Repeat induction of labour for post-term pregnancy.

BACKGROUND: A previous post-term pregnancy is thought to influence the gestation of a subsequent pregnancy. Adverse maternal and perinatal outcomes are associated with post-term pregnancy and routine induction of labour by 42+0 weeks is advised to reduce these complications. OBJECTIVE: To determine the recurrence rate of a post-term pregnancy and the need for repeat induction of labour. METHODS: This observational cohort study featured women with a first and second singleton pregnancy, based on data recorded in the Aberdeen Maternity and Neonatal Databank (1986-2012). Term and post-term pregnancies were defined as ≥37+0 - 40+6 and ≥41+0 weeks, respectively. The exposure was a post-term pregnancy and the control a term pregnancy. Logistic regression was used to assess post-term recurrence and repeat induction of labour. RESULTS: The study population consisted of 25,669 women with 33% of the women delivering post-term in their first pregnancy. In these women, the rate of a subsequent post-term pregnancy was 35.7% compared to 18.6% for women with an initial term pregnancy (adjusted odds ratio (aOR) 2.27, 95% confidence interval (CI) 2.11-2.44). Compared to women who had spontaneous term deliveries in both pregnancies, women who were induced post-term in the second pregnancy had increased odds of having been induced post-term in their first pregnancy. The adjusted odds ratio was found to be 6.08 (95% CI 5.30-6.98). CONCLUSIONS: Women with a first post-term pregnancy are less likely to labour spontaneously and more likely to have a second post-term pregnancy with a higher risk of repeat induction of labour, than women who have previously delivered at term. These findings could be useful in the counselling of women with a previous post-term pregnancy. Given that these women are less likely to labour spontaneously, the offer of an elective induction could also be considered to potentially improve maternal and perinatal outcomes.

Pregnancy, prescription medicines and the potential risk of herb-drug interactions: a cross-sectional survey.

BACKGROUND: Pregnant women are routinely prescribed medicines while self-medicating with herbal natural products to treat predominantly pregnancy related conditions. The aim of this study was to assess the potential for herb-drug interactions (HDIs) in pregnant women and to explore possible herb-drug interactions and their potential clinical significance. METHODS: A cross-sectional survey of women during early pregnancy or immediately postpartum in North-East Scotland. Outcome measures included; Prescription medicines use excluding vitamins and potential HDIs assessed using Natural Medicines Comprehensive Database. RESULTS: The survey was completed by 889 respondents (73% response rate). 45.3% (403) reported the use of at least one prescription medicine, excluding vitamins. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). A total of 91 different prescription medicines were reported by respondents using HNPs. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). Thirty-four herb-drug interactions were identified in 23 (12.7%) women with the potential to increase the risk of postpartum haemorrhage, alter maternal haemodynamics, and enhance maternal/fetal CNS depression. Almost all were rated as moderate (93.9%), one as a potentially major (ginger and nifedipine) and only one minor (ondansetron and chamomile). CONCLUSION: Almost half of pregnant women in this study were prescribed medicines excluding vitamins and minerals and almost half of these used HNPs. Potential moderate to severe HDIs were identified in an eighth of the study cohort. Healthcare professionals should be aware that the concurrent use of HNPs and prescription medicines during pregnancy is common and carries potential risks.

Outcomes of pregnancy in women using illegal drugs and in women who smoke cigarettes.

