Mifepristone and misoprostol compared to osmotic dilators for cervical preparation prior to surgical abortion at 15-18 weeks' gestation: a randomised controlled non-inferiority trial.

OBJECTIVE: Cervical preparation is recommended prior to second-trimester surgical abortion. Osmotic dilators are an effective means to prepare the cervix, but require an additional procedure and may cause discomfort. We compared cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators. STUDY DESIGN: A randomised, controlled, non-inferiority trial was performed to compare cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators in women undergoing surgical abortion between 15 and 18 weeks gestation. The medication group (n=29) received mifepristone 200 mg orally 24 hours prior to uterine evacuation and misoprostol 400 µg buccally 2 hours before the procedure. The dilator group (n=20) underwent osmotic dilator insertion 24 hours prior to the procedure. The primary outcome was total procedure time, from insertion to removal of the speculum. Secondary outcomes included operative time (from intrauterine instrumentation to speculum removal), initial cervical dilation, nausea, pain, ease of procedure, and whether participants would choose the same modality in the future. RESULTS: For mean total procedure time, medication preparation (14.0 min, 95% CI 12.0-16.1) was not inferior to dilators (14.3 min, 95% CI 11.7 to 16.8, p<0.001). Mean operative time and ease of procedure were also similar between groups. More women in the medication group than the dilator group would prefer to use the same method in the future (86% vs 30%, p=0.003). CONCLUSION: Prior to surgical abortion at 15-18 weeks, use of mifepristone and misoprostol did not result in longer procedure times than overnight osmotic dilators. TRIAL REGISTRATION NUMBER: NCT01462.

Applications for Research Concerning Fetal or Placental Tissue and Expected Institutional Review Board Responses.

Proposals for research concerning fetal and/or placental tissue may be refused institutional review board (IRB) review, effectively preventing the research from occurring. We conducted an anonymous electronic survey of IRB chairs to determine their assessment of the likely response to research projects using fetal/placental tissue obtained from various procedures. We found that proposals concerning tissue obtained from diagnostic procedures or miscarriage were anticipated to be considered at most institutions. Tissue obtained after abortion was likely to be refused consideration by more than 25% of respondents. Additional consultation during review was anticipated for up to 30% of scenarios. Responses for fetal and placental tissue were similar. The most frequently anticipated reason for refusal was institutional policy.

Impact of the roll out of comprehensive emergency obstetric care on institutional birth rate in rural Nepal.

BACKGROUND: Increasing institutional births rates and improving access to comprehensive emergency obstetric care are central strategies for reducing maternal and neonatal deaths globally. While some studies show women consider service availability when determining where to deliver, the dynamics of how and why institutional birth rates change as comprehensive emergency obstetric care availability increases are unclear. METHODS: In this pre-post intervention study, we surveyed two exhaustive samples of postpartum women before and after comprehensive emergency obstetric care implementation at a hospital in rural Nepal. We developed a logistic regression model of institutional birth factors through manual backward selection of all significant covariates within and across periods. Qualitatively, we analyzed birth stories through immersion crystallization. RESULTS: Institutional birth rates increased after comprehensive emergency obstetric care implementation (from 30 to 77%, OR 7.7) at both hospital (OR 2.5) and low-level facilities (OR 4.6, p < 0.01 for all). The logistic regression indicated that comprehensive emergency obstetric care availability (OR 5.6), belief that the hospital is the safest birth location (OR 44.8), safety prioritization in decision-making (OR 7.7), and higher income (OR 1.1) predict institutional birth (p ≤ 0.01 for all). Qualitative analysis revealed comprehensive emergency obstetric care awareness, increased social expectation for institutional birth, and birth planning as important factors. CONCLUSION: Comprehensive emergency obstetric care expansion appears to have generated significant demand for institutional births through increased safety perceptions and birth planning. Increasing comprehensive emergency obstetric care availability increases birth safety, but it may also be a mechanism for increasing the institutional birth rate in areas of under-utilization.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

OBJECTIVES: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 µg/24 h over the first year [total content 13.5 mg]) and a 30 µg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. METHODS: Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. RESULTS: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. CONCLUSIONS: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

Determinants of institutional birth among women in rural Nepal: a mixed-methods cross-sectional study.

