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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 -
Journal of Minimally Invasive Gynecology 2017A relatively new type of ectopic pregnancy is cesarean scar pregnancy (CSP). This is related to the increasing number of cesarean deliveries and the advances in... (Review)
Review
A relatively new type of ectopic pregnancy is cesarean scar pregnancy (CSP). This is related to the increasing number of cesarean deliveries and the advances in imaging. There are 2 types of CSP: CSP with progression to the cervicoisthmic space or uterine cavity (type I, endogenic type) or with deep invasion of scar defect with progression toward the bladder and abdominal cavity (type II, exogenic type). The endogenic type of CSP could result in a viable pregnancy, yet with a high risk of bleeding at the placental site. The exogenic type could be complicated with uterine rupture and bleeding early in pregnancy. Because early diagnosis and treatment are important for the best outcome, every pregnant woman with a history of cesarean delivery should be screened early in the first trimester of pregnancy. Diagnosis can be achieved with ultrasound and Doppler imaging. To date, there have been only 5 randomized studies on CSP, and evidence-based management remains unclear. Until then, treatment should be individualized according to many factors including clinical presentation, beta-human chorionic gonadotropin levels, imaging features, and the surgeon's skill.
Topics: Adult; Cesarean Section; Chorionic Gonadotropin, beta Subunit, Human; Cicatrix; Female; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy, Ectopic; Randomized Controlled Trials as Topic; Uterus
PubMed: 28268103
DOI: 10.1016/j.jmig.2017.02.020 -
Frontiers in Endocrinology 2023Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of... (Review)
Review
AIMS/HYPOTHESIS
Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of type 2 diabetes and obesity. The paucity of data regarding their safety during pregnancy and lactation causes a dilemma for the physician. The aim of the present study was to systematically review all available data on the offspring effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation.
METHODS
We systematically searched PubMed, clinicaltrials.gov, FDA and EMA product information on GLP-1 agonists and SGLT2 inhibitors in pregnancy and lactation from inception up to 19 April 2022 without language restrictions. We approached both the Netherlands Pharmacovigilance Centre Lareb on January 17 2023 and the Teratology Information Service (TIS) of Switzerland on February 6 2023. Eligible studies investigating the safety (including congenital anomalies, fetal growth, perinatal demise) in animals or humans, or reporting the degree of transfer of these drugs to the fetus, breast milk or breastfed neonate. Two reviewers independently assessed and selected studies for inclusion and subsequently resolved discrepancies by discussion.
RESULTS
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information). In animal studies, GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants, usually associated with a reduction in maternal weight gain and decreased food consumption. Exendin-4 (GLP1-agonist) was not transported across the maternal-fetal placental interface. In human studies, exenatide (GLP1-agonist) showed a fetal-to-maternal peptide concentration ratio of ≤ 0.017 in ex vivo human placental perfusion in a single placenta. Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject. In animal studies, GLP-1 agonists were excreted in breast milk; human data on excretion were not available. In animal studies, SGLT2 inhibitors were generally safe during the first trimester but exposure during postnatal day 21 to 90 in juvenile rats, a period coinciding with the late second and third trimester of human renal development, caused dilatation of the renal pelvis and tubules. Human data consisted of a pharmaceutical database of inadvertent pregnancies during SGLT2 inhibitor use, which found an increase in miscarriages and congenital malformations. In animal studies SGLT2 inhibitors were excreted in breast milk and affected neonatal growth, but human data are not available.
CONCLUSION/INTERPRETATION
We found evidence for adverse offspring effects of GLP-1 agonists and SGLT2 inhibitors also in human studies. Our findings broadly support the advice to discontinue GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation, and also support the ongoing registration of pregnancy outcomes in pharmacological databases since the amount of available data is scarce and mostly limited to animal studies.
REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=219877.
Topics: Female; Humans; Pregnancy; Rats; Animals; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Breast Feeding; Placenta; Exenatide; Liraglutide; Lactation
PubMed: 37881498
DOI: 10.3389/fendo.2023.1215356 -
Journal of Assisted Reproduction and... Sep 2023The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human... (Meta-Analysis)
Meta-Analysis Review
Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.
PROPOSE
The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles.
METHOD
A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR).
RESULTS
We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]).
CONCLUSION
The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity.
RELEVANCE
After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.
Topics: Pregnancy; Female; Humans; Pregnancy Rate; Ovulation Induction; Gonadotropin-Releasing Hormone; Randomized Controlled Trials as Topic; Fertilization in Vitro; Chorionic Gonadotropin
PubMed: 37466846
DOI: 10.1007/s10815-023-02888-8 -
The Cochrane Database of Systematic... Jul 2015Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques(ART), progesterone and/or hCG levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin-releasing hormone (GnRH) agonists to improve implantation and pregnancy rates.
