Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

[Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy].

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy / 中华妇产科杂志

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion. OBJECTIVE: This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States. STUDY DESIGN: The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders. RESULTS: Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion. CONCLUSION: After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency.

BACKGROUND: Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action. PURPOSE: The present review aims to summarize the efficiency of A. indica treatment as a contraceptive. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. RESULTS: A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles. CONCLUSION: Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.

Cost-Effectiveness of Contraceptive Use in Indonesia after the Implementation of the National Health Insurance System.

Since 2014, Indonesia has initiated to implement a national health insurance system, which included both of short- (SARC) and long-acting reversible contraceptive (LARC) into the benefit package. The aim of this study was to analyze the cost-effectiveness of contraceptive use in Indonesia after the implementation of the national health insurance in 2014-2017. A decision tree model was developed to analyze the cost-effectiveness of contraceptive use in Indonesia in 2014-2017 by comparing two strategies of pregnancy prevention: contraceptive and non-contraceptive. For contraceptive strategy, we took into account SARC and LARC. In a comparison with non-contraceptive, we calculated that the incremental cost-effectiveness ratio (ICER) of SARC would be $5.18, $4.80 and $3.76 per pregnancy averted for injection, condom, and pill, respectively. For LARC, we calculated that the ICER would be $1.67 and $0.84 for implant and intrauterine device (IUD), respectively, compared with non-contraceptive. In general, the cost-effectiveness value of LARC ($1.25) was much better than SARC ($4.58). The cost of contraceptive was considered to be the most influential parameter affecting both the ICER of SARC and LARC. In conclusion, the use of LARC in Indonesia was considered to be more cost-effective than SARC since the implementation of national health insurance system. In particular, IUD yielded the greatest cost-effectiveness value, compared with other methods.

Subdermal Contraceptive Implant Insertion Trends and Retention in Adolescents.

STUDY OBJECTIVE: There is growing advocacy for use of long-acting reversible contraception among sexually active adolescents. Our primary aims were to evaluate the etonogestrel subdermal contraceptive implant (SCI) insertion trends among adolescents, as well as SCI retention at 1, 2, and 3 years, indications for removal, and to identify pregnancies that occurred during SCI use. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective cohort study was conducted of adolescents aged 13-19 years with SCI insertions in 2008-2014 within a large integrated health care system. Demographic and clinical characteristics included age, race/ethnicity, body mass index, gravidity, parity, insertions, reinsertions, indications for removal, and pregnancy. Electronic medical record review was conducted on a randomized sample of 540 adolescents with insertions during 2008-2011 for the retention objective to validate electronically extracted variables. Analyses included descriptive statistics, survival analysis with Kaplan-Meier estimates for implant retention and Cochran-Armitage trend test for insertions according to year during 2008-2014. RESULTS: Most adolescent SCI users were non-Hispanic white (43%), or Hispanic (34.2%) and 16 years or older (84.2%) at the time of insertion. Overall, 1-, 2-, and 3-year retention rates were 78.6%, 59.4%, and 26.2%, respectively, with retention at 44.3% at 2 years 9 months (indicative of removal of method for near expiration of 3-year device). The insertion rate trend showed statistically significant increases annually, from 0.14% in 2008 to 0.91% in 2014; P < .0001. No pregnancies were documented during implant use. The most common indication for SCI removal was device expiration. CONCLUSION: SCI insertions increased annually among adolescents, with more than a sixfold increase over the 6-year study period, and more than half of the SCIs were retained through 2 years of use. The most common indication of SCI removal was completion of Food and Drug Administration-approved duration.

Intracervical block for levonorgestrel-releasing intrauterine system placement among nulligravid women: a randomized double-blind controlled trial.

