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1.	Sundh, Karin Jerhamre, et al. (author) Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS). 2014 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 29:9, s. 2050-7 Journal article (peer-reviewed)abstract Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer?
2.	Wennerholm, Ulla-Britt, 1948, et al. (author) Gestational age in pregnancies after in vitro fertilization: comparison between ultrasound measurement and actual age 1998 In: Ultrasound in Obstetrics and Gynecology. - 0960-7692 .- 1469-0705. ; 12:3, s. 170-4 Journal article (peer-reviewed)
3.	Wennerholm, Ulla-Britt, 1948, et al. (author) Obstetric and perinatal outcome of children conceived from cryopreserved embryos 1997 In: Human Reproduction. - 0268-1161 .- 1460-2350. ; 12:8 Journal article (peer-reviewed)
4.	Wennerholm, Ulla-Britt, 1948, et al. (author) Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection 1996 In: Human Reproduction. - 0268-1161 .- 1460-2350. ; 11:5, s. 1113-9 Journal article (peer-reviewed)
5.	Wennerholm, Ulla-Britt, 1948, et al. (author) Postnatal growth and health in children born after cryopreservation as embryos 1998 In: The Lancet. - 0140-6736. ; 351:9109 Journal article (peer-reviewed)
6.	Ahlin, Kristina, et al. (author) Cerebral palsy and perinatal infection in children born at term. 2013 In: Obstetrics and gynecology. - 1873-233X. ; 122:1, s. 41-9 Journal article (peer-reviewed)abstract To investigate the link between infection-related risk factors for cerebral palsy subtypes in children born at term.
7.	Ahlin, Kristina, et al. (author) Non-infectious risk factors for different types of cerebral palsy in term-born babies: a population-based, case-control study. 2013 In: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 120:6, s. 724-731 Journal article (peer-reviewed)abstract OBJECTIVE: To identify non-infectious antenatal and perinatal risk factors for cerebral palsy (CP) and its subtypes in children born at term. DESIGN: A population-based, case-control study. SETTING: The western healthcare region of Sweden. POPULATION: A population-based series of children with CP born at term during 1983-94 (n=309) was matched with a control group (n=618). METHODS: A total of 62 variables, maternal characteristics, and prepartal, intrapartal and postpartal variables were retrieved from obstetric records. Both univariate and multivariate analyses were performed for spastic and dyskinetic CP, and for the total CP group. MAIN OUTCOME MEASURES: Cerebral palsy (CP) and subtypes. RESULTS: Univariate analysis resulted in 26 significant risk factors for CP. Birthweight (OR0.54, 95%CI0.39-0.74), not living with the baby's father (OR2.58, 95%CI 1.11-5.97), admittance to a neonatal intensive care unit (NICU) (OR 4.43, 95% CI 3.03-6.47), maternal weight at 34weeks of gestation (OR1.02, 95%CI 1.00-1.03) and neonatal encephalopathy (OR69.2, 95%CI 9.36-511.89) were found to be risk factors for CP in the totalCP group in our multivariate analysis. Factors during the periods before, during and after delivery were all shown to increase the risk of spastic diplegia and tetraplegia, whereas mostly factors during the period before delivery increased the risk of spastic hemiplegia, and only factors during delivery increased the risk of dyskinetic CP. Admittance to an NICU was a risk factor for all CP subtypes. CONCLUSIONS: The risk factor pattern differed by CP subtype. The presented risk factors may be useful indicators for identifying children at risk of developing CP, and helpful for targeting individuals for early intervention programmes.
8.	Aittomaki, K, et al. (author) Genetics and assisted reproduction technology 2005 In: Acta Obstet Gynecol Scand. - : Wiley. ; 84:5, s. 463-473 Journal article (peer-reviewed)abstract In the past 20 years, a significant improvement has been shown in the treatment for infertility in both women and men through the development of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Only donated sperm could be previously used for treatment; now oocytes can also be donated. Furthermore, the combination of IVF and ICSI with advanced genetic methods has made preimplantation genetic diagnosis possible for many genetic conditions. These methods enable genetic testing of the early human embryo by using only a single cell, one blastomere biopsied from the embryo, as the sample from which the diagnosis of many chromosome rearrangements and other inherited diseases can be made. It has also been established that a considerable proportion of infertility is caused by genetic defects, which have several implications for infertility treatment. The purpose of this review is to give a concise introduction on how genetics is involved in assisted reproduction technology to specialists who may not be working in this particular field of gynecology, but who would need some knowledge of this for proper care of their patients.
9.	Aittomaki, K, et al. (author) Safety issues in assisted reproduction technology: should ICSI patients have genetic testing before treatment? A practical proposition to help patient information 2004 In: Hum Reprod. - : Oxford University Press (OUP). ; 19:3, s. 472-476 Journal article (peer-reviewed)abstract 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 (<5 x 10(6)/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.
10.	Alkmark, Mårten, 1973, et al. (author) Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS) 2021 In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477 Journal article (peer-reviewed)abstract Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41(+0) to 42(+0 to 1) weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] versus 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] versus 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusion Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
11.	Alkmark, Mårten, 1973, et al. (author) God vetenskaplig grund för att erbjuda kvinnor igångsättning i vecka 41 2021 In: Dagens Nyheter (DN Debatt). - 1101-2447. ; :2021-08-06 Journal article (pop. science, debate, etc.)
12.	Alkmark, Mårten, 1973, et al. (author) Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials. 2020 In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 17:12 Journal article (peer-reviewed)abstract The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD -31/10,000, [95% CI -56/10,000 to -5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD -97/10,000 [95% CI -169/10,000 to -26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174.
13.	Alkmark, Mårten, 1973, et al. (author) Induction of labour at 41weeks of gestation versus expectant management and induction of labour at 42weeks of gestation: a cost-effectiveness analysis 2022 In: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:13, s. 2157-2165 Journal article (peer-reviewed)abstract Objective: To assess the cost-effectiveness of induction of labour (IOL) at 41weeks of gestation compared with expectant management until 42weeks 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 41weeks of gestation to IOL or to expectant management and induction at 42weeks 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 €4108 in the IOL group (n=1373) and €4037 in the expectant management group (n=1373), with a mean difference of €71 (95%CI −€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 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 41weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract: Induction of labour at 41weeks of gestation is cost-effective compared with expectant management until 42weeks of gestation.
