Time to pregnancy recognition among users of an FDA-cleared fertility application.

Background: Previous investigations of time-to-pregnancy recognition have analysed data from national surveys and clinics, but this has not been investigated in the context of digital fertility applications. Timely pregnancy recognition can help individuals in health and pregnancy management, reducing maternal and foetal risk and costs, whilst increasing treatment options, availability, and cost. Methods: This dataset contained 23,728 pregnancies (conceived between June 2018 and December 2022) from 20,429 participants using a Food and Drug Administration (FDA) cleared fertility app in the United States. Most participants (with non-missing information) identified as Non-Hispanic White, and one-third reported obtaining a university degree. We used two-tailed Welch's t-test, Mann-Whitney U-test, and two-tailed Z-tests to compare time to pregnancy recognition between those using the app to conceive or contracept. Results: Participants using an app to conceive recognised pregnancy on average at 31.3 days from last menstrual period (LMP) compared to 35.9 days among those using the app to prevent pregnancy. Conclusion: Generalisability is limited, as all participants were using a fertility app and had relatively homogenous sociodemographic characteristics.

People who recognise pregnancy early may benefit, as earlier recognition can reduce costs and risks, and make more treatment options available. In the past, researchers have studied the time it takes for an individual to recognise that they are pregnant by asking them in national surveys or when they attend a clinic. However, with the advent of digital fertility tracking apps, we investigated the time it takes to recognise pregnancy when using such an app. We analysed data from 23,728 pregnancies from 20,429 users of the Natural Cycles app between June 2018 and December 2022. We found that participants using the app to try to get pregnant recognised pregnancy an average of 4.6 days earlier than those using the app to prevent pregnancy.

Health benefits of combined oral contraceptives - a narrative review.

PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHODS: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULTS: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSIONS: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

Natural Killer Cell Dysfunction in Premenopausal BRCA1 Mutation Carriers: A Potential Mechanism for Ovarian Carcinogenesis.

BACKGROUND: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3- CD56+ natural killer (NK) cells. METHODS: Premenopausal BRCA1 mutation carriers versus age-matched non-carriers were compared. Daily urinary 5ß-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence®) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner. RESULTS: BRCA1 mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in BRCA1 mutation carriers, reflecting a site-specific 'hypoxic niche'. Exposure to hypoxic conditions (1% O2) can further impair tumor cytotoxicity in high-risk carriers. CONCLUSIONS: Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.

Contraceptive uptake and compliance after structured contraceptive counseling - secondary outcomes of the LOWE trial.

INTRODUCTION: Highly effective long-acting reversible contraceptive (LARC) methods reduce unintended pregnancy rates; however, these methods are underutilized. The LOWE trial intervention provided structured contraceptive counseling resulting in increased uptake of LARC. This longitudinal follow up of the LOWE study assessed the long-term impact of the intervention by investigating the contraceptive use at 12 months with a focus on continued use of LARC. MATERIAL AND METHODS: In the cluster randomized LOWE trial, abortion, youth, and maternal health clinics were randomized to provide either structured contraceptive counseling (intervention) or standard contraceptive counseling (control). The intervention consisted of an educational video on contraceptive methods, key questions asked by the health care provider, a tiered effectiveness chart and a box of contraceptive models. Women ≥ age 18, who were sexually active or planned to be in the upcoming 6 months, could participate in the study. We assessed self-reported contraceptive use at three, six and 12 months. Contraceptive choice and switches were analyzed with descriptive statistics. Contraceptive use at 12 months and continued use of LARC were analyzed using mixed logistic regressions, with clinic included as a random effect. Analysis with imputed values were performed for missing data to test the robustness of results. RESULTS: Overall, at 12 months, women in the intervention group were more likely to be using a LARC method (aOR 1.90, 95% CI: 1.31-2.76) and less likely to be using a short-acting reversible contraceptive (SARC) method (aOR 0.66, 95% CI: 0.46-0.93) compared to the control group. Women counseled at abortion (aOR 2.97, 95% CI: 1.36-6.75) and youth clinics (aOR 1.81, 95% CI: 1.08-3.03) were more likely to be using a LARC method, while no significant difference was seen in maternal health clinics (aOR 1.84, 95% CI: 0.96-3.66). Among women initiating LARC, continuation rates at 12 months did not differ between study groups (63.9% vs. 63.7%). The most common reasons for contraceptive discontinuation were wish for pregnancy, followed by irregular bleeding, and mood changes. CONCLUSIONS: The LOWE trial intervention resulted in increased LARC use also at 12 months. Strategies on how to sustain LARC use needs to be further investigated.