BACKGROUND: Fear of pain during the insertion of intrauterine contraceptives is a barrier to using these methods, especially for nulligravidas. An intracervical block may be easier and more reproducible than a paracervical block; however, this intervention has not been evaluated in nulligravid women to reduce pain with intrauterine contraceptive insertion. OBJECTIVE: To evaluate whether a 3.6-mL 2% lidocaine intracervical block reduces pain at tenaculum placement and levonorgestrel-releasing intrauterine system insertion among nulligravidas; and, in addition, to assess whether the intracervical block has any effect on the ease of device insertion and on the overall experience with the procedure. MATERIALS AND METHODS: In this randomized double-blind controlled trial, nulligravidas were block-randomized to 1 of 3 arms prior to 52-mg levonorgestrel-releasing intrauterine system insertion: 3.6-mL 2%-lidocaine intracervical block, sham injection (intracervical dry-needling), or no intervention. The primary outcome was pain at levonorgestrel-releasing intrauterine system insertion. Secondary outcomes were pain at tenaculum placement, ease of insertion (assessed by healthcare providers), and the overall experience with the procedure (pain with levonorgestrel-releasing intrauterine system insertion compared with expectations, discomfort level, wish to undergo another device insertion in the future, and recommendation of the procedure to others). Participants' pain was measured with a 10-cm visual analogue scale and a 5-point Faces Pain Scale. Pain was summarized into categories (none, mild, moderate, severe) and also analyzed as a continuous variable (mean and 95% confidence interval). Our sample size had 80% power (α = 0.05) to detect a 15% difference in pain score measured by visual analogue scale (mean [standard deviation] visual analogue scale score = 5.9 [2.0] cm) and an absolute difference of 20% in the proportion of women reporting severe pain at levonorgestrel-releasing intrauterine system insertion among groups. We used a χ2 test and a mixed-effects linear regression model. We calculated the number needed to treat for the intracervical block to avert severe pain at tenaculum placement and levonorgestrel-releasing intrauterine system insertion. RESULTS: A total of 302 women were randomized (99 to the intracervical block, 101 to the intracervical sham, and 102 to no intervention), and 300 had a successful device insertion. The intracervical block group had fewer women reporting severe pain than the other groups, both at tenaculum placement (intracervical block: 2% vs sham: 30.2% vs no intervention: 15.2%, P < .0001) and at levonorgestrel-releasing intrauterine system insertion (intracervical block: 26.5% vs sham: 59.4% vs no intervention: 50.5%, P < .0001). The mean (95% confidence interval) pain score reported at levonorgestrel-releasing intrauterine system insertion was lower in the intracervical block group than in the other groups (intracervical block: 4.3 [3.8-4.9] vs sham: 6.6 [6.2-7.0], P < .0001; intracervical block: 4.3 [3.8-4.9] vs no intervention: 5.8 [5.3-6.4], P < .0001). Women from the intracervical block group reported less pain than expected (P < .0001), rated the insertion as less uncomfortable (P < .0001), and were more willing to undergo another device insertion in the future (P < .01) than women in the other groups. The ease of insertion were similar among groups. The number needed to treat for the intracervical block to avert severe pain at tenaculum placement and levonorgestrel-releasing intrauterine system insertion was 2 and 4, respectively. CONCLUSION: A 3.6-mL 2% lidocaine intracervical block decreased pain at tenaculum placement and levonorgestrel-releasing intrauterine system insertion among nulligravidas. It also provided a better overall experience during the procedure.

The Effect of Peer Education in Dispelling Myths and Misconceptions about Long-Acting Reversible Contraception among Ethiopian Youth.

Robust evidence, including systematic reviews and recommendations from the 2016 Lancet Commission on Adolescent Health and Wellbeing, does not wholly support the unambiguous endorsement of peer-led community-based interventions. This study evaluated the effectiveness of an intensive three-day training for peer educators (PE) on dispelling myths and misconceptions about long-acting reversible contraceptives (LARCs) among Ethiopian youth. Post-training, PEs conducted demand-generation activities with their peers to encourage LARCs referrals. A convenience purposive sampling technique was used to select 20 health centers where peer educators referred clients: 10 each in Amhara and Tigray regions. The health centers were randomly allocated to the intervention (five) and non-intervention (five) study arms. Data were abstracted from the peer educators' monthly reporting forms over an 11-month period: 5 months pre-intervention and 6 months post-intervention. Analysis of family planning and LARCs referrals and chi-square tests of association were conducted. Odds of LARCs referrals at pre-intervention (0.96), fell to 0.83 for the post-intervention phase (p-value <0.6). Challenges, largely with data collection and reporting, may have exposed the study to Type II errors. We recommend focused and rigorous data collection in a multi-country 2X2 factorial design cluster randomized holistic intervention (service providers/clinic and PEs/community) trial to comprehensively determine effectiveness on demand for and uptake of LARCs among youth.

Acceptability of the community-level provision of Sayana® Press by medical and nursing students in Kinshasa, Democratic Republic of the Congo.

OBJECTIVES: The objectives were to assess acceptors' attitudes toward Sayana® Press as a method and toward the mechanism of community-based distribution by medical and nursing (M/N) students, known locally as "DBCs," in Kinshasa, Democratic Republic of the Congo, and to evaluate the experience of these DBCs. STUDY DESIGN: In 2015, surveys were conducted among (1) acceptors of Sayana® Press on the day of the initial injection, (2) these same acceptors 3 months later and (3) the DBCs providing community-based services. The analysis was descriptive and involved no significance testing. RESULTS: Acceptors of Sayana® Press expressed high levels of satisfaction with the method, despite some pain experienced at injection and subsequent side effects. Although most were satisfied with the counseling and services received from the DBCs, less than one third realized that the providers were M/N students. The DBCs expressed satisfaction in serving as community-based distributors; more than 95% would recommend it to others. Their primary complaints were lack of remuneration, stockouts and need for greater supervision. CONCLUSIONS: Consistent with results from previous pilot introductions of Sayana® Press in three African countries, clients were highly satisfied with Sayana® Press as a method. The reported preference for resupply at health centers may reflect a lack of client awareness that the DBCs administering methods near the health center were not in fact staff from the health center. The pilot served to gain acceptance for the use of M/N students in community-based distribution, paving the way for additional task-shifting pilots in Kinshasa. IMPLICATIONS: Sayana® Press represents a promising new method for increasing access to modern contraception in low-income countries. The Kinshasa experience is the first to test the use of medical and nursing students as providers at the community level. The study reports high levels of satisfaction on three counts: acceptors of the contraceptive method, acceptors of the mode of service delivery, and DBCs in their role as providers of contraception at the community level. However, many clients were not aware that the DBCs were students. The study represents an important contribution to the literature on task-shifting, especially in a country with chronic shortages of healthcare personnel.

