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Journal of Minimally Invasive Gynecology 2016This systematic review and meta-analysis was performed to compare the efficacy and safety of uterine artery embolization (UAE) followed by curettage and methotrexate... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis was performed to compare the efficacy and safety of uterine artery embolization (UAE) followed by curettage and methotrexate (MTX) plus curettage in the treatment of cesarean scar pregnancy (CSP) in China. Studies published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System), and China National Knowledge Information were systematically searched. The main outcome measures included the time for serum β-human chorionic gonadotropin (β-hCG) normalization, the duration of hospital stay, blood losses, and adverse events. Results were expressed as the weighted mean difference (WMD) or risk ratio with 95% confidence intervals (CIs). Results showed that 11 studies involving a total of 725 patients were included in this meta-analysis. Compared with MTX plus curettage, UAE followed by curettage had 16.76 days less time for β-hCG normalization (WMD = -16.76 days; 95% CI, -24.60 to -8.92; p < .001), and 15.05 days less of hospital stay (WMD = -15.05 days; 95% CI, -25.42 to -4.67; p = .004). CSP patients who underwent UAE had 343.24 mL less blood loss compared with those treated with MTX plus curettage (WMD = -343.24 mL; 95% CI, -432.95 to -253.54; p < .001). Moreover, UAE was associated with a lower incidence of adverse events than those treated with MTX plus curettage (relative risk = 0.46; 95% CI, 0.26-0.81; p = .008). In conclusion, UAE combined with curettage significantly shortened the time for β-hCG normalization and hospital stay and reduced blood losses and adverse events compared with the administration of MTX plus curettage. For patients with CSP, UAE followed by curettage appears to be more advantageous and may be a priority option. Further well-conducted, large-scale trials are needed to validate these findings.
Topics: Abortifacient Agents, Nonsteroidal; Cesarean Section; China; Chorionic Gonadotropin, beta Subunit, Human; Cicatrix; Curettage; Female; Humans; Length of Stay; Methotrexate; Pregnancy; Pregnancy, Ectopic; Uterine Artery Embolization
PubMed: 27553186
DOI: 10.1016/j.jmig.2016.08.819 -
BJOG : An International Journal of... Sep 2016Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing.
OBJECTIVES
To evaluate the screening performance of PSMSUM in detecting DS in Chinese women.
SEARCH STRATEGY
An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc.
SELECTION CRITERIA
Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn.
DATA COLLECTION AND ANALYSIS
Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model.
MAIN RESULTS
Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used.
AUTHOR'S CONCLUSIONS
Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization.
TWEETABLE ABSTRACT
Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women.
Topics: Asian People; Biomarkers; China; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Maternal Age; Maternal Serum Screening Tests; Pregnancy; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis; Ultrasonography; alpha-Fetoproteins
PubMed: 27627591
DOI: 10.1111/1471-0528.14009 -
Fertility and Sterility Nov 2016To study the current literature on the association between IVF treatment and maternal serum screening marker levels and nuchal translucency thickness. (Review)
Review
OBJECTIVE
To study the current literature on the association between IVF treatment and maternal serum screening marker levels and nuchal translucency thickness.
DESIGN
Systematic review.
SETTINGS
Not applicable.
PATIENT(S)
Eligible studies included those with an exposed group of pregnant women that used IVF with or without intracytoplasmic sperm injection to conceive and a control group of pregnant women who conceived spontaneously.
INTERVENTION(S)
IVF treatment to conceive.
MAIN OUTCOME MEASURE(S)
Outcomes evaluated included maternal serum screening markers (pregnancy-associated plasma protein A [PAPP-A], alpha-fetoprotein, hCG, unconjugated estriol, dimeric inhibin-A) and nuchal translucency thickness.
RESULT(S)
Database searches identified 4,118 titles and abstracts that were independently screened, which resulted in 76 articles that were assessed for eligibility. Additionally, one study was added for consideration based on expert knowledge. There were 29 cohort and 11 case-control studies in the descriptive review. The most commonly reported markers were PAPP-A and free β-hCG, which were reported in 28 and 26 studies, respectively. The studies that reported effect sizes for PAPP-A and free β-hCG were not statistically significant.
CONCLUSION(S)
A decrease in PAPP-A and an increase in total hCG was consistently reported among the included studies. However, owing to the variability in the levels of the other maternal serum screening markers reported and the inability to conduct a meta-analysis, we were unable to generalize about the differences between prenatal screening results in the IVF population.