14.	Berg, Marie, 1955, et al. (author) Diabetes och graviditet : Den komplicerade graviditeten 2016 In: Reproduktiv hälsa - barnmorskans kompetensområde. Helena Lindgren et al. Del 2, 18.6, s. 357-368. - Lund : Studentlitteratur AB. - 9789144090054 ; , s. 357-368 Book chapter (peer-reviewed)abstract Reproduktiv, perinatal och sexuell hälsa är ett självständigt huvudområde knutet till livets början och området för mänsklig reproduktion i ett livscykel- och genusperspektiv. Inom huvudområdet studeras och utvecklas kunskap om den normala processen och dess avvikelser i samband med graviditet, förlossning och nyföddhetsperiod samt föräldraskapets utveckling. Vidare studeras och utvecklas kunskap och teorier om kvinnors reproduktiva hälsa, sexualitet och fertilitetskontroll samt barnmorskans främjande, förebyggande, vårdande och behandlande arbete - med och för - kvinnan, barnet och familjen. Reproduktiv hälsa omfattar barnmorskans verksamhet inom reproduktiv, perinatal och sexuell hälsa. Boken är uppbyggd utifrån ICM:s (International Confederation of Midwives) beskrivning av barnmorskans kompetensområden, och den omfattar även ett webbmaterial med bland annat sammanfattningar i form av bildspel, tester och undervisningsfilmer. Boken riktar sig till barnmorskestudenter och yrkes verk samma barnmorskor samt till övriga hälsoprofessioner verksamma inom reproduktiv hälsa. Reproduktiv hälsa är framtagen i dialog med, och granskad av, vårt vetenskapliga råd. Vi rekommenderar att den används som lärobok i barnmorskeutbildningen fortsättningsvis.
15.	Berg, Marie, 1955, et al. (author) Diabetes och graviditet. I: Lindgren H., Christensson K., Dykes A-K. Reproduktiv hälsa - barnmorskans kompetensområde (second edition). 2022 Book (other academic/artistic)
16.	Berg, Marie, 1955, et al. (author) Indikation för värkstimulering med oxytocin under aktiv förlossning 2011 Reports (other academic/artistic)
17.	Bergh, Christina, 1953, et al. (author) A certain increased risk of abnormalities after in vitro fertilization 2002 In: Läkartidningen. - 0023-7205. ; 99:26-27, s. 2957-8 Journal article (peer-reviewed)
18.	Bergh, Christina, 1953, et al. (author) Attitudes towards and management of single embryo transfer among Nordic IVF doctors 2007 In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 86:10, s. 1222-1230 Journal article (peer-reviewed)abstract Background. The objective of this study was to investigate the attitudes towards and management of single embryo transfer (SET) among Nordic in vitro fertilisation (IVF) doctors, and to present the rate of SET and multiple pregnancies in the different countries. Methods. A questionnaire was sent to all IVF doctors in the Nordic countries (n=198, 78.5% responded). Pregnancy rates, SET and multiple births rates were extracted from registries. Main outcome measure was attitudes and management of SET. Results. Almost all doctors thought that a twin pregnancy compared unfavourably to a singleton. A twin rate >10% was acceptable for 5% of Swedish doctors. Corresponding figures for Finnish, Danish and Norwegian doctors were 21, 35 and 35%, respectively. For a woman <36 years, performing her first cycle and with two good quality embryos, almost all doctors would recommend SET. For a woman =36 years in a similar situation, SET would be recommended only in Sweden and Finland. The pregnancy rate per embryo transfer (ET), the SET rate 2003, the multiple birth rate, and the estimated SET rate 2004 were 33.3, 21.5, 22.7 and 25% (Denmark), 31.3, 43.4, 14 and 51% (Finland), 40.5, 10.5, 26.5 and 16% (Iceland), 30.6, 18, 25.2 and 26% (Norway), and 35.3, 55.1, 11.8 and 71% (Sweden). Conclusions. The SET and multiple birth rates reflect the attitudes of Nordic IVF doctors to SET and multiple births well. When introducing SET, the attitude of the IVF doctor seems to be important. © 2007 Taylor & Francis.
19.	Bergh, Christina, 1953, et al. (author) Long-term health of children conceived after assisted reproductive technology 2020 In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:2, s. 152-157 Journal article (peer-reviewed)abstract The aim of this narrative review is to summarize the present knowledge on long-term outcome of children born after assisted reproductive technologies (ART). The main outcomes covered are neurodevelopment including cerebral palsy, cognitive development, attention deficit hyperactivity disorder and autism spectrum disease, growth, cardiovascular function, diabetes type 1, asthma, malignancies, and reproductive health. Results have mainly been obtained from systematic reviews/meta-analyses and large registry studies. It has been shown that children born after ART, when restricted to singletons, have a similar outcome for many health conditions as their spontaneously conceived peers. For some outcomes, particularly cardiovascular function and diabetes, studies show some higher risk for ART singletons or subgroup of ART singletons. The fast introduction of new ART techniques emphasizes the importance of continuous surveillance of children born after ART.
20.	Bergh, Christina, 1953, et al. (author) Låg risk för ohälsa hos barn födda efter in vitro-fertilisering : [Low risk of illness among children born after fertilization in vitro] 2010 In: Läkartidningen. - 0023-7205. ; 107:42, s. 2554-2559 Journal article (peer-reviewed)abstract Mer än 4 miljoner barn har fötts i världen efter IVF, och 40000 i Sverige. De senaste åren har ca 3500 IVF-barn fötts i Sverige. De allra flesta barn födda efter IVF är friska. Den största risken med IVF internationellt sett är den höga flerbördsfrekvensen som leder till ökade risker för barnen, framför allt beroende på förtidsbörd. Den höga flerbördsfrekvensen beror på att man återför flera befruktade ägg. I Sverige återför man i dag i allmänhet endast ett befruktat ägg. Därmed har risken för graviditetskomplikationer och förtidsbörd minskat betydligt. Det finns en liten men väldokumenterad ökad risk för missbildningar efter IVF. Utöver förhöjd flerbördsfrekvens beror de ökade riskerna sannolikt på individuella egenskaper hos föräldrarna och inte på IVF-tekniken i sig. Fortsatt uppföljning är nödvändig för att följa barnen högre upp i åldrarna och för att följa riskutvecklingen när nya tekniker införs.
21.	Bergh, Christina, 1953, et al. (author) Obstetric outcome and long-term follow up of children conceived through assisted reproduction. 2012 In: Best practice & research. Clinical obstetrics & gynaecology. - : Elsevier BV. - 1532-1932 .- 1521-6934. ; 26:6, s. 841-852 Journal article (peer-reviewed)abstract Most children born after assisted reproduction techniques are healthy. The most important risk associated with in-vitro fertilisation is the higher multiple birth rate, which may result in increased child morbidity because several embryos are transferred at each cycle. Single-embryo transfer reduces this risk dramatically. Large registry studies and meta-analyses have indicated a small but statistically significantly increased risk of congenital malformations among children born after in-vitro fertilisation. Other risks, such as preterm birth and low birth weight seem to be associated more with parental characteristics than the in-vitro fertilisation technique. All knowledge about children conceived through in-vitro fertilisation is based on observational studies, with risks of bias and confounders. It is possible that pregnancies and children resulting from in-vitro fertilisation are more carefully monitored and seek health care more frequently, resulting in more health problems being discovered. Continuous follow up of children after in-vitro fertilisation is of great importance, particularly as new techniques are constantly being introduced.
