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Objective: To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who conceived without medical assistance and those who conceived through in vitro fertilization (IVF), after fresh or frozen embryo transfer, and evaluate for the predictive factors of success, time to first passage of tissue, and time to complete resolution of pregnancy., Design: Retrospective cohort study., Setting: University hospital., Patient(s): Women who presented with EPL below 13 weeks of gestation between June 2013 and July 2021 who were managed medically with mifepristone 200 mg orally and misoprostol 800 mcg vaginally were included in the study., Intervention(s): Medical management with mifepristone and misoprostol; conception without medical assistance vs. post-IVF, after fresh or frozen embryo transfer., Main Outcome Measure(s): We evaluated overall success and performed subgroup analysis according to the mode of conception and compared fresh vs. frozen-thawed embryo transfers for IVF pregnancies. In all groups, we also calculated success according to gestational age and compared the time to first passage of tissue. The potential predictive factors of treatment success were analyzed. The side effects and complications of treatment were recorded., Result(s): A total of 930 women were included in the study, 99 (11%) of whom achieved pregnancy after IVF. The overall success of medical treatment was 89% with no statistically significant difference according to the mode of conception (89% vs. 89%) or type of transfer (fresh 89% vs. frozen 89%). Only lower gestational age by sonography was independently predictive of treatment success, showing a negative regression coefficient of β = -0.333 and an odds ratio of 0.717. The mean time to first passage of tissue was 5.0 ± 2.1 hours. Altogether, 666 women (72%) showed pregnancy resolution on the day of medication administration, an additional 110 women at 1-week follow-up, and a further 74 women after ≥4 weeks on ultrasound., Conclusion(s): Medical management of EPL with mifepristone and misoprostol is a highly successful treatment option that results in completed abortion in a timely fashion in both pregnancies conceived without medical assistance and those conceived after IVF., Competing Interests: Declaration of interests V.C.-T. has nothing to disclose. M.H. has nothing to disclose. A.C.-K. has nothing to disclose. M.T. has nothing to disclose. S.M. has nothing to disclose. B.T. has nothing to disclose. B.S. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of 3 months of vaginal mifepristone treatment on leiomyoma volume and related symptoms., Design: Prospective, open-label, two tertiary centers, phase II clinical trial., Setting: Two tertiary medical centers in Israel., Patient(s): Thirty-three enrolled women, ages 30-53 years, diagnosed with symptomatic uterine fibroids., Intervention(s): Patients received 10 mg mifepristone vaginally daily for 3 months., Main Outcome Measure(s): Reduction in uterine leiomyoma volume. Improvement in symptoms related to uterine fibroids was assessed with the use of the "Uterine Fibroid Symptoms Quality of Life Questionnaire" (UFS-QoL). The number of bleeding days, safety, and tolerability were secondary measures., Result(s): Mifepristone treatment significantly reduced leiomyoma volume from 135.3 ± 22.9 cc at enrollment to 101.2 ± 22.4 cc after 3 months of treatment. The UFS-QoL Score significantly decreased from 20.7 ± 0.7 at enrollment to 14.0 ± 0.8 after 3 months of treatment. The number of bleeding days significantly decreased by 3.5 days. Endometrial biopsies showed no evidence of endometrial hyperplasia or cellular atypia. There were no major side effects during the course of the study, and treatment was well tolerated., Conclusion(s): Vaginal mifepristone may offer an effective treatment option for women with symptomatic uterine leiomyoma and can improve the patients' quality of life., Clinical Trial Registration Number: NCT00881140., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the expression levels of matrix metalloproteinases 2 and 9 (MMP-2 and -9) and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the villi and the decidua are associated with prolonged bleeding after medical abortion., Design: Case-controlled study., Setting: University hospital., Patient(s): Mifepristone-misoprostol medical abortion patients were divided into two groups (20 women each) based on the length of time (>14 or ≤14 days) of bleeding after the abortion., Intervention(s): Discharged villi and deciduas were collected., Main Outcome Measure(s): The expression levels of MMP-2 and -9 and TIMP-1 and -2 in the villi and deciduas were assessed with semiquantitative immunohistochemistry., Result(s): The median semiquantitative immunohistochemistry staining index (SI) scores for MMP-9 expression in the villi were elevated in the bleeding group compared with the control group (median SI scores 0.31 and 0.03, respectively). TIMP-2 expression was elevated in the decidua in the bleeding group compared with the control group (median SI scores 1.00 and 0.20, respectively). No significant differences were observed between the two groups in the expression levels of MMP-2 in the villi or of MMP-2, MMP-9, or TIMP-1 or of the ratios of MMP-9/TIMP-1 or MMP-2/TIMP-2 in the decidua., Conclusion(s): Elevated expression levels of MMP-9 in the villi and of TIMP-2 in the decidua were associated with prolonged bleeding after medical abortion., (Copyright © 2014. Published by Elsevier Inc.)