OBJECTIVE: To compare obstetric outcomes in women using illegal drugs with women who smoke cigarettes. DESIGN: Retrospective cohort study. SETTING: Aberdeen, UK. POPULATION: All deliveries in Aberdeen in women using illegal drugs and women who smoked cigarettes during 1997-2007. MATERIAL AND METHODS: The women who used illegal drugs were identified from a database of affected pregnant women in Aberdeen. The Aberdeen Maternity and Neonatal Databank was used to identify women who smoke cigarettes and to obtain pregnancy outcome information. Sociodemographic characteristics, maternal and perinatal outcomes were compared using chi-squared test, independent sample t-test and logistic regression analysis. MAIN OUTCOME MEASURES: Preterm delivery, low birthweight (standardized birthweight score <-2) and admission to the neonatal unit. RESULTS: Of the 561 illegal drug users, 96% were also cigarette smokers. Compared with women who smoke cigarettes with no reported illegal drug use, they were significantly more likely to have a preterm delivery [adjusted odds ratio (aOR) 1.6 (95% confidence interval (CI) 1.3-2.1)], low birthweight baby [aOR 1.9 (95%CI 1.4-2.6)], baby admitted to the neonatal unit [aOR 13.3 (95%CI 10.9-16.3)], deep vein thrombosis [aOR (95%CI 8.8-50.8)] and antepartum hemorrhage [aOR (95%CI 1.2-2.1)]. They were less likely to be at the extremes of age, or to develop pregnancy-induced hypertension [aOR 0.3 (95%CI 0.2-0.4)]. CONCLUSION: Illegal drug use in pregnancy appears to increase the risk of adverse outcomes, over and above that related to cigarette smoking, but appears to be associated with lower prevalence of gestational hypertension.

Risk assessment and decision making about in-labour transfer from rural maternity care: a social judgment and signal detection analysis.

BACKGROUND: The importance of respecting women's wishes to give birth close to their local community is supported by policy in many developed countries. However, persistent concerns about the quality and safety of maternity care in rural communities have been expressed. Safe childbirth in rural communities depends on good risk assessment and decision making as to whether and when the transfer of a woman in labour to an obstetric led unit is required. This is a difficult decision. Wide variation in transfer rates between rural maternity units have been reported suggesting different decision making criteria may be involved; furthermore, rural midwives and family doctors report feeling isolated in making these decisions and that staff in urban centres do not understand the difficulties they face. In order to develop more evidence based decision making strategies greater understanding of the way in which maternity care providers currently make decisions is required. This study aimed to examine how midwives working in urban and rural settings and obstetricians make intrapartum transfer decisions, and describe sources of variation in decision making. METHODS: The study was conducted in three stages. 1. 20 midwives and four obstetricians described factors influencing transfer decisions. 2. Vignettes depicting an intrapartum scenario were developed based on stage one data. 3. Vignettes were presented to 122 midwives and 12 obstetricians who were asked to assess the level of risk in each case and decide whether to transfer or not. Social judgment analysis was used to identify the factors and factor weights used in assessment. Signal detection analysis was used to identify participants' ability to distinguish high and low risk cases and personal decision thresholds. RESULTS: When reviewing the same case information in vignettes midwives in different settings and obstetricians made very similar risk assessments. Despite this, a wide range of transfer decisions were still made, suggesting that the main source of variation in decision making and transfer rates is not in the assessment but the personal decision thresholds of clinicians. CONCLUSIONS: Currently health care practice focuses on supporting or improving decision making through skills training and clinical guidelines. However, these methods alone are unlikely to be effective in improving consistency of decision making.

Changing risk factors for placental abruption: A case crossover study using routinely collected data from Finland, Malta and Aberdeen.

OBJECTIVE: To evaluate the effects of changes in risk factors between the first two pregnancies on the occurrence of placental abruption (PA) in the same woman. METHODS: Routinely collected obstetric data from Aberdeen Maternity and Neonatal Databank, the Maltese National Obstetric Information System and the Finnish Medical Birth Register were aggregated. Records of the first two singleton pregnancies from women who had PA in one pregnancy but not the other, were identified from this pooled dataset. A case-crossover study design was used; cases were pregnancies with abruption and matched controls were pregnancies without abruption in the same woman. Conditional logistic regression was used to investigate changes in risk factors for placental abruption in pregnancies with and without abruption. RESULTS: A total of 2,991 women were included in the study. Of these 1,506 (50.4%) had PA in their first pregnancy and 1,485 (49.6%) in a second pregnancy. Pregnancies complicated by preeclampsia {194 (6.5%) versus 115 (3.8%) adj OR 1.69; (95% CI 1.23-2.33)}, antepartum haemorrhage of unknown origin {556 (18.6%) versus 69 (2.3%) adjOR 27.05; 95% CI 16.61-44.03)} and placenta praevia {80 (2.7%) versus 21 (0.7%) (adjOR 3.05; 95% CI 1.74-5.36)} were associated with PA. Compared to 20 to 25 years, maternal age of 35-39 years {365 (12.2) versus 323 (10.8) (adjOR 1.32; 95% CI 1.01-1.73) and single marital status (adjOR 1.36; 95% CI 1.04-1.76) were independently associated with PA. Maternal smoking, BMI and fetal gender were not associated with PA. CONCLUSION: Advanced maternal age, pregnancies complicated with unexplained bleeding in pregnancy, placenta praevia and preeclampsia were independently associated with a higher risk of placental abruption.

