Comparing abortion induced with methotrexate and misoprostol to methotrexate alone.

This was a dual-cohort study performed to determine if, by using methotrexate alone, abortions could be induced with fewer side effects, without sacrificing effectiveness and patient satisfaction. The subjects were 358 consecutive patients who requested elective medical termination of pregnancy at < 7 weeks gestation. Women were given information and allowed to choose between methotrexate alone (50 mg/m2 intramuscularly) or methotrexate followed 4 days later by 800 micrograms misoprostol vaginally. The two groups were compared with respect to the number of surgical aspirations required, the number of days until the abortion was completed, side effects, and the number of women who would choose the same method again. The surgery rate for methotrexate was 17.2%, whereas for the combination it was 10.9%. The mean numbers of days until the abortion were complete was 23 and 12, respectively. Side effects, mean pain scores, total days of bleeding, and satisfaction rates were not significantly different in the two groups. The high failure rate with methotreaxate alone suggests that it should not be offered despite the high level of satisfaction.

PIP: A dual-cohort study was conducted to determine whether abortion induced by methotrexate alone produces fewer side effects than a misoprostol-methotrexate regimen without sacrificing efficacy. 358 consecutive Canadian abortion seekers with pregnancies of 7 weeks' gestation or less were given the choice of a regimen of 50 mg/sq. m of intramuscular methotrexate or methotrexate followed 4 days later by 800 mcg of vaginal misoprostol. 101 women chose the former and 257 opted for the latter regimen. Women tended to choose the methotrexate-only regimen to avoid misoprostol-related side effects; selection of the combination was motivated by a desire for a rapid pregnancy termination. 82 women (82.8%) in the methotrexate-only group and 228 (89.1%) in the combination group aborted successfully. The failure rate in both groups was significantly higher when the procedure was performed at 6 or more weeks of gestation. It took a mean of 23.1 days from injection to complete abortion in the methotrexate-only group compared with 11.7 days in the methotrexate-misoprostol group. More than half the women had medication-related side effects, primarily nausea, vomiting, and diarrhea, with no significant differences between groups. The mean number of days of bleeding was 9.0 in the methotrexate-only group and 10.1 in the combination group. The mean worst pain score (on an 11-point scale) was 6.4 in the former and 6.1 in the latter group. 91.8% of women in the methotrexate-only group and 90.7% of those in the misoprostol-methotrexate group who successfully aborted stated they would chose the same method again. Given the high failure rate, methotrexate alone should not be offered routinely to abortion seekers. Its use should be reserved for women with very early pregnancies who have relative contraindications for misoprostol.

Vaginal misoprostol for late first trimester abortion.

A group of 120 women with gestations from 64 to 84 days received 800 micrograms of vaginal misoprostol every 24 h for a maximum of three doses without performing postexpulsion systematic preventive curettage. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), side effects, and mean time of expulsion and vaginal bleeding. Complete abortion occurred in 104 of 120 (87%, 95% CI 79, 92) subjects. The decrease of hemoglobin was statistically significant (p = 0.0001) but clinically unimportant: 12.2 mg/dL (SD 1.1) before treatment and 11.6 mg/dL (SD 1.0) after treatment. Statistically significant differences were found only between the success rates for white women in comparison with nonwhite women, in which case the success rates were higher for white than for nonwhite women. Vaginal bleeding lasted 8 +/- 5 days, spotting 4 +/- 3, and total bleeding 12 +/- 4 days. The acceptable expulsion time, the fact that postabortion systematic curettage was not needed, the clinically insignificant hemoglobin loss, and the success rate obtained show that misoprostol administered vaginally may be a valid method for interrupting gestations of 10-12 weeks.

PIP: The effectiveness and safety of vaginal misoprostol, without the need for postexpulsion systematic curettage, were investigated in 120 Cuban women seeking late first-trimester abortion (10-12 weeks). Women received 800 mcg of misoprostol vaginally every 24 hours, for a maximum of three doses. Complete abortion occurred in 104 women (87%); 87 women (73%) aborted after a single dose, 11 (9%) required two doses, and 6 (5%) received a third dose. The remaining 16 women (13%) underwent surgical abortion. Mean hemoglobin decreased from 12.2 mg/dl before treatment to 11.6 mg/dl after abortion--a difference that was statistically but not clinically significant. Side effects--which disappeared within 2 hours--included nausea (22%), vomiting (17%), diarrhea (54%), dizziness (25%), headache (19%), and chills (72%). Although 99% of subjects reported pelvic pain (99%), only 10% requested an analgesic for pain relief. Vaginal bleeding persisted for a mean of 8 days. According to logistic regression analysis, the only variable significantly associated with treatment success was race. The success rate was 94% among White women compared with 73% among Black and Black Cuban women. The acceptable expulsion period, the fact that a postabortion systematic curettage was not required, the clinically insignificant hemoglobin loss, and the high success rate all demonstrate that misoprostol administered vaginally may be a valid method for interrupting late first-trimester pregnancies.

