Methotrexate and misoprostol for early abortion: a multicenter trial. I. Safety and efficacy.

A prospective trial was conducted including 300 pregnant women seeking elective abortion to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 56 days gestation. Subjects received methotrexate 50 mg/ m2 intramuscularly followed 7 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated the next day if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), duration of vaginal bleeding, and side effects. Complete abortion occurred in 263/ 300 (87.7%, 95% CI 83.4, 91.2%) patients. The complete abortion rate was higher for early gestations: 183/202 (90.6%, 95% CI 85.7, 94.2%) at < or = 49 days gestation, and 80/98 (81.6%, 95% CI 72.5, 88.7%) from 50-56 days gestation (p = 0.038). Abortion occurred in the 24 hours following the initial or repeat misoprostol dose (immediate success) in 65.0%; the remaining 22.7% of women who aborted did so after a delay of 23.6 +/- 9.1 (mean +/- standard deviation) days. Vaginal bleeding lasted 14 +/- 7 days and 11 +/- 9 days in immediate success and delayed success patients, respectively. Overall, 69.7%, 87.7%, and 91.7% of patients had passed the pregnancy by 14, 28, and 35 days, respectively, after receiving methotrexate. Methotrexate and misoprostol side effects were minimal. This treatment regimen offers an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.

PIP: Clinical researchers recruited 300 healthy English- and Spanish-speaking pregnant women of gestational age no greater than 56 days for a prospective clinical trial of intramuscular 50 mg/sq. m methotrexate and 800 vaginal mcg misoprostol for induced abortion. The women were recruited from San Francisco General Hospital in California; Magee-Women's Hospital in Pittsburgh, Kansas; and Women's Health Care Services in Wichita, Kansas. 87.7% of the women had a complete abortion without need for a surgical procedure. After administration of methotrexate, passage of the conceptus increased as time passed (69.7% for 14 days, 87.7% for 28 days, and 91.7% for 35 days). The complete abortion rate decreased as the gestational age increased (90.6% for 49 days vs. 81.6% for 50-56 days; p = 0.038). Abortion took place within 24 hours of the first or repeat misoprostol dose in 65% of women who aborted. The success rate after the first dose of misoprostol was higher between 43 and 56 days than before 43 days (54.7% vs. 43.5%; p = 0.07). All women with an incomplete abortion experienced persistent and/or heavy vaginal bleeding. Vaginal bleeding lasted, on average, for 14 days in immediate success cases and for 11 days in delayed success cases. Multivariate logistic regression analysis found a significant predictor of success for the methotrexate and misoprostol combination to be gravidity under 3 (p = 0.01, odds ratio [OR] = 2.6). Serum beta-human chorionic gonadotropin of 40,000-80,000 IU/L (p = 0.025, OR = 0.38) and serum beta-human chorionic gonadotropin of 80,000 IU/L (p 0.001, OR = 0.2) were significant predictors of its failure. The rate of side effects was low. These findings show that this treatment regimen is a safe and effective alternative to surgical abortion or the use of antiprogestins and prostaglandins for medical abortion.

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.

Mifepristone (RU486) is licensed for use in France at a dose of 600 mg in combination with 1.0 mg of vaginal gemeprost (a prostaglandin E1 analogue) for medical termination of early pregnancy up to 7 weeks' amenorrhoea resulting in 96% complete abortion rates. This study examines if it is possible to use lower doses of mifepristone and gemeprost to achieve similar success for women with pregnancies up to 56 days' amenorrhoea. Four groups of 25 women were scheduled to be given single oral doses of either 50 mg or 200 mg of mifepristone followed 48 hours later by insertion of a single vaginal pessary of 0.5 mg or 1.0 mg gemeprost. The lowest dose combination (i.e. 50 mg mifepristone + 0.5 mg gemeprost) was found to have unacceptable efficacy with a complete abortion rate of only 82%; the highest dose combination (i.e. 200 mg mifepristone + 1.0 mg gemeprost) resulted in a satisfactory complete abortion rate of 96% which is comparable with the rates for the recommended high 600 mg mifepristone dose (+ 1.0 mg gemeprost) in routine clinical use in France. The current study shows that efficacy can be maintained using a third of the recommended dose of mifepristone.