Herbal Medicinal Product Use During Pregnancy and the Postnatal Period: A Systematic Review.

OBJECTIVE: To report the incidence and nature of herbal medicinal products' adverse events and herb-drug interactions used by some pregnant and postnatal women. DATA SOURCES: The Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, the Cochrane Library, MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched from inception until August 2018. METHODS OF STUDY SELECTION: Any studies reporting adverse events, herb-drug interactions or absence thereof associated with herbal medicinal products used during pregnancy or the postnatal period were included. Conference abstracts, pilot studies, and nonhuman studies were excluded. All included studies were critically appraised by two independent reviewers. TABULATION, INTEGRATION AND RESULTS: Database searches retrieved 3,487 citations. After duplicate removal and review of titles, abstracts, and full-text, 115 articles were critically appraised. After excluding irrelevant and low-quality articles, 74 articles were included for data extraction and synthesis. Adverse drug reactions, congenital malformations, fetal growth retardation or herb-drug interactions were the primary study objective reported by 19 of the 74 included studies, 16 cohort studies, one cross-sectional survey, and two randomized controlled trials. A total of 47 herbal medicinal products and 1,067,071 women were included in this review. Use of almond oil was associated with preterm birth (odds ratio 2.09, 95% CI 1.07-4.08), oral raspberry leaf was associated with cesarean delivery (adjusted odds ratio [AOR] 3.47, 95% CI 1.45-8.28); heavy licorice use was associated with early preterm birth by 3.07-fold (95% CI 1.17-8.05). African herbal medicine mwanaphepo was associated with maternal morbidity (AOR 1.28; 95% CI 1.09-1.50), and neonatal death or morbidity. Fourteen studies reported absence of adverse events. Four studies reported herb-drug interactions, but none studied adverse events arising from them. CONCLUSION: The use of herbal medicinal products during pregnancy and the postnatal period should be discouraged until robust evidence of safety is available. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42017081058.

Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer?

BACKGROUND: Initial observational studies and a systematic review published 5 years ago have suggested that obstetric and perinatal outcomes are better in offspring conceived following frozen rather than fresh embryo transfers, with reduced risks of preterm birth, small for gestational age, low birth weight and pre-eclampsia. More recent primary studies are beginning to challenge some of these findings. We therefore conducted an updated systematic review and cumulative meta-analysis to examine if these results have remained consistent over time. OBJECTIVE AND RATIONALE: The aim of this study was to perform a systematic review and cumulative meta-analysis (trend with time) of obstetric and perinatal complications in singleton pregnancies following the transfer of frozen thawed and fresh embryos generated through in-vitro fertilisation. SEARCH METHODS: Data Sources from Medline, EMBASE, Cochrane Central Register of Clinical Trials DARE and CINAHL (1984-2016) were searched using appropriate key words. Observational and randomised studies comparing obstetric and perinatal outcomes in singleton pregnancies conceived through IVF using either fresh or frozen thawed embryos. Two independent reviewers extracted data in 2 × 2 tables and assessed the methodological quality of the relevant studies using CASP scoring. Both aggregated as well as cumulative meta-analysis was done using STATA. OUTCOMES: Twenty-six studies met the inclusion criteria. Singleton babies conceived from frozen thawed embryos were at lower relative risk (RR) of preterm delivery (0.90; 95% CI 0.84-0.97) low birth weight (0.72; 95% CI 0.67-0.77) and small for gestational age (0.61; 95% CI 0.56-0.67) compared to those conceived from fresh embryo transfers, but faced an increased risk (RR) of hypertensive disorders of pregnancy (1.29; 95% CI 1.07-1.56) large for gestational age (1.54; 95% CI 1.48-1.61) and high birth weight (1.85; 95% CI 1.46-2.33). There was no difference in the risk of congenital anomalies and perinatal mortality between the two groups. The direction and magnitude of effect for these outcomes have remained virtually unchanged over time while the degree of precision has improved with the addition of data from newer studies. WIDER IMPLICATIONS: The results of this cumulative meta-analysis confirm that the decreased risks of small for gestational age, low birth weight and preterm delivery and increased risks of large for gestational age and high birth weight associated with pregnancies conceived from frozen embryos have been consistent in terms of direction and magnitude of effect over several years, with increasing precision around the point estimates. Replication in a number of different populations has provided external validity for the results, for outcomes of birth weight and preterm delivery. Meanwhile, caution should be exercised about embarking on a policy of electively freezing all embryos in IVF as there are increased risks for large for gestational age babies and hypertensive disorders of pregnancy. Therefore, elective freezing should ideally be undertaken in specific cases such as ovarian hyperstimulation syndrome, fertility preservation or in the context of randomised trials.

