Progesterone for women with threatened miscarriage (STOP trial): a placebo-controlled randomized clinical trial.

STUDY QUESTION: In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? SUMMARY ANSWER: In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates. WHAT IS KNOWN ALREADY: Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit. STUDY DESIGN, SIZE, DURATION: We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group. MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes. LIMITATIONS, REASONS FOR CAUTION: Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis. WIDER IMPLICATIONS OF THE FINDINGS: We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research. STUDY FUNDING/COMPETING INTEREST(S): Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. TRIAL REGISTRATION NUMBER: ACTRN12611000405910. TRIAL REGISTRATION DATE: 19 April 2011. DATE OF FIRST PATIENT'S ENROLMENT: 06 February 2012.

Timed intercourse for couples trying to conceive.

BACKGROUND: Fertility problems are very common, as subfertility affects about 10% to 15% of couples trying to conceive. There are many factors that may impact a couple's ability to conceive and one of these may be incorrect timing of intercourse. Conception is only possible from approximately five days before up to several hours after ovulation. Therefore, to be effective, intercourse must take place during this fertile period. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile period to increase the likelihood of conception. Whilst timed intercourse may increase conception rates and reduce unnecessary intervention and costs, there may be associated adverse aspects including time consumption and stress. Ovulation prediction methods used for timing intercourse include urinary hormone measurement (luteinizing hormone (LH), estrogen), tracking basal body temperatures, cervical mucus investigation, calendar charting and ultrasonography. This review considered the evidence from randomised controlled trials for the use of timed intercourse on positive pregnancy outcomes. OBJECTIVES: To assess the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive. SEARCH METHODS: We searched the following sources to identify relevant randomised controlled trials, the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, PubMed, LILACS, Web of Knowledge, the World Health Organization (WHO) Clinical Trials Register Platform and ClinicalTrials.gov. Furthermore, we manually searched the references of relevant articles. The search was not restricted by language or publication status. The last search was on 5 August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing timed intercourse versus intercourse without ovulation prediction or comparing different methods of ovulation prediction for timing intercourse against each other in couples trying to conceive. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were cumulative live birth and adverse events (such as quality of life, depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or self-reported pregnancy, not yet confirmed by ultrasound) and time to conception. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included five RCTs (2840 women or couples) comparing timed intercourse versus intercourse without ovulation prediction. Unfortunately one large study (n = 1453) reporting live birth and pregnancy had not published outcome data by randomised group and therefore could not be analysed. Consequently, four RCTs (n = 1387) were included in the meta-analysis. The evidence was of low to very low quality. Main limitations for downgrading the evidence included imprecision, lack of reporting clinically relevant outcomes and the high risk of publication bias.One study reported live birth, but the sample size was too small to draw any relevant conclusions on the effect of timed intercourse (RR 0.75, 95% CI 0.16 to 3.41, 1 RCT, n = 17, very low quality).One study reported stress as an adverse event. There was no evidence of a difference in levels of stress (mean difference 1.98, 95 CI% -0.87 to 4.83, 1 RCT, n = 77, low level evidence). No other studies reported adverse events.Two studies reported clinical pregnancy. There was no evidence of a difference in clinical pregnancy rates (RR 1.10, 95% CI 0.57 to 2.12, 2 RCTs, n = 177, I(2) = 0%, low level evidence). This suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction is assumed to be 16%, the chance of success following timed intercourse would be between 9% and 33%.Four studies reported pregnancy rate (clinical or self-reported pregnancy). Timed intercourse was associated with higher pregnancy rates compared to intercourse without ovulation prediction in couples trying to conceive (RR 1.35, 95% CI 1.06 to 1.71, 4 RCTs, n = 1387, I(2) = 0%, very low level evidence). This suggests that if the chance of a pregnancy following intercourse without ovulation prediction is assumed to be 13%, the chance following timed intercourse would be between 14% and 23%. Subgroup analysis by duration of subfertility showed no difference in effect between couples trying to conceive for < 12 months versus couples trying for ≥ 12 months. One trial reported time to conception data and showed no evidence of a difference in time to conception. AUTHORS' CONCLUSIONS: There are insufficient data available to draw conclusions on the effectiveness of timed intercourse for the outcomes of live birth, adverse events and clinical pregnancy. Timed intercourse may improve pregnancy rates (clinical or self-reported pregnancy, not yet confirmed by ultrasound) compared to intercourse without ovulation prediction. The quality of this evidence is low to very low and therefore findings should be regarded with caution. There is a high risk of publication bias, as one large study remains unpublished 8 years after recruitment finished. Further research is required, reporting clinically relevant outcomes (live birth, clinical pregnancy rates and adverse effects), to determine if timed intercourse is safe and effective in couples trying to conceive.

