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Human Reproduction Update Mar 2019Early reproductive failure is the most common complication of pregnancy with only 30% of conceptions reaching live birth. Establishing a successful pregnancy depends... (Meta-Analysis)
Meta-Analysis
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.
Topics: Biomarkers; Embryo Implantation; Endometrium; Female; Fertility; Fertilization in Vitro; Humans; Hysteroscopy; Live Birth; Observational Studies as Topic; Pregnancy; Pregnancy, Multiple
PubMed: 30624659
DOI: 10.1093/humupd/dmy044 -
BMJ (Clinical Research Ed.) Sep 2016To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified.
DESIGN
Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.
DATA SOURCES
Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.
APPRAISAL AND DATA EXTRACTION
Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.
RESULTS
25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.
CONCLUSIONS
This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013004608.
Topics: Birth Weight; Diabetes, Gestational; Dystocia; Evidence-Based Medicine; Female; Fetal Macrosomia; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27624087
DOI: 10.1136/bmj.i4694 -
PloS One 2017Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications.
OBJECTIVE
To determine the risk of stillbirth and other adverse pregnancy outcomes in women of AMA.
SEARCH STRATEGY
Embase, Medline (Ovid), Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from ≥2000.
SELECTION CRITERIA
Cohort and case-control studies reporting data on one or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or secondary outcomes in mothers ≥35 years and <35 years.
DATA COLLECTION AND ANALYSIS
The effect of age on pregnancy outcome was investigated by random effects meta-analysis and meta-regression. Stillbirth rates were correlated to rates of maternal diabetes, obesity, hypertension and use of assisted reproductive therapies (ART).
MAIN RESULTS
Out of 1940 identified titles; 63 cohort studies and 12 case-control studies were included in the meta-analysis. AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a population attributable risk of 4.7%. Similar trends were seen for risks of FGR, neonatal death, NICU unit admission restriction and GDM. The relationship between AMA and stillbirth was not related to maternal morbidity or ART.
CONCLUSIONS
Stillbirth risk increases with increasing maternal age. This is not wholly explained by maternal co-morbidities and use of ART. We propose that placental dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective studies are needed to directly test this hypothesis.
Topics: Adult; Diabetes, Gestational; Female; Humans; Infant, Newborn; Maternal Age; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Stillbirth
PubMed: 29040334
DOI: 10.1371/journal.pone.0186287 -
The Lancet. Diabetes & Endocrinology Apr 2022Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia.
METHODS
In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585.
FINDINGS
We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT concentrations were not associated with the outcomes measured.
INTERPRETATION
Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies.
FUNDING
Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.
Topics: Female; Humans; Hypertension, Pregnancy-Induced; Hyperthyroidism; Hypothyroidism; Male; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prospective Studies; Thyroid Diseases; Thyrotropin; Thyroxine
PubMed: 35255260
DOI: 10.1016/S2213-8587(22)00007-9 -
Journal of Obstetrics and Gynaecology :... Dec 2023Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that... (Meta-Analysis)
Meta-Analysis
Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that reported adverse pregnancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English language assessing the association between COVID-19 infection and adverse pregnancy outcomes. Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including 1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort and case-control studies. In this meta-analysis, both fixed and random effect models were used. Publication bias was also assessed by Egger's test and the trim and fill method was conducted in case of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled prevalence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with COVID-19 infection was significantly more than those without COVID-19 infection (<.01). A meta-regression was conducted using the income level of countries. COVID-19 infection during pregnancy may cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate and long-term effects on the newborn are unclear.
Topics: Female; Humans; Infant, Newborn; Pregnancy; COVID-19; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; SARS-CoV-2; Maternal Mortality; Intensive Care Units, Neonatal; Patient Admission
PubMed: 36651606
DOI: 10.1080/01443615.2022.2162867 -
Ultrasound in Obstetrics & Gynecology :... Jul 2019Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to...
OBJECTIVE
Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field.
METHODS
MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding.
RESULTS
From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90 centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation.