RU486: the French experience.

RU486 (mifepristone) followed by a prostaglandin (PG) analogue has been marketed in France since April 1990 as a medical alternative to surgery for early pregnancy termination. By law, the drug is used only in the centres approved for voluntary pregnancy termination, and its distribution is strictly controlled. Before being marketed, it was distributed to more than 20,000 women, as part of a training programme for the prescribers. Analysis confirmed an efficacy rate of 95.3%. Failures included incomplete ovular expulsion (2.8%), premature vacuum aspiration (0.7%) and ongoing pregnancy (1.2%). Pelvic pain and malaise were reported as side-effects in 1.6 and 1.2% of the cases respectively. Infectious complications were reported in 0.2% of the cases. Three severe adverse events (one of which was fatal) occurred, including myocardial infarction and ventricular arhythmia, in the hours following PG administration and justify a careful medical monitoring in the centre 3-4 h after administration of PG. For this reason, a trial was undertaken to evaluate the efficacy of an oral form of a PGE1 analogue (misoprostol). When RU486 was followed 36-48 h later by 400 micrograms of misoprostol, the efficacy rate was 96.9%, indicating an efficacy equivalent to that obtained with the other PG analogues. The distribution procedures were adequately followed by the prescribers and by the patients. In summary, RU486 constitutes a safe and efficient medical means of pregnancy termination, provided that the manufacturer's recommendations are properly followed.

The use of progesterone antagonists in combination with prostaglandin for termination of pregnancy.

Antiprogestin alone is not sufficiently effective in terminating early pregnancy to be clinically useful. The only exception seems to be immediate post-ovulatory administration which inhibits endometrial development to an extent that prevents implantation of the fertilized ovum. During early pregnancy the uterus is inactive. Treatment with antiprogestin with result in an increased uterine contractility and a significant increase of myometrial sensitivity to prostaglandin. The effect is probably mainly due to the release of the inhibitory effect of progesterone. Antiprogestin not only activates the uterus, it also causes a ripening of the cervix. The combination of RU486 and either vaginal administration of gemeprost or i.m. injections of nalador provide a safe and effective medical abortion in the first 8 weeks of pregnancy. Recent clinical studies indicate that it may be possible to replace the prostaglandin analogues in current use by the orally active analogue misoprostol. Misoprostol is inexpensive and stable at room temperature and would facilitate the provision of medical abortion with mifepristone. Experimental data also indicate that a combination of RU486 and misoprostol may be developed into an effective once-a-month late luteal method to regulate fertility. Pre-treatment with RU486 is also useful in later stages of gestation. A combination of RU486 and the vaginal administration of gemeprost is a highly effective, safe and simple non-invasive method for terminating both early and late second trimester pregnancy.

Comparative study of extra-amniotic prostaglandin F2 alpha infusion and increasing intravenous oxytocin for termination of second trimester missed abortion.

Extra-amniotic infusion of prostaglandin F2 alpha (PGF2 alpha) and intravenous (IV) oxytocin in increasing doses were compared in a retrospective study to establish the efficacy of the two methods for termination of pregnancies with second trimester missed abortion. Sixty women with this complication underwent pregnancy termination, 28 by extra-amniotic infusion of PGF2 alpha and oxytocin augmentation, if necessary, and 32 by IV oxytocin in increasing doses. All patients in the PGF2 alpha group aborted within 24 hours from onset of infusion and seven of them needed oxytocin augmentation. There were nine failures in the oxytocin group and the other 23 aborted within 17 hours. The mean (plus or minus standard error of the mean) induction-abortion interval was significantly less in the oxytocin group (6.9 +/- 3.4 hours) than in the PGF2 alpha group (12.6 +/- 5.7 hours) p < 0.001. Eight patients in the group had mild side effects, such as nausea, flushes or transient hypotension. Uterine hypertonus was observed in two women receiving PGF2 alpha and treated by temporary interruption of the infusion. In the oxytocin group, one patient had coagulation disturbances and one, hemorrhage. We conclude that extra-amniotic PGF2 alpha infusion is more effective than IV oxytocin in increasing doses, for termination of second trimester missed abortion, but takes effect more slowly. We can assume that further use of IV oxytocin immediately after termination of the PGF2 alpha administration can shorten the induction-abortion interval.

