Reconceptualizing safe abortion and abortion services in the age of abortion pills: A discussion paper.

At the conference "Developing an Advocacy Agenda for Abortion in the 21st Century and Making Change Happen" held on 5-7 September 2018, Lisbon, Portugal, organized by the International Campaign for Women's Right to Safe Abortion, it was argued that abortion services not only need to be treated as a bona fide form of health care but also completely reconceptualized, particularly because of the influence of medical abortion pills. It emerged, however, that there is no consensus on how this reconceptualization should be configured. Indeed, substantial differences arose, or so it appeared, complicated not only by different exigencies in national settings but also reflecting differing perspectives, specifically, those held primarily by health professionals compared to those held by advocates who felt they spoke for women needing abortions. In the course of these discussions, questions emerged on how much women should be able to do on their own, whether and why services were necessary in every case, where services should be located, what they should offer, who should provide them, and who should be in charge of the process. The biggest discussion was over the extent to which women can safely self-manage use of medical abortion pills for abortion in both the first and second trimester, and to what extent health professional control should be relinquished. Regardless of these arguments, however, since 1988 with the discovery in Brazil that misoprostol is an abortifacient, over-the-counter access to medical abortion (MA) pills began to put self-management of abortion on the map. Today, self-management is happening in almost every country, and we have no idea how many abortions are taking place anymore. Moreover, because of the work of safe abortion information hotlines, there is a growing body of evidence that self-management of abortion by women is safe - or at least far less unsafe than what prevailed in the past. Looking beyond the abortion rights movement, the crux of the issue is whether the state should continue to control abortion, with power over individual decisions delegated to the medical profession - or whether, as has been happening at a snail's pace for the last half century, and as with contraception and emergency contraception too - control can and should be more and more in women's hands. This paper examines these perspectives and attempts to describe what a consensus might look like. It concludes that convincing governments and conservative health professionals to accept a large dose of self-management will not be easy.

Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.

OBJECTIVE: To estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone. METHODS: We planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44-63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14-16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment. RESULTS: We enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported. CONCLUSION: We could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03774745.

Medical management of first trimester missed miscarriage: the efficacy and complication rate.

Our aim of the study was to evaluate the efficacy and complication rate of our inpatient medical management protocol for missed miscarriages. Three-hundred and ninety women hospitalised at our tertiary centre because of a missed miscarriage/anembryonic pregnancy in 2012-2013 were included in this retrospective study. The women underwent either a low (until 9 + 0 weeks of gestation) or high gestational age (from 9 + 1 until 15 + 6 weeks of gestation) management protocol. The success rate, curettage in the first 48 hours after the procedure, the complication rate and the factors that might influence these outcomes were evaluated. The overall success rate was 83.3%. The curettage in the first 48 hours after the procedure was performed in 7.4% of the patients and was more often in the high gestational age protocol. Complications that required another outpatient visit or hospitalisation occurred in 9% of the patients. Higher beta-hCG values 14 days after the procedure and the absence of evacuation of products of conception during hospitalisation were associated with a higher complication rate. IMPACT STATEMENT What is already known on this subject? As much as 10-20% of clinically recognised pregnancies end in a spontaneous abortion. A missed miscarriage and a blighted ovum represent a form of spontaneous abortion, which has long been treated with surgical evacuation. However, nowadays, medical management represents a well-established alternative with very high success rates and is considered as an equivalent and safe method that is also very well accepted by patients. What do the results of this study add? According to our results, a medical management of a first trimester missed miscarriage and a blighted ovum is very effective with an overall success rate of 83.3% and a very low percentage of curettage in the first 48 hours after the procedure (7.4%). Our study was also able to identify higher beta-hCG values 14 days after procedure and absence of evacuation of products of conception during hospitalisation as risk factors for complication occurrence. What are the implications of these findings for clinical practice and/or further research? Our study helps to identify patients who are at greater risk for developing complications after the medical management of a first trimester missed miscarriage.

Management of first-trimester miscarriage: a systematic review and network meta-analysis.

