Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol. (17/197)

OBJECTIVE: To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol. METHODS: Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. RESULTS: The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91 +/- 20.74 IU/mg.protein and 64.25 +/- 35.81 IU/mg.protein respectively, lower than those in the normal decidua group (99.76 +/- 58.61 IU/mg.protein, P < 0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43 +/- 0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90 +/- 0.16) was not significantly different from that in the normal decidua group (0.94 +/- 0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P > 0.05). CONCLUSIONS: Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion.  (+info)

Pharmacokinetics of different routes of administration of misoprostol. (18/197)

BACKGROUND: The pharmacokinetic parameters of four different routes of administration of a single dose of 400 microg of misoprostol were studied. METHODS: A total of 40 women undergoing termination of pregnancy by suction evacuation was randomized by computer model to receive 400 microg of misoprostol by one of four routes: (i) sublingual (ii) oral (iii) vaginal and (iv) vaginal with addition of water. Venous blood samples were taken at 0, 1, 2, 5, 10, 20, 30, 45, 60, 120, 240 and 360 min after the administration of misoprostol. Misoprostol acid (MPA) was determined in serum samples using gas chromatography/tandem mass spectrometry. RESULTS: Sublingual misoprostol achieved the highest serum peak concentration (Cmax) (574.8 +/- 250.7 pg/ml) of MPA and this was significantly higher than those in the other groups [Oral: 287.6 +/- 144.3 pg/ml (P < 0.01), vaginal: 125.2 +/- 53.8 pg/ml (P < 0.001) and vaginal with water: 162.8 +/- 57.1 pg/ml (P < 0.001)]. The time to peak concentration (Tmax) was similar in both the sublingual (26.0 +/- 11.5 min) and oral groups (27.5 +/- 14.8 min) and was significantly shorter than those in both vaginal groups. The area under the MPA concentration versus time curve up to 360 min in the sublingual group (743.7 +/- 291.2 pg.h/ml) was significantly greater than those in oral (402.8 +/- 151.6 pg.h/ml, P < 0.05) and vaginal (433.7 +/- 182.6 pg.h/ml, P < 0.05) groups, but no significant difference was found between sublingual and vaginal administration if water (649.3 +/- 333.8 pg.h/ml) was added. CONCLUSION: The new sublingual route of administration of misoprostol demonstrated a great potential to be developed into a method of medical abortion.  (+info)

Cervical Shirodkar cerclage may be the treatment modality of choice for cervical pregnancy. (19/197)

BACKGROUND: Our objective was to evaluate the use of cervical suture in cervical pregnancy. METHODS AND RESULTS: All cases of cervical pregnancy diagnosed and treated in the gynaecological department at the Sheba Medical Center between 1994-2000 were included in the study. Eight such cases were diagnosed. The first four cases were treated medically. The last four cases (the study group) of cervical pregnancy, including one case of heterotopic pregnancy, were treated successfully with placement of Shirodkar cerclage. CONCLUSION: Cervical cerclage may be considered as the treatment of choice in cases of cervical pregnancies. It may be the only therapy in cases of heterotopic pregnancies (intrauterine and cervical pregnancy).  (+info)

Pilot study on the use of repeated doses of sublingual misoprostol in termination of pregnancy up to 12 weeks gestation: efficacy and acceptability. (20/197)

BACKGROUND: A sublingual misoprostol-alone regimen was used in 50 women requesting medical abortion at up to 12 weeks gestation. The efficacy and acceptability of this regimen were studied. METHODS: The women were given 600 microg misoprostol sublingually every 3 h for a maximum of 5 doses. RESULTS: The overall complete abortion rate was 86% (95% confidence interval: 74-93). The mean number of doses of misoprostol required was 4.1 +/- 1.1. There was no significant change in haemoglobin concentration and the median duration of vaginal bleeding was 15 days (range: 7-56). Diarrhoea, fever and chills were the most common side-effects. The acceptability of this regimen of misoprostol was good: 97.7% of the women who had a complete abortion would choose this method again and 88.4% would recommend it to others. They preferred sublingual misoprostol as it is convenient to take, avoids the painful vaginal administration and gives more privacy during the abortion process. CONCLUSION: This regimen of sublingual misoprostol is an effective and acceptable method of medical abortion. Randomized controlled trials are required to compare the efficacy of various misoprostol-alone regimens of medical abortion. Pharmacokinetic studies and clinical trials are needed to find out the most appropriate dose, dosing interval and route of administration of misoprostol.  (+info)

Medical abortion: overview and management. (21/197)

