SARS-CoV-2 infection during pregnancy and perinatal outcomes in Estonia in 2020 and 2021: A register-based study.

INTRODUCTION: Data from different countries show partly controversial impact of SARS-CoV-2 infection on pregnancy outcomes. A nationwide register-based study was conducted in Estonia to assess the impact of SARS-CoV-2 infection at any time during pregnancy on stillbirth, perinatal mortality, Apgar score at 5 minutes, cesarean section rates, rates of preterm birth and preeclampsia. MATERIAL AND METHODS: Data on all newborns and their mothers were obtained from the Estonian Medical Birth Registry, and data on SARS-CoV-2 testing dates, test results and vaccination dates against SARS-CoV-2 from the Estonian Health Information System. Altogether, 26 211 births in 2020 and 2021 in Estonia were included. All analyses were performed per newborn. Odds ratios with 95% confidence intervals (CI) were analyzed for all outcomes, adjusted for mother's place of residence, body mass index, age of mother at delivery and hypertension and for all the aforementioned variables together with mother's vaccination status using data from 2021 when vaccinations against SARS-CoV-2 became available. For studying the effect of a positive SARS-CoV-2 test during pregnancy on preeclampsia, hypertension was omitted from the models to avoid overadjustment. RESULTS: SARS-CoV-2 infection during pregnancy was associated with an increased risk of stillbirth (adjusted odds ratio [aOR] 2.81; 95% CI 1.37-5.74) and perinatal mortality (aOR 2.34; 95% CI 1.20-4.56) but not with a lower Apgar score at 5 minutes, higher risk of cesarean section, preeclampsia or preterm birth. Vaccination slightly decreased the impact of SARS-CoV-2 infection during pregnancy on perinatal mortality. CONCLUSIONS: A positive SARS-CoV-2 test during pregnancy was associated with higher rates of stillbirth and perinatal mortality in Estonia but was not associated with change in preeclampsia, cesarean section or preterm birth rates.

The cervical transcriptome changes during the menstrual cycle but does not predict the window of implantation.

Introduction: The expression of genes in female reproductive organs is influenced by the cyclic changes in hormone levels during the menstrual cycle. While the molecular changes in the endometrium that facilitate embryo implantation have been extensively studied, there is limited knowledge about the impact of the menstrual cycle on cervical cells. Cervical cells can be easily and routinely collected using a cytobrush during gynecological examination, offering a standardized approach for diagnostic testing. In this study we investigated how the transcriptome of cervical cells changes during the menstrual cycle and assessed the utility of these cells to determine endometrial receptivity. Methods: Endocervical cells were collected with cytobrushes from 16 healthy women at different menstrual cycle phases in natural cycles and from four women undergoing hormonal replacement cycles. RNA sequencing was applied to gain insight into the transcriptome of cervical cells. Results: Transcriptome analysis identified four differentially expressed genes (DEGs) between early- and mid-secretory samples, suggesting that the transcriptome of cervical cells does not change significantly during the opening of the implantation window. The most differences appeared during the transition to the late secretory phase (2136 DEGs) before the onset of menstruation. Cervical cells collected during hormonal replacement cycles showed 1899 DEGs enriched in immune system processes. Conclusions: The results of our study suggested that cervical cells undergo moderate transcriptomic changes throughout the menstrual cycle; however, these changes do not reflect the gene expression pattern of endometrial tissue and offer little or no potential for endometrial receptivity diagnostics.

Lactobacillus crispatus-dominated vaginal microbiome and Acinetobacter-dominated seminal microbiome support beneficial ART outcome.

