IMplementing best practice post-partum contraceptive services through a quality imPROVEment initiative for and with immigrant women in Sweden (IMPROVE it): a protocol for a cluster randomised control trial with a process evaluation.

BACKGROUND: Immigrant women's challenges in realizing sexual and reproductive health and rights (SRHR) are exacerbated by the lack of knowledge regarding how to tailor post-partum contraceptive services to their needs. Therefore, the overall aim of the IMPROVE-it project is to promote equity in SRHR through improvement of contraceptive services with and for immigrant women, and, thus, to strengthen women's possibility to choose and initiate effective contraceptive methods post-partum. METHODS: This Quality Improvement Collaborative (QIC) on contraceptive services and use will combine a cluster randomized controlled trial (cRCT) with a process evaluation. The cRCT will be conducted at 28 maternal health clinics (MHCs) in Sweden, that are the clusters and unit of randomization, and include women attending regular post-partum visits within 16 weeks post birth. Utilizing the Breakthrough Series Collaborative model, the study's intervention strategies include learning sessions, action periods, and workshops informed by joint learning, co-design, and evidence-based practices. The primary outcome, women's choice of an effective contraceptive method within 16 weeks after giving birth, will be measured using the Swedish Pregnancy Register (SPR). Secondary outcomes regarding women's experiences of contraceptive counselling, use and satisfaction of chosen contraceptive method will be evaluated using questionnaires completed by participating women at enrolment, 6 and 12 months post enrolment. The outcomes including readiness, motivation, competence and confidence will be measured through project documentation and questionnaires. The project's primary outcome involving women's choice of contraceptive method will be estimated by using a logistic regression analysis. A multivariate analysis will be performed to control for age, sociodemographic characteristics, and reproductive history. The process evaluation will be conducted using recordings from learning sessions, questionnaires aimed at participating midwives, intervention checklists and project documents. DISCUSSION: The intervention's co-design activities will meaningfully include immigrants in implementation research and allow midwives to have a direct, immediate impact on improving patient care. This study will also provide evidence as to what extent, how and why the QIC was effective in post-partum contraceptive services. TRIAL REGISTRATION: NCT05521646, August 30, 2022.

Modern contraceptive use among female refugee adolescents in northern Uganda: prevalence and associated factors.

BACKGROUND: Adolescent pregnancies are persistently high among refugees. The pregnancies have been attributed to low contraceptive use in this population. The aim of this study was to determine the prevalence and factors associated with modern contraceptive use among female refugee adolescents in northern Uganda. METHODS: This was a cross sectional study using both descriptive and analytical techniques. The study was carried out in Palabek refugee settlement in Northern Uganda from May to July 2019. A total of 839 refugee adolescents who were sexually active or in-union were consecutively enrolled. Interviewer administered questionnaires were used for data collection. RESULTS: Modern contraceptive prevalence was 8.7% (95% CI: 7.0 to 10.8). The injectable was the most commonly used modern contraceptive method [42.5% (95% CI: 31.5 to 54.3)], and most of the participants had used the contraceptives for 6 months or less (59.7%). Reasons for not using modern contraceptives included fear of side effects (39.3%), partner prohibition (16.4%), and the desire to become pregnant (7.0%). Participants who were married (OR = 0.11, 95% CI: 0.04 to 0.35, p < 0.001), cohabiting (OR = 0.43, 95% CI: 0.20 to 0.93, p = 0.032) or having an older partner (OR = 0.93, 95% CI: 0.86 to 0.99, p = 0.046) were less likely to use modern contraceptives. CONCLUSION: Modern contraceptive use among female refugee adolescents was very low, and few reported a desire to become pregnant, leaving them vulnerable to unplanned pregnancies. Least likely to use modern contraceptives were participants who were married/cohabiting and those having older partners implying a gender power imbalance in fertility decision making. There is an urgent need for innovations to address the gender and power imbalances within relationships, which could shape fertility decision-making and increase modern contraceptive use among refugee adolescents.

Management of very early medical abortion-An international survey among providers.