Medical abortion regimens are safe, effective, and offer a new range of choices for patients and providers. In September 2000, the US Food and Drug Administration (FDA) approved a regimen of mifepristone and misoprostol, which effects abortion by luteolysis, uterine contractions, and expulsion of the products of conception without surgical instrumentation. The regimen requires that a provider be capable of diagnosing ectopic gestations and be able to make arrangements for a surgical abortion in the case of failure or medical emergencies. With a medical abortion, the pregnancy is passed spontaneously, and there may not be tissue obtained for confirmation. Physicians must be aware of their state requirements with regard to expulsed tissue examination. Completion of the procedure can be established by ultrasound or by measurement of serum levels of human chorionic gonadotropin (hCG). The FDA-approved protocol allows for use up to 49 days after the first day of the last menstrual period (LMP) and consists of mifepristone 600 mg orally on day 1, misoprostol 400 mcg orally on day 3, and a follow-up appointment on days 12-20. Half of all patients pass their pregnancy in the first few hours after the second visit. It is important to be able to determine the difference between expected bleeding, 14 days on average, and the complication of hemorrhage, as 2% to 10% of patients require a surgical abortion. Continuing viable pregnancies are rare. Several other regimens can safely expand options and reduce expense, including protocols using methotrexate. Medication indications and contraindications, management strategies for patients undergoing treatment with these regimens, and safety issues are reviewed.  (+info)

A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. (22/197)

BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical abortion. This randomized, double-blinded, placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 250 women with gestations < or = 56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol. Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 114 out of 119 subjects (95.7%) after mifepristone followed by vaginal misoprostol. In all, 110 out of 125 subjects (88.0%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (P < 0.05). CONCLUSIONS: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone. The 88% efficacy obtained with vaginal misoprostol alone may be clinically acceptable when mifepristone is not available.  (+info)

Inhibition of progesterone secretion with trilostane for mid-trimester termination of pregnancy: randomized controlled trials. (23/197)

BACKGROUND: Progesterone is central to the maintenance of pregnancy, and is thus the ideal target for fertility regulation. Two mechanisms by which progesterone can be targeted are: receptor blockade and reduction of progesterone production through enzyme inhibition. Mifepristone, a receptor blocker, is usually given as 'pretreatment' prior to prostaglandin administration in mid-trimester termination of pregnancy (TOP). Unfortunately, there are difficulties accessing mifepristone in developing countries, and TOP is therefore performed using prostaglandins alone, which results in unacceptably long induction-to-abortion intervals. Trilostane is a 3beta-hydroxysteroid dehydrogenase inhibitor which reduces progesterone production. In these mid-trimester studies it is evaluated as a method of pretreatment prior to misoprostol administration. METHODS: Three consecutive randomized controlled trials comparing different trilostane regimens for pretreatment were performed. In study 1, trilostane was compared with placebo; in study 2, two doses of trilostane were compared (1080 mg and 720 mg); in study 3, the effect of adding danazol to trilostane as combination therapy was evaluated. The primary outcome in all the studies was the induction-to-abortion interval. Serum progesterone, estradiol and cortisol were measured serially during treatment. RESULTS: In study 1, 48 women were randomized. The median induction-to-abortion interval was 9 h in the trilostane group and 18.5 h in the placebo group (P < 0.0001). Progesterone and estradiol production was significantly reduced in the women receiving trilostane, with maintenance of diurnal cortisol variation. Twenty-eight women were randomized in study 2, which demonstrated that there was no significant difference in the induction-to-abortion interval using 1080 mg and 720 mg trilostane when compared with the higher doses used in study 1. Study 3, in which 40 women were included, failed to show any additional benefit using combination therapy with danazol and trilostane. CONCLUSIONS: Trilostane is an effective pretreatment agent in mid-trimester TOP.  (+info)

Conservative management of two ectopic pregnancies implanted in previous uterine scars. (24/197)

Cesarean section scar pregnancy is rare. A variety of interventions have been implemented to terminate the pregnancy and preserve the uterus; however, the optimal treatment is unknown. We describe two cases of this rare condition diagnosed by transvaginal ultrasound. In the first case the diagnosis of an 8-week non-viable gestation in a uterine scar was made sonographically in a 40-year-old woman. The patient was treated with intramuscular methotrexate. Myometrial integrity was suggested both by ultrasound findings and laparoscopic findings. In the second case, an early cervicoisthmic pregnancy in a uterine scar was diagnosed by sonography in a 39-year-old woman. This patient was treated successfully with a full course of intramuscular methotrexate. Complete disappearance of the gestational sac took place 4 months following beta-human chorionic gonadotrophin normalization. Intramuscular methotrexate may be a treatment alternative for Cesarean section scar pregnancies.  (+info)