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Objective To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. Design A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting Fourteen Swedish hospitals during 2016-2018. Population Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. Methods Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures The cost per gained life year and per gained QALY. Results The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was euro4108 in the IOL group (n = 1373) and euro4037 in the expectant management group (n = 1373), with a mean difference of euro71 (95% CI -euro232 to euro379). The ICER for IOL compared with expectant management was euro545 per life year gained and euro623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.

Study question Are women who give birth after assisted reproductive technology (ART) at higher risk of breast cancer than women who give birth after natural conception? Summary answer Risk of breast cancer was similar or lower for women who gave birth after ART-conception compared to women who gave birth after natural conception. What is known already Most studies indicate no increase in breast cancer risk after use of ART, but results have been conflicting and with limited confounder control. Interpretation of existing knowledge is further complicated by the well-established dual effect of pregnancy on breast cancer risk, with short-term increase in risk and long-term protection. The population of ART-treated women is still relatively young and further studies are needed to understand how fertility treatment, pregnancy and causes of infertility collectively influence breast cancer risk in women treated with ART. Study design, size, duration Cohort study based on data linkage between the Medical Birth Registries, ART Registries, Population and Cause of Death Registries in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015) and the Cancer Registries in each country (1958-2014, 1954-2014, 1953-2015, 1958-2015, respectively). We included 2,283,592 women who gave their first birth during the study period, at age ≥25 years. Among these, 111,781 women had at least one birth after ART conception. Participants/materials, setting, methods Women without prior cancer were followed from first birth to date of first cancer, death, emigration, or end of follow-up. We compared risk of breast cancer in Cox regression for women who ever gave birth after ART (time-dependent) vs women with birth(s) after natural conception only, using age as the time scale. We included age at first birth, parity (time-dependent), country and year of delivery as covariates. Sub-analyses included height, body mass index and smoking. Main results and the role of chance Women who gave birth after ART were on average 3 years older than women who gave birth after natural conception. Among women who gave birth after ART, 1,101 were diagnosed with breast cancer during a median follow-up of 8.8 years (incidence rate 101/100,000 person-years), compared to 26,984 cases during a median follow-up of 12.7 years (incidence rate 91/100,000 person-years) among women with naturally conceived pregnancies. Age-specific rates were similar. After covariate adjustment, risk was slightly lower for women with ART vs natural conception (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.87 - 0.99). Further adjustment for height, body mass index and smoking gave similar results. Age at first birth was not clearly associated with breast cancer risk for women with either conception method. Women with ART-conception in their first two pregnancies had lower risk (HR 0.83, 95% CI 0.70 - 0.98), whereas no clear differences were found for women with both conception methods, compared to women with two naturally conceived pregnancies. Associations according to ART indication (male, ovarian, other female and unexplained infertility) were consistent with the main findings, as were results for treatment type (IVF, ICSI, fresh and frozen transfer, and single or double embryo transfer). Limitations, reasons for caution We had no data on unsuccessful ART treatments, number or type of stimulation cycles. Because only women who gave birth were included, and because a large proportion of ART-treated women had unknown cause of infertility, we cannot exclude residual confounding from causes or severity of infertility. Wider implications of the findings Women with successful ART treatment had similar or slightly lower risk of breast cancer compared to women who gave birth after natural conception. Although this study could not completely rule out adverse effects of ART on breast cancer risk, we found no evidence to support strong adverse effects. Trial registration number Not applicable

To estimate the cost-effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context.We designed a decision analytic model based on the Swedish CERVIX study to estimate the cost-effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision-tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely 'Universal screening', 'High-risk-based screening' (i.e. screening of high-risk women only), 'Low-risk-based screening' (i.e. treatment of high-risk population and screening of remaining women) and 'Nullipara screening' (i.e. treatment of high-risk population and screening of nulliparous women only), included second-trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening ('No screening, treat high-risk group'). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden ('No screening'). Probabilities for a short cervix (CL ≤ 25 mm; base-case) and for spontaneous PTD at 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long-term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33-36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality-adjusted life years (QALYs) and presented cost-effectiveness as average (ACER; average cost per gained QALY compared with 'No screening') and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost-effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost-effectiveness acceptability curves. Willingness-to-pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare.All interventions had better health outcomes than did 'No screening', with fewer screening-year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was 'Low-risk-based screening', irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). 'Low-risk-based screening' at Cx1 was cost-effective, while 'Low-risk-based screening' at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for 'Low-risk-based screening' at Cx1 and 36 800 USD for 'Low-risk-based screening' at Cx2. Cost-effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that 'Low-risk-based screening' at Cx1 is cost-effective compared with 'No screening' was 71%.Interventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost-effective in Sweden. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: The objectives were 1. to evaluate if the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine was altered in mild and severe forms of preeclampsia, and 2. to assess the relationship between dimethylarginines and the cytokine response in preeclampsia. METHODS: Asymmetric and symmetric dimethylarginine were measured with high performance liquid chromatography in women with mild (n=13) and severe (n=32) preeclampsia and in normotensive pregnant controls (n=20). Interleukin-4, -6, -8, -10 and tumor necrosis factor-alpha were analyzed by immunoassays in women with mild (n=8) and severe (n=17) preeclampsia and in normotensive pregnant controls (n=14). The Mann Whitney U-test and Spearman Rank test were used for statistical analysis. RESULTS: The plasma levels of dimethylarginine were increased in preeclamptic subjects. The elevation of symmetric dimethylarginine was more pronounced than that of asymmetric dimethylarginine. The control levels of interleukin-6, -8 and -10 were significantly higher at term than at gestational week 32-36. Interleukin-6 and -8 were significantly elevated in subjects with severe, but not mild, preeclampsia, whereas TNF-alpha and IL-10 were not significantly altered. Symmetric dimethylarginine levels correlated significantly with arterial blood pressure and serum levels of creatinine and uric acid. Dimethylarginine levels in plasma were, however, not related to the cytokine response. CONCLUSIONS: Plasma concentrations of both asymmetric and symmetric dimethylarginine were significantly elevated both in mild and severe preeclampsia. Symmetric, but not asymmetric, dimethylarginine correlated to the severity of the condition. Plasma levels of interleukin-6 and -8 were also elevated in severe preeclampsia but no direct correlations were found between these cytokines and dimethylarginines.

