STUDY QUESTION
What is the optimal management of women with endometriosis based on the best available evidence in the literature?
SUMMARY ANSWER
Using the structured methodology of the Manual for ...ESHRE Guideline Development, 83 recommendations were formulated that answered the 22 key questions on optimal management of women with endometriosis.
WHAT IS KNOWN ALREADY
The European Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis and treatment of endometriosis (2005) has been a reference point for best clinical care in endometriosis for years, but this guideline was in need of updating.
STUDY DESIGN, SIZE, DURATION
This guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline.
PARTICIPANTS/MATERIALS, SETTING, METHODS
NA.
MAIN RESULTS AND THE ROLE OF CHANCE
The guideline provides 83 recommendations on diagnosis of endometriosis and on the treatment of endometriosis-associated pain and infertility, on the management of women in whom the disease is found incidentally (without pain or infertility), on prevention of recurrence of disease and/or painful symptoms, on treatment of menopausal symptoms in patients with a history of endometriosis and on the possible association of endometriosis and malignancy.
LIMITATIONS, REASONS FOR CAUTION
We identified several areas in care of women with endometriosis for which robust evidence is lacking. These areas were addressed by formulating good practice points (GPP), based on the expert opinion of the guideline group members.
WIDER IMPLICATIONS OF THE FINDINGS
Since 32 out of the 83 recommendations for the management of women with endometriosis could not be based on high level evidence and therefore were GPP, the guideline group formulated research recommendations to guide future research with the aim of increasing the body of evidence.
STUDY FUNDING/COMPETING INTEREST(S)
The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the implementation of the guideline. The guideline group members did not receive payment. All guideline group members disclosed any relevant conflicts of interest (see Conflicts of interest).
TRIAL REGISTRATION NUMBER
NA.
Abstract
STUDY QUESTION
What changes have occurred in the incidence of miscarriage, its treatment options, and the profile of the women having miscarriages in Finland between 1998 and 2016?
SUMMARY ...ANSWER
The annual incidence of registry-identified miscarriage has declined significantly between 1998 and 2016, and non-surgical management has become the dominant treatment.
WHAT IS KNOWN ALREADY
Miscarriage occurs in 8–15% of clinically recognized pregnancies and in ~30% of all pregnancies. Increasing maternal age is associated with an increasing risk of miscarriage. The treatment of miscarriage has evolved significantly in recent years: previously, surgical evacuation of the uterus was the standard of care, but nowadays medical and expectant management are increasingly used.
STUDY DESIGN, SIZE, DURATION
We conducted a nationwide retrospective cohort study of 128 381 women that had experienced a miscarriage that was managed in public healthcare between 1998 and 2016 in Finland.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We used the National Hospital Discharge Registry for the data. Women aged 15–49 years that had experienced their first miscarriage during the follow-up period and had miscarriage-related diagnoses during their admission to public hospital were included in the study. Miscarriages were defined by the 10th Revision of the International Statistical Classification of Diseases and related Medical Problems (ICD-10) diagnostic codes O02*, O03* and O08*. Women with ectopic, molar and continuing pregnancies and induced abortions were excluded. Treatment was divided into surgical and non-surgical treatment using the surgical procedure codes.
MAIN RESULTS AND THE ROLE OF CHANCE
The annual incidence of registry-identified miscarriage has declined from 6.8/1000 15–49-year-old women in 1998 to 5.0/1000 in 2016 (P < 0.001). Also, the incidence rate of registry-identified miscarriage (i.e. the proportion of miscarriages of registry-identified pregnancies i.e. deliveries, induced abortions, and miscarriages) has declined from 112/1000 15–49-year-old pregnant women in 1998 to 83/1000 in 2016 (P < 0.001). The largest decrease in this proportion occurred among women over 40 years of age, among whom 26.5% of registry-identified pregnancies in 1998 ended in miscarriage compared to that of 16.4% in 2016. The proportion of missed abortion has increased (30.3 to 38.8%, P < 0.001) whereas that of blighted ovum has decreased (25.4 to 12.8%, P < 0.001). The proportion of registry-identified miscarriages seen among nulliparous women has increased from 43.7 to 49.6% (P < 0.001). Mean age at the time of miscarriage remained at 31 years throughout the study. Altogether, 29% of all miscarriages were treated surgically and 71% underwent medical or expectant management. The proportion of surgical management has decreased from 38.0 to 1.6% for spontaneous abortion, from 60.7 to 9.4% for blighted ovum and 70.9 to 11.2% for missed abortion between 1998 and 2016.
