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The thyroid is a gland located in the neck and is important for many processes in the body. Problems with the thyroid gland are common in women of reproductive age. It is essential to have a normal working thyroid gland in order to achieve a successful pregnancy. One of the most common problems with the thyroid is underactivity (known as hypothyroidism). An early, mild form of an underactive thyroid is called subclinical hypothyroidism. Often people with this condition do not have any symptoms. Another common problem is thyroid autoimmunity. Here, the immune system attacks the thyroid gland, sometimes leading to the development of abnormal thyroid function. This can be diagnosed by the presence of proteins in the bloodstream called antibodies. Mild thyroid problems and the presence of high levels of thyroid antibodies have been linked to miscarriage and premature birth. There is debate in medicine about whether there should be routine testing of thyroid function both in the general population and in individuals who are trying for a baby. In addition, the strategies used to manage certain thyroid problems are questioned. Discussions around testing and subsequent management particularly relate to women with a history of subfertility or repeated miscarriages. This Scientific Impact Paper provides information on thyroid testing and the management of mild thyroid problems and thyroid antibodies in women with a history of subfertility or recurrent miscarriages, using the latest evidence and guidelines. It concludes that there may be a role for treating these women with thyroxine tablets (the hormone produced by the thyroid gland) when subclinical hypothyroidism is present, and gives guidance on the cut-off levels for treatment., (© 2022 Royal College of Obstetricians and Gynaecologists.)

Background: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy., Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data., Results: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups., Conclusions: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes., Objectives: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions., Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search)., Review Methods: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions., Results: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI -0.92 to -0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate -0.10 kg, 95% CI -0.14 to -0.06 kg) and multiparity (summary estimate -0.73 kg, 95% CI -1.24 to -0.23 kg)., Limitations: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies., Conclusion: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes., Future Work: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation., Study Registration: This study is registered as PROSPERO CRD42013003804., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Most maternal deaths are preventable with emergency obstetric care; therefore, ensuring access is essential. There is little focused information on emergency transport of pregnant women., Objectives: The literature on emergency transport of pregnant women in low- and middle-income countries (LMICs) was systematically reviewed and synthesized to explore current practices, barriers, and facilitators for transport utilization., Search Strategy: MEDLINE, EMBASE, BNI, Cochrane Library, CINAHL, African Index Medicus, ASSIA, QUALIDATA, RHL, and Science Citation Index (inception to April 2012) were searched without language restriction., Selection Criteria: Studies using qualitative methodology and reporting on emergency transportation in LMICs were included., Data Collection and Analysis: Thematic framework and synthesis through examination and translation of common elements were used to analyze and synthesize the data., Main Results: Twenty-nine articles were included. Eight major themes were identified: time for transport; transport options; geography; local support; autonomy; culture; finance; and ergonomics. Key issues were transport availability; transport speed; terrain; meteorology; support; dependence for decision making; cultural issues; cost; and lack of safe, comfortable positioning during transport., Conclusion: Themes should be appreciated within local contexts to illuminate barriers and facilitators. Potential solutions include motorcycle ambulance programs, collaboration with taxi services, community education, subsidies, and vehicle maintenance., (Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies., Methods: We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standards., Results: Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission., Conclusion: Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia.

Background: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high‐risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. Objectives: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. Search strategy: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. Selection criteria: We included placebo‐controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. Data collection and analysis: We extracted absolute event numbers for HDP and pre‐eclampsia in women receiving vaginal progesterone or placebo, and meta‐analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. Main results: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53–0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate‐certainty evidence) and pre‐eclampsia (RR 0.61, 95% CI 0.41–0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate‐certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67–2.12, 3 RCTs, n = 1602 women, I2 = 9%; low‐certainty evidence) or pre‐eclampsia (RR 0.97, 95% CI 0.71–1.31, 5 RCTs, n = 4274 women, I2 = 0%; low‐certainty evidence). Conclusions: Our systematic review found first‐trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance.Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit.Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes.Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units. [ABSTRACT FROM AUTHOR]

