Buccal misoprostol for treatment of fetal death at 14-28 weeks of pregnancy: a double-blind randomized controlled trial.

OBJECTIVE: To assess whether buccal misoprostol is effective for the treatment of intrauterine fetal death. STUDY DESIGN: This double-blind randomized trial was conducted at five tertiary-level hospitals in the United States and Vietnam. One hundred fifty-three women with an intrauterine fetal death at 14-28 weeks of pregnancy received either 100 mcg buccal misoprostol or 200 mcg buccal misoprostol every 6 h for a maximum of 8 doses. The main outcome measure was the fetal-placental delivery rate within 48 hours of prostaglandin commencement without any additional intervention. RESULTS: Most of the women (140/153) were recruited at the study site in Vietnam. Expulsion of both fetus and placenta within 48 hours of prostaglandin commencement without any additional interventions occurred in 61.8% (47/76) of women receiving misoprostol 100 mcg and 77.9% (60/77) of women receiving misoprostol 200 mcg. The 200 mcg dose was significantly more effective than the 100 mcg dose at expelling the fetus and placenta within 48 h [RR 0.68 (95% CI: 0.50-0.92; p=.03)]. The mean time to expulsion was significantly shorter using the 200 mcg dose (18.5±11.9 h) than the 100 mcg dose (23.9±12.5 h) (p=.02). Most women in both groups found the procedure satisfactory or very satisfactory (100 mcg: 76.7% (56/73); 200 mcg: 89.5% (68/76) [RR 0.86 (95% CI: 0.74-1.00)]. CONCLUSION: Buccal misoprostol is an effective method for medical induction of labor after intrauterine fetal demise. A 200 mcg dose is significantly more effective than 100 mcg for evacuating the uterus within 48h. The treatment is highly acceptable to women. IMPLICATIONS: Administration of 200 mcg buccal misoprostol every six hours is an effective and acceptable method to effect the delivery of a demised fetus at 14-28 weeks that can be feasibly implemented in a wide variety of settings.

Interruption of nonviable pregnancies of 24-28 weeks' gestation using medical methods: release date June 2013 SFP guideline #20133.

The need to interrupt a pregnancy between 24 and 28 weeks of gestation is uncommon and is typically due to fetal demise or lethal anomalies. Nonetheless, treatment options become more limited at these gestations, when access to surgical methods may not be available in many circumstances. The efficacy of misoprostol with or without mifepristone has been well studied in the first and earlier second trimesters of pregnancy, but its use beyond 24 weeks' gestation is less well described. This document attempts to synthesize the existing evidence for the use of misoprostol with or without mifepristone to induce labor for nonviable pregnancies at gestations of 24-28 weeks. The composite evidence suggests that a regimen combining mifepristone and misoprostol may shorten the time to expulsion, though the overall success rates are similar to those seen with misoprostol-only regimens.

Sharing experiences to improve bereavement support and clinical care after stillbirth: report of the 7th annual meeting of the International Stillbirth Alliance.

Stillbirth remains a global health challenge which is greatly affected by social and economic inequality, particularly the availability and quality of maternity care. The International Stillbirth Alliance (ISA) exists to raise awareness of stillbirth and to promote global collaboration in the prevention of stillbirth and provision of appropriate care for parents whose baby is stillborn. The focus of this ISA conference was to share experiences to improve bereavement support and clinical care. These issues, relevant throughout the globe, are not discrete but closely interrelated, with both similarities and differences depending on the specific country and cultural context. Counting stillbirths and understanding the causes of stillbirth are essential not only for providing optimal care and support to parents whose babies die, but also for reducing the future burden of stillbirth. This summary highlights novel work from obstetricians, midwives, psychologists, parents and peer support organizations that was presented at the ISA meeting. It covers topics including the bereavement process, peer support for parents, support and training for staff, evidence for clinical care, and the need for accurate data on stillbirths and perinatal audits. Representatives from the maternity services of the region presented their outcome data and shared their experiences of clinical and bereavement care. Data and developments in practice within stillbirth and bereavement care must be widely disseminated and acted upon by those responsible for maternity care provision, both to prevent stillbirths and to provide high-quality care when they do occur.

Long-term impact of intrauterine fetal death on quality of life and depression: a case-control study.