22.	Bergh, Christina, 1953, et al. (author) Parental age and child outcomes 2019 In: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 111:6, s. 1036-1046 Journal article (peer-reviewed)abstract This review summarizes the impact of parental age on children's health outcomes beyond the perinatal period. In the last decades, delayed parenthood with both men and women has become a public health issue. For women, in particular, the size of this delay is substantial. For a few medical conditions, older parental age has a pronounced effect on child morbidity. For most other outcomes, a more modest effect is evident. Although these effects might be limited on an individual level, they have a substantial impact at the level of population health. ((C) 2019 by American Society for Reproductive Medicine.)
23.	Berntsen, S, et al. (author) The Health of Children conceived by assisted reproductive technology (ART). "The chicken or the egg?" 2019 In: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 25:2, s. 137-158 Journal article (peer-reviewed)
24.	Bonduelle, M, et al. (author) A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception 2005 In: Hum Reprod. ; 20:2, s. 413-9 Journal article (peer-reviewed)abstract BACKGROUND: Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old children from five European countries were comprehensively assessed, along with 538 matched naturally conceived children and 437 children conceived with standard IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a major congenital malformation. Compared with naturally conceived children, the odds of a major malformation were 2.77 (95% CI 1.41-5.46) for ICSI children and 1.80 (95% CI 0.85-3.81) for IVF children; these estimates were little affected by adjustment for socio-demographic factors. The higher rate observed in the ICSI group was due partially to an excess of malformations in the (boys') urogenital system. In addition, ICSI and IVF children were more likely than naturally conceived children to have had a significant childhood illness, to have had a surgical operation, to require medical therapy and to be admitted to hospital. A detailed physical examination revealed no further substantial differences between the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more likely to need health care resources than naturally conceived children. Assessment of singleton ICSI and IVF children at 5 years of age was generally reassuring, however, we found that ICSI children presented with more major congenital malformations and both ICSI and IVF children were more likely to need health care resources than naturally conceived children. Ongoing monitoring of these children is therefore required.
25.	Bonduelle, M., et al. (author) Medical follow-up study of 5-year-old ICSI children 2004 In: Reprod Biomed Online. ; 9:1, s. 91-101 Journal article (peer-reviewed)abstract Children born after intracytoplasmic sperm injection (ICSI) are still a matter of concern. The purposes of the present study were to investigate the physical outcome in 5-year-old children born after ICSI and compare them with children born after spontaneous conception. Three hundred singleton children from Belgium, Sweden and the USA, born after ICSI, were matched by maternal age, child age and gender. In one centre, matching was also performed for maternal education. The main end-point was growth. Secondary end-points were general health, e.g. common diseases, chronic illnesses, surgical interventions and physical/neurological examinations. Standard deviation scores assessed growth. Growth assessed as stature at follow-up was similar in the two groups, despite a higher rate of preterm birth and low birth weight in the ICSI children. Common diseases and chronic illnesses occurred at similar rates in both groups. More ICSI children underwent surgical interventions and required other therapy e. g. physiotherapy and dietary therapy. Physical/neurological examinations revealed few abnormalities in either group. In conclusion, infertility treatment by ICSI does not adversely affect growth during childhood. The children's general health seems satisfactory.
26.	Cobo, Teresa, et al. (author) Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture. 2012 In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. Journal article (peer-reviewed)abstract Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Population. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0-) 33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20% and 50%, respectively. There was a higher inflammatory response in women with MIAC than without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid Interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
27.	Elden, Helen, 1959, et al. (author) Study protocol of SWEPIS a Swedish multicentre register based randomised controlled trial to compare induction of labour at 41 completed gestational weeks versus expectant management and induction at 42 completed gestational weeks 2016 In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 16:49 Journal article (peer-reviewed)abstract Background: Observational data shows that postterm pregnancy (>= 42 gestational weeks, GW) and late term pregnancy (>= 41 GW), as compared to term pregnancy, is associated with an increased risk for adverse outcome for the mother and infant. Standard care in many countries is induction of labour at 42 GW. There is insufficient scientific support that induction of labour at 41 GW, as compared with expectant management and induction at 42 GW will reduce perinatal mortality and morbidity without an increase in operative deliveries, negative delivery experiences or higher costs. Large randomised studies are needed since important outcomes; such as perinatal mortality and hypoxic ischaemic encephalopathy are rare events. Methods/Design: A total of 10 038 healthy women >= 18 years old with a normal live singleton pregnancy in cephalic presentation at 41 GW estimated with a first or second trimester ultrasound, who is able to understand oral and written information will be randomised to labour induction at 41 GW (early induction) or expectant management and induction at 42 GW (late induction). Women will be recruited at university clinics and county hospitals in Sweden comprising more than 65 000 deliveries per year. Primary outcome will be a composite of stillbirth, neonatal mortality and severe neonatal morbidity. Secondary outcomes will be other adverse neonatal and maternal outcomes, mode of delivery, women's experience, cost effectiveness and infant morbidity up to 3 months of age. Data on background variables, obstetric and neonatal outcomes will be obtained from the Swedish Pregnancy Register and the Swedish Neonatal Quality Register. Data on women's experiences will be collected by questionnaires after randomisation and 3 months after delivery. Primary analysis will be intention to treat. The statistician will be blinded to group and intervention. Discussion: It is important to investigate if an intervention at 41 GW is superior to standard care in order to reduce death and lifelong disability for the children. The pregnant population, >41 GW, constitutes 15-20 % of all pregnancies and the results of the study will thus have a great impact. The use of registries for randomisation and collection of outcome data represents a unique and new study design.
