Safety, efficacy and acceptability of outpatient mifepristone-misoprostol medical abortion through 70 days since last menstrual period in public sector facilities in Mexico City.

Extensive evidence exists regarding the efficacy and acceptability of medical abortion through 63 days since last menstrual period (LMP). In Mexico City's Secretariat of Health (SSDF) outpatient facilities, mifepristone-misoprostol medical abortion is the first-line approach for abortion care in this pregnancy range. Recent research demonstrates continued high rates of complete abortion through 70 days LMP. To expand access to legal abortion services in Mexico City (where abortion is legal through 12 weeks LMP), this study sought to assess the efficacy and acceptability of the standard outpatient approach through 70 days in two SSDF points of service. One thousand and one women seeking pregnancy termination were enrolled and given 200 mg mifepristone followed by 800 µg misoprostol 24-48 hours later. Women were asked to return to the clinic one week later for evaluation. The great majority of women (93.3%; 95% CI: 91.6-94.8) had complete abortions. Women with pregnancies ≤ 8 weeks LMP had significantly higher success rates than women in the 9th or 10th weeks (94.9% vs. 90.5%; p = 0.01). The difference in success rates between the 9th and 10th weeks was not significant (90.0% vs. 91.2%; p = 0.71). The majority of women found the side effects (82.9%) and the use of misoprostol (84.4%) to be very acceptable or acceptable. This study provides additional evidence supporting an extended outpatient medical abortion regimen through 10 weeks LMP.

Late second-trimester abortions induced with mifepristone, misoprostol and oxytocin: a report of 428 consecutive cases.

BACKGROUND: The aim of the study was to assess efficacy and safety of administering 200 mg of mifepristone between 36 and 48 h before the insertion of 800 mcg of vaginal misoprostol to induce late second-trimester abortion between 19.1 and 25.6 weeks gestation. STUDY DESIGN: A consecutive series of 428 women who requested a termination of their pregnancy between 19.1 and 25.6 weeks of gestation were analyzed. METHODS: Each woman received 200 mg of mifepristone orally between 36 and 48 h before the vaginal administration of 800 mcg of misoprostol and the insertion of two Dilapan intracervical tents if the gynecologist deemed necessary. Four hours after misoprostol, amniorrhexis was performed and intravenous oxytocin infusion started. The variables for assessing efficacy were the number of complete abortion without dilation and evacuation (D&E) and the time elapsed since misoprostol administration until the abortion. RESULTS: Complete abortion without surgery occurred in 387/428 (90.4%) subjects, and the mean time for misoprostol to abortion was 6.9+/-3.1 (SD) h. In 32/428 (7.5%) patients, it was necessary to administer a second 600-mcg misoprostol dose. The mean total oxytocin used was 9.7+/-7.9 (SD) IU. In 41/428 (9.6%) women, the abortion process was completed by D&E. A uterine rupture occurred in one woman with a previous cesarean section. CONCLUSION: The method of abortion that combined mifepristone, misoprostol and oxytocin was effective for interrupting pregnancies between 19.1 and 25.6 weeks of gestation. It is advisable to be well trained in D&E technique in case of possible failures and/or abortion inductions that are excessively prolonged.

Arrest of preterm labor in rat and mouse by an oral and selective nonprostanoid antagonist of the prostaglandin F2alpha receptor (FP).

OBJECTIVE: The purpose of this study was to assess the tocolytic effect of AS604872, an orally active, potent, and selective prostanoid prostaglandin F2alpha receptor (FP) antagonist. STUDY DESIGN: Compound AS604872 was characterized and tested for its ability to block uterine contraction and delay preterm parturition in rodent models. RESULTS: AS604872 inhibited spontaneous uterine contractions in pregnant rat near term. In pregnant mouse, AS604872 delayed parturition induced by either the antiprogesterone RU-486 or the endotoxin lipopolysaccharide. Pups from treated mothers were delivered alive. The efficacy of AS604872 was superior to the beta-mimetic drug ritodrine. Combination of AS604872 and ritodrine showed an additive inhibitory effect on spontaneous uterine contractions in rat. CONCLUSION: A selective antagonist of the FP receptor suppresses uterine contractility and delays labor. Our findings identify a new potential modality for the pharmacological management of preterm labor.