Global Transcriptomic Analysis of Placentas from Women with Gestational SARS-CoV-2 Infection during the Third Trimester of Pregnancy.

The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above gap, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women immediately after term delivery, seven of which had SARS-CoV-2 infection confirmed by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We separately extracted total RNA from placental tissues from maternal and fetal compartments, constructed cDNA libraries, and sequenced them to assess mRNA. Our analysis revealed 635 differentially expressed genes when a false discovery rate (FDR ≤ 0.05) was applied in the maternal placental tissue, with 518 upregulated and 117 downregulated genes in the SARS-CoV-2-positive women (n = 6) compared with the healthy SARS-CoV-2-negative women (n = 8). In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. We observed a significant downregulation of nine genes belonging to the pregnancy-specific glycoprotein related to the immunoglobulin superfamily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28; FDR ≤ 0.01). Additionally, comparing symptomatic women with healthy women, we identified 1788 DEGs. Furthermore, a signaling pathway enrichment analysis revealed that pathways related to oxidative phosphorylation, insulin secretion, cortisol synthesis, estrogen signaling, oxytocin signaling, antigen processing, and presentation were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risks of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta's anti-viral effects in maternal SARS-CoV-2 infection.

Plasma cell-free DNA methylation analysis for ovarian cancer detection: Analysis of samples from a case-control study and an ovarian cancer screening trial.

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.

Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial.

OBJECTIVE: To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage. DESIGN: Prospective open-label non-inferiority randomised controlled trial. SETTING: A university-affiliated hospital. POPULATION: We recruited 294 women diagnosed with first-trimester missed miscarriage who opted for medical treatment. METHODS: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24-48 h later by 800 µg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once-a-day for 3 days, followed by 800 µg misoprostol vaginally on the third (i.e. last) day of letrozole administration. MAIN OUTCOME MEASURES: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post-treatment. Secondary outcomes included induction-to-expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. RESULTS: The complete evacuation rates were 97.8% (95% CI 95.1%-100%) and 97.2% (95% CI 94.4%-99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non-inferiority). The mean induction-to-tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post-treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. CONCLUSIONS: Letrozole is non-inferior to mifepristone as a pre-treatment, followed by misoprostol, for the medical treatment of first-trimester missed miscarriage.

Adherence to Modern Contraceptives Among Female Refugee Adolescents in Northern Uganda: A Prospective Single Cohort Study.

Background: Contraceptive adherence is the current and consistent use of a contraceptive method as prescribed by a health worker or family planning provider so as to prevent pregnancy. Globally, adherence is lowest among adolescents. This has greatly contributed to the high burden of adolescent pregnancies. Adherence and reasons for discontinuation among refugee adolescents are poorly understood. The aim of this study was to determine the rates and predictors of adherence to modern contraceptives among female refugee adolescents in northern Uganda. Methods: This was a prospective single cohort study, nested into a randomised controlled trial (RCT) assessing the effect of peer counselling on acceptance of modern contraceptives. The RCT was conducted among female refugee adolescents in Palabek refugee settlement, northern Uganda. The study involved 272 new starters of modern contraceptives who were followed up for six months from May 2019 to January 2020. The outcome was measured at one, three, and six months after receiving a contraceptive method, and the predictors of adherence were determined using Generalised Estimating Equations (GEE). Data were analysed using STATA version 14.0. Results: Adherence rates were low and reduced over time. By the end of the six months, only 44% of the participants were using a contraceptive method. Participants using long-acting reversible contraceptives (LARC) were more likely to adhere compared to those who were using short-acting reversible contraceptives (SARC) (OR: 3.37, 95% CI: 1.914-5.937, p<0.001). Conclusion: Adherence to modern contraceptives was low, leaving adolescents at risk of unintended pregnancies. Participants using LARC were more likely to adhere than those using SARC. Interventions addressing fear of side effects and partner prohibition should be studied and implemented to enable adherence to modern contraceptives.