OBJECTIVE: To record the definition and management of Very Early Medical Abortion (VEMA) in different countries. STUDY DESIGN: An Internet survey was circulated internationally among providers of medical abortion via a website. The questionnaire focused on reasons for performing or delaying medical abortion at a very early gestational age and the perceived advantages and disadvantages of VEMA. RESULTS: Out of 220 completed questionnaires, 50 % came from European abortion providers (n = 110). Most respondents (72 %) defined VEMA as abortion performed in the presence of a positive hCG pregnancy test but with an empty uterine cavity or a gestational sac-like structure, and no signs or symptoms of ectopic pregnancy. A total of 74 % of respondents thought it was not necessary to wait for a diagnosis of intrauterine pregnancy before starting medical abortion. Equally, 74 % were aware of the possibility of an ectopic pregnancy. CONCLUSION: According to European providers of medical abortion, waiting for the diagnosis of an intrauterine pregnancy is not necessary and does not improve treatment of ectopic pregnancy. Providers should know that medical abortion can be performed effectively and safely as soon as the woman has decided. There is no lower gestational age limit.

Sexual and reproductive health and rights of refugee and migrant women: gynecologists' and obstetricians' responsibilities.

Ensuring universal access to sexual and reproductive healthcare services is Target 3.7 of the United Nations Sustainable Development Goals (SDG). Refugee and migrant women and children are at particular risk of being forgotten in the global momentum to achieve this target. In this article we discuss the violations of sexual and reproductive health and rights (SRHR) of particular relevance to the refugee and migrant reality. We give context-specific examples of denial of health services to vulnerable groups; lack of dignity as a barrier to care; the vulnerability of adolescents; child marriage; weaponized rape; gender-based violence; and sexual trafficking. We discuss rights frameworks and models that are being used in response to these situations, as well as what remains to be done. Specifically, we call for obstetricians and gynecologists to act as individual providers and through their FIGO member societies to protect women's health and rights in these exposed settings.

Advantages of determining the fertile window with the individualised Natural Cycles algorithm over calendar-based methods.

Purpose: This study aims to compare the accuracy of fertile window identification with the contraceptive app Natural Cycles against the Rhythm Method and Standard Days Method (SDM).Materials and methods: Menstruation dates, basal body temperature (BBT), and luteinising hormone (LH) test results were collected anonymously from Natural Cycles app users. The fraction of green days (GDs) and wrong green days (WGDs) allocated by the various algorithms was determined over 12 cycles. For comparison of Natural Cycles and the Rhythm Method, 26,626 cycles were analysed.Results: Natural Cycles' algorithms allocated 59% GDs (LH, BBT) in cycle 12, while the fraction of WGDs averaged 0.08%. The Rhythm Method requires monitoring of six cycles, resulting in no GDs or WGDs in cycle 1-6. In cycle 7, 49% GDs and 0.26% WGDs were allocated. GDs and WGDs decreased to 43% and 0.08% in cycle 12. The probabilities of WGDs on the day before ovulation with Natural Cycles were 0.31% (BBT) and 0% (LH, BBT), and 0.80% with the Rhythm Method. The probability of WGDs on the day before ovulation was 6.90% with the SDM.Conclusions: This study highlights that individualised algorithms are advantageous for accurate determination of the fertile window and that static algorithms are more likely to fail during the most fertile days.

Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles.

The use of apps that record detailed menstrual cycle data presents a new opportunity to study the menstrual cycle. The aim of this study is to describe menstrual cycle characteristics observed from a large database of cycles collected through an app and investigate associations of menstrual cycle characteristics with cycle length, age and body mass index (BMI). Menstrual cycle parameters, including menstruation, basal body temperature (BBT) and luteinising hormone (LH) tests as well as age and BMI were collected anonymously from real-world users of the Natural Cycles app. We analysed 612,613 ovulatory cycles with a mean length of 29.3 days from 124,648 users. The mean follicular phase length was 16.9 days (95% CI: 10-30) and mean luteal phase length was 12.4 days (95% CI: 7-17). Mean cycle length decreased by 0.18 days (95% CI: 0.17-0.18, R 2 = 0.99) and mean follicular phase length decreased by 0.19 days (95% CI: 0.19-0.20, R 2 = 0.99) per year of age from 25 to 45 years. Mean variation of cycle length per woman was 0.4 days or 14% higher in women with a BMI of over 35 relative to women with a BMI of 18.5-25. This analysis details variations in menstrual cycle characteristics that are not widely known yet have significant implications for health and well-being. Clinically, women who wish to plan a pregnancy need to have intercourse on their fertile days. In order to identify the fertile period it is important to track physiological parameters such as basal body temperature and not just cycle length.