28.	Fadl, Helena, 1965-, et al. (author) Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol 2019 In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1 Journal article (peer-reviewed)abstract Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
29.	Fagbamigbe, A. F., et al. (author) Comparison of the performances of survival analysis regression models for analysis of conception modes and risk of type-1 diabetes among 1985-2015 Swedish birth cohort 2021 In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6 Journal article (peer-reviewed)abstract The goal is to examine the risk of conception mode-type-1 diabetes using different survival analysis modelling approaches and examine if there are differentials in the risk of type-1 diabetes between children from fresh and frozen-thawed embryo transfers. We aimed to compare the performances and fitness of different survival analysis regression models with the Cox proportional hazard (CPH) model used in an earlier study. The effect of conception modes and other prognostic factors on type-1 diabetes among children conceived either spontaneously or by assisted reproductive technology (ART) and its sub-groups was modelled in the earlier study. We used the information on all singleton children from the Swedish Medical Birth Register hosted by the Swedish National Board of Health and Welfare, 1985 to 2015. The main explanatory variable was the mode of conception. We applied the CPH, parametric and flexible parametric survival regression (FPSR) models to the data at 5% significance level. Loglikelihood, Akaike and Bayesian information criteria were used to assess model fit. Among the 3,138,540 singletons, 47,938 (1.5%) were conceived through ART (11,211 frozen-thawed transfer and 36,727 fresh embryo transfer). In total, 18,118 (0.58%) of the children had type-1 diabetes, higher among (0.58%) those conceived spontaneously than the ART-conceived (0.42%). The median (Interquartile range (IQR)) age at onset of type-1 diabetes among spontaneously conceived children was 10 (14-6) years, 8(5-12) for ART, 6 (4-10) years for frozen-thawed embryo transfer and 9 (5-12) years for fresh embryo transfer. The estimates from the CPH, FPSR and parametric PH models are similar. There was no significant difference in the risk of type-1 diabetes among ART- and spontaneously conceived children; FPSR: (adjusted Hazard Ratio (aHR) = 1.070; 95% Confidence Interval (CI):0.929-1.232, p = 0.346) vs CPH: (aHR = 1.068; 95%CI: 0.927-1.230, p = 0.361). A sub-analysis showed that the adjusted hazard of type-1 diabetes was 37% (aHR = 1.368; 95%CI: 1.013-1.847, p = 0.041) higher among children from frozen-thawed embryo transfer than among children from spontaneous conception. The hazard of type-1 diabetes was higher among children whose mothers do not smoke (aHR = 1.296; 95%CI:1.240-1.354, p<0.001) and of diabetic mothers (aHR = 6.419; 95%CI:5.852-7.041, p<0.001) and fathers (aHR = 8.808; 95%CI:8.221-9.437, p<0.001). The estimates from the CPH, parametric models and the FPSR model were close. This is an indication that the models performed similarly and any of them can be used to model the data. We couldn't establish that ART increases the risk of type-1 diabetes except when it is subdivided into its two subtypes. There is evidence of a greater risk of type-1 diabetes when conception is through frozen-thawed transfer.
30.	Furenäs, Eva, et al. (author) Cardiac Complications during Pregnancy Related to Parity in Women with Congenital Heart Disease 2020 In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 145:8, s. 533-541 Journal article (peer-reviewed)abstract Objective:To describe the frequency of cardiac complications during pregnancy related to parity in women with congenital heart defects.Methods:A retrospective tertiary single-center study at the Adult Congenital Heart Disease Centre that followed 307 women with congenital heart disease during the years 1997-2015 in Gothenburg, Sweden. Ma-ternal cardiac complications were noted for each pregnancy using medical and obstetric records. The CARPREG I and modified WHO (mWHO) risk classifications were used. Twin pregnancies, miscarriages before gestational week 13, and pregnancy terminations were excluded.Results:Five hundred seventy-one deliveries and 9 late miscarriages were analyzed. The mean parity was 1.74 per woman (range 1-8). Eighty-four (14.6%) maternal cardiac complications were experienced; arrhythmia (5.7%) and heart failure (4.4%) being the most prevalent, and there was 1 maternal death. Heart failure occurred during the first pregnancy in 12 women (3.9%), in the second pregnancy in 8 women (4.3%), and in the third pregnancy in 4 women (7.7%). CARPREG I and mWHO scores were associated with an increased risk of having a cardiac complication, while parity per se was not associated. The OR for having a maternally uneventful second pregnancy if the first pregnancy was without cardiac complications was 5.47 (95% CI 1.76-16.94) after controlling for CARPREG I and mWHO scores.Conclusion:The risk of severe maternal cardiac complications during pregnancy in women with congenital heart disease is low. In this largest analysis to date with a focus on parity in 307 women, the risk classification predicts the maternal outcome more than parity per se. If the first pregnancy is uneventful, the OR is 5.5 for an uneventful second pregnancy if CARPREG I and mWHO scores remain unchanged.
31.	Furenäs, Eva, et al. (author) Effect of maternal age and cardiac disease severity on outcome of pregnancy in women with congenital heart disease 2017 In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 243, s. 197-203 Journal article (peer-reviewed)abstract Background: There is an increasing prevalence of women with congenital heart defects reaching childbearing age. In western countries women tend to give birth at a higher age compared to some decades ago. We evaluated the CARdiac disease in PREGnancy (CARPREG) and modified World Health Organization (mWHO) risk classifications for cardiac complications during pregnancies in women with congenital heart defects and analyzed the impact of age on risk of obstetric and fetal outcome. Methods: A single-center observational study of cardiac, obstetric, and neonatal complications with data from cardiac and obstetric records of pregnancies in women with congenital heart disease. Outcomes of 496 pregnancies in 232 women, including induced abortion, miscarriage, stillbirth, and live birth were analyzed regarding complications, maternal age, mode of delivery, and two risk classifications: CARPREG and mWHO. Results: There were 28 induced abortions, 59 fetal loss, 409 deliveries with 412 neonates. Cardiac (14%), obstetric (14%), and neonatal (15%) complications were noted, including one maternal death and five stillbirths. The rate of cesarean section was 19%. Age above 35 years was of borderline importance for cardiac complications (p = 0.054) and was not a significant additional risk factor for obstetric or neonatal complications. Both risk classifications had moderate clinical utility, with area under the curve (AUC) 0.71 for CARPREG and 0.65 for mWHO on cardiac complications. Conclusions: Pregnancy complications in women with congenital heart disease are common but severe complications are rare. Advanced maternal age does not seem to affect complication rate. Existing risk classification systems are insufficient in predicting complications. (C) 2017 Elsevier B.V. All rights reserved.
32.	Furenäs, Eva, et al. (author) Pregnancy in a healthy population: dynamics of NTproBNP and hs-cTroponin T 2020 In: Open Heart. - : BMJ. - 2053-3624. ; 7:2 Journal article (peer-reviewed)abstract Objective To describe the intraindividual changes of heart biomarker levels during and after pregnancy and to evaluate existing cut-off levels for heart failure or myocardial ischaemia in pregnant women. Method A total of 196 healthy pregnant women were recruited from maternal outpatient clinics and included in the study. Blood samples were obtained on four occasions: at 10-12 gestational weeks (gw), 20-25 gw, after delivery and 6 months postpartum and analysed for N-terminal pro-brain natriuretic peptide (NTproBNP) and high sensitive cardiac troponin T (hs-cTNT). Echocardiography ruled out existing cardiac disease. Estimated glomerular filtration rate (eGFR) was calculated. Results There were significant changes in NTproBNP between the measurements with the highest NTproBNP at 10-12 gw and the lowest value being at 20-25 gw, (with eGFR being the highest). Hs-cTNT was significantly higher at the peripartum measurement compared with the other measurements (p<0.05). Regardless, the 95th percentile for both biomarkers was below cut-off levels of 300 ng/L for NTproBNP and 14 ng/L for hs-cTNT. There was an association between NTproBNP above the upper limit of normal of 125 ng/L and eGFR (p=0.04) and between hs-cTNT >5.0 ng/L and time from delivery to blood sample (p=0.001) at the peripartum measurement. Both were associated with the use of oxytocin. Conclusion Existing cut-off values for ruling out heart failure (NTproBNP <300 ng/L) and myocardial ischaemia (hs-cTNT <14 ng/L) are applicable during pregnancy and after delivery. Elevated levels mandate further attention on cardiac symptoms and renal function.
