Original Article
Voluntary Interruption of Pregnancy with Mifepristone (RU 486) and a Prostaglandin Analogue — A Large-Scale French Experience
N Engl J Med 1990; 322:645-648March 8, 1990
- Abstract
- Abstract
In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method.
The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects.
We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy. (N Engl J Med 1990; 322:645–8.)
Media in This Article
Table 1
Characteristics of the Patients and Overall Efficacy of Pregnancy Termination by Mifepristone Combined with a Prostaglandin Analogue.Table 2
Efficacy of Pregnancy Termination, According to the Type and Dose of Prostaglandin Analogue.Article Activity
- Article
MIFEPRISTONE (RU 486) is a 19-norsteroid that has antiprogesterone activity by virtue of its ability to inhibit progesterone binding competitively at the receptor level.1 It was first used to terminate pregnancies in humans in 1982.2 Since then, several clinical trials have demonstrated that the administration of mifepristone is followed by the interruption of early pregnancy when the drug is given in a dose of 600 mg. Maximal efficacy is achieved when a small dose of a prostaglandin derivative is administered 36 to 48 hours later.3 4 5 6 7 8 9 10 In France, mifepristone can now be used as a medical alternative to surgical procedures for voluntary interruption of pregnancy during the first 49 days of amenorrhea, provided that it is followed by administration of a prostaglandin analogue.
This study was designed to evaluate the efficacy and safety of mifepristone administered in combination with a prostaglandin analogue in a large number of women. Although it was not its primary aim, this study also allowed retrospective comparison of the effect of two preparations of prostaglandin analogues, one given in different doses.
Methods
Subjects
In France, pregnancy is terminated only in legally authorized centers. All physicians affiliated with any of these centers could participate in the study if they agreed to follow the Roussel–UCLAF protocol and to complete a case-record form providing information about the efficacy and side effects of mifepristone and the prostaglandin analogue used.
The study subjects were women who had requested the termination of early pregnancy, all of whom gave written, informed consent for their participation in this study. French law permits voluntary interruption of pregnancy until amenorrhea has lasted 84 days. The law also specifies that a woman must allow one week for reflection, between the time of her initial decision and the time of pregnancy interruption, and that the physician must complete a special form for statistical analysis.
Women were included in this study if the duration of their pregnancy was less than or equal to 49 days (duration of amenorrhea), calculated from the first day of the last menstrual period. In case of doubt, the duration of pregnancy was determined by ultrasonographic examination. Women were excluded if an ectopic pregnancy was suspected or there was a contraindication to the use of mifepristone (adrenal insufficiency, long-term administration of glucocorticoids, or clotting disorders) or prostaglandins (asthma or severe hypertension).
Protocol
The study protocol followed the rules for the administration of mifepristone that had been approved by the French health authorities. Mifepristone was given orally in a single dose of 600 mg (three 200-mg tablets) on day 1. On day 3 (36 to 48 hours later) the woman returned to the clinic, where a prostaglandin analogue was administered as either a vaginal suppository (1 mg) of gemeprost (16, 16-dimethyl-trans-Δ2-PGE1 methyl ester; Cervagème [Roger Bellon Laboratories, Neuilly-sur-Seine, France]) or an intramuscular injection (0.25, 0.375, or 0.5 mg) of sulprostone (16-phenoxytetranor-Δ-PGE2 methyl sulfonylamide; Nalador [Schering Laboratories, Lys-lez-Lannoy, France]), unless the conceptus was expelled before that day. The physician was free to determine the prostaglandin analogue and the dose to be used.
After the prostaglandin analogue was administered, the women were monitored as inpatients for four hours and then left the center. The occurrence and intensity of abdominal pain, diarrhea, nausea, or vomiting during this four-hour period were recorded. Abdominal pain was quantified on a 100-mm visual-analogue scale on which 0 denoted the absence of pain and 100 denoted very severe pain; the value was determined by the patient at the end of the four-hour period. The physician was free to prescribe any premedication or analgesic drug that did not inhibit prostaglandin synthesis.
