Karen R. Meckstroth

Misoprostol administered by epithelial routes: Drug absorption and uterine response.

OBJECTIVE: To quantify and compare serum levels and uterine effects following vaginal (dry), vaginal (moistened), buccal, and rectal misoprostol administration. METHODS: Forty women seeking elective abortion between 6 and 12 6/7 weeks were randomly assigned to receive 400 μg of misoprostol by one of four routes. A 2.5-mm pressure monitoring catheter was placed through the cervix to the uterine fundus to record uterine tone and activity during the 5-hour observation period. Serum levels of misoprostol acid were measured at 15 and 30 minutes, then every 30 minutes. RESULTS: The four groups were similar in age, race or ethnicity, body mass index, parity, and gestation. Serum levels after vaginal, vaginal moistened and buccal administration rose gradually, peaked between 15 and 120 minutes and fell slowly. Vaginal and vaginal moistened routes produced higher peak serum levels than buccal and rectal (445.9 and 427.1 compared with 264.8 and 202.2 pg/mL; P=.03) and higher serum concentration area under the curve at 5 hours (1,025.0 and 1279.4 compared with 519.6 and 312.5 pg-hr/mL; P<.001). Uterine tone and activity, however, were similar for buccal and the two vaginal routes. After rectal administration, serum levels peaked earlier (P<.001) then dropped more abruptly, and peak uterine tone (P<.001) and total activity (P=.04) were lower than after the other routes. CONCLUSION: Although serum levels were lower for buccal compared with the vaginal routes, the three routes produced similar uterine tone and activity. Rectal administration produced lower uterine tone and activity. Vaginal serum levels were two to three and a half times higher than those observed in prior misoprostol pharmacokinetic studies. LEVEL OF EVIDENCE: II-1

Serum beta-human chorionic gonadotropin levels and endometrial thickness after medical abortion

Mifepristone is now available in the United States, and it is anticipated that there will be many new providers of medical abortion services. In a national survey, approximately half of women’s health care providers surveyed, including 35% of gynecologists who did not perform surgical abortions, reported that they may offer medical abortion services [1]. Because women who have a medical abortion typically experience symptoms similar to a spontaneous abortion and because uterine curettage is a common intervention for a spontaneous abortion, it is important to establish post medical abortion guidelines to prevent unnecessary surgical intervention. Four parameters can be used to monitor the post-abortion course:

Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis.

The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy < or =56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 mirog of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06-0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20-0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy < or = 56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.

Women's decision making regarding choice of second trimester termination method for pregnancy complications

To describe how women terminating a pregnancy for fetal or maternal complications decide between surgical (dilation and evacuation [D&E]) and medical abortion.

A comparison of tamoxifen and misoprostol to misoprostol alone for early pregnancy termination

A study was undertaken to determine whether the combination of oral tamoxifen and moistened misoprostol administered vaginally was superior to that of placebo and moistened misoprostol administered vaginally for elective termination of early pregnancies.A clinical trial was conducted with a study group of 150 healthy women with pregnancies of </=56 days gestational age who desired pregnancy termination. Subjects were randomized to ingest either 20 mg of tamoxifen (group 1) or placebo (group 2) twice daily for 1 day, followed 48 h later by vaginal administration of 800 micrograms of saline-moistened misoprostol. This dose of misoprostol was repeated 24 h later and 8 days later if an abortion had not occurred. The main outcome measures were incidence of complete abortion, hemoglobin levels, duration of vaginal bleeding, and incidence of side effects. Complete abortion occurred in 709 (93.3%) in group 1 and 68 (90.7%) in group 2. There were no differences in either group between earlier (</=49 days) and later (50-56 days) gestations. The mean duration of uterine bleeding was 7.9 days and 8.2 days in group 1 and group 2, respectively. In group 1, 94.3% who aborted bled for <14 days, and in group 2, 95.6%. No subject required a blood transfusion. There were no significant differences in side effects between the two groups. These data suggest that pretreatment with tamoxifen is not necessary when using moistened vaginal misoprostol for abortion of pregnancies of </=56 days of gestation.

