OBJECTIVETo evaluate the clinical effect and safety of combined use of methotrexate and mifepristone for treatment of ectopic pregnancy.

METHODSBy searching in the major databases of CNKI, CBMdisk and Pubmed according to the criteria of evidence-based medicine, we collected data of randomized controlled trials pertaining to combined use of methotrexate and mifepristone in the treatment of ectopic pregnancy.

RESULTSTwenty-three randomized controlled trials involving totally 1 706 patients were collected according to the inclusion criteria, and meta-analysis of the data indicated that combined use of methotrexate and mifepristone can be of great value in the management of ectopic pregnancy in comparison with exclusive use of methotrexate [ combined odds ratio (OR) was 2.84 with 95%confidence interval [CI] (2.18, 3.69), Z=7.79, P<0.000 01].

CONCLUSIONThe clinical evidence derived from the analysis suggests that the combination of methotrexate and mifepristone for ectopic pregnancy management can be effective with good safety security and minimal side effects, but still, this conclusion needs further verification by randomized, double-blind, and controlled trials with larger sample size and more rigorous trial design.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Abortifacient Agents, Steroidal ; administration & dosage ; Adult ; Drug Therapy, Combination ; Female ; Humans ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Pregnancy ; Pregnancy, Ectopic ; drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome

AIMTo observe the metabolic interaction between diphenytriazol and steroid hormone drugs, and provide some useful information for clinical medication.

METHODSThe steroid hormone drugs which may be co-administrated with diphenytriazol were selected, such as mifepriston, estradiol, medroxyprogesterone acetate, progesterone, norethisterone and so on. Diphenytriazol was incubated with each drug in rat liver microsome. The residual concentration of diphenytriazol or steroid hormone drugs in the microsomal incubates was determined by reversed-phase high-performance liquid chromatography, separately. The inhibition constants (K(i)) for each of them were calculated.

RESULTSThe inhibition constant K(is) of diphenytriazol for the metabolism of mifepristone, estradiol, medroxyprogesterone acetate, progesterone and norethisterone were (201.3 +/- 1.0), (94 +/- 4), (128.7 +/- 2.2), (64 +/- 5) and (80 +/- 4) micromol x L(-1), respectively. The inhibition constants K(i) of steroid hormone drugs for the metabolism of diphenytriazol was (66.9 +/- 2.2) micromol x L(-1) for estradiol, (60.0 +/- 2.3) micromol x L(-1) for medroxyprogesterone acetate, (163 +/- 10) micromol x L(-1) for progesterone and (88 +/- 5) micromol x L(-1) for norethisterone, respectively.

CONCLUSIONDiphenytriazol shows metabolism interaction with steroid hormone drugs such as estradiol, medroxyprogesterone acetate, progesterone and norethisterone.

Abortifacient Agents, Nonsteroidal ; metabolism ; pharmacology ; Abortifacient Agents, Steroidal ; metabolism ; Animals ; Contraceptives, Oral, Synthetic ; metabolism ; Drug Interactions ; Estradiol ; metabolism ; Female ; In Vitro Techniques ; Medroxyprogesterone ; metabolism ; Microsomes, Liver ; metabolism ; Mifepristone ; metabolism ; Rats ; Rats, Sprague-Dawley ; Triazoles ; metabolism ; pharmacology

Abortifacient Agents, Nonsteroidal ; pharmacology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Pinellia ; chemistry ; Plant Proteins ; pharmacology ; Pregnancy