The use and access to contraception in Sweden during the COVID-19 pandemic period.

PURPOSE: Explore perceived access to, the need for, use of, and satisfaction with telemedicine services for contraceptive counselling and prescription-renewal-only during the COVID-19 pandemic, and the impact of the COVID-19 pandemic period on the choice and use of contraceptives. MATERIALS AND METHODS: Internet-based e-survey of Swedish women of fertile age, 16-49 years. RESULTS: In total, 1016 participants completed the survey. Most participants (69.7%) rated their access to contraceptive services 'as usual'. Among the remaining participants, a higher proportion rated their access as deteriorated (73.4%) compared to improved (26.6%; p < 0.001). In total, 38.0% reported a need for contraceptive counselling, whereof 14.0% had used telemedicine for counselling and reported high satisfaction. Telemedicine for prescription-renewal-only was used by 15.1% of the total population. Two per cent reported use of another contraceptive than their intended, whereof long-acting reversible contraceptives were the most common intended method. The proportion of current contraceptive users was lower than in 2017 (62.4% vs 71.1%, p < 0.001), and current users of long-acting reversible contraception decreased from 30.6% to 19.3% (p < 0.001). CONCLUSIONS: During the COVID-19 pandemic period, most women found their access to contraceptive services unaffected, but more women felt that it had deteriorated than improved. The use of telemedicine was low, and the use of contraception overall fell. Efforts are needed to raise awareness of available services, and TM-provided interventions for maintained quality of care and informed decision-making remain to be evaluated.SHORT CONDENSATIONThe COVID-19 period imposed a change in contraceptive service provision, and efforts are needed to raise awareness of available services, including telemedicine. Access to all contraceptives, including LARCs, is crucial and telemedicine-provided interventions need evaluation.

The benefits of estetrol addition to drospirenone for contraception.

Ethinylestradiol and drospirenone combined oral contraceptive formulations have been marketed for >20 years. Drospirenone has antimineralocorticoid and anti-androgenic effects that may offer several health benefits. Recently, 2 new drospirenone-containing oral contraceptives entered the market, 1 as a progestin-only pill containing 4 mg drospirenone and the other as a combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone. Estetrol has a unique differential effect on nuclear and membrane estrogen α-receptors when compared with other estrogens, leading to low impact on the liver, breast, and hemostasis parameters and a beneficial effect on the endometrium, vagina, cardiovascular system, bone, and brain. Phase 3 clinical studies demonstrated that the Pearl Index (pregnancies per 100-woman-years) for drospirenone alone is 4.0 in the United States and 0.93 in the European Union and for the estetrol-drospirenone combination it is 2.65 and 0.44, respectively. Drospirenone alone demonstrates high rates of unscheduled bleeding and low rates of scheduled bleeding, whereas the estetrol-drospirenone combination demonstrates a predictable and regular bleeding profile for most users with a high stable rate of scheduled bleeding and a low rate of unscheduled bleeding, reported primarily as spotting only. The adverse event profiles and discontinuation rates owing to adverse events are comparable, and no clinically significant effects were observed on metabolic parameters with either product. Hemostatic assays for drospirenone do not fully evaluate all parameters although the testing that is available suggests negligible effects, whereas validated hemostatic assays demonstrate that the estetrol-drospirenone combination has limited impact on hemostasis. The introduction of 4 mg drospirenone and 15 mg estetrol with 3 mg drospirenone are valuable additions to the contraceptive market. Adding estetrol to 3 mg drospirenone provides advantages of contraceptive efficacy and a regular, predictable bleeding profile with minimal impact on hemostasis parameters.

