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Pittsburgh, PA, United States

Zorn K.K.,Gynecology and Reproductive science

The treatment strategy of poly(ADP-ribose) polymerase (PARP) inhibition capitalizes on the inherent defect in homologous recombination that occurs in BRCA-deficient tumors by inhibiting the alternative DNA repair pathway involving base excision repair. Although PARP inhibitors were initially considered a potential treatment specifically for tumors with germline BRCA mutations, evidence of frequent somatic deficiency in the BRCA pathway has caused reconsideration of that approach. PARP inhibitors have been shown to have activity in epithelial ovarian, fallopian tube, and primary peritoneal cancer in phase I and II clinical trials. Responses have been seen in both BRCA-deficient and sporadic tumors, and they do not appear to require platinum sensitivity. Although PARP inhibitors are well tolerated as monotherapy, additional study is required to determine their efficacy and toxicity in combination with chemotherapy and other targeted agents. Many hurdles remain along the pathway to drug registration, but the motivation of the community of ovarian cancer patients, researchers, and clinicians to find new treatments may speed the process. Source

Creasman J.S.,Gynecology and Reproductive science | Creasman J.S.,University of San Francisco | Beattie M.S.,University of San Francisco
JAMA Internal Medicine

Background: For women at potentially increased risk for ovarian cancer, data regarding screening are limited. Previous studies have reported on the behaviors of BRCA mutation carriers, but less is behaviors of non-BRCA carriers. We surveyed a large cohort of women after BRCA testing to iden and posttest predictors of risk-reducing and screening interventions. Methods: A median of 3.7 years after BRCA testing, 1447 women who received genetic counseling at 2 hospital sites were surveyed, with a 77.6% response rate. We analyzed data from 1077 survey performed univariate and multivariate logistic regression analyses to identify predictors of risk-red oophorectomy (RRSO), screening transvaginal ultrasonography (TVUS), and screening serum can (CA-125). Results: Among the respondents, 201 women (18.7%) received positive test results for a deleteriou women (9.6%) received true-negative results, and 773 women (71.8%) received uninformative resu of eligible women underwent RRSO and 39.6% used screening procedures. A positive BRCA result (odds ratio [OR], 28.1;95% CI, 16.2-48.6), TVUS (9.5 [4.3-21.0]), and serum CA-125 (13.0 [5.5-29 true-negative BRCA result reduced the OR for RRSO (0.1 [0.0-0.6]), TVUS (0.2 [0.1-0.5]), and ser [0.1-0.7]). Of the 71.8% of women who received uninformative results after BRCA testing, 12.3% underwent RRSO, 33.8% reported ever having undergone screening serum CA-125 since BRCA tes reported ever having undergone screening TVUS since BRCA testing. Conclusions: Results of BRCA testing strongly predict RRSO and ovarian cancer screening. Use of ovarian screening was reported in a sizable percentage of non-BRCA carriers despite insufficient the effectiveness of these interventions. Source

Moise K.J.,Gynecology and Reproductive science | Moise K.J.,Texas Fetal Center
Seminars in Perinatology

Amniotic fluid is typically measured by ultrasound using the amniotic fluid index (AFI) or the maximum vertical pocket (MVP). Although both parameters correlate poorly with the actual amniotic fluid volume measured with dye-dilution methods, cross-sectional studies have been used to establish gestational norms. The current acceptable definition of polyhydramnios in the late second and the third trimester in both singleton and multiple gestations is a MVP > 8. cm, while the definition of oligohydramnios is a MVP < 2. cm. The pocket to be measured should exclude the umbilical cord or fetal parts. Randomized clinical trials have indicated that defining oligohydramnios as a MVP < 2. cm will result in fewer obstetrical interventions and similar perinatal outcomes when compared to an AFI < 5. cm. © 2013 Elsevier Inc. Source

Objective: To estimate whether 6-month use of the levonorgestrel-releasing intrauterine device (IUD) would be higher when insertion occurred within 10 minutes of placental delivery compared with 6-8 weeks postpartum. Methods: We enrolled pregnant women planning vaginal deliveries and desiring a postpartum levonorgestrel-releasing IUD. Patients were randomly assigned when admitted in labor to postplacental or delayed IUD insertion. The women followed up in person at 6-8 weeks and 6 months and were contacted by telephone at 3 months. Women were ineligible for a study IUD postenrollment for intrapartum events including infection, hemorrhage, and cesarean delivery; these women were contacted by phone at 3 and 6 months. Expelled IUDs were replaced per patient preference. Results: Successful IUD placement occurred in 50 of 51 participants (98.0%) and 46 of 51 participants (90.2%) in the postplacental and delayed groups, respectively (P=.2). Expulsion within 6 months occurred in 12 of 50 (24.0%; 95% confidence interval [CI], 13.1-38.2) and two of 46 (4.4%; 95% CI 0.5-14.8) participants, respectively (P=.008). Intrauterine device use at 6 months was 43 of 51 (84.3%; 95% CI 71.4-93.0) and 39 of 51 (76.5%; 95% CI 62.5-87.2), respectively (P=.32). For ineligible patients, only 11 of 41 (26.8%) women were using IUDs at 6 months and two (4.9%) had become pregnant. Conclusion: Intrauterine device use 6 months after delivery is similar in women who have postpartum or scheduled delayed IUD placement through a study after replacement of expelled IUDs. Expulsions are significantly higher with postplacental compared with delayed IUD placement. Women asked to follow up with their own health care providers for delayed insertion are significantly less likely to receive an IUD. © 2010 by The American College of Obstetricians and Gynecologists. Source

Pal L.,Gynecology and Reproductive science

A fraction of cells residing in the uterine endometrium exhibit functional pluripotent potential, allowing them to be classified as adult stem cells. While the physiological relevance of this cell population is mostly conjectural at this juncture, uterine endometrial stem cells (UESC's) may underline pathogenesis of certain common gynecological disorders, such as endometriosis and adenomyosis. The ease of access and harvesting of UESC's and the diverse differentiation potential of this cell population has identified the uterine endometrium as a valuable source of autologous stem cells that can be harnessed through judicious application of principals of regenerative medicine. This mini review offers a glimpse into the journey, and an introduction to the spectrum of disorders that UESC's have the potential of impacting. © 2015 Elsevier Ireland Ltd. Source

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