BACKGROUND: First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis. OBJECTIVES AND RATIONALE: We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC). SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (<14 weeks gestation) and conducted a network meta-analysis generating both direct and mixed evidence on the effectiveness and side effects of available treatment options. The primary outcome was complete evacuation of products of conception. We assessed the risk of bias and the global network inconsistency. We compared the surface under the cumulative ranking curve (SUCRA) for each treatment. OUTCOMES: A total of 46 trials (9250 women) were included. The quality of included studies was overall moderate with some studies demonstrating a high risk of bias. We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it. EXP had lower effectiveness compared to other treatment options. The effectiveness of medical treatments was similar compared to surgery. Mixed evidence of low confidence suggests increased effectiveness for MIFE+MISO compared to MISO alone (RR 1.49, 95% CI: 1.09-2.03). Side effects were similar among all options. Fewer women needed analgesia following EVAC compared to MISO (RR for MISO 0.43, 95% CI: 0.27-0.68) and in the EXP group compared to EVAC (RR 2.07, 95% CI: 1.25-3.41). MVA had higher ranking (low likelihood) for post-treatment infection and serious complications (SUCRA 87.6 and 79.2%, respectively) with the highest likelihood for post-treatment satisfaction (SUCRA 98%). WIDER IMPLICATIONS: Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery. The addition of MIFE could increase the effectiveness of MISO and reduce side effects, although evidence is limited due to inconsistency. EXP has lower effectiveness compared to other treatment options.Systematic review registration: Prospero CRD42016048920.

Update on second trimester medical abortion.

PURPOSE OF REVIEW: To review recent literature on second trimester abortion with medical methods. RECENT FINDINGS: Across studies published in the recent past, it is apparent that women prefer shorter procedures and procedure times. Several randomized controlled trials have confirmed adding mifepristone to the second trimester medication abortion regimen results in shorter abortion intervals from first misoprostol administration to complete fetal expulsion. A study of simultaneous administration of mifepristone and misoprostol yielded shorter mean 'total' abortion times, presenting several logistical advantages. Recent studies on the continuous dosing of misoprostol have produced critical evidence to support continued dosing until expulsion. These studies had a more practical design compared with previous protocols that capped the number of misoprostol doses. SUMMARY: Second trimester surgical abortion is well tolerated and increasingly expeditious. Further research is needed to refine second trimester medical abortion methods, specific to the mifepristone, misoprostol dosing interval. A 12-hour mifepristone to misoprostol interval may be the optimal interval balancing patient preferences and logistical considerations. Pragmatic dosing, including continuous dosing of misoprostol, could yield results that better inform clinical guidelines and reduce burden on patient, provider, and health facility.

Effects of Depot Medroxyprogesterone Acetate Injection Timing on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of timing of depot medroxyprogesterone acetate injection on medical abortion outcome and risk of repeat pregnancy within the subsequent 6 months. METHODS: In a multinational randomized trial, we assigned women undergoing medical abortion who wanted depot medroxyprogesterone acetate to administration either with mifepristone (Quickstart group) or after the abortion (Afterstart group). We ascertained abortion outcome, pregnancies, and contraception use over 7 months. RESULTS: From August 2013 to March 2015, we enrolled 461 participants with pregnancy durations of 75 days or less. Of participants included in the abortion outcome analyses, 14 of 220 (6.4%) and 12 of 226 (5.3%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the upper 90% confidence limit on this difference was 4.9%, within our prestipulated 5% noninferiority margin. Ongoing pregnancy after initial abortion treatment was significantly more common in the Quickstart group (8/220 [3.6%]) than in the Afterstart group (2/226 [0.9%]); the difference was 2.7% (90% confidence interval 0.4-5.6%). By 6 months, 5 of 213 (2.3%) and 7 of 217 (3.2%) in the Quickstart and Afterstart groups, respectively, became pregnant (exact log-rank test, P=.64). Use of highly effective contraceptives was significantly more common in the Quickstart group at 31 days (P<.001), but no difference was apparent at 6 months. The Quickstart group was significantly more satisfied with group assignment. CONCLUSION: Depot medroxyprogesterone acetate administration with mifepristone did not appreciably increase the risk of surgery after medical abortion but did increase the risk of ongoing pregnancy. It enhanced patient satisfaction, but we found no evidence that it decreased 6-month risk of repeat pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01902485.