INTRODUCTION: Despite the considerable progress made in assisted reproductive technologies (ART), the implantation rate of transferred embryos remains low and in many cases, the reasons for failure remain unclear. We aimed to determine the potential impact of female and male partners' reproductive tract microbiome composition on ART outcome. MATERIAL AND METHODS: The ART couples (n = 97) and healthy couples (n = 12) were recruited into the study. The smaller healthy group underwent a careful selection according to their reproductive and general health criteria. Both vaginal and semen samples were subjected to 16S rDNA sequencing to reveal the bacterial diversity and identify distinct microbial community types. Ethics statement The study was approved by the Ethics Review Committee on Human Research of Tartu University, Tartu, Estonia (protocol no. 193/T-16) on 31 May 2010. Participation in the research was voluntary. Written informed consent was obtained from all study participants. RESULTS: The men with Acinetobacter-associated community who had children in the past, had the highest ART success rate (P < 0.05). The women with bacterial vaginosis vaginal microbiome community and with L. iners-predominant and L. gasseri-predominant microbiome had a lower ART success rate than women with the L. crispatus-predominant or the mixed lactic-acid-bacteria-predominant type (P < 0.05). The 15 couples where both partners had beneficial microbiome types had a superior ART success rate of 53%, when compared with the rest of the couples (25%; P = 0.023). CONCLUSIONS: Microbiome disturbances in the genital tract of both partners tend to be associated with couple's infertility as well as lower ART success levels and may thus need attention before the ART procedure. The incorporation of genitourinary microbial screening as a part of the diagnostic evaluation process may become routine for ART patients if our results are confirmed by other studies.

The expression pattern of endometrial receptivity genes is desynchronized between endometrium and matched endometriomas.

RESEARCH QUESTION: Are paired samples of endometrium and ovarian endometriomas synchronous with each other throughout the menstrual cycle? DESIGN: The expression levels of 57 endometrial receptivity-associated genes were determined from matched endometrial and endometrioma samples (n=31) collected from women with endometriosis throughout the menstrual cycle. RESULTS: The expression profile of endometrial receptivity genes divided endometrial samples according to their menstrual cycle phase. Endometrioma samples grouped together irrespective of the menstrual cycle phase and formed a cluster distinct from endometrial samples. Pairwise comparison showed 21, 16, 33 and 23 differentially expressed genes (adjusted P < 0.001-0.05) between the lesions and endometria collected in the proliferative, early-secretory, mid-secretory and late-secretory menstrual cycle phases, respectively, confirming the distinct expression profiles of endometrium and endometrioma. CONCLUSIONS: No menstrual cycle synchronicity was found between matched eutopic and ectopic endometrium, suggesting that the concept of cycling endometrial tissue inside the endometrioma should be revised.

Polyvictimization and the Associations Between Poor Self-Perceived Health, Dissatisfaction With Life, and Sexual Dysfunction Among Women in Estonia.

The severe impact of different forms of violence on health has been demonstrated in a substantial number of studies. At the same time, it has been acknowledged that different forms of violence tend to co-occur, such that many survivors of violence have been exposed to more than one violent event and/or more than one form of violence. Despite mounting evidence concerning the associations between polyvictimization and health, there are still important gaps in this knowledge concerning adult female population's sexual health, including both physical and mental aspects associated with it. The aim of this study was to evaluate the exposure to emotional, physical, and sexual violence among women and associations with poor self-perceived health, dissatisfaction with life, stress, and worry due to sex life and sexual dysfunction. The term polyvictimization is used in this article to express the exposure to more than one form of violence. We used data from a cross-sectional study carried out in Estonia in 2014 among women aged 16 to 44 years. Responses of 2,333 women were analyzed for this article. Of all the respondents, 27.9% were polyvictimized. Women who had been exposed to all three forms of violence had, after adjusting for confounding factors, the highest risk of reporting poor self-perceived health, limited daily activities due to chronic health problems, feelings of depression, dissatisfaction with life, stress, and worry due to sex life and sexual dysfunction. The results of this study demonstrate that exposure to violence is associated with poorer health outcomes and that the association is stronger among those who have been polyvictimized.

What do we know about the impact of sexual violence on health and health behaviour of women in Estonia?

