Treatment Options After a Diagnosis of Early Miscarriage: Expectant, Medical, and Surgical.

BACKGROUND: Approximately 12% of pregnancies end in an early miscarriage (up to week 12 + 0 of pregnancy). Over the past 10 to 15 years, two alternatives to curettage have appeared in the pertinent international treatment guidelines: expectant treatment and medical (drug) treatment. In this review, we discuss the advantages and disadvantages of each of these therapeutic options. METHODS: This review is based on pertinent publications (January 2000 to February 2021) retrieved by a selective search in PubMed, as well as on the guidelines of the American College of Obstetrics and Gynecologists, the Association of the Scientific Medical Societies in Germany, the National Institute for Health and Care Excellence/Royal College of Obstetricians and Gynaecologists, and the International Federation of Gynaecology and Obstetrics. RESULTS: Three effective and safe treatment options are available after a diagnosis of early miscarriage. Expectant treatment yields success rates of 66-91%, depending on the type of miscarriage. Its complications include hemorrhage requiring blood transfusion in 1-2% of cases. If expectant therapy fails, subsequent treatment with misoprostol or curettage is indicated. Drug therapy with misoprostol yields a complete termination in 81-95% of cases and is thus a valid alternative to expectant therapy, with the advantage of better planning capability. The vaginal application of misoprostol is the most effective means of administration, with the fewest side effects. Curettage is needed in 5-20% of cases. Suctional curettage has a success rate of 97-98%, with an associated anesthesia-related risk of 0.2%, a 0.1% risk of perforation, and a 2-3% rate of repeat curettage. CONCLUSION: If there is no acute indication for the surgical treatment of an early miscarriage, the patient can choose among three treatment options. Expectant and medical treatment can be provided on an outpatient basis. Curettage is the treatment of choice in the presence of infection, marked and persistent bleeding, hemodynamic instability, or a pre-existing coagulopathy.

Surgical and Reproductive Outcomes after Hysteroscopic Removal of Retained Products of Conception: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the impact of hysteroscopy for retained products of conception (RPOC) removal on surgical and reproductive outcomes. DATA SOURCES: Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, SciELO, EMBASE, and the Cochrane Central Register of Controlled Trials at the Cochrane Library) were searched from inception to March 2020. METHODS OF STUDY SELECTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Medical Subject Headings terms and text words such as "retained products of conception," "placental remnants," "placenta," and "hysteroscopy" were used for the identification of relevant studies. We included observational and randomized studies that analyzed surgical and/or reproductive outcomes of women who underwent hysteroscopic removal of RPOC. The primary outcome was the complete resection rate after 1 procedure. TABULATION, INTEGRATION, AND RESULTS: Twenty out of 245 studies were applicable, with data provided for 2112 women. The pooled complete resection rate was 91% (95% confidence interval [CI], 0.83-0.96). The incomplete resection rate evaluated was 7% (95% CI, 0.03-0.14), with a complication rate of 2% (95% CI, 0.00-0.04). Out of 1478 procedures, only 12 cases (0.8%) of postsurgical intrauterine adhesions were reported. Regarding post-therapy fecundity, women attempting postoperative conception had a clinical pregnancy rate of 87% (95% CI, 0.75-0.95), with a live birth rate of 71% (95% CI, 0.60-0.81) and a pregnancy loss rate of 9% (95% CI, 0.06-0.12). CONCLUSION: Hysteroscopy has a high rate of completely removing RPOC in a single surgical step, with low complication rates. Subsequent fecundity seems reassuring, with appropriate clinical pregnancy and live birth rates. However, standardization of approach and comparative trials of different hysteroscopic approaches are needed.

Early versus delayed follow-up after misoprostol treatment for early pregnancy loss.