Each woman was asked to return to the center 8 to 12 days after mifepristone administration. At that time, efficacy was assessed either by ultrasonographic examination or by measurement of the serum level of β-chorionic gonadotropin. Success was defined as an interruption of the pregnancy and complete expulsion of the conceptus without a need for any additional surgical procedure. The date of expulsion was recorded whenever possible. Other situations (continuation of the pregnancy or incomplete expulsion) were considered to indicate failure of the procedure; in such situations, the pregnancy was terminated by a surgical method. The need for a hemostatic procedure (vacuum aspiration or dilation and curettage) was also considered to indicate failure. The women were asked about the duration of bleeding and the occurrence of side effects. In some instances (e.g., persistent moderate bleeding or doubt about the outcome of treatment), the women were asked to return for additional follow-up evaluation.
Statistical Analysis
The study was carried out from April to November 1988. The statistical analysis was mainly descriptive. In addition, although the dose levels of the prostaglandin analogues were not distributed randomly among the subjects, the efficacy of and tolerance to the different doses were compared. Qualitative data were analyzed with the chi-square test, and quantitative data with analysis of variance. The Student—Newman—Keuls procedure was used for multiple comparisons. P values (two-tailed) of less than 0.05 were considered to indicate statistical significance.
Results
Seventy-three centers participated in the study, and 2115 women were studied. Seventy-five women did not return for follow-up after they had received a prostaglandin analogue; therefore, only the results in the remaining 2040 women were evaluated. Among these 2040 women, 76 did not receive a prostaglandin-analogue derivative because expulsion took place before day 3 or because vacuum aspiration or dilation and curettage had to be performed before that day.
The overall success rate was 96.0 percent (Table 1Table 1
Characteristics of the Patients and Overall Efficacy of Pregnancy Termination by Mifepristone Combined with a Prostaglandin Analogue.). There was a trend toward higher efficacy among the women who received the high dose of sulprostone (0.5 mg) (Table 2Table 2Efficacy of Pregnancy Termination, According to the Type and Dose of Prostaglandin Analogue.). Table 3Table 3
Failure of Pregnancy Interruption. shows the failures of treatment. Pregnancy was not interrupted in 1.0 percent of the women; it was then terminated in all of them by a surgical method. Vacuum aspiration or dilation and curettage was performed in 0.9 percent of the women because of excessive uterine bleeding. Four underwent the procedure before day 3 and thus did not receive a prostaglandin analogue. One of them received a blood transfusion. In the remaining 2.1 percent of the women in whom pregnancy was interrupted, vacuum aspiration was done after the follow-up visit because the products of conception had been retained.Among the pregnancy terminations that were successful, expulsion occurred in 86 percent of the women within 24 hours after the prostaglandin analogue was administered. As shown in Table 4Table 4
Time to Expulsion, According to the Type and Dose of Prostaglandin Analogue., the mean time to expulsion was significantly shorter when a dose of 0.5 mg of sulprostone was given than when a dose of 0.25 mg of this drug or a dose of gemeprost was given. Accordingly, the percentage of women in whom expulsion occurred within four hours after the administration of a prostaglandin analogue was significantly higher in the group given 0.5 mg of sulprostone.Almost all the women (99.7 percent) had uterine bleeding after they received mifepristone and a prostaglandin analogue, whatever the outcome of treatment. The mean duration of bleeding was 8.9 days (range, 1 to 35), and the median value was 8.0 days. As shown in Table 5Table 5
Duration of Bleeding, According to the Type and Dose of Prostaglandin Analogue., the mean duration of bleeding was significantly longer in the women who received the high and intermediate doses of sulprostone (0.5 mg and 0.375 mg) than in those who received the low dose (0.25 mg) or gemeprost.Most women reported that they had had abdominal pain during the first four hours after they received a prostaglandin analogue (Table 6Table 6