'Asking the Right Question'. A Comparison of Two Approaches to Gathering Data on 'Herbals' Use in Survey Based Studies.

BACKGROUND: Over the last decade academic interest in the prevalence and nature of herbal medicines use by pregnant women has increased significantly. Such data are usually collected by means of an administered questionnaire survey, however a key methodological limitation using this approach is the need to clearly define the scope of 'herbals' to be investigated. The majority of published studies in this area neither define 'herbals' nor provide a detailed checklist naming specific 'herbals' and CAM modalities, which limits inter-study comparison, generalisability and the potential for meta-analyses. The aim of this study was to compare the self-reported use of herbs, herbal medicines and herbal products using two different approaches implemented in succession. METHODS: Cross-sectional questionnaire surveys of women attending for their mid-trimester scan or attending the postnatal unit following live birth at the Royal Aberdeen Maternity Hospital, North-East Scotland. The questionnaire utilised two approaches to collect data on 'herbals' use, a single closed yes/no answer to the question "have you used herbs, herbal medicines and herbal products in the last three months"; and a request to tick which of a list of 40 'herbals' they had used in the same time period. RESULTS: A total of 889 responses were obtained of which 4.3% (38) answered 'yes' to herbal use via the closed question. However, using the checklist 39% (350) of respondents reported the use of one or more specific 'herbals' (p<0.0001). The 312 respondents who reported 'no' to 'herbals' use via the closed question but "yes" via the checklist consumed a total of 20 different 'herbals' (median 1, interquartile range 1-2, range 1-6). CONCLUSIONS: This study demonstrates that the use of a single closed question asking about the use of 'herbals', as frequently reported in published studies, may not yield valid data resulting in a gross underestimation of actual use.

Women's perceptions, expectations and satisfaction with induced labour--a questionnaire-based study.

OBJECTIVES: To evaluate the understanding and expectations of women undergoing labour induction, to assess their actual experience of the process and to compare their satisfaction with labour to those labouring spontaneously. STUDY DESIGN: Four hundred and fifty women at term undergoing induction of labour and cervical ripening with prostaglandinE2 vaginal tablets and 450 women labouring spontaneously were recruited into the study. The induction group were requested to complete a questionnaire prior to the start of their induction process and another questionnaire post-delivery. The post-delivery questionnaire contained two sections, one pertaining to issues to do with the induction and the second with the actual labour process. The spontaneously labouring group was requested to complete a questionnaire post-delivery, which only contained the section pertaining to the actual labour process. The main outcome measures were satisfaction with labour, perception of pain and length of labour between the induced and spontaneous labour groups, and issues that the women might wish changed about their induction. RESULTS: In the induction group, 34.7% were not satisfied with the information they received about the induction prior to the procedure and 27.2% expected to deliver within 12h of the administration of the inducing agent. Post-induction, 40% of the women felt the most important aspect they would like to change about their induction were they to have another one, would be the speed of the induction, 13.6% felt they might wish to take the inducing agent orally, 7% to have fewer vaginal examinations and 9% to have fewer complications. Among the women who returned questionnaires, 26.3% had a caesarean delivery in the induction group and 21.4% in the spontaneous labour group. Significantly more women were satisfied with their labour in the spontaneous labour group 79.5% versus 70.4%, RR 0.89, 95% CI 0.8-0.96, P=0.006). CONCLUSIONS: Labour that is artificially induced does result in lower satisfaction rates as compared to that following spontaneous onset. The longer time delay between the start of the induction and the delivery plays a significant part in this, with the mode of administration of the inducing agent, more vaginal examinations and the increase in caesarean deliveries being perceived as secondary issues. There is a need to improve the information provided to women undergoing labour induction, to counter unrealistic expectations and thereby improve satisfaction.

