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| 2. |
- Henningsen, A. K. A., et al.
(author)
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Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology
- 2018
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In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:7, s. 816-823
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Journal article (peer-reviewed)abstract
- Children born after assisted reproductive technology, particularly singletons, have been shown to have an increased risk of congenital malformations compared with children born after spontaneous conception. We wished to study whether there has been a change in the past 20 years in the risk of major congenital malformations in children conceived after assisted reproductive technology compared with children spontaneously conceived. Material and methodsPopulation-based cohort study including 90 201 assisted reproductive technology children and 482 552 children spontaneously conceived, born in Denmark, Finland, Norway and Sweden. Both singletons and twins born after in vitro fertilization, intracytoplasmatic sperm injection and frozen embryo transfer were included. Data on children were taken from when the national Nordic assisted reproductive technology registries were established until 2007. Multiple logistic regression analyses were used to estimate the risks and adjusted odds ratios for congenital malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003-2007. Only major malformations were included. ResultsThe absolute risk for singletons of being born with a major malformation was 3.4% among assisted reproductive technology children vs. 2.9% among children spontaneously conceived during the study period. The relative risk of being born with a major congenital malformation between all assisted reproductive technology children and children spontaneously conceived remained similar through all four time periods (p = 0.39). However, we found that over time the number of children diagnosed with a major malformation increased in both groups across all four time periods. ConclusionWhen comparing children conceived after assisted reproductive technology and spontaneously conceived, the relative risk of being born with a major congenital malformation did not change during the study period.
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| 3. |
- Opdahl, S., et al.
(author)
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Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group
- 2015
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:7, s. 1724-1731
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Journal article (peer-reviewed)abstract
- STUDY QUESTION: Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? SUMMARY ANSWER: ART pregnancies had a higher risk of hypertensive disorders, in particular following cryopreservation, with the highest risk seen in twin pregnancies following frozen-thawed cycles. WHAT IS KNOWN ALREADY: The risk of hypertensive disorders is higher in ART pregnancies than in SC pregnancies. The increased risk maybe partly explained by multiple pregnancies and underlying infertility, but a contribution from specific ART procedures has not been excluded. STUDY DESIGN, SIZE, DURATION: Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS: All registered ART pregnancies and a sample of SC pregnancies with gestational age >= 22 weeks from 1988 to 2007 were included. ART singleton pregnancies (n = 47 088) were compared with SC singleton pregnancies (n = 268 599), matched on parity and birth year. ART twin pregnancies (n = 10 918) were compared with SC twin pregnancies (46 674). We used logistic regression to estimate adjusted odds ratios and risk differences for hypertensive disorders in pregnancies following IVF, ICSI and fresh or frozen-thawed cycles. We also compared freshand frozen-thawed cycles within mothers who had conceived following both procedures using conditional logistic regression (sibling analysis). MAIN RESULTS AND THE ROLE OF CHANCE: Hypertensive disorders were reported in 5.9% of ART singleton and 12.6% of ART twin pregnancies. Comparing singleton pregnancies, the risk of hypertensive disorders was higher after all ART procedures. The highest risk in singleton pregnancies was seen after frozen-thawed cycles [risk 7.0%, risk difference 1.8%, 95% confidence interval (CI) 1.2-2.8]. Comparing twin pregnancies, the risk was higher after frozen-thawed cycles (risk 19.6%, risk difference 5.1%, 95% CI 3.0-7.1), but not after fresh cycles. In siblings, the risk was higher after frozen-thawed cycles compared with fresh cycles within the same mother (odds ratio 2.63, 95% CI 1.73-3.99). There were no clear differences in risk for IVF and ICSI. LIMITATIONS, REASONS FOR CAUTION: The number of ART siblings in the study was limited. Residual confounding cannot be excluded. In addition, we did not have information on all SC pregnancies in each woman's history, and could therefore not compare risk in ART versus SC pregnancies in the same mother. WIDER IMPLICATIONS OF THE FINDINGS: Pregnancies following frozen-thawed cycles have a higher risk of hypertensive disorders, also when compared with fresh cycle pregnancies by the same mother. The safety aspects in frozen-thawed cycles merit further attention. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the European Society for Human Reproduction and Embryology, the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, the Nordic Federation of Societies of Obstetrics and Gynecology and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. None of the authors has any competing interests to declare.
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| 4. |
- Stormlund, S., et al.
(author)
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Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART): A study protocol for a randomised controlled trial
- 2017
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In: Bmj Open. - : BMJ. - 2044-6055. ; 7:7
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Journal article (peer-reviewed)abstract
- Introduction Pregnancy rates after frozen embryo transfer (FET) have improved in recent years and are now approaching or even exceeding those obtained after fresh embryo transfer. This is partly due to improved laboratory techniques, but may also be caused by a more physiological hormonal and endometrial environment in FET cycles. Furthermore, the risk of ovarian hyperstimulation syndrome is practically eliminated in segmentation cycles followed by FET and the use of natural cycles in FETs may be beneficial for the postimplantational conditions of fetal development. However, a freeze-all strategy is not yet implemented as standard care due to limitations of large randomised trials showing a benefit of such a strategy. Thus, there is a need to test the concept against standard care in a randomised controlled design. This study aims to compare ongoing pregnancy and live birth rates between a freeze-all strategy with gonadotropin-releasing hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG) trigger and fresh embryo transfer in a multicentre randomised controlled trial. Methods and analysis Multicentre randomised, controlled, double-blinded trial of women undergoing assisted reproductive technology treatment including 424 normo-ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2) hCG trigger and single blastocyst transfer in the fresh (stimulated) cycle. The primary endpoint is to compare ongoing pregnancy rates per randomised patient in the two treatment groups after the first single blastocyst transfer. Ethics and dissemination The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committees in Denmark and Sweden. The results of the study will be publically disseminated. Trial registration number NCT02746562; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article).
