Women's decision-making related to induced abortion - a cross sectional study during a period of Covid-19 pandemic, in Sweden.

OBJECTIVES: To investigate women's decision-making on induced abortion. MATERIALS AND METHODS: A multi-centre cross-sectional survey among 623 abortion-seeking women in Sweden (2021). The perceived difficulty to decide on abortion was measured using a 7-point Likert scale, and analysed with univariate and multivariate analysis (odds ratios [OR], 95% confidence intervals [CI]). RESULTS: About half (n = 322;52%) scored 1-4, suggesting the decision was perceived as easier compared to those (n = 292;48%) who scored 5-7. Reasons for the abortion were: poor economy (n = 166;27%), too early in the relationship (n = 154;25.1%), want to work first (n = 147;23.9%), want to study first (n = 132;21.5%), uncertain about the relationship (104;16.9%), and too young (n = 104;16.9%). Predictors for perceiving the decision as difficult: partner's hesitance (OR = 3.18, CI:1.76-5.73), being born outside the Nordic countries (OR = 2.23, CI:1.28-3.87), having discussed the decision with someone (OR = 2.42, CI:1.67-3.50), age ≥30 (OR = 2.22, CI:1.03-4.76), the Covid-19 pandemic (OR = 2.08, CI:1.20-3.59), and the desire to have children in the future (OR = 1.96, CI:1.18-3.28). After confirmed pregnancy, poor mental well-being was more common among those who scored 5-7 (n = 140;47.9%) compared to those who scored 1-4 (n = 122;37.9), p = .029. CONCLUSION: Women's decision-making on abortion is complex; in times of crises, the decision procedure may be even more difficult. This valuable knowledge could be used to improve and promote satisfactory counselling beyond medical routines.

Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D1 receptor dependent mechanism.

Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic- and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateperone, electrophysiology in vitro to study lumateperone's effects on NMDA- and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine- and glutamate release in the rat mPFC. Our results demonstrate that lumateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumateperone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations.

Effect of levonorgestrel emergency contraception on implantation and fertility: A review.

PURPOSE: Levonorgestrel-only emergency contraception (EC) inhibits ovulation to prevent fertilization. Misconceptions regarding its mechanism of action contribute to low use in some settings. We aimed to review the mechanism of action of Levonorgestrel EC and assess the evidence for a postovulatory effect on viable pregnancy development in the exposed and subsequent cycles. BASIC PROCEDURES: We searched Pubmed, Embase, Web of Science, clinicaltrials.gov, the Cochrane database, and the US FDA Adverse Event Reporting System. We included studies reporting on the effect of Levonorgestrel EC exposure on (1) ovulation, (2) conception, (3) implantation, (4) ectopic pregnancy, (5) pregnancy viability, and (6) fertility in subsequent cycles. Data were extracted and tabulated from included studies by two researchers. The results were analyzed and summarized in narrative form. MAIN FINDINGS: We included 33 studies. Women exposed to Levonorgestrel EC at or after the LH (luteinizing hormone) surge had similar rates of inhibited ovulation (3 studies) and conception rates (2 studies) as controls. Nine out of ten studies found no difference in endometrial receptivity to implantation after exposure to Levonorgestrel EC compared to controls. The evidence for an association between Levonorgestrel EC and reduced fallopian tube motility or ectopic pregnancy was conflicting. We found no evidence of increased miscarriage or teratogenicity (3 studies) or disrupted menstrual cycle (3 studies) after Levonorgestrel EC exposure compared to controls. PRINCIPAL CONCLUSIONS: This review supports that Levonorgestrel EC taken after ovulation does not affect implantation and results in similar conception rates compared to placebo. There is no evidence that exposure to Levonorgestrel EC affects fetal development, miscarriage, stillbirth, or subsequent menstruations.

Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.