Objective: To determine the efficacy of pre-emptive administration of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen vs. a placebo on pain relief during medical abortion and to evaluate whether NSAIDs interfere with the action of misoprostol., Design: Prospective, double-blind, randomized, controlled study., Setting: University-affiliated tertiary hospital., Patient(s): Sixty-one women who underwent first-trimester termination of pregnancy., Intervention(s): Patients received 600 mg mifepristone orally, followed by 400 μg oral misoprostol 2 days later. They were randomized to receive pre-emptively two tablets of 400 mg ibuprofen orally or a placebo, when taking the misoprostol. The patients completed a questionnaire about side effects and pain score and returned for an ultrasound follow-up examination 10-14 days after the medical abortion., Main Outcome Measure(s): Significant pain, assessed by the need for additional analgesia, and failure rates, defined by a need for surgical intervention., Result(s): Pre-emptive ibuprofen treatment was found to be more effective than a placebo in pain prevention, as determined by a significantly lower need for additional analgesia: 11 of 29 (38%) vs. 25 of 32 (78%), respectively. Treatment failure rate was not statistically different between the ibuprofen and placebo groups: 4 of 28 (14.2%) vs. 3 of 31 (9.7%), respectively. History of menstrual pain was predictive for the need of additional analgesia., Conclusion(s): Pre-emptive use of ibuprofen had a statistically significant beneficial effect on the need for pain relief during a mifepristone and misoprostol regimen for medical abortion. Ibuprofen did not adversely affect the outcome of medical abortion., Clinical Trial Registration Number: NCT00997074., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report two cases of women who presented with amenorrhea, lower abdominal pain, and vaginal bleeding and who were diagnosed with advanced interstitial pregnancy after initial negative laparoscopies., Design: Case report., Setting: Early pregnancy unit of district general hospital., Patient(s): A 39-year-old woman with a history of right salpingectomy for ectopic pregnancy and a 28-year-old woman with a history of miscarriage., Intervention(s): Laparoscopic salpingocentesis with methotrexate (50 mg/m(2)) after aspiration of an equivalent amount of amniotic fluid. The remainder, based on the calculated dose, was given intramuscularly. Oral mifepristone (200 mg) was given postoperatively., Main Outcome Measure(s): Complete resolution of interstitial pregnancy in both instances with two subsequent, successful intrauterine pregnancies delivered at term in the second patient. There were no intraoperative or postoperative complications., Result(s): Expected decline in beta human chorionic gonadotropin (beta-hCG) levels without the need for any further intervention(s)., Conclusion(s): Interstitial pregnancy may be successfully and safely managed by the use of laparoscopic salpingocentesis with methotrexate and mifepristone despite high initial beta-hCG levels.