An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression.

OBJECTIVE: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications. METHOD: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003. RESULTS: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance. CONCLUSION: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study.

Slowing the progression of cognitive decline in Alzheimer's disease using mifepristone.

High circulating levels of glucocorticoid hormones adversely affect cognition. Previous studies exploring the hypothalamic-pituitary-adrenal (HPA) axis and basal cortisol levels in the elderly reported that subjects with mid-range cortisol levels outperformed subjects with high cortisol levels on assessments of memory and attention. This study examines the efficacy of mifepristone, a glucocorticoid-antagonist, in decelerating the rate of cortisol-related cognitive decline in subjects with mile-to-moderate Alzheimer's disease (AD). Rate of cognitve decline is compared in AD subjects randomized to receive 200 mg of mifepristone daily for 6 mo or placebo. The Alzheimer's Disease Assessment Scale (ADAS) and the Folstein Mini Mental Status Exam (MMSE) will be the primary measures used to assess change in cognitve function over the 6 mo period, supplemented by a neuropsychological battery testing memory and language and reasoning skills. During each visit, subjects will have samples collected for determination of plasma adrenocorticotropin (ACTH), serum cortisol and salivary cortisol levels to assess HPA axis activity. The placebo arm of this study also investigate whether subjects with high baseline cortisol levels experience greater declines in cognitive impairment over time relative to subjects with Ad who have low baseline cortisol levels. Additionally, this study test the hypothesis that AD subjects with elevated cortisol at baseline will perform more poorly on neuropsychological exams that do subjects with low cortisol.

Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception.

OBJECTIVE: To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN: Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING: Community family planning clinic. SUBJECTS: 616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES: Number of pregnancies, incidence of side effects, and timing of next period. RESULTS: The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS: Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.

PIP: In Manchester, England, a physician administered 3 different oral postcoital contraceptives to 616 16-45 year old women who came to the Palatine Centre obstetrics and gynecology clinic within 72 hours after intercourse, most of whom were 25 years old and primigravidae, to compare the effectiveness and acceptability of the 3 different postcoital methods. 66% were using a barrier method when they became pregnant. The probability of pregnancy was 34.7 pregnancies, but only 14 actually occurred. The researchers estimated 11.3 pregnancies for the women who followed the Yuzpe regimen (100 mcg ethinyl estradiol and 500 mcg levonorgestrel every 12 hours), but only 5 resulted for a pregnancy rate of 2.62%. 2 women continued their pregnancies and vaginally delivered full-term infants. They predicted 11.7 pregnancies for the women who took 600 mg danazol every 12 hours, but only 9 happened for a pregnancy rate of 4.66%. Only 1 woman continued her pregnancy and delivered a full term infant. They predicted 11.7 pregnancies for the women who took 1 dose of 600 mg mifepristone (RU-486) and no one became pregnant. There was a significant difference between the pregnancy rates of RU-486 and danazol (p=.004), but not between those of RU-486 and the Yuzpe regimen. The difference between the observed pregnancies and expected number of pregnancies had the women received no treatment was significant for RU-486 (p.001) and the Yuzpe regimen (p=.061). Women who followed the Yuzpe regimen were more likely to have nausea and vomiting (70% and 22%, respectively ) than those in the danazol (30% and 4%, respectively) and RU-486 groups (37% and 3%, respectively). The Yuzpe regimen was less likely to disrupt the regular menstrual cycle than the other 2 methods, however. For example, bleeding occurred 3 days late in only 6% of cases compared with 39% for RU-486 and 9% for danazol. RU-486 was the most effective method and was also acceptable due to minimal side effects.

[Use of mifepristone (RU 486) in pregnancy (excluding abortion on demand). The first clinical trials]. / Utilisation de la mifépristone (RU 486) dans la grossesse (IVG exceptée). Premiers essais thérapeutiques.