OBJECTIVES
To determine the relative effectiveness and safety of methods of luteal phase support provided to subfertile women undergoing assisted reproduction.
SEARCH METHODS
We searched databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and trial registers. We conducted searches in November 2014, and further searches on 4 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of luteal phase support using progesterone, hCG or GnRH agonist supplementation in ART cycles.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, extracted data and assessed risk of bias. We calculated odds ratios (ORs) and 95%confidence intervals (CIs) for each comparison and combined data when appropriate using a fixed-effect model. Our primary out come was live birth or ongoing pregnancy. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
Ninety-four women RCTs (26,198 women) were included. Most studies had unclear or high risk of bias in most domains. The main limitations in the evidence were poor reporting of study methods and imprecision due to small sample sizes.1. hCG vs placebo/no treatment (five RCTs, 746 women)There was no evidence of differences between groups in live birth or ongoing pregnancy (OR 1.67, 95% CI 0.90 to 3.12, three RCTs,527 women, I2 = 24%, very low-quality evidence, but I2 of 61% was found for the subgroup of ongoing pregnancy) with a random effects model. hCG increased the risk of ovarian hyperstimulation syndrome (OHSS) (1 RCT, OR 4.28, 95% CI 1.91 to 9.6, low quality evidence).2. Progesterone vs placebo/no treatment (eight RCTs, 875 women)Evidence suggests a higher rate of live birth or ongoing pregnancy in the progesterone group (OR 1.77, 95% CI 1.09 to 2.86, five RCTs, 642 women, I2 = 35%, very low-quality evidence). OHSS was not reported.3. Progesterone vs hCG regimens (16 RCTs, 2162 women)hCG regimens included comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. No evidence showed differences between groups in live birth or ongoing pregnancy (OR 0.95, 95% CI 0.65 to 1.38, five RCTs, 833 women, I2 = 0%, low quality evidence) or in the risk of OHSS (four RCTs, 615 women, progesterone vs hCG OR 0.54, 95% CI 0.22 to 1.34; four RCTs,678 women; progesterone vs progesterone plus hCG, OR 0.34, 95% CI 0.09 to 1.26, low-quality evidence).4. Progesterone vs progesterone with oestrogen (16 RCTs, 2577 women)No evidence was found of differences between groups in live birth or ongoing pregnancy (OR 1.12, 95% CI 0.91 to 1.38, nine RCTs,1651 women, I2 = 0%, low-quality evidence) or OHSS (OR 0.56, 95% CI 0.2 to 1.63, two RCTs, 461 women, I2 = 0%, low-quality evidence).5. Progesterone vs progesterone + GnRH agonist (seven RCTs, 1708 women)Live birth or ongoing pregnancy rates were lower in the progesterone-only group and increased in women who received progester one and one or more GnRH agonist doses (OR 0.62, 95% CI 0.48 to 0.81, nine RCTs, 2861 women, I2 = 55%, random effects, low quality evidence). Statistical heterogeneity for this comparison was high because of unexplained variation in the effect size, but the direction of effect was consistent across studies. OHSS was reported in one study only (OR 1.00, 95% CI 0.33 to 3.01, 1 RCT, 300 women, very low quality evidence).6. Progesterone regimens (45 RCTs, 13,814 women)The included studies reported nine different comparisons between progesterone regimens. Findings for live birth or ongoing pregnancy were as follows: intramuscular (IM) versus oral: OR 0.71, 95% CI 0.14 to 3.66 (one RCT, 40 women, very low-quality evidence);IM versus vaginal/rectal: OR 1.24, 95% CI 1.03 to 1.5 (seven RCTs, 2309 women, I2 = 71%, very low-quality evidence); vaginal/rectal versus oral: OR 1.19, 95% CI 0.83 to 1.69 (four RCTs, 857 women, I2 = 32%, low-quality evidence); low-dose versus high-dose vaginal: OR 0.97, 95% CI 0.84 to 1.11 (five RCTs, 3720 women, I2 = 0%, moderate-quality evidence); short versus long protocol:OR 1.04, 95% CI 0.79 to 1.36 (five RCTs, 1205 women, I2 = 0%, low-quality evidence); micronised versus synthetic: OR 0.9, 95%CI 0.53 to 1.55 (two RCTs, 470 women, I2 = 0%, low-quality evidence); vaginal ring versus gel: OR 1.09, 95% CI 0.88 to 1.36 (oneRCT, 1271 women, low-quality evidence); subcutaneous versus vaginal gel: OR 0.92, 95% CI 0.74 to 1.14 (two RCTs, 1465 women,I2 = 0%, low-quality evidence); and vaginal versus rectal: OR 1.28, 95% CI 0.64 to 2.54 (one RCT, 147 women, very low-quality evidence). OHSS rates were reported for only two of these comparisons: IM versus oral, and low versus high-dose vaginal. No evidence showed a difference between groups.7. Progesterone and oestrogen regimens (two RCTs, 1195 women)The included studies compared two different oestrogen protocols. No evidence was found to suggest differences in live birth or ongoing pregnancy rates between a short and a long protocol (OR 1.08, 95% CI 0.81 to 1.43, one RCT, 910 women, low-quality evidence) or between a low dose and a high dose of oestrogen (OR 0.65, 95% CI 0.37 to 1.13, one RCT, 285 women, very low-quality evidence).Neither study reported OHSS.