BACKGROUND: Sexual violence against women is a major public health issue and a breach of human rights. Although various consequences of sexual violence on health have been described in a large number of scientific publications, very little is known about this topic in Estonia. The aim of this study was to examine the prevalence of sexual violence and associations between exposure to sexual violence and risky health and sexual behaviours among women in Estonia. METHODS: A population-based cross-sectional study was carried out in Estonia in 2014. Self-reported data regarding selected indicators of risky health and sexual behaviours were collected from 1670 women, aged 18-44 years, via a self-administered questionnaire. To measure the prevalence of sexual violence, questions from the NorVold Abuse Questionnaire were included. Chi-square and multivariate logistic regression were used to analyse the data. RESULTS: Of the respondents, 22.7% (n = 379) reported being exposed to sexual violence during their lifetime, and over half of these women had had these experiences before the age of 18. Statistically significant associations were found between sexual violence and smoking (adjusted odds ratio (AOR) 1.32, 95% CI 1.03-1.70), alcohol consumption (AOR 1.52, 95% CI 1.18-1.95), illicit drug use (AOR 2.21, 95% CI 1.70-2.89), sexual intercourse for money or other material reward (AOR 3.51, 95% CI 1.62-7.61), concurrent sexual relationships (AOR 2.64; 95% CI 1.80-3.86), and being diagnosed with sexually transmitted infections (AOR 1.48, 95% CI 1.09-2.01). CONCLUSIONS: In Estonia, sexual violence against women is widespread and is associated with several risky health and sexual behaviours. Efforts should be made, both among the general public and professionals, to raise awareness regarding the prevalence and negative impact of sexual violence. Women who have been exposed to sexual violence are in need of professional medical, legal and psychological help free from prejudice to help them recover from such traumatic events.

The prevalence and patterns of exposure to interpersonal violence among men and women in Estonia.

BACKGROUND: To understand better the total burden of interpersonal violence on society, it is useful to assess the prevalence of interpersonal violence among both, men and women. Exposure to multiple forms of interpersonal violence, referred to as polyvictimization, has been associated with more severe health consequences than exposure to any form separately. The aims of this study were to assess the prevalence of emotional, physical and sexual interpersonal violence in childhood, adulthood and at both childhood and adulthood among men and women in Estonia, analyze the patterns of interpersonal violence and socio-demographic correlates of polyvictimization in adulthood by gender. METHODS: The analysis was based on two population-based, cross-sectional, self-administered surveys carried out among men and women in Estonia in 2014. In both surveys, the NorVold Abuse questionnaire was used to measure exposure to interpersonal violence. Men and women aged 18-44 were included to the analysis. RESULTS: Among men 66.6% and among women 54.2% had been exposed to at least one form of interpersonal violence during lifetime. Men had been more often exposed to isolated physical interpersonal violence, among women the distribution of different forms of interpersonal violence was more even and exposure to sexual violence was more common. The prevalence of polyvictimization in adulthood was two times higher among women compared to men and more socio-demographic correlates, were associated with it. Exposure to violence in childhood was associated with polyvictimization in adulthood across gender. CONCLUSIONS: The prevalence of interpersonal violence in Estonia is high among men and women. The most prevalent forms and patterns of interpersonal violence, however, differ by gender, as do the socio-demographic correlates. Screening for interpersonal violence, in childhood and adulthood, and gender-specific interventions are needed, especially for high-risk groups identified in this study. Primary prevention of childhood violence should be a priority, as it was associated with higher risk for exposure to violence later in life across gender.

Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe.

OBJECTIVE: To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia. METHODS: This cross-sectional survey was conducted among 382 endocrinologists and obstetrician-gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS. RESULTS: Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non-fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8). CONCLUSION: Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence-based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.

Singleton pregnancies after in vitro fertilization in Estonia: a register-based study of complications and adverse outcomes in relation to the maternal socio-demographic background.

