A A Henningsen1, M Gissler2, R Skjaerven3, C Bergh4, A Tiitinen5, L B Romundstad6, U B Wennerholm7, O Lidegaard8, A Nyboe Andersen9, J L Forman10, A Pinborg11. 1. Fertility Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark anna-karina.aaris.henningsen@rh.regionh.dk. 2. THL, National Institute for Health and Welfare, Helsinki, Finland Nordic School of Public Health, Gothenburg, Sweden. 3. Department of Global Public Health and Primary Health Care, University of Bergen, Bergen, Norway Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway. 4. Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 5. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. 6. Department of Obstetrics and Gynecology, Fertility Clinic, St Olav's University Hospital, Trondheim, Norway Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. 7. Perinatal Centre, Department of Obstetrics and Gynecology, Institute for Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden. 8. Gynecological Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 9. Fertility Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 10. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 11. Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
Abstract
STUDY QUESTIONS: Has the perinatal outcome of children conceived after assisted reproductive technology (ART) improved over time? SUMMARY ANSWER: The perinatal outcomes in children born after ART have improved over the last 20 years, mainly due to the reduction of multiple births. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: A Swedish study has shown a reduction in unwanted outcomes over time in children conceived after ART. Our analyses based on data from more than 92 000 ART children born in four Nordic countries confirm these findings. STUDY DESIGN: Nordic population-based matched cohort study with ART outcome and health data from Denmark, Finland, Norway and Sweden. PARTICIPANTS, SETTING AND METHODS: We analysed the perinatal outcome of 62 379 ART singletons and 29 758 ART twins, born from 1988 to 2007 in four Nordic countries. The ART singletons were compared with a control group of 362 215 spontaneously conceived singletons. Twins conceived after ART were compared with all spontaneously conceived twins (n = 122 763) born in the Nordic countries during the study period. The rates of several adverse perinatal outcomes were stratified into the time periods: 1988-1992; 1993-1997; 1998-2002 and 2003-2007 and presented according to multiplicity. MAIN RESULTS AND ROLE OF CHANCE: For singletons conceived after ART, a remarkable decline in the risk of being born preterm and very preterm was observed. The proportion of ART singletons born with a low and very low birthweight also decreased. Finally, the stillbirth and infant death rates have declined among both ART singletons and twins. Throughout the 20 year period, fewer ART twins were stillborn or died during the first year of life compared with spontaneously conceived twins, presumably due to the lower proportion of monozygotic twins among the ART twins. LIMITATIONS, REASONS FOR CAUTION: We were not able to adjust for some potential confounders such as BMI, smoking, length or cause of infertility. The Nordic ART populations have changed over time, and in recent years, both less as well as severely reproductive ill couples are being treated. This may have affected the observed trends. WIDER IMPLICATIONS OF THE FINDINGS: It is assuring that data from four countries confirm an overall improvement over time in the perinatal outcomes of children conceived after ART. Furthermore, data show the beneficial effect of single embryo transfer, not only in regard to lowering the rate of multiples but also concerning the health of singletons. STUDY FUNDING/COMPETING INTERESTS: The European Society for Human Reproduction and Embryology (ESHRE), the University of Copenhagen and the Danish Agency for Science, Technology and Innovation has supported the project. The CoNARTaS group has received travel and meeting funding from the Nordic Federation of Obstetrics and Gynecology (NFOG). None of the authors has any competing interests to declare.
STUDY QUESTIONS: Has the perinatal outcome of children conceived after assisted reproductive technology (ART) improved over time? SUMMARY ANSWER: The perinatal outcomes in children born after ART have improved over the last 20 years, mainly due to the reduction of multiple births. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: A Swedish study has shown a reduction in unwanted outcomes over time in children conceived after ART. Our analyses based on data from more than 92 000 ART children born in four Nordic countries confirm these findings. STUDY DESIGN: Nordic population-based matched cohort study with ART outcome and health data from Denmark, Finland, Norway and Sweden. PARTICIPANTS, SETTING AND METHODS: We analysed the perinatal outcome of 62 379 ART singletons and 29 758 ART twins, born from 1988 to 2007 in four Nordic countries. The ART singletons were compared with a control group of 362 215 spontaneously conceived singletons. Twins conceived after ART were compared with all spontaneously conceived twins (n = 122 763) born in the Nordic countries during the study period. The rates of several adverse perinatal outcomes were stratified into the time periods: 1988-1992; 1993-1997; 1998-2002 and 2003-2007 and presented according to multiplicity. MAIN RESULTS AND ROLE OF CHANCE: For singletons conceived after ART, a remarkable decline in the risk of being born preterm and very preterm was observed. The proportion of ART singletons born with a low and very low birthweight also decreased. Finally, the stillbirth and infant death rates have declined among both ART singletons and twins. Throughout the 20 year period, fewer ART twins were stillborn or died during the first year of life compared with spontaneously conceived twins, presumably due to the lower proportion of monozygotic twins among the ART twins. LIMITATIONS, REASONS FOR CAUTION: We were not able to adjust for some potential confounders such as BMI, smoking, length or cause of infertility. The Nordic ART populations have changed over time, and in recent years, both less as well as severely reproductive ill couples are being treated. This may have affected the observed trends. WIDER IMPLICATIONS OF THE FINDINGS: It is assuring that data from four countries confirm an overall improvement over time in the perinatal outcomes of children conceived after ART. Furthermore, data show the beneficial effect of single embryo transfer, not only in regard to lowering the rate of multiples but also concerning the health of singletons. STUDY FUNDING/COMPETING INTERESTS: The European Society for Human Reproduction and Embryology (ESHRE), the University of Copenhagen and the Danish Agency for Science, Technology and Innovation has supported the project. The CoNARTaS group has received travel and meeting funding from the Nordic Federation of Obstetrics and Gynecology (NFOG). None of the authors has any competing interests to declare.
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