AUTHORS' CONCLUSIONS
Both progesterone and hCG during the luteal phase are associated with higher rates of live birth or ongoing pregnancy than placebo.The addition of GnRHa to progesterone is associated with an improvement in pregnancy outcomes. OHSS rates are increased with hCG compared to placebo (only study only). The addition of oestrogen does not seem to improve outcomes. The route of progester one administration is not associated with an improvement in outcomes.
Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Live Birth; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Maintenance; Progesterone; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
PubMed: 26148507
DOI: 10.1002/14651858.CD009154.pub3 -
Toxicological Sciences : An Official... Jul 2022Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies...
Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children's health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.
Topics: Animals; Child; Female; Humans; Infant, Newborn; Models, Animal; Phthalic Acids; Placenta; Pregnancy; Premature Birth
PubMed: 35686923
DOI: 10.1093/toxsci/kfac060 -
American Journal of Obstetrics and... Aug 2019To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols.
DATA SOURCES
PubMed, Embase, and the Cochrane library searched up to July 2018.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols.
STUDY APPRAISAL AND SYNTHESIS METHODS
Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias.
RESULTS
The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, -12.2, -3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, -1.3; 95% CI, -5.4, 2.7) were similar.
CONCLUSION
The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Topics: Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Fallopian Tubes; Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic; Randomized Controlled Trials as Topic; Rupture
PubMed: 30629908
DOI: 10.1016/j.ajog.2019.01.002 -
Biomarkers in Medicine 2015Placental malaria (PM) causes significant morbidity in mothers and infants. Diagnosis of PM during pregnancy is however problematic due to placental sequestration of... (Meta-Analysis)
Meta-Analysis Review
Placental malaria (PM) causes significant morbidity in mothers and infants. Diagnosis of PM during pregnancy is however problematic due to placental sequestration of parasites. Host biomarkers may therefore be used as a diagnostic method. In this systematic review most studies focused on inflammatory markers. A trend was observed for increased IL-10 and TNF-α in PM positives. These markers are however unspecific, thus a combination of multiple biomarkers involved in different pathophysiological pathways of PM is indicated. Of interest are inflammatory markers (TNF-R2, CXCL-13), markers of lipid metabolism (APO-B), angiogenesis (sFlt-1) and hormones (estradiol). As the majority of published studies tested biomarker levels only at delivery, more longitudinal cohort studies will be necessary to detect biomarkers during pregnancy that can predict PM.
Topics: Animals; Biomarkers; Female; Gene Expression Regulation; Humans; Malaria; Placenta; Pregnancy; Pregnancy Complications, Infectious
PubMed: 25731209
DOI: 10.2217/bmm.14.117 -
The Cochrane Database of Systematic... Mar 2017Down'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.Non-invasive 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 trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome.
SEARCH METHODS
We carried out extensive literature searches including 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), and The Database of Abstracts of Reviews of Effects (the Cochrane Library 2011, Issue 7). We checked reference lists and published review articles for additional potentially relevant studies.
SELECTION CRITERIA
Studies evaluating tests of first trimester ultrasound screening, alone or in combination with first trimester serum tests (up to 14 weeks' gestation) for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
Data were extracted as test positive/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 criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more.
AUTHORS' CONCLUSIONS
Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% FPR. Although the absence of nasal bone appeared to have a high diagnostic accuracy, only five out of 10 affected Down's pregnancies were detected at a 1% FPR.
Topics: Biomarkers; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; False Positive Reactions; Female; Humans; Maternal Age; Nasal Bone; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28295158
DOI: 10.1002/14651858.CD012600 -
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