Ultrasound-guided manual vacuum aspiration (USG-MVA) with cervical preparation for early pregnancy loss: A cost-effectiveness analysis.

BACKGROUND AND AIM: Approximately one in four women will experience a miscarriage in their lifetime. Ultrasound-guided manual vacuum aspiration (USG-MVA) is an ideal outpatient surgical treatment alternative to traditional surgical evacuation. We aimed to examine the cost-effectiveness of US-MVA with cervical preparation for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong. METHODS: A decision-analytic model was designed to simulate outcomes in a hypothetical cohort of patients with early pregnancy loss on four interventions: (1) US-MVA, (2) misoprostol, (3) surgical evacuation of uterus by dilation and curettage (surgical evacuation), and (4) expectant care. Model inputs were retrieved from published literature and public data. Model outcome measures were total direct medical cost and disutility-adjusted life-year (DALY). Base-case model results were examined by sensitivity analysis. RESULTS: The expected DALYs (0.00141) and total direct medical cost (USD736) of US-MVA were the lowest of all interventions in base-case analysis, and US-MVA was the preferred cost-effective option. One-way sensitivity analysis showed that the misoprostol group became less costly than the US-MVA group if the evacuation rate of misoprostol (base-case value 0.832) exceeded 0.920. In probabilistic sensitivity analysis, At the willingness-to-pay (WTP) threshold of 49630 USD/DALY averted (1x gross domestic product per capita of Hong Kong), the US-MVA was cost-effective in 72.9% of the time. CONCLUSIONS: US-MVA appeared to be cost-saving and effective for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong.

Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer.

Objective: To evaluate the associations between homeostatic model assessment for insulin resistance (HOMA-IR) and pregnancy outcomes in non-dyslipidemic infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Materials and Methods: This is a retrospective study involving 3,615 non-dyslipidemic infertile women who attend to the Reproductive Medicine Center of Xiangya Hospital, Central South University (CSU) between January 2014 and October 2021. Eligible participants were divided into three groups according to the quartiles of HOMA-IR: Group 1 (HOMA-IR <1.46), Group 2 (1.46 to <2.71) and Group 3 (HOMA-IR ≥2.71). Baseline data, clinical characteristics during the assisted reproductive technology (ART) procedure, pregnancy, and neonatal outcomes were compared among the three groups. Subgroup analysis based on presence or absence of the polycystic ovary syndrome (PCOS) status was also performed to analyze the effects of HOMA-IR among non-PCOS populations. Results: The late miscarriage rate and percentage of macrosomia increased with the HOMA-IR group (for late miscarriage rate: 2.23% vs. 3.04% vs. 7.35%, P<0.001; for macrosomia: 0.21% vs. 1.70% vs. 3.23%, P=0.002). Increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.50, 95% CI 1.64-7.47, P=0.001; adjusted OR 3.56, 95% CI 1.56-8.15, P=0.003). In the subgroup analysis, there were 3,165 participants in the non-PCOS group and 450 were assigned to the PCOS group. Late miscarriage rate increased with the HOMA-IR group among non-PCOS populations (2.20% vs. 3.03% vs. 7.67%, P<0.001). Late miscarriage rate of PCOS women were comparable among the three HOMA-IR groups (2.50% vs. 3.06% vs. 5.71%, P=0.634). Among non-PCOS women, increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.71, 95% CI 1.66-8.30, P=0.001; adjusted OR 3.82, 95% CI 1.59-9.17, P=0.003). Conclusions: Late miscarriage rate and prevalence of macrosomia increased with the HOMA-IR index. Preconception HOMA-IR is an independent risk factor for late miscarriage in normolipidemic women undergoing IVF/ICSI-ET. Controlling insulin resistance before ART might prevent the occurrence of late miscarriage and macrosomia.

Assessment of the potential impacts of the Chernobyl nuclear disaster on maternal and fetal health in Hungary.

