Evaluating women's acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians: a mixed methods study.

BACKGROUND: Studies evaluating task sharing in postabortion care have mainly focused on women in first trimester and many lack a qualitative component. We aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences in Uganda. METHODS: Our mixed methods study combined 1140 structured interview data from a randomized controlled equivalence trial and in-depth interviews (n = 28) among women managed with misoprostol for second trimester incomplete abortion at 14 public health facilities in Uganda. Acceptability, our main outcome, was measured at the 14-day follow-up visit using a structured questionnaire as a composite variable of: 1) treatment experience (as expected/ better than expected/ worse than expected), and 2) satisfaction - if patient would recommend the treatment to a friend or choose the method again. We used generalized mixed effects models to obtain the risk difference in acceptable post abortion care between midwife and physician groups. We used inductive content analysis for qualitative data. RESULTS: From 14th August 2018 to 16th November 2021, we assessed 7190 women for eligibility and randomized 1191 (593 to midwife and 598 to physician). We successfully followed up 1140 women and 1071 (94%) found the treatment acceptable. The adjusted risk difference was 1.2% (95% CI, - 1.2 to 3.6%) between the two groups, and within our predefined equivalence range of - 5 to + 5%. Treatment success and feeling calm and safe after treatment enhanced acceptability while experience of side effects and worrying bleeding patterns reduced satisfaction. CONCLUSIONS: Misoprostol treatment of uncomplicated second trimester incomplete abortion was equally and highly acceptable to women when care was provided by midwives compared with physicians. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to postabortion care services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03622073.

Approximately 9.6% of abortion-related deaths occur in Sub-Saharan Africa. These deaths can be prevented if unintended pregnancies are avoided, women can access safe abortions within the expectations of the country's laws, and post abortion care (PAC) services are provided equitably. Previous research shows that women with abortion complications in the first trimester of pregnancy can be treated with misoprostol by either midwives or physicians. This sharing of tasks between the midwives and physicians is safe, effective, and acceptable. However, there is a gap in evidence on task sharing in the second trimester. To check practicability of task sharing in second trimester, we aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences. Our study therefore combined quantitative and qualitative approaches. Women's acceptability of misoprostol treatment for incomplete second trimester abortion was found to be equally acceptable when provided by midwives compared with physicians. Treatment success, feeling calm and safe after treatment increased acceptability, while experience of side effects and worrying bleeding patterns reduced satisfaction. Counselling of women may address some of these problems since it provides reassurance and reduces anxiety. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to PAC services.

Comparison of the effectiveness and safety of treatment of incomplete second trimester abortion with misoprostol provided by midwives and physicians: a randomised, controlled, equivalence trial in Uganda.

BACKGROUND: To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of treatment for incomplete second trimester abortion with misoprostol, comparing care provision by midwives with that provided by physicians in Uganda. METHODS: Our multicentre, randomised, controlled, equivalence trial undertaken in 14 health facilities in Uganda recruited women with incomplete abortion of uterine size 13-18 weeks. We randomly assigned (1:1) women to clinical assessment and treatment by either midwife or physician. The randomisation sequence was computer generated, in blocks of four to 12, and stratified for study site. Participants received sublingual misoprostol (400 µg once every 3 h for up to five doses). The study was not concealed from the health-care providers and study participants. Primary outcome was complete abortion within 24 h that did not require surgical evacuation. Analysis was per-protocol and intention to treat; the intention-to-treat population consisted of women who were randomised, received at least one dose of misoprostol, and reported primary outcome data, and the per-protocol population excluded women with unexplained discontinuation of treatment. We used generalised mixed-effects models to obtain the risk difference. The predefined equivalence range was -5% to 5%. The trial was registered at ClinicalTrials.gov, NCT03622073. FINDINGS: Between Aug 14, 2018, and Nov 16, 2021, 1191 eligible women were randomly assigned to each group (593 women to the midwife group and 598 to the physician group). 1164 women were included in the per-protocol analysis, and 530 (92%) of 577 women in the midwife group and 553 (94%) of 587 women in the physician group had a complete abortion within 24 h. The model-based risk difference for the midwife versus physician group was -2·3% (95% CI -4·4 to -0·3), and within our predefined equivalence range (-5% to 5%). Two women in the midwife group received blood transfusion. INTERPRETATION: Clinical assessment and treatment of second trimester incomplete abortion with misoprostol provided by midwives was equally effective and safe as when provided by physicians. In low-income settings, inclusion of midwives in the medical management of uncomplicated second trimester incomplete abortion has potential to increase women's access to safe post-abortion care. FUNDING: Swedish Research Council and THRiVE-2.