BACKGROUND: Encouraging institutional birth is an important component of reducing maternal mortality in low-resource settings. This study aims to identify and understand the determinants of persistently low institutional birth in rural Nepal, with the goal of informing future interventions to reduce high rates of maternal mortality. METHODS: Postpartum women giving birth in the catchment area population of a district-level hospital in the Far-Western Development Region of Nepal were invited to complete a cross-sectional survey in 2012 about their recent birth experience. Quantitative and qualitative methods were used to determine the institutional birth rate, social and demographic predictors of institutional birth, and barriers to institutional birth. RESULTS: The institutional birth rate for the hospital's catchment area population was calculated to be 0.30 (54 home births, 23 facility births). Institutional birth was more likely as age decreased (ORs in the range of 0.20-0.28) and as income increased (ORs in the range of 1.38-1.45). Institutional birth among women who owned land was less likely (OR = 0.82 [0.71, 0.92]). Ninety percent of participants in the institutional birth group identified safety and good care as the most important factors determining location of birth, whereas 60 % of participants in the home birth group reported distance from hospital as a key determinant of location of birth. Qualitative analysis elucidated the importance of social support, financial resources, birth planning, awareness of services, perception of safety, and referral capacity in achieving an institutional birth. CONCLUSION: Age, income, and land ownership, but not patient preference, were key predictors of institutional birth. Most women believed that birth at the hospital was safer regardless of where they gave birth. Future interventions to increase rates of institutional birth should address structural barriers including differences in socioeconomic status, social support, transportation resources, and birth preparedness.

Second-trimester postabortion care for ruptured membranes, fetal demise, and incomplete abortion.

BACKGROUND: Guidance for postabortion care (PAC) is established for the first trimester but limited in the second trimester. OBJECTIVES: To establish evidence-based recommendations for PAC in the second trimester. SEARCH STRATEGY: Medline, POPLINE, and the Cochrane Central Register of Controlled Trials were searched with terms related to second-trimester PAC, including fetal demise, ruptured membranes, and incomplete abortion. The reference lists of retrieved articles were also searched. SELECTION CRITERIA: Clinical trials and comparative studies of women presenting in the second trimester (12-28weeks) were included if more than 50% of participants met PAC criteria or if outcomes for PAC were analyzed separately. DATA COLLECTION AND ANALYSIS: Data were extracted from included studies. When interventions in at least two articles were comparable, a meta-analysis was performed. MAIN RESULTS: Overall, 17 studies of 1419 women met inclusion criteria. Misoprostol given vaginally, sublingually, or buccally was associated with shorter expulsion times than was oral misoprostol. Additionally, 200µg of misoprostol was more effective than lower doses. Pretreatment with mifepristone decreased expulsion time. Misoprostol was more effective than oxytocin. CONCLUSION: Misoprostol with or without mifepristone is an effective treatment for second-trimester PAC. The minimum misoprostol dose is 200µg vaginally, sublingually, or buccally every 6-12hours.

Administration of depot medroxyprogesterone acetate on the day of mifepristone for medical abortion: a pilot study.

OBJECTIVE: We sought to evaluate satisfaction with timing of administration and continuation rates of depot medroxyprogesterone (DMPA) when given on the initial visit for first-trimester medical abortion. STUDY DESIGN: In this pilot study, we administered DMPA within 15 min of mifepristone administration. Participants were followed up in the clinic 7 days after enrollment and were contacted at 14 days, 28 days and 3, 6, 9 and 12 months by telephone. We assessed satisfaction with contraception timing, DMPA continuation, bleeding patterns and abortion completion. RESULTS: Twenty women were enrolled. At 7-day follow-up, 18 of 19 contacted participants (94.7%) were satisfied with timing of DMPA administration. Ten of 19 participants (52.6%) discontinued DMPA after the first injection. At 1 year, 3 participants out of 19 were continuing DMPA (15.7%). The median number of bleeding days after abortion was 19. Three participants had medical abortion failure. In the first year after abortion, there were four known repeat pregnancies. CONCLUSIONS: The timing of initiation of DMPA on the initial visit for medical abortion is satisfactory to women, but its influence on medical abortion efficacy requires further study. Continuation rates for DMPA were low in our sample. IMPLICATIONS: This pilot study provides groundwork for future larger studies to assess initiation of the injectable contraceptive DMPA on the day of mifepristone for medical abortion, but low continuation rates of DMPA in our sample emphasize the importance of access to intrauterine devices and implants after abortion.