Evaluating the safety, effectiveness and acceptability of treatment of incomplete second-trimester abortion using misoprostol provided by midwives compared with physicians: study protocol for a randomized controlled equivalence trial.

BACKGROUND: A large proportion of abortion-related mortality and morbidity occurs in the second trimester of pregnancy. The Uganda Ministry of Health policy restricts management of second-trimester incomplete abortion to physicians who are few and unequally distributed, with most practicing in urban regions. Unsafe and outdated methods like sharp curettage are frequently used. Medical management of second-trimester post-abortion care by midwives offers an advantage given the difficulty in providing surgical management in low-income settings and current health worker shortages. The study aims to assess the safety, effectiveness and acceptability of treatment of incomplete second-trimester abortion using misoprostol provided by midwives compared with physicians. METHODS: A randomized controlled equivalence trial implemented at eight hospitals and health centers in Central Uganda will include 1192 eligible women with incomplete abortion of uterine size > 12 weeks up to 18 weeks. Each participant will be randomly assigned to undergo a clinical assessment and treatment by either a midwife (intervention arm) or a physician (control arm). Enrolled participants will receive 400 µg misoprostol administered sublingually every 3 h up to five doses within 24 h at the health facility until a complete abortion is confirmed. Women who do not achieve complete abortion within 24 h will undergo surgical uterine evacuation. Pre discharge, participants will receive contraceptive counseling and information on what to expect in terms of side effects and signs of complications, with follow-up 14 days later to assess secondary outcomes. Analyses will be by intention to treat. Background characteristics and outcomes will be presented using descriptive statistics. Differences between groups will be analyzed using risk difference (95% confidence interval) and equivalence established if this lies between the predefined range of - 5% and + 5%. Chi-square tests will be used for comparison of outcome and t tests used to compare mean values. P ≤ 0.05 will be considered statistically significant. DISCUSSION: Our study will provide evidence to inform national and international policies, standard care guidelines and training program curricula on treatment of second-trimester incomplete abortion for improved access. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03622073 . Registered on 9 August 2018.

Trial protocol: a parallel group, individually randomized clinical trial to evaluate the effect of a mobile phone application to improve sexual health among youth in Stockholm County.

BACKGROUND: Genital Chlamydia trachomatis infection is a major public health problem worldwide affecting mostly youth. Sweden introduced an opportunistic screening approach in 1982 accompanied by treatment, partner notification and case reporting. After an initial decline in infection rate till the mid-90s, the number of reported cases has increased over the last two decades and has now stabilized at a high level of 37,000 reported cases in Sweden per year (85% of cases in youth). Sexual risk-taking among youth is also reported to have significantly increased over the last 20 years. Mobile health (mHealth) interventions could be particularly suitable for youth and sexual health promotion as the intervention is delivered in a familiar and discrete way to a tech savvy at-risk population. This paper presents a protocol for a randomized trial to study the effect of an interactive mHealth application (app) on condom use among the youth of Stockholm. METHODS: 446 youth resident in Stockholm, will be recruited in this two arm parallel group individually randomized trial. Recruitment will be from Youth Health Clinics or via the trial website. Participants will be randomized to receive either the intervention (which comprises an interactive app on safe sexual health that will be installed on their smart phones) or a control group (standard of care). Youth will be followed up for 6 months, with questionnaire responses submitted periodically via the app. Self-reported condom use over 6 months will be the primary outcome. Secondary outcomes will include presence of an infection, Chlamydia tests during the study period and proxy markers of safe sex. Analysis is by intention to treat. DISCUSSION: This trial exploits the high mobile phone usage among youth to provide a phone app intervention in the area of sexual health. If successful, the results will have implications for health service delivery and health promotion among the youth. From a methodological perspective, this trial is expected to provide information on the strength and challenges of implementing a partially app (internet) based trial in this context. TRIAL REGISTRATION: ISRCTN 13212899, date of registration June 22, 2017.