Objective: Radiation exposure is known to be mutagenic and teratogenic. The aim of this study was to analyze the effects of the increased ionizing radiation emitted by the Chernobyl nuclear disaster on maternal and fetal outcomes in Hungary.Methods: A retrospective analysis of abortion, stillbirth, and congenital anomaly data for pregnancies in Hungary between 1 January 1981 and 31 December 1991 was conducted.Results: Trend analysis revealed increasing trends in spontaneous and voluntary abortion rates in Hungary during the study time period, while late pregnancy losses showed a decreasing trend. Overall, there were generally decreasing incidence rates for birth defects throughout the 1980s. Increased voluntary abortions over the study period might reflect, at least in part, maternal anxiety in the post-Chernobyl years. Decreased late pregnancy loss over the same period may be attributable to improvements in prenatal diagnostics. A notable weakness of this study is that missing data could not be complemented due to the decades that have passed since the incident.Conclusions: In conclusion, the present data suggest that the nuclear catastrophe in 1986 did not cause a significant increase in pregnancy loss or congenital malformations in Hungary.

Radiation exposure in Hungary caused by the Chernobyl nuclear power plant disaster did not results in increases in fetal death or congenital anomaly rates.

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth-study protocol for a randomised controlled trial.

BACKGROUND: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. METHODS: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0-27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. DISCUSSION: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018.

Analysis of maternal and neonatal outcomes using cervical cerclage or conservative treatment in singleton gestations with a sonographic short cervix.

ABSTRACT: To investigate the effect of cervical cerclage or conservative treatment on maternal and neonatal outcomes in singleton gestations with a sonographic short cervix, and further compare the relative treatment value.A retrospective study was conducted among women with singleton gestations who had a short cervical length (<25 mm) determined by ultrasound during the period of 14 to 24 weeks' gestation in our institution. We collected clinical data and grouped the patients according to a previous spontaneous preterm birth (PTB) at <34 weeks of gestation or second trimester loss (STL) and sub-grouped according to treatment option, further comparing the maternal and neonatal outcomes between different groups.In the PTB or STL history cohort, the cerclage group had a later gestational age at delivery (35.3 ±â€Š3.9 weeks vs 31.6 ±â€Š6.7 weeks) and a lower rate of perinatal deaths (2% vs 29.3%) compared with the conservative treatment group. In the non-PTB-STL history cohort, the maternal and neonatal outcomes were not significantly different between the cerclage group and conservative treatment group. More importantly, for patients with a sonographic short cervix who received cervical cerclage, there was no significant difference in the maternal and neonatal outcomes between the non-PTB-STL group and PTB or STL group.For singleton pregnant with a history of spontaneous PTB or STL and a short cervical length (<25 mm), cervical cerclage can significantly improve maternal and neonatal outcomes; however, conservative treatment (less invasive and expensive than cervical cerclage) was more suitable for those pregnant women without a previous PTB and STL history.

Eliciting women's preference for prenatal testing in China: a discrete choice experiment.

BACKGROUND: Pregnancy tests can be used for the early diagnosis of fetal problems and can prevent abnormal birth in pregnancies. Yet, testing preferences among Chinese women are poorly investigated. METHODS: We developed a Discrete Choice Experiment with 5 attributes: test procedure, detection rate, miscarriage rate, time to wait for result, and test cost. By studying the choices that the women make in the hypothetical scenarios and comparing the attributes and levels, we can analyze the women's preference of prenatal testing in China. RESULTS: Ninety-two women completed the study. Respondents considered the test procedure as the most important attribute, followed by detection rate, miscarriage rate, wait time for result, and test cost, respectively. The estimated preference weight for the non-invasive procedure was 0.928 (P < 0.0001). All other attributes being equal, the odds of choosing a non-invasive testing procedure over an invasive one was 2.53 (95% confidence interval, 2.42-2.64; P < 0.001). Participants were willing to pay up to RMB$28,810 (approximately US$4610) for a non-invasive test, RMB$6061(US$970) to reduce the miscarriage rate by 1% and up to RMB$3356 (US$537) to increase the detection rate by 1%. Compared to other DCE (Discrete Choice Experiment) studies regarding Down's syndrome screening, women in our study place relatively less emphasis on test safety. CONCLUSIONS: The present study has shown that Chinese women place more emphasis on detection rate than test safety. Chinese women place great preference on noninvasive prenatal testing, which indicate a popular need of incorporating noninvasive prenatal testing into the health insurance coverage in China. This study provided valuable evidence for the decision makers in the Chinese government.