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.

To individualise breast cancer (BC) prevention, markers to follow a person's changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID™-qtBC index, can identify women with breast cancer in hormone-sensitive tissues (AUC = 0.71 [95% CI: 0.65-0.77] in cervical samples). Women in the highest combined risk group (high polygenic risk score and WID™-qtBC) had a 9.6-fold increased risk for BC [95% CI: 4.7-21] compared to the low-risk group and tended to present at more advanced stages. Importantly, the WID™-qtBC is influenced by non-genetic BC risk factors, including age and body mass index, and can be modified by a preventive pharmacological intervention, indicating an interaction between genome and environment recorded at the level of the epigenome. Our findings indicate that methylation levels at mQTLs in relevant surrogate tissues could enable integration of heritable and non-heritable factors for improved disease risk stratification.

Preabortion ultrasound - a patient perspective.

PURPOSE: To explore women's perception of the need for an ultrasound scan before medical abortion provided by telemedicine services. METHODS: We have analysed women's requests for medical abortion through the website www.womenonweb.org from the 1st of January 2019 to the 5th of October 2020. Before receiving abortion drugs for self-managed medical abortion, women received online counselling and were asked to complete an online survey on pre-abortion ultrasound scan and the reasons for having or not having one. The initial dataset included 62641 entries from 207 countries. Each entry corresponded to a person's request for medical abortion. Women reported only one or multiple reasons for not having a pre-abortion ultrasound scan. RESULTS: Among 59648 women requesting a medical abortion, 45653 (76,54%) did not have any pre-abortion ultrasound scan and specified a reason for that. The countries with the highest rates of women not having a pre-abortion ultrasound scan were Thailand, Poland, Northern Ireland, Mexico, South Korea, Japan, Chile, Indonesia, Germany, and Brazil. The main reasons for not having a pre-abortion ultrasound scan were being confident regarding pregnancy length; and thus, no need for a scan stated by 10910/34390 women (31.7%), lack of resources stated by 10589/34390 women (30.8%), and privacy issues stated by 6472/34390 women (18.8%). CONCLUSION: Most women opting for medical abortion through telemedicine did not undergo a pre-abortion ultrasound scan. The main reason stated was that women did not find it necessary, lack of resources and privacy issues.

Women requesting medical abortion through telemedicine were asked about their views and experiences regarding pre-abortion ultrasound scan. Of 59648 women included in the study, 76% did not have a scan. The main reason stated was that women did not find it necessary, lack of resources and privacy issues.

Levonorgestrel intrauterine device and depression: A Swedish register-based cohort study.

BACKGROUND: The levonorgestrel intrauterine device (LNG-IUD) is traditionally viewed as a safe contraceptive with limited systemic effects. However, three recent studies have indicated an increased risk of depression subsequent to LNG-IUD use. This study aimed to examine the potential associated risk between LNG-IUDs and depression, and determine which women are at risk. METHODS: This longitudinal cohort study was based on data from seven Swedish national population-based registers. All Nordic-born women aged 15-24 years residing in Sweden between 2010 and 2017 were included. Cox regression was implemented to estimate the adjusted hazard ratio (AHR) for developing depression, defined as first depression diagnosis or redeemed prescription for antidepressant treatment. We adjusted for age, education level, parental country of origin, parental psychiatric health, previous hormonal contraceptive use and medical indications for contraceptive use. FINDINGS: 703,157 women were included in the analysis. The LNG-IUD was associated with 57 % increased risk of depression [AHR 1.57 (95 % CI 1.51-1.64)]. The greatest risk increase was seen in adolescent women [AHR 2.57, (95 % CI 2.36-2.80)] and women who used the LNG-IUD as their first hormonal contraceptive method [AHR 1.63, (95 % CI 1.50-1.78)]. The risk of depression decreased at the end of study period [AHR 1.43, (95 % CI 1.36-1.51)], once the LNG-IUD became more widely accessible among nulliparous women. CONCLUSIONS: Adolescent women who use the LNG-IUD as their first-ever hormonal contraceptive are at increased risk of developing depression. However, additional impact from confounding factors is likely as risk estimates decreased over the study period. Further research needs to determine if there is a causal relationship between LNG-IUDs and depression.