Objective: To evaluate the effect of mifepristone on the expression of endometrial steroid receptors and their co-factors in depot medroxyprogesterone acetate (DMPA) users., Design: A prospective, randomized, placebo-controlled trial., Setting: Reproductive research center., Patient(s): Fifty healthy women with regular menstrual cycle., Intervention(s): One hundred fifty milligrams of DMPA were given every 3 months. Two pills (25 mg each) of placebo or mifepristone were administered every 14 days during the DMPA therapy. Four endometrial biopsy specimens were obtained from each patient., Main Outcome Measure(s): The expression of estrogen receptor subtypes alpha and beta (ERalpha and ERbeta), progesterone receptors A and B (PRAB and PRB), and androgen receptor messenger RNA and protein was detected by real-time polymerase chain reaction and immunohistochemistry, respectively. Steroid receptor coactivator 1 (SRC-1), silencing mediator for retinoid and thyroid-hormone receptors, and cell proliferation were evaluated by immunohistochemistry., Result(s): The expression of endometrial ERalpha, PRAB, PRB, and SRC-1 was increased significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks. A positive correlation between endometrial ERalpha, PRAB, PRB, and SRC-1 production and proliferation was demonstrated., Conclusion(s): Short-term exposure of mifepristone in new starters of DMPA increases the expression of endometrial ERalpha, PRAB, PRB, and SRC-1 and promotes cell proliferation. Prolonged exposure to mifepristone does not alter the suppression of these receptors that are caused by DMPA and continues to result in endometrial atrophy.

Objective: To test the feasibility of timing the administration of mifepristone as a once-a-month contraceptive pill on the 12th day before the next menses, as calculated from the length of the previous menstrual cycles., Design: Double-blind, randomized, controlled trial., Setting: Five family planning centers across the world., Patient(s): Three hundred ninety-nine women attending family planning clinics., Intervention(s): Randomized to receive 10, 25, or 200 mg of mifepristone or a placebo., Main Outcome Measure(s): Lengthening or shortening of the normal menstrual cycle length following administration of the drug by at least 5 days., Result(s): The menstrual period came within 5 days of the predicted date in 88% of women receiving the placebo, 84% of women receiving 10 mg, 72% of women receiving 25 mg of mifepristone, and only 48% of women treated with 200 mg of mifepristone. Increasing the dose of mifepristone was associated with an increased chance of having a delayed period (P<.001). Only 45% of women were in the peri-ovulatory phase of the cycle according to LH and P measurements on the day of drug administration. Women treated before ovulation were more likely to have delayed menses with all three doses of mifepristone., Conclusion(s): Because of the disruption in cycle length, it appears unlikely that mifepristone administered once a month, at a calendar-based time, would provide a reliable method of contraception.

Objective: To compare the effectiveness and safety of misoprostol and mifepristone, followed when needed by misoprostol, for the treatment of women with early pregnancy failure., Design: Prospective randomized nonblinded controlled trial., Setting: University-affiliated tertiary medical center., Patient(s): One hundred fifteen consecutive women diagnosed as having a blighted ovum or missed abortion of <9 weeks of gestation enrolled., Intervention(s): The patients received orally 600 mg mifepristone (group I) or orally 800 microg misoprostol (group II). Most patients in both groups subsequently received 48 hours later orally 800 microg misoprostol., Main Outcome Measure(s): Failure was defined as surgical intervention due to retained gestational sac 48 hours after completion of the drug protocol, severe symptoms, or suspected retained products of conception after the menstrual period., Result(s): The success rate was similar in groups I and II: 38 of 58 patients (65.5%) versus 42 of 57 patients (73.6%), respectively. No cases of severe infection or bleeding necessitating blood transfusion occurred., Conclusion(s): Misoprostol is an effective and safe treatment for early pregnancy failure and could replace surgical curettage in over two-thirds of the patients. Mifepristone offers no advantage compared with misoprostol as initial treatment.

Objective: To study the effect of mifepristone on heparin-binding epidermal growth factor (HB-EGF) and its receptors HER1 and HER4 in the fallopian tube and in the endometrium., Design: Prospective clinical study., Setting: Hospital-based unit for obstetrics and gynecology and research laboratories., Patient(s): Healthy women divided into two groups: controls and patients treated with a single dose of 200 mg mifepristone on day LH+2., Intervention(s): Endometrial biopsies from 30 women were obtained during one control cycle or one treatment cycle. Fallopian tubes from 14 women were collected during laparoscopic sterilizations., Main Outcome Measure(s): Immunohistochemistry and reverse transcriptase-polymerase chain reaction., Result(s): The staining intensity of HB-EGF was not affected by mifepristone treatment. Treatment with mifepristone increased the immunostaining on HER1 in the epithelium and the stroma of the endometrium, which was not seen in the fallopian tube. The immunostaining of HER4 decreased in the stroma of the fallopian tube, while an increase was seen in the epithelial cells of the endometrium., Conclusion(s): Treatment with mifepristone has a limited effect on HB-EGF and its receptors in the fallopian tube, while the increase in HER1 and HER4 in the endometrium probably reflects defective endometrial maturation.