Administration of the etonogestrel contraceptive implant on the day of mifepristone for medical abortion: a pilot study.

OBJECTIVE: We sought to determine satisfaction and continuation rates of the contraceptive implant when placed on the initial visit for first-trimester medical abortion. STUDY DESIGN: In this pilot study, we placed the implant within 15 min of mifepristone administration. We assessed satisfaction with implant placement timing, 1-year implant continuation and abortion completion. RESULTS: We enrolled 20 participants. Sixteen (80%) returned for follow-up, and all had complete abortion. At 1 year, of 16 participants contacted, 14 (87.5%) were satisfied with implant insertion timing, and 14 (87.5%) continued the implant. CONCLUSIONS: Initiation of the contraceptive implant on the initial visit for medical abortion resulted in high satisfaction and continuation rates. IMPLICATIONS: This pilot study provides important groundwork for future larger studies to assess initiation of the contraceptive implant on the day of mifepristone for medical abortion.

One-year continuation of the etonogestrel contraceptive implant in women with postabortion or interval placement.

BACKGROUND: Our study investigated whether women with etonogestrel implant placement in the immediate postabortion period have similar continuation rates to women with interval placement. STUDY DESIGN: This is a prospective cohort study of women at Boston Medical Center. We compared 1-year continuation rates in women who had immediate postabortion placement to interval placement using Cox proportional hazard models. RESULTS: One hundred five women were enrolled, 53 in the abortion and 52 in the interval group. There were two losses to follow-up leaving 103 women for analysis. The overall 1-year continuation rate was 74.8%, with 68.6% postabortion continuation and 80.8% interval continuation. The risk of discontinuation in women with postabortion placement was higher but not statistically different than women with interval placement (unadjusted hazard ratio: 1.79, 95% confidence interval: 0.81-3.96). CONCLUSION: Overall etonogestrel implant continuation was acceptable with similar rates for postabortion and interval placement. For women who want a contraceptive implant after an abortion, immediate placement should be available.

Tuboovarian abscess. Factors associated with operative intervention after failed antibiotic therapy.

OBJECTIVE: To evaluate whether size of tuboovarian abscess (TOA) and other clinical characteristics were associated with the need for surgical intervention. STUDY DESIGN: A retrospective chart review of patients hospitalized at an inner city hospital between January 1998 and December 2007 with the diagnosis of TOA. Demographics, medical history, clinical markers of infection, radiology, pathology, and operative reports were examined. Student's t test and Fisher's exact test were utilized to analyze differences between groups. Multiple logistic regression analysis was performed to identify significant predictors of surgery. Receiver operating characteristic (ROC) analysis was used to assess how well TOA size and other significant variables were associated with the need for operative or procedural intervention. RESULTS: A total of 163 patients with TOA were identified; 41 patients were excluded based on specific criteria. Of the remaining 122 women, 65.6% responded to antibiotic therapy, and 34.4% had surgery or ultrasound-guided drainage. Mean TOA size in the medical group was 4.4 cm as compared to 7.3 cm in the surgical group (p < 0.0001). Maximal leukocyte count, older age, and parity were associated with significantly higher risk of surgery. The significant univariate variables remained significant after multivariate analysis. ROC curve analysis revealed an excellent discrimination of the need for surgical treatment as predicted by TOA size, with increased likelihood of surgical or procedural intervention with increasing TOA size. CONCLUSION: Radiographic size, leukocyte count, age, and parity are associated with operative or procedural treatment of tuboovarian abscess.

Inflammation or infection at the time of second trimester induced abortion.

