Medication and procedural abortions before 13 weeks gestation and risk of psychiatric disorders.

BACKGROUND: The proportion of abortions provided by medication in the United States and worldwide has increased greatly since the U.S. Food and Drug Administration approved mifepristone in 2000. While existing research has shown that abortion does not increase risk of mental health problems, no population-based study has examined specifically whether a procedural or medication abortion increases risk of mental health disorders. OBJECTIVE: This study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion. STUDY DESIGN: Using Danish population registers' data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980 and 2006, who were ages 12 to 38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000 to 2018. Females with no previous psychiatric diagnoses were followed from 1 year before their abortion until their first psychiatric diagnosis, December 31, 2018, emigration from Demark, or death, whichever came first. Risk of any first psychiatric disorder was defined as a recorded psychiatric diagnosis at an in- or out-patient facility from the 1 year after to more than 5 years after a medication or procedural abortion relative to the year beforehand. Results were adjusted for calendar year, age, gestational age, partner status, prior mental and physical health, childbirth history, childhood environment, and parental mental health history. RESULTS: Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before their abortion (medication abortion adjusted incidence rate ratio [MaIRR]=1.02, 95% confidence interval [CI]: 0.93-1.12; procedural abortion adjusted incidence rate ratio [PaIRR]=0.94, 95% CI: 0.86-1.02). Moreover, as more time from the abortion passed, the risk of a psychiatric diagnoses decreased relative to the year before their abortion for each abortion method (MaIRR 1-2 years after=0.89, 95% CI: 0.80-0.98; PaIRR 1-2 years after=0.81, 95% CI: 0.88-1.05; MaIRR 2-5 years after=0.77, 95% CI: 0.71-0.84; PaIRR 2-5 years after=0.72, 95% CI: 0.67-0.78; MaIRR 5+ years after=0.58, 95% CI: 0.53-0.63; PaIRR 5+ years after=0.54, 95% CI: 0.50-0.58). CONCLUSION: Because the risk of psychiatric diagnoses was the same in the year after relative to the year before a medication and procedural abortion and the risk did not increase as more time after the abortion increased, neither abortion method increased risk of mental health disorders in the shorter or longer-term.

Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study.

BACKGROUND AND PURPOSE: Sex differences in multiple sclerosis (MS) prevalence and disease course are thought to be driven by hormones. Exogenous exposure to estrogens may affect MS disease course. Thus, our aim was to investigate the association between hormone therapy (HT) and disease activity and disability accrual among women with MS. METHODS: A register-based cohort study was conducted with prospectively enrolled cases from the Danish MS registry. Information on hormone exposure was retrieved from the National Prescription Registry. Outcomes were relapse rate, relapse rate ratio, recurrent relapses, 6-month confirmed and sustained Expanded Disability Status Scale (EDSS) milestones 4 and 6, and recurrent EDSS worsening. RESULTS: In all, 3325 women were eligible for analyses, of whom 333 (10%) were ever on HT at some time during follow-up. We found no association between HT and disability accrual, although a trend for increasing risk with increasing length of use was seen. The risk of reaching 6-month confirmed and sustained EDSS 4 among users was 0.6 (95% confidence interval [CI] = 0.3-1.2) after <1 year of use and 1.4 (95% CI = 0.9-2.2) after >5 years of HT compared to never use. The risk of recurrent relapse was increased by 20% (95% CI = 1.0-1.4) among current users of HT compared to nonusers. However, the risk of recurrent relapses was driven by the first calendar period (1996-2005) before the introduction of high-efficacy disease-modifying therapy. CONCLUSIONS: Our findings from this nationwide MS population suggest that HT does not affect disability accrual in women with MS, especially if used for <5 years.

Cancer in pregnancy and the risk of adverse pregnancy and neonatal outcomes: A nationwide cohort study.