Topics: Biomarkers; Chorionic Gonadotropin; Chromosome Disorders; Estriol; Female; Fertility; Fertilization in Vitro; Humans; Infertility; Inhibins; Nuchal Translucency Measurement; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Reproducibility of Results; Sperm Injections, Intracytoplasmic; Treatment Outcome; alpha-Fetoproteins
PubMed: 27530061
DOI: 10.1016/j.fertnstert.2016.07.1120 -
Annals of the Rheumatic Diseases Mar 2017Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).
EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.
OBJECTIVES
Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).
METHODS
Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.
RESULTS
Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease.
CONCLUSIONS
Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
Topics: Antiphospholipid Syndrome; Contraceptives, Oral, Hormonal; Delphi Technique; Early Detection of Cancer; Estrogen Replacement Therapy; Family Planning Services; Female; Fertility Preservation; Fetal Monitoring; Genital Neoplasms, Female; Humans; Lupus Erythematosus, Systemic; Menopause; Preconception Care; Pregnancy; Pregnancy Complications; Reproductive Techniques, Assisted; Risk Assessment
PubMed: 27457513
DOI: 10.1136/annrheumdis-2016-209770 -
Reproductive Biomedicine Online Sep 2016In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and... (Meta-Analysis)
Meta-Analysis Review
In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence.
Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Humans; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Control Agents
PubMed: 27317131
DOI: 10.1016/j.rbmo.2016.05.010 -
The Cochrane Database of Systematic... May 2016Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction.
OBJECTIVES
To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using GRADE methods.
MAIN RESULTS
Twelve RCTs investigated the effect of intrauterine administration of hCG for 4038 subfertile women undergoing assisted reproduction. The intra-cavity hCG (IC-hCG) was administered in variable doses at different timings before the ET. The source of hCG was from the urine of pregnant women or from cell cultures using recombinant DNA technology.Most of the studies (9/12) were at high risk of bias in at least one of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.For the analyses of live birth and clinical pregnancy, there was considerable heterogeneity (I(2) greater than 75%) and we did not undertake a meta-analysis. Exploration for the sources of heterogeneity identified two key pre-specified variables as important determinants: stage of ET (cleavage versus blastocyst stage) and dose of IC-hCG (less than 500 international units (IU) versus 500 IU or greater). We then performed meta-analysis for these analyses within the subgroups defined by stage of embryo and dose of IC-hCG.There was an increase in live birth rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (risk ratio (RR) 1.57, 95% confidence interval (CI) 1.32 to 1.87, three RCTs, n = 914, I(2) = 0%, moderate quality evidence). In a clinic with a live birth rate of 25% per cycle then the use of IC-hCG -500 IU or greater would be associated with a live birth rate that varies from 33% to 46%. We did not observe a significant effect on live birth in any of the other subgroups.The was an increase in clinical pregnancy rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (RR 1.41, 95% CI 1.25 to 1.58, seven RCTs, n = 1414, I(2) = 0%, moderate quality evidence). We did not observe a significant effect on clinical pregnancy in either of the other subgroups.There was no evidence that miscarriage was influenced by intrauterine hCG administration (RR 1.09, 95% CI 0.83 to 1.43, seven RCTs, n = 3395, I(2) = 0%, very low quality evidence).Other complications reported in the included studies were ectopic pregnancy (three RCTs, n = 915, three events overall), heterotopic pregnancy (one RCT, n = 495, one event), intrauterine death (two RCTs, n = 978, 21 events) and triplets (one RCT, n = 48, three events). There was no evidence of a difference between the groups, but there were too few events to allow any conclusions to be drawn and the evidence was very low quality.
AUTHORS' CONCLUSIONS
The pregnancy outcome for cleavage-stage ETs using an IC-hCG dose of 500 IU or greater is promising. However, given the small size and the variable quality of the trials and the fact that the positive finding was from a subgroup analysis, the current evidence for IC-hCG treatment does not support its use in assisted reproduction cycles. A definitive large clinical trial with live birth as the primary outcome is recommended. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of IC-hCG. There were too few events to allow any conclusions to be drawn with regard to other complications.
Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Humans; Infertility, Female; Live Birth; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Uterus
PubMed: 27195724
DOI: 10.1002/14651858.CD011537.pub2 -
The Cochrane Database of Systematic... Apr 2016For the last few decades urinary human chorionic gonadotrophin (uhCG) has been used to trigger final oocyte maturation in cycles of in vitro fertilization (IVF) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
For the last few decades urinary human chorionic gonadotrophin (uhCG) has been used to trigger final oocyte maturation in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Recombinant technology has allowed the production of two drugs, recombinant human chorionic gonadotrophin (rhCG) and recombinant luteinising hormone (rLH), that can be used for the same purpose, to mimic the endogenous luteinising hormone (LH) surge. This allows commercial manufacturers to adjust production according to market requirements and to remove all urinary contaminants, facilitating the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, it is necessary to compare the effectiveness of the recombinant drugs to the currently used urinary human chorionic gonadotrophin (uhCG).
OBJECTIVES
To assess the effects of subcutaneous rhCG and high dose rLH versus uhCG for inducing final oocyte maturation in subfertile women undergoing IVF and ICSI cycles.
SEARCH METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE (1946 to April 2015), EMBASE (1980 to April 2015) and PsycINFO (1806 to April 2015) as well as trial registers at ClinicalTrials.gov on 13 May 2015 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal on 14 May 2015.
SELECTION CRITERIA
Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. We included randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normogonadotropic women.
DATA COLLECTION AND ANALYSIS
Two authors independently performed assessment for inclusion or exclusion, quality assessment and data extraction. We discussed any discrepancies in the presence of a third author to reach a consensus. The primary review outcomes were ongoing pregnancy/live birth and incidence of ovarian hyperstimulation syndrome (OHSS). Clinical pregnancy, miscarriage rate, number of oocytes retrieved and adverse events were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) and assessed statistical heterogeneity using the I(2) statistic. We evaluated the overall quality of the evidence for the main comparisons using GRADE methods.
MAIN RESULTS
We included 18 RCTs involving 2952 participants; 15 compared rhCG with uhCG, and 3 compared rhLH with uhCG. The evidence for different comparisons ranged from very low to high quality: limitations were poor reporting of study methods and imprecision. Pharmaceutical companies funded 9 of the 18 studies, and 5 studies did not clearly report funding source. Ongoing pregnancy/live birthThere was no conclusive evidence of a difference between rhCG and uhCG (OR 1.15, 95% CI 0.89 to 1.49; 7 RCTs, N = 1136, I(2) = 0%, moderate quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.51 to 1.78, 2 RCTs, N = 289, I(2) = 0%, very low quality evidence) for ongoing pregnancy/live birth rates. OHSS There was no evidence of a difference between rhCG and uhCG in the incidence of OHSS: moderate to severe OHSS (OR 1.76, 95% CI 0.37 to 8.45; 3 RCTs, N = 417, I(2) = 0%, low quality evidence), moderate OHSS (OR 0.78, 95% CI 0.27 to 2.27; 1 RCT, N = 243, I(2) = 0%, low quality evidence), mild to moderate OHSS (OR 1.00, 95% CI 0.42 to 2.38; 2 RCTs, N = 320, I(2) = 0%, low quality evidence) or undefined OHSS (OR 1.18, 95% CI 0.50 to 2.78; 3 RCTs, N = 495, I(2) = 0%, low quality evidence). Likewise, there was no evidence of a difference between rhLH and uhCG in OHSS rates for moderate OHSS (OR 0.82, 95% CI 0.39 to 1.69, 2 RCTs, N = 280, I(2) = 5%, very low quality evidence). Other adverse events There was no evidence of a difference in miscarriage rates between rhCG and uhCG (OR 0.72, 95% CI 0.41 to 1.25; 8 RCTs, N = 1196, I(2) = 0%, low quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.38 to 2.40; 2 RCTs, N = 289, I(2) = 0%, very low quality evidence). For other adverse effects (most commonly injection-site reactions) rhCG was associated with a lower number of adverse events than uhCG (OR 0.52, 95% CI 0.35 to 0.76; 5 RCTS, N = 561; I(2) = 67%, moderate quality evidence). However, when we used a random-effects model due to substantial statistical heterogeneity, there was no evidence of a difference between the groups (OR 0.56, 95% CI 0.27 to 1.13). Only one study comparing rLH and uhCG reported other adverse events, and it was impossible to draw conclusions.