RESEARCH QUESTION: Does extending the follow-up after misoprostol treatment for early pregnancy loss increase the success rate? DESIGN: Patients who had experienced early pregnancy loss (<12 weeks) and were treated with misoprostol in a single university-affiliated medical centre were prospectively followed before and after the implementation of a new treatment protocol extending the follow-up from 1 to 2 weeks. All patients received misoprostol 800 µg vaginally on day 1 and a second dose, when needed, on day 4 or 8. Patients underwent surgical aspiration after 1 week in the early follow-up group (n = 84) or 2 weeks in the delayed follow-up group (n = 85) if complete expulsion was not achieved (defined as endometrial thickness ≤15 mm and absence of gestational sac on transvaginal sonography). The primary outcome was treatment success, defined as no need for surgical aspiration. RESULTS: Women in the delayed follow-up group had a higher rate of successful treatment compared with women in the early follow-up group (88.2% versus 76.2%, respectively; P = 0.040), and a lower rate of second dose administration (32.9% versus 51.2%, respectively; P = 0.016). The incidence of non-expulsion of the gestational sac was also lower in the delayed follow-up group (1.2% versus 10.7%; P = 0.009). Treatment acceptability did not differ between the study groups. CONCLUSION: In women with early pregnancy loss treated with misoprostol, extending the follow-up protocol from 1 to 2 weeks resulted in an increase in treatment success.

Same-day confirmation of intrauterine pregnancy failure in women with first- and early second-trimester bleeding.

OBJECTIVE: To determine if alpha-fetoprotein (AFP) concentration in vaginal blood, in the setting of dissolved fetal tissue, is significantly higher than its concentration in the maternal serum. DESIGN: A prospective cohort study. SETTING: Medical center. PATIENT(S): Four groups of women were evaluated: 1) with missed/incomplete miscarriage with vaginal bleeding; 2) with threatened miscarriage; 3) with vaginal bleeding during cerclage placement; and 4) undergoing dilation and curettage (D&C). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): In each patient, AFP concentration in the vaginal blood or in the liquid component of the evacuated products of conception (POC; D&C group) was compared with the AFP concentration in the maternal serum. RESULT(S): The median (range) concentration ratios of AFP in vaginal blood (or POC) to AFP in maternal serum were 24.5 (5.1-8,620) and 957 (4.6-24,216) for the missed/incomplete (n = 30) and the D&C (n = 22) groups, respectively, whereas they were only 1.2 (0.4-13.4) and 1.01 (0.7-1.5) for the threatened miscarriage (n = 15) and cerclage (n = 9) groups, respectively. Receiver operating characteristic (ROC) analysis demonstrated 100% sensitivity and 86.7% specificity for the detection of the passage of fetal tissue (ratio 4.3, area under the ROC curve 0.96). CONCLUSION(S): Higher concentrations of AFP in vaginal blood than in maternal serum may indicate the presence of dissolved fetal tissue (i.e., confirming a failed pregnancy).

Misoprostol-induced Acute Coronary Syndrome in a Premenopausal Woman: A Case Report with Literature Review.

BACKGROUND: Misoprostol is a synthetic analog of prostaglandin-E1 and it is the most widely used drug for the medical management of incomplete abortion. Acute Coronary Syndrome (ACS) rarely occurs in perimenopausal women, in addition, its presentation is atypical, so the disease is not always recognized. CASE REPORT: We describe a case of 39-year-old woman with no major underlying cardiovascular risk factors, who developed an episode of ACS following the administration of two doses of misoprostol. After the discontinuation of misoprostol treatment, there was a complete resolution of patient's symptoms. The case draws attention to a rare side effect of a commonly used drug and alerts the clinicians to be cautious in those patients having baseline risk factors which make the patient more susceptible to such serious adverse drug effect.

'The more we change, the more we remain the same': female feticide continues unabated in India.

In North India, preference for sons has been blamed for repeated incidents of female feticide, despite the legislation in the form of the Pre-Conception and Pre-Natal Diagnostic Techniques Act, 2002. We describe how a team of local private doctors offer package deals to pregnant women and their families in rural areas. The fetal sex is determined at night using a portable ultrasonography machine.If the fetus is a girl, an immediate induced abortion is offered in the clients' home. If complications arise, women are advised to attend hospital. Such a patient visited us with a history of bleeding per vagina following incomplete induced abortion. This case study highlights the fact that female feticide continues to occur in India.