OBJECTIVES: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. DESIGN: Multicenter, open-label, phase 3 trial. SETTING: Sixty-nine sites in Europe and Russia. POPULATION: Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 . METHODS: E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary. MAIN OUTCOME MEASURES: Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs. RESULTS: A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events. CONCLUSION: E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile. TWEETABLE ABSTRACT: A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

10-year evaluation of the use of medical abortion through telemedicine: a retrospective cohort study.

OBJECTIVE: To provide a descriptive overview and evaluate changes in the use and outcome of abortions provided worldwide by telemedicine in the past 10 years. DESIGN: Retrospective cohort study. SETTING: Multi-country. POPULATION/SAMPLE: 30 344 women who completed the follow-up survey of the telemedical abortion service Women on Web from January 2009 till January 2020. METHODS: Analyses of follow-up surveys, binary logistic regressions to test the association between year and outcomes. MAIN OUTCOME MEASURES: Rate of complete abortions, surgical interventions, ongoing pregnancies, blood transfusions per year, socio-economic situation, knowledge on medical abortion, acceptability of receiving service, appropriateness of method and the likelihood of recommending the service to a friend. RESULTS: Medical abortions were provided to 81 683 women, of whom 30 344 (37.2%) completed the follow-up survey. In total, 26 076 women reported doing the medical abortion, of whom 1.5% reported an ongoing pregnancy, 10.2% a surgical intervention and 0.6% a blood transfusion. Acceptability of the service was 99%, and 59.2% of the users reported previous knowledge of medical abortion. We found a significant increase in complete abortions in 2019 (odds ratio 1.92; 95% CI 1.59-2.31) and decrease in surgical interventions (odds ratio 0.49; 95% CI 0.40-0.60) compared with 2009. CONCLUSION: Low follow-up rates present a limitation in analysing trends in telemedical abortion usage. However, our findings suggest that it is a highly acceptable method around the world and that there has been an increase in complete abortions by telemedical abortions and a decrease in surgical interventions in the last 10 years. TWEETABLE ABSTRACT: In the last 10 years, there has been an increase in complete abortions and decrease in surgical interventions of telemedical abortion.

There is no association between combined oral hormonal contraceptives and depression: a Swedish register-based cohort study.

OBJECTIVE: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. DESIGN: Register-based cohort study. SETTING: Sweden. SAMPLE: Women aged 15-25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585). METHODS: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others. MAIN OUTCOME MEASURES: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register. RESULTS: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87-0.91) and 1.03 (95% CI 0.99-1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93-0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07-1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30-1.58), implant (RR 1.38, 95% CI 1.30-1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46-1.73) were associated with increased risks. CONCLUSIONS: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. TWEETABLE ABSTRACT: There is no association between combined hormonal contraceptives and depression.

Increasing uptake of long-acting reversible contraception with structured contraceptive counselling: cluster randomised controlled trial (the LOWE trial).

OBJECTIVE: To evaluate the effect of structured contraceptive counselling on the uptake of long-acting reversible contraceptives (LARCs) and pregnancy rates. DESIGN: Cluster randomised trial. SETTING: Abortion, youth and maternal health clinics in Stockholm, Sweden. POPULATION: Sexually active women aged ≥18 years without a wish for pregnancy seeking abortion and/or contraceptive counselling. METHODS: For participants in clinics randomised to intervention, trained healthcare providers implemented a study-specific intervention package designed for structured contraceptive counselling. Participants in the control clinics received routine counselling. MAIN OUTCOME MEASURES: The primary outcome was choice of LARCs at first visit. Secondary outcomes were LARC initiation at 3 months and pregnancy rates at 3 and 12 months. We used logistic mixed-effects models with random intercept for clinic to account for clustering. RESULTS: From September 2017 to May 2019, 28 randomised clinics enrolled 1364 participants. Analyses including 1338 subjects showed that more participants in the intervention group compared with the control group chose LARCs: 267/658 (40.6%) versus 206/680 (30.3%) (OR 2.77, 95% CI 1.99-3.86). LARC initiation was higher in the intervention group compared with the control group: 213/528 (40.3%) versus 153/531 (28.8%) (OR 1.74, 95% CI 1.22-2.49). At the abortion clinics, the pregnancy rate was significantly lower at 12 months in the intervention group compared with the control group: 13/101 (12.9%) versus 28/103 (27.2%) (OR 0.39, 95% CI 0.18-0.88). CONCLUSIONS: Structured contraceptive counselling increased LARC uptake in all clinics and significantly reduced unintended pregnancy rates in abortion clinics at the 12 months follow-up. TWEETABLE ABSTRACT: Structured contraceptive counselling increased LARC uptake and reduced pregnancy rates at 12 months.