Repeat testing for chlamydia trachomatis, a "safe approach" to unsafe sex? a qualitative exploration among youth in Stockholm.

BACKGROUND: Chlamydia trachomatis testing is offered to youth in Sweden, through a network of Youth Health Clinics, free at the point of care, in an attempt to bring down the prevalence and incidence of the infection. Nevertheless, infections rates have continued to rise during the past two decades and re-testing rates among youth for Chlamydia trachomatis has been reported to be high in Stockholm County. A few literature reports suggest that testing for sexually transmitted infections and the test result itself can have an undesirable impact on the sexual behaviour for the individual, i.e. increase sexual risk-taking. METHODS: This qualitative study aimed to explore the motives for repeated testing for Chlamydia trachomatis among youth using the services of the Youth Health Clinics in Stockholm, and how testing affects their subsequent risk-taking. We interviewed 15 repeat testers aging 18-22 years. RESULTS: Our main findings were that the fear of social stigma related to infecting a peer was a major driver of the re-testing process. The repetitive testing process, the test result, and the encounter with personnel did not decrease sexual risk-taking among this group. CONCLUSIONS: While testing and treatment services are an important part of Chlamydia trachomatis prevention it must not take the focus away from primary prevention strategies. Testing should be encouraged, but not to the exclusion of risk reduction measures. The testing services must be complemented with stronger emphasis on safe sex, especially for those who attend the clinics repeatedly, otherwise the easy accessible testing services risk counteracting its own purpose. Future research should focus on developing and evaluating youth appropriate interventions to increase condom use, taking into consideration factors which youth perceive as important to drive this behaviour change.

Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle-A double-blind, placebo-controlled randomized trial.

OBJECTIVE: Ever since the introduction of combined oral contraception (COC), one of the major reasons for discontinuing the pill use has been mood-related side effects. Moreover, women who discontinue the pill turn to less effective methods whereby the probability of an unintended conception increases. Approximately 4-10% of COC users complain of depressed mood, irritability or increased anxiety, but drug-related causality has been difficult to prove. Given the lack of randomized controlled trials in this area, we aimed to prospectively estimate the severity of adverse mood in COC users that would be as representative of general users as possible. METHODS: This investigator-initiated, multi-center, randomized, double-blinded, placebo-controlled study included 202 healthy women. Women were randomized to a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo for three treatment cycles. Main outcome measure was the Daily Record of Severity of Problems (DRSP), which was filled out daily during one baseline cycle and the final treatment cycle. RESULTS: Results from 84 women in the COC group and 94 women in the placebo group were analysed. COC use was associated with small, but statistically significant, increases in mean anxiety (0.22; 95% CI: 0.07-0.37, p=0.003), irritability (0.23; 95% CI: 0.07-0.38, p=0.012), and mood swings scores (0.15; 95% CI: 0.00-0.31, p=0.047) during the intermenstrual phase, but a significant premenstrual improvement in depression (-0.33; 95% CI: -0.62 to -0.05, p=0.049). Secondary analyses showed that women with previous adverse hormonal contraceptive experience reported significantly greater mood worsening in the intermenstrual phase in comparison with healthy women, p<0.05. The proportion of women who reported a clinically relevant mood deterioration did not differ between those allocated to COC (24.1%) or placebo (17.0%), p=0.262. CONCLUSION: COC use is associated with small but statistically significant mood side effects in the intermenstrual phase. These findings are driven by a subgroup of women who clearly suffer from COC-related side effects. However, positive mood effects are noted in the premenstrual phase and the proportion of women with clinically relevant mood worsening did not differ between treatment groups.

Prevention of unintended pregnancy and use of contraception-important factors for preconception care.