Mode of birth and early postnatal psychological morbidity.

BACKGROUND: Postnatal depression affects the well-being of women and families. While several studies have shown an association between mode of birth and symptoms of postnatal depression, others have found no relationship. AIMS: To determine whether women who have instrumental or caesarean births report higher levels of poor coping, sleep or appetite disturbance, or relationship difficulties, than women who have vaginal births, at the time of Universal Postnatal Contact (7-10 days post-discharge). MATERIALS AND METHODS: Retrospective cohort study of term, singleton births from 1st January 2013 to 31st December 2013 at a tertiary obstetric facility. Outcomes were compared for 1816 women having vaginal births versus 1205 women having instrumental or caesarean births. RESULTS: When adjusted for confounders, no association could be demonstrated between mode of birth and reporting of any postnatal symptom of psychological morbidity. However, the model did demonstrate an association between reporting of symptoms and nulliparity (aOR 1.69 (1.08-2.63); P = 0.02), as well as having an unplanned pregnancy with a supportive partner (aOR 0.54 (0.29-0.97); P = 0.04). CONCLUSIONS: Mode of birth does not appear to be associated with the reporting of symptoms of psychological morbidity in the early postnatal period. However, these symptoms may be associated with nulliparity and in the context of an unplanned pregnancy, a lack of partner support. These findings highlight the ongoing need for antenatal screening with respect to pregnancy intention and the presence of a social support system, to facilitate the implementation of interventions for women at risk of postnatal depression.

Does preconception care work?

BACKGROUND: To date, there is a lack of evidence to suggest that a systematic and coordinated approach to prepregnancy care might make a difference. AIMS: To evaluate whether women who receive preconception care through a structured approach will be more likely to be healthy around the time of conception compared with women who plan their pregnancy but have not been exposed to preconception care. METHODS: A case control study was undertaken of women who attended the preconception care service and subsequently conceived, received maternity care and gave birth at Mater Health Services Brisbane between January 2010 and January 2013. Pregnancy information and birth outcomes for each woman who attended the service were matched with those of three women who reported that they had planned their pregnancy but did not attend the service. Records were matched for prepregnancy BMI, age, parity, prepregnancy smoking status and number of health conditions. RESULTS: Pregnant women who attended preconception care were more likely to have received adequate peri-conceptual folate, to report being vaccinated against influenza and hepatitis B, to have consulted with a specialist with the specific aim of optimising a pre-existing health condition and to report less weight gain up until booking. Preterm birth and hypertensive disorders of pregnancy were less common amongst women who had attended preconception care, and there were trends towards a decreased incidence of gestational diabetes, LGA and fetal anomalies. CONCLUSION: These preliminary data provide some optimism that a comprehensive preconception care service may positively influence maternal and neonatal outcomes.

Antenatal perineal massage for reducing perineal trauma.