Management of pain associated with up-to-9-weeks medical termination of pregnancy (MToP) using mifepristone-misoprostol regimens: expert consensus based on a systematic literature review.

Evidence-based guidelines on the management of pain associated with first-trimester medical abortion are lacking. Most published clinical trials have failed to report on this important aspect of the procedure. The aim of this comprehensive work was to provide clinical advice based on a comprehensive literature review, supplemented by the clinical experience of a group of European experts in case no evidence is available. Pain level ranged from 5 to 8 in 80% of studies where pain was measured on a 0-10 visual analogue scale; severe pain was reported by 20-80% of women. Pain assessment was rarely reported in studies. Pain treatment should be preventive and avoidance of unnecessary uterine contractions should be considered. Analgesic treatment should follow the WHO three-step ladder, starting with the use of NSAIDs and allowing for easily available back-up treatment with weak opioids.

Slow-release vaginal insert of misoprostol versus orally administrated solution of misoprostol for the induction of labour in primiparous term pregnant women: a randomised controlled trial.

OBJECTIVE: To compare the World Health Organization (WHO) recommended orally administrated dosage of misoprostol (25 µg) with a vaginal slow-release (7 µg/hour) insert of misoprostol regarding time from induction to delivery and safety of the method. DESIGN: Open label, Randomised controlled trial (RCT). SETTING: Delivery ward at a secondary referral hospital in Stockholm, Sweden, from 1 October 2016 to 21 February 2018. POPULATION: One hundred and ninety-six primiparous women with singletons in cephalic presentation at ≥37 weeks of gestation and with a Bishop score of ≤4. METHODS: Women were randomised to an oral solution of misoprostol (Cytotec® n = 99) or vaginal slow-release misoprostol (Misodel® [MVI] n = 97). MAIN OUTCOME MEASURES: Primary outcome: time from induction to vaginal delivery. SECONDARY OUTCOMES: mode of delivery; proportion of vaginal deliveries within 24 hours (VD24); neonates with an Apgar score of <7 at 5 minutes; pH < 7.10; postpartum haemorrhage (PPH) of >1000 ml; hyperstimulation; and women's delivery experience (VAS). RESULTS: There was no difference in the time to delivery [corrected] (median 21.1 hours in the MVI group and 23.2 hours in the oral group; Kaplan-Mayer log rank P = 0.31). There was no difference regarding the proportion of VD24 (50.5 versus 55.7%, P = 0.16). Hyperstimulation with non-reassuring cardiotocography (CTG) was more common in the MVI group (14.4 versus 3.0%, P < 0.01). Terbutaline (Bricanyl® ) was used more often for hyperstimulation in the MVI group (22.7 versus 4.0%, P < 0.01). There was no difference in the numbers of children admitted to the neonatal intensive care unit (NICU). CONCLUSIONS: Vaginal delivery after induction of labour (IOL) with slow-release misoprostol did not result in a shorter time from induction to vaginal delivery, compared with oral misoprostol solution, but was associated with a higher risk for hyperstimulation and fetal distress. There were no differences in mode of delivery or neonatal outcome. TWEETABLE ABSTRACT: IOL with MVI was similar to oral solution of misoprostol but hyperstimulation and fetal distress were more common.