Induced abortion.

Abortion is common. Data on abortion rates are inexact but can be used to explore trends. Globally, the estimated rate in the period 2010-2014 was 35 abortions per 1000 women (aged 15-44 years), five points less than the rate of 40 for the period 1990-1994. Abortion laws vary around the world but are generally more restrictive in developing countries. Restrictive laws do not necessarily deter women from seeking abortion but often lead to unsafe practice with significant mortality and morbidity. While a legal framework for abortion is a prerequisite for availability, many laws, which are not evidence based, restrict availability and delay access. Abortion should be available in the interests of public health and any legal framework should be as permissive as possible in order to promote access. In the absence of legal access, harm reduction strategies are needed to reduce abortion-related mortality and morbidity. Abortion can be performed surgically (in the first trimester, by manual or electric vacuum aspiration) or with medication: both are safe and effective. Cervical priming facilitates surgery and reduces the risk of incomplete abortion. Diagnosis of incomplete abortion should be made on clinical grounds, not by ultrasound. Septic abortion is a common cause of maternal death almost always following unsafe abortion and thus largely preventable. While routine follow-up after abortion is unnecessary, all women should be offered a contraceptive method immediately after the abortion. This, together with improved education and other interventions, may succeed in reducing unintended pregnancy.

Operative hysteroscopy versus vacuum aspiration for incomplete spontaneous abortion (HY-PER): study protocol for a randomized controlled trial.

BACKGROUND: Incomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion. METHODS: After providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team. DISCUSSION: If our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22 weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02201732 ; registered on 17 July 2014.

Individualistic approach to the management of complete hydatidiform mole with coexisting live fetus.

Complete hydatidiform mole with a coexisting live fetus (CHMCF) is a rare obstetric occurrence. So far, approximately 177 cases have been documented in the literature with consequent 66 live births. We report a review article along with two cases of CHMCF, one presenting as incomplete abortion and other continued as CHMCF but terminated because of antepartum hemorrhage. Both had histopathologically proven one normal and other complete molar placenta with coexisting normal fetus. No evidence of persistent trophoblastic disease was observed. The dilemma of continuation versus termination of pregnancy is being emphasized in the review of literature. Pregnancy complicated by CHMCF may result in a viable live born infant in approximately one third of the cases. A potentially viable fetus with CHMCF may result in normal live birth with antecedent high risk maternal complications. A decision of termination of pregnancy in all CHMCF will however nullify all the chances of a live birth. An individualistic approach and an informed doctor patient consensus may improve the likely outcome. Appropriate counseling of the mother regarding high incidence of antenatal complications plays an integral part of decision of continuation of such pregnancies.

Serum biomarkers may help predict successful misoprostol management of early pregnancy failure.

In order to simplify management of early pregnancy loss, our goal was to elucidate predictors of successful medical management of miscarriage with a single dose of misoprostol. In this secondary analysis of data from a multicenter randomized controlled trial, candidate biomarkers were compared between 49 women with missed abortion who succeeded in passing their pregnancy with a single dose of misoprostol and 46 women who did not pass their pregnancy with a misoprostol single dose. We computed the precision of trophoblastic protein and hormone concentrations to discriminate between women who succeed or fail single dose misoprostol management. We also included demographic factors in our analyses. We found overlap in the concentrations of the individual markers between women who succeeded and failed single-dose misoprostol. However, hCG levels ≥ 4000 mIU/mL and ADAM-12 levels ≥ 2500 pg/mL were independently associated with complete uterine expulsion after one dose of misoprostol in our population. A multivariable logistic model for success included non-Hispanic ethnicity and parity <2 in addition to hCG ≥ 4000 mIU/mL and ADAM-12 ≥ 2500 pg/mL and had an area under the receiver operating characteristic (ROC) of 0.81 (95% confidence interval: 72-90%). Categorizing women with a predicted probability of ≥ 0.65 resulted in a sensitivity of 75.0%, specificity 77.1% and positive predictive value of 81.8%. While preliminary, our data suggest that serum biomarkers, especially when combined with demographic characteristics, may be helpful in guiding patient decision-making regarding the management of early pregnancy failure (EPF). Further study is warranted.