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| 5. |
- Wennberg, Anna Lena, 1968, et al.
(author)
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Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology
- 2016
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 106:5, s. 1142-1149
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Journal article (peer-reviewed)abstract
- Objective: To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. Design: Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. Patient(s): A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. Main Outcome Measure(s): Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; <37 weeks), low birth weight (LBW; <2,500 g), small for gestational age (SGA), and perinatal mortality (>= 28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. Result(s): The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. Conclusion(s): Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously. (C) 2016 by American Society for Reproductive Medicine.
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| 7. |
- Kluge, Linda, 1968, et al.
(author)
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Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial.
- 2019
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In: Human reproduction open. - : Oxford University Press (OUP). - 2399-3529. ; 2019:4
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Journal article (peer-reviewed)abstract
- Did weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2years?Weight loss prior to IVF did not increase CLBR.Few studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity.A 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study.Nine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38years of age having a BMI ≥30 and<35kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12weeks and 3-5weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies.42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P=0.56; odds ratio (OR) 1.16, 95% CI: 0.74-1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2years. The mean weight gain over the 2years was 8.6kg, while women in the IVF-only group had a mean weight loss of 1.2kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and-0.055 (1.271) (mean, SD) in the IVF-only group (P=0.25; mean difference between groups, 0.327; 95% CI: -0.272 to 0.932).All data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR.The follow-up indicates that for women with a BMI ≥30 and<35kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred.The 2-year follow-up was financed by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-70940 and ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose.ClinicalTrials.gov number, NCT01566929.
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| 8. |
- Oldereid, N. B., et al.
(author)
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The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis
- 2018
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In: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 24:3, s. 320-389
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Journal article (peer-reviewed)abstract
- BACKGROUND: Maternal factors, including increasing childbearing age and various life-style factors, are associated with poorer short- and long-term outcomes for children, whereas knowledge of paternal parameters is limited. Recently, increasing paternal age has been associated with adverse obstetric outcomes, birth defects, autism spectrum disorders and schizophrenia in children. OBJECTIVE AND RATIONALE: The aim of this systematic review is to describe the influence of paternal factors on adverse short- and long-term child outcomes. SEARCH METHODS: PubMed, Embase and Cochrane databases up to January 2017 were searched. Paternal factors examined included paternal age and life-style factors such as body mass index (BMI), adiposity and cigarette smoking. The outcome variables assessed were short-term outcomes such as preterm birth, low birth weight, small for gestational age (SGA), stillbirth, birth defects and chromosomal anomalies. Long-term outcome variables included mortality, cancers, psychiatric diseases/disorders and metabolic diseases. The systematic review follows PRISMA guidelines. Relevant meta-analyses were performed. OUTCOMES: The search included 14 371 articles out of which 238 met the inclusion criteria, and 81 were included in quantitative synthesis (meta-analyses). Paternal age and paternal life-style factors have an association with adverse outcome in offspring. This is particularly evident for psychiatric disorders such as autism, autism spectrum disorders and schizophrenia, but an association is also found with stillbirth, any birth defects, orofacial clefts and trisomy 21. Paternal height, but not BMI, is associated with birth weight in offspring while paternal BMI is associated with BMI, weight and/or body fat in childhood. Paternal smoking is found to be associated with an increase in SGA, birth defects such as congenital heart defects, and orofacial clefts, cancers, brain tumours and acute lymphoblastic leukaemia. These associations are significant although moderate in size, with most pooled estimates between 1.05 and 1.5, and none exceeding 2.0. WIDER IMPLICATIONS: Although the increased risks of adverse outcome in offspring associated with paternal factors and identified in this report represent serious health effects, the magnitude of these effects seems modest.
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| 9. |
- Storgaard, M., et al.
(author)
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Obstetric and neonatal complications in pregnancies conceived after oocyte donation: a systematic review and meta-analysis
- 2017
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In: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328. ; 124:4, s. 561-572
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Research review (peer-reviewed)abstract
- Background Approximately 50 000 oocyte donation OD) treatment cycles are now performed annually in Europe and the US. Objectives To ascertain whether the risk of adverse obstetric and perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in-vitro fertilisation IVF)/intracytoplasmic sperm injection ICSI) or spontaneously. Search Strategy A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982-2016. Primary outcomes were hypertensive disorders of pregnancy, preeclampsia PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age. Selection criteria Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with > 500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded. Data collection and analysis Thirty-five studies met the inclusion criteria. A random-effects model was used for the meta-analyses. Main results For OD pregnancies versus conventional IVF/ ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42-3.15) in singleton and AOR 3.31 (95% CI, 1.616.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39-2.20) and 1.53 (95% CI, 1.16-2.01), respectively. Conclusions OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single-embryo transfer should be the choice of option in OD cycles.
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| 10. |
- Bergh, Christina, 1953, et al.
(author)
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Parental age and child outcomes
- 2019
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 111:6, s. 1036-1046
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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.)
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