Evaluation of a "smart" screening tool for asynchronous assessment of medication abortion eligibility: A pilot study.

OBJECTIVES: This study aimed to assess the feasibility, safety, and acceptability of asynchronous screening for medication abortion eligibility using a programmed questionnaire. STUDY DESIGN: For this study, we developed an informational website about medication abortion with a linked questionnaire programmed to produce a conclusion regarding eligibility according to standard criteria. We enrolled people in Colorado and Minnesota who submitted questionnaires indicating eligibility. A study physician reviewed each questionnaire and medical records if available and determined whether the responses warranted treatment without a synchronous clinical consultation or ultrasound. If so, the physician prescribed a standard regimen of mifepristone and misoprostol. We collected posttreatment data on abortion outcome, adverse events, and satisfaction. RESULTS: We received questionnaires from 197 individuals, of whom 160 remained in the study until the physician made a final treatment decision. Physicians prescribed medication abortion to 156 (97.5%) individuals based on the questionnaire responses, whereas four needed further assessment to confirm eligibility. Of the 156 individuals, 130 had sufficient follow-up to assess abortion outcome, and 123 (95%) had complete medication abortions without additional treatment. One participant was hospitalized for bleeding, and one expelled a 15-week fetus; however, it is not clear that conventional synchronous history-based screening would have averted these events. Of the 197 questionnaires, 42% were submitted outside business hours. On satisfaction questionnaires, 134 (96%) of 144 participants said they would recommend the study to a friend who needed an abortion. CONCLUSIONS: Data from this pilot project suggest that providing medication abortion based only on a self-administered, programmed questionnaire is likely to be effective, safe, efficient, and acceptable. IMPLICATIONS: A programmed self-administered patient questionnaire to assess eligibility for medication abortion could reduce the cost of the service, augment clinic efficiency, improve quality of care, and enhance access to abortion.

PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population.

Introduction: Prior studies indicate that PAPP-A could serve as a marker of gestational age (GA) with the potential to determine eligibility for medication abortion. The authors validated the relationship between PAPP-A and GA in an actual-use population. Materials & methods: The authors collected blood samples, medical histories and ultrasound-determined GA from patients presenting for abortion services. They measured PAPP-A using two immunoassays and assessed diagnostic accuracy for predicting GA ≥71 days. Results: The Ansh Labs and R&D Systems immunoassays produced an area under the ROC curve of 0.982 (95% CI: 0.958-0.994) and 0.986 (95% CI: 0.963-0.996), respectively, for predicting GA ≥71 days. Conclusion: This validation study in an intended-use population confirmed that PAPP-A has a strong ability to distinguish pregnancies above and below 71 days' gestation. Clinical trial registration: NCT04232189 (ClinicalTrials.gov).

In the USA, abortion with pills is an option for people with pregnancies of less than 71 days. Usually, people use ultrasound to find out how far along a pregnancy is. Ultrasound can be pricey and hard to find. Some studies show that a protein in blood, called PAPP-A, may be another option. The authors took blood from and did ultrasounds for people who wanted an abortion. They measured how much PAPP-A was in the blood using two different methods. The level of PAPP-A in the blood did a good job of distinguishing pregnancies that were higher and lower than 71 days.

Abortion bans and their impacts: A view from the United States.

A retrospective study of abortion facilities in and around Texas by White et al.1 and a spatial analysis by Rader et al.2 are combined to illustrate the detrimental effects of abortion bans enacted in the United States.

Single dose letrozole and misoprostol for termination of pregnancy through 63 days' gestation: A pilot study.

OBJECTIVES: We conducted a pilot study to evaluate a single dose of letrozole 30 mg prior to misoprostol 800 mcg buccally for medication abortion STUDY DESIGN: We enrolled 40 participants seeking medication abortion up to 63 days' gestation at a site in Salt Lake City, UT. Participants received a single dose of letrozole 30 mg in-clinic followed 2 days later by misoprostol 800 mcg buccally at home. They took a second dose of misoprostol if they had no bleeding within 24 hours of the first. Participants returned 7 to 10 days later for assessment of abortion outcome and side effects RESULTS: Thirty-seven participants (93%) returned for follow-up and 2 (5%) went to another facility from which research staff obtained outcome data. Three-fourths (29/39, 74%, 95% CI: 60%-89%) had a complete abortion; 4 (10%, 95% CI: 0.3%-20%) had an incomplete abortion and opted for aspiration, and 6 (15%, 95% CI: 4%-27%) had an ongoing pregnancy. All subjects with follow-up reported taking the first dose of misoprostol. Ten (27%) took the second dose as well; only three did so due to no bleeding. Nineteen participants (51%) reported side effects after letrozole prior to misoprostol and two people (5%) rated these effects as severe. Side effects following misoprostol occurred in 33 participants (89%) and were as expected based on previous literature. No serious adverse events were reported CONCLUSION: A single dose of letrozole 30 mg followed by misoprostol had lower than desirable efficacy and does not warrant further study. IMPLICATIONS: A single dose of letrozole does not appear to be an effective adjunct to misoprostol for medication abortion.