Factors associated with spontaneous abortion: a systematic review / Fatores associados ao aborto espontâneo: uma revisão sistemática

Abstract Objectives: to compile studies produced regardinggenetic and non-genetic risks factors associated with occurrence of spontaneous abortion. Methods: it talks about a systematic review article, with studies between January of 2008 to November of 2018 according to SciELO, PubMed, Lilacs and BVS. Results: in total, 567 articles were found. After applying the definedeligibility criteria, 44 articles made part of the review, being the majority published on Asia between 2008 and 2011, and 10 articles published on Brazil. Not genetic causes like sociodemographic factors and healthy state were among the most associated conditions of spontaneous abortion. Asiatic continent had predominance about the correlation of spontaneous abortion with factors related to life style like obesity, smoking and labor activities, on the other hand, in the Americas, causes related to sociodemographics factors like low pay and low studies are high-lighted. Conclusions: the risk factors change about the occurrence region, being important to make local studies capable of subsidize the implantation of public politics and to reduce abortions.

Resumo Objetivos: compilar estudos produzidos acerca dos fatores de risco genéticos e não genéticos associados a ocorrência de aborto espontâneo. Métodos: trata-se de um artigo de revisão sistemática, com estudos publicados entre janeiro de 2008 a novembro de 2018 nas bases de dados SciELO, PubMed, Lilacs e BVS. Resultados: um total de 567 artigos foram encontrados. Após aplicação dos critérios de elegibilidade definidos, 44 artigos compuseram a presente revisão com a maioria publicada na Ásia, entre os anos de 2008 a 2011, e 10 artigos publicados no Brasil. Causas não genéticas, como fatores sociodemográficos e estado de saúde, estiveram entre as condições mais associadas ao abortamento espontâneo. No continente asiático houve predominância na correlação do aborto espontâneo com fatores relacionados ao estilo de vida como obesidade, tabagismo e atividades laborais; já nas Américas destacam-se causas relacionadas aos fatores sociodemográficos, como baixa renda e baixa escolaridade. Conclusões: os fatores de risco diferem em relação a região de ocorrência, sendo importante a realização de estudos detalhados para que sejam capazes de subsidiar a implantação de políticas públicas e, assim, minorar a ocorrência de abortos.

Pregnancy loss: A 40-year nationwide assessment.

INTRODUCTION: Pregnancy loss is frequent. We aimed to assess the frequency and trends in pregnancy losses according to female age and mode of conception over a 40-year follow-up period. MATERIAL AND METHODS: In a national historical prospective cohort study, we followed all Danish women 10-49 years over the 40-year study period 1978-2017. Data on pregnancies and their outcomes were obtained from the National Health Registry, the Medical Birth Registry and the National Fertility Registry. Incidence rates per 100 pregnancies and per 1,000 women-years as well as lifetime risks per 100 women were calculated. Women included in the lifetime analysis were followed from age 12 to age 49. Pregnancy loss included spontaneous abortion, missed abortion and anembryonic pregnancy. RESULTS: In 3 519 455 recorded pregnancies, 337 008, or 9.6%, were diagnosed with a pregnancy loss. The proportion increased from 7.5% in 1978-1979, peaked at 10.7% in 2000 and thereafter decreased to 9.1% in 2015-2017. Pregnancy loss rate in women 10-14 years was 3.9%, increasing gradually with age to 26.9% in pregnant women 45-49 years, a 6.9-fold increase. Loss rates were slightly lower in naturally conceived pregnancies than in assisted pregnancies except for women above 45 years, where the risk of loss was higher in the spontaneously conceived group. Lifetime risk of specific numbers of losses were: 0: 76.9%, 1: 17.9%, 2: 3.9%, 3: 0.87%, and 4+: 0.35%. CONCLUSIONS: The proportion of women experiencing pregnancy loss has changed little throughout four decades and is still primarily influenced by female age. More than 75% of pregnant women are never recorded with a pregnancy loss, and <1.5% will experience three or more losses.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Septate uterus according to ESHRE/ESGE, ASRM and CUME definitions: association with infertility and miscarriage, cost and warnings for women and healthcare systems.