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.

PIP: In Brazil and other South and Central American countries where abortion is illegal, misoprostol is widely available and commonly used to induce abortion. However, misoprostol is not very effective as an abortifacient agent and can cause fetal abnormalities. The present study reviewed the cases of 42 infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first trimester of pregnancy and then born with a congenital abnormality. 17 children had equinovarus with cranial nerve deficiencies and 10 had equinovarus as part of a more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (5 cases) and terminal transverse limb defects (9 cases). Congenital hydrocephalus was present in 8 children. The most commonly taken dose of misoprostol was 800 mcg (range, 200-16,000 mcg). Greater awareness of the widespread use of misoprostol to induce abortion should lead to public health interventions to prevent teratogenic effects.

Vaginal dinoprostone versus oral misoprostol for predilatation of the cervix in first trimester surgical abortion.

Prostaglandins are effective in predilatation of the cervix prior to first trimester surgical termination of pregnancy under local analgesia. Arandomized open comparative trial was devised to compare the effectiveness and acceptability of vaginal dinoprostone with oral misoprostol. Two groups were randomized to control for age, parity and ethnicity. The operation was easier and less painful in older, parous, and Polynesian women. Both methods were effective with respect to ease of dilatation. Both were acceptable and equal with respect to the level of pain experienced by the woman during the operation. Vaginal dinoprostone is more gradual in its action, but it is more expensive, has to be refrigerated and self-insertion may sometimes cause problems. Oral misoprostol is considerably cheaper and does not require refrigeration, but it was associated with more preoperative nausea, cramping and occasional heavy bleeding.

PIP: The effectiveness and side effects of vaginal dinoprostone and oral misoprostol for cervical predilatation in first-trimester surgical abortion were compared in a study conducted at a New Zealand abortion clinic. Over a 3-month period in 1995, abortion patients at Parkview Clinic (Wellington South, New Zealand) were randomized to produce two groups matched for age, parity, and ethnicity. The first group (n = 153) received a vaginal suppository containing 3 mg of dinoprostone, which they inserted themselves at least 12 hours in advance of surgery; women in the second group (n = 160) were given 400 mcg of oral misoprostol at the clinic at least 1 hour in advance of abortion. Misoprostol was associated with more cramping, preoperative vaginal bleeding, and nausea than dinoprostone. Pain ratings did not differ significantly between groups. Overall, dilatation was slightly easier with misoprostol than with dinoprostone. The operation was also easier and less painful in older, parous, and Polynesian women. In the 54 cases where dilatation was rated as difficult, 48 women (88.9%) were nulliparous. Misoprostol is less expensive than dinoprostone and does not require refrigeration. As a result of these findings, Parkview Clinic has decided to use misoprostol for cervical dilatation.

Acute intravaginal misoprostol toxicity with fetal demise.

We report a case of an overdose with fetal demise from the intravaginal administration of misoprostol. A 25-yr-old gravid female self-administered 6000 micrograms misoprostol intravaginally and 600 micrograms orally. She rapidly developed shaking chills, abdominal and extremity cramping, emesis, and confusion. Hyperthermia and hypotension developed within 3.5 h after drug administration, with a temperature of 41.4 degrees C (106 degrees F). Ultrasound at 3.5 h after drug administration showed no fetal movement or heart motion. A nonviable fetus was delivered by emergent cesarean section. Treatment of the mother was supportive and included intravaginal decontamination and endotracheal intubation with neuroparalytic therapy to control agitation and hyperthermia. Recovery was complete within 15 h of drug administration.

PIP: Reported is a case of fetal death associated with a misoprostol overdose. The 25-year-old US woman, gravida 3 para 0 abortion 2, at 36 weeks' gestation presented to the hospital 3 hours after self-administering 6000 mcg of misoprostol intravaginally and 600 mcg orally, reportedly to induce and shorten the duration of labor. Prior to this regimen, the woman was experiencing mild contractions every 15-20 minutes and was aware of fetal movement. She presented with agitation and confusion, shaking chills, abdominal and extremity cramping, emesis, tachycardia, hypotension, and hyperthermia. Pelvic ultrasonography performed 3.5 hours after misoprostol administration showed no fetal movement or heart motion. A nonviable fetus was delivered by emergency cesarean section. Hypotension has not been previously reported in an overdose case and may reflect a direct vasodilatory effect of misoprostol on systemic vascular tone. Marginal placental abruption also may have contributed to the hypotension. The patient's clinical course resolved over 15 hours with supportive care, including intravaginal saline irrigation and endotracheal intubation with neuroparalytic therapy to control agitation and hyperthermia. Divided intravaginal doses of 50 mcg of misoprostol every 4 hours, for a total dose of 50-600 mcg, have effectively induced labor with no significant neonatal or maternal adverse outcomes. In developing countries, doses of 800-1600 mcg of misoprostol administered intravaginally have successfully induced first-trimester abortion.