BACKGROUND: An increased risk of adverse conditions related to in vitro fertilization (IVF) pregnancies has been repeatedly reported. Our study aimed to summarize outcome differences between pregnancies after IVF and after spontaneous conception (SC) in Estonia. METHODS: Data on all liveborn singletons to primiparas women aged 25-40 years during the period 2005-2014 were obtained from the Estonian Medical Birth Registry. There were 1778 and 33,555 newborns in the IVF and SC cohort, respectively. The relative risk of pregnancy-related complications and adverse pregnancy outcomes in the IVF cohort in comparison with the SC cohort was quantified by prevalence proportion ratios (RR) with 95% confidence intervals (CI) using modified Poisson regression models adjusted for maternal age, education, ethnicity, marital status and study period. RESULTS: The cohort of IVF singletons experienced a higher risk of preterm birth (RR 1.51; 95% CI 1.28-1.78), iatrogenic preterm birth (RR 1.62; 95% CI 1.32-1.98), very preterm birth (RR 1.49; 95% CI 1.00-2.23), low birthweight (RR 1.47; 95% CI 1.20-1.80), congenital anomalies (RR 1.51; 95% CI 1.08-2.11), and admission to a neonatal intensive care unit (RR 1.13; 95% CI 1.01-1.26). Somewhat elevated risk of spontaneous preterm birth did not reach statistical significance (RR 1.32; 95% CI 0.97-1.80). IVF mothers were at increased risk of placenta previa (RR 7.15; 95% CI 4.04-12.66), placental abruption (RR 2.12; 1.43-3.14) and cesarean section (RR 1.28; 95% CI 1.20-1.37). The risk of pre-eclampsia was borderline (RR 1.25; 95% CI 0.98-1.59). Adjustment for maternal age attenuated the associations between IVF and adverse outcomes. Maternal education, ethnicity and marital status had no effect on the magnitude of the risk estimates. CONCLUSIONS: The increased risk of pregnancy-related complications and adverse pregnancy outcomes was observed in the Estonian cohort of IVF singletons in comparison with the cohort of SC singletons. The relative risk estimates grew with maternal age but were not influenced by the maternal education, ethnicity and marital status. To monitor the efficacy and safety of the used assisted reproductive technology, a specialized country-wide register should be created in Estonia.

Differentially-Expressed miRNAs in Ectopic Stromal Cells Contribute to Endometriosis Development: The Plausible Role of miR-139-5p and miR-375.

microRNA (miRNA) expression level alterations between endometrial tissue and endometriotic lesions indicate their involvement in endometriosis pathogenesis. However, as both endometrium and endometriotic lesions consist of different cell types in various proportions, it is not clear which cells contribute to variability in miRNA levels and the overall knowledge about cell-type specific miRNA expression in ectopic cells is scarce. Therefore, we utilized fluorescence-activated cell sorting to isolate endometrial stromal cells from paired endometrial and endometrioma biopsies and combined it with high-throughput sequencing to determine miRNA alterations in endometriotic stroma. The analysis revealed 149 abnormally expressed miRNAs in endometriotic lesions, including extensive upregulation of miR-139-5p and downregulation of miR-375 compared to eutopic cells. miRNA transfection experiments in the endometrial stromal cell line ST-T1b showed that the overexpression of miR-139-5p resulted in the downregulation of homeobox A9 (HOXA9) and HOXA10 expression, whereas the endothelin 1 (EDN1) gene was regulated by miR-375. The results of this study provide further insights into the complex molecular mechanisms involved in endometriosis pathogenesis and demonstrate the necessity for cell-type-specific analysis of ectopic tissues to understand the interactions between different cell populations in disease onset and progression.

Knowledge and Practices Regarding Polycystic Ovary Syndrome among Physicians in Europe, North America, and Internationally: An Online Questionnaire-Based Study.

