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Associations of Glyphosate Exposure in Pregnancy with Preterm Birth: a Longitudinal Birth Cohort Study

Herrera, Teresa; Fragoman, Fiona; Ghassabian, Akhgar; Cowell, Whitney; Cajachagua Torres, Kim N; Ard, Natasha; Kannan, Kurunthachalam; Li, Zhongmin; Mehta-Lee, Shilpi; Liu, Mengling; Burris, Heather H; Trasande, Leonardo
BACKGROUND:Emerging data suggests that glyphosate, a non-selective herbicide, can influence reproductive health. We investigated associations of prenatal exposure to glyphosate and aminomethylphosphonic acid (AMPA), with preterm birth and its subtypes. METHODS:We used data from the NYU Children's Health and Environmental Study, a prospective birth cohort in New York City (2016-2019). Participants (n=1450) provided urine samples at 4 to <18 weeks and 18 to 25 weeks gestation. Exposure was adjusted for creatinine and natural log transformed. Preterm birth was defined as a birth occurring before 37 weeks of gestation. We also explored preterm birth subtypes, spontaneous preterm births and medically indicated preterm births as secondary outcomes. To examine associations between glyphosate and AMPA at both timepoints with preterm birth, we used generalized estimating equations with a logit link function. RESULTS:Overall, 7% (n=103) of births were preterm. Glyphosate concentrations at 18-25 weeks was associated with preterm birth (OR: 1.35, 95% CI: 1.04, 1.76) and spontaneous preterm birth (OR: 2.01, 95% CI: 1.40, 2.90). AMPA was not associated with preterm birth in any model. CONCLUSIONS:These results support evidence that glyphosate may act upon pathways leading to preterm birth and spontaneous preterm birth. Our study highlights pregnancy as a vulnerable period to glyphosate exposure.
PMID: 42448271
ISSN: 1873-6424
CID: 6066702

MLH1 promoter hypermethylation and associations with survival outcomes: A real-world endometrial cancer molecularly targeted therapy consortium cohort study

Borden, Lindsay E; Cosgrove, Casey M; Washington, Christina R; Thomas, Samantha M; Haight, Paulina J; Brown, Ashley; Powell, Kristina; Harsono, Adrian; Mullen, Margaret; Crafton, Sarah; Jackson, Amanda L; Corr, Bradley R; Wright, Jason D; Konecny, Gottfried E; Bae-Jump, Victoria L; Podwika, Sarah E; Smitherman, Carson; Maxwell, G Larry; Backes, Floor J; Pothuri, Bhavana; Ko, Emily M; Arend, Rebecca C; Thaker, Premal H; Duska, Linda R; Secord, Angeles Alvarez; Moore, Kathleen N
OBJECTIVE:We assessed the underlying etiology of MMR deficiency (dMMR), genetic (germline/somatic) versus epigenetic hMLH1, and associations between response rate, and survival outcomes in patients with advanced and recurrent dMMR endometrial adenocarcinoma treated with immune checkpoint inhibitors. METHODS:The Endometrial Cancer Molecularly Targeted Therapy Consortium (ECMT2) database was used to identify patients with mismatch repair deficient (dMMR) tumors treated with pembrolizumab or dostarlimab from 2016 to 2023. Cases were categorized into two groups- germline Lynch Syndrome mutation (gLS) and somatic Lynch Syndrome mutation (sLS), or MLH1 promoter hypermethylation (hMLH1). Clinical and pathologic data included patient demographics, tumor characteristics, recurrence date, survival, and treatment. RESULTS:A total of 133 patients were included: gLS/sLS (n = 34, 25.6%) or hMLH1 (n = 99, 74.4%). Demographic and tumor characteristics, including stage at diagnosis and histology were similar between groups. The response rate was 57.1% for the entire cohort [55.9% gLS/sLS, 57.6% hMLH1; (p = 0.90)]. The survival outcomes were not significantly different in the gLS/sLS and hMLH1 groups [2-year progression-free survival: 68.0% and 59.0% (p = 0.77); 2-year overall survival: 70.9% and 62.2% (p = 0.55)], respectively. CONCLUSION/CONCLUSIONS:Our findings suggest that response to immune checkpoint inhibitors and survival outcomes are not associated with different mechanisms of dMMR.
PMID: 42468445
ISSN: 1095-6859
CID: 6067452

