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.

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.

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.

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.

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.

Expectant management versus elective curettage for the treatment of spontaneous abortion.

OBJECTIVE: To determine whether the amount of intrauterine tissue was prognostic of the risk of complications associated with the management of nonviable pregnancies diagnosed in the first trimester before cervical dilatation (termed here impending abortion) with either expectant observation or elective curettage. DESIGN: Historic cohort study. SETTING: University Infertility Service. PATIENT(S): All women with nonviable pregnancies followed by the Division of Reproductive Endocrinology during a 5-year period. The patients were divided into those with significant intrauterine tissue (gestational sac > 10 mm) and those with minimal intrauterine tissue. INTERVENTION(S): Women either underwent elective curettage or were followed expectantly. MAIN OUTCOME MEASURE(S): Complication rates. RESULT(S): In 89 women with minimal tissue, no complications occurred regardless of treatment mode. In 63 women with significant intrauterine tissue, expectant management resulted in more complications (9/24) than elective curettage (1/39). In the expectant group, complications included missed abortion, septic abortion, and incomplete abortion requiring emergency curettage, with one patient requiring a transfusion. In the curettage group one uterine perforation occurred. CONCLUSION(S): In women with impending abortions and minimal intrauterine tissue, expectant treatment is safe after ectopic pregnancy has been excluded. In patients with significant intrauterine tissue, the risk of complications may be decreased by elective uterine curettage compared with expectant management.

Epidural analgesia in midtrimester abortion.

Epidural analgesia was performed in 78 women with abortion in the midtrimester or pre-term delivery of up to 27 weeks of pregnancy. The patients were divided into three groups. The first group included thirty women with signs of inevitable abortion. The second group comprised of 9 cases of induced abortion and the third one of 39 cases of pre-term delivery. The three groups were statistically evaluated in relation to time of abortion or labor, fetal weight, weeks of pregnancy, parity and patient's age and were consequently compared with 90 women divided into three similar control groups. The effect of the epidural analgesia was satisfactory in all cases in the three experimental groups, and no complications or side-effects were observed. The advantages of the use of epidural analgesia were the diminished psychological reaction to the abortion, the possibility to perform surgical procedures without any additional anesthesia and the reduction in the duration of the abortion or labor. These advantages justified in our opinion the use of the procedure.

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.

The management of first trimester miscarriage by general practitioners in Ireland.

A single shot questionnaire was sent to 500 general practitioners, with 39 per cent valid response, to audit first trimester miscarriage management. With threatened miscarriage 60 per cent were cared for at home (10 per cent of these had ultrasound) and 40 per cent were transferred to hospital. The miscarriage rate was 14 per cent-61.7 per cent had no symptoms (of these 42.2 per cent had a positive pregnancy test), 24.4 per cent had threatened miscarriage with 11.6 per cent incomplete and 2.3 per cent complete. The general practitioner is ideally placed to develop initial clinical management strategies and direct access to ultrasound would be helpful.

[Does the '(Imminent) miscarriage standard of the Dutch College of Family Physicians correspond to the management by gynecologists?]. / Sluit de standaard '(Dreigende) miskraam' van het Nederlands Huisartsen Genootschap aan bij het beleid van gynaecologen?

OBJECTIVE: To determine if the '(Imminent) miscarriage' standard issued by the Dutch College of General Practitioners corresponds to the management by obstetricians. DESIGN: Postal questionnaire. SETTING: Research Centre Primary/Secondary Health Care, Free University Hospital Amsterdam. METHOD: A postal questionnaire was sent in 1994 to all partnerships of obstetricians (n = 122) in the Netherlands about their management in case of an imminent miscarriage. RESULTS: The response rate was 86% (n = 105). Nearly all partnerships (94%) had an agreement about their management in case of an imminent miscarriage, but the individual protocols varied. In case of a miscarriage or an imminent miscarriage 10% and 28% respectively of all partnerships said they would refer the woman to the GP or midwife. Furthermore, 21% of all partnerships said that the GP or midwife could not have an ultrasound scan made themselves, i.e. without referring to the obstetrician. Many respondent knowing the GP standard (64%) did not agree with the guidelines restricting ultrasound scans (39%) or advising expectative management (24%). They thought that an ultrasound scan was essential to diagnosis and that an expectative management would increase the risk of severe blood loss. On the other hand 15% agreed to all the guidelines. CONCLUSION: The management of obstetricians with respect to (imminent) miscarriage is diverse and does not correspond to the guidelines of the '(Imminent) miscarriage' GP standard, notably with respect to the advised expectative management.