Mifepristone and misoprostol for cervical ripening in surgical abortion between 12 and 14 weeks of gestation: a randomized controlled trial.

OBJECTIVE: Misoprostol and mifepristone are the two substances recommended for cervical preparation during first-trimester surgical abortions to decrease intraoperative bleeding and complications. The objective of the study was to evaluate whether the combination of mifepristone and misoprostol for cervical preparation in an elective surgical abortion between 12 and 14 weeks of gestation can reduce blood loss in comparison to misoprostol or mifepristone alone. STUDY DESIGN: A randomized controlled trial was performed in Marseille, France between May 2013 and May 2014. Women requesting a surgical abortion under general anesthesia between 12 and 14 weeks of gestation were 198, randomized into three groups: one received 400µg oral misoprostol 3h before surgery, one 200mg oral mifepristone 36h before surgery, and the other, both treatments. The main outcome was the quantity of intraoperative bleeding. The secondary outcomes were duration of intervention, ease of dilatation, and complications. RESULTS: The quantity of intraoperative bleeding differed significantly between the groups (p=0.001): 222±64mL in the combination group, 329±129mL in the misoprostol group, and 276±119mL in the mifepristone group. The combination was associated with a shorter operative duration (p=0.001): 5±2min in the combination group, 7±5min in the misoprostol group, and 7±3min in the mifepristone group. A hemorrhage was observed for 5 of 55 women (9%) in the combination group, 13 of 51 (25%) in the misoprostol group, and 9 of 56 (16%) in the mifepristone group (p=0.08). No cervical laceration or uterine perforation was reported. CONCLUSIONS: The combination of mifepristone and misoprostol in cervical preparation for elective surgical abortions between 12 and 14 weeks of gestation significantly reduced blood loss in comparison to misoprostol or mifepristone alone.

The Architecture and Function of Monoclonal Antibody-Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention.

The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.

Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone.

OBJECTIVE: Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs. METHODS: The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses. RESULTS: Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight. CONCLUSION: The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses.

Continuing pregnancy after mifepristone and "reversal" of first-trimester medical abortion: a systematic review.

OBJECTIVE: We conducted a systematic review of the literature on the effectiveness of medical abortion "reversal" treatment. Since the usual care for women seeking to continue pregnancies after ingesting mifepristone is expectant management with fetal surveillance, we also performed a systematic review of continuing pregnancy after mifepristone alone. STUDY DESIGN: We searched PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus and the Cochrane Library for articles published through March 2015 reporting the proportion of pregnancies continuing after treatment with either mifepristone alone or after an additional treatment following mifepristone aimed at reversing its effect. RESULTS: From 1115 articles retrieved, 1 study met inclusion criteria for abortion reversal, and 13 studies met criteria for continuing pregnancy after mifepristone alone. The one report of abortion reversal was a case series of 7 patients receiving varying doses of progesterone in oil intramuscularly or micronized progesterone orally or vaginally; 1 patient was lost to follow-up. The study was of poor quality and lacked clear information on patient selection. Four of six women continued the pregnancy to term [67%, 95% confidence interval (CI) 30-90%]. Assuming the lost patient aborted resulted in a continuing pregnancy proportion of 57% (95% CI 25-84%). The proportion of pregnancies continuing 1-2 weeks after mifepristone alone varied from 8% (95% CI 3-22%) to 46% (95% CI 37-56%). Continuing pregnancy was more common with lower mifepristone doses and advanced gestational age. CONCLUSIONS: In the rare case that a woman changes her mind after starting medical abortion, evidence is insufficient to determine whether treatment with progesterone after mifepristone results in a higher proportion of continuing pregnancies compared to expectant management. IMPLICATIONS: Legislation requiring physicians to inform patients about abortion reversal transforms an unproven therapy into law and represents legislative interference in the patient-physician relationship.