Tracking Cesarean Scar Morphology by Sonohysterography After Consecutive Cesarean Deliveries with Endometrium-Free Closure

Antoine, Clarel; Ibietatorremendia, Olivia; Timor-Tritsch, Ilan E
OBJECTIVE:To evaluate the impact of an endometrium-free closure on uterine scar morphology by comparing sonohysterograms in the same women, first after a cesarean with a standard or an endometrium-free closure, and then after a subsequent cesarean with an endometrium-free closure. MATERIALS AND METHODS/METHODS:This small retrospective longitudinal study used saline infusion sonohysterography to assess uterine scar morphology in 25 asymptomatic women who underwent 2 to 5 sonographic examinations following 2 to 9 consecutive cesarean deliveries. Forty paired consecutive procedures in which the second delivery used an endometrium-free closure technique met the inclusion criteria, categorized as "Transition Group" (n=9), in which a standard closure was followed by an endometrium-free closure, and "Successive Group" (n=31), in which women received the endometrium-free closure technique in two successive deliveries. Paired sonohysterographic analyses were performed after each cesarean delivery and longitudinally compared to evaluate niche development and scar morphology. Niche depth and residual myometrial thickness were measured; a niche depth greater than 2 mm was considered sonographically significant. A change greater than ±2 mm in depth or residual myometrial thickness was operationally defined as morphologically significant and not clinically validated. Generalized estimating equations (GEE) with robust standard errors were used to account for within-patient correlation (p-value < 0.05). RESULTS:By GEE analysis, the Transition Group had 4.67-fold higher odds of new niche development compared to the Successive Group (OR = 4.67; 95% CI: 0.71-30.77; p = 0.109). This difference did not reach statistical significance. Mean depth change was 1.31 mm greater in the Transition Group (B = 1.31; 95% CI: -0.25 to 2.87; p = 0.099). Transition Group pairs showed larger depth increases (median 4.6 mm, range: 3.0-5.0 mm) compared with Successive Group pairs (median 3.6 mm, range: 2.6-5.3 mm). These findings should be interpreted as hypothesis-generating only, not as evidence of clinical significance. Across both groups, 22/40 pairs (55.0%) ended without a niche after the second endometrium-free closure, including 21 (21/22, 95.5%) that initially presented without a niche and 1 (1/22, 4.5%) that initially presented with a niche. Ten pairs (10/40, 25.0%) that presented with pre-existing niches showed stable or improved niche depth, and nine pairs (9/40, 22.5%) of these cases showed stable or improved residual myometrial thickness, 3/40 (7.5%) worsened in depth, 2/40 (5.0%) simultaneously worsened in residual myometrial thickness, 6/40 (15.0%) developed a de novo niche, mean depth 4.2 mm (2.6 mm-6.5 mm), and mean residual myometrial thickness of 5.72 mm (3.50 mm -7.30 mm). CONCLUSION/CONCLUSIONS:In this small retrospective intraindividual cohort, the endometrium-free closure maintains favorable sonographic scar morphology in most women, with morphology reflecting both prior scar status and the technique at delivery. Repeated surgery may limit the benefit of closure technique in some women, although many maintained scar morphology even at higher-order cesareans. Results are limited by single observer measurements without reproducibility assessment, use of ±2 mm threshold, and absence of clinical outcomes. These paired observations warrant prospective evaluation in larger studies.
PMID: 42471172
ISSN: 1097-6868
CID: 6067522

Endometrial Cancer by ERBB2 Amplification (ERBB2amp) Status: Differences in Molecular Subtypes, Ancestry, and Real-World Outcomes

Cantillo, Evelyn; Podder, Vivek; Danziger, Natalie; Lobo, Dale; Lin, Douglas I; Graf, Ryon P; Coleman, Robert L; Pothuri, Bhavana; Eskander, Ramez N; Herzog, Thomas J; Slomovitz, Brian M
PURPOSE/OBJECTIVE:amp prevalence, molecular subtype, and histologic associations, as well as prognostic impact across diverse genetic ancestries using a large clinicogenomic database (CGDB). METHODS:amp prevalence, histologic and molecular correlations, and associations with OS were examined. RESULTS: CONCLUSION/CONCLUSIONS:
PMID: 42430697
ISSN: 2473-4284
CID: 6064302

