First dose of misoprostol administration at home or in hospital for medical abortion between 12-22 gestational weeks in Sweden (PRIMA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Medical abortion after 12 gestational weeks often requires a stay in hospital. We hypothesised that administering the first misoprostol dose at home could increase day-care procedures as compared with overnight care procedures, shorten inpatient stays, and improve patient satisfaction. METHODS: This multicentre, open-label, randomised controlled trial was done at six hospitals in Sweden. Participants were pregnant people aged 18 years and older who were undergoing medical abortion at 85-153 days of pregnancy. Randomisation was done in blocks 1:1 to mifepristone administered in-clinic followed by home administration or hospital administration of the first dose of misoprostol. Allocation was done by opening of opaque allocation envelopes. Due to the nature of the intervention, masking was not feasible. Between 24-48 h after mifepristone 200 mg, the participants administered 800 µg of misoprostol either at home 2 h before admission to hospital or in hospital. The primary outcome was the proportion of day-care procedures (defined as abortion completed in <9 h). The intention-to-treat analysis included all participants randomly assigned to receive the study drug and who had known results for the primary outcome. Individuals who received any treatment were included in the safety analyses. This trial is registered at ClinicalTrials.gov, NTC03600857, and EudraCT, 2018-000964-27. FINDINGS: Between Jan 8, 2019, and Dec 21, 2022, 457 participants were randomly assigned to treatment groups. In the intention-to-treat-population, 220 participants were assigned to the home group and 215 to the hospital group. In the home group, 156 (71%) of 220 participants completed the abortion as day-care patients, compared with 99 (46%) of 215 in the hospital group (difference 24·9%, 95% CI 15·4-34·3; p<0·0001). In total, 97 (22%) of 444 participants in the safety analysis had an adverse event. Seven (2%) of 444 participants aborted after mifepristone only. Two (1%) of 220 in the home group aborted after the first dose of misoprostol, before hospital admission. INTERPRETATION: Home administration of misoprostol significantly increases the proportion of day-care procedures in medical abortion after 12 gestational weeks, offering a safe and effective alternative to in-clinic protocols. FUNDING: Region Västra Götaland, Hjalmar Svensson's Fund, the Gothenburg Society of Medicine, Karolinska Institutet-Region Stockholm, and The Swedish Research Council.

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.

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.

Placement of an intrauterine device within 48 hours after second-trimester medical abortion: a randomized controlled trial.

BACKGROUND: International guidelines recommend placement of intrauterine devices immediately after second-trimester medical abortion, but evidence concerning the optimal time for intrauterine device placement is lacking from clinical trials. OBJECTIVE: This study aimed to investigate effectiveness, safety, and acceptability of intrauterine device placement within 48 hours, compared with placement at 2 to 4 weeks after second-trimester medical abortion. We hypothesized that intrauterine device placement within 48 hours would be superior compared with placement at 2 to 4 weeks after the abortion, in terms of the proportion of intrauterine device use after 6 months, with maintained safety and acceptability. STUDY DESIGN: In this open-label, randomized, controlled, superiority trial, we recruited participants at 8 abortion clinics in Sweden. Eligible participants were aged ≥18 years, requesting medical abortion with gestation ≥85 days, and opting for use of a postabortion intrauterine device. Participants were randomized (1:1) to intrauterine device placement either within 48 hours of complete abortion (intervention) or after 2 to 4 weeks (control). Our primary outcome was self-reported use of an intrauterine device after 6 months. Secondary outcomes included expulsion rates, pain at placement, adverse events and complications, acceptability, and subsequent pregnancies and abortions. Differences in nonnormal continuous variables were analyzed with the Mann-Whitney U test, and differences in dichotomous variables with the chi-square or Fisher exact tests. A P value <.05 was considered statistically significant. Group differences are presented by modified intention-to-treat and per-protocol analyses. RESULTS: Between January 2019 and June 2022, we enrolled 179 participants, of whom 90 were assigned to the intervention and 89 to the control arm. Enrollment was prematurely stopped after an interim analysis exceeded a predefined intrauterine device expulsion rate of 20%. According to modified intention-to-treat analysis, use of intrauterine device after 6 months was 50.7% (34/67) in the intervention group vs 71.6% (48/67) in the control group (proportion difference, 20.9%; 95% confidence interval, 4.4%-35.9%; P=.02). The intrauterine device expulsion rate was 30.1% (22/73) in the intervention group vs 2.9% (2/70; P<.001) in the control group. Other adverse events were rare and patient acceptability was high in both groups. CONCLUSION: Intrauterine device placement within 48 hours after second-trimester medical abortion was nonsuperior in terms of the proportion of intrauterine device use after 6 months when compared with placement after 2 to 4 weeks. Placement within 48 hours after second-trimester abortion can be used in selected individuals after counseling on expulsion risk.

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.

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.

Effects of structured contraceptive counseling in young women: Secondary analyses of a cluster randomized controlled trial (the LOWE trial).