Background: Early reproductive failure is the most common complication of pregnancy with only 30% of conceptions reaching live birth. Establishing a successful pregnancy depends upon implantation, a complex process involving interactions between the endometrium and the blastocyst. It is estimated that embryos account for one-third of implantation failures, while suboptimal endometrial receptivity and altered embryo-endometrial dialogue are responsible for the remaining two-thirds. Endometrial receptivity has been the focus of extensive research for over 80 years, leading to an indepth understanding of the processes associated with embryo-endometrial cross-talk and implantation. However, little progress has been achieved to translate this understanding into clinically meaningful prognostic tests and treatments for suboptimal endometrial receptivity.Objective and Rationale: The objective of this systematic review was to examine the evidence from observational studies supporting the use of endometrial receptivity markers as prognostic factors for pregnancy outcome in women wishing to conceive, in order to aid clinicians in choosing the most useful marker in clinical practice and for informing further research.Search Methods: The review protocol was registered with PROSPERO (CRD42017077891). MEDLINE and Embase were searched for observational studies published from inception until 26 February 2018. We included studies that measured potential markers of endometrial receptivity prior to pregnancy attempts and reported the subsequent pregnancy outcomes. We performed association and accuracy analyses using clinical pregnancy as an outcome to reflect the presence of receptive endometrium. The Newcastle-Ottawa scale for observational studies was employed to assess the quality of the included studies.Outcomes: We included 163 studies (88 834 women) of moderate overall quality in the narrative synthesis, out of which 96 were included in the meta-analyses. Studies reported on various endometrial receptivity markers evaluated by ultrasound, endometrial biopsy, endometrial fluid aspirate and hysteroscopy in the context of natural conception, IUI and IVF. Associations were identified between clinical pregnancy and various endometrial receptivity markers (endometrial thickness, endometrial pattern, Doppler indices, endometrial wave-like activity and various molecules); however, their poor ability to predict clinical pregnancy prevents them from being used in clinical practice. Results from several modern molecular tests are promising and further data are awaited.Wider Implications: The post-test probabilities from our analyses may be used in clinical practice to manage couples' expectations during fertility treatments (IUI and IVF). Conventionally, endometrial receptivity is seen as a dichotomous outcome (present or absent), but we propose that various levels of endometrial receptivity exist within the window of implantation. For instance, different transcriptomic signatures could represent varying levels of endometrial receptivity, which can be linked to different pregnancy outcomes. Many studies reported the means of a particular biomarker in those who achieved a pregnancy compared with those who did not. However, extreme values of a biomarker (as opposite to the means) may have significant prognostic and diagnostic implications that are not captured in the means. Therefore, we suggest reporting the outcomes by categories of biomarker levels rather than reporting means of biomarker levels within clinical outcome groups. [ABSTRACT FROM AUTHOR]

Background: A large number of studies have shown an association between inherited thrombophilia and recurrent miscarriage. It has been hypothesized that anticoagulant therapy might reduce the number of miscarriages and stillbirth in these women. In the absence of randomized controlled trials evaluating the efficacy of anticoagulant therapy in women with inherited thrombophilia and recurrent miscarriage, a randomized trial with adequate power that addresses this question is needed. The objective of the ALIFE2 study is therefore to evaluate the efficacy of low-molecular-weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage, with live birth as the primary outcome. Methods/Design: Randomized study of LMWH plus standard pregnancy surveillance versus standard pregnancy surveillance alone. Study population: pregnant women of less than 7 weeks' gestation, and confirmed inherited thrombophilia with a history of 2 or more miscarriages or intra-uterine fetal deaths, or both. Setting: multi-center study in centers from the Dutch Consortium of Fertility studies; centers outside the Netherlands are currently preparing to participate. Intervention: LMWH enoxaparin 40 mg subcutaneously once daily started prior to 7 weeks gestational age plus standard pregnancy surveillance or standard pregnancy surveillance alone. Main study parameters/endpoints: the primary efficacy outcome is live birth. Secondary efficacy outcomes include adverse pregnancy outcomes, such as miscarriage, pre-eclampsia, syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP syndrome), fetal growth restriction, placental abruption, premature delivery and congenital malformations. Safety outcomes include bleeding episodes, thrombocytopenia and skin reactions. Discussion: After an initial period of slow recruitment, the recruitment rate for the study has increased. Improved awareness of the study and acknowledgement of the need for evidence are thought to be contributing to the improved recruitment rates. We aim to increase the number of recruiting centers in order to increase enrollment into the ALIFE2 study. The study website can be accessed via www.ALIFE2study.org. Trial registration: The ALIFE2 study was registered on 19 March 2012 under registration number NTR3361 [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. Design: Randomized controlled trial. Setting: Tertiary referral fertility units. Patient(s): Women with previous poor ovarian response undergoing IVF. Intervention(s): One hundred eleven women were randomized to the long GnRH agonist, short agonist, and antagonist regimens. Main Outcome Measure(s): The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching ET, and clinical and ongoing pregnancy rates. Result(s): Number of oocytes retrieved was significantly higher with long GnRH agonist compared with the short agonist regimen (4.42 ± 3.06 vs. 2.71 ± 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 ± 3.06 vs. 3.30 ± 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1% with long and short agonist regimens and 16.2% with the antagonist regimen. Conclusion(s): Long GnRH agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved. [ABSTRACT FROM AUTHOR]