Performance of Lung Cancer Risk Prediction Models in Different Racial and Ethnic Groups in the United States: Results From the Lung Cancer Cohort Consortium

Feng, Xiaoshuang; Guida, Florence; Guenoun, Aghiles; Alcala, Karine; Aldrich, Melinda C; Arslan, Alan A; Cai, Qiuyin; Zheng, Wei; Chen, Chu; Triplette, Matthew; Tinker, Lesley F; Patel, Alpa V; Liao, Linda M; Sinha, Rashmi; Rohan, Thomas E; Sesso, Howard D; Zhang, Xuehong; Visvanathan, Kala; Wang, Ying; Johansson, Mattias; Robbins, Hilary A
BACKGROUND/UNASSIGNED:Racial and ethnic disparities are a concern in lung cancer screening. OBJECTIVE/UNASSIGNED:To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups. DESIGN/UNASSIGNED:Cohort study. SETTING/UNASSIGNED:United States, Lung Cancer Cohort Consortium. PARTICIPANTS/UNASSIGNED:641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants. MEASUREMENTS/UNASSIGNED:Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group. RESULTS/UNASSIGNED:General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences. LIMITATION/UNASSIGNED:Smaller sample for Asian and Hispanic participants. CONCLUSION/UNASSIGNED:To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed. PRIMARY FUNDING SOURCE/UNASSIGNED:U.S. National Cancer Institute, Lung Cancer Research Foundation, and Cancer Research UK.
PMID: 42372272
ISSN: 1539-3704
CID: 6062412

Updated patient-reported outcomes and the effect of disease progression on health-related quality of life in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer

Shahin, Mark S; Lorusso, Domenica; Backes, Floor J; Barretina-Ginesta, Maria-Pilar; O'Malley, David M; Forget, Frédéric; Pothuri, Bhavana; Hietanen, Sakari; McCormick, Colleen C; Abadie-Lacourtoisie, Sophie; O'Cearbhaill, Roisin E; Heitz, Florian; Moore, Richard G; Amit, Amnon; Willmott, Lyndsay J; Pérez, María-Jesús Rubio; Burger, Robert A; Redondo, Andrés; Chase, Dana M; Romero, Ignacio; Moore, Kathleen N; Vergote, Ignace; Cloven, Noelle; Haslund, Charlotte A; Graybill, Whitney S; Bergamini, Alice; Berton, Dominique; Braicu, Elena I; Lim, Jonathan T; Golembesky, Amanda K; Shtessel, Luda; Monk, Bradley J; González-Martín, Antonio
OBJECTIVE:To report updated patient-reported (PRO) health-related quality of life (HRQOL) findings and evaluate the effect of disease progression on HRQOL using data from the final analysis of the PRIMA/ENGOT-OV26/GOG-3012 trial. METHODS:Patients were randomized 2:1 to niraparib first-line maintenance or placebo. Longitudinal HRQOL was a prespecified secondary endpoint assessed via European Organisation for Research and Treatment of Cancer QOL-Core Questionnaire (EORTC QLQ-C30) and -Ovarian Cancer module (EORTC QLQ-OV28), Functional Assessment of Cancer Therapy Ovarian Cancer Symptom Index (FOSI), and EuroQol 5-dimension 5-level questionnaire with visual analog scale (EQ-VAS). Post hoc analyses evaluated least-squares mean change from baseline or last on-treatment visit before disease progression (clinical cutoff: April 8, 2024). RESULTS:Questionnaire completion rates exceeded 89% through cycle 24 and were 80% at end of treatment. Early differences in gastrointestinal symptom scores between arms resolved over time, and no differences in overall HRQOL were observed. Disease progression reduced overall HRQOL across arms, with marked reductions in EORTC QLQ-C30 overall HRQOL, FOSI, and EQ-VAS scores that never recovered to pre-progression levels. Progression also resulted in sustained deterioration across all EORTC QLQ-C30 and QLQ-OV28 functional scales and worsening symptom scores, particularly for fatigue, dyspnea, pain, and appetite loss. Similar results were observed when patients were evaluated by homologous recombination deficiency status. CONCLUSION/CONCLUSIONS:In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT02655016.
PMID: 42385609
ISSN: 1095-6859
CID: 6063102