BACKGROUND: Intrauterine fetal death (IUFD) is a serious incidence that has been shown to impact mothers' psychological well-being in the short-term. Long-term quality of life (QOL) and depression after IUFD is not known. This study aimed to determine the association between intrauterine fetal death and long-term QOL, well-being, and depression. METHODS: Analyses were performed on collected data among 106 women with a history of intrauterine fetal death (IUFD) and 262 women with live births, 5-18 years after the event. Univariable and multivariable linear and logistic regression models were used to quantify the association between previous fetal death and long-term QOL, well-being and depression. QOL was assessed using the QOL Index (QLI), symptoms of depression using the Center for Epidemiological Studies Depression Scale (CES-D), and subjective well-being using the General Health Questionnaire 20 (GHQ-20). RESULTS: More of the cases had characteristics associated with lower socioeconomic status and did not rate their health as good as did the controls. The QLI health and functioning subscale score was slightly but significantly lower in the cases than in the controls (22.3. vs 23.5, P = .023). The CES-D depressed affect subscale score (2.0 vs 1.0, P = 0.004) and the CES-D global score (7.4 vs 5.0, P = .017) were higher in the cases. Subjective well-being did not differ between groups (20.6 vs 19.4, P = .094). After adjusting for demographic and health-related variables, IUFD was not associated with global QOL (P = .674), subjective well-being (P = .700), or global depression score (adjusted odds ratio = 0.77, 95% confidence interval 0.37-1.57). CONCLUSIONS: Women with previous IUFD, of which the majority have received short-term interventions, share the same level of long-term QOL, well-being and global depression as women with live births only, when adjusted for possible confounders. TRIAL REGISTRATION: The study was registered at http://www.clinicaltrials.gov, with registration number NCT 00856076.

Management of fetal death with placenta previa.

Management of second- and third-trimester fetal death in the presence of placenta previa is a dilemma for obstetricians. We herein describe a case of fetal death occurring at 23 weeks' gestation in the presence of placenta previa. Three weeks of expectant management failed to reduce uteroplacental blood perfusion evaluated with pulsatility index of the uterine artery. Labor was then induced with gemeprost vaginal pessary following overnight laminaria pretreatment. Vaginal delivery was achieved with total blood loss of 1900 ml. Homologous blood transfusion was obviated owing to autologous blood that had been stored during the waiting period.

Intra-vaginal use of misoprostol for induction of labour in intrauterine death.

This prospective study was done in the Department of Obstetric & Gynaecology in Mymensingh Medical College & Hospital during the period of February 2006 to January 2007, to assess the efficacy of vaginal misoprostol for induction of labour in intrauterine foetal death cases and to detect any intrapartum or postpartum complications. For this study, 50 cases of IUD were selected among admitted patients who were diagnosed by detailed history, clinical examination and by USG. Fifty microgram of misoprostol was given per vaginally, which was repeated 4 hours interval upto effective uterine contraction to a maximum six doses. All the informations were recorded in a predesigned structured data collection sheet and data had been interpreted through appropriate statistical analysis. In this study, 46% patients were within 18-25 years of age and gestational age between 28-37 weeks was 80%. Regarding causes of IUD, commonest was idiopathic (52%), next was gestational hypertension, pre-eclampsia, impending eclampsia (28%). Most of the patients (80%) had no history of antenatal checkup and belongs to below average socioeconomic status. Most case (64%) had less Bishop's score (<3) & all cases had unfavourable cervix, score <6. Vaginal delivery was 98% and 2% needed caesarean section. Mean induction delivery interval was 11.8 hours. Induction delivery interval was within 6-23 hours and 66% cases needed 2-3 doses of vaginal misoprostol. Complications were found in a minor group of patients. Nausea, vomiting, occurred in 12% of cases. Others were fever (2%), shivering (6%), PPH (4%), chorioamniotitis (2%) etc. Vaginal misoprostol for cervical ripening and labour induction is very effective and shorten the time of induction delivery interval. On the other hand, misoprostol is quite cheap, easy to administer, well tolerability and less side effects.

Low-dose vaginal misoprostol in the management of intrauterine fetal death.