BACKGROUND: Perineal trauma following vaginal birth can be associated with significant short-term and long-term morbidity. Antenatal perineal massage has been proposed as one method of decreasing the incidence of perineal trauma. OBJECTIVES: To assess the effect of antenatal digital perineal massage on the incidence of perineal trauma at birth and subsequent morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (22 October 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 10), PubMed (1966 to October 2012), EMBASE (1980 to October 2012) and reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials evaluating any described method of antenatal digital perineal massage undertaken for at least the last four weeks of pregnancy. DATA COLLECTION AND ANALYSIS: Both review authors independently applied the selection criteria, extracted data from the included studies and assessed study quality. We contacted study authors for additional information. MAIN RESULTS: We included four trials (2497 women) comparing digital perineal massage with control. All were of good quality. Antenatal digital perineal massage was associated with an overall reduction in the incidence of trauma requiring suturing (four trials, 2480 women, risk ratio (RR) 0.91 (95% confidence interval (CI) 0.86 to 0.96), number needed to treat to benefit (NNTB) 15 (10 to 36)) and women practicing perineal massage were less likely to have an episiotomy (four trials, 2480 women, RR 0.84 (95% CI 0.74 to 0.95), NNTB 21 (12 to 75)). These findings were significant for women without previous vaginal birth only. No differences were seen in the incidence of first- or second-degree perineal tears or third-/fourth-degree perineal trauma. Only women who have previously birthed vaginally reported a statistically significant reduction in the incidence of pain at three months postpartum (one trial, 376 women, RR 0.45 (95% CI 0.24 to 0.87) NNTB 13 (7 to 60)). No significant differences were observed in the incidence of instrumental deliveries, sexual satisfaction, or incontinence of urine, faeces or flatus for any women who practised perineal massage compared with those who did not massage. AUTHORS' CONCLUSIONS: Antenatal digital perineal massage reduces the likelihood of perineal trauma (mainly episiotomies) and the reporting of ongoing perineal pain, and is generally well accepted by women. As such, women should be made aware of the likely benefit of perineal massage and provided with information on how to massage.

Dietary supplements for preventing postnatal depression.

BACKGROUND: Postnatal depression is a medical condition that affects many women and the development of their infants. There is a lack of evidence for treatment and prevention strategies that are safe for mothers and infants. Certain dietary deficiencies in a pregnant or postnatal woman's diet may cause postnatal depression. By correcting these deficiencies postnatal depression could be prevented in some women. Specific examples of dietary supplements aimed at preventing postnatal depression include: omega-3 fatty acids, iron, folate, s-adenosyl-L-methionine, cobalamin, pyridoxine, riboflavin, vitamin D and calcium. OBJECTIVES: To assess the benefits of dietary supplements for preventing postnatal depression either in the antenatal period, postnatal period, or both. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). SELECTION CRITERIA: Randomised controlled trials, involving women who were pregnant or who had given birth in the previous six weeks, who were not depressed or taking antidepressants at the commencement of the trials. The trials could use as intervention any dietary supplementation alone or in combination with another treatment compared with any other preventive treatment, or placebo, or standard clinical care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed the risk of bias for the two included studies. Two review authors extracted data and the data were checked for accuracy. MAIN RESULTS: We included two randomised controlled trials.One trial compared oral 100 microgram (µg) selenium yeast tablets with placebo, taken from the first trimester until birth. The trial randomised 179 women but outcome data were only provided for 85 women. Eighty-three women were randomised to each arm of the trial. Sixty-one women completed the selenium arm, 44 of whom completed an Edinburgh Postnatal Depression Scale (EPDS). In the placebo arm, 64 women completed the trial, 41 of whom completed an EPDS. This included study (n = 85) found selenium had an effect on EPDS scores but did not reach statistical significance (P = 0.07). There was a mean difference (MD) of -1.90 (95% confidence interval (CI) -3.92 to 0.12) of the self-reported EPDS completed by participants within eight weeks of delivery. There was a high risk of attrition bias due to a large proportion of women withdrawing from the study or not completing an EPDS. This included study did not report on any of the secondary outcomes of this review.The other trial compared docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) with placebo. The trial randomised 126 women at risk of postpartum depression to three arms: 42 were allocated to EPA, 42 to DHA, and 42 to placebo. Three women in the EPA arm, four in the DHA arm, and one woman in the placebo arm were lost to follow-up. Women who were found to have major depressive disorder, bipolar disorder, current substance abuse or dependence, suicidal ideation or schizophrenia at recruitment were excluded from the study. The women who discontinued the intervention (five in the EPA arm, four in the DHA arm and seven in the placebo arm) were included in the intention-to-treat analysis, while those who were lost to follow-up were not. Women received supplements or placebo from recruitment at a gestational age of 12 to 20 weeks until their final review visit six to eight weeks postpartum. The primary outcome measure was the Beck Depression Inventory (BDI) score at the fifth visit (six to eight weeks postpartum). No benefit was found for EPA-rich fish oil (MD 0.70, 95% CI -1.78 to 3.18) or DHA-rich fish oil supplementation (MD 0.90, 95% CI -1.33 to 3.13) in preventing postpartum depression. No difference was found in the effect on postnatal depression comparing EPA with DHA (MD -0.20, 95% CI -2.61 to 2.21). No benefit or significant effect was found in terms of the secondary outcomes of the presence of major depressive disorder at six to eight weeks postpartum, the number of women who commenced antidepressants, maternal estimated blood loss at delivery or admission of neonates to the neonatal intensive care unit. AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.