LIMITATIONS, REASONS FOR CAUTION
This study includes only women with registry-identified pregnancies, i.e. women who were treated in public hospitals. However, the number of women treated elsewhere is presumed to be small. Neither can this study estimate the number of women having spontaneous miscarriage with no hospital contact.
WIDER IMPLICATIONS OF THE FINDINGS
Both the annual incidence and incidence rate of miscarriage of all registry-identified pregnancies has decreased, and non-surgical management has become the standard of care. These findings are of value when planning allocation of healthcare resources and at individual level considering fertility and miscarriage questions. We speculate that improving ultrasound diagnostics explains the increasing proportion of missed abortion relative to other types of miscarriage. More investigation is needed to examine potential risk factors, complications and morbidity associated with miscarriages.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the research funds of the Helsinki and Uusimaa hospital system, by a personal grant from Viipurin Tuberkuloosisäätiö to R.L. and by a personal grant from The Finnish Cultural Foundation to N.H. The authors have no conflicts of interest to declare.
Objective
To assess the incidence of lichen sclerosus (LS) in women and the all‐cause and cause‐specific mortality of women with LS.
Design
Population‐based descriptive study.
Setting
Finland.
...Population
All Finnish women, including 7790 women diagnosed with LS during the period 1969–2012.
Methods
Information gathered from the Finnish Hospital Discharge Register on women with LS was combined with dates and causes of death from Statistics Finland and the Finnish Cancer Registry. Population statistics are from Statistics Finland.
Main outcome measures
Crude and age‐adjusted incidence rates of LS and standardised mortality ratios (SMRs).
Results
The incidence rate of LS adjusted for age (European Standard Population) increased from 14 per 100 000 woman‐years in 2003 to 22 per 100 000 woman‐years in 2010–2012. The age‐specific incidence rate was highest in postmenopausal women (24–53 per 100 000) but was also elevated in girls aged 5–9 years (seven per 100 000). The all‐cause mortality of women with LS was lower than in the general female population (SMR 0.84, 95% CI 0.78–0.90), mostly as a result of decreased mortality from circulatory diseases (SMR 0.80, 95% CI 0.72–0.89) and dementia and Alzheimer’s disease (SMR 0.75, 95% CI 0.62–0.88). The cancer mortality equalled that of the population, but the vulvar cancer mortality was increased (SMR 28.1, 95% CI 19.3–39.4).
Conclusions
Lichen sclerosus is a common disease of elderly women. The overall mortality is decreased whereas the mortality as a result of vulvar cancer is increased.
Tweetable
The likelihood of getting LS by age 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population.
Tweetable
The likelihood of getting LS by 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population.
Introduction
Depression is twice as common in women as in men, especially in the young age group. Multiple factors may contribute to this gender difference. Growing attention is being focused on the ...role of sex hormones, including those of hormonal contraception
(HC). Some recent studies have indicated a higher risk of depression among women using HC, although the results are inconclusive.
Objectives
The aim of this study is to examine the associations between the use of hormonal contraception and the risk of depression in childbearing age women.
Methods
The original cohorts for the study included all women aged 15-49 years with at least one redeemed prescriptions for HC in Finland in 2017 (n=294,356), and a 1:1 age-matched cohort of non-users. After exclusion of prevalent cases (n=35,102), all incident cases of depression (as recorded in the Care Register of Health Care and Register of Primary Health Care Visits) in 2018-2019 were identified (n=23,480), and a 4:1 age-matched control group (n=93,920) was selected from the above cohorts. Current use of HC in the 180 days before the event was compared in cases and controls, and associations with risk of depression were tested via conditional multivariate logistic regression models.