AUTHORS' CONCLUSIONS
We conclude that there is no evidence of a difference between rhCG or rhLH and uhCG for live birth or ongoing pregnancy rates or rates of OHSS.
Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Ovulation Induction; Randomized Controlled Trials as Topic; Recombinant Proteins; Sperm Injections, Intracytoplasmic
PubMed: 27106604
DOI: 10.1002/14651858.CD003719.pub4 -
The Cochrane Database of Systematic... Dec 2015Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome.
SEARCH METHODS
We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles.
SELECTION CRITERIA
Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR).
AUTHORS' CONCLUSIONS
Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.
Topics: Biomarkers; Chorionic Gonadotropin; Down Syndrome; Estriol; False Positive Reactions; Female; Gonadotropins; Humans; Maternal Age; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Sensitivity and Specificity; alpha-Fetoproteins
PubMed: 26662198
DOI: 10.1002/14651858.CD011984 -
The Cochrane Database of Systematic... Nov 2015Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. However, no test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
The aim of this review was to estimate and compare the accuracy of first trimester serum markers for the detection of Down's syndrome in the antenatal period, both as individual markers and as combinations of markers. Accuracy is described by the proportion of fetuses with Down's syndrome detected by screening before birth (sensitivity or detection rate) and the proportion of women with a low risk (normal) screening test result who subsequently had a baby unaffected by Down's syndrome (specificity).
SEARCH METHODS
We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 25 August 2011), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (Archived 2007), Health Services Research Projects in Progress database (25 August 2011). We did forward citation searching ISI citation indices, Google Scholar and PubMed 'related articles'. We did not apply a diagnostic test search filter. We also searched reference lists and published review articles.
SELECTION CRITERIA
We included studies in which all women from a given population had one or more index test(s) compared to a reference standard (either chromosomal verification or macroscopic postnatal inspection). Both consecutive series and diagnostic case-control study designs were included. Randomised trials where individuals were randomised to different screening strategies and all verified using a reference standard were also eligible for inclusion. Studies in which test strategies were compared head-to-head either in the same women, or between randomised groups were identified for inclusion in separate comparisons of test strategies. We excluded studies if they included less than five Down's syndrome cases, or more than 20% of participants were not followed up.
DATA COLLECTION AND ANALYSIS
We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC meta-analytical methods or random-effects logistic regression methods to analyse test performance and compare test accuracy as appropriate. Analyses of studies allowing direct and indirect comparisons between tests were undertaken.
MAIN RESULTS
We included 56 studies (reported in 68 publications) involving 204,759 pregnancies (including 2113 with Down's syndrome). Studies were generally of good quality, although differential verification was common with invasive testing of only high-risk pregnancies. We evaluated 78 test combinations formed from combinations of 18 different tests, with or without maternal age; ADAM12 (a disintegrin and metalloprotease), AFP (alpha-fetoprotein), inhibin, PAPP-A (pregnancy-associated plasma protein A, ITA (invasive trophoblast antigen), free βhCG (beta human chorionic gonadotrophin), PlGF (placental growth factor), SP1 (Schwangerschafts protein 1), total hCG, progesterone, uE3 (unconjugated oestriol), GHBP (growth hormone binding protein), PGH (placental growth hormone), hyperglycosylated hCG, ProMBP (proform of eosinophil major basic protein), hPL (human placental lactogen), (free αhCG, and free ßhCG to AFP ratio. Direct comparisons between two or more tests were made in 27 studies.Meta-analysis of the nine best performing or frequently evaluated test combinations showed that a test strategy involving maternal age and a double marker combination of PAPP-A and free ßhCG significantly outperformed the individual markers (with or without maternal age) detecting about seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). Limited evidence suggested that marker combinations involving PAPP-A may be more sensitive than those without PAPP-A.
AUTHORS' CONCLUSIONS
Tests involving two markers in combination with maternal age, specifically PAPP-A, free βhCG and maternal age are significantly better than those involving single markers with and without age. They detect seven out of 10 Down's affected pregnancies for a fixed 5% FPR. The addition of further markers (triple tests) has not been shown to be statistically superior; the studies included are small with limited power to detect a difference.The screening blood tests themselves have no adverse effects for the woman, over and above the risks of a routine blood test. However some women who have a 'high risk' screening test result, and are given amniocentesis or chorionic villus sampling (CVS) have a risk of miscarrying a baby unaffected by Down's. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a 'high risk' screening test result.