33.	Ginström Ernstad, Erica, et al. (author) Hur går det för IVF-barnen och vilka är riskerna för mödrarna? 2022 In: Läkartidningen. - 0023-7205. ; 119 Research review (peer-reviewed)
34.	Ginström Ernstad, Erica, et al. (author) Neonatal and maternal outcome after blastocyst transfer: a population-based registry study 2016 In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 214:3 Journal article (peer-reviewed)abstract BACKGROUND: Previous studies have shown a higher risk of birth defects and preterm birth (PTB) in singletons born after blastocyst transfer as compared to singletons born after cleavage-stage transfer. Few studies have investigated the maternal outcomes. OBJECTIVE: We sought to analyze the neonatal and maternal outcome after blastocyst transfer (day 5-6) compared to transfer of cleavage-stage embryos (day 2-3) and spontaneous conception. STUDY DESIGN: This was a population-based retrospective registry study including all singleton deliveries after blastocyst transfer in Sweden from 2002 through 2013. The in vitro fertilization register was cross-linked with the Swedish Medical Birth Register, the Register of Birth Defects, and the National Patient Register. Deliveries after blastocyst transfer were compared with deliveries after cleavage-stage transfer and deliveries after spontaneous conception. Outcome measures included birth defects, PTB, low birthweight, small for gestational age, large for gestational age, perinatal mortality, placenta previa, placental abruption, and preeclampsia. Crude and adjusted odds ratios (AOR) with 95% confidence interval (CI) were calculated. Adjustment was made for year of birth of child, maternal age, parity, smoking, body mass index, years of involuntary childlessness, and child's sex and, for cleavage stage, also for number of oocytes retrieved, number of embryos transferred, and fresh/frozen embryo transfer. RESULTS: There were 4819 singletons born after blastocyst transfer, 25,747 after cleavage-stage transfer, and 1,196,394 after spontaneous conception. Singletons born after blastocyst transfer had no increased risk of birth defects compared to singletons born after cleavage-stage transfer (AOR, 0.94; 95% CI, 0.79-1.13) or spontaneous conception (AOR, 1.09; 95% CI, 0.92-1.28). Perinatal mortality was higher in the blastocyst vs the cleavage-stage group (AOR, 1.61; 95% CI, 1.14-2.29). When comparing singletons born after blastocyst transfer to singletons born after spontaneous conception, a higher risk of PTB (<37 weeks) was seen (AOR, 1.17; 95% CI, 1.05-1.31). Singletons born after blastocyst transfer had a lower rate of low birthweight (AOR, 0.83; 95% CI, 0.71-0.97) as compared to cleavage-stage transfer. The rate of being small for gestational age was lower in singletons born after blastocyst transfer as compared to both cleavage-stage and spontaneous conception (AOR, 0.71; 95% CI, 0.56-0.88 and AOR, 0.70; 95% CI, 0.57-0.87, respectively). The risk of placenta previa and placental abruption was higher in pregnancies after blastocyst transfer as compared to pregnancies after cleavage-stage (AOR, 2.08; 95% CI, 1.70-2.55 and AOR, 1.62; 95% CI, 1.15-2.29, respectively) and spontaneous conception (AOR, 6.38; 95% CI, 5.31-7.66 and AOR, 2.31; 95% CI, 1.70-3.13, respectively). CONCLUSION: No increased risk of birth defects was found in singletons born after blastocyst transfer. Perinatal mortality and risk of placental complications were higher in the blastocyst group as compared to the cleavage-stage group, observations that need further investigations.
35.	Ginström Ernstad, Erica, et al. (author) Neonatal and maternal outcome after frozen embryo transfer: increased risks in programmed cycles. 2019 In: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 221:2 Journal article (peer-reviewed)abstract Frozen embryo transfer is associated with better perinatal outcome regarding preterm birth and low birth weight yet higher risk of large for gestational age and macrosomia compared to fresh transfer. Further, higher rates of hypertensive disorders in pregnancy are noted after frozen embryo transfer. Whether these differences are due to the protocol used in frozen cycles remains unknown.To analyze the obstetric outcome after frozen embryo transfer depending on protocol used. Comparison was also made for frozen vs. fresh transfer and for frozen transfer vs. spontaneous conception.A population-based retrospective registry study including all singletons born after frozen embryo transfer in Sweden from 2005 to 2015. The IVF register was cross-linked with the Medical Birth Register, the Register of Birth Defects, the National Patient Register, the Swedish Neonatal Quality Register and the Prescribed Drug Register. Singletons after FET were compared depending on the presence of a corpus luteum in the actual cycle. All frozen transfer singletons were also compared with fresh transfer and spontaneous conception singletons. Primary outcomes were preterm birth (<37 w), low birth weight (<2500 g), hypertensive disorders in pregnancy and postpartum hemorrhage (>1000 ml). Crude and adjusted odds ratio (AOR) with 95% confidence interval (CI) were calculated and adjustment made for relevant confounders.9726 singletons were born after frozen embryo transfer (natural cycles, n=6297, stimulated cycles, n=1983, programmed cycles, n=1446), 24,365 after fresh transfer and 1,127,566 after spontaneous conception. No significant differences were noticed for preterm birth and low birth weight between the different protocols used in frozen embryo transfer. Compared to natural and stimulated frozen cycles programmed frozen cycles were associated with a higher risk of hypertensive disorders in pregnancy (AOR 1.78, 95% CI, 1.43-2.21 and AOR 1.61; 1.22-2,10, respectively) and postpartum hemorrhage (AOR 2.63, 95% CI, 2.20-3.13 and AOR 2.87; 95% CI, 2.29-2.60, respectively). Moreover higher risks for postterm birth (AOR 1.59; 95% CI 1.27-2.01 and AOR 1.98; 95% CI 1.47-2.68) and macrosomia (AOR 1.62; 95% CI, 1.26-2.09 and AOR 1.40; 95% CI 1.03-1.90) were detected. There were no significant differences in any outcomes between stimulated and natural cycles. Frozen cycles in general compared to fresh cycles and compared to spontaneous conceptions showed neonatal and maternal outcomes in agreement with earlier studies.No significant difference could be seen regarding preterm birth and low birth weight between the different protocols. However, higher rates of hypertensive disorders in pregnancy, postpartum hemorrhage, postterm birth and macrosomia were detected in programmed cycles. Stimulated cycles had outcomes similar to natural cycles. These findings are important in view of the increasing use of frozen cycles and the new policy of freeze-all cycles in IVF. The results suggest a link between the absence of corpus luteum and adverse obstetric outcomes.