Primate placentation involves a series of cell proliferation, immigration and apoptosis which account for the progressive tissue remodelling at the implantation site. p53 is an important proto-oncogene involved in the regulation of cell-cycle and apoptosis. To study the effect of RU486 on apoptosis and expression of p53 at the fetal-maternal interface, the location of apoptotic cells and expression of p53 were examined using in situ 3'-end labeling method, immunohistochemistry and Western blot assay at the fetal-maternal interface of normal and RU486 treated rhesus monkey. Western blot analysis showed the specificity of the anti-human antibody used with the monkey tissue. In the placental villi, the apoptotic nuclei were observed mainly in the syncytiotrophoblast and part of the cytotrophoblast within the cell column; p53 protein was detected mainly in the cytotrophoblast. In the endometrium, positive signals for apoptosis and p53 were detected in some stromal cells. After two days of mifepristone treatment, the apoptotic cells increased significantly in both placental villi and endometrium. In the villi, the increased apoptotic nuclei were mainly localized to the cytotrophoblast. At the same time, p53-positive nuclei also increased in both villous cytotrophoblast cells and endometrial stromal cells, after the treatment of RU486. These results suggest that apoptosis and expression of p53 are essential in regulating trophoblastic homeostasis by controlling its proliferation in normal placenta, whereas the up-regulation of p53 protein may play an important role in apoptosis that happens at the fetal-maternal interface induced by RU486.
Abortifacient Agents, Steroidal ; pharmacology ; Animals ; Apoptosis ; drug effects ; Chorionic Villi ; pathology ; Female ; Macaca mulatta ; Mifepristone ; pharmacology ; Placentation ; drug effects ; physiology ; Pregnancy ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

AIMTo establish a RP-HPLC method for determination of diphenytriazol (DL111-IT) in rat hepatic microsomes.

METHODSDL111-IT in rat hepatic microsomal incubates was extracted with chloroform, using diazepam as internal standard. The determination was performed on a Lichrospher ODS-C18 reversed column (25 cm x 0.46 cm ID) with mobile phase of methanol-pH 7.5 phosphate buffer (70:30) at a flow-rate of 1.0 mL.min-1. A UVVIS detector was operated at 235 nm.

RESULTSThe assaywas linear from 1.01-101.0 micrograms.mL-1 for DL111-IT. The limit of detection was 0.15 microgram.mL-1 (signal-to-noise ratio 3) and the limit of quantification was 1.01 micrograms.mL-1(RSD < 10%, n = 4). The method afforded average recoveries of (100.3 +/- 1.9)% (n = 5), and intra-day and inter-day RSD were less than 5.0%(n = 5). The method allowed study of the in vitro phase I metabolism of DL111-IT in rat liver microsomal incubates. The microsomes induced by beta-naphthoflavone showed high enzymatic activity for DL111-IT phase I metabolism.

CONCLUSIONThe method is simple, accurate and can be used to study the metabolism of DL111-IT in rat hepatic microsomes.

Abortifacient Agents, Nonsteroidal ; analysis ; metabolism ; Animals ; Cell Separation ; Chromatography, High Pressure Liquid ; methods ; Female ; Microsomes, Liver ; metabolism ; Rats ; Rats, Sprague-Dawley ; Triazoles ; analysis ; metabolism

OBJECTIVETo select a safe, quick and effective method for terminating ectopic pregnancy (EP) with few adverse effects.

METHODSPatients were divided into 2 groups. The observed group was treated with methotrexate (MTX, 50 mg/m2 for single dose intramuscular injection) plus RU 486 (600 mg taken orally in the morning with empty stomach, followed with fasting for 2 hrs) and Waiyun Zhuyu decoction (WZD, one dose a day for 7-10 days). The control group was only treated with MTX, with the same regimen as used in the observed group.

RESULTSThe curative rate, time for blood beta-HCG recovering, lump absorption time, and tube recanalization rate in the observed group were better than those in the control group (P < 0.01). CONCLUSION; The key links for successfully treating EP with conservative drug therpy are to diagnose the disease early and clearly, and to select indicative subject strictly. The scheme of single dose administration of MTX plus RU486 combined with WZD, with its high efficacy and few adverse reaction, may be used as the first choice for referential clinical drugs administration.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Phytotherapy ; Pregnancy ; Pregnancy, Ectopic ; drug therapy ; Retrospective Studies ; Treatment Outcome