[Cause for referral by family physicians and obstetricians in Amsterdam in (threatened) miscarriage as reflected in the guideline '(Threatened) abortion' of the Dutch Society for Family Physicians]. / Verwijsredenen van huisartsen en verloskundigen in Amsterdam bij (dreigende) miskraam gespiegeld aan de standaard '(Dreigende) miskraam' van het Nederlands Huisartsen Genootschap.

OBJECTIVE: To determine the reasons general practitioners (GPs) and midwives have for referring patients with symptoms of imminent miscarriage to hospital and the management in hospital. DESIGN: Prospective and descriptive. SETTING: Research Centre Primary/Secondary Health Care, University Hospital Free University, the "Onze Lieve Vrouwe Gasthuis' hospital, both in Amsterdam, the Netherlands. METHOD: During the period August 1994-February 1995 anamnesis, diagnostics, diagnosis and further management were recorded for all patients who visited the "Onze Lieve Vrouwe Gasthuis' hospital with blood loss and/or pain in the first 16 weeks of gestation. Patients revealed their wishes concerning referral by filling in questionnaires. Their GPs/midwives were asked about the referral motives in a telephone interview. RESULTS: In the hospital 105 patients were recorded; 34% came on their own initiative. In hospital none of the patients with the diagnosis "imminent miscarriage' was referred back to the GP/midwife. Only 59% of the GPs/midwives performed the physical examinations the (imminent) miscarriage guideline of the Dutch College of General Practitioners advises. In 56% of the 32 patients referred there was no reason for referral according to the (imminent) miscarriage guideline. CONCLUSION: The (imminent) miscarriage guideline issued by the Dutch College of General Practitioners was not always followed because patients went to the hospital on their own account, GPs/midwives did not agree with the guideline, patients wanted another policy and obstetricians kept patients in their own care.

[Vaginal bleeding in the first trimester]. / Vaginalblødning i første trimester.

Significant changes in attitudes towards patients with vaginal bleeding during the first trimester of pregnancy are taking place at the moment, and it is with this in mind that the relevant literature dealing with these patients is reviewed. The rate of miscarriage in an asymptomatic population of pregnant women is 2-4%. If vaginal bleeding occurs, about half the fetuses will have no detectable heartbeat by the time symptoms appear and miscarriage is taking place. Of the remainder, where heartbeat is demonstrated, only ten percent will miscarry despite the bleeding. The presence of an intrauterine haematoma will at most have marginal significance for the prognosis. There is no treatment that has a documented effect amongst these patients, which is why hospitalization can no longer be recommended. A possible investigational program is suggested.

[Intrauterine hematoma in threatened abortion]. / Intrauterint haematom ved truende abort.

In order to demonstrate the consequences of intrauterine haematoma demonstrated by ultrasound in hospitalised patients with imminent abortion, the course of pregnancy and delivery in patients with demonstrated intrauterine haematoma and patients in whom intrauterine haematoma could not be demonstrated were compared retrospectively. Intrauterine haematoma was demonstrated in 29% of patients with immiment abortion in The Department of Gynaecology and Obstetrics in Herlev Hospital. Patients with intrauterine haematoma were hospitalised more frequently and for more prolonged periods for imminent abortion and for imminent premature delivery. On the other hand, no differences were found in the frequencies of abortion, the birth weights, gestational age on delivery, number of preterm deliveries, frequencies of Caesarean section and adherent placenta between the two groups. Therapeutic bias may have been the cause of the increased number of days of hospitalisation in patients with intrauterine haematoma demonstrated by ultrasound.

"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.