Telemedicine for medical abortion: a systematic review.

BACKGROUND: Telemedicine is increasingly being used to access abortion services. OBJECTIVE: To assess the success rate, safety, and acceptability for women and providers of medical abortion using telemedicine. SEARCH STRATEGY: We searched PubMed, EMBASE, ClinicalTrials.gov, and Web of Science up until 10 November 2017. STUDY CRITERIA: We selected studies where telemedicine was used for comprehensive medical abortion services, i.e. assessment/counselling, treatment, and follow up, reporting on success rate (continuing pregnancy, complete abortion, and surgical evacuation), safety (rate of blood transfusion and hospitalisation) or acceptability (satisfaction, dissatisfaction, and recommendation of the service). DATA COLLECTION AND ANALYSIS: Quantitative outcomes were summarised as a range of median rates. Qualitative data were summarised in a narrative synthesis. MAIN RESULTS: Rates relevant to success rate, safety, and acceptability outcomes for women ≤10+0 weeks' gestation (GW) ranged from 0 to 1.9% for continuing pregnancy, 93.8 to 96.4% for complete abortion, 0.9 to 19.3% for surgical evacuation, 0 to 0.7% for blood transfusion, 0.07 to 2.8% for hospitalisation, 64 to 100% for satisfaction, 0.2 to 2.3% for dissatisfaction, and 90 to 98% for recommendation of the service. Rates in studies also including women >10+0 GW ranged from 1.3 to 2.3% for continuing pregnancy, 8.5 to 20.9% for surgical evacuation, and 90 to 100% for satisfaction. Qualitative studies on acceptability showed no negative impacts for women or providers. CONCLUSION: Based on a synthesis of mainly self-reported data, medical abortion through telemedicine seems to be highly acceptable to women and providers, success rate and safety outcomes are similar to those reported in literature for in-person abortion care, and surgical evacuation rates are higher. TWEETABLE ABSTRACT: A systematic review of medical abortion through telemedicine shows outcome rates similar to in-person care.

Safety and acceptability of medical abortion through telemedicine after 9 weeks of gestation: a population-based cohort study.

OBJECTIVE: To assess the safety and acceptability of abortion through telemedicine at >9+0  weeks of gestation. DESIGN: Cohort study. SETTING: Poland. POPULATION: Six hundred and fifteen women who requested and underwent a abortion through telemedicine from 1 June to 31 December 2016. METHODS: Risks of adverse outcomes were calculated as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) by unconditional logistic regression according to gestational age at abortion: ≤9 or >9 weeks of gestation. MAIN OUTCOME MEASURES: Self-reported clinical visits for complaints related to the abortion within 0-1 days of the treatment, heavy bleeding, pain or bleeding more than expected, and low satisfaction. RESULTS: Among women undergoing a abortion at ≤9 or >9 weeks of gestation, 3.3 versus 11.7% went to hospital with concerns within 0-1 days of the termination (aOR 3.82, 95% CI 1.90-7.69). Among women undergoing a abortion from 11+1 to 14+2  weeks of gestation, the rate was 22.5% (aOR 9.20, 95% CI 3.58-23.60). Among women undergoing a abortion at ≤9 or >9 weeks of gestation, the rate of heavy bleeding was 6.8 versus 10.1% (aOR 1.65, 95% CI 0.90-3.04), the rate of low satisfaction was 2.4 versus 1.6% (aOR 0.69, 95% CI 0.14-3.36), the rate of bleeding more than expected was 45.6 versus 57.8% (aOR 1.26, 95% CI 0.78-2.02), and the rate of pain more than expected was 35.6 versus 38.8% (aOR 1.11, 95% CI 0.71-1.71). CONCLUSIONS: Medical abortion through telemedicine at >9 weeks of gestation is associated with a higher risk of same-day or day-after clinical visits for concerns related to the procedure, and this risk increases with gestational age. Self-reported rates of heavy bleeding, low satisfaction, or unmet expectations with medical abortion do not increase with gestational age. TWEETABLE ABSTRACT: A cohort study shows that abortion through telemedicine at >9 weeks of gestation is associated with more hospital visits but not with increased bleeding.

