Subject(s)
Ovarian Hyperstimulation Syndrome/genetics , Point Mutation , Pregnancy Complications , Receptors, FSH/genetics , Adult , Animals , Cell Line , Chlorocebus aethiops , Chorionic Gonadotropin/metabolism , Female , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Germ-Line Mutation , Gonadal Steroid Hormones/blood , Heterozygote , Humans , Ovarian Hyperstimulation Syndrome/blood , Ovarian Hyperstimulation Syndrome/diagnosis , Ovary/diagnostic imaging , Ovary/pathology , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/diagnosis , Receptors, FSH/metabolism , Receptors, LH/metabolism , Sequence Analysis, DNA , Sex Hormone-Binding Globulin/analysis , UltrasonographyABSTRACT
BACKGROUND: Medical treatment of ectopic pregnancies is common. To increase the efficacy of methotrexate, the association of mifepristone has been proposed. METHODS: We performed a large prospective multicentre double-blind sequential randomized trial in order to compare the efficacy of methotrexate and mifepristone (600 mg given orally) versus methotrexate and placebo. RESULTS: A total of 212 ectopic pregnancies was randomized. There was no significant difference in the initial characteristics between the two groups. There was no significant difference in the success rate of medical treatment between the methotrexate-mifepristone (n = 113) and the methotrexate-placebo group (n = 99): 79.6% (90/113) versus 74.2% (72/97) respectively, RR (95% CI): 1.07 (0.92-1.25), P = 0.41, non-significant. However, there was a quantitative interaction between progesterone level and effect of treatment: when progesterone level was >/=10 ng/l, the efficacy of the combination of mifepristone and methotrexate was significantly higher than the combination of methotrexate and placebo, with an 83.3% success rate (15/18) versus 38.5% (5/13) respectively. CONCLUSIONS: Our study failed to demonstrate any benefit of the addition of mifepristone to methotrexate. By contrast, the quantitative interaction between treatment effect and baseline serum progesterone suggested that this combination could be limited to ectopic pregnancies associated with high serum progesterone concentrations.
Subject(s)
Abortifacient Agents, Nonsteroidal/therapeutic use , Abortifacient Agents, Steroidal/therapeutic use , Methotrexate/therapeutic use , Mifepristone/therapeutic use , Pregnancy, Ectopic/drug therapy , Abortifacient Agents, Nonsteroidal/adverse effects , Abortifacient Agents, Steroidal/adverse effects , Adult , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Methotrexate/adverse effects , Mifepristone/adverse effects , Placebos , Pregnancy , Pregnancy, Ectopic/blood , Progesterone/blood , Treatment OutcomeABSTRACT
This study was designed to evaluate high-frequency power Doppler (PDS) and to quantify treatment-induced changes in an experimental autochthonous mammary tumour model in rats. A total of 13 rats with N-methyl, N-nitroso urea-induced mammary tumours were split into three courses; 6 rats were treated with epirubicin, 3 received a placebo injection and 4 had irradiation of their tumour with a direct electron beam using a single dose of 18 Gy. In all groups, treatment began when the tumour area reached at least 1 cm(2) and was preceded by the first power Doppler sonography study of the tumour (Echo #1). Echo #2 was carried out in the middle of the placebo or epirubicin treatment (after 3 weeks) or 7 days after irradiation in the irradiated group. Echo #3 was carried out at the end of placebo or epirubicin treatment or 28 days after irradiation. Then colour pixel density (CPD) and vascularity index (VI) were quantitated. Intraobserver and interobserver variability of the CPD and VI quantitation was low (r = 0.99 and 0.97, respectively, for intraobserver and interobserver variability of the CPD values). The monitoring of CPD and VI showed an increase with time during the observation period. No increase in CPD or VI was observed in treated mammary tumours (p < 0.01). Power Doppler sonography quantitation of angiogenesis is reproducible, noninvasive and feasible in this in vivo breast cancer model. The monitoring of angiogenesis according to different treatments is feasible in real-time. Further studies are needed to investigate the predictive value of CPD and VI on sensitivity of mammary tumours to anticancer treatment.
