Background Uterine Fibroids (UFs) growth is ovarian steroid-dependent. Previous studies have shown that estrogen and progesterone play an important role in UF development. However, the mechanism underlying progesterone induced UF pathogenesis is largely unknown. In this study, we determined the expression of progesterone receptor and compared the expression level of progesterone-regulated genes (PRGs) in human myometrial cells from normal uteri (MyoN) versus uteri with UFs (MyoF) in response to progesterone. Methods Primary human myometrial cells were isolated from premenopausal patients with structurally normal uteri (PrMyoN). Primary human myometrial cells were also isolated from uterus with UFs (PrMyoF). Isolated tissues were excised at least 2 cm from the closest UFs lesion(s). Progesterone receptor (PR) expression was assessed using Western blot (WB). Expression levels of 15 PRGs were measured by qRT-PCR in PrMyoN and PrMyoF cells in the presence or absence of progesterone. Results WB analysis revealed higher expression levels of PR in PrMyoF cells as compared to PrMyoN cells. Furthermore, we compared the expression patterns of 15 UF-related PRGs in PrMyoN and PrMyoF primary cells in response to progesterone hormone treatment. Our studies demonstrated that five PRGs including Bcl2 , FOXO1A, SCGB2A2, CYP26a1 and MMP11 exhibited significant progesterone-hyper-responsiveness in human PrMyoF cells as compared to PrMyoN cells ( P < 0.05). Another seven PRGs, including CIDEC, CANP6, ADHL5 , ALDHA1, MT1E, KIK6, HHI showed gain in repression in response to progesterone treatment ( P > 0.05). Importantly, these genes play crucial roles in cell proliferation, apoptosis, cell cycle, tissue remodeling and tumorigenesis in the development of UFs. Conclusion These data support the idea that progesterone acts as contributing mechanism in the origin of UFs. Identification and analysis of these PRGs will help to further understand the role of progesterone in UF development.
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Purpose: To evaluate and compare the reliability, accuracy and the cost benefit ratio of vaginal washing fluid urea, creatinine, Beta Human Chorionic Gonadotropin (β-HCG) and placental alpha Microglobulin-1 (PAMG-1) for diagnosis of premature rupture of membranes (PROM). Material and Methods: A diagnostic study conducted on 70 patients. The patients were divided into three groups: Group A (n = 25): (Confirmed PROM group) patients who were either in labor or not in labor, Gestational age was from 24 weeks onwards and fulfilled the following criteria and/or two of these criteria with low AFI positive pooling, positive nitrazine paper test, positive fern test. Group B (n = 25): (Suspected PROM group) patients who fulfilled the following criteria: Patients with fluid leakage complaint with negative pooling and/or negative nitrazine paper test and/or negative fern test. Group C (n = 25): (Control group with no PROM) patients that were admitted to prenatal clinic for their regular prenatal control visit with 24 -42 weeks of gestational age without any complaint or complication and with negative pooling, negative nitrazine paper test and/or negative fern test. The vaginal washing fluid urea, creatinine, Beta-Human Chorionic Gonadotropin (β-HCG) and placental alpha Microglobulin-1 (PAMG-1) were determined for diagnosis of premature rupture of membranes (PROM). Results: PAMG-1 detection in cervico vaginal discharge was a very good test for diagnosis of PROM with high sensitivity, specificity, positive predictive value, negative predictive value, accuracy and P-value (96%, 100%, 100%, 95.84%, 97.78% and <0.0001 respectively). Urea and Creatinine is the second option in diagnosis of PROM with high sensitivity, and specificity after PAMG-1 with a privilege of low cost than PAMG-1. Furthermore they were more accurate than β-HCG. Conclusion: Detection of PAMG-1 in cervico vaginal discharge is promising How to cite this paper: Borg, H.M., Omar, M. and Suliman, G.A. (2019) The Study of Vaginal Fluid Urea, Creatinine, B-HCG and Placental Alpha-1 Microglobulin in Diagnosis of Premature Rupture of Membranes. Open Journal of Obstetrics and Gynecology, 9, 811-826.
We report the results of ASTEROID1, examining the efficacy and safety of the novel SPRM, vilaprisan, in women with UFs.DESIGN: In this multicenter, randomized, double-blind, placebocontrolled, parallel-group study, women were randomized to oral placebo or vilaprisan 0.5 mg, 1 mg, 2 mg, 4 mg, once daily. Treatment began during the first week of the menstrual cycle and continued for 12 weeks, with a 24 week follow-up. The primary efficacy variable was amenorrhea.MATERIALS AND METHODS: HMB was assessed using a daily bleeding diary, alkaline hematin method (except in Japan), and menstrual pictogram. UFs were assessed using transvaginal/abdominal ultrasound, and pelvic magnetic resonance imaging. Fibroid related symptoms and health-related quality of life (HRQoL) were assessed. Safety parameters included adverse events (AEs), laboratory evaluations, and endometrial biopsies to assess progesterone receptor modulator-associated endometrial changes (PAECs). Statistical analyses were performed using Statistical Analysis Software (SAS Institute Inc, Cary, NC, USA). All variables were analyzed consistent with their type using descriptive statistics methods.RESULTS: 309 women were randomized equally to the 5 study arms; 286 women completed treatment. At doses R 1 mg, controlled bleeding (< 80 ml in all subsequent 28-day intervals) was achieved within 3 days in the majority of patients; 97-100% of patients achieved controlled bleeding by the end of the treatment course; amenorrhea (<2 mL/28 days) was achieved in 87%-92% of patients by the end of the treatment course. Dose-dependent reductions in fibroid volume were seen with vilaprisan, up to approximately 40% at the highest dose. Fibroid related symptoms and HRQoL scores improved in all groups. The number of patients with treatment-emergent AEs was similar between the active and placebo groups, with no dose-dependent pattern. Laboratory parameters did not indicate any safety signal. No treatment-emergent critical endometrial findings were found in biopsies. PAECs were observed in 40% of patients at the end of treatment and their frequency returned to baseline levels during follow up.CONCLUSIONS: In ASTEROID1, vilaprisan 1-4 mg effectively stops HMB, shrinks UFs, and improves quality of life. Vilaprisan was well tolerated. Expected PAECs were observed and were reversible after treatment. Further long-term studies of efficacy and safety are warranted.
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