An audit of the initial resuscitation of severely ill patients presenting with septic incomplete miscarriages at a tertiary hospital in South Africa.

BACKGROUND: Septic incomplete miscarriages remain a cause of maternal deaths in South Africa. There was an initial decline in mortality when a strict protocol based approach and the Choice of Termination of Pregnancy Act in South Africa were implemented in this country. However, a recent unpublished audit at the Pretoria Academic Complex (Kalafong and Steve Biko Academic Hospitals) suggested that maternal mortality due to this condition is increasing. The objective of this investigation is to do a retrospective audit with the purpose of identifying the reasons for the deteriorating mortality index attributed to septic incomplete miscarriage at Steve Biko Academic Hospital. METHODS: A retrospective audit was performed on all patients who presented to Steve Biko Academic Hospital with a septic incomplete miscarriage from 1(st) January 2008 to 31(st) December 2010. Data regarding patient demographics, initial presentation, resuscitation and disease severity was collected from the "maternal near-miss"/SAMM database and the patient's medical record. The shock index was calculated for each patient retrospectively. RESULTS: There were 38 SAMM and 9 maternal deaths during the study period. In the SAMM group 86.8% and in the maternal death group 77.8% had 2 intravenous lines for resuscitation. There was no significant improvement in the mean blood pressure following resuscitation in the SAMM group (p 0.67), nor in the maternal death group (p 0.883). The shock index before resuscitation was similar in the two groups but improved significantly following resuscitation in the SAMM group (p 0.002). Only 31.6% in the SAMM group and 11.1% in the maternal death group had a complete clinical examination, including a speculum examination of the cervix on admission. No antibiotics were administered to 21.1% in the SAMM group and to 33.3% in the maternal death group. CONCLUSION: The strict protocol management for patients with septic incomplete miscarriage was not adhered to. Physicians should be trained to recognise and react to the seriously ill patient. The use of the shock index in the identification and management of the critically ill pregnant patient needs to be investigated.

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.

Can women determine the success of early medical termination of pregnancy themselves?

OBJECTIVE: To determine the outcome of early medical termination of pregnancy (TOP) among women who choose a "self assessment" follow up comprising a self-performed low sensitivity urine pregnancy test with instructions on signs/symptoms that mandate contacting the TOP service. STUDY DESIGN: A retrospective review of computer databases of 1726 women choosing self-assessment after early medical TOP (<9 weeks) in the UK. The main outcome measures were (a) number of women choosing self-assessment, (b) contact rates with TOP service and (c) time to presentation with an ongoing pregnancy (failed TOP). RESULTS: Ninety-six percent of women having an early medical TOP and going home to expel the pregnancy chose self-assessment. Two percent of women made unscheduled visits to the TOP service. One hundred and eighty-eight women (11%) telephoned the service about concerns related to complications or the success of treatment. There were eight ongoing pregnancies (0.5%; 95% confidence interval 0.2-0.9%). Four were detected within 4 weeks of treatment; the remainder were not detected until one or more missed menses after the procedure. CONCLUSIONS: Most women having an early medical TOP, who go home to expel the pregnancy, choose self-assessment. Relatively few women make unscheduled visits or telephone the TOP service. Most ongoing pregnancies are recognized at an early stage, although late presentation (as with all methods of follow up) does still occur. IMPLICATIONS STATEMENT: If women are given clear instructions on how and when to conduct a urine pregnancy test and on signs/symptoms that mandate contacting the TOP service, then they can confirm the success of early medical TOP themselves. Late presentation due to failure to recognize an ongoing pregnancy is rare.

Acceptability and feasibility of phone follow-up with a semiquantitative urine pregnancy test after medical abortion in Moldova and Uzbekistan.