BACKGROUND: Induced abortion via dilation and evacuation (D&E) typically involves cervical preparation. Some clinicians also induce fetal death in the second trimester. We designed this study to determine if the combination of intra-amniotic digoxin and osmotic dilators induced intrauterine inflammatory changes. STUDY DESIGN: Twenty-two women requesting abortion at 19-23 weeks gestation had amniotic fluid sent for measurement of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count and anaerobic and aerobic cultures on day 1, before dilators and digoxin amnioinjection. Sampling was repeated on Day 2, prior to D&E. RESULTS: All subjects had significantly elevated IL-6, IL-8 and TNF-α in the amniotic fluid on Day 2. The median difference for IL-6 was 19,893.4 pg/mL (p<.0001), 7040.7 pg/mL (p<.0001) for IL-8 and 181.0 pg/mL (p<.0001) for TNF-α. There was no significant difference in WBC count. There were no clinically significant positive cultures and no clinical infections. CONCLUSION: The administration of intra-amniotic digoxin and the placement of osmotic dilators prior to D&E create an intrauterine inflammatory response.

Mifepristone vs. osmotic dilator insertion for cervical preparation prior to surgical abortion at 14-16 weeks: a randomized trial.

BACKGROUND: Cervical preparation is recommended before second-trimester abortion. We investigated the use of a pharmacologic method of preparation, mifepristone, as compared to osmotic dilators for surgical abortions at 14-16 weeks. STUDY DESIGN: This was a randomized, parallel-group study with concealed allocation. Women were allocated to receive osmotic dilators or mifepristone 200 mg orally 24 h prior to abortion. The study population was 50 women seeking surgical abortion at 14-16 menstrual weeks in a hospital-based abortion service. The primary outcome was the length of time to perform the procedure; the study had 80% power to detect a difference of more than 3 min in procedure time. Secondary outcomes included cervical dilation, side effects and acceptability. RESULTS: The mean abortion time for the osmotic dilator group was 8.00 min [95% confidence interval (CI) 6.75-11.47], and that for the mifepristone group was 9.87 min (95% CI 8.93-11.36). Side effects of pain were more common in the osmotic dilator group. CONCLUSION: Mifepristone did not increase the time for abortion by more than the prespecified margin (3 min). Women preferred mifepristone to osmotic dilators.

Clinical guidelines. Labor induction abortion in the second trimester.

Labor induction abortion is effective throughout the second trimester. Patterns of use and gestational age limits vary by locality. Earlier gestations (typically 12 to 20 weeks) have shorter abortion times than later gestational ages, but differences in complication rates within the second trimester according to gestational age have not been demonstrated. The combination of mifepristone and misoprostol is the most effective and fastest regimen. Typically, mifepristone 200 mg is followed by use of misoprostol 24-48 h later. Ninety-five percent of abortions are complete within 24 h of misoprostol administration. Compared with misoprostol alone, the combined regimen results in a clinically significant reduction of 40% to 50% in time to abortion and can be used at all gestational ages. However, mifepristone is not widely available. Accordingly, prostaglandin analogues without mifepristone (most commonly misoprostol or gemeprost) or high-dose oxytocin are used. Misoprostol is more widely used because it is inexpensive and stable at room temperature. Misoprostol alone is best used vaginally or sublingually, and doses of 400 mcg are generally superior to 200 mcg or less. Dosing every 3 h is superior to less frequent dosing, although intervals of up to 12 h are effective when using higher doses (600 or 800 mcg) of misoprostol. Abortion rates at 24 h are approximately 80%-85%. Although gemeprost has similar outcomes as compared to misoprostol, it has higher cost, requires refrigeration, and can only be used vaginally. High-dose oxytocin can be used in circumstances when prostaglandins are not available or are contraindicated. Osmotic dilators do not shorten induction times when inserted at the same time as misoprostol; however, their use prior to induction using misoprostol has not been studied. Preprocedure-induced fetal demise has not been studied systematically for possible effects on time to abortion. While isolated case reports and retrospective reviews document uterine rupture during second-trimester induction with misoprostol, the magnitude of the risk is not known. The relationship of individual uterotonic agents to uterine rupture is not clear. Based on existing evidence, the Society of Family Planning recommends that, when labor induction abortion is performed in the second trimester, combined use of mifepristone and misoprostol is the ideal regimen to effect abortion quickly and completely. The Society of Family Planning further recommends that alternative regimens, primarily misoprostol alone, should only be used when mifepristone is not available.