Perceived stress levels and associated stressors in patients undergoing planned oocyte cryopreservation

Voigt, Paxton; Parra, Carlos M; Quinn, Gwendolyn P; Mendoza, Clarisa; Chamberlin, Martine; Kunamneni, Sruthi; Licciardi, Frederick
OBJECTIVE:To assess perceived stress levels and to identify key stressors before and after planned oocyte cryopreservation. DESIGN/METHODS:Cross-sectional mixed methods study. SETTING/METHODS:Academic fertility center. SUBJECTS/METHODS:Patients who underwent their first planned oocyte cryopreservation cycle. MAIN OUTCOME MEASURES/METHODS:Comparison of composite Perceived Stress Scale-10 (PSS-10) scores before and after oocyte cryopreservation, and qualitative thematic analysis of interview transcripts. EXPOSURE/METHODS:Planned oocyte cryopreservation. RESULTS:Of the 471 pre-oocyte cryopreservation orientees contacted, 110 (23.4%) volunteered to participate and 81 (17.2%) were ultimately included in the study analysis after completing both the pre- and post-oocyte cryopreservation surveys; 20 participated in post-treatment interviews. The median composite PSS-10 score was 17 before and after oocyte cryopreservation, indicating moderate perceived stress that did not significantly change after cycle completion. Before oocyte cryopreservation, the most commonly reported stressors were procedural, occupational, and partner-related. Afterwards, procedural stressors largely shifted toward outcome-related concerns. Qualitative analysis identified six major themes influencing stress throughout treatment: financial considerations, medication management, physical and logistical demands, stress surrounding fertility, support systems, and a sense of empowerment coupled with future uncertainty. CONCLUSION/CONCLUSIONS:By integrating quantitative and qualitative findings, this study provides a nuanced understanding of how stress is shaped by financial, procedural, occupational, and emotional factors across the oocyte cryopreservation process. These insights may inform more tailored pre-cycle counseling, strengthen patient-centered support infrastructure, and guide the development of targeted interventions to improve the emotional and psychological well-being of planned oocyte cryopreservation patients.
PMID: 42419676
ISSN: 1556-5653
CID: 6063982

Comparative effectiveness of 200mcg versus 400mcg misoprostol dosing for medication abortion from 24-27 weeks' gestation

Christensen, Theresa; Kakkad, Nikita A; Oot, Antoinette; Friedman, Steven; Brandt, Justin S; Jung, Christina
OBJECTIVES/OBJECTIVE:To assess efficacy and adverse outcomes of misoprostol 200mcg versus 400mcg every three hours buccal or vaginal for medication abortion (MAb) from 24-27 weeks' gestation. STUDY DESIGN/METHODS:This retrospective cohort study included MAbs from 24 0/7-27 0/7 weeks' gestation at Bellevue Hospital from 7/2022-6/2025. All patients received digoxin 2mg intraamniotic injection and mifepristone 200mg oral followed at 24-48hrs by misoprostol 200mcg or 400mcg every three hours buccal or vaginal based on hospital policy at time of admission. The primary outcome was time from first misoprostol dose to placental expulsion. Secondary outcomes were procedural complications. Primary statistical analysis was performed with Fisher's exact and Wilcox rank-sum tests. RESULTS:Of 55 patients, 27 (49%) received 200mcg doses of misoprostol and 28 (51%) received 400mcg doses of misoprostol. Median time to expulsion was 13hrs in the 200mcg group versus 9.5hrs in the 400mcg group (p=0.144). More patients in the 200mcg group versus the 400mcg group had blood loss ≥500mL (11.1% vs 0%, p=0.11) and retained placenta at four hours (3.7% vs 0%, p=0.49). No patients in either group had uterine rupture. CONCLUSIONS:Misoprostol 200mcg versus 400mcg every three hours buccal or vaginal for MAb from 24-27 weeks' gestation had overall similar outcomes. Although this single site retrospective study is underpowered to significantly differentiate between the two regimens, we observe that 200mcg dosing may be associated with higher risk of complications. Larger studies are needed to clarify optimal misoprostol dosing for 24-27 week MAb. IMPLICATIONS/CONCLUSIONS:For medication abortion from 24-27 weeks' gestation, serial doses of misoprostol 200mcg versus 400mcg every three hours have similar rates of complications, though there is a signal that 200mcg dosing may be associated with longer time to expulsion, higher blood loss, and more incidences of retained placenta.
PMID: 42401255
ISSN: 1879-0518
CID: 6063972