Methotrexate and misoprostol for early abortion.

Methotrexate is cytotoxic to trophoblast and, in low doses, has minimal side effects. It is used to treat both gestational trophoblastic neoplasia and ectopic pregnancy. The cytotoxic effects of methotrexate on intrauterine trophoblast should be equivalent. To test this hypothesis, ten pregnant women, < 8 weeks' gestation were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days later by misoprostol, a prostaglandin E1 analogue. The first 4 patients received misoprostol 600 micrograms orally; none aborted soon after the misoprostol. Two patients aborted 25 and 26 days after the methotrexate injection and two elected a suction abortion after 14 days (one by choice and one because the pregnancy was still viable). The last 6 patients received misoprostol 800 micrograms vaginally and aborted within 3-8 hours. One patient had an incomplete abortion requiring a suction curettage 34 days after the misoprostol. Vaginal bleeding for these 6 patients lasted an average of 29 +/- 11 days (range, 12-42 days). No methotrexate side effects were observed. Vaginal misoprostol (800 micrograms) was significantly more effective (p = 0.005) than oral misoprostol (600 micrograms) in effecting abortion after intramuscular methotrexate.

The effectiveness of intravaginal misoprostol (Cytotec) in inducing abortion after eleven weeks of pregnancy.

At Maputo Central Hospital in Mozambique, intravaginal misoprostol, a PGE2 methyl-analogue, was used by 169 women whose request for interruption of pregnancy had been approved. The drug was used by women who had completed between 12 and 23 weeks of gestation. The initial dose was 800 micrograms, repeated 24 hours later if abortion had not occurred or was not in progress. The treatment was considered a failure when abortion was not advanced by 48 hours after the initial dose, and curettage was performed in all but one of such cases. During the course of the study, the dosage was successively reduced to 600, 400, and 200 micrograms. Abortion was successfully induced in 154 women (91.1 percent); there were 10 failures (5.9 percent), and five women (3.0 percent) dropped out of the study. The mean time from initial dose to abortion was 14.3 hours. No significant association of success rate and time from dosage to expulsion was found with age, parity, previous abortion, or gestational age. Preventive vacuum aspiration of the uterine cavity was carried out on all subjects.

The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol.

Although it has been demonstrated that a combination of mifepristone and a prostaglandin is an effective method of inducing abortion in early pregnancy, the optimum dose of the antigestogen is unknown. Women (n = 220) requesting abortion in early pregnancy (< or = 63 days amenorrhoea) were randomized to receive a single dose of either 600 or 200 mg mifepristone followed 48 h later by a single dose of 600 micrograms misoprostol by mouth. The percentage of women who had a complete abortion (93.6% confidence interval 90.4-95.5%) was identical in the two groups. There was no significant difference in the number of women who passed the fetus within 4 h of receiving the prostaglandin (64 versus 74%), the days of bleeding (14.6 +/- 1.1 versus 15.3 +/- 0.9) nor in the onset of the next period (39.7 +/- 1.3 versus 36.7 +/- 1.3) respectively between the groups receiving 200 or 600 mg mifepristone. However, the complete abortion rate was significantly higher in women < or = 49 days compared to women 50-63 days amenorrhoea (97.5 versus 89.1% respectively; P < 0.02). There was no difference in any of the other parameters at different weeks of gestation. We conclude: (i) that the recommended dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical efficacy, (ii) that the combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing abortion in women < 50 days amenorrhoea and (iii) at gestation > 56 days, this combination may result in too many incomplete abortions to be clinically acceptable.

