Novel approach using serum progesterone as a triage to guide management of patients with threatened miscarriage: a prospective cohort study.

Threatened miscarriage is a common gynaecological emergency, with up to 25% of women eventually progressing to spontaneous miscarriage. The uncertainty of pregnancy outcomes results in significant anxiety. However, there is currently no acceptable framework for triaging patients presenting with threatened miscarriage. We aim to evaluate the efficacy and safety of a novel clinical protocol using a single serum progesterone level to prognosticate and guide management of patients with threatened miscarriage. 1087 women presenting with threatened miscarriage were enrolled in the study. The primary outcome was spontaneous miscarriage by 16 weeks' gestation. Among the 77.9% (847/1087) of study participants with serum progesterone ≥ 35 nmol/L who were not treated with oral dydrogesterone, the miscarriage rate was 9.6% (81/847). This did not differ significantly from the 8.5% (31/364) miscarriage rate observed in our prior studies; p = 0.566. Among women with serum progesterone < 35 nmol/L who were treated with dydrogesterone, the miscarriage rate was 70.8% (170/240). Our novel clinical triage protocol using a single serum progesterone level allowed both effective risk stratification and a reduction in progestogen use with no significant adverse pregnancy outcomes. This protocol, based on a single serum progesterone cutoff, can be readily adapted for use in other healthcare institutions.

Does acupuncture have a role in the treatment of threatened miscarriage? Findings from a feasibility randomised trial and semi-structured participant interviews.

BACKGROUND: Threatened miscarriage is a common complication of early pregnancy increasing the risk of miscarriage or premature labour. Currently there is limited evidence to recommend any biomedical pharmacological or self-care management, resulting in a 'watchful waiting' approach. The objective of this study was to examine the feasibility of offering acupuncture as a therapeutic treatment for women presenting with threatened miscarriage. METHODS: A mixed methods study involving a randomised controlled trial and semi structured interviews. A pragmatic acupuncture protocol including medical self-care advice was compared to an active control receiving touch intervention and medical self-care advice. Descriptive statistics were used to examine the demographic and baseline characteristics. Endpoints were analysed between groups using a mean t-test and chi-square tests with P < 0.05 considered statistically significant. Dichotomous data was expressed as Risk Ratio with 95 % confidence intervals. Eleven participants were purposively interviewed about their experiences on exiting the trial with interviews analysed using thematic analysis. RESULTS: Forty women were successfully randomised. For women receiving acupuncture there was a statically significant reduction with threatened miscarriage symptoms including bleeding, cramping and back pain compared with the control (p = 0.04). Thematic analysis revealed women were dissatisfied with the medical support and advice received. An overarching theme emerged from the data of 'finding something you can do.' This encompassed the themes: 'they said there was nothing they could do,' 'feeling the benefits' and 'managing while marking time.' CONCLUSION: Acupuncture was a feasible intervention and reduced threatened miscarriage symptoms when compared to a touch intervention. Further research is required to further explore acupuncture use for this common complication and whether it can reduce the incidence of miscarriage. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12610000850077 . Date of registration 12/10/2010. Retrospectively registered, with first participant enrolled 11/10/2012.

[LEFT AND RIGHT UTERINE ARTERY DOPPLER AS EARLY SKREENING TEST OF THREATENED ABORTION OUTCOME.]

Human reproduction entails a fundamental paradox: although critical to the survival of the species, many aspects are inefficient and wastage seems excessive. Only 50-60% of all conceptions advance beyond 20 weeks of gestation. Miscarriage was defined by WHO as a loss of pregnancy before 20 weeks of gestation or weight of baby under 500 gr. Threatened abortion is the first, reversible phase of miscarriage. The pregnancy outcome doesn't always correlate to severe of its cardinal symptoms- vaginal bleeding and abdominal pain. The measure of HHG can't accurately predict the pregnancy outcome. Ultrasound scanning is probably the best single diagnosic and prognostic test in managing cases of threatened abortion. Uterine artery Dopler waveforms analysis in patients with threatened abortion is non-invasive method, which can find pathological signs in the beginning of pregnancy. Development of a molecular biology give an opportunity to find out problems of pregnancy in the process of implantation, a technical progress in ultrasound give a chance to sudy changes in uterine blood flew in early deadlines and to finding new addictions between uterine perfusion and embryo development.