BACKGROUND: The influence of fibroids on fertility is poorly understood. Submucosal and intramural fibroids that distort the endometrial cavity have been associated with decreased pregnancy rates (PRs) following IVF treatment. However, there is uncertainty about the effect of intramural fibroids that do not distort the endometrial cavity on IVF outcomes. [ABSTRACT FROM PUBLISHER]

Background: Pre-eclampsia is associated with several complications. Early prediction of complications and timely management is needed for clinical care of these patients to avert fetal and maternal mortality and morbidity. There is a need to identify best testing strategies in pre eclampsia to identify the women at increased risk of complications. We aim to determine the accuracy of various tests to predict complications of pre-eclampsia by systematic quantitative reviews. Method: We performed extensive search in MEDLINE (1951-2004), EMBASE (1974-2004) and also will also include manual searches of bibliographies of primary and review articles. An initial search has revealed 19500 citations. Two reviewers will independently select studies and extract data on study characteristics, quality and accuracy. Accuracy data will be used to construct 2 x 2 tables. Data synthesis will involve assessment for heterogeneity and appropriately pooling of results to produce summary Receiver Operating Characteristics (ROC) curve and summary likelihood ratios. Discussion: This review will generate predictive information and integrate that with therapeutic effectiveness to determine the absolute benefit and harm of available therapy in reducing complications in women with pre-eclampsia. [ABSTRACT FROM AUTHOR]

The article discusses the launch of the United Kingdom Early Pregnancy Surveillance Service (UKEPSS) in February 14, 2014 which aimed to investigate uncommon disorders in emergency gynaecology and early pregnancy in Great Britain. It states the use of UKEPPS platform in the nationwide collaboration to improve knowledge and provide better care in women. It also mentions the significant of research outputs and improvement in patient care under the healthcare system National Health Service (NHS).

The article discusses various reports published within the issue, including one on the risks off women who have gestational diabetes mellitus to have diabetes in the future and another on the implications of obesity for pregnancy.

Objective: To assess the availability of key resources for the management of maternal sepsis and evaluate the feasibility of implementing the Surviving Sepsis Campaign (SSC) recommendations in Malawi and other low-resource settings.Methods: A cross-sectional study was conducted at health facilities in Malawi, other low-income countries, and lower-middle-income countries during January-March 2016. English-speaking healthcare professionals (e.g. doctors, nurses, midwives, and administrators) completed a questionnaire/online survey to assess the availability of resources for the management of maternal sepsis.Results: Healthcare centers (n=23) and hospitals (n=13) in Malawi showed shortages in the resources for basic monitoring (always available in 5 [21.7%] and 10 [76.9%] facilities, respectively) and basic infrastructure (2 [8.7%] and 7 [53.8%], respectively). The availability of antibiotics varied between Malawian healthcare centers (9 [39.1%]), Malawian hospitals (8 [61.5%]), hospitals in other low-income countries (10/17 [58.8%]), and hospitals in lower-middle-income countries (39/41 [95.1%]). The percentage of SSC recommendations that could be implemented was 33.3% at hospitals in Malawi, 30.3% at hospitals in other low-income countries, and 68.2% at hospitals in lower-middle-income countries.Conclusion: The implementation of existing SSC recommendations is unrealistic in low-income countries because of resource limitations. New maternal sepsis care bundles must be developed that are applicable to low-resource settings. [ABSTRACT FROM AUTHOR]