Objective: To determine clinical side effects and biochemical and hematological abnormalities in patients with nonresectable meningioma on long-term mifepristone (RU 486) therapy., Design: Long-term mifepristone administration in patients with meningioma., Setting: Outpatient clinic of a university hospital., Patient(s): Sixteen women and 9 men aged 22-80 years with nonresectable meningioma., Intervention(s): Mifepristone (200 mg daily). One patient received treatment for more than 13 years; six received treatment for 10-12 years; five received treatment for 4-9 years; eight received treatment for 1-4 years; and the remainder received treatment for 4-10 months., Main Outcome Measure(s): Evaluation of side effects and of hematological and biochemical abnormalities., Result(s): Fatigue was observed in 22 of 25 patients. Endometrial hyperplasia occurred in one premenopausal woman and one postmenopausal woman. Another two women had endometrial thickening without hyperplasia. There were no consistent abnormalities in liver or renal function or in any other biochemical or hematological parameters. One subject (on long-term dexamethasone) developed hypoadrenalism, which responded to treatment., Conclusion(s): Mifepristone can be administered for prolonged periods. Ultrasound should be performed if irregular vaginal bleeding occurs. In asymptomatic women, it should be performed annually. If endometrial thickening is observed, then endometrial biopsy is recommended. Because biochemical hypothyroidism has been reported during long-term mifepristone therapy, thyroid function tests should be performed annually.

Objective: To investigate the expressions of estrogen (E) receptor and progesterone (P) receptor in human eutopic and ectopic endometrium and the effect of mifepristone (RU486) on them., Design: Prospective study., Setting: University hospital., Patient(s): Twenty-two patients with ovarian endometriosis and 13 patients with uterine leiomyoma were recruited., Intervention(s): Samples of ovarian endometrioma cyst tissue and endometrium were obtained from the 22 patients. A sample of endometrium was obtained from the 13 patients., Main Outcome Measure(s): Expressions of E and P receptors were determined using immunocytochemical method., Result(s): P receptor expression in endometrial epithelial cells with endometriosis was significantly higher than that without endometriosis in the early secretory phase. Estrogen receptor and epithelial P receptor expressions in endometriotic cells were significantly lower than those of endometrial cells during the proliferative phase, similar with the latter during the early secretory phase and significantly higher during the late secretory phase. RU486 down-regulated the expressions of E and P receptors in both the eutopic and the ectopic endometrial cells, and in some cases this down-regulating effect was more apparent when the concentration of RU486 was higher., Conclusion(s): Different steroid receptor expressions indicate different hormonal regulation between endometriotic and endometrial cells. The down-regulating effect on E and P receptors may be one of the therapeutic mechanisms of RU486 on endometriosis.

Objective: To compare the incidence of noncompliance measured objectively by a home use fertility monitor with the traditional self-reported incidence of compliance in a study of a new method of contraception., Design: Prospective cohort study., Setting: A large family planning clinic in Edinburgh., Patient(s): Thirty-two healthy women who took part in a trial assessing the efficacy of a novel method of contraception involving accurately timed administration of a single dose of mifepristone., Intervention(s): Mifepristone was administered orally and a blood sample was collected on the same day., Main Outcome Measure(s): Percentage of missed tests detected by the monitor against the self-reported percentage during the critical period., Result(s): Women failed to perform 24.2% (95% confidence interval, 16.5-31.5) of the tests in the 162 cycles analyzed. They missed tests at an absolutely vital time for contraceptive efficacy in 42% of cycles according to the monitor while admitting to missing tests in 14.8%. Poor compliance was associated with younger women, those who discontinued the study before completion, and cycles in which women were not relying on the contraceptive method., Conclusion(s): The use of microelectronic monitoring systems may improve our understanding of the extent of patient noncompliance, providing objective information that no other monitoring technique can produce. This understanding provides the opportunity to make the optimum use of potentially effective treatments while validating research evidence.