OBJECTIVES: To estimate the differences in frequency of diagnosis of septate uterus using three different definitions and determine whether these differences are significant in clinical practice, and to examine the association between diagnosis of septate uterus, using each of the three definitions, and infertility and/or previous miscarriage as well as the cost of allocation to surgery. METHODS: This was a secondary analysis of data from a prospective study of 261 consecutive women of reproductive age attending a private clinic focused on the diagnosis and treatment of congenital uterine malformations. Reanalysis of the datasets was performed according to three different means of defining septate uterus: following the recommendations of the American Society for Reproductive Medicine (ASRM), a 2016 update of those of the American Fertility Society from 1988 (ASRM-2016: internal fundal indentation depth ≥ 1.5 cm, angle of internal indentation < 90° and external indentation depth < 1 cm); following the recommendations of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE/ESGE), published in 2013 and reaffirmed in 2016 (ESHRE/ESGE-2016: internal fundal/uterine indentation depth > 50% of uterine-wall thickness and external indentation depth < 50% of uterine-wall thickness, with uterine-wall thickness measured above interostial/intercornual line); and using a definition published last year which was based on the decision made most often by a group of experts (Congenital Uterine Malformation by Experts; CUME) (CUME-2018: internal fundal indentation depth ≥ 1 cm and external fundal indentation depth < 1 cm). We compared the rate of diagnosis of septate uterus using each of these three definitions and, for each, we estimated the association between the diagnosis and infertility and/or previous miscarriage, and anticipated the costs associated with their implementation using a guesstimation method. RESULTS: Although 32.6% (85/261) of the subjects met the criteria for one of the three definitions of septate uterus, only 2.7% (7/261) of them were defined as having septate uterus according to all three definitions. We diagnosed significantly more cases of septate uterus using ESHRE/ESGE-2016 than using ASRM-2016 (31% vs 5%, relative risk (RR) = 6.7, P < 0.0001) or CUME-2018 (31% vs 12%, RR = 2.6, P < 0.0001) criteria. We also observed frequent cases that could not be classified definitively by ASRM-2016 (gray zone: neither normal/arcuate nor septate; 6.5%). There were no significant differences (P > 0.05) in the prevalence of septate uterus in women with vs those without infertility according to ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) or CUME-2018 (11% vs 12%). Septate uterus was diagnosed significantly more frequently in women with vs those without previous miscarriage according to ASRM-2016 (11% vs 3%; P = 0.04) and CUME-2018 (22 vs 10%; P = 0.04), but not according to ESHRE/ESGE-2016 (42% vs 28%; P = 0.8) criteria. Our calculations showed that global costs to the healthcare system would be highly dependent on the criteria used in the clinical setting to define septate uterus, with the costs associated with the ESHRE/ESGE-2016 definition potentially being an extra US$ 100-200 billion over 5 years in comparison to ASRM-2016 and CUME-2018 definitions. CONCLUSIONS: The prevalence of septate uterus according to ESHRE/ESGE-2016, ASRM-2016 and CUME-2018 definitions differs considerably. An important limitation of the ASRM classification, which needs to be addressed, is the high proportion of unclassifiable cases originally named, by us, the 'gray zone'. The high rate of overdiagnosis of septate uterus according to ESHRE/ESGE-2016 may lead to unnecessary surgery and therefore unnecessary risk in these women and may impose a considerable financial burden on healthcare systems. Efforts to define clinically meaningful and universally applicable criteria for the diagnosis of septate uterus should be encouraged. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Útero septo según las definiciones de ESHRE/ESGE, ASRM y CUME: la relación con la infertilidad y el aborto espontáneo, el costo y advertencias para las mujeres y los sistemas de salud OBJETIVO: Evaluar el rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal (MCA-PSV, por sus siglas en inglés) ≥1,5 múltiplos de la mediana (MdM) para la predicción de la anemia moderada-severa en fetos sometidos a transfusión y no sometidos. MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales relevantes reportados en el período 2008-2018 que evaluaron el rendimiento de la MCA-PSV, utilizando un umbral de 1,5MdM para la predicción de la anemia fetal. El diagnóstico de la anemia fetal mediante la toma de muestras de sangre fue el estándar de referencia. Se utilizaron modelos de efectos aleatorios para la elaboración de una curva jerárquica resumen de las características operativas del receptor (hSROC, por sus siglas en inglés). Se realizaron análisis de subgrupos y metarregresión, según el número de transfusiones intrauterinas previas. RESULTADOS: En el metaanálisis se incluyeron doce estudios y 696 fetos. El área bajo la curva (ABC) hSROC para la anemia moderada-severa fue del 83%. La sensibilidad y especificidad agrupadas (IC 95%) fueron del 79% (70-86%) y 73% (62-82%), respectivamente, y los cocientes de verosimilitud positivos y negativos fueron 2,94 (IC 95%: 2,13-4,00) y 0,272 (IC 95%: 0,188-0,371). Cuando solo se consideraron los fetos no sometidos a transfusión, la predicción mejoró, pues se logró un ABC del 87%, una sensibilidad del 86% (IC 95%: 75-93%) y una especificidad del 71% (IC 95%: 49-87%). Se observó una disminución en la sensibilidad de la predicción de la anemia moderada-severa mediante la MCA-PSV ≥1.5MdM (estimación, -5,5% (IC 95%: -10,7 a -0,3%), P=0,039) en función del aumento del número de transfusiones previas. CONCLUSIONES: El uso de la MCA-PSV ≥1.5MdM para la predicción de la anemia moderada-severa en fetos no sometidos a transfusión muestra una precisión moderada (86% de sensibilidad y 71% de especificidad), que disminuye con el aumento del número de transfusiones intrauterinas.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