The Quality of Postabortion Care in Tanzania: Service Provider Perspectives and Results From a Service Readiness Assessment.

INTRODUCTION: In 2015, the government of Tanzania launched an effort to strengthen the quality of postabortion care (PAC), an integrated health service that includes treatment for abortion complications and provision of family planning counseling and voluntary services, in 25 facilities in mainland Tanzania and in Zanzibar. METHODS: To help guide the government's initiative, we conducted a mixed-method study in 2016 using health facility surveys and in-depth interviews with health care workers that offer PAC. Surveys of the 25 facilities assessed the current use of services and readiness to deliver them. Provider performance in PAC was assessed through direct observation of client-provider interactions. In-depth interviews (IDIs) with 30 staff from the facilities provided qualitative information on priorities for PAC quality improvement. RESULTS: In the 6 months preceding the study, 2,175 PAC clients sought care at the facilities. Of these PAC clients, 55% chose a family planning method, of whom 6% chose a voluntary long-acting reversible contraceptive. The median facility PAC readiness scores were 45% for health centers, 49% for district hospitals, and 61% for regional referral hospitals. Direct observations of manual vacuum aspiration provision for PAC revealed that providers implemented, on average, 69% of the critical clinical steps. For misoprostol provision, PAC providers implemented, on average, 42% of the critical steps. Multilevel influences affected PAC providers' work, often adversely, by shaping their confidence in their technical competency, confusing their role as health care workers and as clients' peers, and coloring their attitudes toward clientele. The PAC providers also felt that their ability to implement their responsibilities was shaped by lapses in essential support and functionality of the health care system, as well as by social and cultural norms. CONCLUSIONS: Technical assistance approaches that blend training, clinical quality improvement, systems strengthening, and social interventions that address demand-side barriers are needed to ensure providers achieve their potential and are able to deliver high-quality PAC.

Post-abortion care with misoprostol - equally effective, safe and accepted when administered by midwives compared to physicians: a randomised controlled equivalence trial in a low-resource setting in Kenya.

OBJECTIVE: To assess the effectiveness of midwives administering misoprostol to women with incomplete abortion seeking post-abortion care (PAC), compared with physicians. DESIGN: A multicentre randomised controlled equivalence trial. The study was not masked. SETTINGS: Gynaecological departments in two hospitals in a low-resource setting, Kenya. POPULATION: Women (n=1094) with incomplete abortion in the first trimester, seeking PAC between 1 June 2013 to 31 May 2016. Participants were randomly assigned to receive treatment from midwives or physicians. 409 and 401 women in the midwife and physician groups, respectively, were included in the per-protocol analysis. INTERVENTIONS: 600 µg misoprostol orally, and contraceptive counselling by a physician or midwife. MAIN OUTCOME MEASURES: Complete abortion not needing surgical intervention within 7-10 days. The main outcome was analysed on the per-protocol population with a generalised estimating equation model. The predefined equivalence range was -4% to 4%. Secondary outcomes were analysed descriptively. RESULTS: The proportion of complete abortion was 94.8% (768/810): 390 (95.4%) in the midwife group and 378 (94.3%) in the physician group. The proportion of incomplete abortion was 5.2% (42/810), similarly distributed between midwives and physicians. The model-based risk difference for midwives versus physicians was 1.0% (-4.1 to 2.2). Most women felt safe (97%; 779/799), and 93% (748/801) perceived the treatment as expected/easier than expected. After contraceptive counselling the uptake of a contraceptive method after 7-10 days occurred in 76% (613/810). No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol provided by midwives is equally effective, safe and accepted by women as when administered by physicians in a low-resource setting. Systematically provided contraceptive counselling in PAC is effective to mitigate unmet need for contraception. TRIAL REGISTRATION NUMBER: NCT01865136; Results.

