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Mifepristone (an antiprogesterone) and misoprostol (a synthetic analogue of prostaglandin E1) were administered to 60 women diagnosed with missed abortion or anembryonic pregnancy (gestation sac present but no developing embryo) equivalent to 13 weeks' gestation or less who were recruited after counselling. The median age was 227 (range 15-44), and the median duration of amenorrhoea was 71 (42-110) days. 25 of the women had been referred for ultrasound scanning because of bleeding in early pregnancy, while the rest were diagnosed by routine scanning. 29 patients had anembryonic pregnancies, and 31 had a missed abortion. Each patient received a 600 mg single oral dose of mifepristone, and 36-48 hours later misoprostol 600 mcg was given orally (400 mcg and, 2 hours later, 200 mcg). If the products of conception were not expelled within 4 hours, vaginal ultrasonography was performed. 8 patients aborted with mifepristone alone, 43 aborted after taking 600 mcg of misoprostol, and 5 more aborted after receiving a 2nd divided dose of 600 mcg misoprostol. In 3 patients the treatment failed, and they underwent evacuation of the uterus under general anaesthesia. Exploratory curettage was performed in 2 other patients at 14 and 22 days after treatment with misoprostol, but no products of conception were obtained. The median time from administration of misoprostol to abortion was 4 (1-11) hours. The median duration of bleeding after abortion was 10 (2-22) days. Side effects included nausea, vomiting (5 patients received antiemetic drugs), and diarrhoea (7 patients) from misoprostol treatment. 39 women did not want any pain relief, 13 asked for oral analgesia, and 7 obtained parenteral analgesia.
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PMID:Medical management of missed abortion and anembryonic pregnancy. 148 4

Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that offers an effective medical means of inducing abortion in early pregnancy. Since progesterone is essential for implantation, the authors tested the use of mifepristone for emergency postcoital contraception. 800 women and adolescents were studied who requested emergency postcoital contraception and who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 mcg of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy) and 402 women and adolescents who were randomly assigned to receive 600 mg of mifepristone. None of the women or adolescents who received mifepristone became pregnant, as compared with 4 of those who received standard therapy; the difference in failure rates between the 2 regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (p0.001). In many subjects, the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40% vs. 60%) and vomiting (3% vs. 17%) on the day of treatment, as well as lower rates of other side effects, than those subjects treated with the standard regimen. However, they were more likely to have a delay in the onset of the next menstrual period (42% vs. 13%). Mifepristone is a highly effective postcoital contraceptive agent which, if more widely used, could help reduce the number of unplanned and unwanted pregnancies.
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PMID:Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. 848 75

To identify risk factors for gastroschisis other than drug use in pregnancy, an analysis of data collected in a case-control surveillance program of birth defects (1976-1990) was conducted. Drug use is considered in Werler et al., Teratology, 45:361-367, 1992. Maternal demographic, reproductive, and medical factors, and first trimester environmental exposures, were compared between 76 gastroschisis cases and 2,581 malformed controls. A strong inverse association was found for maternal age: relative to women 30 years or older, relative risks for 25-29, 20-24, and less than 20-year-old women were 1.7, 5.4, and 16, respectively. Multivariate relative risks (and 95% confidence intervals) for alcohol use were as follows: for 1-5 drinks per week, 1.6 (0.7-3.4); for greater than or equal to 6 drinks per week, 2.5 (0.9-6.8); for a maximum of 1-4 drinks at any one time, 0.8 (0.4-1.6); and for a maximum of greater than or equal to 5 drinks, 2.8 (1.2-6.5). With the effect of age taken into account, no associations were identified for cigarette smoking, consumption of caffeinated or decaffeinated coffee, unplanned pregnancy, 12 or less years of education, or a parity of two or more. Other medical and reproductive factors, including weight gain, vaginal bleeding, nausea or vomiting, influenza, "other" infection, and history of spontaneous abortion or elective abortion did not increase the risk.
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PMID:Demographic, reproductive, medical, and environmental factors in relation to gastroschisis. 153 57