INTRODUCTION: Unwanted pregnancy constitutes a huge health issue. Long-acting reversible contraception (LARC) are the most effective methods for preventing unwanted pregnancy, especially among young women. This study evaluates the intervention effect of structured contraceptive counseling on the choice, initiation, and use of LARC in young women. MATERIAL AND METHODS: This is a secondary analysis of women aged 18-25, enrolled in a multicenter cluster randomized controlled trial performed in abortion, youth, and maternal health clinics across the Stockholm County in Sweden. Clinics were randomized (1:1) to provide structured contraceptive counseling (intervention) or standard counseling (control). Surveys were administered at the clinic visit and follow-ups at 3, 6, and 12 months. Primary outcome focused on the choice of LARC among women 18-25 years of age. Secondary outcomes included initiation, and use of LARC at 3 and 12 months, satisfaction with the counseling received and information on extended use of combined hormonal contraceptives. The study was registered at Clinicaltrials.gov (NCT03269357). RESULTS: From September 2017 to May 2019, 770 women aged 18-25 years from 28 clinics/clusters were recruited. There was a significant intervention effect on LARC choice (aOR 5.96, 95% CI 3.25-10.94), initiation (aOR 4.43, 95% CI 2.32-8.46), and use at 12 months (aOR 2.21, 95% CI 1.31-3.73). The odds of LARC choice at pre-booked visits were higher and more women received information about extended-use regimen for short-acting reversible contraception in the intervention group compared to the control group. The intervention package was well received, but with higher satisfaction at pre-booked compared to drop-in visits. CONCLUSIONS: Our study demonstrates that comprehensive structured contraceptive counseling significantly increases LARC choice, initiation and use, with high satisfaction among young participants, especially at pre-booked visits. The results highlight an approach that merits implementation to increase quality of care in contraceptive services, to enhance reproductive health for adolescents and young adults.

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.

Transcriptomic Profile of Breast Tissue of Premenopausal Women Following Treatment with Progesterone Receptor Modulator: Secondary Outcomes of a Randomized Controlled Trial.

Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examines changes in breast mRNA expression following mifepristone treatment in healthy premenopausal women. We analyzed 32 paired breast biopsies from 16 women at baseline and after two months of mifepristone treatment. In total, 27 differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristone in vivo was rather similar to the in vitro signature. Furthermore, this gene expression signature was linked to breast carcinogenesis and notably linked with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transcriptome following mifepristone treatment in normal breast tissue in vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer.

Postpartum contraception provision across Europe: preliminary findings from a multi country survey.

INTRODUCTION: Looking after a baby and recovering from birth pose barriers to accessing and initiating effective contraception in the postpartum period. Another pregnancy at this time can end in abortion or a short interbirth interval. These are preventable if contraception is provided immediately from maternity settings. Our aim was to survey contraceptive experts across Europe about provision of postpartum contraception (PPC) in their country to develop a greater understanding of availability of and delivery of PPC services within the region. MATERIALS AND METHODS: Contraceptive experts across Europe were invited to participate in an anonymous mixed-methods online survey consisting of free text and fixed-response questions focusing on: (1) national guidelines/policy (2) antenatal contraceptive discussion and (3) immediate postpartum provision of methods. Respondents were asked to rate PPC provision in their region and detail perceived facilitators or barriers. RESULTS: Experts from 28 countries completed the survey. Fifteen (40%) reported their country had national guidelines for PPC provision, 40% reported that some antenatal contraceptive counselling was offered and 51% reported that contraceptive methods were provided in some (43%) or all (8%) maternity settings. Country-level PPC provision was reported as 'poor' or 'very poor' by 54% of respondents. Reported barriers to PPC provision included: cost, lack of policy/government support, awareness and training of maternity staff. CONCLUSIONS: There is significant variation in PPC provision across Europe. Few countries offer antenatal contraceptive counselling or provide contraception from maternity settings. Introduction of supportive PPC policies, funding and training for staff could improve outcomes for mothers and babies.

There is a need for improvement in postpartum contraception provision across Europe, and only a few countries offer women routine antenatal contraceptive counselling or provide contraception directly from maternity settings.

Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia.

PURPOSE: To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms. MATERIALS AND METHODS: We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain. RESULTS: Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect). CONCLUSION: E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.

A phase 3 study in Europe and Russia showed that Estetrol/Drospirenone, a new combined oral contraceptive, significantly improved the MDQ scores for domains Pain, Water Retention and Negative Affect in women starting COC use, while switchers showed minimal changes.

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.

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.

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.

A telemedicine model for abortion in South Africa: a randomised, controlled, non-inferiority trial.