OBJECTIVES: To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes. DESIGN: A nationwide cohort study. SETTING AND POPULATION: We included all pregnancies (n = 4 071 848) in Denmark from 1 January 1973 to 31 December 2018. METHODS: Exposure was defined as pregnancies exposed to maternal cancer (n = 1068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders. MAIN OUTCOME MEASURES: The outcomes were induced abortion, preterm birth and adverse neonatal outcomes. RESULTS: More women with cancer in pregnancy, as compared with the control group, experienced induced abortion (24.8% vs. 20.0%); first-trimester induced abortion adjusted odds ratio (aOR) 3.5 (95% confidence interval [CI] 2.7-4.5), second-trimester induced abortion; aOR 8.8 (95% CI 6.3-12.3), planned preterm birth (11.8% vs. 1.3%); aOR 10.8 (95% CI 8.0-14.6) and planned preterm birth at <32 gestational weeks; aOR 16.3 (95% CI 8.3-31.7). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 3.5 (95% CI 2.8-4.4), low birthweight; aOR 3.8 (95% CI 3.1-4.8), admission to neonatal intensive care unit for >7 days; aOR 5.1 (95% CI 3.9-6.6), neonatal infection; aOR 1.8 (95% CI1.1-3.1) and neonatal mortality; aOR 4.7 (95% CI 2.7-8.2), but not of SGA; aOR 1.0 (95% CI 0.6-1.5) and malformations; 1.2 (95% CI 0.9-1.7). CONCLUSION: Cancer in pregnancy increases the risk of induced abortion and planned premature birth. Neonates born to mothers with cancer in pregnancy had an increased risk of neonatal morbidity and mortality, presumably due to prematurity. TWEETABLE ABSTRACT: Cancer in pregnancy is associated with an increased risk of premature birth leading to adverse neonatal outcomes.

Reproductive changes among women in their 40s: A cross-sectional study.

INTRODUCTION: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia. MATERIAL AND METHODS: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries. RESULTS: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at ~11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period. CONCLUSIONS: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries.

Contemporary hormonal contraception and cervical cancer in women of reproductive age.

To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person-years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval [CI] 1.10-1.29). Increased risks were seen in current or recent users of any hormonal: RR 1.30 (95% CI 1.20-1.42) and combined: RR 1.40 (95% CI 1.28-1.53), but not progestin-only contraception: RR 0.91 (95% CI 0.78-1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05-1.60) and squamous cancer (RR 1.31, 95% CI 1.19-1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.

Chance of live birth: a nationwide, registry-based cohort study.

STUDY QUESTION: Does the sequence of prior pregnancy events (pregnancy losses, live births, ectopic pregnancies, molar pregnancy and still birth), obstetric complications and maternal age affect chance of live birth in the next pregnancy and are prior events predictive for the outcome? SUMMARY ANSWER: The sequence of pregnancy outcomes is significantly associated with chance of live birth; however, pregnancy history and age are insufficient to predict the outcome of an individual woman's next pregnancy. WHAT IS KNOWN ALREADY: Adverse pregnancy outcomes decrease the chance of live birth in the next pregnancy, whereas the impact of prior live births is less clear. STUDY DESIGN, SIZE, DURATION: Nationwide, registry-based cohort study of 1 285 230 women with a total of 2 722 441 pregnancies from 1977 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women living in Denmark in the study period with at least one pregnancy in either the Danish Medical Birth Registry or the Danish National Patient Registry. Data were analysed using logistic regression with a robust covariance model to account for women with more than one pregnancy. Model discrimination and calibration were ascertained using 20% of the women in the cohort randomly selected as an internal validation set. MAIN RESULTS AND THE ROLE OF CHANCE: Obstetric complications, still birth, ectopic pregnancies and pregnancy losses had a negative effect on the chance of live birth in the next pregnancy. Consecutive, identical pregnancy outcomes (pregnancy losses, live births or ectopic pregnancies) immediately preceding the next pregnancy had a larger impact than the total number of any outcome. Model discrimination was modest (C-index = 0.60, positive predictive value = 0.45), but the models were well calibrated. LIMITATIONS, REASONS FOR CAUTION: While prior pregnancy outcomes and their sequence significantly influenced the chance of live birth, the discriminative abilities of the predictive models demonstrate clearly that pregnancy history and maternal age are insufficient to reliably predict the outcome of a given pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Prior pregnancy history has a significant impact on the chance of live birth in the next pregnancy. However, the results emphasize that only taking age and number of losses into account does not predict if a pregnancy will end as a live birth or not. A better understanding of biological determinants for pregnancy outcomes is urgently needed. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by the Novo Nordisk Foundation, Ole Kirk Foundation and Rigshospitalet's Research Foundation. The authors have no financial relationships that could appear to have influenced the work. TRIAL REGISTRATION NUMBER: N/A.

The impact of early pregnancy complications on completed family size-A nationwide, registry-based cohort study with 40 years of data.