Preservation of fertility and optimizing health before pregnancy is becoming increasingly important in societies where childbirth often is postponed. Research shows that as women postpone childbirth they achieve higher levels of education and higher incomes. This leads to advantages for their children and for society. However, as women postpone childbearing they are at risk for contracting conditions which may affect fertility and/or pregnancies, pregnancy outcome, and the newborn child. Preconception counseling is therefore becoming increasingly important. Women are often unaware of the added health benefits of contraception and have the right to be well informed so they can make decisions to fulfill their reproductive desires. Contraception can reduce the risk of unintended pregnancies, ectopic and molar pregnancies, and sexually transmitted infections. In addition, hormonal contraceptives reduce the risk of some types of cancer, dysmenorrhea, heavy menstrual bleeding, and anemia and are a treatment for endometriosis. Contraception should increasingly be looked upon as a means of preserving fertility and optimizing health status before a planned pregnancy. Thus, effective contraception can provide women with a possibility of achieving their long-term reproductive goals, although childbearing is actually postponed. The most effective contraceptive methods are the long-acting reversible contraceptives, which have been shown to be highly effective especially in young women who have difficulties with adherence to user-dependent methods. Therefore, these methods should increasingly be promoted in all age groups.

"Who Wants to Go Repeatedly to the Hospital?" Perceptions and Experiences of Simplified Medical Abortion in Rajasthan, India.

The aim of this study is to explore women's experiences and perceptions of home use of misoprostol and of the self-assessment of the outcome of early medical abortion in a low-resource setting in India. In-depth interviews were conducted with 20 women seeking early medical abortion, who administered misoprostol at home and assessed their own outcome of abortion using a low-sensitivity pregnancy test. With home use of misoprostol, women were able to avoid inconvenience of travel, child care, and housework, and maintain confidentiality. The use of a low-sensitivity pregnancy test alleviated women's anxieties about retained products. Majority said they would prefer medical abortion involving a single visit in future. This study provides nuanced understanding of how women manage a simplified medical abortion in the context of low literacy and limited communication facilities. Service delivery guidelines should be revised to allow women to have medical abortion with fewer visits.

The importance of considering the evidence in the MTP 2014 Amendment debate in India - unsubstantiated arguments should not impede improved access to safe abortion.

With the objective to improve access to safe abortion services in India, the Ministry of Health and Welfare, with approval of the Law Ministry, published draft amendments of the MTP Act on October 29, 2014. Instead of the expected support, the amendments created a heated debate within professional medical associations of India. In this commentary, we review the evidence in response to the current discourse with regard to the amendments. It would be unfortunate if unsubstantiated one-sided arguments would impede the intention of improving access to safe abortion care in India.

Familial cancer among consecutive uterine cancer patients in Sweden.

BACKGROUND: Uterine cancer (UC) represents 5.1% of all female malignancies in Sweden. Accumulation of UC in families occurs in around 5% of cases. We wanted to identify any familial association between UC and other selected cancers and to study the frequency of Lynch,Cowden and cancer syndromes among consecutive UC patients in Sweden. METHODS: 481 UC patients were included. Information on the cancer diagnoses of their relatives (first- (FDRs) and second-degree (SDRs) relatives and first cousins) was obtained. The relative frequencies of different cancers among relatives were compared to those in the Swedish general cancer population in 1970 and 2010. Families that fulfilled the criteria for hereditary cancer syndromes were tested for mutations in the causative genes. Families with at least one case of UC in addition to the index patient were compared to families with no additional cases to investigate possible characteristics of putative hereditary cancer syndromes. RESULTS: There was an increased prevalence of UC in our study population compared to the Swedish general cancer population in 1970 and 2010 (6% vs. 4% and 3%, respectively). Seven families had Lynch Syndrome according to the Amsterdam II criteria. No families fulfilled the criteria for Cowden syndrome. In total 13% of index patients had at least one relative with UC and these families tended to have more cases of early onset cancer among family members. In addition, 16% of index patients were diagnosed with at least one other cancer. No families fulfilled the criteria for Cowden syndrome. CONCLUSION: We showed a familial clustering of UC among relatives of our index patients. Of the seven families with mutation-verified Lynch Syndrome, only one had been previously diagnosed, highlighting the need to increase gynecologists' awareness of the importance of taking family history. Our data on multiple cancers and young age of onset in families with uterine cancer is compatible with the existence of additional hereditary uterine cancer syndromes.

Attachment and biofilm forming capabilities of Staphylococcus epidermidis strains isolated from preterm infants.