Results
During the follow-up, 23,480 incident cases of depression were identified. Current use (in the 180 days before the event) of HC (OR 0.82, 95% CI 0.79-0.85), in particular of estradiol- or
ethinylestradiol-containing combined HC was associated with a lower risk of depression (OR 0.83, 95% CI 0.76–0.89; OR 0.74, 95% CI 0.71–0.78, respectively) compared to non-use of HC. The results remained significant (OR 0.87, 95% CI 0.81-0.95; and OR 0.77, 95% CI 0.73-0.81, respectively) after controlling for covariates (marital and socioeconomic status, education level, chronic diseases). Use of progestin-only contraception was not associated with altered risk of depression.
Conclusions
Use of HC in childbearing age women is not associated with increased risk of depression. Rather, the use of estradiol- or ethinylestradiol-containing HC is associated with a lower risk of depression.
Disclosure of Interest
None Declared
Abstract
The number of cormorants has rapidly increased in the northernmost Baltic Sea. In 2018, 50 km × 50 km ICES catch rectangle 55H1 had 3140 breeding pairs. To estimate the predation effect of ...cormorants on perch populations, we Passive Integrated Tags tagged 1977 perch and 9.9% of tags were found. The median instantaneous cormorant-induced mortality during the breeding time, with consumption by non-breeding individuals, was estimated at 0.23 and at 0.35 during the whole residing period. We estimated with a yeild-per-recruit model that the long-term maximum loss of perch yield of tagged sub-population would be at 80% probability interval 32–67%, and when extended to the entire 55H1, 10–33%, respectively. The cormorants’ share of the >2-year-old perch biomass and production would be 8%, while that of other natural mortality would be 63% and that of fishing 29% in 55H1. The yield-per-recruit-results should be interpreted as an estimate of maximum cormorant effect because the dependence of predation rate on prey density was not accounted for, and density-dependence of growth, mortality, and reproduction of perch could partly compensate the loss. The results indicate that high density of cormorants can reduce the perch stocks and catches locally.
Introduction
In Finland more than 40% of fertile aged women used some type of hormonal contraception (HC) in the period 2010-2013. A proportion of women using HC complains of side effects, including ...mood symptoms. The relationship between the use of HC and the risk of attempted suicide (AS) is still a matter of debate.
Objectives
To assess the association of the use of HC with the risk of AS during 2017-2019.
Methods
Data were retrieved from the Prescription Centre, Care Register of Health Care, Register of Primary Health Care Visits and Statistics Finland. A total of 587 823 women, aged 15-49 years, using and not using HC in 2017 were analysed in the initial incidence study. All incident AS cases during 2018-2019, and their 4:1 age-matched controls (1 174 346 person-years) were analysed in a nested case-control setting via conditional logistic regression models.
Results
Altogether 818 AS cases occurred during the follow-up (incidence rate: 0.70/1000 person-years, 95% CI 0.65–0.75), with an IRR of HC vs. no-HC use of 0.73 (0.63–0.83). Current use (in the 180 days before the event) of estradiol- or ethinylestradiol-containing HC was associated with a lower risk of AS (0.53, 0.33–0.87; 0.49, 0.37–0.64, respectively) compared to non-use of HC. After controlling for covariates (marital and socioeconomic status, education level, use of psychotropic medications), only current use of HC containing ethinylestradiol remained significant (0.39, 0.23–0.65).
Conclusions
A lower risk of AS is associated with the use of HC, and specifically of ethinylestradiol-containing
HC.
Disclosure
No significant relationships.
Objective
To assess the 1‐year continuation rates and new pregnancies following immediate versus delayed insertion of the levonorgestrel‐releasing intrauterine system (LNG‐IUS) after medical ...termination of pregnancy (MTOP) up to 20 weeks of gestation.
Design
A randomised controlled trial.
Setting
Helsinki University Hospital, Finland, January 2013 to December 2014.
Population
A total of 267 women requesting MTOP and planning LNG‐IUS for post‐MTOP contraception.
Methods
Insertion of LNG‐IUS occurred immediately (0–3 days) or after a delay (2–4 weeks) following MTOP. Follow‐up visits were at 3 months and 1 year after MTOP.
Main outcome measures
LNG‐IUS use at 1 year after MTOP.