BACKGROUND: To inform knowledge translation by identifying evidence-practice gaps in polycystic ovary syndrome (PCOS) care and variations between disciplines and across world regions via an online, anonymous, devised questionnaire distributed via professional societies and completed by 1,495 physicians (2015-2016). METHODS: Multivariable logistic regression analyses generated adjusted odds ratios (OR) and 95% confidence intervals (CI) for associations between outcome measures and world region, specialty, annual patients with PCOS, age, and sex. RESULTS: Features corresponding to Rotterdam diagnostic criteria were well recognized (e.g., irregular menstrual cycles by 99% of physicians), but psychological implications were recognized only by 29 to 64%. Reproductive endocrinologists were more likely to use Rotterdam diagnostic criteria (OR: 3.1; 95% CI: 2.3-4.3; p < 0.007) than obstetrician-gynecologists. Reproductive (OR: 2.0; 95% CI: 1.5-2.8; p < 0.007) and medical endocrinologists (OR: 3.1; 95% CI: 1.7-5.7; p < 0.007) were more likely to recommend lifestyle management than obstetrician-gynecologists. Physicians in Europe (OR: 4.7; 95% CI: 3.5-6.1; p < 0.007) and other regions (OR: 4.0; 95% CI: 2.8-5.9; p < 0.007) were more likely to use Rotterdam diagnostic criteria than physicians in North America. CONCLUSION: Knowledge gaps in PCOS care to be addressed internationally include physician awareness of the breadth of PCOS features, application of diagnostic criteria, and recommending lifestyle management effectively.

Quality of IVF status registration in the Estonian Medical Birth Registry: a national record linkage study.

BACKGROUND: Information regarding in vitro fertilization (IVF) as a pregnancy risk factor (yes/ no) is stored in each birth record of the Estonian Medical Birth Registry (EMBR). This study aimed to assess the validity of registration of newborns' IVF status in the EMBR. METHODS: To identify the newborns conceived by IVF, the birth records in the EMBR were compared to individual records on the embryo transfer procedures in the Estonian Health Insurance Fund (EHIF) database as a reference. Maternal age was restricted to 40 years, the age limit for IVF treatment covered by the EHIF. The embryo transfer procedures, that dated up to eight weeks before pregnancy, were additionally checked in the infertility treatment clinics. The validity of IVF status was measured by sensitivity, specificity, positive and negative predictive values (PPV and NPV). Relative risk (RR) of unrecorded IVF status among IVF mothers by socio-demographic characteristics and birth plurality was estimated using modified Poisson regression models. RESULTS: There were 3198 newborns identified as conceived by IVF in the EMBR in 2005-2014. Eight of them were incorrectly entered as born after IVF. The record linkage with the EHIF database revealed 1014 newborns with unrecorded IVF status in the EMBR. A total of 4204 newborns were verified as conceived by IVF, 24.1% of them were not categorized as born after IVF. The sensitivity of the IVF status registration was poor (75.9%), specificity (100.0%), PPV (99.8%) and NPV (99.3%) were high. The misclassifications were significantly more common among mothers of younger age or non-Estonians or with singleton birth. CONCLUSION: Information based on mother's self-report or her antenatal chart does not accurately identify the newborn's IVF status. The lack of a specialized country-wide assisted reproductive technology register in Estonia requires routine record linkage of the EMBR, EHIF and the infertility treatment clinics' databases to obtain adequate information regarding IVF status in the EMBR. Electronic record linkages between databases would help considerably to improve the validity of data to be used in medical decision making, in research and for statistical purposes.

High-throughput mRNA sequencing of stromal cells from endometriomas and endometrium.