Staphylococcus epidermidis, a human commensal, is an important opportunistic, biofilm-forming pathogen and the main cause of late onset sepsis in preterm infants, worldwide. In this study we describe the characteristics of S. epidermidis strains causing late onset (>72 h) bloodstream infection in preterm infants and skin isolates from healthy newborns. Attachment and biofilm formation capability were analyzed in microtiter plates and with transmission electron microscopy (TEM). Clonal relationship among strains was studied with pulsed-field gel electrophoresis. Antimicrobial susceptibility testing was performed, as well as the detection of biofilm-associated genes and of the invasiveness marker IS256 with polymerase chain reaction. Blood and skin isolates had similar attachment and biofilm-forming capabilities and biofilm formation was not related to the presence of specific genes. Filament-like membrane structures were seen by TEM early in the attachment close to the device surface, both in blood and skin strains. Nine of the ten blood isolates contained the IS256 and were also resistant to methicillin and gentamicin in contrast to skin strains. S. epidermidis strains causing bloodstream infection in preterm infants exhibit higher antibiotic resistance and are provided with an invasive genetic equipment compared to skin commensal strains. Adhesion capability to a device surface seems to involve bacterial membrane filaments.

Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.

Vulvar squamous cell carcinoma (VSCC) is the fourth most common gynecological cancer. Based on etiology VSCC is divided into two subtypes; one related to high-risk human papilloma virus (HPV) and one HPV negative. The two subtypes are proposed to develop via separate intracellular signaling pathways. We investigated a suggested link between HPV infection and relapse risk in VSCC through in-depth protein profiling of 14 VSCC tumor specimens. The tumor proteomes were analyzed by liquid-chromatography tandem mass spectrometry. Relative protein quantification was performed by 8-plex isobaric tags for relative and absolute quantification. Labeled peptides were fractionated by high-resolution isoelectric focusing prior to liquid-chromatography tandem mass spectrometry to reduce sample complexity. In total, 1579 proteins were regarded as accurately quantified and analyzed further. For classification of clinical groups, data analysis was performed by comparing protein level differences between tumors defined by HPV and/or relapse status. Further, we performed a biological analysis on individual tumor proteomes by matching data to known biological pathways. We here present a novel analysis approach that combines pathway alteration data on individual tumor level with multivariate statistics for HPV and relapse status comparisons. Four proteins (signal transducer and activator of transcription-1, myxovirus resistance protein 1, proteasome subunit alpha type-5 and legumain) identified as main classifiers of relapse status were validated by immunohistochemistry (IHC). Two of the proteins are interferon-regulated and on mRNA level known to be repressed by HPV. By both liquid-chromatography tandem mass spectrometry and immunohistochemistry data we could single out a subgroup of HPV negative/relapse-associated tumors. The pathway level data analysis confirmed three of the proteins, and further identified the ubiquitin-proteasome pathway as altered in the high risk subgroup. We show that pathway fingerprinting with resolution on individual tumor level adds biological information that strengthens a generalized protein analysis.

Evaluation of preoperative lymphoscintigraphy and sentinel node procedure in vulvar cancer.

OBJECTIVE: To assess the value of preoperative lymphoscintigraphy, and to evaluate the validity and feasibility of the sentinel node (SN) procedure in vulvar carcinoma. STUDY DESIGN: Retrospective clinical and histopathological review of 77 patients with invasive squamous cell carcinoma in vulva who were treated at Karolinska University Hospital Stockholm, Sweden, from 2000 to 2007. The patients underwent SN mapping preoperatively with radioactive tracer and blue dye (n=60) or only blue dye (n=17). The SN was removed separately followed by complete inguinofemoral lymphadenectomy. RESULTS: The relation between SNs detected on the scintigram and those found during surgery showed good agreement using weighted kappa. The detection rate of SN was 98% for radioisotope plus blue dye, and 94% for blue dye alone. Two cases of false negative SN (false negative rate 2.7%) were found, both with large midline tumors. CONCLUSION: Preoperative scintigram is a valuable help to identify and localize the SNs and gives the best estimate of the accurate number but cannot determine if unilateral or bilateral groins should be explored in cases of midline tumors. Our results are in favor of using radioisotope and blue dye to identify the SNs. This study support previous reports that the method is not recommended for tumors larger than 40 mm to optimize detection of SN and minimize the false negative detection rate.