In Ohio, a 33-year old woman who had never had an ectopic pregnancy presented at an emergency facility not physically attached to a hospital with abdominal pain over 24 hours which had become more intense during the preceding 4 hours. She did not have vaginal bleeding, diarrhea, vomiting, or pain while urinating. 2 weeks earlier she had a voluntary intrauterine abortion at 8 weeks' gestation. She had intercourse 1 week before coming to the emergency facility. She had widespread tenderness in her abdomen, especially in the lower areas. Blood cell studies suggested an infection. The attending physician presumed her to have pelvic inflammatory disease (PID) as a result of either sexual intercourse or the elective abortion. The physician called for a urinary beta human chorionic gonadotropin test to determine whether placental tissue remained in the uterus. It was positive. 60 minutes after admission, the supine patient's pain increased and her blood pressure dropped to 80/50 mm Hg from 100/60 mm Hg at admission. After administering Ringer's solution, the health team sat her up and she fainted. A repeat cell count indicated sepsis. Her blood pressure decreased to 60 by Doppler and the physician continued to give her fluids and began dopamine. After the team stabilized her, they transferred her to a hospital. Her private physician examined her and then began surgery. The physician found a tubal pregnancy and removed the affected tube and ovary. She recuperated completely. Combined intrauterine and extrauterine pregnancy occurs once in every 30,000 cases. Previous PID, use of ovulation inducing medication, and in vitro fertilization with embryo transfer increases the likelihood of this type of pregnancy occurring. Physicians should consider this possibility if a woman has any of these histories and a combination of abdominal pain, adnexal mass with pain and tenderness, peritoneal irritation, and an enlarged uterus.
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PMID:Ruptured ectopic pregnancy in a patient with a recent intrauterine abortion. 157 Sep 21

60,000 women in France have received RU 486 and a prostaglandin to induce abortion. In the late 1980's, clinical researchers assessed the safety and effectiveness of 600 mg of oral RU 486 in 2040 French women. 2 days later, health workers either injected 0.25-0.5mg of sulprostone or inserted a 1mg vaginal suppository of gemeprost in 1964 women who had not yet aborted. 96% experienced complete abortions. Physicians needed to conduct either a vacuum aspiration of dilation and curettage on the other 4%. RU 486 was most successful with 0.5mg of sulprostone, but these women also experienced considerable vaginal bleeding and pain. Overall uterine bleeding occurred for 8.9 days. The researchers recommended that adequate medical facilities be accessible to women using this method. Mild side effects were nausea, vomiting, and diarrhea. Efficacy and safety matched those of other early abortion methods. In April 1991, a grand multiparous women who smoked heavily and received RU 486 and a prostaglandin died--the 1st reported RU 486 related death. RU 486 may be able to treat fibroids, endometriosis, premenstrual syndrome, meningioma, hypertension, adrenal cancer, glaucoma, some forms of Cushing's syndrome, and breast cancer. The US Food and Drug Administration forbade the commercial import of RU 486 in 1989, even though it deemed RU 486 safe and effective. FDA considered the antiabortion view of the Bush Administration when making this decision. It made this decision despite the fact that abortion was still legal. RU 486 should be available soon for use as an abortifacient in the UK, the Netherlands, Sweden, Norway, Denmark, and Finland. These countries do not intent providing it to US women, however. Further the manufacturer is not willing to provide it to US researchers because it is afraid of antiabortion repercussions which may jeopardize WHO's approval of RU 486.
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PMID:The RU 486 story: the French experience. 173 8