Mifepristone treatment prior to insertion of a levonorgestrel releasing intrauterine system for improved bleeding control - a randomized controlled trial.

STUDY QUESTION: Does pre-treatment with a low dose of mifepristone improve irregular vaginal bleeding patterns during the initial 3 months after LNG-IUS placement? SUMMARY ANSWER: Mifepristone treatment prior to LNG-IUS insertion results in significantly lower bleeding and spotting rates but no significant reduction post insertion. WHAT IS KNOWN ALREADY: One of the leading causes of premature discontinuation of the LNG-IUS is unscheduled bleeding in the first months following its insertion. Up to now, there has been no effective treatment to prevent this side effect which reduces continuation rates for one of the most effective contraceptives. STUDY DESIGN, SIZE, DURATION: This randomized, double blinded, controlled trial was conducted between 2009 and 2015. In total, 68 women opting for a LNG-IUS were screened for eligibility, of whom 58 were randomized at a ratio of 1:1 in blocks of 10 to pre-treatment with mifepristone or a comparator. The main outcome was the rate of bleeding and spotting days reported during the first 3 months post LNG-IUS 52 mg placement. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy women with regular and normal menstrual cycles aged 18-43 years were enrolled at a single center in a university hospital; 29 were allocated to 2 months pre-treatment with a low dose mifepristone and 29 to the comparator prior to insertion of the LNG-IUS. Women were advised to use barrier methods during the pre-treatment period. Bleeding diaries were collected for the pre-treatment period and for the first 6 months after the LNG-IUS placement. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in demographics or baseline characteristics between the study groups. Data for analysis of the main outcome were contributed by a per protocol population of 19 women per group. There was a significant lower bleeding and spotting rate in the mifepristone group (-17.8% points, P < 0.001) after 2 months of pretreatment but after the LNG-IUS insertion no significant difference could be seen. While no pregnancies occurred prior to LNG-IUS insertion in the mifepristone group, there were three unintended pregnancies in the comparator group which emphasizes the need for a reliable contraceptive potential in any pre-treatment regiment used in clinical practice. LIMITATIONS, REASONS FOR CAUTION: The use of mifepristone prior to the LNG-IUS insertion in this trial was used as prophylaxis against unscheduled bleeding after the placement of the device. Although this side effect constitutes a major concern in a clinical setting, only a subset of women are at risk. This is the first study using pre-treatment to attempt improved bleeding control. The differences were small and the effect was short lasting but the reduced rate of bleeding and spotting observed during the first month following LNG-IUS insertion, even though not statistically significant, indicates that this approach may be further explored. The fact that there were three pregnancies in the comparator group stresses the need for any pre-treatment to also protect against unplanned pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Modified treatment protocols of mifepristone could be used prior to the LNG-IUS insertion to investigate possible further improvement of the outcome. The effect size of the current dose used might have been more prominent in women with LNG-IUS if the treatment also continued some weeks after the placement of the device. Although the low dose of mifepristone used in this trial is not available in Europe, other progesterone receptor modulators currently available could be investigated in larger clinical trials. To avoid unintended pregnancy in the pretreatment period, the dosage used should, ideally, also be effective for contraception and the pretreatment period should be kept as short as possible. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Swedish Research Council (2012-2844, 2017-00932), Stockholm County Council and Karolinska Institutet (ALF). Conflicts of interests for K.G.D. and H.K.K. are listed at the end of the paper. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: EudraCT number 2009-009014-40. Regional ethical review board at Karolinska Institutet permit 2009/144-31/4. TRIAL REGISTRATION DATE: 20 July 2009. DATE OF FIRST PATIENT'S ENROLMENT: 24 November 2009.