OBJECTIVES: To assess the effectiveness and side effects of vaginal misoprostol (Vagiprost® tablet) termination of second and third trimester pregnancy complicated with intrauterine fetal death (IUFD). DESIGN: A prospective observational cohort study. SETTING: Tanta University Hospital. Patients. The study carried out on 324 women with fetal demise in the second and third trimesters, from January 2008 to December 2009. INTERVENTION: All patients were subjected to history taking, physical examination, and the Bishop Scoring. Application of 25 µg misoprostol in the posterior fornix of the vagina, this was repeated every 4 h over 24 h. We assessed the adverse effects, progress, and outcomes. RESULTS: The success rate was 90% and 45% in women in the third and second trimesters, respectively. The mean induction-termination interval was 8.95 ± 2.63 and 15.3 ± 5.37 h for women in the third and second trimesters, respectively. The induction termination interval correlated negatively with the duration of gestation. Approximately, 90% of second trimester and 55% of third trimester women required oxytocin augmentation. The mean value of total required dose of misoprostol was 166.3 ± 7.5 and 120 ± 28.79 µg for women in the second and third trimesters, respectively. CONCLUSION: Vagiprost appears to be a safe, effective, practical, and inexpensive method for termination of third trimester pregnancy complicated with of IUFD.

Use of misoprostol for pregnancy termination in women with prior classical cesarean delivery: a report of 3 cases.

BACKGROUND: Misoprostol has been used for induction of labor either as a cervical ripening agent or as an abortifacient. Its use in women with previous cesarean births may be associated with an increased risk of uterine rupture. CASE: We describe 3 cases of pregnancy termination between 18 and 24 weeks' gestation in women with previous classical cesarean deliveries. Misoprostol was used successfully in all three cases without complications. CONCLUSION: Judicious use of misoprostol results in successful pregnancy termination in women with previous classical cesarean deliveries without uterine rupture.

Uterine evacuation for second-trimester fetal death and maternal morbidity.

OBJECTIVE: To estimate maternal morbidity associated with uterine evacuation for second-trimester fetal demise compared with that associated with induced second-trimester abortion. METHODS: This retrospective cohort study compared the maternal outcomes of two cohorts: 1) women diagnosed with fetal demise between 14 and 24 weeks who subsequently underwent dilation and evacuation or induction of labor; and 2) women undergoing induced abortion between 14 and 24 weeks by either dilation and evacuation or induction of labor. The primary outcome was major maternal morbidity. Assuming morbidity rates of 11% for fetal demise and 1% for induced second-trimester abortion, 94 patients were needed per group to detect significant difference in maternal morbidity (80% power, 5% alpha). RESULTS: We identified 121 women with fetal demise and 121 women who underwent induced abortion for inclusion. There were no maternal deaths. In crude and adjusted analyses, treatment for fetal demise was not associated with increased maternal morbidity (25 of 121) compared with induced abortion (27 of 121) (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 0.57-2.32). There were more blood transfusions in the fetal demise group (N=7) compared with the induced-abortion group (N=1) (P=.07). Induction of labor was more morbid than dilation and evacuation after adjusting for confounders (OR 5.36; 95% CI 2.46-11.69), primarily as a result of increased odds of infection requiring intravenous antibiotics. Gestational age of 20 weeks or greater was significantly associated with maternal morbidity (OR 2.59; 95% CI 1.39-4.84). CONCLUSION: In the second trimester, uterine evacuation for fetal demise was not significantly associated with maternal morbidity compared with induced abortion. Induction of labor was more morbid than dilation and evacuation as a result of an increased risk of presumed infection. LEVEL OF EVIDENCE: II.

Lupus and pregnancy: integrating clues from the bench and bedside.

Adequate pregnancy care of women with systemic lupus erythematosus (SLE) rests on three pillars: a coordinated medical-obstetrical care, an agreed and well-defined management protocol and a good neonatal unit. Pregnancy should be planned following a preconceptional visit for counselling. Women with severe active disease or a high degree of irreversible damage, such as those with symptomatic pulmonary hypertension, heart failure, severe restrictive pulmonary disease or severe chronic renal failure should best avoid pregnancy. Treatment is based on hydroxychloroquine, low-dose steroids and azathioprine. Patients with antiphospholipid antibodies/syndrome should receive low-dose aspirin +/- low molecular weight heparin. The addition and the dose of heparin depend on the clinical profile of the patient, i.e. a previous history of miscarriage, foetal loss, placental insufficiency or thrombosis. A close surveillance, with monitoring of blood pressure, proteinuria and placental blood flow by Doppler studies helps the early diagnosis and treatment of complications such as preeclampsia and foetal distress. Postpartum follow-up is important.