The development of the antiprogestin RU-486, and its current use in France and the UK, potential other application, politics in the US, and future are presented. Ru-486, as commonly known by its company code name, rather than its generic name mifepristone, is an analogue of a progestin used in oral contraceptives, with an added chemical group that allows it to link up with the progesterone receptor, but prevents progesterone's effects. It was approved in France in 1988, and has been used for early abortion up to 7 weeks LMP on 80,000 women. French women, after an initial diagnostic appointment, take 3 200 mg tablets of RU-486, then 36-48 hr later return for a Sulprostone (prostaglandin) injection, and are checked up 4-6 weeks later. About 96% abort completely. Some have nausea, vomiting, or pain. Bleeding averages 9 days, and 1% require treatment for bleeding. 2 cardiovascular events and 1 heart attack have been associated with the prostaglandin, now contraindicated in smokers or women 35. In England, RU-486 abortions began in late 1991, for pregnancies up to 9 weeks, using a gentler prostaglandin, Gemeprost, in a vaginal suppository. Only company-trained doctors may order the drug. Research continues on lower doses of RU-486, other prostaglandins, and effects on the fetus if abortion fails. While there is no known basis for a teratogenic effect of the antiprogestin, strong uterine contractions brought on by prostaglandins, such as misoprostol, as abused for illegal abortion in Latin America, may cause birth defects. RU-486 is expected to be useful for inducing labor, dilating the cervix, emergency contraception, pre-surgical management of Cushing's syndrome, brain cancers with profesterone receptors, among other conditions. Several of the 400 or so antiprogestins known are being tested clinically, notably HRP 2000 by WHO. Political controversy is so intense in the US that Roussel, the maker of RU-486, has no intention of marketing it, and even research supplies are unreliable. Meanwhile, pro-choice groups are innovating ways to test and market antiprogestins legally, perhaps inside state lines. It is expected that a suitable prostaglandin, misoprostol, licensed for peptic ulcer, will be available soon, and even RU-486 will become generic by 1998 when its patent expires.
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PMID:Antiprogestins and the abortion controversy: a progress report. 178 9

Natural PGF administered at a dose of at least 250 micrograms/kg twice daily subcutaneously for at least 4 days starting no earlier than day 5 of cytologic diestrus induces luteolysis and pregnancy termination in the mated bitch. The resulting shortening of the luteal phase is associated with a shortening of the interestrous interval from 1 to 4 months. Bitches treated with PGF show emesis, diarrhea, and panting within 5 minutes and transient hypothermia which lasts 2 to 3 hours but generally have no further reaction. Bitches with cardiac or respiratory dysfunctions are not considered safe patients for early pregnancy termination with PGF because of the cardiovascular effects of this drug. Bitches treated with this regime early in diestrus resorb their conceptuses; those treated after days 35 to 40 show clinical abortion of viable fetuses.
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PMID:Use of prostaglandin F2 alpha for early pregnancy termination in the mismated bitch. 185 44

Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.
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PMID:Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy. 187 72

The International Planned Parenthood Federation (IPPF) new statement on the diagnosis of pregnancy was drawn up in April 1990. A pregnancy diagnosis includes clinical evaluation of the woman's history, symptoms, physical examination, and pregnancy tests. Pregnancy symptoms may include amenorrhea, nausea, vomiting, enlargement and tenderness of the breasts, frequent urination, and changes in appetite and food and drink habits. If biochemical testing is not possible, a reliable clinical diagnosis of pregnancy cannot take place before 6-8 weeks. At this time, the clinician can observe cervical softening and uterine softening and enlargement if a woman is pregnant. If the uterine size does not match the length of amenorrhea, clinicians should suspect the following: earlier or later conception than indicated, ectopic pregnancy, incomplete or missed spontaneous abortion, twin gestation, hydatidiform mole, or other uterine anomaly. They should suspect ectopic pregnancy in women with smaller than expected uterine size when they have been sterilized or are using an IUD or are using low-dose progestogen-only pills or Norplant. They should refer women with smaller than expected uterine size who are experiencing bleeding and/or pain to a more sophisticated clinical facility, where an accurate diagnosis of and adequate treatment for ectopic pregnancy can be done. Biochemical pregnancy tests consist of antibodies that mark human chorionic gonadotropin (hCG) from a urine or serum sample. hCG levels increase beginning about 10 days after fertilization. The most convenient and inexpensive pregnancy test for clinics is the immunoassay test (slide test), which requires a urine or serum sample. It can provide reliable results a few days after the missed menstrual period. Clinicians should provide appropriate counseling regardless of whether the client wishes to continue or terminate the pregnancy.
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PMID:New IPPF statement on the diagnosis of pregnancy. 192 37

Pretreatment with laminaria tent is often used in prostaglandin-induced second-trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects.
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PMID:The use of antiprogestin (RU 486) for termination of second trimester pregnancy. 192 96


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