36.	Ginström Ernstad, Erica, et al. (author) Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group. 2019 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 34:11, s. 2282-2289 Journal article (peer-reviewed)abstract Is transfer of vitrified blastocysts associated with higher perinatal and maternal risks compared with slow-frozen cleavage stage embryos and fresh blastocysts?Transfer of vitrified blastocysts is associated with a higher risk of preterm birth (PTB) when compared with slow-frozen cleavage stage embryos and with a higher risk of a large baby, hypertensive disorders in pregnancy (HDPs) and postpartum hemorrhage (PPH) but a lower risk of placenta previa when compared with fresh blastocysts.Transfer of frozen-thawed embryos (FETs) plays a central role in modern fertility treatment, limiting the risk of ovarian hyperstimulation syndrome and multiple pregnancies. Following FET, several studies report a lower risk of PTB, low birth weight (LBW) and small for gestational age (SGA) yet a higher risk of fetal macrosomia and large for gestational age (LGA) compared with fresh embryos. In recent years, the introduction of new freezing techniques has increased treatment success. The slow-freeze technique combined with cleavage stage transfer has been replaced by vitrification and blastocyst transfer. Only few studies have compared perinatal and maternal outcomes after vitrification and slow-freeze and mainly in cleavage stage embryos, with most studies indicating similar outcomes in the two groups. Studies on perinatal and maternal outcomes following vitrified blastocysts are limited.This registry-based cohort study includes singletons born after frozen-thawed and fresh transfers following the introduction of vitrification in Sweden and Denmark, in 2002 and 2009, respectively. The study includes 3650 children born after transfer of vitrified blastocysts, 8123 children born after transfer of slow-frozen cleavage stage embryos and 4469 children born after transfer of fresh blastocysts during 2002-2015. Perinatal and maternal outcomes in singletons born after vitrified blastocyst transfer were compared with singletons born after slow-frozen cleavage stage transfer and singletons born after fresh blastocyst transfer. Main outcomes included PTB, LBW, macrosomia, HDP and placenta previa.Data were obtained from the CoNARTaS (Committee of Nordic ART and Safety) group. Based on national registries in Sweden, Finland, Denmark and Norway, the CoNARTaS cohort includes all children born after ART treatment in public and private clinics 1984-2015. Outcomes were assessed with logistic multivariable regression analysis, adjusting for the country and year of birth, maternal age, body mass index, parity, smoking, parental educational level, fertilisation method (IVF/ICSI), single embryo transfer, number of gestational sacs and the child's sex.A higher risk of PTB (<37weeks) was noted in the vitrified blastocyst group compared with the slow-frozen cleavage stage group (adjusted odds ratio, aOR [95% CI], 1.33 [1.09-1.62]). No significant differences were observed for LBW (<2500g), SGA, macrosomia (≥4500g) and LGA when comparing the vitrified blastocyst with the slow-frozen cleavage stage group. For maternal outcomes, no significant difference was seen in the risk of HDP, placenta previa, placental abruption and PPH in the vitrified blastocyst versus the slow frozen cleavage stage group, although the precision was limited.When comparing vitrified and fresh blastocysts, we found higher risks of macrosomia (≥4500g) aOR 1.77 [1.35-2.31] and LGA aOR 1.48 [1.18-1.84]. Further, the risks of HDP aOR 1.47 [1.19-1.81] and PPH aOR 1.68 [1.39-2.03] were higher in singletons born after vitrified compared with fresh blastocyst transfer while the risks of SGA aOR 0.58 [0.44-0.78] and placenta previa aOR 0.35 [0.25-0.48] were lower.Since vitrification was introduced simultaneously with blastocyst transfer in Sweden and Denmark, it was not possible to explore the effect of vitrification per se in this study.The results from the change of strategy to vitrification of blastocysts are reassuring, indicating that the freezing technique per se has no major influence on the perinatal and maternal outcomes. The higher risk of PTB may be related to the extended embryo culture rather than vitrification.The study is part of the ReproUnion Collaborative study, co-financed by the European Union, Interreg V ÖKS. The study was also financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (LUA/ALF 70940), Hjalmar Svensson Research Foundation and NordForsk (project 71450). There are no conflicts of interest to declare.ISRCTN11780826.
37.	Ginström Ernstad, Erica, et al. (author) Preimplantation genetic testing and child health: a national register-based study 2023 In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 739-750 Journal article (peer-reviewed)abstract STUDY QUESTION Is preimplantation genetic testing (PGT) associated with adverse perinatal outcome and early childhood health? SUMMARY ANSWER Children born after PGT had comparable perinatal outcomes to children born after IVF/ICSI and comparable findings regarding early childhood health. WHAT IS KNOWN ALREADY PGT is offered to couples affected by monogenic disorders (PGT-M) or inherited chromosomal aberrations (PGT-SR), limiting the risk of transferring the disorder to the offspring. PGT, an invasive technique, requires genetic analysis of one or up to ten cells from the embryo and is combined with IVF or ICSI. Several studies, most of them small, have shown comparable results after PGT and IVF/ICSI concerning perinatal outcome. Only a few studies with limited samples have been published on PGT and childhood health. STUDY DESIGN, SIZE, DURATION We performed a register-based study including all singletons born after PGT (n = 390) in Sweden during 1 January 1996-30 September 2019. Singletons born after PGT were compared with all singletons born after IVF/ICSI (n = 61 060) born during the same period of time and with a matched sample of singletons (n = 42 034) born after spontaneous conception selected from the Medical Birth Register. Perinatal outcomes, early childhood health, and maternal outcomes were compared between pregnancies after PGT and IVF/ICSI as well as between pregnancies after PGT and spontaneous conception. Primary outcomes were preterm birth (PTB) and low birthweight (LBW) whereas childhood morbidity was the secondary outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on women who went through PGT and gave birth were obtained from the local databases at the two PGT centres in Sweden, whereas data on IVF treatment for the IVF/ICSI group were obtained from the national IVF registers. These data were then cross-linked to national health registers; the Medical Birth Register, the Patient Register, and the Cause of Death Register. Logistic multivariable regression analysis and Cox proportional hazards models were performed with adjustment for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE The mean follow-up time was 4.6 years for children born after PGT and 5.1 years for children born after spontaneous conception, whereas the mean follow-up time was 9.0 years for children born after IVF/ICSI. For perinatal outcomes, PTB occurred in 7.7% of children after PGT and in 7.3% of children after IVF/ICSI, whereas the rates were 4.9% and 5.2% for LBW (adjusted odds ratio (AOR) 1.22, 95% CI 0.82-1.81 and AOR 1.17, 95% CI 0.71-1.91, respectively). No differences were observed for birth defects. In comparison to spontaneous conception, children born after PGT had a higher risk for PTB (AOR 1.73, 95% CI 1.17-2.58). Regarding early childhood health, the absolute risk of asthma was 38/390 (9.7%) in children born after PGT and 6980/61 060 (11.4%) in children born after in IVF/ICSI, whereas the corresponding numbers were 34/390 (8.7%) and 7505/61 060 (12.3%) for allergic disorders. Following Cox proportional hazards models, no significant differences were found for these outcomes. Sepsis, hypothyroidism, attention deficit hyperactivity disorder, autism spectrum disorders, mental retardation, cerebral palsy, and epilepsy were diagnosed in a maximum of three PGT children. No PGT children died during the follow-up period. Regarding maternal outcomes, the rates of placenta praevia and caesarean delivery were significantly higher after PGT in comparison to spontaneous conception (AOR 6. 46, 95% CI 3.38-12.37 and AOR 1.52, 95% CI 1.20-1.92, respectively), whereas no differences were seen comparing pregnancies after PGT and IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION The rather small sample size of children born after PGT made it impossible to adjust for all relevant confounders including fertilization method and culture duration. Moreover, the follow-up time was short for most of the children especially in the PGT group, probably lowering the absolute number of diagnoses in early childhood. WIDER IMPLICATIONS OF THE FINDINGS The results are reassuring and indicate that the embryo biopsy itself has no adverse effect on the perinatal, early childhood, or maternal outcomes. Although the results are comparable to IVF/ICSI also regarding early childhood outcome, they should be taken with caution due to the low number of children with diagnoses and short follow-up time. Long-term follow-up studies on children born after PGT are scarce and should be conducted considering the invasiveness of the technique. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), the Board of National Specialised Medical Care at Sahlgrenska University Hospital and Hjalmar Svensson Research Foundation. There are no conflicts of interest to declare.
