Department of Obstetrics and Gynecology Works

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Creation of a Novel 3D-Printed Amniocentesis Simulation Model and Impact on Resident Confidence
(European Society of medicine, 2024-08-31) Pape, Kelsey J.; Wilson, Ashtin; Cronin, Nichole; Parmenter, Jacob; Ellis, Nick; Rouse, Caroline E.; Shanks, Anthony L.
Background: Non-invasive prenatal screening has decreased opportunities for diagnostic antenatal procedures during residency training. Commercially available models are often cost prohibitive while homemade models can be low fidelity and non-reusable. Objective: To create a training tool with realistic anatomy, tissue-specific tactile sensation, and cost-effective assembly for amniocentesis procedural technique practice and evaluate its impact on trainee confidence with performance. Study Design: Collaborating with biomedical engineering students, our team defined several characteristics to achieve a high-fidelity model: compatible with ultrasound, anatomically accurate, demonstrate tactile realism, endure repeat use, and be cost-effective. A 3-D printed model was created that satisfied fidelity guidelines after rigorous materials and imaging testing. Results: We implemented the model in the observed structured clinical exam for Obstetrics and Gynecology residents in which trainees (PGY2-4) performed an amniocentesis after guided practice with Maternal-Fetal Medicine faculty. Residents were given pre and post-simulation Likert scale surveys regarding confidence and satisfaction with the model. Descriptive analyses and paired t-test were used for analysis. 19 residents completed both pre and post surveys. Mean resident confidence in performing an amniocentesis increased from 1.6 to 3.2 (p<0.001, scale 1-5) after the practice session. Most residents (89.5%) strongly agreed that the model was easy to use and would use it to practice independently. Conclusion: This novel 3-D printed, ultrasound compatible, anatomically accurate, and cost-effective amniocentesis model provides high-fidelity procedural practice and improved trainee confidence. Models such as these have the potential to greatly impact skill development for rare procedures. Future directions include modifying this model for additional fetal procedures, such as cordocentesis.
Cracking the Code: Interpreting Content and Phrases Used in Maternal-Fetal Medicine Fellowship Letters of Recommendation
(Elsevier, 2024-06-12) Dotters-Katz, Sarah K.; Grace, Matthew R.; Pilliod, Rachel; Hofler, Lisa G.; Temming, Lorene; Shanks, Anthony L.
Background: Letters of recommendation for Maternal-Fetal Medicine(MFM) fellowship are a critical part of the applicant selection process. However, data regarding best practices for how to write LOR for MFM is limited. Similarly, within letters of recommendation, differences in the 'code' or meaning of summative words/phrases used at the end of letters of recommendation are seen between surgery, pediatrics and medicine. However, data regarding code MFM Letters of recommendation are quite limited. Objective: We sought to describe what Maternal-Fetal Medicine program directors value in letters of recommendation for fellowship applicants and how PDs interpret commonly used summative words/phrases. Study design: After IRB exemption, subject matter experts developed an e-survey querying the importance of various letters of recommendation 'best practices' described by other specialties. Content and face validation were performed prior to dissemination. This cross-sectional survey was administered to MFM program directors in February 2023. The primary outcome was the relative importance of letters of recommendation content areas. Secondary outcomes included the strength of each summative 'code' phrase. Descriptive analysis was performed and principal component analysis (PCA) was then used to reduce the list of phrases to their underlying dimensions. Statistical analysis was performed by SPSS 29.0. Results: Of 104 MFM program directors sent the survey, 70 (67%) responded. MFM program directors reviewed an average of 78 applications (SD, 30) with 60% writing ≥3 letters/year. Ninety-one percent of respondents noted that letters of recommendation are important/very important in shaping impressions of an applicant. Respondents reported the depth of interaction with an applicant, the applicant's specific behavior traits, the applicant's abilities and a summative statement including strength of the recommendation as important content for MFM fellowship letters of recommendation. Letter length, use of bold/italics, and restating the applicant's curriculum vitae were considered not important. Following PCA with varimax rotation, 14 specific phrases used in letters of recommendation were reduced to 5 themes: high qualitative assessments, average qualitative assessments, objective metrics, exceeding expectations and grit. These themes accounted for 64.6% of the variance in the model (KMO 0.7, Bartlett's Test of Sphericity p<0.01). Phrases that respondents considered positive included: 'Top 5%', 'Want to keep', and 'highest recommendation', (all mean score≥4.5/5), while 'expected level', 'showed improvement', and '2nd quartile' were negatively associated code words (all mean score <2.5/5). Conclusions: MFM program directors reported that descriptions of an applicant's abilities, behavior traits, and depth of the writer's interactions with the applicant were all important components of an MFM fellowship letters of recommendation. Letter length, bold/italics, and highlights from the CV were not important. A clear 'code' emerged regarding summative phrases included in letters of recommendation. Dissemination of these data might help less experienced letter writers send a clearer message and ensure all letter writers have a shared mental model.