One-year follow up of contraceptive use and pregnancy rates after early medical abortion: Secondary outcomes from a randomized controlled trial of immediate post-abortion placement of intrauterine devices.

INTRODUCTION: Intrauterine devices (IUDs) effectively prevent unwanted pregnancies. Little is known about long-term outcomes of women choosing an IUD after early medical abortion. MATERIAL AND METHODS: We present secondary outcome data of continuation rates, factors associated with continuation and discontinuation, choice of IUD type, women's satisfaction with IUD, and IUD expulsions, subsequent pregnancies, and abortions within 1 year post-abortion in a randomized, controlled, multicenter trial on IUD placement within 48 hours compared with placement 2-4 weeks after medical abortion up to 63 days' gestation (ClinicalTrials.gov NCT03603145). RESULTS: Of the 240 women studied, 112/120 (93.3%) in the intervention group vs 113/120 (94.2%) in the control group completed the 12-month follow-up. The rate of IUD use at 12 months was 84/112 (75%) in the intervention group vs 75/113 (66.4%) in the control group (P = 0.19). Attendance at the IUD placement visit was the only predictor of long-term IUD use (relative risk [RR] = 5.7, 95% confidence interval [CI] 2.03-16.0; P = 0.001). The main reason for choosing an IUD was high contraceptive effectiveness. The most common reasons for IUD discontinuation were bleeding problems and abdominal pain. IUD expulsion was rare and did not differ between groups. Satisfaction among IUD users at 1 year was high (>94%) and the majority of all participants would recommend IUD to a friend (65.8%). Use of no contraception and experience of unprotected intercourse were less common in the intervention group (11/112 [9.8%] vs 25/113 [22.1%], P = 0.02 and 17/112 [15.2%] vs 32/113 [28.3%], P = 0.02, respectively). There was no difference in the rate of subsequent pregnancies and abortions (pregnancies 14/112, 12.5% in the intervention group vs 8/113, 7.1% in the control group, P = 0.19; abortions 5/112, 4.5% vs 3/113, 2.7%, P = 0.5). CONCLUSIONS: IUD placement after medical abortion led to high continuation and satisfaction rates with no difference between groups. We found no difference in IUD expulsions after immediate compared with later placement. Unprotected intercourse was significantly less common in the immediate group. In clinical practice, immediate placement of IUDs available free of charge at the abortion clinic is likely to increase attendance to the placement visit and continued use of IUDs after abortion.

Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial.