38.	H Petersen, Sindre, et al. (author) Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study With Within-Sibship Analysis. 2022 In: Hypertension (Dallas, Tex. : 1979). - 1524-4563. ; 80:2 Journal article (peer-reviewed)abstract Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown.Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4426691 naturally conceived, 78300 fresh embryo transfer, and 18037 frozen-ET singleton pregnancies, of which 33209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh embryo transfer and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country.Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh embryo transfer, risk was similar to natural conception, both at population level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]).Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
39.	Hagman, Anna, et al. (author) Morbidity and mortality after childbirth in women with Turner karyotype. 2013 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 28:7, s. 1961-1973 Journal article (peer-reviewed)abstract STUDY QUESTION: Do women with Turner karyotype have increased mortality and morbidity in the years after childbirth? SUMMARY ANSWER: No mortality occurred during pregnancy and follow-up in women with Turner karyotype, but a higher rate of circulatory and endocrine diseases and a high risk of aortic aneurysm were confirmed. WHAT IS KNOWN ALREADY: Pregnancies in women with Turner karyotype are high-risk pregnancies with an increased risk of maternal mortality from aortic dissection and morbidity from hypertensive disorders. STUDY DESIGN, SIZE, DURATION: A retrospective Swedish population-based registry study of 124 women with Turner karyotype born between 1957 and 1987 and who gave birth between 1973 and 2010. Women with Turner karyotype without childbirth (n = 378) were selected as controls. A second control group consisted of women from the Swedish Medical Birth Register (MBR) (n = 1230) matched for maternal age, number of children and year of birth of the first child. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Women with Turner karyotype were identified in the Swedish Genetic Turner Register. Data were obtained by using the unique personal identification number with cross linkage to the Swedish MBR, the Cause of Death Register, the National Patient Register and the Swedish Cancer Register. Hazard ratio (HR) with 95% confidence interval (CI) was used in the analysis of morbidity. MAIN RESULTS AND THE ROLE OF CHANCE: No mortality occurred in women with Turner karyotype and childbirth. Diseases of the circulatory system occurred more often in women with Turner syndrome under the age of 40 years compared with the MBR control group (HR 4.59; 95% CI 2.75-7.66) but was similar at or above the age of 40 years. Morbidity from circulatory diseases was increased before pregnancy (HR 3.83; 95% CI 1.02-14.43) and during pregnancy or within 1 year after (HR 5.78; 95% CI 1.94-17.24), but was similar after 1 or more years after delivery (HR 1.91; 95% CI 0.74-4.96). Aortic aneurysm occurred in 11/502 (2.2%) women with Turner karyotype and in three women (2.4%) during pregnancy. The long-term follow-up showed that aortic dissection was a common cause of death in young women with Turner karyotype without childbirth. A thorough cardiac evaluation before pregnancy in women with Turner karyotype is of utmost importance. LIMITATIONS, REASONS FOR CAUTION: Although this was a population-based registry study performed over a period of more than 20 years, a much longer follow-up and larger series are needed to assess rare events. The study also lacks information on phenotype and mode of conception in women with Turner karyotype. Women who gave birth probably represent a selection of healthier women with Turner karyotype. WIDER IMPLICATIONS OF THE FINDINGS: The high risk of aortic aneurysm in young women with Turner karyotype is in agreement with the literature. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest exist. The study has been supported by grants from the Gothenburg Medical Society, the Medical Care executive Board of the Region Västra Götaland, grants from the ALF agreement at the Sahlgrenska University Hospital, the Hjalmar Svensson foundation, the Swedish Board of Health and Welfare, the Swedish Heart Lung Foundation and the Swedish Council for Working Life and Social Research. TRIAL REGISTRATION NUMBER: None.