Intrauterine device insertion after medical abortion.

BACKGROUND: Studies comparing immediate intrauterine device (IUD) insertion after first-trimester surgical abortion with interval insertion show similar efficacy and expulsion rates. However, women randomized to interval insertion of an IUD are less likely to return for device placement. An ideal time to insert intrauterine contraception may be the day a woman presents for verification of a completed medical abortion. We examined immediate insertion of IUDs after completed first-trimester medical abortion. STUDY DESIGN: This is a prospective, observational clinical study to determine expulsion rates of intrauterine contraception placed immediately after confirmed, completed first-trimester medical abortion. RESULTS: Of 118 subjects, 78 women had levonorgestrel IUDs placed, whereas 41 women received copper IUDs. Of 97 subjects who completed the study, there were 4 clinical expulsions (4.1%) during 3 months of follow-up. There were no diagnosed pelvic infections, pregnancies, or uterine perforations. The continuation rate at 3 months was 80%. CONCLUSION: Intrauterine devices inserted at the time of completed, confirmed first-trimester medical abortion have low rates of expulsion.

Relationship of intraamniotic digoxin to fetal demise.

BACKGROUND: Induced fetal demise by intraamniotic injection of digoxin is an alternative to methods using intracardiac or umbilical vein injection. This study was designed to evaluate the effectiveness of intraamniotic injection and the timing of fetal demise after injection. STUDY DESIGN: Twenty-two women had ultrasonic fetal cardiac assessments 1, 2, 4 and 20 to 24 h after intraamniotic injection of 1.5 mg digoxin. RESULTS: Fetal cardiac activity was absent in 21/21 women assessed at least 20 h after injection. One woman had agonal (40 bpm) fetal cardiac activity at 14 h. Most women had fetal cardiac activity 4 h after injection. Signs of toxicity were not seen. CONCLUSION: Intraamniotic injection of digoxin 1.5 mg is effective at causing fetal demise by 20 to 24 h. However, for most women, fetal demise is not obtained within 4 h.

Cervical obstruction complicating second-trimester abortion: treatment with misoprostol.

BACKGROUND: Cervical cone biopsy or loop electrosurgical excision procedures (LEEP) may lead to cervical scarring, agglutination, or stenosis. Leiomyomas may also obstruct the lower uterine segment such that instruments cannot be passed from the vagina to the gestation. CASE: Two women requested second trimester abortion. Both women had undergone cervical LEEP. In addition, one woman had a 10-cm leiomyoma, which seemed to be obstructing the lower segment. In both, the external cervical os was essentially obliterated. After administration of misoprostol, the cervix softened markedly in 18-24 hours. In both women, the cervix dilated readily and allowed dilation and evacuation of the uterus. CONCLUSION: Misoprostol resulted in the ability to evacuate the uterus vaginally, in a situation that might have otherwise resulted in hysterotomy.

Relationship of obesity to outcome of medical abortion.

OBJECTIVE: The purpose of this study was to compare the outcome of medical abortion for obese women and nonobese women. STUDY DESIGN: We conducted a chart review of women having medical abortions in 2005-2007. Outcomes were classified as surgical intervention, need for additional visits, and complete abortion. The rate of surgical intervention was compared for women with BMI less than 30 to women with BMI greater than 30. RESULTS: Of the 1202 eligible procedures using mifepristone and misoprostol, there were 861 women with BMI less than 30 and 341 women with BMI greater than 30. Women with BMI less than 30, and women with BMI greater than 30 had identical rates of surgical intervention, 5% and 6%, respectively (P = .72). CONCLUSION: In light of the additional risks of surgical abortion to obese women, medical abortion should be considered for these women.