The purpose of this study is to evaluate predictors of success of repeated injections of methotrexate in the single-dose regimen for the treatment of tubal ectopic pregnancy. All patients who had ectopic tubal pregnancy and were treated with a single dose regimen were retrospectively identified. 126 patients were treated with methotrexate. Among them, 39 patients were adequate for this study. 33 were treated with the 2nd dose and 27 were successfully cured. Additionally, 6 who were injected with the 3rd dose were all cured as well. Therefore, in our study, the success rate for the repeated injections of methotrexate was found to be 84.6% (33/39). The mean initial beta-hCG level was significantly lower in patients who were successfully treated than in patients who failed (3915.3+/-3281.3 vs. 8379.7+/-2604.4 IU/mL, p<0.05). The success rate is 96% when the beta-hCG level is less than 6,000 IU/mL and is 58% when beta-hCG is greater than 6,000 IU/mL (OR=18.57, 95% CI 1.86-185.89). The initial beta-hCG level is the only factor that has significant meaning as predictor of success of repeated injections of methotrexate in the single-dose regimen. Repeated injections of methotrexate may be particularly effective when the initial beta-hCG level is below 6,000 IU/mL.
Abortifacient Agents, Nonsteroidal/administration & dosage/therapeutic use ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Female ; Humans ; Injections ; Methotrexate/administration & dosage/*therapeutic use ; Predictive Value of Tests ; Pregnancy ; Pregnancy, Tubal/blood/*drug therapy ; Retrospective Studies ; Time Factors ; Treatment Outcome

The objective of this study is to describe the clinical outcomes of patients treated for cervical pregnancy with or without methotrexate (MTX) and to evaluate the effects of MTX in the treatment of cervical pregnancy. Between January 1993 and February 2000, 31 patients were diagnosed with cervical pregnancy. Twenty-two patients were treated with MTX chemotherapy and nine patients were treated with surgical procedures without MTX treatment. In the non-MTX treatment group, three patients underwent total abdominal hysterectomy, five required adjuvant procedures to control the bleeding during dilatation and curettage (D&C) and only one patient was treated with a simple D&C. In the MTX treatment group, fourteen (63.6%) patients were treated with only MTX and eight (36.4%) cases underwent concomitant procedures (simple curettage, curettage and Foley catheter tamponade, cer-vical cerclage, ligation of the descending branches of uterine arteries, or ligation of hypogastric arteries). The uterus was preserved in all cases and three women delivered healthy babies in their subsequent pregnancy. In conclusion, early diagnosis, appropriate MTX regimen in combination of necessary adjuvant conservative procedures could contribute to successful treatment with preservation of the uterus and future reproductive ability.
Abortifacient Agents, Nonsteroidal/administration & dosage ; Comparative Study ; Dilatation and Curettage/*statistics & numerical data ; Female ; Humans ; Incidence ; Korea/epidemiology ; Methotrexate/*administration & dosage ; Pregnancy ; Pregnancy, Ectopic/*drug therapy/epidemiology/*surgery ; Retrospective Studies ; Risk Assessment/*methods ; Risk Factors ; Treatment Outcome

OBJECTIVETo evaluate the therapeutic effect and safety of pelvic methotrexate (MTX) injection via the posterior fornix for treatment of tubal pregnancy.

METHODSNinety-six patients with tubal pregnancy (mean age 21-40 years) were randomized into 3 groups for treatment with pelvic MTX injection via the posterior fornix+mifepristone+traditional Chinese medicine (experiment group), intramuscular MTX injection+mifepristone+traditional Chinese medicine (control group I), or mifepristone+traditional Chinese medicine (control group II). On days 4 and 7 of the treatment, blood β-HCG of the patients in different groups was detected, and in cases with continuous reduction of blood β-HCG or a reduction by over 15%, β-HCG was checked every week. One week after the treatment, the size of the mass was measured by B-mode ultrasound. The clearance time of β-HCG and the hospital stay of the patients were recorded.

RESULTSTwenty-nine patients in the experimental group were treated successfully, with a cure rate of 90.6%, which was significantly higher than those in the two control groups (P<0.05). The clearance time of β-HCG and hospital stay were also much shorter in the experimental group (P<0.05).

CONCLUSIONPelvic MTX injection via the posterior fornix is a convenient procedure associated with minimal complications and serves as a good alternative for treatment of tubal pregnancy.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Adult ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Injections ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Pelvis ; Phytotherapy ; Pregnancy ; Pregnancy, Tubal ; drug therapy ; Vagina ; Young Adult

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.
Abortifacient Agents, Nonsteroidal/adverse effects ; Abortion, Induced/*adverse effects ; Capsules ; Drugs, Chinese Herbal/*therapeutic use ; Menstruation/*drug effects ; Phytotherapy ; Pregnancy Trimester, First ; Uterine Hemorrhage/etiology ; Uterine Hemorrhage/*prevention & control