INTRODUCTION: The impact of early pregnancy complications on completed family size is unknown. Here, we hypothesize that early pregnancy complications and adverse outcomes may influence family size. MATERIAL AND METHODS: In this nationwide, registry-based study we included all 458 475 women born 1957-1972 who lived in Denmark from age 20-45 years with at least one registered pregnancy. The main outcome of the study was number of children per woman by age 45, estimated using a Generalized Linear Mixed Model. Exposures were: (a) total number of pregnancy losses experienced (0, 1, 2, ≥3); (b) highest number of consecutive pregnancy losses (0, 1, 2, ≥3); (c) sex of firstborn child; (d) outcome of first pregnancy (live birth, stillbirth, pregnancy loss, ectopic pregnancy, or molar pregnancy). RESULTS: Number of live births was negatively influenced by maternal age and adverse first pregnancy outcomes, especially ectopic pregnancies. A 30-year-old woman with a first ectopic pregnancy was expected to have 1.16 children (95% CI 1.11-1.22) compared with 1.95 children (95% CI 1.86-2.03) with a first live birth. Three or more consecutive losses also decreased number of live births significantly: 1.57 (95% CI 1.50-1.65) compared with 1.92 (95% CI 1.84-2.0) with only live births. The total number of pregnancy losses had no effect before the age of 35 years. Sex of firstborn had no effect. CONCLUSIONS: Previous pregnancy history has a significant effect on number of children per woman, which is important at both individual and societal levels. Pathophysiological research of adverse pregnancy outcomes should be an urgent priority as the causes remain poorly understood.

Gender incongruence in Denmark, a quantitative assessment.

INTRODUCTION: The number of persons with gender incongruence referred to health care is increasing, but national data on the incidence of gender incongruence are lacking. The aim of this study was to quantify the development in number of individuals with gender incongruence over time and to estimate the national incidence in Denmark. MATERIAL AND METHODS: Historical descriptive cohort study. Individuals older than 18 years with legal sex-change in their person registration number were achieved from Statistics Denmark, and the National Health Register provided data on contact diagnoses related to gender-identity conditions. By combining these two data sources, we made estimates on incidence and incidence rates for individuals with gender incongruence in Denmark through a 41-year period 1980-2020. RESULTS: Through 1980-2020, the annual number of legal sex-changes increased in individuals assigned female at birth from 5 to approximately 170 and among individuals assigned male at birth from 10 to approximately 150. The cumulative number of legal sex-changes at the end of 2019 was 1275 assigned female at birth and 1422 assigned male at birth and 66% of the legal sex-changes were in individuals below 30 years. Correspondingly, the annual number of contacts with the healthcare system due for gender-identity-related conditions increased from 30 during 1990-1999 to around 500 in 2017 (both genders combined), with a 10-fold increase from 2010 to 2017. CONCLUSIONS: The number of legal sex-changes and healthcare contacts due to gender-identity-related diagnoses increased substantially over the last 40 years with a more than 10-fold increase during the last decade. This calls for research on possible explanations for this increase, for research on the short-term and long-term health consequences of hormonal and surgical treatment regimens and for ensuring adequate healthcare facilities.

Association of Labor Epidural Analgesia With Autism Spectrum Disorder in Children.

Importance: A recent cohort study found that epidural analgesia during labor was associated with an increased risk of autism in offspring. Objective: To investigate if labor epidural increases the risk of autism in offspring. Design, Setting, and Participants: This nationwide retrospective cohort study identified all live-born children in Denmark between January 2006 and December 2013. Follow-up commenced at children's first birthday and ended in December 2017. Among 485 093 live-born children, 5915 were excluded because of occurrences during the first year of life including death, emigration, misregistration of birth, diagnosis of disease inherently linked to autism, or diagnosis of autism. Exposures: Administration of epidural analgesia during labor, as identified by procedure code. Main Outcomes and Measures: The main outcome of interest was incident diagnosis of autism spectrum disorder based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes in the Danish Psychiatric Central Register or National Patient Register. Hazard ratios were estimated using Cox regression, adjusted for covariates describing maternal comorbidity, sociodemographic factors, lifestyle, pregnancy, psychiatric illness, psychotropic medication, medical-seeking behavior, and family history of autism. A secondary analysis used a within-mother design including only children of mothers with both exposure and nonexposure to labor epidural analgesia in different deliveries. Results: The cohort included 479 178 children (233 405 girls [48.7%]; median maternal age at delivery, 30.9 [IQR, 27.6-34.2] years); of these, 92 900 (19.4%) were exposed to epidural analgesia during labor. Median follow-up was 7.0 years (IQR, 4.9-9.0 years), and by the end of follow-up, 6428 children (1.3%) had been diagnosed with autism. Exposed children had an autism diagnosis incidence rate of 23.1 per 10 000 person-years compared with 18.5 per 10 000 person-years in the unexposed group (crude hazard ratio, 1.29 [95% CI, 1.21-1.37]; adjusted hazard ratio, 1.05 [95% CI, 0.98-1.11]). A secondary within-mother analysis including 59 154 children (12.3%) estimated an autism diagnosis incidence rate of 20.8 per 10 000 person-years in the exposed group and 17.1 per 10 000 person-years in the unexposed group (adjusted hazard ratio, 1.05 [95% CI, 0.90-1.21]). Conclusions and Relevance: In this nationwide cohort study of Danish children, maternal exposure to epidural analgesia during labor was not significantly associated with autism spectrum disorder in offspring.