"Well I'm safe because " - acupuncturists managing conflicting treatment recommendations when treating threatened miscarriage: a mixed-methods study.

OBJECTIVE: To explore how contraindications to the use of acupuncture during pregnancy are managed in clinical practice. DESIGN: Acupuncturists' views on their management of threatened miscarriage were sought by using a mixed-methods design involving a self-completed questionnaire and semi-structured interviews. An online survey was distributed through the Australian and New Zealand acupuncture associations requesting practitioners' to access an online link to a questionnaire hosted by Survey Monkey. This questionnaire examined acupuncturist's views on safety and the use of Traditional Chinese Medicine treatment modalities. Descriptive and bivariate statistics were used to analyze data. Thirteen participants were purposefully selected from the survey responses to further explore treatment management. These interviews were recorded via Skype, transcribed, and analyzed by using thematic analysis. RESULTS: Of 370 respondents, 214 (58%) had treated women for threatened miscarriage within the previous year. Approximately half (58%) had treated four or fewer women, while a minority (14%) had treated 15 or more. The use of abdominal and blood invigorating points reflected diverse treatment strategies within acupuncture textbooks. While the majority avoided acupuncture points traditionally cautioned against in pregnancy, 13% would use LI 4, 22% would use SP 6, and 31% would use BL 32. Two safety themes emerged: "Well I'm safe because…justifying diverse approaches" and "A limited knowledge base-sorting it out for yourself," illustrating how practitioners justified safe practice and had difficulty obtaining trustworthy treatment knowledge. CONCLUSION: Practitioners demonstrated interest in treating threatened miscarriage. All practitioners saw themselves as providing safe treatment. Those using historically contraindicated points justified their use on the basis of personal opinion, advice from trusted others, and clinical experience with a small number of women. In treating at-risk pregnancies, these justifications may be inadequate. Further research exploring the views of practitioners who are experienced in this specialized area would inform clinical practice for this common complication of early pregnancy.

Niveles séricos de la progesterona en las gestantes con amenaza de aborto espontáneo y embarazo normal en el Centro Médico Naval CMST / Serum levels of progesterone levels in pregnant women with threatened spontaneous abortion and normal pregnancy at the Medical Center Naval CMST

INTRODUCCION: La progesterona es el principal esteroide secretado por el cuerpo lútea y es vital para el desarrollo de la gestación. Hasta la fecha, en muchas instituciones como el Centro Médico Naval, dan progesterona a toda mujer con amenaza de aborto, sin previa justificación de niveles bajos de progesterona, tampoco existen estudios locales publicados que docén progesterona en la amenaza de aborto espontáneo comparándolo con las que llevan un embarazo normal. MATERIAL y METODOS: Se realizó un estudio transversal-analítico, comparativo en base a la ficha de datos clínicos y de laboratorio de un grupo de gestantes con el diagnóstico clínico de Amenaza de aborto y otro grupo con el diagnóstico de Embarazo normal, atendidas en los servicios de emergencia y consultorios externos del Centro Médico Naval "CMST", con una gestación entre 5 a 13 semanas corroborada por ecografía transvaginal, durante el periodo comprendido entre agosto del 2012 y marzo del 2013. Se seleccionaron los datos de edad, paridad, número de abortos anteriores, progesterona sérica, nivel de hormona gonadotrofina coriónica sub unidad Beta (Beta hCG), y además en el grupo de gestantes con amenaza de aborto se tomó las variables de sangrado por vía vaginal y dolor pélvico. RESULTADOS: Durante el periodo comprendido entre agosto de 2012 a marzo de 2013 se lograron obtener 152 registros válidos para nuestro análisis en ambos grupos; de los cuales 80 (52.6 por ciento) correspondían a gestantes con Amenaza de aborto y 72 (47.4 por ciento) con embarazo Normal. La edad promedio de nuestra población fue 28.3 años, el promedio de la semana de gestación fue 7.6 semanas, el promedio del nivel sérico de progesterona fue 22.9 ng/ml (17.68 y 28.6 ng/ml, del grupo con Amenaza de aborto y embarazo Normal respectivamente). Los porcentajes de niveles séricos de progesterona: <14, entre 14 y 25 y >=25 ng/mI, fueron 42.5 por ciento, 37.5 por ciento y 20 por ciento en las gestantes con amenaza de aborto...