Use of complementary and alternative medicines during the third trimester.

OBJECTIVE: To estimate the prevalence, indications, and associated factors for complementary and alternative medicine use during the last trimester of pregnancy. METHODS: A questionnaire survey was conducted of women with a live birth (N=700) admitted to the postnatal unit at the Royal Aberdeen Maternity Hospital, northeast Scotland. Outcome measures included: complementary and alternative medicine used; vitamins and minerals used; reasons for complementary and alternative medicine use; independent associated factors for use; views; and experiences. Descriptive and inferential statistical analysis was performed. RESULTS: The response rate was 79.6% of eligible women. Two thirds of respondents (61.4%) reported using complementary and alternative medicine, excluding vitamins and minerals, during the third trimester. Respondents reported using a total of 30 different complementary and alternative medicine modalities, of which oral herbal products were the most common (38% of respondents, 40 different products). The independent associated factors for complementary and alternative medicine use identified were: complementary and alternative medicine use before pregnancy (odds ratio [OR] 4.36, 95% confidence interval [CI] 2.39-7.95, P<.001); a university education (OR 2.41, 95% CI 1.46-4.0, P=.001), and complementary and alternative medicine use by family or friends (OR 2.36, 95% CI 1.61-3.47, P<.001). There was no association with health care professional recommendations. Users were significantly more likely than nonusers to agree that complementary and alternative medicines were safer than prescribed medicines (P=.006), less likely to be associated with side effects (P≤.001), and could interfere with conventional medicines (P≤.001). CONCLUSION: Despite the majority of respondents, and notably users, being uncertain about their safety and effectiveness, complementary and alternative medicine modalities and complementary and alternative medicine products are widely used during the third trimester of pregnancy in this study population. Although prior use was the most significant independent associated factor, the role of family and friends, rather than health professionals, in the decision to use complementary and alternative medicine may be of concern. LEVEL OF EVIDENCE: III.

The curious case of free-floating pelvic cysts.

The case of a healthy 33-year-old woman who underwent an elective caesarean section with incidental finding of small free-floating cysts within the pelvic peritoneum is presented. Gross examination could not identify the specimens. Histopathological investigation was necessary to classify the specimens as benign mesothelial cysts. The patient had no medical or surgical history and no other risk factors. The presented case is particularly interesting as the cysts were non-adherent to any pelvic or abdominal structure, as is commonly described. Similarly, there are few descriptions of mesothelial cyst diagnosis during pregnancy.

Complementary and alternative medicine use during early pregnancy.