A descriptive analysis of medical abortion commodity availability and pricing at retail outlets in 44 countries across four regions globally.

Pharmacies in low- and middle-income countries play an important role in increasing the availability of medical abortion to individuals for self-use. We aimed to document the costs to users of medical abortion products at outlets across geographies and understand the diversity of available products, primarily in low- and middle-income countries or in places where access to abortion is restricted. A descriptive analysis of price data was completed for identified medical abortion products at retail outlets visited in 44 countries from November 2017 to February 2018. Median prices and ranges are reported in $US for mifepristone 200 mg tablets, misoprostol 200 mcg tablets, and combipacks. Misoprostol, mifepristone, and combipacks were found in 44, 19, and 16 countries, respectively. Nearly two-thirds of products (321/508) required a prescription. The median price of misoprostol was $0.63 per tablet (range $0.09-$27.63) based on 304 price points. Mifepristone and combipacks had fewer price points available (n = 59 and n = 44, respectively). Median prices were $11.78 per mifepristone tablet (range $1.77-$37.83) and $11.18 per combipack (range $3.50-$35.86). Overall, prices were highest in Latin America and lowest in South/Southeast Asia. Only 11.5% (7/61) of the total unique misoprostol brands were quality-assured (i.e. approved by a stringent regulatory authority or pre-qualified by the World Health Organization), compared to 25.0% (4/16) of unique combipack products. There was wide variation in product pricing and availability across settings. The infrequent availability of mifepristone and combipacks, in addition to the limited availability of quality-assured medicines and high cost of abortion medications, are important factors affecting access to high-quality abortion care.

Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

BACKGROUND: Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings. METHODS: We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34-231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios. RESULTS: All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays. CONCLUSIONS: Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.

Postpartum infection, pain and experiences with care among women treated for postpartum hemorrhage in three African countries: A cohort study of women managed with and without condom-catheter uterine balloon tamponade.

OBJECTIVE: We aimed to determine the risk of postpartum infection and increased pain associated with use of condom-catheter uterine balloon tamponade (UBT) among women diagnosed with postpartum hemorrhage (PPH) in three low- and middle-income countries (LMICs). We also sought women's opinions on their overall experience of PPH care. METHODS: This prospective cohort study compared women diagnosed with PPH who received and did not receive UBT (UBT group and no-UBT group, respectively) at 18 secondary level hospitals in Uganda, Egypt, and Senegal that participated in a stepped wedge, cluster-randomized trial assessing UBT introduction. Key outcomes were reported pain (on a scale 0-10) in the immediate postpartum period and receipt of antibiotics within four weeks postpartum (a proxy for postpartum infection). Outcomes related to satisfaction with care and aspects women liked most and least about PPH care were also reported. RESULTS: Among women diagnosed with PPH, 58 were in the UBT group and 2188 in the no-UBT group. Self-reported, post-discharge antibiotic use within four weeks postpartum was similar in the UBT (3/58, 5.6%) and no-UBT groups (100/2188, 4.6%, risk ratio = 1.22, 95% confidence interval [CI]: 0.45-3.35). A high postpartum pain score of 8-10 was more common among women in the UBT group (17/46, 37.0%) than in the no-UBT group (360/1805, 19.9%, relative risk ratio = 3.64, 95% CI:1.30-10.16). Most women were satisfied with their care (1935/2325, 83.2%). When asked what they liked least about care, the most common responses were that medications (580/1511, 38.4%) and medical supplies (503/1511, 33.3%) were unavailable. CONCLUSION: UBT did not increase the risk of postpartum infection among this population. Women who receive UBT may experience higher degrees of pain compared to women who do not receive UBT. Women's satisfaction with their care and stockouts of medications and other supplies deserve greater attention when introducing new technologies like UBT.

Sensitivity and specificity of placental proteins for gestational age screening: An exploratory study.