Ileocecal endometriosis: diagnosis and management.

OBJECTIVE: Ileocecal endometriosis is rare. Symptoms range from no symptoms, cramps, vomiting, to acute intestinal obstruction. Our objective was to review our cases, clarify, and resume its most appropriate management focusing on the factors to determine diagnosis. This is a retrospective study by revision of medical charts of all ileal endometriosis cases of our unit from 2006 to 2014. CASE REPORT: Seven cases were found; three (43%) had previous endometriosis laparoscopic diagnosis, four (57%) had partial bowel obstruction episodes, three (43%) had chronic pelvic pain, and one developed acute intestinal obstruction in postoperative ileostomy closure. In three (43%), the diagnosis was made with magnetic resonance imaging (MRI) and double contrast barium enema, in one (14%) only with MRI, and the other three (43%) during surgery. All patients underwent resection of the ileum and evolved favorably. CONCLUSION: Variability in symptoms hinders diagnosis. The gold standard for diagnosis is MRI, but clinical suspicion optimizes imaging test diagnosis. Segmental resection should be indicated in the majority of the cases.

Menorrhagia Outcomes of Minimally Invasive Treatments (MOMITS): A 2 to 5-year follow-up.

We conducted a retrospective postal questionnaire-based study to assess the effectiveness and patient experience of minimally invasive treatments for menorrhagia by performing a two- to five-year follow up of patient symptoms. Questionnaires were distributed to 111 and 117 women following thermal balloon endometrial ablation (TBEA) and levonorgestrel intrauterine system (LNG-IUS), with response rates of 58.5% and 43.6% respectively. Sanitary pad use during the heaviest day of bleeding reduced by 8.4 and 5.2 pads in the TBEA and LNG-IUS groups respectively (p<0.05). An improvement in patients' quality of life (QOL) score exceeding 10 points was found in 79% and 61% in the TBEA and LNG-IUS groups respectively. Patient satisfaction (PS) improved in all areas, more so regarding participation in social activities in the TBEA group (p<0.05). Women undergoing TBEA would recommend the procedure to other women in 95%, and 93% in the LNG-IUS group. TBEA and LNG-IUS are highly acceptable management options for the treatment of menorrhagia, with improvement in QOL, PS and menstrual blood loss.

Safety and Acceptability of Community-Based Distribution of Injectable Contraceptives: A Pilot Project in Mozambique.

Mozambique has witnessed a climbing total fertility rate in the last 20 years. Nearly one-third of married women have an unmet need for family planning, but the supply of family planning services is not meeting the demand. This study aimed to explore the safety and effectiveness of training 2 cadres of community health workers-traditional birth attendants (TBAs) and agentes polivalentes elementares (APEs) (polyvalent elementary health workers)-to administer the injectable contraceptive depot-medroxyprogesterone acetate (DMPA), and to provide evidence to policy makers on the feasibility of expanding community-based distribution of DMPA in areas where TBAs and APEs are present. A total of 1,432 women enrolled in the study between February 2014 and April 2015. The majority (63% to 66%) of women in the study started using contraception for the first time during the study period, and most women (over 66%) did not report side effects at the 3-month and 6-month follow-up visits. Very few (less than 0.5%) experienced morbidities at the injection site on the arm. Satisfaction with the performance of TBAs and APEs was high and improved over the study period. Overall, the project showed a high continuation rate (81.1%) after 3 injections, with TBA clients having significantly higher continuation rates than APE clients after 3 months and after 6 months. Clients' reported willingness to pay for DMPA (64%) highlights the latent demand for modern contraceptives. Given Mozambique's largely rural population and critical health care workforce shortage, community-based provision of family planning in general and of injectable contraceptives in particular, which has been shown to be safe, effective, and acceptable, is of crucial importance. This study demonstrates that community-based distribution of injectable contraceptives can provide access to family planning to a large group of women that previously had little or no access.

Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation.

OBJECTIVE: Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. METHODS: We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. RESULTS: On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. CONCLUSIONS: There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.