Occurrence and Intensity of Pain during the Four-Hour Period after Administration of the Prostaglandin Analogue.). The percentage of women who required an analgesic was higher in the groups given the high and intermediate doses of sulprostone. The percentage in whom pain was quantified as more than 50 mm on the visual-analogue scale was also significantly higher in these two groups than in the groups given the low dose or gemeprost. Furthermore, in the group who received 0.5 mg of sulprostone, the majority (76 percent) had received premedication, unlike the patients in the other groups. Overall, 1 percent of all women required analgesia with opiates.In the four hours after the prostaglandin analogue was administered, nausea, vomiting, and diarrhea occurred in 33.8 percent, 15.3 percent, and 7.5 percent of the women, respectively. These side effects were usually mild and did not necessitate any treatment. The side effects reported at the time of the follow-up visit are listed in Table 7Table 7
Side Effects at the Time of the Follow-up Visit.. The most frequent were nausea and vomiting, dizziness, asthenia, and abdominal pain. Fever was reported by 0.3 percent of the women, among whom one had endometritis and another had salpingitis.Discussion
This large study involved 73 centers, approximately 1/10 of the centers in France that are legally authorized to perform voluntary interruption of pregnancy. Mifepristone administration was followed by the administration of a prostaglandin analogue to more than 2000 women. The analogues used were gemeprost and sulprostone, both derivatives of prostaglandin E. The results obtained in previous smaller series of patients4 , 6 , 9 , 10 were confirmed in the patients described here: the medical method used to terminate pregnancy in this study is effective in more than 95 percent of patients regardless of the prostaglandin analogue administered. The success rate is higher than that achieved with mifepristone alone, with which the rate is never more than 90 percent, even among women who have been pregnant for shorter periods (amenorrhea lasting less than 42 days).3 , 5 , 7 , 8
Mifepristone and prostaglandins exert a synergistic action on the myometrium.4 The doses of prostaglandin analogues used in this study were one fifth to one third of the doses needed when the same analogues were used alone to terminate pregnancy.11 , 12 Nevertheless, in the present trial the efficacy rate tended to be higher among the women who received 0.5 mg of sulprostone than among those who received gemeprost or lower doses of sulprostone. This finding requires confirmation by a prospective, controlled study of several hundred women. Since the doses of prostaglandin analogues that we administered were small, the percentage of women requiring analgesia was lower than in other studies in which women received a prostaglandin analogue alone.11 12 13 Similarly, gastrointestinal side effects attributable to the prostaglandin analogue were less frequent and less intense than those in women who received only a prostaglandin.11 12 13 That the intensity of pain is influenced by the size of the dose of prostaglandin analogue is demonstrated by the finding that pain was more intense in the women who received the high and intermediate doses of sulprostone. Our results also indicate that the size of the dose of analogue influenced the speed with which the conceptus was expelled. Although expulsion was more rapid in the women who received the high dose of sulprostone, uterine bleeding was significantly more prolonged than in those who received the low dose of sulprostone or gemeprost —an unexpected and unexplained finding. Gastrointestinal and other side effects were rare in all groups. In practical terms, the physician may choose the type and dose of the prostaglandin analogue, bearing in mind that although higher doses tend to increase the rate and speed of expulsion, they also increase pain and the duration of bleeding. As in previous studies of pregnancy interruption,2 3 4 5 6 7 8 9 10 none of the women had symptoms attributable to the antiglucocorticosteroid properties of the mifepristone molecule.1
The efficacy of the combination of mifepristone and a prostaglandin analogue described here makes it comparable with vacuum aspiration for the termination of pregnancies at the same stage.13 14 15 Similarly, the hemorrhagic complications were no more frequent than those of vacuum aspiration.14 15 16 Although infrequent, these possible complications justify medical supervision. In practical terms, the woman must be informed and must have access to adequate medical facilities.
Like vacuum aspiration,13 14 15 the administration of mifepristone in combination with a prostaglandin analogue did not result in the termination of all pregnancies. The question arises whether the fetus is harmed if the pregnancy continues (1 percent of the pregnancies in this series). In rabbits, deformities of the skull of the fetus have been observed after mifepristone administration,17 and attributed to uterine contractions secondary to decreased progesterone activity. Prostaglandins have been reported to be teratogenic in both animals18 and humans.19 Thus, women must be duly informed and understand the potential risks of choosing such a method of pregnancy termination.
