Samuel Santos-Ribeiro1, Herman Tournaye2, Nikolaos P Polyzos3. 1. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium Department of Obstetrics, Gynaecology and Reproductive Medicine, Santa Maria University Hospital, Avenida Professor Egas Moniz, Lisbon 1649-035, Portugal. 2. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium. 3. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium Department of Clinical Medicine, Faculty of Health, University of Aarhus, Incuba/Skejby, bld.2, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark n.polyzos@gmail.com nikolaos.polyzos@uzbrussel.be.
Abstract
STUDY QUESTION: Have the advancement of assisted reproductive technologies (ART) and changes in the incidence of specific causes of infertility-altered ectopic pregnancy (EP) rates following ART over time in the UK? SUMMARY ANSWER: EP rates in the UK following IVF/ICSI have progressively decreased, and this appears to be associated with a reduction in the incidence of tubal factor infertility and the increased use of both a lower number of embryos transferred and extended embryo culture. WHAT IS KNOWN ALREADY: Historically, EP rates following ART are known to have increased over time. However, the impact of progress in ART procedures and changes in both policy and the incidence of specific causes of infertility on the overall EP rate in the UK has yet to be studied. STUDY DESIGN, SIZE, DURATION: A population-based retrospective analysis was carried out on all pregnancies following ART cycles carried out in the UK between 2000 and 2012 included in the anonymized database of the Human Fertilisation and Embryology Authority. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 161 967 treatment cycles resulting in a pregnancy were included in the analysis. Among them, 8852 pregnancies occurred after intrauterine insemination (IUI) and 153 115 following IVF/ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: During this period of 12 years, ∼1.4% (n = 2244) of all pregnancies following ART were an EP. Crude EP rates were significantly higher after IVF/ICSI when compared with following IUI (1.4 versus 1.1%, P = 0.043). The incidence of EP decreased significantly over time for IVF/ICSI cycles [incidence rate ratios (IRR) 0.96 per year, 95% confidence interval (CI) 0.94-0.97], but not after IUI (IRR 0.96 per year, 95% CI 0.91-1.03).Among pregnancies resulting from IVF/ICSI, multivariable logistic regression analysis demonstrated that the major risk factor for EP was the presence of tubal infertility [adjusted odds ratio (aOR) 2.23, 95% CI 1.93-2.58), followed by the increased number of embryos transferred (aOR 1.29 for 2 versus 1 embryo transferred, 95% CI 1.11-1.49; aOR 1.69 for 3 or more versus 1 embryo transferred, 95% CI 1.35-2.11). The use of extended embryo culture to Days 3-4 or 5-7 significantly reduced the risk of EP, when compared with the transfer of early cleavage (Days 1-2) embryos (respectively, aOR 0.85, 95% CI 0.76-0.94; and aOR 0.73, 95% CI 0.63-0.84). Finally, frozen embryo transfer (ET) had no effect on the risk of EP following IVF/ICSI (aOR 0.92, 95% CI 0.76-1.11). LIMITATIONS, REASONS FOR CAUTION: Owing to the use of this particular registry data, well-established risk factors of EP, such as smoking habits or uterine surgery, could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide the first evidence of a potential benefit-in terms of the reduction in EP rates-of the implementation of national programmes aiming to reduce the incidence of tubal infertility, such as the National Chlamydia Screening Programme. In addition, campaigns for the widespread introduction of single ET may not only reduce the incidence of multiple pregnancies but also the incidence of EP following IVF/ICSI. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study, and there are no conflicts of interest to declare.
STUDY QUESTION: Have the advancement of assisted reproductive technologies (ART) and changes in the incidence of specific causes of infertility-altered ectopic pregnancy (EP) rates following ART over time in the UK? SUMMARY ANSWER: EP rates in the UK following IVF/ICSI have progressively decreased, and this appears to be associated with a reduction in the incidence of tubal factor infertility and the increased use of both a lower number of embryos transferred and extended embryo culture. WHAT IS KNOWN ALREADY: Historically, EP rates following ART are known to have increased over time. However, the impact of progress in ART procedures and changes in both policy and the incidence of specific causes of infertility on the overall EP rate in the UK has yet to be studied. STUDY DESIGN, SIZE, DURATION: A population-based retrospective analysis was carried out on all pregnancies following ART cycles carried out in the UK between 2000 and 2012 included in the anonymized database of the Human Fertilisation and Embryology Authority. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 161 967 treatment cycles resulting in a pregnancy were included in the analysis. Among them, 8852 pregnancies occurred after intrauterine insemination (IUI) and 153 115 following IVF/ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: During this period of 12 years, ∼1.4% (n = 2244) of all pregnancies following ART were an EP. Crude EP rates were significantly higher after IVF/ICSI when compared with following IUI (1.4 versus 1.1%, P = 0.043). The incidence of EP decreased significantly over time for IVF/ICSI cycles [incidence rate ratios (IRR) 0.96 per year, 95% confidence interval (CI) 0.94-0.97], but not after IUI (IRR 0.96 per year, 95% CI 0.91-1.03).Among pregnancies resulting from IVF/ICSI, multivariable logistic regression analysis demonstrated that the major risk factor for EP was the presence of tubal infertility [adjusted odds ratio (aOR) 2.23, 95% CI 1.93-2.58), followed by the increased number of embryos transferred (aOR 1.29 for 2 versus 1 embryo transferred, 95% CI 1.11-1.49; aOR 1.69 for 3 or more versus 1 embryo transferred, 95% CI 1.35-2.11). The use of extended embryo culture to Days 3-4 or 5-7 significantly reduced the risk of EP, when compared with the transfer of early cleavage (Days 1-2) embryos (respectively, aOR 0.85, 95% CI 0.76-0.94; and aOR 0.73, 95% CI 0.63-0.84). Finally, frozen embryo transfer (ET) had no effect on the risk of EP following IVF/ICSI (aOR 0.92, 95% CI 0.76-1.11). LIMITATIONS, REASONS FOR CAUTION: Owing to the use of this particular registry data, well-established risk factors of EP, such as smoking habits or uterine surgery, could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide the first evidence of a potential benefit-in terms of the reduction in EP rates-of the implementation of national programmes aiming to reduce the incidence of tubal infertility, such as the National Chlamydia Screening Programme. In addition, campaigns for the widespread introduction of single ET may not only reduce the incidence of multiple pregnancies but also the incidence of EP following IVF/ICSI. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study, and there are no conflicts of interest to declare.