Impact of Dobbs Decision on Retention of Indiana Medical Students for Residency
(Elsevier, 2023-10-08) Hulsman, Luci; Bradley, Paige K.; Caldwell, Amy; Christman, Megan; Rusk, Debra; Shanks, Anthony L.
Background: As medical students consider residency training programs, access to comprehensive training in abortion care and the legal climate influencing abortion care provision are likely to affect their decision process. Objective: This study aimed to determine medical students' desire to stay in a state with an abortion ban for residency. Study design: A cross-sectional survey was distributed to all medical students at a large allopathic medical school. Anonymous survey questions investigated the likelihood of seeking residency training in states with abortion restrictions and the likelihood of considering obstetrics and gynecology as a specialty. Qualitative responses were also captured. Results: The survey was distributed to 1424 students, and 473 responses yielded a 33.2% completion rate; 66.8% of students were less likely to pursue residency training in Indiana following a proposed abortion ban. Moreover, 70.0% of students were less likely to pursue residency in a state with abortion restrictions. Approximately half of respondents (52.2%) were less likely to pursue obstetrics and gynecology as a specialty after proposed abortion restrictions. Qualitative remarks encompassed 6 themes: comprehensive health care access, frustration with the political climate, impact on health care providers, relocation, advocacy, and personal beliefs and ethical considerations. Conclusion: Most medical students expressed decreased likelihood of remaining in Indiana or in states with abortion restrictions for residency training. The field of obstetrics and gynecology has been negatively affected, with medical students indicating lower likelihood to pursue obstetrics and gynecology. Regardless of specialty, the physician shortage may be exacerbated in states with abortion restrictions. The overturn of Roe v Wade has the potential for significant effects on medical student plans for residency training location, thereby shaping the future of the physician workforce.
Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer
(Springer Nature, 2023) Mondal, Tanmoy; Gaur, Himanshu; Wamba, Brice E. N.; Michalak, Abby Grace; Stout, Camryn; Watson, Matthew R.; Aleixo, Sophia L.; Singh, Arjun; Condello, Salvatore; Faller, Roland; Leiserowitz, Gary Scott; Bhatnagar, Sanchita; Tushir-Singh, Jogender; Obstetrics and Gynecology, School of Medicine
Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors.
The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review
(MDPI, 2023-09-22) Moawad, Gaby; Youssef, Youssef; Fruscalzo, Arrigo; Faysal, Hani; Kheil, Mira; Pirtea, Paul; Guani, Benedetta; Ayoubi, Jean Marc; Feki, Anis; Obstetrics and Gynecology, School of Medicine
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: “medical treatment”, “non-steroidal anti-inflammatory”, “progesterone intrauterine device”, “dienogest”, “combined oral contraceptives”, “gonadotropin releasing hormone agonist”, “gonadotropin releasing hormone antagonist”, “danazol”, “aromatase inhibitors”, “ulipristal acetate”, “anti-platelet therapy”, “dopamine”, “oxytocin antagonists”, “STAT3”, “KRAS”, “MAPK”, “micro-RNA”, “mifepristone”, “valproic acid”, “levo-tetrahydropalamatine”, and “andrographolide”. The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.