Epstein-Barr virus is not detected in mucosal lichen planus.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory, immunological, mucocutaneous disease can affect skin, genital and oral mucosa. Oral lichen planus (OLP) is the most common noninfectious, chronic inflammatory oral disease affecting 1-2% of the general adult population. World Health Organization (WHO) classifies OLP as a potentially malignant disorder. Epstein Barr virus or human herpesvirus-4, is a member of the herpes virus family and one of the most ubiquitous viruses known to human, infecting approximately 90% of the world's adult population. The virus often infects B lymphocytes resulting in a wide spectrum of mucocutaneous and systemic diseases, ranging from mild lesions to aggressive malignancies. The aim of this study was to investigate expression of the EBV encoded RNAs EBER1 and EBER2 in oral and genital lichen planus and compare results with normal tissues in situ hybridization which is considered the golden standard for detection of EBER. MATERIAL AND METHODS: A total of 68 biopsies, 25 oral LP, 26 genital LP, 10 oral controls and finally 7 genital controls were analysed using situ hybridization. RESULT: All samples had RNA as shown by the control slide, whereas no case contained neither EBER1 nor EBER2. CONCLUSIONS: Based on results from our study EBV is not involved in aetiology of lichen planus.

Effect of mifepristone on the transcriptomic signature of endometrial receptivity.

STUDY QUESTION: How does a single dose of mifepristone on Day 2 after the LH peak (LH + 2) affect the endometrial receptivity transcriptome as assessed by the receptive signature established by the endometrial receptivity analysis (ERA)? SUMMARY ANSWER: A single dose of mifepristone on day LH + 2 renders the endometrium non-receptive by altering the transcriptome associated with endometrial receptivity. WHAT IS KNOWN ALREADY: Mifepristone is a progesterone receptor modulator that has been shown to alter endometrial receptivity. The ERA is a computational predictor that utilizes gene expression data of 248 genes from next generation sequencing to identify endometrial receptivity status. STUDY DESIGN, SIZE, DURATION: Endometrial biopsies were collected on day LH + 7 from controls (n = 11) and from women treated with mifepristone (n = 7). For further comparative analysis, samples were also obtained from women in the proliferative phase (n = 7). PARTICIPANTS/MATERIALS, SETTING, METHODS: Mifepristone treatment consisted of 200 mg administered on day LH + 2. Endometrial biopsies were treated for RNA isolation and cDNA conversion and sequencing. Endometrial receptivity status was assessed by the ERA computational predictor. Differential gene expression between groups was also assessed. Ingenuity Pathway Analysis was used for network analysis. Validation of gene expression results was done by qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: Control samples were all staged around 'receptive' as would be clinically expected for LH + 7. Treatment samples were all staged as non-receptive (all but one was classified as 'proliferative' and the last as 'pre-receptive'). Differential gene expression analysis yielded 60 differentially expressed genes between the control and treatment groups. Bioinformatic pathway analysis for differential expression showed inactivation of the progesterone and glucocorticoid receptors, consistent with mifepristone action. LIMITATIONS, REASONS FOR CAUTION: The primary limitations are the relative small number of subjects and the use of a limited gene panel. WIDER IMPLICATIONS OF THE FINDINGS: This study sheds further light on the endometrial receptivity altering effects of mifepristone and on progesterone action. It further shows the capacity of the ERA to identify pharmacologically induced non-receptive endometrium, which expands its possible use clinically and in research. STUDY FUNDING/COMPETING INTEREST(S): C.v.G. and N.R.B. have no conflicts of interest. P.G.L. reports honorarium from University of HK/Shenzhen, other from NIF, India, outside the submitted work. K.G.D. reports consultancy for Bayer AG, Exelgyn, HRA-Pharma, Gedeon Richter, MSD, Mithra, Exeltis and Natural cycles, payment for lectures from Bayer AG, NSD, Ferring, HRA-Pharma, Exelgyn and Exeltis and clinical trials for Bayer AG, MSD, Exeltis, Mithra, HRA-Pharma and Sun Pharma. C.S. has a patent gene expression profile (ERA) issued to Igenomix and is scientific director of Igenomix S.L. M.R., R.N. and J.M.V. are employees of Igenomix S.L. TRIAL REGISTRATION NUMBER: N/A.