Clinical use of mifepristone (RU 486).

Because progesterone is essential for the establishment and maintenance of pregnancy, it has long been recognized that a substance which antagonized the action of progesterone would have potential as an antifertility agent. Within 2 years of the synthesis of the progesterone antagonist RU 486 (mifepristone) it was demonstrated that bleeding and uterine contractions occurred following its administration in non-pregnant and pregnant women. Extensive trials over the last 10 years have established that a single dose of mifepristone followed 36-48 hours later by a prostaglandin, is an effective, safe alternative to vacuum aspiration for the termination of early pregnancy. Although this combination is licensed in France, China and the United Kingdom for induction of abortion, research is continuing to determine the minimum effective dose of mifepristone and type of prostaglandin which is associated with minimum side effects without loss of efficacy. In addition, studies to determine the acceptability of this type of medical abortion to women in different cultures and societies are required. The facilities necessary for medical termination differ from those for surgical abortion, although the requirements for access to emergency resuscitation and treatment of (rare) complications are similar for the two methods. Mifepristone is very effective in the management of prostaglandin-induced midtrimester abortion. By sensitizing the uterus to prostaglandin, the dose of prostaglandin can be reduced with a shortened prostaglandin-abortion interval. Administration of mifepristone in the early luteal phase of the cycle delays the development of a secretory endometrium. Preliminary studies suggest that it may be highly effective when given at this time as a post-coital contraceptive or 'once a month' pill. Although antigestagens offer great promise as agents to help regulate human fertility, their widespread use may be constrained more by religious and political factors, rather than by demonstration of clinical efficacy.

Conditions for choosing between drug-induced and surgical abortions.

In France, pregnant women with amenorrhoea of no more than 49 days intending to terminate pregnancy can choose between a surgical abortion via vacuum aspiration under local or general anesthesia and a drug method combining Mifepristone orally administered (RU 486 degrees), with a prostaglandin analogue. This prospective survey was conducted to study the conditions under which women choose their abortion method, and to evaluate the acceptability of each method after the abortion. The data gathered from 488 women were analyzed according to their initial decision, and then according to the method actually used. The majority (62%) chose RU 486. The women's choice was found to be linked to sociodemographic characteristics such as age, education, occupation, geographic origin, and certain attitudes towards pregnancy, as well as to the individual criteria of each method. The women who chose the drug protocol had most often already made their decision before going to the family planning center (68%), having been advised by their doctor (20%). They were slightly less satisfied with the abortion experience than they had expected: 12.4% were unsatisfied in the RU group and 3.6% in the aspiration group. They needed more rest and quiet afterwards (50%) than the other women. They were distinguished by their desire to verify the expulsion (63%). The length of pregnancy is therefore not the only criterion to be considered when recommending one or other of these methods: the women concerned have different requirements and should have several possibilities to choose from.

Labor characteristics of uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2 gel versus intravenous oxytocin.

Labor characteristics after intracervical application of 0.5 mg prostaglandin (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections, instrumental deliveries and fetal distress had the same frequency, but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second PGE2 dose, and almost half of the women in the PGE2 group experienced 'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores < 7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for mother and fetus.

PIP: Labor characteristics after intracervical application of 0.5 mg prostaglandin E2 (PGE2) gel (n=83) vs iv administration of oxytocin (n=82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction-to-delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p0.001). Cesarean sections, instrumental deliveries, and fetal distress occurred with the same frequency, but the failures of trail were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs 6%, p0.01). 24% of the women required a 2nd dose of PGE2, and almost 1/2 of the women in the PGE2 group experiences spontaneous labor. More neonates in the oxytocin group had 5-minute Apgar scores 7 (p0.05). Intracervical PGE2 gel application is superior to iv oxytocin in terms of shortening the induction-to-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for both mother and fetus.

Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone.