Uterine artery pseudoaneurysm manifesting as postpartum hemorrhage after uneventful second-trimester pregnancy termination.

Uterine artery pseudoaneurysm is a rare complication mainly of abdominal or interventional delivery that can cause profuse postpartum hemorrhage if unrecognized or inadequately treated. There has been no report of this disorder accompanying uneventful second-trimester pregnancy termination. A primiparous Japanese woman underwent pregnancy termination at 24 weeks' gestation due to fetal death. Gradual dilatation of the cervix followed by administration of vaginal gemeprost led to an uneventful delivery without curettage. After 41 days, profuse vaginal bleeding occurred. Ultrasound revealed a mass within the uterine cavity and color Doppler indicated the presence of high-speed flow within the mass. Selective angiography revealed that the mass was connected to the right uterine artery, from which extravasation was observed. Uterine artery pseudoaneurysm was diagnosed, and we performed successful uterine artery embolization. This is the first report of uterine artery pseudoaneurysm after second-trimester pregnancy termination. Our experience indicates that even after uneventful pregnancy termination, clinicians must remain aware of the possibility of pseudoaneurysm, manifesting as postpartum/post-termination hemorrhage.

Leptospirosis as a cause of intrauterine fetal demise: short report of rare presentation.

We present a rare severe leptospirosis in a patient who presented with fever, jaundice, coagulopathy and intrauterine fetal demise. Possibility of leptospirosis should be kept in an obstetric patient with such clinical profile particularly in endemic areas or if there is recent outbreak of disease.

The use of misoprostol in obstetrics and gynaecology.

Misoprostol, although originally introduced as a therapy for gastric ulcers, is now widely used in reproductive health. For some indications it is now the optimal choice, whilst for others it provides an important alternative, especially in low-resource settings. The optimal dose varies widely from 20 to 600 mcg depending on the indication and gestation. Use of the correct dose is important, too low a dose will be ineffective and overdosage can be dangerous for mother and baby. Evidence-based information about the safest regimens for multiple pregnancy indications are therefore provided in this review.

Arteriovenous malformation of the uterus after a midtrimester loss: a case report.

BACKGROUND: Arteriovenous malformations (AVMs) of the uterus are rare but potentially life-threatening lesions. The typical presentation includes intermittent, heavy and profuse vaginal bleeding, often refractory to medical therapy. CASE: We present the case of a 25-year-old woman presenting 18 months after a 22-week pregnancy loss complicated by a postpartum curettage for retained placenta. The patient's initial symptoms included irregular and extremely heavy vaginal bleeding. Several transfusions of packed red blood cells were required because of severe anemia. On transfer to our institution, evaluation with ultrasound and hysteroscopy revealed a large AVM in the fundus of the uterus, apparently fed by both the right and left uterine arteries. After 2 embolization procedures of the uterine arteries, the patient experienced a recurrence of her symptoms, requiring definitive treatment with a hysterectomy. CONCLUSION: AVMs of the uterus are a rare cause of vaginal bleeding. AVMs should be considered in the differential diagnosis for the patient with bleeding refractory to medical management and a history of prior uterine surgery. Although unsuccessful in our case, uterine artery embolization remains a viable treatment option, particularly in patients wishing to retain their reproductive capacity.

Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review.