Co-creation to scale up provision of simplified high-quality comprehensive abortion care in East Central and Southern Africa.

Universal access to comprehensive abortion care (CAC) is a reproductive right and is essential to reduce preventable maternal mortality and morbidity. In East Africa, abortion rates are consistently high, and the vast majority of all abortions are unsafe, significantly contributing to unnecessary mortality and morbidity. The current debate article reflects and summarises key action points required to continue to speed the implementation of and expand access to CAC in the East, Central, and Southern African (ECSA) health community. To ensure universal access to quality CAC, a regional platform could facilitate the sharing of best practices and successful examples from the region, which would help to visualise opportunities. Such a platform could also identify innovative ways to secure women's access to quality care within legally restrictive environments and would provide information and capacity building through the sharing of recent scientific evidence, guidelines, and training programmes aimed at increasing women's access to CAC at the lowest effective level in the healthcare system. This type of infrastructure for exchanging information and developing co-creation could be crucial to advancing the Sustainable Development Goals 2030 agenda.

Molecular characterization of PRM-associated endometrial changes, PAEC, following mifepristone treatment.

OBJECTIVE: The progesterone receptor modulator (PRM) mifepristone holds the potential to be developed for regular contraception. However, long-term treatment can cause thickening of the endometrium and PRM-associated endometrial changes (PAEC). The objective of this study was to explore the molecular expression of endometrium displaying PAEC after mifepristone treatment in order to understand the future implications of PAEC and safety of long-term use. STUDY DESIGN: Endometrial biopsies were obtained from premenopausal women following 3 months of continuous mifepristone treatment. The biopsies were evaluated regarding occurrence of PAEC and followed up by a comparative analysis of gene expression in PAEC endometrium (n=7) with endometrium not displaying PAEC (n=4). Methods used included microarray analysis, Ingenuity Pathway Analysis (IPA) and real-time polymerase chain reaction. RESULTS: Three genes relevant within endometrial function were up-regulated with PAEC: THY1 (p=.02), ADAM12 (p=.04) and TN-C (p=.04). The proliferation marker MKi67 was not altered (p=.31). None of the differentially regulated genes were involved in the endometrial cancer-signaling pathway (based on IPA knowledge database). CONCLUSION: The genes altered in endometrium displaying PAEC after 3 months of mifepristone exposure are mainly involved in the structural architecture of tissue. IMPLICATIONS: PAEC features may be explained by the altered genes and their networks affecting tissue architecture although not involved in endometrial cancer signaling pathways, and thus, treatment with mifepristone at this dosage does not show any adverse effect at endometrial level.

The human genital tubercle is steroidogenic organ at early pregnancy.

It is generally accepted that androgens produced by fetal Leydig cells (FLC) control proper masculinization of the male external genitalia. Here, we hypothesized that the human genital tubercle (GT) has potential to synthesize androgens independently of FLC at early pregnancy. We observed that human GT of both genders have capacity to synthesize steroids of the Δ4, Δ5 and alternative pathway of DHT synthesis including the androgen itself. The presence of steroids in the GT was associated with the expression of corresponding steroidogenic enzymes. Levels of steroids and the expression of steroidogenic enzymes were similar in the GT from male and female fetuses. In contrast to the GT, the human fetal testis synthesized DHT from testosterone but not via the alternative pathway. Our findings strongly suggest that the human GT at early pregnancy can synthesize DHT via the alternative pathway, which may play an important role in organogenesis of the urethra.