Management of suspected primary Toxoplasma gondii infection in pregnant women in Norway: twenty years of experience of amniocentesis in a low-prevalence population.

BACKGROUND: Primary infection with Toxoplasma gondii during pregnancy may pose a threat to the fetus. Women infected prior to conception are unlikely to transmit the parasite to the fetus. If maternal serology indicates a possible primary infection, amniocentesis for toxoplasma PCR analysis is performed and antiparasitic treatment given. However, discriminating between primary and latent infection is challenging and unnecessary amniocenteses may occur. Procedure-related fetal loss after amniocentesis is of concern. The aim of the present study was to determine whether amniocentesis is performed on the correct patients and whether the procedure is safe for this indication. METHODS: Retrospective study analysing data from all singleton pregnancies (n = 346) at Oslo University Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma infection during 1993-2013. Maternal, neonatal and infant data were obtained from clinical hospital records, laboratory records and pregnancy charts. All serum samples were analysed at the Norwegian Institute of Public Health or at the Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses were performed at Oslo University Hospital by experienced personnel. Time of maternal infection was evaluated retrospectively based on serology results. RESULTS: 50% (173) of the women were infected before pregnancy, 23% (80) possibly in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring were infected with toxoplasma, one of them with negative PCR in the amniotic fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs) (Q1 = 15, Q3 = 22), with median sample volume 4 ml (Q1 = 3, Q3 = 7). Two miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One of these had severe fetal toxoplasma infection. CONCLUSIONS: Half of our study population were infected before pregnancy. In order to reduce the unnecessary amniocenteses we advise confirmatory serology 3 weeks after a suspect result and suggest that the serology is interpreted by dedicated multidisciplinary staff. Amniocentesis is safe and useful as a diagnostic procedure in diagnosing congenital toxoplasma infection when performed after 15 GW.

A general framework for the regression analysis of pooled biomarker assessments.

As a cost-efficient data collection mechanism, the process of assaying pooled biospecimens is becoming increasingly common in epidemiological research; for example, pooling has been proposed for the purpose of evaluating the diagnostic efficacy of biological markers (biomarkers). To this end, several authors have proposed techniques that allow for the analysis of continuous pooled biomarker assessments. Regretfully, most of these techniques proceed under restrictive assumptions, are unable to account for the effects of measurement error, and fail to control for confounding variables. These limitations are understandably attributable to the complex structure that is inherent to measurements taken on pooled specimens. Consequently, in order to provide practitioners with the tools necessary to accurately and efficiently analyze pooled biomarker assessments, herein, a general Monte Carlo maximum likelihood-based procedure is presented. The proposed approach allows for the regression analysis of pooled data under practically all parametric models and can be used to directly account for the effects of measurement error. Through simulation, it is shown that the proposed approach can accurately and efficiently estimate all unknown parameters and is more computational efficient than existing techniques. This new methodology is further illustrated using monocyte chemotactic protein-1 data collected by the Collaborative Perinatal Project in an effort to assess the relationship between this chemokine and the risk of miscarriage. Copyright © 2017 John Wiley & Sons, Ltd.

Spontaneous Pregnancy Loss in Denmark Following Economic Downturns.