Women's Acceptability of Misoprostol Treatment for Incomplete Abortion by Midwives and Physicians - Secondary Outcome Analysis from a Randomized Controlled Equivalence Trial at District Level in Uganda.

OBJECTIVE: This study aimed to assess women´s acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi-centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024.

Comparison of treatment of incomplete abortion with misoprostol by physicians and midwives at district level in Uganda: a randomised controlled equivalence trial.

BACKGROUND: Misoprostol is established for the treatment of incomplete abortion but has not been systematically assessed when provided by midwives at district level in a low-resource setting. We investigated the effectiveness and safety of midwives diagnosing and treating incomplete abortion with misoprostol, compared with physicians. METHODS: We did a multicentre randomised controlled equivalence trial at district level at six facilities in Uganda. Eligibility criteria were women with signs of incomplete abortion. We randomly allocated women with first-trimester incomplete abortion to clinical assessment and treatment with misoprostol either by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and was stratified for study site. Primary outcome was complete abortion not needing surgical intervention within 14-28 days after initial treatment. The study was not masked. Analysis of the primary outcome was done on the per-protocol population with a generalised linear-mixed effects model. The predefined equivalence range was -4% to 4%. The trial was registered at ClinicalTrials.gov, number NCT01844024. FINDINGS: From April 30, 2013, to July 21, 2014, 1108 women were assessed for eligibility. 1010 women were randomly assigned to each group (506 to midwife group and 504 to physician group). 955 women (472 in the midwife group and 483 in the physician group) were included in the per-protocol analysis. 452 (95·8%) of women in the midwife group had complete abortion and 467 (96·7%) in the physician group. The model-based risk difference for midwife versus physician group was -0·8% (95% CI -2·9 to 1·4), falling within the predefined equivalence range (-4% to 4%). The overall proportion of women with incomplete abortion was 3·8% (36/955), similarly distributed between the two groups (4·2% [20/472] in the midwife group, 3·3% [16/483] in the physician group). No serious adverse events were recorded. INTERPRETATION: Diagnosis and treatment of incomplete abortion with misoprostol by midwives is equally safe and effective as when provided by physicians, in a low-resource setting. Scaling up midwives' involvement in treatment of incomplete abortion with misoprostol at district level would increase access to safe post-abortion care. FUNDING: The Swedish Research Council, Karolinska Institutet, and Dalarna University.

Effects of gefitinib, an epidermal growth factor receptor inhibitor, on human placental cell growth.

OBJECTIVE: Placenta has the highest expression of epidermal growth factor (EGF) receptor of all tissues, a cell signaling pathway promoting survival and growth. Therefore, EGF receptor inhibition could potentially treat ectopic pregnancy. We undertook preclinical studies to examine whether gefitinib (orally available EGF receptor inhibitor) with or without methotrexate inhibits placental cell growth. METHODS: Gefitinib and methotrexate were added to placental cells and their ability inhibit cell growth, block EGF receptor signaling, and induce apoptosis (programmed cell death) was examined. They were also administered to two animal mouse models to examine their effects on placental tissue in vivo. RESULTS: Epidermal growth factor receptor was highly expressed in placental tissue from ectopic pregnancies. Combining gefitinib with methotrexate potently inhibited growth of placental cells, including placental cell lines (JEG3, BeWo cells) and cells isolated from first-trimester placenta. These drugs were additive in blocking EGF receptor signaling and inducing apoptosis. Gefitinib and methotrexate administered together were more potent in decreasing the volume of human placental cells xenografted subcutaneously onto mice compared with either alone. By day 19 after xenografting, mean (± standard error of the mean), xenograft volumes were: 821 (± 68) mm after gefitinib treatment, 901 (± 204) mm after methotrexate treatment, and 345 (±137) mm after both drugs were given (P<.01 for both comparisons of single therapy compared with combination therapy). Combining these agents doubled rates of fetal resorption in pregnant mice compared with each drug alone. CONCLUSION: Combining gefitinib with methotrexate potently inhibits placental cell growth in vitro and in mouse models. The combination may have potential in treating ectopic pregnancies.

