Browsing by Author "Department of Obstetrics and Gynecology, School of Medicine"

Now showing 1 - 5 of 5
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    Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice
    (Society for the Study of Reproduction, 2016-04) Wang, Xiyin; Khatri, Shikha; Broaddus, Russell; Wang, Zhong; Hawkins, Shannon M.; Department of Obstetrics and Gynecology, School of Medicine
    Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor 2-Cre Female Arid1a conditional knockout mice exhibited a progressive decrease in number of pups per litter, with a precipitous decline after the second litter. We observed no tumors in virgin mice, although one knockout mouse developed a uterine tumor after pregnancy. Unstimulated virgin female knockout mice showed normal oviductal, ovarian, and uterine histology. Uteri of Arid1a knockout mice showed a normal decidualization response and appropriate responses to estradiol and progesterone stimulation. In vitro studies using primary cultures of human endometrial stromal fibroblasts revealed that small interfering RNA knockdown of ARID1A did not affect decidualization in vitro. Timed pregnancy studies revealed the significant resorption of embryos at Embryonic Day 16.5 in knockout mice in the third pregnancy. In addition to evidence of implantation site hemorrhage, pregnant Arid1a knockout mice showed abnormal placental morphology. These results suggest that Arid1a supports successful pregnancy through its role in placental function.
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    Risk of Maternal Morbidity with Increasing Number of Cesareans
    (Thieme Publishing, 2019-03) Sondgeroth, Kristina E.; Wan, Leping; Rampersad, Roxane M.; Stout, Molly J.; Macones, George A.; Cahill, Alison G.; Tuuli, Methodius G.; Department of Obstetrics and Gynecology, School of Medicine
    Objective To estimate the risk of perioperative morbidity with increasing number of cesareans. Study Design We conducted a retrospective cohort study from 2004 to 2010. Patients delivered by cesarean were included. Outcome measures were a composite organ injury (bowel or bladder), hysterectomy, hemorrhage requiring transfusion, severe morbidity, or surgical site complications. The Cochran–Armitage's test of trend was used to assess increasing incidence of each morbidity with number of prior cesareans. Multivariable logistic regression was used to estimate adjusted risks for each morbidity with increasing number of cesareans compared with primary cesarean. Results Of the 15,872 women in the cohort, 5,144 had cesarean delivery: 3,113 primary, 1,310 one prior, 510 two prior, and 211 three or more prior cesareans. There was a significant increase in organ injury, hysterectomy, and surgical site complications with increasing number of cesareans. In multivariable analysis, the risk of organ injury and hysterectomy was increased compared with primary cesarean after two prior cesareans, and after three or more cesareans for hemorrhage requiring transfusion and surgical site complications. Conclusion The risks of organ injury and hysterectomy are increased after two or more prior cesareans, and risks of hemorrhage and surgical site complications are increased after three or more cesareans.
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    Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women
    (Elsevier, 2017) Parry, Samuel; Sciscione, Anthony; Haas, David M.; Grobman, William A.; Iams, Jay D.; Mercer, Brian M.; Silver, Robert M.; Simhan, Hyagriv N.; Wapner, Ronald J.; Wing, Deborah A.; Elovitz, Michal A.; Schubert, Frank P.; Peaceman, Alan; Esplin, M. Sean; Caritis, Steve; Nageotte, Michael P.; Carper, Benjamin A.; Saade, George R.; Reddy, Uma M.; Parker, Corette B.; Department of Obstetrics and Gynecology, School of Medicine
    Background Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. Objective We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. Study Design Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days’ and 22 weeks 6 days’ gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. Results Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. Conclusion In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.
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    Surgical Management of Benign Adnexal Masses in the Pediatric/Adolescent Population: An 11-Year Review
    (Elsevier, 2017-02) Bergeron, Lauren M.; Bishop, Katherine C.; Hoefgen, Holly R.; Abraham, Margaret S.; Tutlam, Nhial T.; Merritt, Diane F.; Peipert, Jeffrey F.; Department of Obstetrics and Gynecology, School of Medicine
    Study Objective The purpose of this study was to compare ovarian conservation rates and surgical approach in benign adnexal surgeries performed by surgeons vs gynecologists at a tertiary care institution. Design A retrospective cohort review. Setting Children's and adult tertiary care university-based hospital. Participants Patients 21 years of age and younger who underwent surgery for an adnexal mass from January 2003 through December 2013. Interventions Patient age, demographic characteristics, menarchal status, clinical symptoms, radiologic imaging, timing of surgery, surgeon specialty, mode of surgery, rate of ovarian conservation, and pathology were recorded. Patients were excluded if they had a uterine anomaly or pathology-proven malignancy. Main Outcome Measures The primary outcome was the rate of ovarian conservation relative to surgical specialty; secondary outcome was surgical approach relative to surgical specialty. Results Of 310 potential cases, 194 met inclusion criteria. Gynecologists were more likely than surgeons to conserve the ovary (80% vs 63%; odds ratio, 2.28; 95% confidence interval, 1.16-4.48). After adjusting for age, body mass index, mass size, and urgency of surgery, the difference was attenuated (adjusted odds ratio, 1.84; 95% confidence interval, 0.88-3.84). Surgeons and gynecologists performed minimally invasive surgery at similar rates (62% vs 50%; P = .11). A patient was more likely to receive surgery by a gynecologist if she was older (P < .001) and postmenarchal (P = .005). Conclusion Results of our study suggest that gynecologists are more likely to perform ovarian-conserving surgery. However, our sample size precluded precise estimates in our multivariable model. Educational efforts among all pediatric and gynecologic surgeons should emphasize ovarian conservation and fertility preservation whenever possible.
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    Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA HOTAIR activity in ovarian and breast cancer
    (SpringerNature, 2017-04-18) Özeş, Ali R.; Wang, Yinu; Zong, Xingyue; Fang, Fang; Pilrose, Jay; Nephew, Kenneth P.; Department of Obstetrics and Gynecology, School of Medicine
    Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum. Treatment of HOTAIR-overexpressing ovarian and breast cancer cell lines with PNAs decreased invasion and increased chemotherapy sensitivity. Furthermore, the mechanism of action correlated with reduced nuclear factor-kappaB (NF-κB) activation and decreased expression of NF-κB target genes matrix metalloprotease 9 and interleukin 6. To deliver the anti-lncRNA to the acidic (pH approximately 6) tumor microenvironment, PNAs were conjugated to pH-low insertion peptide (pHLIP). Treatment of mice harboring platinum-resistant ovarian tumor xenografts with pHLIP-PNA constructs suppressed HOTAIR activity, reduced tumor formation and improved survival. This first report on pHLIP-PNA lncRNA targeting solid tumors in vivo suggests a novel cancer therapeutic approach.