The aetiology of endometriosis is still unclear and to find mechanisms behind the disease development, it is important to study each cell type from endometrium and ectopic lesions independently. The objective of this study was to uncover complete mRNA profiles in uncultured stromal cells from paired samples of endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed over 1300 dysregulated genes in stromal cells from ectopic lesions, including several novel genes in the context of endometriosis. Functional annotation analysis of differentially expressed genes highlighted pathways related to cell adhesion, extracellular matrix-receptor interaction and complement and coagulation cascade. Most importantly, we found a simultaneous upregulation of complement system components and inhibitors, indicating major imbalances in complement regulation in ectopic stromal cells. We also performed in vitro experiments to evaluate the effect of endometriosis patients' peritoneal fluid (PF) on complement system gene expression levels, but no significant impact of PF on C3, CD55 and CFH levels was observed. In conclusion, the use of isolated stromal cells enables to determine gene expression levels without the background interference of other cell types. In the future, a new standard design studying all cell types from endometriotic lesions separately should be applied to reveal novel mechanisms behind endometriosis pathogenesis.

The influence of menstrual cycle and endometriosis on endometrial methylome.

BACKGROUND: Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes, and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. RESULTS: Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 31 patients with endometriosis and 24 healthy women. The DNA methylation profile of patients and controls was highly similar and only 28 differentially methylated regions (DMRs) between patients and controls were found. However, the overall magnitude of the methylation differences between patients and controls was rather small (Δß ranging from -0.01 to -0.16 and from 0.01 to 0.08, respectively, for hypo- and hypermethylated CpGs). Unsupervised hierarchical clustering of the methylation data divided endometrial samples based on the menstrual cycle phase rather than diseased/non-diseased status. Further analysis revealed a number of menstrual cycle phase-specific epigenetic changes with largest changes occurring during the late-secretory and menstrual phases when substantial rearrangements of endometrial tissue take place. Comparison of cycle phase- and endometriosis-specific methylation profile changes revealed that 13 out of 28 endometriosis-specific DMRs were present in both datasets. CONCLUSIONS: The results of our study accentuate the importance of considering normal cyclic epigenetic changes in studies investigating endometrium-related disease-specific methylation patterns.

Contraceptive use among young women in Estonia: Association with contraceptive services.

OBJECTIVES: Our study aimed to explore the association between the use of effective contraceptive methods and access to different contraceptive services, as well as to describe accessibility-related obstacles when using contraceptive services and satisfaction with those services. METHODS: From a population-based cross-sectional study carried out in 2004 (response rate 53.8%), the data of 16- to 24-year-old women requiring contraception (N = 868) were analysed. Factors associated with the use of effective contraceptive methods and, specifically, hormonal methods, were explored using multiple logistic regression analysis. RESULTS: Effective contraception was used by 75.1% of the respondents. The use of effective contraceptive methods was associated with school-based sexuality education (adjusted prevalence odds ratio 2.69; 95% confidence interval 1.32 - 5.50), visiting a youth-friendly clinic (YFC) (1.82; 1.03-3.23) or a private gynaecologist (2.08; 1.11-3.92). The use of hormonal methods was additionally associated with being a native Estonian speaker and visiting a family doctor. More than half of the respondents reported some obstacle in accessing contraceptive services. The highest satisfaction ratings were given to YFCs. CONCLUSIONS: Steps to promote the use of services that are youth-friendly and associated with better uptake of effective contraceptive methods are needed among all 16- to 24-year-old women.

Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time.

OBJECTIVE: To determine whether circulating micro-RNA (miR) 200a, miR-200b, and miR-141 have altered levels in patients with endometriosis compared with control individuals. DESIGN: Experimental laboratory study. SETTING: University. PATIENT(S): Patients with endometriosis (n = 61), laparoscopically confirmed endometriosis-free women (n = 35), and self-reported healthy women (n = 30) were included in the study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Plasma miRNA levels in endometriosis patients and control subjects. RESULT(S): We found that the levels of studied miRNAs varied with blood collection time, being lower in the morning than in the evening. When blood collection time was taken into account, the results revealed significantly lower levels of miR-200a and miR-141 in the evening plasma samples of women with endometriosis compared with surgically confirmed disease-free patients. However, the evening-sample levels of all three miRNAs were significantly lower in patients with stage I-II endometriosis than in endometriosis-free control subjects. In cases of stage III-IV endometriosis, only miR-200a levels were significantly lower compared with patients without endometriosis. Circulating miR-200a showed the best discriminative power to differentiate women with endometriosis from patients with similar complaints but without the disease. CONCLUSION(S): Our findings suggest that miR-200a and miR-141 have a potential as novel noninvasive biomarkers for endometriosis. In addition, we found that the plasma miR-200a, miR-200b and miR-141 levels vary with blood sampling time, so it is important to take the sample collection time into account when studying miRNAs as biomarkers.