Objectively assessed sleep-disordered breathing during pregnancy and infant birthweight
(Elsevier, 2021) Hawkins, Marquis; Parker, Corette B.; Redline, Susan; Larkin, Jacob C.; Zee, Phyllis P.; Grobman, William A.; Silver, Robert M.; Louis, Judette M.; Pien, Grace; Basner, Robert C.; Chung, Judith H.; Haas, David M.; Nhan-Chang, Chia-Ling; Simhan, Hyagriv N.; Blue, Nathan R.; Parry, Samuel; Reddy, Uma; Facco, Francesca; NICHD NuMoM2b; NHLBI NuMoM2b Heart Health Study Networks; Obstetrics and Gynecology, School of Medicine
Background: Sleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight. Methods: We measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA: <10th percentile for gestational age) birthweights. Results: The prevalence of early-pregnancy SDB was nearly 4%. The incidence of mid-pregnancy SDB was nearly 6.0%. The prevalence of LGA and SGA was 7.4% and 11.9%, respectively. Early-pregnancy SDB was associated with a higher risk of LGA in unadjusted models (RR 2.2, 95% CI 1.3-3.5) but not BMI-adjusted models (aRR 1.0, 95% CI 0.6-1.8). Mid-pregnancy SDB was not associated with SGA or LGA. Mid-pregnancy nocturnal hypoxemia (% of sleep time <90% oxygen saturation) and increasing nocturnal hypoxemia from early to mid-pregnancy were associated with a higher risk of LGA in BMI-adjusted models. SDB and nocturnal hypoxemia were not associated with SGA. Conclusions: SDB in pregnancy was not associated with an increased risk of LGA or SGA birthweight, independent of BMI. Some measures nocturnal hypoxemia were associated with an increase in LGA risk, independent of BMI.
Incremental Propensity Score Effects for Time-Fixed Exposures
(Wolters Kluwer, 2021) Naimi, Ashley I.; Rudolph, Jacqueline E.; Kennedy, Edward H.; Cartus, Abigail; Kirkpatrick, Sharon I.; Haas, David M.; Simhan, Hyagriv; Bodnar, Lisa M.; Obstetrics and Gynecology, School of Medicine
When causal inference is of primary interest, a range of target parameters can be chosen to define the causal effect of interest, such as average treatment effects (ATEs). However, ATEs may not always align with the research question at hand. Furthermore, the assumptions needed to interpret estimates as ATEs, such as exchangeability, consistency, and positivity, are often not met. Here, we present the incremental propensity score (incremental PS) approach to quantify the effect of shifting each person’s exposure propensity by some pre-determined amount. Compared to the ATE, incremental PS may better reflect the impact of certain policy interventions, and do not require that positivity hold. Using the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b), we quantified the relation between total vegetable intake and the risk of preeclampsia, and compared it to average treatment effect estimates. The ATE estimates suggested a reduction of between two and three preeclampsia cases per 100 pregnancies for consuming at least 1/2 a cup of vegetables per 1,000 kcal. However, positivity violations obfuscate the interpretation of these results. In contrast, shifting each woman’s exposure propensity by odds ratios ranging from 0.20 to 5.0 yielded no difference in the risk of preeclampsia. Our analyses show the utility of the incremental propensity score effects in addressing public health questions with fewer assumptions.
Remote Monitoring Compared With In-Office Surveillance of Blood Pressure in Patients With Pregnancy-Related Hypertension: A Randomized Controlled Trial
(Wolters Kluwer, 2023) Arkerson, Brittany J.; Finneran, Matthew M.; Harris, Solita R.; Schnorr, Jessica; McElwee, Eliza R.; Demosthenes, Lauren; Sawyer, Renata; Obstetrics and Gynecology, School of Medicine
Objective: To compare the rate of blood pressure ascertainment within 10 days of postpartum discharge among individuals with hypertensive disorders of pregnancy randomized either to in-office blood pressure assessment or at-home monitoring. Methods: This was a multisite randomized controlled trial of postpartum patients diagnosed with a hypertensive disorder of pregnancy before discharge between April 2021 and September 2021 and was performed at two academic training institutions. Patients were randomized to either an in-office blood pressure check or remote monitoring through a web-enabled smartphone platform. The primary outcome was the rate of any blood pressure ascertainment within 10 days of discharge. Secondary outcomes include rates of initiation of antihypertensive medication, readmission, and additional office or triage visits for hypertension. Assuming a 10-day postdischarge blood pressure ascertainment rate of 50% in the in-office arm, we estimated that 186 participants would provide 80% power to detect a 20% difference in the primary outcome between groups. Results: One hundred ninety-seven patients were randomized (96 remote, 101 in-office). Patients with remote monitoring had higher rates of postpartum blood pressure ascertainment compared with in-office surveillance (91.7% [n=88] vs 58.4% [n=59]; P<.001). There were 11 (11.5%) patients in the intervention arm whose only qualifying blood pressure was a postdischarge in-person ascertainment, yielding a true remote monitoring uptake rate of 80.2%. In those with remote blood pressure uptake (n=77), the median number of blood pressure checks was 15 (interquartile range 6-26) and the median duration of remote monitoring use was 14 days (interquartile range 9-16). There were no differences in rates of readmission for hypertension (5.0% [n=5] vs 4.2% [n=4], P=.792) or initiation of antihypertensive medications after discharge (9.4% [n=9] vs 6.9% [n=7], P=.530). Rates of unscheduled visits were increased in the remote monitoring arm, but this did not reach statistical significance (5.0% [n=5] vs 12.5% [n=12], P=.059). When stratifying the primary outcome by race and randomization group, Black patients had lower rates of blood pressure ascertainment than White patients when assigned to in-office surveillance (41.2% [n=14] vs 69.5% [n=41], P=.007), but there was no difference in the remote management group (92.9% [n=26] vs 92.9% [n=52], P>.99). Conclusion: Remote monitoring can increase postpartum blood pressure ascertainment within 10 days of discharge for women with hypertensive disorders of pregnancy and has the potential to promote health equity.