OBJECTIVE: To determine the prevalence and explore predictors of Complementary and Alternative Medicine (CAM) use during early pregnancy. STUDY DESIGN: A questionnaire survey of pregnant women (500) attending for mid trimester scan at the maternity services in Grampian, North-East Scotland. Outcome measures included; CAM used; vitamins and minerals used; independent predictors of use; views and experiences. Descriptive and inferential statistical analysis. RESULTS: The response rate was 66%. Two thirds of respondents (63%) reported using CAM, excluding vitamins and minerals, during early pregnancy. Respondents reported using a total of 28 different CAM modalities, of which oral herbal products were the most common (37% of respondents, 25 different products). The independent predictors of CAM use identified were: use by family and friends (OR 4.1, 95% CI 2.3-7.3, p<0.001); ethnicity (non-white British) (OR 3.4, 95% CI 1.8-6.8, p<0.001); and use prior to pregnancy (OR 2.4, 95% CI 1.2-4.8, p=0.014). In comparison to prescribed medicines, most users were uncertain if CAM were safer (63%), more effective (66%), free from possible adverse effects (46%) or drug-CAM interactions (50%). CONCLUSIONS: Despite the majority of respondents being uncertain about their safety and effectiveness, CAM modalities and CAM products are widely used during the early stages of pregnancy in this study population. The role of family and friends rather than health professionals in the decision to use CAM may be of concern and requires further investigation.

Maternal and neonatal outcomes following additional doses of vaginal prostaglandin E2 for induction of labour: a retrospective cohort study.

OBJECTIVE: To assess maternal and neonatal outcomes following the use of additional doses of vaginal prostaglandins (PGE2) above the recommended dose for induction of labour in post-dates pregnancies. STUDY DESIGN: Retrospective cohort study set in Aberdeen Maternity Hospital, Aberdeen, UK. A total of 3514 nulliparous women with labour induced with vaginal PGE2 (3mg tablet or 2mg gel) for a post-dates singleton pregnancy from January 1994 to December 2009 were included. Women receiving≤2 doses of PGE2 were compared with those receiving>2 doses (maximum 5 doses). Binary logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Primary outcomes included mode of delivery, terbutaline use, indication for CS, postpartum haemorrhage, neonatal unit admission, and Apgar score<7. A further analysis was conducted which stratified for number of doses of PGE2 given. RESULTS: Of the 3514 women who met inclusion criteria, 605 (17%) received PGE2 that exceeded the licensed dose. They were more likely to deliver by caesarean section (53.4% vs. 31.8%, OR 2.2, 95% CI 1.8-2.6), have a caesarean section for 'failed' induction of labour (11.4% vs. 1.9%, OR 4.1, 95% CI 1.3-13.2) or lack of progress in labour (37% vs. 17%, OR 2.8, 95% CI 2.3-3.4), but not for fetal concerns (8.2% vs. 8.8% OR 0.9, 95% CI 0.7-1.3). Terbutaline use and postpartum haemorrhage was no more likely (0.7% vs. 0.9% OR 0.6 95% CI 0.3-1.5 and 19.8% vs. 18.9% OR1.01, 95% CI 0.97-1.06 respectively). Apgar score<7 (1.1% vs. 1.3% OR 0.9 95% CI 0.8-1.1) and neonatal unit admission (13.7% vs. 10.7% OR 1.2 95% CI 0.8-1.6) were similar in both groups. CONCLUSION: The use of additional doses of vaginal PGE2 above the recommended dose for induction of labour was not associated with increased maternal or neonatal morbidity and almost half of these women achieved a vaginal delivery.

Complementary and Alternative Medicines Use during Pregnancy: A Systematic Review of Pregnant Women and Healthcare Professional Views and Experiences.

Aims. To undertake a systematic review of the recent (2008-2013) primary literature, describing views and experiences of CAM use during pregnancy by women and healthcare professionals. Method. Medline, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Review Library and Allied, and Complementary Medicine Database were searched. Studies reporting systemic CAM products (homeopathic preparations, herbal medicines, Vitamins and minerals, homeopathy, and special diets) alone or in combination with other nonsystemic CAM modalities (e.g., acupuncture) were included. Results. Database searches retrieved 2,549 citations. Removal of duplicates followed by review of titles and abstracts yielded 32 relevant studies. Twenty-two reported the perspectives of women and their CAM use during pregnancy, while 10 focused on healthcare professionals. The majority of studies had significant flaws in study design and reporting, including a lack of appropriate definitions of CAM and associated modalities, absence of detailed checklists provided to participants, the use of convenience sampling, and a general lack of scientific robustness in terms of data validity and reliability. Conclusion. To permit generalisability of study findings, there is an urgent need to expand the evidence base assessing CAMs use during pregnancy using appropriately designed studies.

Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions. METHODS: Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 × 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I(2) > 50%). RESULTS: There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53). CONCLUSIONS: Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.

Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of obstetric and perinatal complications in singleton pregnancies after the transfer of frozen thawed and fresh embryos generated through IVF. DESIGN: Systematic review. SETTING: Observational studies, comparing obstetric and perinatal outcomes in singleton pregnancies subsequent to frozen thawed ET versus fresh embryo transfer, were included from Medline, EMBASE, Cochrane Central Register of Clinical Trials, DARE, and CINAHL (1984-2012). PATIENT(S): Women undergoing IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Two independent reviewers extracted data and assessed the methodological quality of the relevant studies using critical appraisal skills program scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. Subgroup analysis was performed on matched cohort studies. MAIN OUTCOME MEASURE(S): Antepartum hemorrhage, very preterm birth, preterm birth, small for gestational age, low birth weight, very low birth weight, cesarean section, congenital anomalies, perinatal mortality, and admission to neonatal intensive care unit. RESULT(S): Eleven studies met the inclusion criteria. Singleton pregnancies after the transfer of frozen thawed embryos were associated with better perinatal outcomes compared with those after fresh IVF embryos. The relative risks (RR) and 95% confidence intervals (CI) of antepartum hemorrhage (RR = 0.67, 95% CI 0.55-0.81), preterm birth (RR = 0.84, 95% CI 0.78-0.90), small for gestational age (RR = 0.45, 95% CI 0.30-0.66), low birth weight (RR = 0.69, 95% CI 0.62-0.76), and perinatal mortality (RR = 0.68, 95% CI 0.48-0.96) were lower in women who received frozen embryos. CONCLUSION(S): Although fresh ET is the norm in IVF, results of this systematic review of observational studies suggest that pregnancies arising from the transfer of frozen thawed IVF embryos seem to have better obstetric and perinatal outcomes.

Obstetric outcome in women with threatened miscarriage in the first trimester.

OBJECTIVE: To assess pregnancy outcomes in women with threatened miscarriage in the first trimester. METHODS: This was a retrospective cohort study based on data extracted from the Aberdeen Maternity and Neonatal Databank. Cases included all primigravid women with first-trimester vaginal bleeding who delivered after 24 weeks of gestation between 1976 and 2004. The control group comprised all other women who had first pregnancies during the same period. Data were analyzed by univariate and multivariate statistical methods. RESULTS: Compared with the control group (n = 31,633), women with threatened miscarriage (n = 7,627) were more likely to have antepartum hemorrhage of unknown origin (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.73-2.01). Elective cesarean (OR 1.30, 95% CI 1.14-1.48) and manual removal of placenta (OR 1.40, 95% CI 1.21-1.62) were performed more frequently in these women, who also had a higher risk of preterm delivery (OR 1.56, 95% CI 1.43-1.71) and malpresentation (OR 1.26, 95% CI 1.13-1.40). Threatened miscarriage in the first trimester is required in 112, 112, 17, 85, 32 patients, respectively, for each additional case of manual removal of placenta, elective cesarean, antepartum hemorrhage of unknown origin, malpresentation, and preterm delivery. CONCLUSION: Pregnancies complicated by threatened miscarriage are at a slightly higher risk of obstetric complications and interventions. LEVEL OF EVIDENCE: II-2.

Sublingual misoprostol for the induction of labor at term.