OBJECTIVE: To evaluate the feasibility and acceptability of phone follow-up with a home semiquantitative pregnancy test and standardized checklist, and compare the alternative method of follow-up with in-clinic follow-up after medical abortion. STUDY DESIGN: Two thousand four hundred women undergoing medical abortion with mifepristone and misoprostol in Moldova and Uzbekistan were randomized to phone or clinic follow-up. All women in the clinic group returned to the clinic 2 weeks later. Women randomized to phone follow-up used a semiquantitative pregnancy test at the initial visit and repeated the test at home 2 weeks later when they also filled out a symptom checklist. Women were called at 2 weeks to review the test results and checklist. Participants who screened "positive" were referred to clinic to verify abortion completion. RESULTS: Most women in the phone group were successfully contacted on the phone (97.6%). Staff were unable to contact one woman in the phone follow-up group, and all women in clinic group returned to the clinic. The ongoing pregnancy rate was similar in both groups (0.4-0.6%), and the semiquantitative pregnancy test identified all ongoing pregnancies in the phone follow-up group. Women in the phone group found the test and checklist easy to use, and most (76.1%) preferred phone follow-up in the future. Overall, 92.8% of women in the phone group did not undergo in-clinic follow-up. CONCLUSION: Phone follow-up with a semiquantitative urine pregnancy test and symptom checklist is a feasible and a highly effective approach in identifying ongoing pregnancy after medical abortion. IMPLICATIONS: The semiquantitative pregnancy test can make home follow-up after medical abortion possible for many women and provide reassurance that ongoing pregnancies will be detected.

Iatrogenic uterine perforation with abdominal extrusion of fetal parts: a rare radiological diagnosis.

BACKGROUND: Failure to detect uterine perforation during surgical abortion may result in adverse patient outcome besides having medicolegal implications. This rare case of uterine perforation was diagnosed seven days after abortion and underscores the importance of remaining vigilant for this complication during and after the procedure. CASE: A female underwent surgical abortion at sixteen weeks gestation and was discharged after the procedure, assuming no complication. She presented with abdominal pain seven days after the event. Ultrasound and CT revealed uterine perforation with abdominal expulsion of fetal parts. CONCLUSION: A patient complaining of abdominal pain following recent abortion related instrumentation should alert the clinician regarding possibility of perforation. Secondary signs on ultrasound may reveal the diagnosis even if rent is not identified. CT is valuable in emergent situations.

A trial of expectant management in incomplete miscarriage.

INTRODUCTION: Incomplete miscarriage is often treated with surgical evacuation in Sri Lanka. Expectant management, which is an alternative treatment, was assessed for efficacy and safety in a local setting. METHODS: Randomised clinical trial of two treatment groups of expectant and surgical management with 71 and 69 participants, respectively, was done at the University Gynaecology Unit of the Colombo North Teaching Hospital, Ragama, from December 2007 to July 2009. Women with incomplete miscarriage at a period of amenorrhoea of < 14 weeks and retained products of conception of < 50mm were included. Expectant management involved in-ward treatment till resolution of heavy bleeding and pain and follow up for two weeks. In surgical treatment, evacuation was undertaken and the patient sent home from hospital after bleeding settled with follow up. The maximum anteroposterior diameter of the endometrial cavity was measured with transvaginal ultrasonography and a diameter < 15mm was considered as complete miscarriage. RESULTS: Expectant management had a treatment success of 90.1% at one week and 94.4% at two weeks. For surgical treatment this was 95.7%. Infection was noted in one subject from the surgical group and none in the expectant group. Fall in the haemoglobin concentration in the two groups was clinically not significant. The expectantly managed group had a shorter hospital stay than the surgically managed group (1.58 vs 2.57 days, p = 0.008). CONCLUSIONS: Expectant management is an effective and safe alternative to surgical evacuation in management of incomplete miscarriage in the local setting. It relieves the burden on the healthcare provider by shortening the hospital stay and avoiding the need for evacuation of retained products of conception under anaesthesia.