BACKGROUND: Telemedicine for medical abortion increases access to safe abortion but its use has not been described in a controlled trial. We aimed to investigate the effectiveness, adherence, safety, and acceptability of a modified telemedicine protocol for abortion compared with standard care in a low-resource setting. METHODS: In this randomised, controlled, non-inferiority trial we recruited women seeking medical abortion at or before 9 gestational weeks at four public health clinics in South Africa. Participants were randomly allocated (1:1) by computer-generated blocks of varying sizes to telemedicine or standard care. The telemedicine group received asynchronous online abortion consultation and instruction, self-assessed gestational duration, and had a uterine palpation as a safety measure. Participants in this group took 200 mg mifepristone and 800 µg misoprostol at home. The standard care group received in-person consultation and instruction together with an ultrasound, took 200 mg mifepristone in clinic and 800 µg misoprostol at home. Our primary outcome was complete abortion after initial treatment, assessed at a 6-week interview. Our non-inferiority margin was 4%. Group differences were assessed by modified intention-to-treat (mITT) analysis and per protocol. The trial is registered at ClinicalTrials.gov, NCT04336358, and the Pan African Clinical Trials Registry, PACTR202004661941593. FINDINGS: Between Feb 28, 2020, and Oct 5, 2021, we enrolled 900 women, 153 (17·0%) of whom were discontinued before the abortion and were not included in the analysis. By mITT analysis, 355 (95·4%) of 372 women in the telemedicine group had a complete abortion compared with 338 (96·6%) of 350 in the standard care group (odds ratio 0·74 [95% CI 0·35 to 1·57]). The risk difference was -1·1% (-4·0 to 1·7). Among women who completed treatment as allocated (per protocol), 327 (95·6%) of 342 women in telemedicine group had complete abortion, compared with 338 (96·6%) of 350 in the standard care group (0·77 [0·36 to 1·68]), with a risk difference of -1·0% (-3·8 to 1·9). One participant (in the telemedicine group) had a ruptured ectopic pregnancy, and a further four participants were admitted to hospital (two in each group), of whom two had blood transfusions (one in each group). INTERPRETATION: Asynchronous online consultation and instruction for medical abortion and home self-medication, with uterine palpation as the only in-person component, was non-inferior to standard care with respect to rates of complete abortion, and did not affect safety, adherence, or satisfaction. FUNDING: Grand Challenges Canada and the Swedish Research Council.

Placement of an intrauterine device within 48 hours after early medical abortion-a randomized controlled trial.

BACKGROUND: Intrauterine devices are safe, well-tolerated, and known to reduce the risk of unwanted pregnancies. At medical abortion, intrauterine devices are placed at a follow-up visit. Patients who miss this visit risk being left without contraception. OBJECTIVE: This study aimed to investigate if placement of an intrauterine device within 48 hours of completed medical abortion at up to 63 days' gestation leads to higher user rates at 6 months after the abortion compared with placement at 2 to 4 weeks after abortion. Furthermore, we aimed to compare continued use of intrauterine devices, safety, and patient satisfaction between groups. STUDY DESIGN: We performed an open-label, randomized, controlled, multicenter, superiority trial (phase 3). A total of 240 patients requesting medical abortion at up to 63 days' gestation and opting for an intrauterine device were allocated to placement within 48 hours of complete medical abortion (intervention group) or at 2 to 4 weeks after abortion (control group). We defined the abortion as complete after bleeding with clots and cessation of heavy bleeding following the use of misoprostol. Patients answered questionnaires at 3, 6, and 12 months. The primary outcome was use of intrauterine device at 6 months postabortion. Secondary outcomes included expulsion rate, pain at placement, adverse events and complications from the abortion, acceptability, and pregnancies and their outcomes. Differences in nonparametric continuous variables were analyzed with the Mann-Whitney U test and differences in dichotomous variables with the chi square or Fisher exact tests. A P value of <.05 was considered statistically significant. RESULTS: In the intervention group, 91 of 111 (82%) participants used an intrauterine device at 6 months after the abortion vs 87 of 112 (77.7%) in the control group, with a difference in proportion of 4.3% (95% confidence interval, -0.062 to 0.148; P=.51). Attendance rate and rate of successful intrauterine device placement were similar between the groups. Patients in the intervention group had lower pain scores at placement of the intrauterine device (mean pain score [visual analogue scale], 32.3; standard deviation, 29) compared with the control group (mean pain score [visual analogue scale], 43.4; standard deviation, 27.9; P=.002). Patients preferred their allocated time of placement significantly more often in the intervention group (83/111, 74.8%) than in the control group (70/114, 61.4%; P=.03). Use of ultrasound at intrauterine device placement (because of doubts concerning complete abortion) was more common in the intervention group (43/108, 39.8%) than in the control group (15/101, 14.9%; P<.001), and in one patient in the control group a retained gestational sac was found. Three patients in the intervention group and 2 in the control group had a vacuum aspiration. No difference was found in intrauterine device expulsion rates between the groups. Expulsion during the first 6 months after abortion was experienced by 9 of 97 (9.3%) patients in the intervention group and 4 of 89 (4.5%; P=.25) in the control group. There were no perforations or infections requiring antibiotic treatment. CONCLUSION: Placement of an intrauterine device within 48 hours after medical abortion at ≤63 days' gestation does not lead to higher user rates at 6 months after the abortion compared with intrauterine device placement at 2 to 4 weeks after abortion. When compared with placement at a follow-up visit after 2 to 4 weeks, intrauterine device placement within 48 hours after early medical abortion seems safe, is preferred by patients, and is associated with lower pain scores.

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.

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.

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.

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.