New hope: community-based misoprostol use to prevent postpartum haemorrhage.

The wide gap in maternal mortality ratios worldwide indicates major inequities in the levels of risk women face during pregnancy. Two priority strategies have emerged among safe motherhood advocates: increasing the quality of emergency obstetric care facilities and deploying skilled birth attendants. The training of traditional birth attendants, a strategy employed in the 1970s and 1980s, is no longer considered a best practice. However, inadequate access to emergency obstetric care and skilled birth attendants means women living in remote areas continue to die in large numbers from preventable maternal causes. This paper outlines an intervention to address the leading direct cause of maternal mortality, postpartum haemorrhage. The potential for saving maternal lives might increase if community-based birth attendants, women themselves, or other community members could be trained to use misoprostol to prevent postpartum haemorrhage. The growing body of evidence regarding the safety and efficacy of misoprostol for this indication raises the question: if achievement of the fifth Millennium Development Goal is truly a priority, why can policy makers and women's health advocates not see that misoprostol distribution at the community level might have life-saving benefits that outweigh risks?

Misoprostol as first-line treatment for incomplete abortion at a secondary-level health facility in Nigeria.

OBJECTIVE: To determine the feasibility of introducing misoprostol as first-line treatment for incomplete abortion at a secondary-level health facility. METHODS: An open-label prospective study was conducted in a secondary-level health facility in Nigeria. Eligible women diagnosed with incomplete abortion received 400-µg sublingual misoprostol as first-line treatment. Nurse-midwives took the lead in diagnosis, counseling, treatment, and assessment of final outcome. The primary outcome was the proportion of women who completed the abortion process. RESULTS: Complete evacuation was achieved in 83 of 90 (92.2%) eligible women. The most common adverse effects were abdominal pain/cramps (58 [64.4%]), heavy bleeding (21 [23.3%]), spotting (15 [16.7%]), and fever/chills (11 [12.2%]). More than 90% of women reported that the procedure was satisfactory, that pain and adverse effects were tolerable, and that bleeding was acceptable. Eighty-four (93.3%) and 86 (95.6%) women, respectively, would use the method in the future and recommend it to friends. CONCLUSION: Misoprostol is an effective, safe, and acceptable method for treating incomplete abortion. It can be successfully used as first-line treatment by nurse-midwives. Success rates over 90% are consistent with findings from previous studies in which drug administration was controlled solely by physicians.

Effects of progressive muscle relaxation training on anxiety and quality of life of inpatients with ectopic pregnancy receiving methotrexate treatment.

We explored the effects of progressive muscle relaxation training on anxiety and health-related quality of life of patients with ectopic pregnancy receiving methotrexate treatment. Ninety inpatients receiving this treatment were randomly assigned to a progressive muscle relaxation group (n = 45) or a control group (n = 45). The control group received standard single-dose methotrexate treatment, and the experimental group received methotrexate and additional muscle relaxation training until hospital discharge. The patients were evaluated with the state form of the State-Trait Anxiety Inventory and SF-36 shortly after admission and before discharge from the hospital. Both covariance analysis and repeated measures ANOVA showed that muscle relaxation training can effectively improve the anxiety and health-related quality of life of patients with ectopic pregnancy receiving methotrexate treatment in an inpatient setting.