An estimated 11%-20% of clinically recognized pregnancies result in spontaneous abortion. The literature finds elevated risk of spontaneous abortion among women who report adverse financial life events. This work suggests that, at the population level, national economic decline-an ambient and plausibly unexpected stressor-will precede an increase in spontaneous abortion. We tested this hypothesis using high-quality information on pregnancy and spontaneous loss for all women in Denmark. We applied time-series methods to monthly counts of clinically detected spontaneous abortions (n = 157,449) and the unemployment rate in Denmark beginning in January 1995 and ending in December 2009. Our statistical methods controlled for temporal patterns in spontaneous abortion (e.g., seasonality, trend) and changes in the population of pregnancies at risk of loss. Unexpected increases in the unemployment rate preceded by 1 month a rise in the number of spontaneous abortions (ß = 33.19 losses/month, 95% confidence interval: 8.71, 57.67). An attendant analysis that used consumption of durable household goods as an indicator of financial insecurity supported the inference from our main test. Changes over time in elective abortions and in the cohort composition of high-risk pregnancies did not account for results. It appears that in Denmark, ambient stressors as common as increasing unemployment may precede a population-level increase in spontaneous abortion.

Women's and healthcare professionals' preferences for prenatal testing: a discrete choice experiment.

OBJECTIVE: This study evaluates pregnant women's and healthcare professionals' preferences regarding specific prenatal screening and diagnostic test characteristics. METHOD: A discrete choice experiment was developed to assess preferences for prenatal tests that differed in seven attributes: minimal gestational age, time to test results, level of information, detection rate, false positive rate, miscarriage risk and costs. RESULTS: The questionnaire was completed by 596 (70.2%) pregnant women and 297 (51.7%) healthcare professionals, of whom 507 (85.1%) and 283 (95.3%), respectively, were included in further analyses as their choice behavior indicated prenatal testing was an option to them. Comparison of results showed differences in relative importance attached to attributes, further reflected by differences in willingness to trade between attributes. Pregnant women are willing to accept a less accurate test to obtain more information on fetal chromosomal status or to exclude the risk of procedure-related miscarriage. Healthcare professionals consider level of information and miscarriage risk to be most important as well but put more emphasis on timing and accuracy. CONCLUSION: Pregnant women and healthcare professionals differ significantly in their preferences regarding prenatal test characteristics. Healthcare professionals should take these differences into consideration when counseling pregnant women on prenatal testing.

The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis.

OBJECTIVE: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great potential for prenatal medicine is evident, more information regarding the consequences of implementing NIPT in a national programme for prenatal screening is required. STUDY DESIGN: A decision-analytic model was developed to compare costs and outcomes of current clinical practice in The Netherlands using conventional screening only, with two alternatives: implementing NIPT as an optional secondary screening test for those pregnancies complicated by a high risk for T21, and implementing NIPT as primary screening test, replacing conventional screening. Probability estimates were derived from a systematic review of international literature. Costs were determined from a health-care perspective. Data were analysed to obtain outcomes, total costs, relative costs and incremental cost-effectiveness ratios (ICERs) for the different strategies. Sensitivity analysis was used to assess the impact of assumptions on model results. RESULTS: Implementing NIPT as an optional secondary, or as primary screening test will increase T21 detection rate by 36% (from 46.8% to 63.5%) and 54% (from 46.8% to 72.0%), simultaneously decreasing the average risk of procedure-related miscarriage by 44% (from 0.0168% to 0.0094% per pregnant woman) and 62% (from 0.0168% to 0.0064% per pregnant woman), respectively. None of the strategies clearly dominated: current clinical practice is the least costly, whereas implementing NIPT will cause total costs of the programme to increase by 21% (from €257.09 to €311.74 per pregnant woman), leading to an ICER of k€94 per detected case of T21, when utilised as an optional secondary screening test and by 157% (from €257.09 to €660.94 per pregnant woman), leading to an ICER of k€460 per detected case of T21, when utilised as primary screening test. However, implementing NIPT as triage test did result in the lowest expected relative costs per case of T21 diagnosed (k€141). CONCLUSION: NIPT should be implemented in national health care as an optional secondary screening test for those pregnancies complicated by a high risk for T21.

Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK National Health Service.

BACKGROUND: Non-invasive prenatal testing (NIPT) for Down's syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service. METHODS: We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost. RESULTS: At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs. CONCLUSIONS: NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.