The unique pharmacological characteristics of mifepristone (RU486): from terminating pregnancy to preventing cancer metastasis.

Mifepristone (RU486) is a born-for-woman molecule discovered three decades ago. Unlike those antihypertensive and antipsychotic pharmaceutical blockbusters, this abortifacient offers relatively low profit potential. Current understanding of mechanism of action of mifepristone and its on-going clinical trials are changing our views on the drug beyond its abortifacient scope. Here we briefly review its metabolism and pharmacokinetic properties including its unique enterohepatic circulation, its mechanisms of actions involving antiprogesterone and antiglucocorticoid, growth inhibition of various cancer cell lines, suppression of invasive and metastatic cancer potential, downregulation of Cdk2, Bcl-2, and NF-kappa B, interference of heterotypic cell adhesion to basement membrane, and cell migration. We comprehensively analyze recent results from preclinical and clinical studies using mifepristone as an anticancer drug for breast, meningioma, and gliomas tumors in the central nervous system, prostate cancer, ovarian and endometrial cancer, and gastric adenocarcinoma. Although mifepristone has more benefits for global public health than we originally thought, its effect as a postmetastatic chemotherapeutic agent is limited. Nonetheless, owing to its unique safe, metabolism and other pharmacological properties, metapristone (the primary metabolite of mifepristone) may have potential for cancer metastatic chemoprevention.

Sonographic patterns of the endometrium in assessment of medical abortion outcomes.

BACKGROUND: We aimed to define endometrial pattern and endometrial thickness in predicting the outcome of early medical abortion. STUDY DESIGN: While blinded to outcomes of abortion, we retrospectively reviewed the ultrasound scan performed 14-21 days after medical abortion. We assessed the endometrial pattern and endometrial thickness. A total of 943 women at or before 56 days of gestation who underwent medical abortions were included. Abortion was induced with mifepristone (600 mg) orally followed 48 h later with oral misoprostol (600 mcg). A successful medical abortion was defined as complete abortion without surgical intervention. Three sonographic patterns (homogenous, heterogeneous and multilayered) were devised to correlate with the outcome. RESULTS: Of the 940 women, 92 (9.8%) had failed medical abortions. Eighty-seven (94.6%) patients with failed treatment outcomes had a heterogeneous pattern, while no patients with failed treatments had a multilayered pattern. Based on multivariable logistic regression, women who had an endometrial thickness in the range of 10-15 or >15 mm were more likely to have failed outcomes than those with a thickness <10 mm, with ORs of 3.69 (p=.001) and 8.82 (p<.001). Compared to those with a homogenous pattern, women with a heterogeneous endometrial pattern were more likely to have failed outcomes (OR 4.5, p=.003). In addition, an endometrial thickness >10 mm in combination with a heterogeneous pattern had the highest balanced accuracy in the prediction of failed outcome (81.9%; 95% CI, 77.6-86.3). CONCLUSION: Women with a multilayered pattern could be reassured that they have successful medical abortion, while those with a heterogeneous pattern and/or endometrium >10 mm may need follow-up. Sonographic endometrial pattern and endometrial thickness may serve as objective criteria in the management of early medical abortions.

Acceptability and feasibility of the use of 400 µg of sublingual misoprostol after mifepristone for medical abortion up to 63 days since the last menstrual period: evidence from Uzbekistan.

OBJECTIVE: To examine the efficacy, acceptability and feasibility of early medical abortion, with the option of home administration of misoprostol, in Uzbekistan. METHODS: A total of 450 women were enrolled at national, municipal and private facilities in Tashkent, Uzbekistan. Women who presented for termination of pregnancy with gestations up to 63 days were recruited to participate in the study. All eligible pregnant women who consented to participate swallowed a 200 mg mifepristone pill in the clinic and were given the option of taking 400 µg misoprostol sublingually either at the clinic or at home 24-48 hours after mifepristone administration. Abortion status was determined two weeks later. RESULTS: Almost all women (99.5%) chose home administration of misoprostol. The sublingual route of misoprostol administration was acceptable or very acceptable to 89% of participants. Ninety-five percent of women had complete abortions after mifepristone and misoprostol. Almost all participants preferred a medical abortion to surgery for a future procedure (95%). CONCLUSIONS: Mifepristone medical abortion with home administration of misoprostol is an acceptable and feasible option for women in Uzbekistan. The method worked well at all three facility types.