INTRODUCTION: Progesterone is the principal steroid secreted by the corpus luteum and is vital for the development of pregnancy. To date, in many institutions such as the Naval Medical Center, give progesterone to women with threatened abortion, without justification of low progesterone levels, there are no published local studies that measure progesterone in threatened spontaneous abortion compared with that has a normal pregnancy. MATERIALS AND METHODS: We performed a cross-sectional study - analytical, comparative profile based on clinical data and laboratory of a group of pregnant women with the clinical diagnosis of threatened abortion and another group with the diagnosis of normal pregnancy, treated in the emergency services and outpatient Naval Medical Center "CMST" with a gestation from 5 to 13 weeks confirmed by transvaginal ultrasound during the period between August 2012 and March 2013. We selected data on age, parity, number of previous abortions, progesterone serum level of human chorionic gonadotropin Beta subunit (hCG Beta), and also in the group of pregnant women with threatened abortion variables took vaginal bleeding and pelvic pain. RESULTS: During the period from August 2012 to March 2013 were achieved for 152 valid records for our analysis in both groups, of which 80 (52.6 per cent) were pregnant women with threatened abortion and 72 (47.4 per cent) with Pregnancy Normal. The average age of our population was 28.3 years, the average week of gestation was 7.6 weeks, the mean serum progesterone IeveI was 22.9 ng/mI (17.68 and 28.6 ng/mI, the group threatened abortion and pregnancy Normal respectively). The percentages of serum progesterone IeveIs: <14, 14 to 25 and >=25 ng/mI were 42.5 per cent, 37.5 per cent and 20 per cent in pregnant women with threatened abortion, respectiveIy. In pregnant women with normal pregnancy values were 2.8 per cent, 52.8 per cent and 44.4 per cent, respectively. The percentages of progesterone serum IeveIs...

Acupuncture as a therapeutic treatment option for threatened miscarriage.

BACKGROUND: Threatened miscarriage involves vaginal bleeding in a pregnancy that remains viable. This is a common early pregnancy complication with increased risk factors for early pregnancy loss, preterm premature rupture of membranes (PPROM), preterm delivery, low birth weight babies and maternal antepartum haemorrhage. Currently there are no recommended medical treatment options, rather women receive advice that centres on a 'wait and see' approach. For women with a history of unexplained recurrent miscarriage providing supportive care in a subsequent pregnancy improves live birthing outcomes, but the provision of supportive care to women experiencing threatened miscarriage has to date not been examined. DISCUSSION: While it is known that 50-70% of miscarriages occur due to chromosomal abnormalities, the potential for therapeutic intervention amongst the remaining percentage of women remains unknown. Complementary and alternative medicine (CAM) therapies have the potential to provide supportive care for women presenting with threatened miscarriage. Within fertility research, acupuncture demonstrates beneficial hormonal responses with decreased miscarriage rates, raising the possibility acupuncture may promote specific beneficial effects in early pregnancy. With the lack of current medical options for women presenting with threatened miscarriage it is timely to examine the possible treatment benefits of providing CAM therapies such as acupuncture. SUMMARY: Despite vaginal bleeding being a common complication of early pregnancy there is often reluctance from practitioners to discuss with women and medical personal how and why CAM may be beneficial. In this debate article, the physiological processes of early pregnancy together with the concept of providing supportive care and acupuncture are examined. The aim is to raise awareness and promote discussion as to the beneficial role CAM may have for women presenting with threatened miscarriage.