An Evidence-based Approach to the Medical Management of Fibroids: A Systematic Review.

Fibroids are the most common tumor of the female reproductive tract, but approved medical treatments are limited. Patients demand uterine-sparing treatments which preserve fertility and avoid surgery. We systematically reviewed PubMed and Cochrane databases from January 1985 to November 2015 for evidence-based medical therapies for fibroids in the context of disease prevention, treatment of early disease, treatment of symptomatic disease, and preoperative management. We identified 2182 studies, of which 52 studies met inclusion and exclusion criteria. Published data affirm the efficacy of multiple agents, which are promising avenues for the development of medical alternatives to surgery.

Antifertility activity of Thevetia peruviana (Pers.) K. Schum leaf in female Sprague-Dawley rat.

OBJECTIVES: Thevetia peruviana (Pers.) K. Schum. (Apocynaceae) is known to possess cardioactive glycoside such as thevetin A, thevetin B, neriifolin, peruvoside, thevetoxin, and ruvoside. Traditionally, T. peruviana leaves are used as abortifacient. The aim of the present study is to evaluate antifertility potential of T. peruviana leaves. SUBJECTS AND METHODS: Cardiac glycoside freed leaves of T. peruviana were extracted with methanol using maceration method. The dried cardiac glycoside-free methanolic extract of T. peruviana leaves (TPL-Me-G) was screened for phytoconstituents and evaluated for its effect on estrogen-primed female Sprague-Dawley rat uterus model. It was further studied for effects on the estrous cycle, implantation, and effect on estrogen and progesterone. STATISTICAL ANALYSIS USED: Statistical analysis was done by ANOVA followed by Dunnett's t-test. RESULTS: Alkaloids, flavonoids, essential oils, carbohydrates, and amino acids were found to be present in the glycoside-free extract. Thin-layer chromatography (TLC) in n-butanol: acetone: water (4:1:5) revealed the presence of quercetin and kaempferol. The presence of flavonoids (quercetin 0.0326% and kaempferol 0.138% on dry weight basis) was reconfirmed by high-performance TLC analysis. The extract was able to induce uterine contractions (EC50, 0.170 mg/ml) in a dose-dependent manner. Further investigation showed significant (P < 0.001) extension of estrous cycle and anti-implantation activity of the extract by reduction of the progesterone level. CONCLUSIONS: Methanolic extract of T. peruviana leaves (TPL-Me-G) containing quercetin 0.0326% and kaempferol 0.138% possesses a significant (P < 0.001) antifertility potential by virtue of decreasing the progesterone level.

Integration of family planning with maternal health services: an opportunity to increase postpartum modern contraceptive use in urban Uttar Pradesh, India.

BACKGROUND: Maternal health (MH) services provide an invaluable opportunity to inform and educate women about family planning (FP). It is expected that this would enable women to choose an appropriate method and initiate contraception early in the postpartum period. In this study we examined interactions with health providers for MH services, and the effect of FP information provision during these interactions on the postpartum use of modern contraceptive methods. METHODS: This study used midline data collected from 990 women who had delivered a live birth between January 2010 and the date of the midline survey in 2012. These women were asked a series of questions about their last delivery, including interactions with health providers during pregnancy, delivery and the postpartum period, if they received FP information during these interactions, and their contraceptive use during the postpartum period. RESULTS: The study found that FP information provision as part of antenatal care in the third trimester, delivery and the postpartum period have a positive association with postpartum modern contraceptive use in urban Uttar Pradesh. However, health providers often miss these opportunities. Despite a high proportion of women coming into contact with health providers when utilising MH services, only a small proportion received FP information during these interactions. CONCLUSIONS: Integration of FP with MH services can increase postpartum modern contraceptive use. With the launch of the National Urban Health Mission, there now exists appropriate policy and programmatic environments for integration of FP and MH services in urban settings in India. However, this will require a concentrated effort both to enhance the capacity of health providers and encourage supportive supervision.

Curcumin: a novel non-steroidal contraceptive with antimicrobial properties.

Women face unique pathologies and challenges related to the female genital tract (FGT), including vaginal infections and gynecologic cancers. Vaginal infections faced by women include bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and sexually transmitted infections (STIs). Curcumin, a component of the dietary spice turmeric, has immense biological properties, including antioxidant, anti-inflammatory/immunomodulatory, and anticancer effects. It has no side effects and is well-tolerated, making it an ideal treatment modality highly desired by women. Recently, our laboratory showed, for the first time ever, that curcumin exhibits a spermicidal and broad-spectrum microbicidal activity against several species of bacteria and yeast involved in vaginal infections. Thus, it could provide a novel, non-steroidal contraceptive having both spermicidal and microbicidal properties and can be panacea in women for treatment of several FGT pathologies, including gynecologic cancers.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.