A combination of the antiprogestagen mifepristone and an exogenous prostaglandin given by intramuscular injection or intravaginal pessary is a highly effective means of inducing abortion in early pregnancy. However, the search for a stable oral prostaglandin preparation has been largely unsuccessful. The effect of misoprostol, an orally active prostaglandin used to treat peptic ulcer, on uterine contractility was investigated in 33 women in early pregnancy (under 56 days' amenorrhoea). After administration of misoprostol in doses ranging from 200 micrograms to 600 micrograms, there was a significant increase in uterine pressure. In a second group of women who were given 200-1000 micrograms misoprostol 48 h after the administration of 200 mg mifepristone, there was a significant increase in the amplitude and frequency of uterine contractions. Complete abortion took place in 18 of the 21 women who received misoprostol after mifepristone, but in only 2 of 40 women given misoprostol alone. Our findings show that misoprostol increases uterine activity in early pregnancy and suggest that, in combination with mifepristone, it may be a highly effective method of inducing therapeutic abortion.

Induction of labour in nulliparas with poor cervical score: oxytocin or prostaglandin vaginal pessaries?

In a previous study nulliparas with poor cervical score (less than 5 out of 10) had a 43.5% Caesarean section (CS) rate of which 55% were for failed induction when labour was induced by artificial rupture of membranes and oxytocin infusion. In this study induction of labour by 2 doses of 3 mg prostaglandin E2 (PGE2) vaginal pessaries, 4 hours apart, and if necessary by artificial rupture of membranes and oxytocin infusion 24 hours later, resulted in a CS rate of 23.7% of which 38.9% were for failed induction. The latter regimen resulted in a significantly lower CS rate compared with labour induced by oxytocin infusion and rupture of membranes without the use of prostaglandins (p less than 0.001). In the prostaglandin group 53.3% were established in labour within 24 hours of inserting the pessary and in these patients the CS rate was 18.5%. In those who did not start labour and needed rupture of membranes and oxytocin infusion 24 hours after the first pessary, 34 (47.9%) had a good cervical score (greater than or equal to 6 out of 10) and 37 (52.1%) had a poor cervical score (less than or equal to 5 out of 10) at the time of amniotomy. The CS rates in these groups were 8.8% and 48.6% respectively (p less than 0.001). In nulliparas with poor cervical score induction is better performed with vaginal prostaglandin pessaries in order to reduce the high CS rate associated with artificial rupture of membranes and oxytocin infusion.

Late midtrimester medical pregnancy terminations: three different procedures with prostaglandin F2 alpha and laminaria tents.

One hundred twenty eight women underwent midtrimester induced abortion with: 1) combined regimen of intramniotic prostaglandin (PG) F2a injection and intracervical laminaria tents (group A, 50 women), 2) intramniotic PGF2a injection only (group B, 51 women) and 3) laminaria tents followed by intracervical PGF2a tablets insertion (group C, 27 women). The mean induction-abortion time (+/- SE) was 24.9 +/- 1.7 hours for group A, 28.2 +/- 2.2 hours for group B (p greater than 0.05) and 42.1 +/- 3.4 hours for group C, significantly longer than goup A and B (p less than 0.001 and p less than 0.01 respectively). In 48 hours 98% of the patients of group A, 90% of group B (p less than 0.05) and 59% of group C (p less than 0.001) completed the abortion procedure. Parous women of group A and B presented similar induction - abortion time, while in nulliparous the use of laminaria shortened the abortion procedure significantly (p less than 0.05). The complications rate was low. In conclusion, the intracervical PGF2a insertion is a simple but very slow abortion procedure with high failure rates. The intramniotic PGF2a injection is a successful method for late midtrimester medical pregnancy termination and the concurrent use of laminaria tents shortens the abortion procedure, particularly in nulliparous, reduces the number of prostaglandins' reinjections and increases the incidence of successful abortion within 48 hours.