Women who miscarry: The effectiveness and clinical utility of the Kessler 10 questionnaire in screening for ongoing psychological distress.

BACKGROUND: Early pregnancy loss has been linked to enduring psychological morbidity. AIMS: This study aimed to investigate the utility of the Kessler 10 (K10) questionnaire as a brief screening instrument to identify women at risk for the development of psychiatric diagnoses three months post-miscarriage. METHOD: Participants were 117 consecutive women presenting at a public hospital emergency department and receiving a diagnosis of miscarriage. MAIN OUTCOME MEASURES: K10 screen for psychological distress and the Structured Clinical Interview for DSM Disorders to determine psychiatric diagnoses. RESULTS: A majority of women (81.2%) experienced elevated levels of distress initially, 24.8% in the very high range. They were not at increased risk of psychiatric diagnoses at three months compared with the general population; however, they were significantly more likely to report subsyndromal symptoms at this time compared with the general population. The baseline K10 score was the only significant predictor of distress at follow-up (r = 0.45, P < 0.001). The receiver operating characteristic curve shows that a cut-off of 14 on the K10 has suitable sensitivity (97%) and specificity (82%) for predicting ongoing psychological distress in women who miscarry. CONCLUSIONS: The K10 is effective in identifying women at risk for ensuring psychological symptoms following miscarriage.

Is that realistic? The development of a realism assessment questionnaire and its application in appraising three simulators for a gynaecology procedure.

INTRODUCTION: There is no standard approach to determining the realism of a simulator, valuable information when planning simulation training. The aim of this research was to design a generic simulator realism questionnaire and investigate the contributions of different elements of simulator design to a user's impression of simulator realism and performance. METHODS: A questionnaire was designed with procedure-specific and non-procedure-specific (global) questions, grouped in subscales related to simulator structure and function. Three intrauterine contraceptive device (IUCD) simulators were selected for comparison. Participants were doctors of varying experience, who performed an IUCD insertion on each of the three models and used the questionnaire to rate the realism and importance of each aspect of the simulators. The questionnaire was evaluated by correlation between procedure-specific and global items and the correlation of these items to overall realism scores. Realism scores for each simulator were compared by Kruskal-Wallis and subsequent between-simulator comparison by Dunn's test. RESULTS: Global question scores were highly related to procedure-specific scores. Comparison revealed global item subscale scores were significantly different across models on each of the nine subscales (P < 0.001). Function items were rated of higher importance than structure items (mean function item importance 5.36 versus mean structure item importance 5.02; P = 0.009). CONCLUSIONS: The designed questionnaire was able to discriminate between the models for perceived simulator realism. Findings from this study may assist simulator design and inform future development of a generic questionnaire for assessing user perceptions of simulator realism.