Extract of Artemisia dracunculus L. Modulates Osteoblast Proliferation and Mineralization
(MDPI, 2023-08-30) Scott, Matthew C.; Bourgeois, Aleah; Yu, Yongmei; Burk, David H.; Smith, Brenda J.; Floyd, Z. Elizabeth; Obstetrics and Gynecology, School of Medicine
Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2′,4′-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity.
Risks of Uterine Perforation and Expulsion Associated With Intrauterine Devices
(Wolters Kluwer, 2023) Fassett, Michael J.; Reed, Susan D.; Rothman, Kenneth J.; Pisa, Federica; Schoendorf, Juliane; Wahdan, Yesmean; Peipert, Jeffrey F.; Gatz, Jennifer; Ritchey, Mary E.; Armstrong, Mary Anne; Raine-Bennett, Tina; Postlethwaite, Debbie; Getahun, Darios; Shi, Jiaxiao M.; Xie, Fagen; Chiu, Vicki Y.; Im, Theresa M.; Takhar, Harpreet S.; Wang, Jinyi; Anthony, Mary S.; Obstetrics and Gynecology, School of Medicine
Objective: The APEX-IUD (Association of Perforation and Expulsion of Intrauterine Devices) study evaluated the association of postpartum timing of intrauterine device (IUD) insertion, breastfeeding, heavy menstrual bleeding, and IUD type (levonorgestrel-releasing vs copper) with risks of uterine perforation and IUD expulsion in usual clinical practice. We summarize the clinically important findings to inform counseling and shared decision making. Methods: APEX-IUD was a real-world (using U.S. health care data) retrospective cohort study of individuals aged 50 years and younger with IUD insertions between 2001 and 2018 and with electronic health record data. Cumulative incidences of uterine perforation and IUD expulsion were calculated. Adjusted hazard ratios (aHRs) and 95% CIs were estimated from proportional hazards models with control of confounding. Results: Among the study population of 326,658, absolute risk of uterine perforation was low overall (cumulative incidence, 0.21% [95% CI 0.19-0.23%] at 1 year and 0.61% [95% CI 0.56-0.66% at 5 years]) but was elevated for IUDs inserted during time intervals within 1 year postpartum, particularly among those between 4 days and 6 weeks postpartum (aHR 6.71, 95% CI 4.80-9.38), relative to nonpostpartum insertions. Among postpartum insertions, IUD expulsion risk was greatest for insertions in the immediate postpartum period (0-3 days after delivery) compared with nonpostpartum (aHR 5.34, 95% CI 4.47-6.39). Postpartum individuals who were breastfeeding had a slightly elevated risk of perforation and lowered risk of expulsion than those not breastfeeding. Among nonpostpartum individuals, those with a heavy menstrual bleeding diagnosis were at greater risk of expulsion than those without (aHR 2.84, 95% CI 2.66-3.03); heavy menstrual bleeding also was associated with a slightly elevated perforation risk. There was a slightly elevated perforation risk and slightly lower expulsion risk associated with levonorgestrel-releasing IUDs compared with copper IUDs. Conclusion: Absolute risk of adverse outcomes with IUD insertion is low. Clinicians should be aware of the differences in risks of uterine perforation and expulsion associated with IUD insertion during specific postpartum time periods and with a heavy menstrual bleeding diagnosis. This information should be incorporated into counseling and decision making for patients considering IUD insertion.

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