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      Reproductive outcomes in women and men conceived by assisted reproductive technologies in Norway: prospective registry based study

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          Abstract

          Objectives

          To determine whether the perinatal outcomes of women or men who were conceived by assisted reproductive technologies are different compared with their peers who were naturally conceived.

          Design

          Prospective registry based study.

          Setting

          Medical Birth Registry of Norway.

          Participants

          People born in Norway between 1984 and 2002 with a registered pregnancy by the end of 2021.

          Exposure

          People who were conceived by assisted reproductive technologies and have had a registered pregnancy.

          Main outcome measures

          Comparing pregnancies and births of people who were conceived by assisted reproductive technologies and people who were naturally conceived, we assessed mean birth weight, gestational age, and placental weight by linear regression, additionally, the odds of congenital malformations, a low 5 min Apgar score (<7), transfer to a neonatal intensive care unit, delivery by caesarean section, use of assisted reproductive technologies, hypertensive disorders of pregnancy and pre-eclampsia, preterm birth, and offspring sex, by logistic regression. The occurrence of any registered pregnancy from people aged 14 years until age at the end of follow-up was assessed using Cox proportional regression for both groups.

          Results

          Among 1 092 151 people born in Norway from 1984 to 2002, 180 652 were registered at least once as mothers, and 137 530 as fathers. Of these, 399 men and 553 women were conceived by assisted reproductive technologies. People who were conceived by assisted reproductive technologies had little evidence of increased risk of adverse outcomes in their own pregnancies, increased use of assisted reproductive technologies, or any difference in mean birth weight, placental weight, or gestational age. The only exception was for an increased risk of the neonate having a low Apgar score at 5 min (adjusted odds ratio 1.86 (95% confidence interval 1.20 to 2.89)) among women who were conceived by assisted reproductive technologies. Odds were slightly decreased of having a boy among mothers conceived by assisted reproductive technologies (odds ratio 0.79 (95% confidence interval 0.67 to 0.93)). People conceived by assisted reproductive technologies were slightly less likely to have a registered pregnancy within the follow-up period (women, adjusted hazard ratio 0.88 (95% CI 0.81 to 0.96); men, 0.91 (0.83 to 1.01)).

          Conclusions

          People conceived by assisted reproductive technologies were not at increased risk of obstetric or perinatal complications when becoming parents. The proportion of people conceived by assisted reproductive technologies with a registered pregnancy was lower than among people who were naturally conceived, but a longer follow-up is required to fully assess their fertility and reproductive history.

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          Most cited references50

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          The International Glossary on Infertility and Fertility Care, 2017.

          Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems?
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            Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

            Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design Systematic review and meta-analysis of cohort studies. Data sources PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
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              Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study

              Abstract Objectives To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. Design Prospective register based study. Setting Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. Participants All Norwegian women that were pregnant between 2009-13. Main outcome measure Risk of miscarriage according to the woman’s age and pregnancy history estimated by logistic regression. Results There were 421 201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% confidence interval 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (adjusted odds ratio 1.22, 95% confidence interval 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). Conclusions The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.
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                Author and article information

                Journal
                BMJ Med
                BMJ Med
                bmjmed
                bmjmed
                BMJ Medicine
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2754-0413
                2023
                14 February 2023
                : 2
                : 1
                : e000318
                Affiliations
                [1 ] departmentCentre for Fertility and Health , Norwegian Institute of Public Health , Oslo, Norway
                [2 ] departmentDepartment of Community Medicine , University of Oslo , Oslo, Norway
                [3 ] departmentEpidemiology Branch , National Institute of Environmental Health Sciences , Durham, NC, USA
                [4 ] departmentDepartment of Fertility , Telemark Hospital Trust , Porsgrunn, Norway
                Author notes
                [Correspondence to ] Dr Ellen Øen Carlsen, Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; EllenOen.Carlsen@ 123456fhi.no
                Author information
                http://orcid.org/0000-0003-1615-5536
                Article
                bmjmed-2022-000318
                10.1136/bmjmed-2022-000318
                10083741
                e8a8f4e7-1479-40fa-816c-801a44b9d9d1
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 12 July 2022
                : 27 January 2023
                Funding
                Funded by: European Research Council;
                Award ID: 947684
                Funded by: FundRef http://dx.doi.org/10.13039/501100013958, Sykehuset Telemark;
                Funded by: Norwegian Institute of Public Health (NIPH);
                Funded by: Research Council of Norway;
                Award ID: 262700
                Award ID: 320656
                Categories
                Research
                1506
                1612
                Custom metadata
                unlocked
                press-release
                press-release

                epidemiology,obstetrics,infertility, male,reproductive medicine

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