OBJECTIVE: To evaluate the efficacy, safety, and patient acceptability of sublingual misoprostol compared with an equivalent dose administered orally for labor induction at term. STUDY DESIGN: One hundred women with medical or obstetric indications for induction of labor after 37 weeks of gestation and unfavorable cervices were randomized to receive 50 microg of misoprostol either orally or sublingually. The dose was repeated every 4 hours to a maximum of 5 doses if indicated. Previous cesarean delivery was a criteria for exclusion. Our primary outcome measure was the number of patients who went on to have a vaginal delivery within 24 hours of the induction. The need for oxytocin, mode of delivery, number of cesarean deliveries for fetal distress, uterine hyperstimulation rates, and neonatal outcomes were secondary outcome measures. Patient acceptability was assessed by questionnaires completed after delivery. RESULTS: Significantly more patients were delivered of infants within 24 hours (73.8% versus 45.7%; relative risk, 1.6; 95% confidence interval, 1.1 to 2.4) and the induction to delivery intervals were significantly shorter (20 hours versus 28.3 hours; mean difference, 8.3 hours; 95% confidence interval, 1.2 to 15.4) in the sublingual group compared with the oral group. There was 1 case of uterine hyperstimulation in the sublingual group. There were no significant differences in the mode of delivery, interventions for fetal distress, or neonatal outcomes in the 2 groups. The satisfaction rates were 82.5% and 85.7% in the oral and sublingual groups respectively, and 9.5% of patients thought that the sublingual tablets did not dissolve completely. CONCLUSION: There has been no previous report in the literature of misoprostol given sublingually for labor induction. Sublingual misoprostol seems to have better efficacy than oral misoprostol, seems to be acceptable to patients, and is an option to be considered to induce labor at term.

A comparison of two dosage regimens of oral misoprostol for labor induction at term.

METHODS: 251 women with indications for labor induction at term were randomised to receive either 50 or 100 microgs of oral misoprostol, repeated every 4 h to a maximum of 5 doses. Parous women in the higher dose group received 50 microgs as their first dose, subsequent doses being 100 microgs. Women who failed to respond to the 5 doses of misoprostol had the option of having vaginal PGE2 gel. The primary outcome measure was the induction to delivery interval in those who delivered vaginally. Patient satisfaction was assessed by postnatal questionnaire. RESULTS: The induction to vaginal delivery interval, although shorter in the 100 microgs group was not statistically significant (26.8 versus 33.7 h, mean difference 6.9 h, 95% CI 0.4-13). There were, however, more failed inductions with misoprostol in the 50 microgs group (12.7% Vs 4.8%, RR 2.6, 95% CI 1.07-6.5). There were no differences in the modes of delivery, number of caesarean sections for fetal distress or in the neonatal outcomes in the two groups. Most patients, 83% and 92% in the 50 and 100 microgs, respectively, were satisfied with their inductions, and 64% of patients would prefer to have the inducing agent given orally if they were to have another induction. CONCLUSION: Oral misoprostol is effective in inducing labor and seems acceptable to patients. Both the 50 and 100 microgs dose regimens have a reasonable safety profile, but in view of the higher incidence of failed inductions with the 50 microgs dosage, the 100 microgs dose regimen may be the preferred dose regimen.

Oral misoprostol (100 microg) versus vaginal misoprostol (25 microg) in term labor induction: a randomized comparison.

OBJECTIVE: To compare the efficacy of vaginal misoprostol (25 microg) to oral misoprostol (100 microg) in labor induction at term. METHODS: One hundred and one women at term, with indications for labor induction and cervical Bishop's scores of less than 8, were randomly assigned to receive 100 microg of oral misoprostol or 25 microg vaginal misoprostol after random allocation. This could be repeated every 4 h to a maximum of five doses. The number delivering vaginally within 24 h of the induction was the main outcome measure. RESULTS: Of those who delivered vaginally (74.5% in the oral group vs. 72% in the vaginal group), significantly fewer women delivered within 24 h of induction in the oral group (42.1% vs. 72.2%, RR 0.6, 95% CI 0.4-0.9), with more women receiving more than one dose (45.7% vs. 16.7%, RR 2.7, 95% CI 1.2-6.0). More women in the oral group received oxytocin (68.6% vs. 44%, RR 1.6, 95% CI 1.1-2.2), and the induction to delivery interval was shorter in the vaginal group, although this was not statistically significant [28.9 h (SD 20.2) vs. 20.6 h (SD 16.1), mean difference - 8.3 h, 95% CI - 16.8 to 0.2]. There were no differences in the modes of delivery, uterine hyperstimulation rates or in the neonatal outcomes. CONCLUSION: Vaginal misoprostol in its currently recommended dose of 25 microg seems to be more efficacious than the 100 microg oral dose.