Análisis comparativo de dos protocolos de misoprostol en abortos de segundo trimestre de la gestación / Comparative analysis of two misoprostol protocols in second-trimester pregnancy termination

Objetivo. Comparar el tiempo medio de expulsión de dos protocolos de misoprostol vaginal en abortos de segundo trimestre. Material y métodos. Estudio retrospectivo de 281 casos entre enero de 2000 y diciembre de 2005 (protocolo A: 800mg/24h) y junio de 2007 y diciembre de 2008 (protocolo B: 400mg/4h). Se recogió como variable principal el tiempo de expulsión. Resultados. El tiempo medio de expulsión fue similar para los dos protocolos (19,7h para el A y 17,7h para el B). Tampoco encontramos diferencias significativas en cuanto a las tasas de expulsión a las 12, 24 y 48h. El efecto adverso observado con mayor frecuencia fue la fiebre, siendo más frecuente en el protocolo B. No hubo efectos adversos mayores como rotura uterina o hemorragia severa. Conclusiones. No existen diferencias significativas entre los dos protocolos en cuánto a tiempo medio de expulsión fetal, aunque sí mayor porcentaje de fiebre en el protocolo B (AU)

Objective. To compare the mean induction-expulsion times in two regimens of vaginal misoprostol for second-trimester pregnancy termination. Material and methods. We performed a retrospective study of 281 pregnancies between January 2000 and December 2005 (regimen A: 800mg /24h) and between June 2007 and December 2008 (regimen B: 400mg /4h). Induction-expulsion time was taken as the main outcome. Results. The mean expulsion time was similar in both regimens (19.7h for A and 17.7h for B). No significant differences were found in the expulsion rate at 12, 24 and 48h. The most commonly observed adverse effect was fever, which was more frequent in regimen B. No major adverse effects such as uterine rupture or severe hemorrhage were observed. Conclusions. No significant differences were found between regimens A and B in the mean fetal expulsion time, although fever was more common in regimen B (AU)

Obstetric outcome and cytokine levels in threatened miscarriage.

OBJECTIVES: To evaluate the proportion of women with threatened miscarriage (TM) who proceed to miscarriage in a population of single ethnicity and to investigate prospectively their risk of adverse pregnancy outcome in relationship with the cytokines levels in their circulation. METHODS: We conducted a prospective observational study over a period of 1 year of 94 Maltese women presenting with TM at the same hospital and compared their clinical data with those of 564 age-matched controls from the National Obstetric Information System (NOIS) of Malta. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcomes. A pilot study was carried out, where in subgroups of 10 women with TM (n=10), non-pregnant women (n=12), normal pregnant controls (n=9) and women presenting with missed-miscarriage (n=11), the plasma levels of ß-human chorionic gonadotrophin (ß-hCG), tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin-6 (IL-6), interleukin-10 (IL-10) and TNF-receptors 1 (R1) and 2 (R2) were measured. RESULTS: Of the women presenting with TM, 25 (26.6%) proceeded to complete miscarriage. The TM group had also a significantly higher incidence of antepartum haemorrhage (p<0.005), pre-eclampsia (p<0.05), foetal growth restriction (p<0.05), premature labour (p<0.001) and retained placenta (p<0.005). In the pilot biochemical analysis, significantly (p<0.05) higher levels of TNFα and lower levels of TNFR2 were found in the TM subgroup compared to non-pregnant controls. The ratio TNFα/IL-10 was significantly (p<0.05) higher and the ß-hCG levels was significantly lower (p<0.01) in missed-miscarriage and non-pregnant subgroups than in TM and normal pregnant controls. The IFNγ/1L-10 and IFNγ/1L-6 ratio were significantly (<0.001) different between the four subgroups with the lowest level found in TM. No similar gradient was found for the TNFα/1L-6 ratio. CONCLUSION: Women presenting with TM are at significantly increased risk of adverse pregnancy outcome and the pathophysiology of these conditions involves a change in the Th1/Th2 balance. Changes in levels of cytokines could help to predict and thus prevent the development of some of these complications.

Ameaça de aborto: conduta baseada em evidências / Threatened miscarriage: conduct based on evidences

A ameaça de aborto é definida como sangramento vaginal, geralmente indolor, que ocorre na primeira metade da gravidez com concepto vivo sem dilatação cervical. Muitas intervenções são utilizadas para a ameaça de aborto espontâneo. Quando uma causa específica é identificada, o tratamento direcionado pode reduzir taxas de abortamento. No entanto, na maioria dos casos, a fisiopatologia permanece desconhecida. Intervenções inespecíficas como repouso no leito e ausência de relações sexuais, apesar de comumente aconselhadas pelos médicos, não têm comprovação de benefício. A didrogesterona, um derivado progestínico, parece reduzir o risco de abortamento. Esta revisão mostra a qualidade das evidências científicas e o grau de recomendação das várias condutas para o tratamento da ameaça de aborto, concluindo que ainda é necessário realizar outros ensaios clínicos maiores, placebo-controlados e randomizados sobre o tratamento da ameaça de aborto para definir a eficácia da maioria das intervenções