PIP: 128 women underwent midtrimester induced abortion with the following: 1) a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) injection and intracervical laminaria tents (group A, 50 women); 2) intraamniotic PGF2alpha injection only (group B, 51 women); and 3) laminaria tents followed by intracervical PGF2alpha tablets insertion (group C, 27 women). The mean induction-abortion time (+or -SE) was 23.9 +or-1.7 hours for group A, 28.2 +or-2.2 hours for group B (p0.05), and 42.1 +or-3.4 hours for group C, which was significantly longer than groups A or B (p0.001 and p0.01). In 48 hours, 98% of the patients in group A, 90% of group (p0.05), and 59% of group C (p0.001) completed the abortion procedure. Parous women in groups A and B presented similar induction-abortion time, while among nulliparous women, the use of laminaria shortened the abortion procedure significantly (p0.05). The complications rate was low. In conclusion, the intracervical PGF2alpha insertion is a simple but very slow abortion procedure with high failure rates. The intraamniotic PGF2alpha injection is a successful method for late midtrimester medical pregnancy termination and the concurrent use of laminaria tents shortens the abortion procedure, particularly in nulliparous women, reduces the number of PG reinjections, and increases the incidence of successful abortion within 48 hours.

Midtrimester abortion induction with intraamniotic prostaglandin F2 alpha in women with previous uterine surgery.

Of 207 women who underwent midtrimester induced abortion with intraamniotic prostaglandin F 2 alpha instillation, 30 (14.5%) had had one or more previous uterine operations. Multivariate analysis showed no correlation between a previous uterine operation and the hospitalization length, procedure complication rate or length of the injection-delivery interval (IDI). The IDI was similar in patients with and without a previous uterine operation. No case of uterine rupture occurred. Intraamniotic prostaglandin instillation for midtrimester abortion induction seems to be an effective procedure without severe complications in women with previous uterine operations.

PIP: Of 207 women who underwent midtrimester induced abortion with intraamniotic prostaglandin (PG) F2alpha instillation, 30 (14.5%) had 1 or more previous uterine operations. Multivariate analysis showed no correlation between a previous uterine operation and the hospitalization length, procedure complication rate, or length of the injection-delivery interval (IDI). The IDI was similar in both patients with and without a previous uterine operation. No case of uterine rupture occurred. Intraamniotic PG instillation for midtrimester abortion induction seems to be an effective procedure without severe complications in women with previous uterine operations.

The use of 16.16-dimethyl-PGE1-delta-methyl ester (Cervagem) vaginal pessaries for cervical dilatation prior to evacuation for second trimester termination.

The results of a study of 101 consecutive second trimester terminations by Dilatation and Evacuation (D & E) under ultrasound control is presented. All had a Cervagem pessary inserted into the vagina prior to the procedure. The PGE1 analogue was assessed as 'effective' in 97% of patients. Concomitant ultrasound resulted in no patient leaving the operating table with retained products. The high efficacy of the single pessary associated with a low incidence of side-effects makes this combination the method of choice for nearly all second trimester terminations.

The use of antiprogestin (RU 486) for termination of second trimester pregnancy.

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.

[Rupture of a healthy uterus in a prostaglandin-induced abortion in the second trimester]. / Rupture d'un utérus sain lors d'une interruption de grossesse par prostaglandines au deuxième trimestre.

The authors report one case of uterine rupture in a non scarred uterus when an analogue of prostaglandin E2 was being transfused. It was Sulprostone used to terminate a pregnancy because of fetal death in utero after 27 weeks of amenorrhea. This case history and an analysis of the literature makes it possible to point out the need to reach the diagnosis before signs become too severe and to show that pharmacological knowledge of the drug has to be improved as well as the ways of administering prostaglandin analogue. This is to be conducted together with improving the ways of terminating pregnancies in the second trimester. It shows that mechanical accidents can occur even where there are no obvious risk factors. In this case, pain continued from the time of the rupture under epidural anaesthesia. The physiopathology is reviewed. Finally, conservative treatment of the uterus should be carried out whenever possible in order to allow a new pregnancy to occur and to lessen the morbidity of the operation.