BACKGROUND: Levonorgestrel, a standard drug for emergency contraception (EC), is not effective if administered post-ovulation. A cyclo-oxygenase inhibitor could contribute synergistic effects. We investigated whether a single 40 mg oral dose of piroxicam as co-treatment with levonorgestrel improved emergency contraceptive efficacy. METHODS: This was a randomised double-blind placebo-controlled trial carried out in a major community sexual and reproductive health service in Hong Kong. Women who required levonorgestrel EC within 72 h of unprotected sexual intercourse were recruited and block-randomised in a 1:1 ratio to receive a single supervised dose of levonorgestrel 1·5 mg plus either piroxicam 40 mg or placebo orally. Group assignment was concealed in opaque envelopes and masked to the women, clinicians, and investigators. At follow-up 1-2 weeks after the next expected period, the pregnancy status was noted by history or pregnancy test. The primary efficacy outcome was the proportion of pregnancies prevented out of those expected based on an established model. All women randomised to receive the study drug and who completed the follow-up were analysed. The trial was registered with ClinicalTrials.gov, NCT03614494. FINDINGS: 860 women (430 in each group) were recruited between Aug 20, 2018, and Aug 30, 2022. One (0·2%) of 418 efficacy-eligible women in the piroxicam group were pregnant, compared with seven (1·7%) of 418 in the placebo group (odds ratio 0·20 [95% CI 0·02-0·91]; p=0·036). Levonorgestrel plus piroxicam prevented 94·7% of expected pregnancies compared with 63·4% for levonorgestrel plus placebo. We noted no significant difference between the two groups in the proportion of women with advancement or delay of their next period, or in the adverse event profile. INTERPRETATION: Oral piroxicam 40 mg co-administered with levonorgestrel improved efficacy of EC in our study. Piroxicam co-administration could be considered clinically where levonorgestrel EC is the option of choice. FUNDING: None.

Inter-Rater Agreement for Diagnosing Adenomyosis Using Magnetic Resonance Imaging and Transvaginal Ultrasonography.

Our aim was to compare the inter-rater agreement about transvaginal ultrasonography (TVS) with magnetic resonance imaging (MRI) with regard to diagnosing adenomyosis and for assessing various predefined imaging features of adenomyosis, in the same set of women. The study cohort included 51 women, prospectively, consecutively recruited based on a clinical suspicion of adenomyosis. MRIs and TVS videoclips and 3D volumes were retrospectively assessed by four experienced radiologists and five experienced sonographers, respectively. Each rater subjectively evaluated the presence or absence of adenomyosis, as well as imaging features suggestive of adenomyosis. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data, and the intraclass correlation coefficient (ICC) was used to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ = 0.42 vs. 0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry, irregular junctional zone (JZ), and the presence of myometrial cysts, while TVU had a better agreement for assessing globular shape. MRI showed a moderate to good reliability for measuring the JZ (ICC = 0.57-0.82). For TVS, the JZ was unmeasurable in >50% of cases, and the remaining cases had low reliability (ICC = -0.31-0.08). We found that inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite the fact that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.

"I hope to all the world they don't forget women of Afghanistan": An interrupted survey among doctors in Afghanistan.

OBJECTIVE: To assess current access to essential sexual and reproductive health (SRHR) services in Afghanistan and how access has changed with the transition of power. METHODS: This is a cross-sectional study based on data from an anonymous survey among doctors in Afghanistan in May 2022, analyzed using descriptive statistics. The survey recorded subjective estimates of access to SRHR services, barriers to access, extent of maternal mortality or near miss due to preventable factors, and the effect of the regime change on access. RESULTS: The data collection was interrupted after 60 responses. A majority of providers responded that their population went hungry often or always. According to our criteria for "access", that 75% or more of the population was estimated to have it, no respondents (0%) assessed that access existed for services for gender-based violence. The corresponding proportion responding that access existed was 3.4% for services after rape, 12.6% for legal abortion, 13.3% for antenatal care, and 20% for labor care. According to 41.7% of respondents, untreated postpartum hemorrhage accounted for a large or very large proportion of preventable maternal mortality or near miss. Almost half of respondents (47.4%) reported the same for lack of skilled providers, 66.2% reported it for the concept "too many pregnancies", and 55% reported it for malnutrition and poor health. According to 43.3% of respondents, the regime change had reduced access to labor care to a large extent, 33.9% of respondents said this in relation to access to contraceptives, and 43.1% for overall access for internally displaced persons. CONCLUSION: Interim data suggest that women in some settings in Afghanistan have no access to SRHR services, that preventable factors account for a large portion of maternal deaths or near miss, and that access has deteriorated since the transition of power.

Contraceptive use among women seeking an early induced abortion in Sweden.

