Objectives To compare the side effect profiles of regimens of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate patients' perceptions of medical abortion. Design Double-blind, randomised controlled trial.Setting Fifteen gynaecological clinics in 11 countries.Population A total of 2219 healthy pregnant women requesting medical abortion with 63 days of amenorrhoea. Two thousand women were asked about their perceptions of the method. Methods Mifepristone 200 mg orally on day one, followed by 0.8 mg misoprostol either orally or vaginally on day three. The oral group (O/O group) and one of the vaginal groups (V/O group) continued with 0.4 mg of oral misoprostol, and the vaginal-only group (V-only group) with oral placebo, twice daily for seven days. Side effects were recorded daily by women and reported at each visit. After misoprostol administration at the clinic, side effects were recorded at 1-hour interval up to 3 hours. Patients' perceptions were asked at the second follow up visit, six weeks after treatment. Main outcome measures The outcome measures were the following: pregnancy-related symptoms (nausea, vomiting, breast tenderness, fatigue, dizziness, headache), drug-related side effects (diarrhoea, fever, rash and blood pressure change), side effects related to the abortion process (lower abdominal pain) and women's perceptions of the method. Results The pregnancy-related symptoms decreased in all groups after misoprostol, and breast tenderness decreased already after mifepristone. Oral administration of misoprostol was associated with a higher frequency of nausea and vomiting than vaginal administration at 1 hour after administration. With oral misoprostol, diarrhoea was more frequent at 1, 2 and at 3 hours after administration than with vaginal administration. Misoprostol induced fever during at least 3 hours after administration in up to 6% of the women, this peak being slightly higher and taking place later with the vaginal route. Lower abdominal pain peaked at 1 and 2 hours after oral misoprostol, while it did so at 2 and 3 hours after vaginal misoprostol. In the two groups that continued misoprostol, 27% of women had diarrhoea between the misoprostol visit and the two-week follow up visit, compared with 9% in the placebo group. Among the women studied, 84% would choose medical abortion again, 9% would choose surgical abortion and 7% did not know. Twentythree percent of the women would choose to have a possible future abortion at home, 70% at a health facility and 7% did not know. Conclusions The pregnancy-related symptoms decrease significantly with time during medical abortion. BJOG: an International Journal of Obstetrics and GynaecologyNausea, vomiting and diarrhoea were more frequent after oral administration of misoprostol. Pain related to the abortion process occurs earlier after oral misoprostol. Should a need arise, a majority of women would choose medical abortion again and would prefer to have it at a health facility rather th...

The route and duration of misoprostol administration have no effect on the kinetics of serum hCG or progesterone during medical termination of early pregnancy.

For amenorrhoea length > or =57 days, vaginal misoprostol is more effective than oral when continued with 0.4 mg oral misoprostol twice daily for seven days. Misoprostol continuation improved the efficacy in this amenorrhoea group compared with a single dose of vaginal misoprostol on day three, but it did not shorten the duration of bleeding. No differences in efficacy were observed when amenorrhoea length was < 57 days.

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Mifepristone is a potent antiglucocorticoid, the administration of which results in a dose-dependent activation of the hypothalamic-pituitary-adrenal axis. However, the net effect of this compound on circulating glucocorticoid activity is not known. We have used a recombinant cell bioassay to study glucocorticoid bioactivity (GBA), measured directly from serum, in 18 women undergoing medical termination of an early pregnancy with 200 mg mifepristone, followed by 0.8 mg misoprostol, a prostaglandin. Increased serum mifepristone was accompanied by an increase in serum cortisol that was insufficient to maintain circulating GBA within the normal (pre-mifepristone) range (34.7-93.8 nM cortisol equivalents); after approximately 43, 46, and 68 h of mifepristone ingestion, the mean serum GBA levels were much lower than the mean pre-mifepristone level (P < 0.0001). At the corresponding times, 16, 13, and 12 women displayed subnormal serum GBA levels (ranges, <15.6-23, <15.6-25.6, and <15.6-32.5 nM cortisol equivalents, respectively). Altogether 11 subjects displayed subnormal serum GBA (range, <15.6-32.5 nM cortisol equivalents) continuously in the presence of high concentrations of mifepristone. Two weeks after mifepristone administration, circulating GBA had returned to normal levels in all subjects. We conclude that 200 mg mifepristone elicits a significant suppression of serum GBA, to one third of the pretreatment value, despite the compensatory increase in the serum cortisol concentration.

The kinetics of cervical and circulating phosphoisoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) in normal and pathological early pregnancy are not well known. We investigated the profiles of IGFBP-1 in serum and in cervical secretion during medical termination of early pregnancy. Sixteen women requesting termination of pregnancy, with <63 days of amenorrhoea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Serum and cervical swab samples, collected up to 6 weeks following the beginning of the treatment, were analysed for IGFBP-1 using two immunoenzymometric assays recognizing different patterns of IGFBP-1 phosphoisoforms. Serum mifepristone was also assayed. In the cervical samples, IGFBP-1 concentration, measured with both assays, increased substantially 2 days following administration of mifepristone. At 3 h after administration of misoprostol, IGFBP-1 had further increased several-fold in the cervix, but the increase was more pronounced as measured by the assay with preference for the amniotic fluid isoforms of IGFBP-1. A strong negative correlation was found between the time to abortion and the increase in cervical IGFBP-1 after administration of misoprostol, as measured by the assay preferring the phosphorylated isoforms of IGFBP-1. At 6 weeks, IGFBP-1 in the cervix had decreased to lower than pre-treatment levels, as measured by both assays. In serum, both assays showed a significant increase in IGFBP-1 concentrations after administration of mifepristone, and the highest values were measured on day 2, already before misoprostol administration. Thus, the kinetics of circulating and cervical IGFBP-1 differed from each other, indicating different sources and regulation of serum and cervical IGFBP-1.

The fall in leptin levels following mifepristone implies a role for P4 in the regulation of leptin in early pregnancy. Moreover, the significant correlation between the changes in leptin and those of P4 and E2 at the time of luteolysis suggests that corpus luteum may also play a role in the regulation of circulating leptin in early pregnancy.

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