CONCLUSIONS
This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Mass Screening; Meta-Analysis as Topic; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Prospective Studies; Pulsatile Flow; Risk Factors; Sensitivity and Specificity; Ultrasonography; Uterine Artery
PubMed: 30267475
DOI: 10.1002/uog.20117 -
Fertility and Sterility Mar 2020To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
University obstetrics and gynecology departments.
PATIENT(S)
Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment.
RESULT(S)
After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%-35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43-2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity.
CONCLUSION(S)
Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed.
Topics: Abortion, Habitual; Asymptomatic Diseases; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Diagnosis; Risk Factors; Thyroid Function Tests; Thyroiditis, Autoimmune
PubMed: 32192591
DOI: 10.1016/j.fertnstert.2019.11.003 -
Prenatal Diagnosis Jun 2017With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly... (Review)
Review
With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.
Topics: Chromosome Aberrations; False Negative Reactions; False Positive Reactions; Female; Humans; Maternal Serum Screening Tests; Pregnancy
PubMed: 28382695
DOI: 10.1002/pd.5049 -
JAMA Aug 2019Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent,... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.
OBJECTIVE
To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.
DATA SOURCES AND STUDY SELECTION
Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.
DATA EXTRACTION AND SYNTHESIS
The primary authors provided individual participant data that were analyzed using mixed-effects models.
MAIN OUTCOMES AND MEASURES
The primary outcome was preterm birth (<37 weeks' gestational age).
RESULTS
From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).
CONCLUSIONS AND RELEVANCE
Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Female; Gestational Age; Humans; Hypothyroidism; Infant, Newborn; Iodide Peroxidase; Pregnancy; Pregnancy Complications; Premature Birth; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyroxine
PubMed: 31429897
DOI: 10.1001/jama.2019.10931 -
BJOG : An International Journal of... Jan 2019There is no international consensus on how to manage women with a pregnancy of unknown location (PUL). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no international consensus on how to manage women with a pregnancy of unknown location (PUL).
OBJECTIVES
To present a systematic quantitative review summarising the evidence related to management protocols for PUL.
SEARCH STRATEGY
MEDLINE, COCHRANE and DARE databases were searched from 1 January 1984 to 31 January 2017. The primary outcome was accurate risk prediction of women initially diagnosed with a PUL having an ectopic pregnancy (high risk) as opposed to either a failed PUL or intrauterine pregnancy (low risk).
SELECTION CRITERIA
All studies written in the English language, which were not case reports or series that assessed women classified as having a PUL at initial ultrasound.
DATA COLLECTION AND ANALYSIS
Forty-three studies were included. QUADAS-2 criteria were used to assess the risk of bias. We used a novel, linear mixed-effects model and constructed summary receiver operating characteristic curves for the thresholds of interest.
MAIN RESULTS
There was a high risk of differential verification bias in most studies. Meta-analyses of accuracy were performed on (i) single human chorionic gonadotrophin (hCG) cut-off levels, (ii) hCG ratio (hCG at 48 hours/initial hCG), (iii) single progesterone cut-off levels and (iv) the 'M4 model' (a logistic regression model based on the initial hCG and hCG ratio). For predicting an ectopic pregnancy, the areas under the curves (95% CI) for these four management protocols were as follows: (i) 0.42 (0.00-0.99), (ii) 0.69 (0.57-0.78), (iii) 0.69 (0.54-0.81) and (iv) 0.87 (0.83-0.91), respectively.
CONCLUSIONS
The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of PUL.
TWEETABLE ABSTRACT
Pregnancy of unknown location meta-analysis: M4 model has best test performance to predict ectopic pregnancy.
Topics: Chorionic Gonadotropin; Decision Support Techniques; Female; Humans; Logistic Models; Pregnancy; Pregnancy, Ectopic; Progesterone; ROC Curve; Risk Assessment; Sensitivity and Specificity
PubMed: 30129999
DOI: 10.1111/1471-0528.15442