Pregnancy loss is associated with type 2 diabetes: a nationwide case-control study.

AIMS/HYPOTHESIS: Type 2 diabetes is killing more people than ever, and early-life predictors remain critical for the development of effective preventive strategies. Pregnancy loss is a common event associated with later atherosclerotic disease and ischaemic heart failure and might constitute a predictor for type 2 diabetes. The objective of this study was to investigate whether pregnancy loss is associated with later development of type 2 diabetes. METHODS: Using a Danish nationwide cohort, we identified all women born from 1957 through to 1997 and who had a diagnosis of type 2 diabetes during the period 1977 to 2017. The women were matched 1:10 on year of birth and educational level to women without diabetes in the general Danish population. Conditional logistic regression models provided odds ratios for type 2 diabetes with different numbers of pregnancy losses. RESULTS: We identified 24,774 women with type 2 diabetes and selected 247,740 controls without diabetes. Women who had ever been pregnant (ever-pregnant women) with 1, 2 and ≥ 3 pregnancy losses had ORs of type 2 diabetes of 1.18 (95% CI 1.13, 1.23), 1.38 (95% CI 1.27, 1.49) and 1.71 (95% CI 1.53, 1.92) compared with ever-pregnant women with no pregnancy losses, respectively. Women who never achieved a pregnancy had an OR of type 2 diabetes of 1.56 (95% CI 1.51, 1.61) compared with ever-pregnant women with any number of losses. Similar results were found after adjustment for obesity and gestational diabetes. CONCLUSIONS/INTERPRETATION: We found a significant and consistent association between pregnancy loss and later type 2 diabetes that increased with increasing number of losses. Thus, pregnancy loss and recurrent pregnancy loss are significant risk factors for later type 2 diabetes. Future studies should explore whether this association is due to common background factors or whether prediabetic metabolic conditions are responsible for this association. Graphical abstract.

Contemporary Hormonal Contraception and the Risk of Breast Cancer.

BACKGROUND: Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. METHODS: We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).

Use of antidepressants in women after prophylactic bilateral oophorectomy: A Danish national cohort study.

OBJECTIVE: To investigate the association between prophylactic bilateral oophorectomy and use of antidepressants in women with a family history of cancer. METHODS: Nationwide population-based cohort study using Danish National Registries including women oophorectomized due to a family history of cancer (n = 2,002) and an age matched reference group (n = 18,018). Analyses were stratified by age at time of bilateral oophorectomy and use of hormone replacement therapy (HRT). RESULTS: Women oophorectomized at age ≤ 45 years were more likely to use antidepressants from the first year after bilateral oophorectomy (OR = 1.34; 95 % CI: 1.08-1.65) compared to the reference group. Women oophorectomized at age 46-55 years and at age >55 years had no significantly increased use of antidepressants (OR = 0.90; 95 % CI: 0.68-1.18 and OR = 1.14; 95 % CI: 0.81-1.61). The increased use of antidepressants in women oophorectomized at age ≤ 45 years was limited to women treated with HRT (OR = 1.51; 95 % CI: 1.18-1.94) whereas women oophorectomized at age ≤ 45 years not treated with HRT had no increased use of antidepressants (OR = 1.03; 95 % CI: 0.70-1.51). CONCLUSIONS: Women oophorectomized due to a family history of cancer at age ≤ 45 years were more likely to use antidepressants after bilateral oophorectomy. The increased use of antidepressants was limited to women treated with HRT. The study calls for further large-scale studies to understand how bilateral oophorectomy and concomitant HRT affects risk of depression in women with a family history of cancer.

Pregnancy loss: A 40-year nationwide assessment.