Termination of second trimester pregnancy with gemeprost and misoprostol: a randomized double-blind placebo-controlled trial.

A prospective randomized double-blind placebo-controlled trial was conducted in 70 subjects to determine whether pre-treatment with misoprostol could facilitate termination of second trimester pregnancy by gemeprost. The women received either 400 micrograms oral misoprostol or placebo tablets 12 hours before the administration of vaginal pessary of gemeprost 1 mg every 3 hours. There were no significant differences in induction-abortion interval and the amount of gemeprost required between the misoprostol and the placebo group. There was no significant difference in the incidence of side effects or analgesic requirement between the two groups. We conclude that oral misoprostol is not useful in facilitating termination of second trimester pregnancy by gemeprost.

PIP: In Hong Kong, 70 healthy women aged 16-40 years at the gestational age of 14-20 weeks who requested legal termination of pregnancy were randomly allocated to receive either 400 mg misoprostol or a placebo (vitamin B6) 12 hours before initial administration of intravaginal gemeprost pessary (1 mg) every three hours. This double-blind study aimed to determine whether pretreatment with oral misoprostol can improve the efficacy of intravaginal gemeprost pessary to effect induced abortion. The two groups responded essentially the same in terms of the incidence of nausea, vomiting, dizziness, fatigue, breast tenderness, or lower abdominal pain during the interval between misoprostol administration and gemeprost administration. Similarly, side effects and analgesic requirements did not differ significantly. The complete abortion rate was not significantly different between the two groups (62.9% for misoprostol and 68.6% for placebo). Even though the induction-abortion interval was shorter and the amount of gemeprost required was smaller in the misoprostol group than the placebo group (27.3 vs. 28.2 hours and 4.9 vs. 5.7 mg, respectively), the differences were not significant (p = 0.0863 and 0.0957, respectively). These findings suggest that oral misoprostol does not facilitate termination of second trimester pregnancy by intravaginal gemeprost pessary.

Change in serum beta-human chorionic gonadotropin after abortion with methotrexate and misoprostol.

OBJECTIVE: The purpose of this study was to determine the normal beta-human chorionic gonadotropin change within 24 hours after a medical abortion. Because a medical abortion creates a "miscarriage," these data can represent the serum beta-human chorionic gonadotropin changes that would occur with a complete spontaneous abortion. Knowledge of normal beta-human chorionic gonadotropin changes after a spontaneous abortion may help to differentiate within a 24-hour period a complete from an incomplete spontaneous abortion or an ectopic pregnancy. STUDY DESIGN: Data from recent trials that used methotrexate and misoprostol for abortion at < or = 56 day's gestation were reviewed. Patients from each of four trials were included in this analysis if (1) they received both methotrexate intramuscularly and misoprostol vaginally and (2) they had serum beta-human chorionic gonadotropin levels drawn on both the day of misoprostol administration and the next day. RESULTS: The change in serum beta-human chorionic gonadotropin was evaluated in 86 patients. Subjects who had a complete abortion after receiving methotrexate and a single dose of misoprostol had a decline in serum beta- human chorionic gonadotropin of 66% +/- 8%. All other subjects had a decline of 25% +/- 19% (p=0.0001). CONCLUSIONS: An aborting pregnancy, if the abortion has occurred, should have a beta-human chorionic gonadotropin decrease of at least 48% within approximately 24 hours. This decline, however, does not guarantee that the abortion is complete. A patient with a serum beta-human chorionic gonadotropin level that has not declined by a minimum of approximately 50% over 24 hours is unlikely to have a complete abortion.