Topics: ADAM Proteins; ADAM12 Protein; Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Maternal Age; Membrane Proteins; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis; alpha-Fetoproteins
PubMed: 26617074
DOI: 10.1002/14651858.CD011975 -
The Cochrane Database of Systematic... Sep 2015Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in the short- and long-term. Managing the thyroid dysfunction (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes. The best method of screening to identify and subsequently manage thyroid dysfunction pre-pregnancy and during pregnancy is unknown.
OBJECTIVES
To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials, comparing any screening method (e.g. tool, program, guideline/protocol) for detecting thyroid dysfunction (including hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity) pre-pregnancy or during pregnancy with no screening, or alternative screening methods.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies.
MAIN RESULTS
We included two randomised controlled trials (involving 26,408 women) - these trials were considered to be at low risk of bias. Universal screening (screening all women) versus case finding (screening only those at perceived increased risk) in pregnancy for thyroid dysfunctionOne trial (4562 women) compared universal screening with case finding for thyroid dysfunction. Before 11 weeks' gestation, women in the universal screening group, and 'high-risk' women in the case finding group had their sera tested for TSH (thyroid stimulating hormone), fT4 (free thyroxine) and TPO-Ab (thyroid peroxidase antibody); women with hypothyroidism (TSH > 2.5 mIU/litre) received levothyroxine; women with hyperthyroidism (undetectable TSH and elevated fT4) received antithyroid medication.In regards to this review's primary outcomes, compared with the case finding group, more women in the universal screening group were diagnosed with hypothyroidism (risk ratio (RR) 3.15, 95% confidence interval (CI) 1.91 to 5.20; 4562 women; GRADE: high quality evidence), with a trend towards more women being diagnosed with hyperthyroidism (RR 4.50, 95% CI 0.97 to 20.82; 4562 women; P = 0.05; GRADE: moderate quality evidence). No clear differences were seen in the risks of pre-eclampsia (RR 0.87, 95% CI 0.64 to 1.18; 4516 women; GRADE: moderate quality evidence), or preterm birth (RR 0.99, 95% CI 0.80 to 1.24; 4516 women; GRADE: high quality evidence) between groups. This trial did not report on neurosensory disability for the infant as a child.Considering this review's secondary outcomes, more women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 3.15, 95% CI 1.91 to 5.20; 4562 women). No clear differences between groups were observed for miscarriage (RR 0.90, 95% CI 0.68 to 1.19; 4516 women; GRADE: moderate quality evidence), fetal and neonatal death (RR 0.92, 95% CI 0.42 to 2.02; 4516 infants; GRADE: moderate quality evidence), or other secondary outcomes: pregnancy-induced hypertension, gestational diabetes, congestive heart failure, thyroid storm, mode of birth (caesarean section), preterm labour, placental abruption, respiratory distress syndrome, low birthweight, neonatal intensive care unit admission, or other congenital malformations. The trial did not report on a number of outcomes including adverse effects associated with the intervention. Universal screening versus no screening in pregnancy for hypothyroidismOne trial (21,846 women) compared universal screening with no screening for hypothyroidism. Before 15 + 6 weeks' gestation, women in the universal screening group had their sera tested; women who screened 'positive' (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine.Considering primary review outcomes, compared with the no screening group, more women in the universal screening screened 'positive' for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high quality evidence). No data were provided for the outcome pre-eclampsia, and for preterm birth, the trial reported rates of 5.6% and 7.9% for the screening and no screening groups respectively (it was unclear if these percentages related to the entire cohort or women who screened positive). No clear difference was seen for neurosensory disability for the infant as a child (three-year follow-up IQ score < 85) (RR 0.85, 95% CI 0.60 to 1.22; 794 infants; GRADE: moderate quality evidence).More women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; 1050 women); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. No clear differences were observed for other secondary outcomes, including developmental delay/intellectual impairment at three years. Most of our secondary outcomes, including miscarriage, fetal or neonatal death were not reported.
AUTHORS' CONCLUSIONS
Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.
Topics: Adult; Female; Humans; Hypothyroidism; Infant Health; Infant, Newborn; Mass Screening; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Thyroid Diseases
PubMed: 26387772
DOI: 10.1002/14651858.CD011263.pub2