Evaluation of a Low-Fidelity Surgical Simulator for Large Loop Excision of the Transformation Zone (LLETZ).

INTRODUCTION: Large loop excision of the transformation zone (LLETZ) is a common gynecological treatment for cervical dysplasia but can be challenging to teach. There is no widely adopted simulator for this procedure in Australia, so a new low-fidelity simulator was designed and evaluated. METHOD: A simulator for a LLETZ procedure was developed. Doctors (N = 29), varied in experience level in gynecology at a tertiary hospital, performed a LLETZ procedure using the simulator. The procedures were filmed, and two independent assessors rated the deidentified videos. The assessment involved a checklist (of crucial procedural steps) and global rating scale to evaluate whether the simulator facilitated the demonstration of LLETZ procedure skills. Participants completed a questionnaire evaluating the performance and utility of the simulator to determine participant perceptions of simulator realism and acceptability. RESULTS: The participant questionnaire revealed positive evaluations of realism and acceptability of the simulator. Performance scores were significantly different across experience levels (P < 0.001) with post hoc pairwise comparison between levels confirming significant differences between each group in assessed simulator performance for global rating scale and overall performance scores. The interrater reliability of the assessors was high (0.84). CONCLUSIONS: A low-fidelity simulator for a LLETZ procedure seems to adequately demonstrate procedural performance reflecting doctor experience level. Participant questionnaire responses were positive, supporting further evaluation of the simulator for use in training.

Clinician's Attitudes to the Introduction of Routine Weighing in Pregnancy.

Background. Excessive gestational weight gain poses significant short- and long-term health risks to both mother and baby. Professional bodies and health services increasingly recommend greater attention be paid to weight gain in pregnancy. A large Australian tertiary maternity hospital plans to facilitate the (re)introduction of routine weighing of all women at every antenatal visit. Objective. To identify clinicians' perspectives of barriers and enablers to routinely weighing pregnant women and variations in current practice, knowledge, and attitudes between different staff groups. Method. Forty-four maternity staff from three professional groups were interviewed in four focus groups. Staff included midwives; medical staff; and dietitians. Transcripts underwent qualitative content analysis to identify and examine barriers and enablers to the routine weighing of women throughout pregnancy. Results. While most staff supported routine weighing, various concerns were raised. Issues included access to resources and staff; the ability to provide appropriate counselling and evidence-based interventions; and the impact of weighing on patients and the therapeutic relationship. Conclusion. Many clinicians supported the practice of routine weighing in pregnancy, but barriers were also identified. Implementation strategies will be tailored to the discrete professional groups and will address identified gaps in knowledge, resources, and clinician skills and confidence.

Bakri balloon during cesarean delivery for placenta previa.

OBJECTIVE: To determine if the use of a Bakri balloon at cesarean delivery (CD) for placenta previa is associated with a reduced need for additional surgical or pharmacologic measures and less blood loss than usual practices. METHODS: In a randomized controlled trial, 52 women undergoing CD for placenta previa were randomly allocated 1:1 into an intervention arm (prophylactic Bakri balloon immediately following placental delivery) or a control arm (use of any usual surgical/pharmacologic measures to achieve hemostasis). The primary outcomes were a clinician's decision to undertake further intervention to control bleeding, and the difference between preoperative and postoperative hemoglobin levels. RESULTS: Although fewer women in the intervention group required additional measures to achieve hemostasis during CD, the difference between the groups was not significant (relative risk 0.54; 95% confidence interval, 0.19-1.57). The change in hemoglobin level among women in the intervention arm was also similar to that among controls (2.3g/dL; 95% confidence interval, -4.4 to 8.9). CONCLUSION: The prophylactic use of a Bakri balloon at CD for placenta previa tended to be of benefit, with no evidence of harm or patient dissatisfaction, but the need for additional medical/surgical measures to control blood loss was not significantly reduced. Australian New Zealand Clinical Trials Registry:ACTRN12613000348752.