Objective: To determine the effects of a low-dose mifepristone regimen on endometrium in the rhesus monkey by endometrial staging and analysis of molecular markers of endometrial receptivity., Design: A prospective, randomized comparative study., Setting: Academic research environment., Animal(s): Normally cycling rhesus (Macaca mulatta) monkeys., Intervention(s): Monkeys (5 per control or treatment group) received 0.03 mg of mifepristone in vehicle (sesame oil) per kilogram of body weight or vehicle daily from day 2 of the menstrual cycle to 7 days after the midcycle E2 surge., Main Outcome Measure(s): Serum estradiol (E2) and progesterone (P) levels; endometrial staging and immunoreactivity of leukemia inhibitory factor and interleukin-6 performed on fixed endometrial tissues; and relative abundance of endometrial estrogen and P receptor mRNA evaluated with semiquantitative reverse transcriptase polymerase chain reaction in which cyclophilin mRNA, a housekeeping gene product, was coamplified as the reference standard., Result(s): Mifepristone at 0.03 mg/kg/d induced a delay in the endometrial cycle with a shift from the late to midsecretory phase. This treatment regimen did not suppress the midcycle gonadotropin surge or, presumably, ovulation because P levels were normal during the midluteal phase. The staining intensity of leukemia inhibitory factor and interleukin-6 was dependent upon the endometrial stage and was decreased in treated monkeys. E and P receptor mRNAs increased significantly with mifepristone treatment compared with controls, another indication of delayed uterine staging., Conclusion(s): Mifepristone at 0.03 mg/kg/d had no antiovulatory effect but delayed development of the endometrium from the late to midsecretory phase. This study provides further evidence that endometrial maturation can be altered without affecting ovarian cyclicity.

Objective: To study the response of uterine leiomyomata to three daily doses of RU486 (5, 25, and 50 mg)., Design: Prospective nonrandomized trial of women with symptomatic leiomyomata., Setting: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center., Patients: Ten patients with symptomatic leiomyomata previously reported after treatment with 50 mg of RU486 daily for 3 months. Eleven patients treated with 25 mg of RU486 daily and nine patients placed on 5 mg of RU486 daily for 12 weeks., Main Outcome Measures: Changes in leiomyomata volume as measured with vaginal ultrasounds at baseline and monthly thereafter. Frequent blood samples for hematology, chemistry, and hormone levels were obtained. Twenty-four-hour urine collections for free cortisol and creatinine were obtained at baseline and at 12 weeks., Results: All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% +/- 4.8% of baseline at 4 weeks, 60.5% +/- 6.6% at 8 weeks, and 51.0% +/- 9.2% after 12 weeks of treatment. Regressive response in patients treated with 25 mg of RU486 daily was 76.3% +/- 5.0% of baseline at 4 weeks, 54.0% +/- 5.1% at 8 weeks, and 44.0% +/- 5.0% after 12 weeks. At 5 mg of RU486 leiomyomata volume was 80.6% +/- 8.3% of baseline after 4 weeks, 63.7% +/- 14.6% after 8 weeks, and 74.4% +/- 19.8% after 12 weeks of therapy., Conclusions: Although acyclicity is seen at all three doses, an effective dose to cause a clinically significant (50%) decrease in leiomyomata volume appears to be 25 mg daily.

Objective: To examine endometrial response to long-term low-does RU486 administration., Design: Retrospective controlled study of women with endometriosis treated for 6 months with 50 mg RU486 daily for 6 months. Controls consisted of women in the follicular phase of a spontaneous cycle undergoing endometrial biopsy., Setting: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center., Patients and Interventions: Nine patients treated with long-term low-dose RU486 and nine normal cycling controls undergoing hysterectomy or endometrial biopsy for benign disease., Main Outcome Measures: Changes in endometrial morphology and immunohistochemical analysis for estrogen receptor (ER) and progesterone receptor (PR) protein., Results: All patients treated with RU486 exhibited abnormal endometrial morphology. The endometrial glands were irregular in size and shape. The stroma was varied but consisted predominantly of dense cellular stroma with frequent mitotic figures. The glands were lined by a combination of epithelial types some of which were secretory. No cytologic atypia was seen. Levels of ER immunoreactivity, as determined by image analysis, were greater in the stroma with no difference in PR immunoreactivity compared with controls. No difference in ER and PR immunoreactivity were seen in the glands compared with normal controls., Conclusion: The generalized cystic changes demonstrated are consistent with a chronic unopposed estrogen effect and are concordant with hormonal data showing early to midfollicular phase levels of estrogens. They also are consistent with our findings of increased ER immunoreactivity in the stroma. Evidence of minimal P agonist effect was noted.