Progesterone use to reverse the effects of mifepristone.

OBJECTIVE: To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process. CASE REPORTS: Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg. DISCUSSION: Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone. CONCLUSIONS: Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.

Regional differences in surgical intervention following medical termination of pregnancy provided by telemedicine.

OBJECTIVE: Analysis of factors influencing surgical intervention rate after home medical termination of pregnancy (TOP) by women in countries without access to safe services using the telemedical service 'Women on Web'. DESIGN: Cohort study. SETTING: Women with an unwanted pregnancy less than nine weeks pregnant who used the telemedicine service of Women on Web between February 2007 and September 2008 and provided follow-up information. SAMPLE: Women who used medical TOP with a known follow up. METHODS: Information from the online consultation, follow-up form and emails was used to analyze the outcome of the TOP. MAIN OUTCOME MEASURES: Ongoing pregnancy, reason for surgical intervention, perceived complications and satisfaction. RESULTS: Of the 2 323 women who did the medical TOP and had no ongoing pregnancy, 289 (12.4%) received a surgical intervention. High rates were found in Eastern Europe (14.8%), Latin America (14.4%) and Asia/Oceania (11.0%) and low rates in Western Europe (5.8%), the Middle East (4.7%) and Africa (6.1%; p=0.000). More interventions occurred with longer gestational age (p=0.000). Women without a surgical intervention more frequently reported satisfaction with the treatment (p=0.000). CONCLUSIONS: The large regional differences in the rates of reported surgical interventions after medical TOP provided by telemedicine cannot be explained by demographic factors or differences in gestational length. It is likely that these differences reflect different clinical practice and local guidelines on (incomplete) abortion rather than complications that genuinely needed surgical intervention. Surgical interventions significantly influenced womens' views on the acceptability of the TOP.

Mifepristone in combination with prostaglandins for termination of 10-16 weeks' gestation: a systematic review.

OBJECTIVES: Medical regimens using mifepristone in combination with prostaglandins have been widely available for women undergoing termination of pregnancy (TOP) at 10-16 weeks' gestation in China. We undertook a systematic review to compare different regimens of mifepristone with prostaglandins for TOP at 10-16 weeks' gestation. METHODS: We searched multiple electronic databases for English and Chinese language reports (1990-2007) including MEDLINE, the Cochrane Library and the Chinese Biomedical Literature Database. Included were trials comparing mifepristone with prostaglandins (misoprostol, gemeprost or carboprost (PG05)) to each other for women at 10-16 weeks' gestation. Outcomes were successful abortion rates, induction-to-expulsion time, blood loss and side effects. Data were processed with RevMan 5 software. RESULTS: Nineteen trials comparing mifepristone with prostaglandin (misoprostol and PG05) were found of which 14 contributed to meta-analyses (4206 women). The quality of reports was poor. The effectiveness of vaginal mifepristone/misoprostol was super than mifepristone/PG05 (RR 1.14, 95%CI 1.05-1.22) as was induction-to-expulsion time, blood loss and side effects. When comparing misoprostol/mifepristone 150mg to misoprostol/mifepristone 200mg, no difference in TOP success rates were found (RR 0.98, 95%CI 0.96-1.01). Misoprostol vaginally compared to orally significantly increased the TOP success rate (RR 1.12, 95%CI 1.01-1.24). Gastrointestinal symptoms and fever occurred more often in misoprostol oral group (RR 1.67, 95%CI 1.46-1.91). CONCLUSIONS: Medical regimens of mifepristone/prostaglandins were effective and safe for TOP at 10-16 weeks' gestation. Misoprostol was super than PG05, and misoprostol vaginally was found to have better effectiveness than misoprostol orally. Further research should evaluate the relative effectiveness of medical methods compared to surgery.