Tratamento clínico da gravidez ectópica com metotrexato / Medical treatment of ectopic pregnancy with methotrexate

A gravidez ectópica é uma importante causa de morbimortalidde materna no primeiro trimestre gestacional. As dosagens hormonais seriadas e a ultrassonografia endovaginal, realizadas atualmente, facilitaram o diagnóstico e tratamento da gravidez ectópica, antes que ocorresse a ruptura tubária. O tratamento clínico medicamentoso com o metotrexato, um antagonista do ácido fólico altamente tóxico a tecidos em rápida replicação, é bastante utilizado em gestações ectópicas íntegras, adequadamente selecionadas. Muitos estudos vêm sendo realizados a fim de tentar definir quais grupos de pacientes se beneficiariam desse tratamento e, qual seria o melhor esquema de administração dessa droga, com redução dos efeitos colaterais e melhores taxas de sucesso. Esta revisão expõe as opções de tratamento medicamentoso mais estudadas para tratamento da gravidez ectópica íntegra, com ênfase nas taxas de sucesso de tratamento (cura, persistência de tecido trofoblástico e permeabilidade tubária) e no prognóstico a longo prazo.

Ectopic pregnancy is a significant cause of morbity and mortality in the first trimester of pregnancy. Serial hormone assays and transvaginal ultrasonography facilitate the diagnosis and treatment of ectopic pregnancy before rupture occurs. Early nonsurgical diagnosis and appropiate treatment have resulted in diversity of management options and decline in mortality, due to this pathology. Treatment with methotrexate, a folic acid antagonist, highly toxic to rapidly replicating tissues, can be applied on selected patients with non-ruptured ectopic pregnancy. Many studies have been developed intending to define which patients would be benefited by this treatment and how to administer this drug, with low side effects and good successful rates. This review refers to the best practice on non-ruptured ectopic pregnancy, with emphasis on treatment success rates (cure rate, incidence of persistent trophoblast and tubal patency) and long-term prognosis.

The delivery of medical abortion services: the views of experienced providers.

This study examined beliefs about the delivery of medical abortion services and current roles of 76 providers of methotrexate-induced abortion. The sample included physicians, midlevel professionals, administrators, and counselors/other medical staff. Over 75% of participants believed that, given proper training and emergency backup, physicians and midlevel clinicians alike could provide medical abortions. Over 85% agreed that methotrexate-induced abortions could be provided in any physician's office or medical facility. There were no differences in perceptions by participant group. Involvement of midlevel providers in provision of medical abortion could potentially increase access and options for women seeking to terminate an early pregnancy.

Studies on the mechanisms of abortion induction by Trichosanthin.

Radix trichosanthis, an abortifacient drug of mid-gestation, is extracted from the root tuber of Trichosanthes kirilowii Maxim, Cucurbitaceae. Its purified effective principle is a basic protein of molecular weight of approximately 18,000 and is named trichosanthin. By authorization it has been proved to be very effective in abortion induction of mid-gestation, particularly effective in curing ectopic pregnancy, hydatidiform mole, and invasive mole, and it has also some therapeutic action on choriocarcinoma. From the analysis of the experimental results on its initial site of action, the morphological and functional injury of trophoblast cells of placenta and of cultures in vitro and the effect on prostaglandin synthesis, the following conclusions are drawn concerning the mechanisms of abortion induction by trichosanthin: (1) Trichosanthin exerts its action directly on the placental trophoblasts and possesses a certain degree of specificity; (2) It selectively causes the necrotic denaturation of the syncytiotrophoblasts of placental villi, which makes fragments of the disintegrated cells clumped in the blood sinus, hence the coagulation of blood and the circulation hindrance, and tissue necrosis over large areas follows. The necrosis of placental villi is the primary response, and circulation hindrance secondary; (3) Structural injuries have been reflected on the impairment of functional activities; the concentrations of HCG and steroid hormones fall rapidly below the threshold values of threatened abortion. Serious structural and functional injuries bring about destructive disturbances on the normal endocrine relationship between the mother and the fetus and on metabolic exchanges. It is further postulated that through certain unknown mechanism the synthesis of prostaglandins increases, uterine contraction is initiated and abortion ensues. In summary, trichosanthin, a plant protein discovered from Chinese medicinal herbs, is a drug effective in abortion induction and against trophoblastic neoplasms. Preliminary elucidation of the mechanisms of abortion induction by trichosanthin has afforded a basis for the clinical application with better efficacy and its possible abortifacient use in early pregnancy and for the discovery of newer cancer chemotherapeutic agents.