Finally, although the acceptability of the medical method of pregnancy termination described here was high, prospective studies will be necessary to evaluate criteria according to which physicians may choose between medical and surgical methods, as well as to evaluate women's perceptions of these methods.
In accordance with the Journal's policy, the authors have stated that Dr. Silvestre, Dr. Dubois, Mme. Renault, Dr. Rezvani, and Dr. Ulmann are employees of Roussel–UCLAF, the manufacturer of mifepristone, and that Dr. Baulieu is a consultant to that firm.
We are indebted to the physicians of the participating centers for filling out the case-record forms, to Ms. Anne-Marie Gérard for excellent assistance in preparing the manuscript, and to Ms. Kimberly Carr for editorial review.
Source Information
From Roussel–UCLAF (L.S., C.D., M.R., Y.R., A.U.), Paris, and INSERM U.33, Hôpital de Bicêtre (E.-E.B.), Bicêtre, France. Address reprint requests to Dr. Ulmann at Roussel–UCLAF, 35 boulevard des Invalides, 75007 Paris, France.
- References
References
1
Moguilewsky M, Philibert D. Biochemical profile of RU 486. In: Baulieu E-E, Segal SJ, eds. The antiprogestin steroid RU 486 and human fertility control. New York: Plenum Press, 1985:87–97.
2
Herrmann 3
Ulmann
CrossRef | Web of Science | Medline4
Swann ML, Cekan S, Wang G, Lundstrom V, Bygdeman M. Pharmacokinetic and clinical studies of RU 486 for fertility regulation. In: Baulieu E-E, Segal SJ, eds. The antiprogestin steroid RU 486 and human fertility control. New York: Plenum Press, 1985:249–58.
5
Couzinet
Full Text | Web of Science | Medline6
Cameron
CrossRef | Web of Science | Medline7
Maria
CrossRef | Web of Science | Medline8
Shoupe
CrossRef | Web of Science | Medline9
Dubois
Web of Science | Medline10
Gao
CrossRef | Web of Science | Medline11
Smith
CrossRef | Medline12
Bygdeman
CrossRef | Medline13
Cameron
CrossRef | Medline14
Castadot
Web of Science | Medline15
Bendel
Web of Science | Medline16
Brenner
Web of Science | Medline17
Jost
Web of Science | Medline18
Persaud TVN, ed. Teratological testing. Vol. 2. Advances in the study of birth defects. Baltimore: University Park Press, 1979:161–77.
19
Collins
CrossRef | Web of Science | Medline
- Citing Articles (82)
Citing Articles
1
2011. Bibliography. , 211-244.
CrossRef2
YaLing Zhuang, XiuYing Chen, LiLi Huang. (2011) Mifepristone may shorten the induction-to-abortion time for termination of second-trimester pregnancies by ethacridine lactate. Contraception
CrossRef3
Satu Suhonen, Marja Tikka, Seppo Kivinen, Timo Kauppila. (2011) Pain during medical abortion: predicting factors from gynecologic history and medical staff evaluation of severity. Contraception 83:4, 357-361
CrossRef4
Sharon L. Achilles, Matthew F. Reeves. (2011) Prevention of infection after induced abortion. Contraception 83:4, 295-309
CrossRef5
Satu Suhonen, Marja Tikka, Seppo Kivinen, Timo Kauppila. (2011) The level of unpleasantness of pain influences the choice of home treatment during medical abortion. Scandinavian Journal of Pain 2:1, 19-23
CrossRef6
K Blanchard, D Cooper, K Dickson, L Cullingworth, N Mavimbela, C Von Mollendorf, LJ Van Bogaert, B Winikoff. (2007) A comparison of women’s, providers’ and ultrasound assessments of pregnancy duration among termination of pregnancy clients in South Africa. BJOG: An International Journal of Obstetrics & Gynaecology 114:5, 569-575
CrossRef7
C. Soulat, M. Gelly. (2006) Complications immédiates de l’IVG chirurgicale. La Revue Sage-Femme 5:3, 131-136