Results
Women were randomised to immediate (n = 134) or delayed (n = 133) insertion of the LNG‐IUS, and 133 and 131 were analysed; 127 (95.5%) women received immediate insertion and 111 (84.7%) women had delayed insertion of the LNG‐IUS (risk ratio RR 1.13, 95% CI 1.04–1.22). The verified numbers of women continuing the LNG‐IUS use at 1 year were 83 (62.4%) and 52 (39.7%) (RR 1.57, 95% CI 1.23–2.02). The numbers of new pregnancies were 6 (4.5%) and 16 (12.2%) (RR 0.37, 95% CI 0.15–0.91), and numbers of subsequent TOPs were 4 (3.0%) and 5 (3.8%) (RR 0.79, 95% CI 0.22–2.87).
Conclusions
Immediate insertion of the LNG‐IUS following MTOP resulted in higher 1‐year continuation rates compared with delayed insertion. In addition, those receiving immediate insertion demonstrated a decreased new pregnancy rate, but no difference in the numbers of another TOP.
Tweetable
Immediate LNG‐IUS insertion after MTOP results in a higher 1‐year continuation compared with delayed insertion.
Tweetable
Immediate LNG‐IUS insertion after MTOP results in a higher 1‐year continuation compared with delayed insertion.
Abstract
STUDY QUESTION
Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis?
SUMMARY ANSWER
Compared to reference women, ...the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis.
WHAT IS KNOWN ALREADY
Endometriosis is associated with pain and reduced fertility. The mechanism of infertility is partly explained by anatomical, endocrinological, and immunological changes. Over the past decades, the treatment of both endometriosis and infertility has evolved. Knowledge of fertility far before surgical diagnosis of endometriosis in large cohorts and of different types of endometriosis has been lacking. The diagnostic delay of endometriosis is long, 6–7 years.
STUDY DESIGN, SIZE, DURATION
Retrospective population-based cohort study focused on the time period before the surgical verification of endometriosis. All women with surgical verification of endometriosis in 1998–2012 were identified from the Finnish Hospital Discharge Register and the reference cohort from the Central Population Register. Data on deliveries, gynecological care, and sociodemographic factors before the surgical diagnosis were gathered from Finnish national registers maintained by the Finnish Institute for Health and Welfare, the Digital and Population Data Services Agency, and Statistics Finland.
PARTICIPANTS/MATERIALS, SETTING, METHODS
All women aged 15–49 years at the time of surgical verification of endometriosis (ICD-10: N80.1–N80.9) in Finland during 1998–2012 were identified (n = 21 620). Of them, we excluded women born in 1980–1999 due to the proximity of the surgical diagnosis (n = 3286) and women left without reference (n = 10) for the final endometriosis cohort of 18 324 women. From the final cohort, we selected sub-cohorts of women with isolated diagnosis of ovarian (n = 6384), peritoneal (n = 5789), and deep (n = 1267) endometriosis. Reference women were matched by age and residence and lacked registered clinical or surgical diagnosis of endometriosis (n = 35 793). The follow-up started at the age of 15 years and ended at the first birth, sterilization, bilateral oophorectomy, hysterectomy, or until the surgical diagnosis of endometriosis or corresponding index day—whichever came first. Incidence rate (IR) and the incidence rate ratio (IRR) of first live birth before the surgical verification of endometriosis with corresponding CIs were calculated. In addition, we reported the fertility rate of parous women (the number of all children divided by the number of parous women in the cohort) until the surgical verification of endometriosis. The trends in first births were analysed according to the women’s birth cohort, type of endometriosis, and age.