BACKGROUND: A systematic review was conducted to compare with other methods, using the best available evidence, the benefits and risks associated with the administration of misoprostol to terminate pregnancy with fetal demise in the second and third trimesters (defined as gestational age of more than 14 weeks). STUDY DESIGN: We assessed all published randomized controlled trials identified from the Cochrane Pregnancy and Childbirth Group Trials Register, MEDLINE, POPLINE, LILACS and CINHAL from 1987 to 2008 comparing misoprostol alone (vaginal, oral or sublingual administration) with placebo or no treatment or any other method of uterine evacuation (including cervical ripening with other prostaglandins administered vaginally or extra-amniotically, oxytocin, as well as mechanical methods of evacuation including extra-amniotic Foley catheter or laminaria placement) in women with diagnosis of intrauterine fetal death in the second and third trimester of pregnancy. We also evaluated the use of misoprostol alone with misoprostol plus other adjuncts such as intravenous oxytocin. Meta-analyses were performed using relative risks (RRs) as the measure of effect size for binary outcomes and weighted mean differences for continuous outcome measures. For all data, 95% confidence intervals (CIs) were also computed. RESULTS: Fourteen studies comparing different interventions were included. The induction regimens varied considerably in the number of applications of medication, dosages and time intervals between doses. The main outcome was uterine evacuation at 48 h. In all studies evaluated, both vaginal and oral misoprostol showed 100% success rate in achieving uterine evacuation at 48 h. We also evaluated the success at achieving uterine evacuation at 24 h. Although the differences were not statistically significant and heterogeneity was observed, vaginal misoprostol was as effective as oral administration, achieving uterine evacuation within 48 h (RR=0.96, 95% CI=0.85 to 1.09). Oral administration was associated with more side effects than vaginal administration. The mean time intervals from induction to delivery were not significantly different between the vaginal and oral treatment groups [-1.97 (95% CI=-3.22 to 0.72)], so that the clinical benefit of oral administration and avoidance of repeated vaginal administration is probably marginal. Vaginal misoprostol alone was less effective in achieving uterine evacuation at 24 h compared with vaginal misoprostol plus oxytocin. However, there was no statistically significant difference (RR=1.00, 95% CI=0.89 to 1.12) in uterine evacuation at 48 h for vaginal misoprostol either with or without oxytocin administration. CONCLUSIONS: Overall, the body of evidence regarding induction of labor and delivery for second and third trimester of pregnancy is limited and the studies vary in methodology and selected outcome measures, making direct comparisons difficult. Vaginal misoprostol was less effective than oral misoprostol for effecting delivery within 24 h, but not within 48 h.

Misoprostol for intrauterine fetal death.

The frequency of intrauterine fetal death (IUFD) with retained fetus varies, but is estimated to occur in 1% of all pregnancies. The vast majority of women will spontaneously labor and deliver within three weeks of the intrauterine death. The complexity in medical management increases significantly when the cervix is unripe or unfavorable, or when the woman develops disseminated intravascular coagulation. Misoprostol regimens for the induction of labor for second and third trimester IUFDs, range from 50 to 400 microg every 3 to 12 h, and are all clinically effective. Nevertheless, the current scientific evidence supports vaginal misoprostol dosages, which are adjusted to gestational age: between 13-17 weeks, 200 microg 6-hourly; between 18-26 weeks, 100 microg 6-hourly; and more than 27 weeks, 25-50 microg 4-hourly. In women with a previous cesarean, lower doses should be used and doubling of doses should not occur. Clinical monitoring should continue after delivery or expulsion because of the risk of postpartum atony and/or placenta retention.

Fusobacterium nucleatum induces fetal death in mice via stimulation of TLR4-mediated placental inflammatory response.

Intrauterine infection plays a pivotal role in preterm birth (PTB) and is characterized by inflammation. Currently, there is no effective therapy available to treat or prevent bacterial-induced PTB. Using Fusobacterium nucleatum, a Gram-negative anaerobe frequently associated with PTB, as a model organism, the mechanism of intrauterine infection was investigated. Previously, it was shown that F. nucleatum induced preterm and term stillbirth in mice. Fusobacterial-induced placental infection was characterized by localized bacterial colonization, inflammation, and necrosis. In this study, F. nucleatum was shown to activate both TLR2 and TLR4 in vitro. In vivo, the fetal death rate was significantly reduced in TLR4-deficient mice (C57BL/6 TLR4(-/-) and C3H/HeJ (TLR4(d/d))), but not in TLR2-deficient mice (C57BL/6 TLR2(-/-)), following F. nucleatum infection. The reduced fetal death in TLR4-deficient mice was accompanied by decreased placental necroinflammatory responses in both C57BL/6 TLR4(-/-) and C3H/HeJ. Decreased bacterial colonization in the placenta was observed in C3H/HeJ, but not in C57BL/6 TLR4(-/-). These results suggest that inflammation, rather than the bacteria per se, was the likely cause of fetal loss. TLR2 did not appear to be critically involved, as no difference in bacterial colonization, inflammation, or necrosis was observed between C57BL/6 and C57BL/6 TLR2(-/-) mice. A synthetic TLR4 antagonist, TLR4A, significantly reduced fusobacterial-induced fetal death and decidual necrosis without affecting the bacterial colonization in the placentas. TLR4A had no bactericidal activity nor did it affect the birth outcome in sham-infected mice. TLR4A could have promise as an anti-inflammatory agent for the treatment or prevention of bacterial-induced preterm birth.