CrossRef8
Nathalie Kapp, Lynn Borgatta, Sacheen Carr Ellis, Phillip Stubblefield. (2006) Simultaneous very low dose mifepristone and vaginal misoprostol for medical abortion. Contraception 73:5, 525-527
CrossRef9
Eric A. Schaff, Robert DiCenzo, Stephen L. Fielding. (2005) Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception 71:1, 22-25
CrossRef10
Christina Rørbye, Mogens Nørgaard, Lisbeth Nilas. (2004) Medical versus surgical abortion efficacy, complications and leave of absence compared in a partly randomized study. Contraception 70:5, 393-399
CrossRef11
Caitlin Shannon, L.Perry Brothers, Neena M. Philip, Beverly Winikoff. (2004) Infection after medical abortion: A review of the literature. Contraception 70:3, 183-190
CrossRef12
Caitlin Shannon, L Perry Brothers, Neena M. Philip, Beverly Winikoff. (2004) Ectopic Pregnancy and Medical Abortion. Obstetrics & Gynecology 104:1, 161-167
CrossRef13
Phillip G. Stubblefield, Sacheen Carr-Ellis, Lynn Borgatta. (2004) Methods for Induced Abortion. Obstetrics & Gynecology 104:1, 174-185
CrossRef14
Linda A. Bartlett, Cynthia J. Berg, Holly B. Shulman, Suzanne B. Zane, Clarice A. Green, Sara Whitehead, Hani K. Atrash. (2004) Risk Factors for Legal Induced Abortion–Related Mortality in the United States. Obstetrics & Gynecology 103:4, 729-737
CrossRef15
Richard Hausknecht. (2003) Mifepristone and misoprostol for early medical abortion: 18 months experience in the United States. Contraception 67:6, 463-465
CrossRef16
Stephen L. Fielding, Eric A. Schaff, Na-yon Nam. (2002) Clinicians’ perception of sonogram indication for mifepristone abortion up to 63 days. Contraception 66:1, 27-31
CrossRef17
Eric A. Schaff, Stephen L. Fielding, Steven Eisinger, Lisa Stadalius. (2001) Mifepristone and misoprostol for early abortion when no gestational sac is present. Contraception 63:5, 251-254
CrossRef18
John K. Jain, Bryna Harwood, Karen R. Meckstroth, Daniel R. Mishell. (2001) Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis. Contraception 63:4, 217-221
CrossRef19
Lara J. De Nonno, Carolyn Westhoff, Stephen Fielding, Eric Schaff. (2000) Timing of pain and bleeding after mifepristone-induced abortion. Contraception 62:6, 305-309
CrossRef20
Wood, Alastair J.J., , Christin-Maitre, Sophie, Bouchard, Philippe, Spitz, Irving M., . (2000) Medical Termination of Pregnancy. New England Journal of Medicine 342:13, 946-956
Full Text21
Carolyn Westhoff, Radhika Dasmahapatra, Beverly Winikoff, Shelley Clarke. (2000) Predictors of analgesia use during supervised medical abortion. Contraception 61:3, 225-229
CrossRef22
Eric A Schaff, Stephen L Fielding, Steven H Eisinger, Lisa S Stadalius, Lisa Fuller. (2000) Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception 61:1, 41-46
CrossRef23
James G Kahn, Betsy Jane Becker, Laura MacIsaa, John K Amory, John Neuhaus, Ingram Olkin, Mitchell D Creinin. (2000) The efficacy of medical abortion: a meta-analysis. Contraception 61:1, 29-40
CrossRef24
Mitchell D. Creinin, Irving M. Spitz. (1999) Use of various ultrasonographic criteria to evaluate the efficacy of mifepristone and misoprostol for medical abortion. American Journal of Obstetrics and Gynecology 181:6, 1419-1424
CrossRef25
John K. Jain, Karen R. Meckstroth, Daniel R. Mishell. (1999) Early pregnancy termination with intravaginally administered sodium chloride solution–moistened misoprostol tablets: Historical comparison with mifepristone and oral misoprostol. American Journal of Obstetrics and Gynecology 181:6, 1386-1391