OBJECTIVE: To examine the possibility that serum or urine concentrations of pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloproteinase 12 (ADAM-12), placental growth factor (PlGF), human placental lactogen (HPL), glypican-3, pregnancy specific beta-1-glycoprotein 1 (PSG-1) or prolactin could predict gestational age (GA) >70 days, the currently recommended limit for medical abortion in the United States. STUDY DESIGN: In this exploratory observational study, we collected serum and urine specimens from 245 healthy individuals with singleton intrauterine pregnancies at GA <40 weeks by ultrasound. We assayed the serum specimens for all seven proteins and the urine specimens for PAPP-A and ADAM-12. We used scatterplots and receiver operating characteristic curves to identify a concentration for each protein that would differentiate GAs above and below 70 days. RESULTS: All seven proteins showed significant ability to distinguish GAs >70 days from earlier gestations. A PAPP-A concentration ≥5.591 ng/ml provided 100% sensitivity and 90% specificity for identifying GAs >70 days. An ADAM-12 concentration of ≥3.11 ng/ml provided 98.5% sensitivity and 77% specificity for identifying GAs >70 days. Serum concentrations of the other compounds showed less diagnostic discrimination. PAPP-A was not detected in urine, and urinary ADAM-12 concentrations were not useful in identifying GAs above 70 days. CONCLUSION: PAPP-A and ADAM-12 showed considerable promise as bases for a sensitive and specific serum test for identifying pregnancies with GA >70 days. If these results are confirmed by future research, such a test could obviate the need for routine ultrasound before medical abortion. IMPLICATIONS: Two placental proteins, PAPP-A and ADAM-12, showed considerable promise as bases for a serum test for identifying pregnancies with gestational age >70 days. Such a test could be highly useful in screening patients for eligibility for medical abortion.

A cross-sectional analysis of mifepristone, misoprostol, and combination mifepristone-misoprostol package inserts obtained in 20 countries.

OBJECTIVES: To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and middle-income countries. STUDY DESIGN: From November 2017 to February 2018 mifepristone, misoprostol, and combined mifepristone-misoprostol (combipack) products were collected to populate the Medical Abortion Commodities Database. We extracted stated indications for use, storage instructions, and date of last revision from each package insert obtained. For those inserts listing medical abortion as an indication, we also extracted eligibility criteria, recommended regimens, side effects, and contraindications. RESULTS: We identified 41 package inserts from 20 countries; 19 (46%) listed medical abortion as an indication including all 7 combipacks, all 7 mifepristone products, and 5/27 (19%) misoprostol products. Date of last insert revision ranged from 1991 to 2016. Gestational age limits for early medical abortion ranged from 49 days to "first trimester." Three (43%) mifepristone products recommended a 600 mg oral dose and two (29%) recommended regimens with gemeprost. Eighteen (67%) misoprostol and one (14%) combipack inserts recommended protection from moisture. CONCLUSIONS: The characteristics, clinical information, and storage instructions in medical abortion product package inserts from a variety of field settings in low- and middle-income countries included inadequate storage instructions and outdated gestational age limits and regimens. IMPLICATIONS: There is an urgent need to revisit approved inserts for medical abortion products in low- and middle-income countries to ensure information is accurate and reflects the current evidence base. Simultaneously, providing supplemental instructions targeted at users may fill some gaps. People have a right to accurate information to ensure a safe and effective medical abortion experience.

Achieving community-based postpartum follow up in eastern Uganda: the field experience from the MamaMiso Study on antenatal distribution of misoprostol.

BACKGROUND: Advance provision of misoprostol to women during antenatal care aims to achieve broader access to uterotonics for the prevention of postpartum hemorrhage. Studies of this community-based approach usually involve antenatal education as well as timely postpartum follow-up visits to confirm maternal and neonatal outcomes. The MamaMiso study in Mbale, Uganda sought to assess the feasibility of conducting follow-up visits in the postpartum period following advance provision of misoprostol for postpartum hemorrhage prevention. MamaMiso recruited women during antenatal care visits. Participants were asked to contact the research team within 48 h of giving birth so that postpartum follow-up visits could be carried out at their homes. Women's baseline and delivery characteristics were collected and analyzed with respect to follow-up time ('on time' ≤ 7 days, 'late' > 7 days, and 'lost to follow up'). Every woman who was followed up late due to a failure to report the delivery was asked for the underlying reasons for the delay. When attempts at following up participants were unsuccessful, a file note was generated explaining the details of the failure. We abstracted data and identified themes from these notes. RESULTS: Of 748 recruited women, 700 (94%) were successfully followed up during the study period, 465 (62%) within the first week postpartum. The median time to follow up was 4 days and was similar for women who delivered at home or in facilities and for women who had attended or unattended births. Women recruited at the urban hospital site (as opposed to rural health clinics) were more likely to be lost to follow up or followed up late. Of the women followed up late, 202 provided a reason. File notes explaining failed attempts at follow up were generated for 164 participants. Several themes emerged from qualitative analysis of these notes including phone difficulties, inaccurate baseline information, misperceptions, postpartum travel, and the condition of the mother and neonate. CONCLUSIONS: Keeping women connected to the health system in the postpartum period is feasible, though reaching them within the first week of their delivery is challenging. Understanding characteristics of women who are harder to reach can help tailor follow-up efforts and elucidate possible biases in postpartum study data. Trial Registration Number ISRCTN70408620 December 28, 2011.

A crossover pharmacokinetic study of misoprostol by the oral, sublingual and buccal routes.