Threatened miscarriage is defined as a vaginal bleeding, usually painless, which occurs in the first half of viable pregnancy without cervical dilatation. Many interventions are used for threatened and recurrent miscarriage. When a specific cause is identified, directed treatment may reduce miscarriage rates. However, in the majority of cases, the pathophysiology remains unknown. Unspecific interventions, as bed rest and avoidance of sexual intercourse, though commonly advised, are of no proven benefit. Dydrogesterone, a progesterone derivative, may further reduce miscarriage rates. This review shows the scientific evidence and classification quality of several interventions for the treatment of threatened miscarriage. Larger, randomized and controlled trials on the treatment of threatened miscarriage are needed to support the majority of the interventions

Non-surgical interventions for threatened and recurrent miscarriages.

Many surgical and non-surgical interventions are used in the management of threatened and recurrent miscarriages. Evidence-based management of recurrent miscarriages requires investigations into the underlying aetiology. When a specific cause is identified, directed treatment may reduce miscarriage rates. Combined aspirin and heparin for antiphospholipid syndrome, and screening and treatment of bacterial vaginosis between ten and 22 weeks of pregnancy with clindamycin, are the only interventions proven to be useful in randomised controlled trials (RCTs). The use of periconceptional metformin for polycystic ovarian (PCO) syndrome is promising, though data from RCTs are still required. The use of heparin in inherited thrombophilias, bromocriptine in hyperprolactinaemia and luteinising hormone suppression in fertile patients with PCO syndrome are more controversial. In threatened miscarriages, or when no cause is found, treatment becomes empirical. Supportive care may reduce miscarriage rates. Dydrogesterone, a progesterone derivative, may further reduce miscarriage rates. Bed rest and avoidance of sexual intercourse, though commonly advised, are of no proven benefit. Use of uterine relaxing agents, human chorionic gonadotrophin, immunotherapy and vitamins remain controversial in idiopathic recurrent miscarriages.

[Emergency obstetrical care in Benin referral hospitals: 'near miss' patients' views]. / La qualité de prise en charge des urgences obstétricales dans les maternités de référence au Bénin: le point de vue des "Echappées Belles" et leurs attentes.

OBJECTIVE: To evaluate emergency obstetric care and the perceptions and expectations of women who experienced 'near miss' events to improve maternal health in Benin. METHODS: Qualitative survey in seven hospitals at the three referral levels of the health pyramid from July to October 2003. We used two methods: 557 women with near miss events were interviewed in hospital and a standard questionnaire completed; then semi-structured individual interviews were conducted at home with 42 of these 557 women. RESULTS: Provided care, accommodation, facilities, costs and modalities of recovery, hygiene of the premises, dynamism, expertise, social support, behaviours and attitude of staff were the criteria used to express patients' satisfaction. Most women interviewed in hospital were happy with physical access, organization, functioning and environment. However, excessive costs and coercive recovery of the expenses, failure of the referral system, lack of empathy and discrimination of the nursing staff, lack of resources for emergencies, lack of hygiene and comfort of the premises were criticized by the women interviewed at home. CONCLUSION: The current maternal care system fails to effectively deal with obstetric complications. It needs to be better resourced, more easily available, cheaper and take into account the women's needs.

The use of gene therapy tools in reproductive immunology research.

Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus, while still being effective against pathogens. Gene therapy approaches have the potential to treat devastating inherited diseases for which there is a little hope of finding a conventional cure. In reproductive medicine, experimental trials have been made so far only for correcting gene defects in utero. The use of gene therapy for improving pregnancy-rate success or avoiding pregnancy-related diseases i.e. miscarriage or pre-eclampsia, remains a very distant goal with unresolved moral and ethical aspects. However, gene therapy may help determining the role of several genes in supporting fetal growth and/or avoiding its rejection experimentally and might further help to identify new targets of intervention. Gene therapy strategies to avoid fetal rejection may include the transfer and expression of cyto-protective molecules locally at the fetal-placental interface. In addition, the ex-vivo genetic modification of immune cells for tolerance induction is a novel and tempting approach. In this regard, we have confirmed the role of the cyto-protective and immunomodulatory molecule Heme Oxygenase-1 (HO-1), by treating animals undergoing abortion with an adenovirus coding for HO-1. Since the sole application of a control vector did not provoke deleterious effects in pregnancy outcome, we propose the use of experimental gene therapy for unveiling molecular and cellular pathways leading to pregnancy success.

Pregnancy outcome of threatened abortion with subchorionic hematoma: possible benefit of bed-rest?

BACKGROUND: Bleeding in the first trimester of pregnancy is a common phenomenon, associated with early pregnancy loss. In many instances a subchorionic hematoma is found sonographically. OBJECTIVE: To evaluate the possible benefit of bed-rest in women with threatened abortion and sonographically proven subchorionic hematoma, and to examine the possible relationship of duration of vaginal bleeding, hematoma size, and gestational age at diagnosis to pregnancy outcome. METHODS: The study group consisted of 230 women of 2,556 (9%) referred for ultrasound examination because of vaginal bleeding in the first half of pregnancy, who were found to have a subchorionic hematoma in the presence of a singleton live embryo or fetus. All patients were advised bed-rest at home; 200 adhered to this recommendation for the duration of vaginal bleeding (group 1) and 30 continued their usual lifestyle (group 2). All were followed with repeated sonograms at 7 day intervals until bleeding ceased, the subchorionic hematoma disappeared, or abortion occurred. The groups were compared for size of hematoma, duration of bleeding, and gestational age at diagnosis in relation to pregnancy outcome (spontaneous abortion, term or preterm delivery). RESULTS: The first bleeding episode occurred at 12.6 +/- 3.4 weeks of gestation (range 7-20 weeks) and lasted for 28.8 +/- 19.1 days (range 4-72 days). The women who adhered to bed-rest had fewer spontaneous abortions (9.9% vs. 23.3%, P = 0.006) and a higher rate of term pregnancy (89 vs. 70%, P = 0.004) than those who did not. There was no association between duration of vaginal bleeding, hematoma size, or gestational age at diagnosis of subchorionic hematoma and pregnancy outcome. CONCLUSIONS: Fewer spontaneous abortions and a higher rate of term pregnancy were noted in the bed-rest group. However, the lack of randomization and retrospective design of the outcome data collection preclude a definite conclusion. A large prospective randomized study is required to confirm whether bed-rest has a real therapeutic effect.

Reported management of early-pregnancy bleeding and miscarriage by general practitioners in Victoria.

OBJECTIVES: To describe the management of early-pregnancy bleeding and miscarriage reported by general practitioners in Victoria. DESIGN, SETTING, AND PARTICIPANTS: Self-administered, mailed survey of a stratified random sample of GPs in Victoria. Responses weighted by strata to reflect GP population. MAIN OUTCOME MEASURES: Reported management in referral; investigation (especially ultrasound); expectant versus interventional management; and prevention of rhesus iso-immunisation RESULTS: 382 of 621 eligible GPs responded (response rate, 62%). GPs' reported referral was more likely if the patient had painful bleeding (55%) or if the pregnancy was not viable (77%). Ultrasound strongly influenced the assessment of bleeding. Two-thirds of doctors (262/369; 66%) would routinely order ultrasound for painless bleeding, and 328/369 (84%) for painful bleeding. Expectant management was recommended by 15/353 (4%) for incomplete miscarriage with light bleeding and by 6/351 (2%) when bleeding was heavy. Some GPs are uncertain of the indications for anti-D prophylaxis, including instrumentation of the uterus, for which 261/337 (77%) said they would routinely offer anti-D. There was less agreement about anti-D after threatened miscarriage, for which 213/353 (57%) said they offered the injection. CONCLUSIONS: GPs need a working knowledge of the management of early-pregnancy bleeding, and can probably encourage more rational management. There are significant areas where GPs are uncertain, often reflecting uncertainty elsewhere, and some areas where a minority of GPs are not aware of essential requirements.