CrossRef26
James Trussell, Charlotte Ellertson. (1999) Estimating the efficacy of medical abortion. Contraception 60:3, 119-135
CrossRef27
Ellen R Wiebe. (1999) Tamoxifen compared to methotrexate when used with misoprostol for abortion. Contraception 59:4, 265-270
CrossRef28
Jeffrey T Jensen, Susan J Astley, Elizabeth Morgan, Mark D Nichols. (1999) Outcomes of suction curettage and mifepristone abortion in the United States. Contraception 59:3, 153-159
CrossRef29
SHAKUNTALA KOTHARI. (1999) Prevention and Medical Management of Unwanted Pregnancy: The Physician's Role. Journal of Women's Health 8:1, 59-64
CrossRef30
Eric A Schaff, Steven H Eisinger, Lisa S Stadalius, Peter Franks, Bernard Z Gore, Suzanne Poppema. (1999) Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 59:1, 1-6
CrossRef31
JOHN M. WESTFALL, ANN O'BRIEN-GONZALES, GWYN BARLEY. (1998) Update on Early Medical and Surgical Abortion. Journal of Women's Health 7:8, 991-995
CrossRef32
P Thonneau. (1998) Complications of abortion performed under local anesthesia. European Journal of Obstetrics & Gynecology and Reproductive Biology 81:1, 59-63
CrossRef33
Francisco Tejada, Asunción Cremades, Francisco Monserrat, Rafael Peñafiel. (1998) Interference of the antihormone RU486 in the determination of testosterone and estradiol by enzyme-immunoassay. Clinica Chimica Acta 275:1, 63-69
CrossRef34
Spitz, Irving M., Bardin, C. Wayne, Benton, Lauri, Robbins, Ann, . (1998) Early Pregnancy Termination with Mifepristone and Misoprostol in the United States. New England Journal of Medicine 338:18, 1241-1247
Full Text35
S. Nielsen, M. Hahlin, J. J. PtetZrChristensen. (1997) Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandin E1 analogue. BJOG: An International Journal of Obstetrics and Gynaecology 104:9, 1094-1096
CrossRef36
G.P. Talwar, S. Shah, S. Mukherjee, R. Chabra. (1997) Induced Termination of Pregnancy by Purified Extracts of Azadirachta Indica (Neem): Mechanisms Involved. American Journal of Reproductive Immunology 37:6, 485-491
CrossRef37
Antonio Tovar, Amelia Sánchez-Capelo, Jesus D. Galindo, Asunción Cremades, Rafael Peñafiel. (1997) Antiandrogenic effect of RU-486 in the mouse kidney. The International Journal of Biochemistry & Cell Biology 29:2, 361-366
CrossRef38
D Jannet. (1996) Termination of 2nd and 3rd trimester pregnancies with mifepristone and misoprostol. European Journal of Obstetrics & Gynecology and Reproductive Biology 70:2, 159-163
CrossRef39
A. Kulczycki, M. Potts, A. Rosenfield. (1996) Abortion and fertility regulation. The Lancet 347:9016, 1663-1668
CrossRef40
B Haddad. (1996) Mifepristone (RU 486) and its incidence on amniotic fluid volume in near term fetal macaque monkeys. European Journal of Obstetrics & Gynecology and Reproductive Biology 66:2, 179-182
CrossRef41
Sutapa Mukherjee, N.K. Lohiya, Rahul Pal, M.G. Sharma, G.P. Talwar. (1996) Purified neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in primates. Contraception 53:6, 375-378
CrossRef42
R.N.V. Prasad, M. Choolani. (1996) Termination of Early Human Pregnancy with Either 50 mg or 200 mg Single Oral Dose of Mifepristone (RU486) in Combination with Either 0.5 mg or 1.0 mg Vaginal Gemeprost*. The Australian and New Zealand Journal of Obstetrics and Gynaecology 36:1, 20-23
CrossRef43
Sutapa Mukherjee, G.P. Talwar. (1996) Termination of Pregnancy in Rodents by Oral Administration of Praneem, a Purified Neem Seed Extract. American Journal of Reproductive Immunology 35:1, 51-56