MAIN RESULTS AND THE ROLE OF CHANCE
Surgical diagnosis of endometriosis was set at the median age of 35.0 years (IQR 30.0–41.4). Altogether 7363 women (40.2%) with endometriosis and 23 718 (66.3%) women without endometriosis delivered a live born infant before the index day (surgery). The IRs of the first live birth per 100 person-years were 2.64 (95% CI 2.58–2.70) in the endometriosis cohort and 5.21 (95% CI 5.15–5.28) in the reference cohort. Between the endometriosis sub-cohorts, the IRs were similar. The IRR of the first live birth was 0.51 (95% CI 0.49–0.52) between the endometriosis and reference cohorts. Fertility rate per parous woman before the surgical diagnosis was 1.93 (SD 1.00) and 2.16 (SD 1.15) in the endometriosis and reference cohorts (P < 0.01). The median age at the first live birth was 25.5 (IQR 22.3–28.9) and 25.5 (IQR 22.3–28.6) years (P = 0.01), respectively. Between the endometriosis sub-cohorts, women in the ovarian sub-cohort were the oldest at the time of surgical diagnosis with the median age of 37.2 years (IQR 31.4–43.3), (P < 0.001). Altogether 44.1% (2814) of the women with ovarian, 39.4% (2282) with peritoneal, and 40.8% (517) with deep endometriosis delivered a live born infant before the diagnosis. IRRs between the endometriosis sub-cohorts did not differ. Fertility rate per parous woman was lowest, 1.88 (SD 0.95), in the ovarian sub-cohort compared to 1.98 (SD 1.07) in the peritoneal and 2.04 (SD 0.96) in deep endometriosis (P < 0.001). Women with ovarian endometriosis were oldest at first live birth compared to women in other sub-cohorts with a median age of 25.8 years (IQR 22.6–29.1) (P < 0.001). Cumulative distributions of first live birth were presented according to age at first live birth and birth cohorts of the participants.
LIMITATIONS, REASONS FOR CAUTION
The increasing age at first live birth, increasing practice of clinical diagnostics, conservative treatment of endometriosis, a possible effect of coexisting adenomyosis, and use of artificial reproductive treatments should be considered when assessing the results. In addition, the study is limited due to possible confounding effects of socioeconomic factors, such as level of education. It should be noted that, in this study, we assessed parity only during the years preceding the surgical verification of endometriosis.
WIDER IMPLICATIONS OF THE FINDINGS
The need for early diagnosis and relevant treatment of endometriosis appears clear given the impairment of fertility prior to its surgical verification.
STUDY FUNDING/COMPETING INTEREST(S)
The study was funded by the Hospital District of Helsinki and Uusimaa and by Finska Läkaresällskapet. The authors report no conflicts of interest. All authors have completed the ICMJE Disclosure form.
TRIAL REGISTRATION NUMBER
N/A.
Objectives
To compare expulsions and adverse events (AEs) between immediate and delayed insertion of a levonorgestrel‐releasing intrauterine system (LNG‐IUS) following medical termination of ...pregnancy (MTOP).
Design
Randomised controlled trial.
Setting
Helsinki University Hospital, Finland, January 2013–December 2014.
Population
Cohorts of 102 (gestational age 64–84 days, late first trimester) and 57 (gestational age 85–140 days, second trimester) women requesting MTOP and LNG‐IUS contraception.
Methods
LNG‐IUS insertion occurred immediately (same day) or 2–4 weeks following MTOP. Follow‐up visits were at 2–4 weeks, 3 months, and 1 year.
Main outcome measures
LNG‐IUS expulsion by 3 months and 1 year. AEs and bleeding profiles within 3 months.
Results
Following late first‐trimester MTOP the LNG‐IUS expulsion rates by 3 months were 14 (27.5%) in the immediate‐insertion group and two (4.0%) in the delayed‐insertion group (risk ratio, RR 6.86; 95% confidence interval, 95% CI 1.64–28.66). By 1 year the expulsion rates were 17 (33.3%) and six (12.0%) (RR 2.78, 95% CI 1.19–6.47). Following second‐trimester MTOP LNG‐IUS expulsion rates by 3 months and 1 year were five (18.5%) in the immediate‐insertion group and one (3.6%) in the delayed‐insertion group (RR 5.19, 95% CI 0.65–41.54). No differences in AEs and bleeding profiles emerged between the groups.
Conclusions
Immediate LNG‐IUS insertion after late first‐ or second‐trimester MTOP is feasible, does not increase the complication rate, or alter the uterine bleeding patterns; however, immediate insertion increased the expulsion rate, which may limit the cost‐effectiveness.
Tweetable
Immediate insertion of LNG‐IUS following MTOP at 9–20 weeks of gestation is feasible and safe.
Tweetable
Immediate insertion of LNG‐IUS following MTOP at 9–20 weeks of gestation is feasible and safe.