PIP: The authors report a case of uterine rupture in a nonscarred uterus when an analogue of prostaglandin E2 (PGE2) was being transfused. The drug sulprostone was used to terminate a pregnancy due to fetal death in utero after 27 weeks of amenorrhea. This case history and an analysis of the literature makes it possible to point out the need to reach a diagnosis before the symptoms become too severe. It is also to show that pharmacological knowledge about the drug must be improved as well as the ways to administer the PG analogue. This should be done simultaneous to improving ways to terminate pregnancies during the 2nd trimester. It demonstrates that mechanical accidents can occur even where there are no obvious risk factors. In this case, pain continued from the time of the rupture under epidural anesthesia. In this article, physiopathology is reviewed. Finally, conservative treatment of the uterus should be conducted whenever possible in order to allow a new pregnancy to occur and reduce the likelihood of morbidity following the procedure. (author's modified)

Vacuum aspiration for termination of early second trimester pregnancy after treatment with vaginal prostaglandin.

Vaginal and intramuscular administration of prostaglandin analogues are routinely used for dilatation of the cervical canal prior to vacuum aspiration in first trimester abortion. Whether the same procedure is also useful during the first weeks of the second trimester has been much less investigated. In the present study, 127 women in the 13th and 14th week of pregnancy were pretreated with 3 mg 9-deoxo-16,16-dimethyl-9-methylene PGE2 administered vaginally 12 hours before surgery. At surgery the cervical canal was dilated to 9.8 mm +/- 2.5 mm (mean +/- SD) and the evacuation of the uterus was uneventful. In 21% of the patients vaginal bleeding occurred prior to the operation. The mean blood loss at surgery was 49 ml and exceeded 100 ml in only 6 patients. Gastrointestinal side effects were rare but analgesic injections were demanded by 29% of the patients during the pretreatment period. No subsequent curettage was performed during the follow-up period but 2 patients (1.6%) were readmitted because of post-abortion endometritis. It can be concluded that after pretreatment with PG, vacuum aspiration can be safely performed during the first weeks of the second trimester.

[Effect of hormonal contraceptives on eicosanoid content of menstrual blood]. / Einfluss hormoneller Kontrazeptiva auf den Eicosanoidgehalt des Menstrualblutes.

PIP: The derivatives of arachidonic acid are generally called by the term eicosanoid. Arachidonic acid is a starting material for a series of biologically highly active metabolites that are formed either through cyclooxygenase, e.g., the prostaglandins (PG), or through various lipoxygenase ways, e.g., hydroxyarachidonic acids (HETE), leukotriene (LT), and peptide-LT. Eicosanoids also take part in menstrual bleeding; in dysmenorrhea also cyclooxygenase inhibitors, e.g., indomethacin have been proven to fight pain in addition to spasmolytics and the preventive action of hormonal contraceptives. PGs and peptide-LT could be shown in relative high concentrations in the endometrium of dysmenorrheic women. An analytic method in which menstrual blood was used as test material was developed. Women were given standardized tampons and holders filled with acidified alcohol. The holders were weighed for determination of the amount of blood. A special high performance liquid chromatography separation system was developed for purification, and radioimmunoassay was subsequently used for analysis of 60keto-PGF1alpha, and PGE2. 103 tampons of 14 subjects from 24 menstrual cycles were evaluated in 4 groups; no hormonal contraceptive use, contraceptive use, no pain, and pain. The taking of a pill significantly affected the blood volume; it was only 1/2 as much as in the control group without the taking of a pill. In the control group with a pill and pain 12 HETE was quantitatively the most important eicosanoid with a 60% share. F2alpha dominated among PGs. In patients with pain without pill use the average values of 6-keto, PGE2, 12-HETE, and LTB 4 were 50% higher. After pill use PG concentrations dropped significantly by 80% compared with controls. 12-HETE and PGF2alpha were the main metabolites of arachidonic acid in menstrual blood, in pain some metabolites were higher, and OCs reduced eicosanoid excretion significantly.^ieng