CrossRef44
R. N. V. Prasad, M. Choolani, S. S. Ratnam. (1995) Blood Loss in Termination of Early Pregnancy with Mifepristone and Gemeprost. The Australian and New Zealand Journal of Obstetrics and Gynaecology 35:3, 329-331
CrossRef45
ANDRÉ ULMANN, RÉMI PEYRON, LOUISE SILVESTRE. (1995) Clinical Uses of Mifepristone (MFP). Annals of the New York Academy of Sciences 761:1, 248-260
CrossRef46
El-Refaey, Hazem, Rajasekar, Dhamnasekar, Abdalla, Mona, Calder, LyndaTempleton, Allan, . (1995) Induction of Abortion with Mifepristone (RU 486) and Oral or Vaginal Misoprostol. New England Journal of Medicine 332:15, 983-987
Full Text47
Christina Wang, Amiya Sinha-Hikim, Andrew Leung. (1995) The anti-progestin CDB 2914 has no antifertility effect in male rats. Contraception 51:3, 215-218
CrossRef48
Seth G. Derman, Ligia M. Peralta. (1995) Postcoital contraception: Present and future options. Journal of Adolescent Health 16:1, 6-11
CrossRef49
Guo-wei Sang, Li-ju Weng, Qing-xiang Shao, Ming-kun Du, Xue-zhe Wu, Yu-lan Lu, Li-nan Cheng. (1994) Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05—a multicentre randomized clinical trial in China. Contraception 50:6, 501-510
CrossRef50
Hazem El-Refaey, Allan Templeton. (1994) Early abortion induction by a combination of mifepristone and oral misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood pressure. BJOG: An International Journal of Obstetrics and Gynaecology 101:9, 792-796
CrossRef51
Rebecca S. Dresser. (1994) Freedom of Conscience, Professional Responsibility, and Access to Abortion. The Journal of Law, Medicine & Ethics 22:3, 280-285
CrossRef52
P.V. Peplow. (1994) RU486 combined with PGE1 analog in voluntary termination of early pregnancy—A comparison of recent findings with gemeprost or misoprostol. Contraception 50:1, 69-75
CrossRef53
H. El-Refaey, A. Templeton. (1994) Early induction of abortion by a combination of oral mifepristone and misoprostol administered by the vaginal route. Contraception 49:2, 111-114
CrossRef54
K. Joo Thong, Jane E. Norman, David T. Baird. (1993) Changes in the concentration of alpha-fetoprotein and placental hormones following two methods of medical abortion in early pregnancy. BJOG: An International Journal of Obstetrics and Gynaecology 100:12, 1111-1114
CrossRef55
Irving M. Spitz, C.W. Bardin. (1993) Clinical pharmacology of RU 486—an antiprogestin and antiglucocorticoid. Contraception 48:5, 403-444
CrossRef56
Wood, Alastair J.J., , Spitz, Irving M.Bardin, C.W.. (1993) Mifepristone (RU 486) -- A Modulator of Progestin and Glucocorticoid Action. New England Journal of Medicine 329:6, 404-412
Full Text57
David T Baird, Jane E Norman. (1993) Antifertility effects of antigestogens. Reproductive Medicine Review 2:02, 95
CrossRef58
Csilla Muhl. (1993) Ru‐486: Legal and policy issues confronting the food and drug administration. Journal of Legal Medicine 14:2, 319-347
CrossRef59
Rosenfield, Allan, . (1993) Mifepristone (RU 486) in the United States -- What Does the Future Hold?. New England Journal of Medicine 328:21, 1560-1561
Full Text60
Peyron, RemiAubeny, ElisabethTargosz, VeroniqueSilvestre, LouiseRenault, MaguyElkik, FrancoisLeclerc, PhilippeUlmann, AndreBaulieu, Etienne-Emile. (1993) Early Termination of Pregnancy with Mifepristone (RU 486) and the Orally Active Prostaglandin Misoprostol. New England Journal of Medicine 328:21, 1509-1513
Full Text61