Objective: To investigate the use of oral mifepristone (RU486; Roussel-Uclaf, Paris, France) associated with IM injection of sulprostone (Schering, Lys-Lez-Lannoy, France) for the induction of legal abortion (7 weeks of amenorrhea in France)., Design: An uncontrolled observational study., Setting: A public family planning center in Paris., Patients: Three hundred sixty-nine (369) pregnant women with up to 7 weeks amenorrhea undergoing legal abortion., Interventions: Six hundred milligrams (600 mg) of oral mifepristone followed 48 hours later by an IM injection of 250 micrograms of sulprostone., Main Outcome Measures: Frequency of complete abortion and the need for subsequent surgical evacuation, hospitalization, and blood transfusion. Measurement of the beta-hCG concentration before and 14 days after the oral administration of mifepristone., Results: There was complete abortion in 93.2% of the cases. Of the 25 failures, 8 were continued pregnancies, 6 terminated pregnancy but without expulsion of the conceptus, and 11 were placenta retentions. Eight women required short hospitalization, but none needed blood transfusion. Among the 25 failures, 23 had a beta-hCG concentration > 500 IU/mL [sensitivity 92%, specificity 83%]., Conclusion: The sequential use of oral mifepristone and IM injection of sulprostone is effective in inducing abortion up to 7 weeks of amenorrhea. Nevertheless the risk of maternal morbidity associated with sulprostone and also the risk of fetal malformations in cases of continued pregnancy indicate that this method should only be used in specialist centers.

Objective: To examine the effect of sequential use of the antiprogesterone RU486 and synthetic progestin on ovarian function of healthy women., Design: Healthy women were given a sequential antiprogesterone-progestin treatment. Blood samples were taken twice a week during one control cycle and one to three treatment cycles; prospective analysis., Setting: The outpatient clinic of the Helsinki City Maternity Hospital, Helsinki, Finland, and Steroid Research Laboratory, Department of Medical Chemistry, University of Helsinki, Helsinki, Finland., Patients: Eleven healthy women, volunteers, 20 to 34 years of age., Interventions: A dose of 25 mg/d of RU486 was given during cycle days 1 to 21, and synthetic progestin (5 mg of norethisterone to six and 5 mg of medroxyprogesterone acetate to five women) during cycle days 22 to 31., Main Outcome Measures: Serum P, E2, FSH, and LH were measured from serum samples., Results: In 20 of the 24 treatment cycles analyzed the serum concentrations of P were anovulatory. In the remaining 4 cycles, P levels rose above 3 ng/mL, suggestive of ovulation. Folliculogenesis was not completely inhibited, but serum E2 profiles were subnormal and delayed. Bleeding control was satisfactory., Conclusions: Antiprogesterone RU486 hampers or delays follicular development, suggesting a possible use as an estrogen-free oral contraceptive. However, the synthetic progestins used in this regimen induced serum P rises in some cycles. The synthetic progestin provides the cycle control, but its possible effect on the reliability of the method remains to be evaluated.

Objective: To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function., Design: Three different regimens of RU486 were tested., Participants: Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization., Interventions: Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10-day intervals for 80 days., Main Outcome Measures: Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects., Results: The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation., Conclusion: Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration.