Safety and clinical considerations of alopecia therapies during pregnancy, fertility treatment, and polycystic ovary syndrome workup

Brinks, Anna L; Lawrence, Carli Needle; Kearney, Caitlin A; Rachko, Grace; Bieber, Amy K; DeVore, Shannon; Shapiro, Jerry; Lo Sicco, Kristen I; Majerson, Daniela
OBJECTIVE/UNASSIGNED:To evaluate the safety of alopecia treatments during pregnancy, in-vitro fertilization (IVF), and polycystic ovary syndrome (PCOS) workup, with a focus on potential maternal and fetal risks. DATA SOURCES/UNASSIGNED:A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus from November 2024 to December 2024. Search terms included medication names in combination with "pregnancy," "IVF," "in-vitro fertilization," and "PCOS." STUDY SELECTION/UNASSIGNED:Peer-reviewed studies addressing the use of therapies for androgenetic alopecia, alopecia areata, and scarring alopecias in the contexts of pregnancy, IVF, and PCOS were included. Articles evaluating maternal safety, fetal risks, and treatment timing were prioritized. Only English-language publications were reviewed. RESULTS/UNASSIGNED:Despite increasing therapeutic options for alopecia, significant knowledge gaps remain regarding their safety during pregnancy. Pregnant women are often excluded from clinical trials, leading to a reliance on older treatments with limited data on dosing or pharmacokinetics in the pregnant population. Unfortunately, there are few alopecia medications with robust safety data in pregnancy, and many medications are contraindicated during this period. Some medications may be used with caution, while others require additional investigation. During IVF, there are alopecia medications with potential benefit in women experiencing implantation failure or PCOS. For patients undergoing PCOS workup, some alopecia medications may impact hormonal labs or mask PCOS symptoms. CONCLUSION/UNASSIGNED:There is a critical need for more targeted research on alopecia treatments in pregnancy, IVF, and PCOS contexts. This review provides current evidence to guide clinicians and support informed, individualized treatment decisions during this vulnerable period.
PMCID:13308938
PMID: 42369849
ISSN: 2352-6475
CID: 6062292

Importance of abortion training to residency program applicants: A national survey of OBGYN residents

Beasley, Anitra; Keller, Jennifer Mendillo; Sierra, Gracia; Ogburn, Tony; White, Kari; George, Karen; Connolly, AnnaMarie; Banks, Erika
OBJECTIVES/OBJECTIVE:This study evaluates how access to abortion training influenced OBGYN residents who selected residency programs before and after the Dobbs decision. STUDY DESIGN/METHODS:Current OBGYN residents completed a survey in January 2024 as part of their annual in-training exam. Residents rated the importance of abortion training and compared access to abortion training to other factors (e.g., residency culture and happiness, geographic location) when selecting and ranking programs. We computed the percentage of residents reporting abortion training as important and a top factor when ranking programs. We used chi-squared test to compare differences between cohorts. RESULTS:Of the 6,134 residents surveyed, 3,182 consented to participation and had complete responses (52%). Overall, 2,281 (72%) considered abortion training important when choosing programs and 2,179 (69%) when ranking programs; 1,105 (71%) of post-Dobbs and 1,074 (66%) of pre-Dobbs residents considered abortion training important when ranking programs (p<0.01). Access to abortion training was a top three factor for 741 (23%) respondents when ranking programs. More post-Dobbs (392, 25%) than pre-Dobbs residents (349, 21%) considered access to abortion training as a top factor when ranking programs (p=0.01). CONCLUSIONS:Applicants weigh a variety of factors when selecting programs and may match to abortion restricted environments - this includes the 23% who considered abortion training a top factor. Future work should continue to focus on the impact of the Dobbs decision on residency program selection and the ability of all residents to develop abortion-care skills. IMPLICATIONS/CONCLUSIONS:Abortion training is an important consideration in residency program selection and essential for patient care. Without prioritization of abortion education, programs risk losing viable candidates and graduating residents without essential skills.
PMID: 42349603
ISSN: 1879-0518
CID: 6056212