Effectiveness and acceptability of medical abortion provided through telemedicine.

OBJECTIVE: To estimate the effectiveness and acceptability of telemedicine provision of early medical abortion compared with provision with a face-to-face physician visit at a Planned Parenthood affiliate in Iowa. METHODS: Between November 2008 and October 2009, we conducted a prospective cohort study of women obtaining medical abortion by telemedicine or face-to-face physician visits. We collected clinical data, and women completed a self-administered questionnaire at follow-up. We also compared the prevalence of reportable adverse events between the two service delivery models among all patients seen between July 2008 and October 2009. RESULTS: Of 578 enrolled participants, follow-up data were obtained for 223 telemedicine patients and 226 face-to-face patients. The proportion with a successful abortion was 99% for telemedicine patients (95% confidence interval [CI] 96-100%) and 97% for face-to-face patients (95% CI 94-99%). Ninety-one percent of all participants were very satisfied with their abortion, although in multivariable analysis, telemedicine patients had a higher odds of saying they would recommend the service to a friend compared with face-to-face patients (odds ratio, 1.72; 95% CI 1.26-2.34). Twenty-five percent of telemedicine patients said they would have preferred being in the same room with the doctor. Younger age, less education, and nulliparity were significantly associated with preferring face-to-face communication. There was no significant difference in the prevalence of adverse events reported during the study period among telemedicine patients (n = 1,172) (1.3%; 95% CI 0.8-2.1%) compared with face-to-face patients (n = 2,384) (1.3%; 95% CI 0.9-1.8%) (82% power to detect difference of 1.3%). CONCLUSION: Provision of medical abortion through telemedicine is effective and acceptability is high among women who choose this model. LEVEL OF EVIDENCE: II.

Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century.

Administration of mifepristone followed by the prostaglandin, misoprostol, has been used successfully in the medical termination of pregnancy for over 25 years, and the method is registered in 35 countries. Single doses of mifepristone are also effective as an emergency postcoital contraceptive. Mifepristone administered for 3 months or longer to women with uterine leiomyomas, is associated with a reduction in pain and bleeding with improvement in quality of life and decrease in fibroid size. Mifepristone is also effective in decreasing pain in women with endometriosis. In both these conditions, serum estradiol levels are in the range of those in the early follicular phase. A daily dose of at least 2 mg mifepristone blocks ovulation. In contrast, weekly administration of 25 or 50 mg does not consistently block ovulation but has contraceptive potential by delaying endometrial development. Mifepristone in a dose of 200 mg, administered 48 h after the Luteinizing Hormone (LH) surge, also acts as a contraceptive, but this strategy is not practical for widespread use. Administration of mifepristone for 4-6 months or longer may lead to endometrial thickening. Endometrial histology reveals cystic glandular dilation together with admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histological pattern does not represent endometrial hyperplasia.

Medical abortion at 63 to 90 days of gestation.

OBJECTIVE: To evaluate medical abortion as a treatment alternative for late first-trimester abortions and to evaluate the decrease in beta-hCG after abortion at 63-90 days of gestation. METHODS: All women received mifepristone 200 mg orally, followed by 800 micrograms misoprostol vaginally 48 hours later. Misoprostol was repeated every 3 hours orally, to a maximum of five doses if needed. A clinical examination including ultrasonography was performed 8-14 days after treatment. beta-hCG level was determined before treatment and at follow-up. RESULTS: A total of 254 pregnant women with gestational age 63 to 90 days were included. The successful termination rate was 91.7%. Surgical evacuation was carried out in 21 (8.3%) women. Most women (91.0%) found the method of treatment highly acceptable. The beta-hCG levels of women with successful termination had decreased more than 97.5% at follow-up. CONCLUSION: Medical abortion is an effective and acceptable method for termination of pregnancy in late first trimester.