Objective: To study the direct effects of progesterone (P) and its antagonist RU486 (mifepristone) on sperm hyperactivation (HA) and acrosome reaction., Design: Prospective evaluation of semen samples incubated in capacitation media with P and/or RU486., Setting: University-affiliated tertiary care center., Patients: Normal healthy volunteers., Interventions: Semen samples were incubated in media with P or RU486 alone or in combination, and aliquots were taken at 10 minutes, 1, 5, and 24 hours for HA analyses by computer-aided sperm analysis system, and at 0, 5, and 24 hours for assessment of acrosome reaction by fluorescein-labeled Pisum sativum (pea) agglutinin., Main Outcome Measures: HA and acrosome reaction., Results: Sperm HA was significantly increased at 10 minutes by P both at 10(-7) M (9.27 +/- 1.59%; mean +/- SEM) and 10(-6) M (9.39 +/- 1.94%) when compared with untreated spermatozoa (5.62 +/- 1.59%). The stimulatory effect of P on sperm HA was transient because this was not observed after 1, 5, and 24 hours of incubation. The antiprogesterone RU486 (10(-6) M) alone had no effect and did not abolish the stimulatory effect of P on HA. The %HA was further enhanced by the addition of RU486 at 10(-6) M to P at 10(-7) M (12.43 +/- 3.31%) or P at 10(-6) M (13.52 +/- 4.10%); however, this effect was not significantly different from P alone. Coincubation of P or RU486 with spermatozoa during capacitation did not stimulate the acrosome reaction in the concentrations tested., Conclusion: Progesterone directly stimulates human sperm HA transiently. Progesterone has no significant effect on acrosome reaction in capacitating spermatozoa. The effects of P are rapid and not counteracted by RU486, suggesting that the mechanism of action of P may not be mediated by specific P nuclear receptors.

Objective: To examine hormonal and endometrial responses to intermittent low-dose RU486 administration in the luteal phase of the menstrual cycle., Design: Prospective open trial in which subjects serve as their own controls., Patients/participants: Eight normal cycling women., Interventions: RU486 (10 mg, orally) was administered 5 and 8 days after urinary luteinizing hormone (LH) surge of treatment cycle., Main Outcome Measures: Daily serum concentrations of LH, follicle-stimulating hormone, estradiol (E2), and progesterone (P) were determined in control, treatment, and recovery cycles (n = 5) or treatment and recovery cycles (n = 3). Changes in endometrial morphology and immunohistochemical staining for P receptor (PR) and E2 receptor (ER) were determined during control (or recovery) and treatment cycles., Results: Cycle length and hormonal patterns were unaltered after treatment with RU486. As demonstrated by reduced stromal edema and delayed glandular development, endometrial dyssynchrony occurred in all eight treatment cycles. In addition, seven of eight treatment cycle endometria demonstrated a decrease in PR staining without consistent change in ER staining., Conclusions: Two low doses of RU486 given 72 hours apart during the luteal phase of the cycle disrupted ongoing endometrial maturation without altering the hormonal and time course of the menstrual cycle. This study provides a basis for the development of a novel form of luteal contraception.

Objective: To compare two regimens of mifepristone plus gemeprost for early pregnancy termination., Design: A prospective, randomized, multicenter trial., Setting: Ten gynecological services, mostly in academic hospitals., Participants: Three hundred eighty-five healthy women up to 35 years of age with amenorrhea less than or equal to 49 days requesting pregnancy termination., Treatment: Mifepristone, 25 mg five times at 12-hour intervals (n = 192) or 600 mg as a single dose (n = 193) followed by 1 mg gemeprost 60 hours after the start of mifepristone., Main Outcome Measures: Pregnancy outcome, time of onset and duration of vaginal bleeding, subjective complaints, and hormone changes during treatment and 6-week follow-up., Results: Treatment outcome was identical in both groups with an overall complete abortion rate of 92.7% among the 385 women included in the analysis. The frequency of complaints, bleeding patterns, and changes in hemoglobin, beta-human chorionic gonadotropin, estradiol, and progesterone were also similar in both groups. Cortisol (at 12 and 36 hours after mifepristone) and prolactin (at 12 hours) were significantly higher in the single 600-mg dose group., Conclusion: When used for early pregnancy termination with prostaglandin, a lower dose of mifepristone than the currently recommended single 600-mg dose may suffice.

Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.