40.	Hagman, Anna, et al. (author) Obstetric and neonatal outcome after oocyte donation in 106 women with Turner syndrome: a Nordic cohort study. 2013 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 28:6, s. 1598-609 Journal article (peer-reviewed)abstract What are the obstetric and neonatal outcomes of deliveries after oocyte donation (OD) in women with Turner syndrome (TS)? SUMMARY ANSWER: Pregnancies among women with TS carry a substantial risk, particularly for hypertensive disorders. Potentially life-threatening complications occurred in 3.3% of pregnancies. The neonatal outcomes were generally reassuring, with similar rates of preterm birth and low birthweight (LBW) as after conventional IVF and better than previously reported in deliveries after OD in women with TS. WHAT IS KNOWN ALREADY: OD pregnancies in women with TS are known to be high-risk pregnancies. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 106 women with TS who delivered after OD (n = 122 deliveries, n = 131 newborns) in three Nordic countries (Finland, Denmark, Sweden) between 1992 and 2011. PARTICIPANTS, SETTING AND METHODS: Women with TS who delivered after OD in three Nordic countries were identified (n = 110). Four women declined to participate or were lost to follow-up, thus 106 women were included in the study. The medical data from fertility clinics, antenatal clinics and the hospitals where the women had been treated and/or delivered were scrutinized. MAIN RESULTS AND THE ROLE OF CHANCE: In this cohort, the karyotype was 45,X in 44% of the women with TS. Ten women (9.4%) had a known cardiac defect before pregnancy. Single embryo transfer was performed in 70.3% of the cases and the multiple birth rate was 7.4%. In total, 35.0% of the pregnancies were associated with a hypertensive disorder including pre-eclampsia in 20.5%. Potentially life-threatening complications occurred in four pregnancies (3.3%), including one woman with aortic dissection, one with mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) and one who underwent a post-partum hysterectomy due to severe haemorrhaging. Neonatal outcomes were reassuring, with a preterm birth rate of 8.0% and LBW rate of 8.8% in singletons. Major birth defects were found in 3.8% of the children. The perinatal mortality was 2.3% (3/131), including a set of extremely preterm twins. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed over a period of almost 20 years in three different countries, with a low drop-out rate and little missing data, much larger series are needed to assess rare events. This study also lacks an appropriate control group. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that cardiovascular evaluation before and during pregnancy may contribute to favourable obstetric outcomes in many cases. Maternal outcomes were in agreement with the literature while neonatal outcomes were generally better than previously reported. The outcomes were consistent across the three countries, supporting generalizability to similar populations. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest was reported. The study was supported by grants from the Gothenburg Medical Society, the Medical Care Executive Board of the Region Västra Götaland, grants from the ALF agreement at the Sahlgrenska University Hospital, the Hjalmar Svensson foundation, NFOG Nordic Fund, the Finnish Society of Paediatric and Adolescent Gynecology and Liv och hälsa Foundation in Finland. The Nordic Expert group's research work was unconditionally supported by MSD Finland, Norway and Denmark.
41.	Hagman, Anna, et al. (author) Obstetric Outcomes in Women with Turner Karyotype. 2011 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:11, s. 3475-3482 Journal article (peer-reviewed)abstract Context: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. Objective: This study compared obstetric outcome in women with TS karyotype with women in the general population. Design: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. Results: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. Conclusions: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls.
42.	Hagman, Anna, et al. (author) Perinatal outcome in women with Turner karyotype 2010 In: Human Reproduction. - 0268-1161. ; 25, s. 23-23 Conference paper (peer-reviewed)
43.	Hagman, Anna, et al. (author) Women who gave birth to girls with Turner syndrome: maternal and neonatal characteristics. 2010 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:6, s. 1553-60 Journal article (peer-reviewed)abstract BACKGROUND: The aim was to identify maternal risk factors in women giving birth to girls with Turner syndrome (TS) and to describe the characteristics of newborns with TS. METHODS: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register. Between 1973 and 2005, 494 children with TS were born. Maternal age, parity, height, smoking habits and neonatal characteristics; mode of delivery, gestational age, size at birth and Apgar score, were compared with women in the general population who gave birth to girls during the same period. RESULTS: More women with advanced maternal age (40+) delivered girls with TS, 3.2% when compared with 1.8% in the general population [OR 1.83, 95% confidence interval (CI) 1.09-3.08, after adjustment for year of birth]. Maternal height was inversely associated with TS pregnancies (P = 0.005). Late preterm birth occurred in newborns with TS in 10.5% when compared with 4.8% in the general population (OR 2.23; 95% CI: 1.67-2.97, after adjustment for year of birth and maternal age). Newborns with TS had birthweight less than -2SD in 17.8% and birth length less than -2SD in 21.0% when compared with 3.5 and 3.4%, in the general population (OR 6.55; 95% CI: 5.12-8.38 and OR 8.69; 95% CI: 6.89-10.97, after adjustment for year of birth and maternal age). CONCLUSION: Advanced maternal age and short stature were risk factors for giving birth to a girl with TS. More TS girls were born late preterm and were smaller for gestational age than non-TS girls in the general population.
44.	Hamberger, Lars, 1939, et al. (author) Microfertilization techniques - the Swedish experience 1995 In: Reproduction, Fertility and Development. - 1031-3613. ; 7:2, s. 263-7 Journal article (peer-reviewed)
45.	Henningsen, A. A., et al. (author) Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group 2020 In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:5, s. 1178-1184 Journal article (peer-reviewed)abstract STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART? SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART. WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders. STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART. LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum. WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome.
46.	Henningsen, A A, et al. (author) Risk of stillbirth and infant deaths after assisted reproductive technology: a Nordic study from the CoNARTaS group. 2014 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 29:5, s. 1090-1096 Journal article (peer-reviewed)abstract Is the risk of stillbirth and perinatal deaths increased after assisted reproductive technology (ART) compared with pregnancies established by spontaneous conception (SC)?
47.	Henningsen, A A, et al. (author) Trends in perinatal health after assisted reproduction: a Nordic study from the CoNARTaS group. 2015 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 30:3, s. 710-6 Journal article (peer-reviewed)abstract Has the perinatal outcome of children conceived after assisted reproductive technology (ART) improved over time?
48.	Henningsen, Anna-Karina A, et al. (author) Infant and maternal health monitoring using a combined Nordic database on ART and safety. 2011 In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 90:7, s. 683-691 Journal article (peer-reviewed)abstract Objective. To evaluate infant and maternal health after assisted reproductive technology (ART), using data on over 90 000 ART children and their mothers in Denmark, Finland, Norway and Sweden. Data have been combined and will be compared with a control group of spontaneously conceived children and their mothers. The overall aim of this project is to evaluate the safety of ART. The size of the cohort should enable estimation of the prevalence of rare conditions such as birth defects, cancers, neurological impairments and imprinting diseases in the ART population compared to control children. Outcome data on the mothers of ART children can be used to study risks during pregnancy and obstetric complications after ART. Methods. A personal identification number given to all Nordic residents allows cross-linkage of the national health registers and enables long-term follow-up of ART children. The medical birth registers in the Nordic countries make it possible to cross-link data from mother and child. When a child is identified as conceived by ART, we can obtain a list of all International Classification of Diseases (ICD) codes ever registered on that specific child. Conclusion. Combining the Nordic ART and health registers is a complicated but feasible task. The main strengths of this ongoing study are the size of the cohort of ART children and their mothers and the possibility to follow the children through the health registers. The limitations are related to the national differences in reporting and recording of data together with the heterogeneity of data.
49.	Henningsen, Anna-Karina Aaris, et al. (author) Reply: Implication of the liberal use of ART in Nordic countries: should stricter guidelines be created to prevent unnecessary stillbirth and preterm delivery? 2014 In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 29:11, s. 2600-1 Journal article (other academic/artistic)
50.	Henningsen, A. K. A., et al. (author) Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group 2023 In: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 120:5, s. 1033-1041 Journal article (peer-reviewed)abstract Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)?Design: Nordic register-based cohort study.Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos.Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryoICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23- 1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period.Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility. (Fertil Sterile 2023;120:1033-41. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.

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