Screening for autoimmune thyroid disorders after spontaneous abortion is cost-saving and it improves the subsequent pregnancy rate.

BACKGROUND: Hypothyroidism and/or autoimmune thyroid disorders (AITD) may contribute to spontaneous abortions (SpA). Cost-effectiveness analyses of thyroid screening in women after SpA are lacking. Our aim was to evaluate the cost-effectiveness of screening for AITD and/or hypothyroidism and their treatment in women after SpA with regard to their reproductive health. METHODS: We performed a cross-sectional non-randomized study with follow-up in 2008-2011 in the settings of Departments of Endocrinology and Obstetrics/Gynecology of a university hospital. We enrolled 258 women after SpA before the 12th gestational week and followed them for a median of 3 years. At enrollment, serum concentrations of thyroid stimulatory hormone (TSH), antibodies to thyroid peroxidase (TPOAb) and free thyroxine (FT4) were measured and thyroid ultrasound performed. Women with overt hypothyroidism were treated with levothyroxine (n = 45; 61.6%) and women with subclinical hypothyroidism or euthyroid AITD were treated (n = 28; 38.4%) or left untreated (n = 38; 14.7%). Euthyroid women without signs of AITD served as controls (n = 147; 57.0%). RESULTS: Of the 38 untreated women with AITD and/or subclinical hypothyroidism, 8 (21.1%) reported secondary infertility as compared to 16/147 (10.9%) controls and 3/73 (4.1%) treated women (p = 0.021). Treatment was associated with an increased rate of successfully completed subsequent pregnancies (increment of 6 newborns/100 women) and a savings of €19,539/100 women. Total costs per successfully completed pregnancy were €1,189 in controls, €1,564 in the treated, and €2,488 in the untreated women. CONCLUSIONS: Screening for thyroid disorders in women after SpA and treatment with levothyroxine is cost-saving and it improves the subsequent pregnancy rate.

Prenatal screening for Down syndrome in Australia: costs and benefits of current and novel screening strategies.

OBJECTIVE: To analyse the cost-effectiveness and performance of noninvasive prenatal testing (NIPT) for high-risk pregnancies following first-trimester screening compared with current practice. METHODS: A decision tree analysis was used to compare the costs and benefits of current practice of first-trimester screening with a testing pathway incorporating NIPT. We applied the model to 32 478 singleton pregnancies screened between January 2005 and December 2006, adding Medicare rebate data as a measure of public health system costs. The analyses reflect the actual uptake of screening and diagnostic testing and pregnancy outcomes in this cohort. RESULTS: The introduction of NIPT would reduce the number of invasive diagnostic procedures and procedure-related fetal losses in high-risk women by 88%. If NIPT was adopted by all women identified as high risk by first-trimester combined screening, up to 7 additional Down syndrome fetuses could be confirmed. The cost per trisomy 21 case confirmed, including NIPT was 9.7% higher ($56,360) than the current prenatal testing strategy ($51,372) at a total cost of $3.91 million compared with $3.57 million over 2 years. CONCLUSION: Based on the uptake of screening and diagnostic testing in a retrospective cohort of first-trimester screening in Western Australia, the implementation of NIPT would reduce the number of invasive diagnostic tests and the number of procedure-related fetal losses and increase the cost by 9.7% over two years. Policy planning and guidelines are urgently required to manage the funding and demand for NIPT services in Australia.

A tradeoff analysis of risk cutoffs for the quadruple serum screen for Down syndrome.

OBJECTIVES: In maternal serum screening for Down syndrome, a cutoff of 1 : 270 is often used as a decision point to recommend invasive confirmatory testing. However, it has not been established how well this or any other cutoff relates to patient preferences, that is, the values that pregnant women attach to various screening outcomes. The purpose of this study was to examine the clinical and economic tradeoffs of a wide range of risk cutoffs for the quadruple screen. METHODS: Screening costs and outcomes for multiple risk cutoffs were modeled using a Monte Carlo simulation. RESULTS: The optimal cutoff for maternal serum screening depends on the relative values placed by the patient on different outcomes. Total societal costs were similar across the range of cutoffs. CONCLUSIONS: Given that different screening outcomes are optimized by different cutoff values, a one-size-fits-all approach may not be appropriate.