Microbial invasion of the amniotic cavity is a major cause of preterm delivery and the diagnosis is dependent on invasive amniocentesis. The objective was to determine whether specific proteins in amniotic and cervical fluids alone, or in combination, could identify bacterial invasion.A prospective follow-up study.Women with singleton pregnancies presenting with preterm labour between 22 and 33 weeks of gestation (n = 89).Sahlgrenska University Hospital, Gothenburg, Sweden.Amniotic and cervical fluid was analysed with polymerase chain reaction for Mycoplasmas, and was cultured for aerobic and anaerobic bacteria. Twenty-seven proteins were analysed using multiplex technology. Individual levels of each protein were compared in order to find associations between different proteins and microbial invasion of the amniotic cavity. Predictive models based on multiple proteins were created using stepwise binary logistic regression.The main outcome measure was microbial invasion of the amniotic cavity.Microbial invasion of the amniotic cavity was present in 17% (15/89) of the women. Concentration levels of several amniotic and cervical proteins were significantly higher in women with microbial invasion of the amniotic cavity. Three multivariate predictive models were found. The predictive power of the non-invasive model (73% sensitivity, 88% specificity, 55% positive predictive value, 94% negative predictive value) was as good as the invasive models. Area under the receiver operating characteristic (ROC) curve and likelihood ratio were 0.87 and 6.0, respectively.Prediction of intra-amniotic infection using selected cervical proteins was equally good as prediction using the same proteins collected from amniotic fluid, or a combination of cervical and amniotic proteins.

ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (

This paper provides an overview of the effects of cryopreservation on obstetric outcome and child development. Cryopreservation of embryos has no apparent negative impact on perinatal outcome and early infant development. The available data do not indicate an elevated congenital malformation rate. Intracytoplasmic sperm injection and cryopreservation is comparable with conventional in-vitro fertilization and cryopreservation. It remains unclear if embryo freezing poses long-term risks to children so conceived. There are several potential advantages of oocyte freezing which, however, is still a research procedure.

The purpose was to determine the prognostic value of interleukin (IL) 1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (37 weeks of gestation) in twin pregnancies.The study included screening of 121 women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal fluid was smeared and dried for later evaluation of bacterial vaginosis (presence of clue cells).Spontaneous preterm birth occurred in 36 women and 65 women were delivered at term. IL-8 was significantly higher (p=0.03) in samples from women delivered preterm (median 3.72 ng/g mucus, range0.07-220.00) compared with samples from women delivered at term (median 3.03 ng/g mucus, range0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a sensitivity, specificity, positive and negative predictive value of 78.8, 45.8, 44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not significantly associated with preterm birth. Bacterial vaginosis was found in 47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were significantly higher in samples positive for bacterial vaginosis than in negative samples (p0.0001 and p0.01, respectively). There was no significant association between the level of IL-6 and bacterial vaginosis.IL-8, but not IL-1alpha and IL-6, was associated with preterm delivery but the relationship was too weak to be of predictive value for preterm birth in twin pregnancies. IL-1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.

Two hundred and six pregnancies occurring after in vitro fertilization (IVF) and embryo transfer (ET) during a 7-year period in Goteborg were analysed with respect to pregnancy outcome. The clinical abortion rate was 26%, the rate of ectopic pregnancy was 10%, the rate of ongoing pregnancies beyond 24 weeks was 15%, and the rate of deliveries was 49% (n = 100). The hospital records of 98 women with the 100 deliveries resulting in 131 infants were studied. Multiple pregnancy occurred in 27%, including one quadruplet and two triplet pregnancies. Preterm birth occurred in 30% of all pregnancies and in 20% of singleton pregnancies. Thirty-four percent of the infants had a birth weight of less than 2500 g. The perinatal mortality was 46/1000, as estimated from the 24th week of pregnancy. The incidence of major malformation, 2.3%, was similar to that reported from studies in the general population. The first 100 infants born were followed up for 18 months to 8 years. Long-term sequelae were associated with immaturity and low birth weight. No problems during follow-up were disclosed in children who had had an uneventful neonatal period. It is concluded that IVF pregnancies are an obstetric risk group requiring special attention.