PIP: The purpose of the study was to determine the normal beta-human chorionic gonadotropin change within 24 hours after a medical abortion to differentiate a complete from an incomplete spontaneous abortion or an ectopic pregnancy. 171 English- and Spanish-speaking pregnant women were recruited for four prospective trials by the University of California, San Francisco. Three trials included women under 56 days' gestation and a fourth trial included women between 57 and 63 days' gestation. Patients from the 1st trial group received methotrexate 50 mg/sq. meter im, followed 3 days later by misoprostol 800 mcg vaginally. In the 2nd trial group, patients were randomized to receive methotrexate 50 mg/sq. meter im, followed by misoprostol or misoprostol alone. In the 3rd trial group, patients were randomized to receive methotrexate 50 mg/sq. meter im, followed by misoprostol 3 days later (group 1) or 7 days later (group 2). In the 4th trial group patients between 57 and 63 days' gestation received methotrexate 50 mg/square meter im followed 3 days later by misoprostol 800 mcg vaginally. 86 women met the criteria for evaluation of the change in serum beta-hCG levels on the day after misoprostol administration. 3 of these patients had incomplete abortion (1 immediate success and 2 delayed successes). The change in beta-hCG on the day after the initial misoprostol administration for these was -67%, -20%, and -19%, respectively. 48 women received the first dose of misoprostol 3 days after methotrexate and 38 women received misoprostol 7 days later. Subjects who had complete abortion after receiving methotrexate and a single dose of misoprostol had a decline in serum beta-hCG of 66% +or- 8%. All other subjects had a decline of 25% +or- 19% (p = .0001). An aborting pregnancy, if the abortion has occurred, should have a beta-hCG decrease of approximately 50% within about 24 hours. However, a patient with a serum beta-hCG level that has not declined approximately 50% over 24 hours is unlikely to have a complete abortion.

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.

BACKGROUND: Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone. METHODS: The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol. RESULTS: Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion.

PIP: During June 1993-January 1994 in Scotland, clinicians recorded data on 270 women attending the fertility control clinic at Aberdeen Royal Hospitals for voluntary termination of early pregnancy (within 63 days from onset of amenorrhea). They received 600 mg of oral RU-486 on day 1 and either 800 mcg of oral misoprostol or 800 mcg misoprostol inserted deep into the vagina 36-48 hours later. Researchers wanted to compare the safety and efficacy of 800 mcg oral misoprostol with the safety and efficacy of 800 mcg vaginal misoprostol in women who had previously received RU-486. 2.6% aborted before receiving misoprostol. Complete abortion without surgical intervention was more frequent in the vaginal misoprostol group than the oral misoprostol group (95% vs. 87%; p = 0.03). The continued pregnancy rate was lower in the vaginal misoprostol group than the oral misoprostol group (1% vs. 7%; p = 0.01). Expulsion of the conceptus was more likely to occur within 4 hours of receiving misoprostol among the vaginal group than the oral group (93% vs. 78%; p 0.001). The oral misoprostol group had a higher incidence than the vaginal misoprostol group of vomiting (44% vs. 31%; p = 0.04) and diarrhea (36% vs. 18%; p = 0.002). The two groups did not differ significantly with respect to other side effects or severity of symptoms. The women in the oral misoprostol group were more likely to think that the antiemetic drug took minutes rather than 1 or more hours to act than those in the vaginal misoprostol group (61% vs. 34%; p 0.001). These findings show that, following administration of RU-486, vaginal misoprostol was better tolerated and more effective than oral misoprostol at inducing abortion in women in the first trimester of pregnancy.

Brazil investigates drug's possible link with birth defects.

PIP: In Brazil, many women are using the synthetic prostaglandin misoprostol to induce abortion. Since abortion is illegal in Brazil, they take misoprostol without any medical supervision. It was introduced in Brazil in 1986 as a treatment for gastric ulcers. Its brand name is Cytotec. The prescription drug is widely available on the black market, where the price for 4 200-mg tablets begins at US$100. Use of the drug with failure to abort may be linked to birth defects. A geneticist and a neuropediatrician at the Children's Institute of the Sao Paulo Hospital das Clinicas are studying 9 children with congenital or neurological abnormalities. Physicians in other parts of Brazil are following another 30 children with the same circumstances. A physician in Porto Alegre is following 40 women who took misoprostol but did not abort. As of mid 1994, she had found 3 cases of congenital abnormalities. The Brazilian Society for Clinical Genetics is overseeing an epidemiologic study in 10 major maternity hospitals where researchers will examine all neonates and ask all mothers about the possible use of misoprostol. Staff at the genetics outpatient clinics of 6 leading hospitals are about to conduct a related study among mothers. Both of these studies run the risk of low reporting, since mothers may be disinclined to admit to criminal use of misoprostol. Almost 50% of all women who want pregnancy termination in Brazil use misoprostol. The abortion fails in about 33% of these cases. The evidence suggests an 8-10% risk of abnormalities among women who use misoprostol and experience abortion failure. Ministry of Health sources unofficially appreciate that misoprostol use is reducing the number of women hospitalized with infections caused by abortion attempts with sharp instruments, which in turn has reduced maternal mortality.^ieng