INTRODUCTION: In spite of societal efforts to strengthen women's sexual and reproductive health in Sweden, many women have unmet contraceptive needs and the abortion rate remains high. The aim of this study was to investigate contraceptive use among abortion-seeking women. MATERIAL AND METHODS: Swedish-speaking women seeking an induced abortion up to the end of gestational week 12 at seven hospitals filled out an anonymous paper questionnaire between January and June 2021. Data were analyzed using frequencies and cross-tabulations, and the Chi-square test was used to compare age-groups. Valid percentages are presented. RESULTS: In total, 623 women participated. Median age was 29 years and 13% were born outside the Nordic countries. In the year preceding the abortion, condoms (37%, n = 228) were the most commonly used contraceptive method, followed by short-acting reversible contraception (SARC) (35%, n = 213) and withdrawal (25%, n = 152). Around one in five (n = 113) had not used any method in the year preceding the abortion. Sixteen percent (n = 96) had changed contraceptive method in the last year. At the time around conception, 15% (n = 90) reported use of SARC and 2% (n = 12) of long-acting reversible contraception (LARC). Four out of 10 women (n = 268) reported non-use of contraception at the time around conception, with a higher proportion among adolescents (70%, n = 30, P = 0.001). Among the women who responded to why they had not used any method (n = 387), the main reasons were that they did not believe they could become pregnant at that time (37%, n = 144) or had negative experiences from using contraceptives (32%, n = 123). A majority (88%, n = 527) planned to use contraception after the abortion. Of the women who had decided on method, 55% (n = 271) planned to use LARC, and 38% (n = 188) planned to use SARC. CONCLUSION: The unmet need for contraception appears to be high among abortion-seeking women in Sweden. Many had discontinued contraception use during the last year, and the main reasons for avoidance were beliefs that one could not become pregnant and negative experiences of contraceptives. The underestimation of pregnancy risk indicates limited fertility awareness, thus our recommendation would be to strengthen the sexual and reproductive knowledge among this group.

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

Effectiveness and acceptability of home use of misoprostol for medical abortion up to 10 weeks of pregnancy.

INTRODUCTION: The administration of mifepristone, followed by misoprostol, is widely used for medical abortion. Many studies have demonstrated home abortion to be safe in pregnancies up to 63 days of gestation, and recent data support its safety when extended to more advanced pregnancies. We studied the efficacy and acceptability of home use of misoprostol up to 70 days of gestation in a Swedish setting and compared the outcomes between pregnancies with a gestational age of up to 63 days and pregnancies with gestational age 64-70 days. MATERIAL AND METHODS: This prospective cohort study was performed between November 2014 and November 2021 at Södersjukhuset and Karolinska University Hospital, Stockholm, and some patients were also recruited from Sahlgrenska University Hospital, Göteborg and Helsingborg Hospital. The primary outcome was the rate of complete abortions and was defined as complete abortion without any need for surgical or medical intervention and assessed by clinical assessment, pregnancy test and/or vaginal ultrasound. Secondary objectives were assessed by daily self-reporting in a diary and included pain, bleeding, side effects and women's satisfaction and perception of home use of misoprostol. A comparison of categorical variables was made with Fisher's exact test. The significance level was set to a p-value ≤0.05. The study was registered at Clinicaltrials.gov on July 14, 2014 (NCT02191774). RESULTS: During the study period we enrolled 273 women opting for medical abortion with home use of misoprostol. In the early group, up to 63 days of gestation, 112 women were included with a mean gestational length of 45 days and in the late group, 64-70 days of gestation, 161 women with a mean gestations length of 66.3 days were included. Complete abortion occurred in 95% (95% CI 89-98) of women in the early group and in 96% (95% CI 92-99) in the late group. No differences were found regarding side effects and acceptability was similarly high in both groups. CONCLUSIONS: Our results show high efficacy and acceptability of medical abortion when misoprostol is administered at home up to 70 days of gestation. This supports previous findings about maintained safety when misoprostol is administered at home even past a very early pregnancy.