Distance Traveled for an Abortion and Source of Care After Abortion

OBJECTIVE To examine the association between distance traveled for an abortion and site of postabortion care among low-income women. METHODS We conducted a retrospective cohort study using claims data from 39,747 abortions covered by Californias Medicaid program in 2011-2012. Primary outcomes were the odds of abortion-related visits to an emergency department (ED) and the original abortion site, and the secondary outcome was total abortion care costs. We used mixed-effects logistic regression adjusting for patient and abortion characteristics to examine the associations between distance traveled and subsequent abortion-related care at each location. RESULTS Among all abortions (N=39,747), 3% (95% CI 2.9-3.3, n=1,232) were followed by an ED visit (3% first-trimester aspirations, 2% second trimester or later, and 4% medication abortions) and 25% (95% CI 24.1-24.9, n=9,745) were followed by a visit to the original abortion site (4% first-trimester aspirations, 3% second-trimester or later, and 77% medication abortions). Women traveling farther for their abortions had higher odds of visiting an ED (100 or more miles compared with less than 25 miles, first-trimester aspirations: adjusted odds ratio [OR] 2.29, 95% CI 1.50-3.49; medication abortions: adjusted OR 2.30, 95% CI 1.34-3.93) and lower odds of returning to their abortion site for follow-up (100 or more miles compared with less than 25 miles, first-trimester aspirations: adjusted OR 0.36, 95% CI 0.18-0.70; second trimester or later: adjusted OR 0.52, 95% CI 0.31-0.88; and medication abortions: adjusted OR 0.33, 95% CI 0.23-0.50). Costs were consistently higher when subsequent care occurred at an ED rather than the abortion site (median cost

Claims of misoprostol use based on blood sampling should be viewed with skepticism

941 compared with

A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy

536, P<.001). CONCLUSION For most patients, greater distance traveled for abortion was associated with increased likelihood of seeking subsequent care at an ED. Increasing the number of rural Medicaid abortion providers and reimbursing providers for telemedicine and alternatives to routine follow-up would likely improve continuity of care and reduce state costs by shifting the location of follow-up from EDs back to abortion providers.

Misoprostol compared with laminaria before early second-trimester surgical abortion: a randomized trial.

Efforts to prosecute women for induced abortion have included allegations that misoprostol was found in body fluids. These claims, however, are questionable owing to the timing of specimen collection for accurate results, the scarcity and expense of validated assays, and the onerous lab procedures required to determine the presence of the substance. Adequate scrutiny should be applied each time such a claim is made.

Early pregnancy termination with intravaginally administered sodium chloride solution–moistened misoprostol tablets: Historical comparison with mifepristone and oral misoprostol

Several large-scale clinical trials have shown that a regimen of 600 mg of mifepristone, followed by 400 μg of the prostaglandin analogue misoprostol, delivered orally, is a safe and effective means of inducing medical abortion. Misoprostol alone may be an easier and more rapidly effective approach to elective termination, and it is less expensive than the combination. In this randomized, double-blind trial, 250 women with gestations of 56 or fewer days were randomly assigned to receive either 200 mg of mifepristone orally or a vitamin C placebo, followed after 48 hours by 800 μg of vaginal misoprostol. Misoprostol was repeated up to three times at 24-hour intervals until abortion took place. A complete abortion without the need for surgical aspiration was the criterion for success. Medical abortion was successfully achieved in 95.7% of 119 women given mifepristone and vaginal misoprostol. After treatment with the oral placebo and vaginal misoprostol, 88% of 125 women had a successful outcome. The difference in success rates was significant at the 0.05 level. Comparable results were achieved when the gestational age was 49 days or less and 50 to 56 days. Five women given combined treatment had surgical evacuation without a medical indication, three because of mild persistent bleeding. The commonest reasons for surgical evacuation in 15 placebo recipients were the presence of an ongoing pregnancy and incomplete evacuation of gestational tissue without a visible gestational sac. Side effects were similar in the two treatment groups, as were bleeding patterns. The two regimens were comparably acceptable; 91% of all women were satisfied. Nearly 80% of respondents would choose medical abortion again, and 90% would recommend it to a friend. Adding oral mifepristone to vaginal misoprostol seems to have enhanced the success of medically induced abortion in this series. Nevertheless, misoprostol alone remains useful where mifepristone is unavailable or contraindicated.