OBJECTIVES: The aim of the study was to compare the pharmacokinetic parameters of 800 µg oral, sublingual and buccal misoprostol in healthy non-pregnant women. METHODS: This was an open-label, randomised study with a three-way crossover design. Eighteen participants were randomly assigned to treatment sequences of 800 µg oral, sublingual and buccal misoprostol administered under fasting conditions, with a 7-day washout period. Ten participants completed all routes. The primary pharmacokinetic parameters measured were the area under the plasma misoprostol acid concentration-time curve (AUC) from dosing to last quantifiable concentration (AUC0-t), the AUC from 0 to infinity (AUC0-∞) and the maximum plasma concentration (Cmax). Secondary parameters included the plasma elimination rate constant (ke), the half-life and the mean residence time (MRT). RESULTS: There were statistically significant differences in AUC0-∞, AUC0-t and Cmax at the p < 0.05 level for the three routes of administration. The sublingual route achieved the highest bioavailability, and the buccal route achieved the lowest peak concentration. The oral and buccal routes had a similar AUC0-∞ and the buccal route had the highest MRT and ke. There were no differences in half-lives, and no serious adverse events were reported. CONCLUSIONS: This study shows variability in Cmax and AUC by three by-mouth routes of misoprostol administration. The dose in this study was 800 µg, which is among the highest doses seen in current guidelines. These data contribute to the understanding of efficacy and safety of different routes and could provide a basis for deciding whether certain routes are preferable for particular indications.

The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial.

BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620).

A prospective, non-randomized study of home use of mifepristone for medical abortion in the U.S.

OBJECTIVE: To determine the acceptability of taking mifepristone at home for early medical abortion in the United States. STUDY DESIGN: This prospective, non-randomized, open-label study at six Planned Parenthood centers gave women with pregnancies up to 63 days' gestation seeking medical abortion the choice of taking mifepristone in the center or at home. Participants were interviewed at a follow-up visit 1-2 weeks after mifepristone administration to assess their experience with the option they selected. RESULTS: Four-hundred women were enrolled between April 2013 and June 2014 of which 32% (n=128) chose to take mifepristone at home. Abortion success rates did not differ between home and center users (96% and 97%). Among home users, 82% reported taking the mifepristone at the time they planned with their provider and no participant took it after 63 days' gestation. The most common reason cited for selecting home use was scheduling flexibility and significantly more home users took misoprostol on the weekend (50% vs. 36%, p=.02). Home users were more likely than center users to report missing no days of work due to the abortion (47% vs. 28%, p=.08). Ninety-nine percent of home users reported that they would take mifepristone at home again and 96% would recommend home use to a friend. Offering this option did not increase the service delivery burden on study providers, who would recommend home use in the future for most participants. CONCLUSIONS: Home use of mifepristone is a highly acceptable practice for which there is current demand, and it should be offered as part of routine medical abortion services. IMPLICATIONS: Offering the option of home use of mifepristone to medical abortion patients can provide women and clinics with more flexibility while maintaining a safe, effective and acceptable service. These results provide support for telemedicine or pharmacy distribution.

What happens when we routinely give doxycycline to medical abortion patients?

OBJECTIVES: Routine provision of antibiotics following medical abortion is common yet practitioners and professional societies differ on its utility. Our study compares the side effects experienced by women who were prescribed doxycycline following medical abortion to those who were not and assesses the adherence to one prescribed regimen. STUDY DESIGN: This was a prospective, observational, open-label study from a convenience sample. Women seeking medical abortion were enrolled in nine study sites, including four clinics that routinely prescribe a seven-day course of doxycycline (Doxycycline arm) and five clinics that do not routinely prescribe any antibiotics (No Doxycycline arm). Seven to fourteen days following the administration of mifepristone, women were asked to self-administer a computer-based survey. The survey asked about side effects experienced (both arms) and adherence to the regimen (Doxycycline arm only). RESULTS: Five hundred eighty-one women were enrolled (278 in the Doxycycline arm and 303 in the No Doxycycline arm). There was a trend toward increased nausea in the Doxycycline arm (47.8% vs. 40.9%; p=.056) and a statistically significant difference in vomiting (25.2% vs. 18.5%; p=.032). Almost all women in the Doxycycline arm reported taking at least one pill, however only 28.3% reported "perfect adherence." The most common reasons reported for taking fewer pills than instructed were that participants were still taking them (beyond 7 days) or that they forgot to take them. CONCLUSION: Women who were prescribed doxycycline following medical abortion reported moderate adherence and experienced significantly more vomiting than their counterparts. IMPLICATIONS: In the absence of robust evidence that prescribing 7 days of doxycycline following medical abortion is effective at reducing serious infections, these data can assist the public health community with deciding whether routine provision is the most appropriate strategy.

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

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.