The use of RH 486 in terminating missed abortions, in inducing labour for therapeutic abortions and in cases of fetal death in utero. Mifepristone (RU 486) is an anti-progesterone steroid and it is known to be effective in terminating early pregnancies. The authors report 34 cases of evacuation of the uterus after pregnancy has ceased to progress (because of an empty sac or the loss of fetal heart beat) using Mifepristone, after prostaglandins had been inserted. In eleven out of 18 cases Mifepristone by itself was adequate to empty the uterus with the preliminary administration of prostaglandin analogues. In 5 cases the uterus had to be curetted. In 3 cases this was not necessary. Mifepristone given 48-72 hours before prostaglandin is first administered in order to procure a termination of pregnancy makes it possible to empty the uterus within 6 to 15 hours after first giving the prostaglandins. It lessens the dose of prostaglandins needed and shortens the labour. There was no haemorrhage or obstetric complication in our cases. We cannot make any conclusion about fetal death in utero because our series is too small, but it does seem to confirm the works of Cabroll et al.

Emergency contraception by low-dose mifepristone: observation of 150 cases.

For various reasons, each community may vary in their measures taking for emergency contraception, which has been a frequent necessity especially in the out-patient department of gynecology. In this article, the authors report the effect of single oral administration of low-dose mifepristone (25 mg) in emergency contraception, with a total effective rate of 80.89%.

Effects of neonatal corticosteroid treatment on hippocampal synaptic function.

There is growing concern about long-term neurodevelopmental outcomes after neonatal corticosteroid treatment for chronic lung disease (CLD). Here, we use a protocol with tapering doses of dexamethasone (DEX) or hydrocortisone (HC) proportional to those used in preterm infants to examine the long-term consequences of these treatments on hippocampal synaptic plasticity and associative memory in later life. We found that neonatal DEX, but not HC, treatment impairs long-term potentiation (LTP) but enhances long-term depression (LTD) induction in adolescent rats. The effects of neonatal DEX treatment on LTP and LTD were prevented when the animals were given glucocorticoid receptor antagonist, RU38486, before DEX administration. We also found that neonatal DEX, but not HC, treatment induces a profound increase in the autophosphorylation of a isoform of Ca2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. In addition, only neonatal DEX treatment disrupts memory retention in rats subjected to passive avoidance learning tasks. These results demonstrate that only neonatal DEX treatment alters the hippocampal synaptic plasticity and associative memory formation in later life and thus suggest that HC may be a safer alternative to DEX for the treatment of CLD in the neonatal period.

Antiglucocoticoid treatments for depression.

OBJECTIVE: To selectively review the literature germane to antiglucocoticoid treatments for depression. METHOD: Selective review of the relevant literature. RESULTS: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in both bipolar and unipolar depression. Hypercortisolaemia, possibly secondary to breakdown in glucocorticoid-receptor-mediated negative feedback mechanisms within the HPA axis, may be central to the pathogenesis of both depressive symptoms and the neurocognitive deficits which characterize these disorders. Strategies to counteract the effects of elevated cortisol, which may potentially restore HPA axis integrity, have been the focus of recent research. CONCLUSIONS: Both preclinical and clinical studies report encouraging results which suggest that lowering circulating cortisol levels or blocking the effects of elevated cortisol with antagonists, which may up-regulate glucocorticoid receptors, has therapeutic benefits in terms of improvements in depressive symptoms and some domains of neurocognitive function.

Current medical abortion care.

Medical abortion using mifepristone and a prostaglandin analogue is a highly effective option for early abortion. Since the clinical introduction of mifepristone to the world in 1988, millions of women have had the opportunity to have a safe abortion without primary surgical intervention. The standard method of providing medical abortion has evolved through well-done studies to develop regimens that decrease cost and time to abortion. Currently, mifepristone with misoprostol is the most widely used medical abortion regimen. The most effective option available involves mifepristone 200 mg followed at least 24 hours later by misoprostol 800 microg vaginally. Women can self-administer the misoprostol, with complete abortion rates exceeding 95%. Researchers continue to refine the available regimens to improve outcomes and acceptability.