G. Vanage, P.A. Kadam, C.W. Bardin, S.S. Koide. (1993) Potentiating effect of epostane on pregnancy terminating activity of RU 486 in the rat. Contraception 47:5, 499-506
CrossRef62
K.Gemzell Danielsson, M.L. Swahn, M. Bygdeman. (1993) Effect of antiprogestin, hCG and a prostaglandin analogue on human uterine contractility. Contraception 47:3, 295-301
CrossRef63
Y.F. Chan, P.C. Ho, H.K. Ma. (1993) Blood loss in termination of early pregnancy by vacuum aspiration and by combination of mifepristone and gemeprost. Contraception 47:1, 85-95
CrossRef64
Marc Bygdeman, Marja-Liisa Swahn, Kristina Gemzell-danielsson, Peter Svalander. (1993) Mode of Action of RU 486. Annals of Medicine 25:1, 61-64
CrossRef65
David T. Baird. (1993) Clinical Use of Mifepristone (RU 486). Annals of Medicine 25:1, 65-69
CrossRef66
K. JOO THONG, DAVID T. BAIRD. (1992) Induction of abortion with mifepristone and misoprostol in early pregnancy. BJOG: An International Journal of Obstetrics and Gynaecology 99:12, 1004-1007
CrossRef67
Glasier, Anna, Thong, K.J., Dewar, Maria, Mackie, MayBaird, David T., . (1992) Mifepristone (RU 486) Compared with High-Dose Estrogen and Progestogen for Emergency Postcoital Contraception. New England Journal of Medicine 327:15, 1041-1044
Full Text68
Nancy L. Buc. (1992) RU 486, the FDA and Free Enterprise. The Journal of Law, Medicine & Ethics 20:3, 224-225
CrossRef69
Anita Petra Hardon. (1992) The needs of women versus the interests of family planning personnel, policy-makers and researchers: Conflicting views on safety and acceptability of contraceptives. Social Science & Medicine 35:6, 753-766
CrossRef70
Amanda Le Grand. (1992) The abortion pill: A solution for unsafe abortions in developing countries?. Social Science & Medicine 35:6, 767-776
CrossRef71
Henry P. David. (1992) Acceptability of Mifepristone for Early Pregnancy Interruption. The Journal of Law, Medicine & Ethics 20:3, 188-194
CrossRef72
J. E. NORMAN, K. J. THONG, M. W. RODGER, D. T. BAIRD. (1992) Medical abortion in women of <=56 days amenorrhoea; a comparison between gemeprost (a PGE1 analogue) alone and mifepristone and gemeprost. BJOG: An International Journal of Obstetrics and Gynaecology 99:7, 601-606
CrossRef73
A. Bachelot, L. Cludy, A. Spira. (1992) Conditions for choosing between drug-induced and surgical abortions. Contraception 45:6, 547-559
CrossRef74
Arne Rådestad, Marc Bygdeman. (1992) Cervical softening with mifepristone (RU 486) after pretreatment with naproxen. Contraception 45:3, 221-227
CrossRef75
E. Aubeny. (1991) RU486 combined with PG analogs in voluntary termination of pregnancy. Advances in Contraception 7:4, 339-343
CrossRef76
E. E. Baulieu. (1991) RU486 and the early nineties. Advances in Contraception 7:4, 345-351
CrossRef77
(1991) Misoprostol and legal medical abortion. The Lancet 338:8777, 1241-1242
CrossRef78
M.L. Swahn, K. Gemzell, M. Bygdeman. (1991) Contraception with mifepristone. The Lancet 338:8772, 942-943
CrossRef79
ETIENNE-EMILE BAULIEU. (1991) On the Mechanism of Action of RU486. Annals of the New York Academy of Sciences 626:1 Frontiers in, 545-560
CrossRef80
M. BYGDEMAN, K. GEMZELL, C. GOTTLIEB, M.-L. SWAHN. (1991) Uterine Contractility and Interaction between Prostaglandins and Antiprogestins Clinical Implications. Annals of the New York Academy of Sciences 626:1 Frontiers in, 561-567
CrossRef81
(1990) REPRODUCTIVE HEALTH AND MIFEPRISTONE. The Lancet 336:8729, 1480-1481
CrossRef82
Segal, Sheldon J., . (1990) Mifepristone (RU 486). New England Journal of Medicine 322:10, 691-693
Full Text
