants in the neonatal intensive care unit (NICU) and nursery. Materials and Methods: We conducted a self-administered, anonymous survey in women with infants in three local NICUs and two postpartum units from November 2018 to May 2019. Women were recruited while visiting their infants in the NICU or in their postpartum rooms. Our survey included adapted questions from the Centers for Disease Control and Prevention (CDC) Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire, the National Institute of Drug Abuse (NIDA) Modified ASSIST Screening Tool, and ones written by our team. The questions asked about contraceptive use and opioid use. We compared the responses of women with and without a history of opioid use. We conducted a multivariable regression analysis and applied the backward elimination method to identify whether opioid use was a predictor of tier 1 contraceptive use or plan to use. Results: A total of 122 women completed the survey. Fifty-three women (43.4%) reported opioid use in the month before pregnancy and/or during pregnancy, while 69 (56.6%) women reported no opioid use and comprised the control group. Multivariable regression analysis showed that opioid use was not associated with the use or planned use of tier 1 contraceptives (adjusted odds ratio [aOR] 1.47; confidence interval [95% CI] 0.54-4.01). Older maternal age predicted tier 1 choice (aOR 1.12; 95% CI 1.04-1.21), while African American women were less likely to use or plan to use tier 1 contraceptives compared with white women (aOR 0.21; 95% CI 0.08-0.56). Conclusion: A history of opioid use was not independently associated with women using or planning to use tier 1 methods, while age and race were predictors.