Pregnancy intendedness and the association with physical, sexual and emotional abuse - a European multi-country cross-sectional study.

BACKGROUND: Unintended pregnancies are common and when not resulting in a termination of pregnancy may lead to unintended childbirth. Unintended pregnancies are associated with increased health risks, also for women for whom pregnancy continues to childbirth. Our objective was to present the prevalence of unintended pregnancy in six European countries among pregnant women attending routine antenatal care, and to investigate the association with a history of physical, sexual and emotional abuse. METHODS: A prospective cross-sectional study, of 7102 pregnant women who filled out a questionnaire during pregnancy as part of a multi-country cohort study (Bidens) with the participating countries: Belgium, Iceland, Denmark, Estonia, Norway and Sweden. A validated instrument, the Norvold Abuse Questionnaire (NorAq) consisting of 10 descriptive questions measured abuse. Pregnancy intendedness was assessed using a single question asking women if this pregnancy was planned. Cross-tabulation, Chi-square tests and binary logistic regression analysis were used. RESULTS: Approximately one-fifth (19.2 %) of all women reported their current pregnancy to be unintended. Women with an unintended pregnancy were significantly younger, had less education, suffered economic hardship, had a different ethnic background from the regional majority and more frequently were not living with their partner. The prevalence of an unintended pregnancy among women reporting any lifetime abuse was 24.5 %, and 38.5 % among women reporting recent abuse. Women with a history of any lifetime abuse had significantly higher odds of unintended pregnancy, also after adjusting for confounding factors, AOR for any lifetime abuse 1.41 (95 % CI 1.23-1.60) and for recent abuse AOR 2.03 (95 % CI 1.54-2.68). CONCLUSION: Women who have experienced any lifetime abuse are significantly more likely to have an unintended pregnancy. This is particularly true for women reporting recent abuse, suggesting that women living in a violent relationship have less control over their fertility.

Fear of childbirth and risk of cesarean delivery: a cohort study in six European countries.

BACKGROUND: Few studies have examined the mode of birth among women with fear of childbirth, and the results are conflicting. The objective of this study was to assess the association between fear of childbirth and cesarean delivery in North European women. METHODS: A longitudinal cohort study was conducted among 6,422 pregnant women from Belgium, Iceland, Denmark, Estonia, Norway, and Sweden. Fear of childbirth was measured by the Wijma Delivery Expectancy Questionnaire during pregnancy and linked to obstetric information from hospital records. RESULTS: Among 3,189 primiparous women, those reporting severe fear of childbirth were more likely to give birth by elective cesarean, (OR, 1.66 [95% CI 1.05-2.61]). Among 3,233 multiparous women, severe fear of childbirth increased the risk of elective cesarean (OR 1.87 [95% CI 1.30-2.69]). Reporting lack of positive anticipation, one of six dimensions of fear of childbirth, was most strongly associated with elective cesarean (OR 2.02 [95% CI 1.52-2.68]). A dose-effect pattern was observed between level of fear and risk of emergency cesarean in both primiparous and multiparous women. Indications for cesarean were more likely to be reported as "nonmedical" among those with severe fear of childbirth; 16.7 versus 4.6 percent in primiparous women, and 31.7 versus 17.5 percent in multiparous women. CONCLUSION: Having severe fear of childbirth increases the risk of elective cesarean, especially among multiparous women. Lack of positive anticipation of the upcoming childbirth seems to be an important dimension of fear associated with cesarean delivery. Counseling for women who do not look forward to vaginal birth should be further evaluated.