INTRODUCTION: Pregnancy loss is frequent. We aimed to assess the frequency and trends in pregnancy losses according to female age and mode of conception over a 40-year follow-up period. MATERIAL AND METHODS: In a national historical prospective cohort study, we followed all Danish women 10-49 years over the 40-year study period 1978-2017. Data on pregnancies and their outcomes were obtained from the National Health Registry, the Medical Birth Registry and the National Fertility Registry. Incidence rates per 100 pregnancies and per 1,000 women-years as well as lifetime risks per 100 women were calculated. Women included in the lifetime analysis were followed from age 12 to age 49. Pregnancy loss included spontaneous abortion, missed abortion and anembryonic pregnancy. RESULTS: In 3 519 455 recorded pregnancies, 337 008, or 9.6%, were diagnosed with a pregnancy loss. The proportion increased from 7.5% in 1978-1979, peaked at 10.7% in 2000 and thereafter decreased to 9.1% in 2015-2017. Pregnancy loss rate in women 10-14 years was 3.9%, increasing gradually with age to 26.9% in pregnant women 45-49 years, a 6.9-fold increase. Loss rates were slightly lower in naturally conceived pregnancies than in assisted pregnancies except for women above 45 years, where the risk of loss was higher in the spontaneously conceived group. Lifetime risk of specific numbers of losses were: 0: 76.9%, 1: 17.9%, 2: 3.9%, 3: 0.87%, and 4+: 0.35%. CONCLUSIONS: The proportion of women experiencing pregnancy loss has changed little throughout four decades and is still primarily influenced by female age. More than 75% of pregnant women are never recorded with a pregnancy loss, and <1.5% will experience three or more losses.

Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology.

INTRODUCTION: 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 METHODS: Population-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. RESULTS: The 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. CONCLUSION: When 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.

Ectopic Pregnancy Risk in Users of Levonorgestrel-Releasing Intrauterine Systems With 52, 19.5, and 13.5 mg of Hormone.

This study assesses the association between use of levonorgestrel intrauterine systems containing 52, 19.5, and 13.5 mg of hormone and ectopic pregnancy in a nationwide cohort study.

Correction to: Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC).

Following the publication of this article [1], the authors noticed that they incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contraception and migraine status due to a miscalculation. They apologize for this misreported result.

Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH).

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

Low oocyte yield during IVF treatment and the risk of a trisomic pregnancy.

A low number of antral follicles may result in the selection of suboptimal oocytes that are prone to meiotic errors. The aim of this case-control study was to evaluate women receiving IVF treatment with low oocyte yield (defined as three or fewer oocytes retrieved after ovarian stimulation) who are at an increased risk of a trisomic pregnancy. Data were obtained from Danish and Dutch medical registries between 1983 and 2011. Analyses were carried out in 105 cases and 442 controls matched by age and year of IVF treatment. Cases were women with a trisomic pregnancy (trisomies 13, 18 or 21) resulting from fresh IVF treatment and confirmed by karyotyping. Cases were included regardless of pregnancy outcome. Controls were women with a live born child without a trisomy, resulting from fresh IVF treatment. Low oocyte yield was observed in 6.6% (29/440) of the women, of which 8.4% (7/83) were cases and 6.2% (22/357) controls. Low oocyte yield in IVF treatment was not associated with a higher risk of trisomic pregnancy (OR 1.43, 95% CI 0.64 to 3.19). Stratification for female age, adjustment for history of ovarian surgery, and gonadotrophin-releasing hormone protocol used did not change the results.

Endometriosis increases the risk of obstetrical and neonatal complications.

INTRODUCTION: The objective of this study was to assess obstetrical complications and neonatal outcomes in women with endometriosis as compared with women without endometriosis. MATERIAL AND METHODS: National cohort including all delivering women and their newborns in Denmark 1997-2014. Data were extracted from the Danish Health Register and the Medical Birth Register. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI). Sub-analyses were made for primiparous women with a singleton pregnancy and for women with endometriosis who underwent gynecological surgery before pregnancy. RESULTS: In 19 331 deliveries, women with endometriosis had a higher risk of severe preeclampsia (OR 1.7, 95% CI 1.5-2.0), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0-2.5), placental abruption (OR 2.0, 95% CI 1.7-2.3), placenta previa (OR 3.9, 95% CI 3.5-4.3), premature rupture of membranes (OR 1.7, 95% CI 1.5-1.8), and retained placenta (OR 3.1, 95% CI 1.4-6.6). The neonates had increased risks of preterm birth before 28 weeks (OR 3.1, 95% CI 2.7-3.6), being small for gestational age (OR 1.5, 95% CI 1.4-1.6), being diagnosed with congenital malformations (OR 1.3, 95% CI 1.3-1.4), and neonatal death (OR 1.8, 95% CI 1.4-2.1). Results were similar in primiparous women with a singleton pregnancy. Gynecological surgery for endometriosis before pregnancy carried a further increased risk. CONCLUSION: Women with endometriosis had a significantly higher risk of several complications, such as preeclampsia and placental complications in pregnancy and at delivery. The newborns had increased risk of being delivered preterm, having congenital malformations, and having a higher neonatal death rate. Pregnant women with endometriosis require increased antenatal surveillance.