A statement on abortion by 900 professors of obstetrics and gynecology after the reversal of Roe vWade.

In the American Journal of Obstetrics and Gynecology in 1972 and 2013, 100 leaders in obstetrics and gynecology wrote calls to action-in 1972 in anticipation of the Roe v Wade decision and in 2013 in concern over the increasing restrictions to abortion care. In this article, 900 professors support a call to action for reinstating federal protections for abortion. Over a year ago, the Supreme Court handed down the Dobbs decision, overturning nearly 50 years of precedent in retracting the constitutionally protected right to abortion. The medical community is already seeing the harms of this decision on the lives and health of our patients and on the ability to train upcoming physicians in this medically necessary evidence-based care. Further harms are anticipated, including negative effects on maternal mortality. The 900 professors of obstetrics and gynecology whose signatures appear at the conclusion of this article stand together in support of reproductive freedom, including the right to affordable, accessible, safe, and legal abortion care.

Intrauterine device-related uterine perforation incidence and risk (APEX-IUD): a large multisite cohort study.

BACKGROUND: Reports of perforation risk related to intrauterine devices (IUDs) inserted immediately post partum and among non-post-partum individuals are scarce, and previous studies with only 12-month follow-ups underestimate the risk. Breastfeeding at IUD insertion and insertion within 36 weeks post partum have been associated with increased risk of uterine perforation. The aim of these analyses was to compare the incidence and risks of IUD-related uterine perforations by non-post-partum and post-partum intervals at IUD insertion, and among post-partum individuals, to assess the impact of breastfeeding on these outcomes. METHODS: We did a multisite cohort study in the USA, using electronic health records (EHR). Study sites were three health-care systems and a site that used data from a health-care information exchange. The study population included individuals who were aged 50 years or younger and had an IUD insertion between Jan 1, 2001, and April 30, 2018. Individuals were excluded if they had not been in the health-care system for at least 12 months before IUD insertion. The primary outcome for this analysis was any IUD-related uterine perforation diagnosis for the first IUD insertion in this time period. Both complete and partial IUD-related perforations were identified. Chart abstraction was done to validate EHR-based algorithms or confirm perforations. The crude rate and cumulative incidence of uterine perforation were evaluated by non-post-partum and post-partum intervals at IUD insertion in the full cohort, and by breastfeeding status in a subcohort of post-partum individuals. Cox models estimated crude and adjusted hazard ratios (aHRs). FINDINGS: Data from 326 658 individuals in the full cohort and 94 817 individuals in the post-partum subcohort were analysed. In the full cohort, we identified 1008 uterine perforations (51·2% complete), with the 5-year cumulative incidence being the lowest in the non-post-partum group (0·29%, 95% CI 0·26-0·34). The aHR for the post-partum interval relative to non-post partum ranged from 2·73 (95% CI 1·33-5·63; 0 to 3 days post partum) to 6·71 (4·80-9·38; 4 days to ≤6 weeks post partum). The post-partum subcohort of individuals with breastfeeding information had 673 uterine perforations (62% complete), with a 5-year cumulative incidence of 1·37% (95% CI 1·24-1·52) and an increased risk with breastfeeding (aHR 1·37, 95% CI 1·12-1·66). INTERPRETATION: Although the risk for uterine perforation with IUD insertion 4 days to 6 weeks or less post partum is nearly seven times that of insertion non-post partum, perforation remains an incredibly rare event for all clinical time points. Despite a slight increased risk of perforation with breastfeeding at IUD insertion, the benefits of breastfeeding and effective contraception generally outweigh risks and should have little clinical impact. Therefore, IUD insertion timing should be based on individual desire for IUD contraception and patient convenience to assure an IUD insertion can occur. Careful follow-up of individuals at higher risk of uterine perforation is warranted. FUNDING: Bayer AG.

Association between intrauterine device use and endometrial, cervical, and ovarian cancer: an expert review.

The intrauterine device is one of the most effective forms of contraception. Use of the intrauterine device has increased in the United States over the last 2 decades. Two formulations are commercially available in the United States: the levonorgestrel-releasing intrauterine device and the copper intrauterine device. The levonorgestrel intrauterine device releases progestin, causing endometrial suppression and cervical mucus thickening, whereas the primary mechanism of action of the copper intrauterine device is to create a local inflammatory response to prevent fertilization. Whereas the protective effects of combined hormonal contraception against ovarian and endometrial cancer, and of tubal sterilization against ovarian cancer are generally accepted, less is known about the effects of modern intrauterine devices on the development of gynecologic malignancies. The best evidence for a protective effect of intrauterine device use against cancer incidence pertains to levonorgestrel intrauterine devices and endometrial cancer, although studies suggest that both copper intrauterine devices and levonorgestrel intrauterine devices reduce endometrial cancer risk. This is supported by the proposed dual mechanisms of action including both endometrial suppression and a local inflammatory response. Studies on the relationship between intrauterine device use and ovarian cancer risk show conflicting results, although most data suggest reduced risk of ovarian cancer in intrauterine device users. The proposed biological mechanisms of ovarian cancer reduction (foreign-body inflammatory response, increased pH, antiestrogenic effect, ovulation suppression) vary by type of intrauterine device. Whereas it has been well established that use of copper intrauterine devices confers a lower risk of cervical intraepithelial neoplasms, the effect of levonorgestrel intrauterine device use on cervical cancer remains unclear. Older studies have linked its use to a higher incidence of cervical dysplasia, but more recent literature has found a decrease in cervical cancer with intrauterine device use. Various mechanisms of protection are postulated, including device-related inflammatory response in the endocervical canal and prostaglandin-mediated immunosurveillance. Overall, the available evidence suggests that both levonorgestrel intrauterine devices and copper intrauterine devices reduce gynecologic cancer risk. Whereas there is support for the reduction of endometrial cancer risk with hormonal and copper intrauterine device use, and reduction of cervical cancer risk with copper intrauterine device use, evidence in support of risk reduction with levonorgestrel intrauterine device use for cervical and ovarian cancers is less consistent.

The effect of a combined indomethacin and levonorgestrel-releasing intrauterine system on short-term postplacement bleeding profile: a randomized proof-of-concept trial.

BACKGROUND: Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period. OBJECTIVE: This proof-of-concept study aimed to establish whether the addition of indomethacin to the currently available levonorgestrel-releasing intrauterine system (average in vivo levonorgestrel release rate of 8 µg/24 h during the first year of use) reduces the number of bleeding and spotting days during the first 90 days of use compared with the unmodified system. The dose-finding analysis included 3 doses of indomethacin-low (6.5 mg), middle (12.5 mg), and high (15.4 mg)-to determine the ideal dose of indomethacin to reduce bleeding and spotting days with minimal side-effects. STUDY DESIGN: This was a multicenter, single-blinded, randomized, controlled phase II trial conducted between June 2018 and June 2019 at 6 centers in Europe. Three indomethacin dose-ranging treatment groups (low-, middle-, and high-dose indomethacin/levonorgestrel-releasing intrauterine system) were compared with the unmodified levonorgestrel-releasing intrauterine system group, with participants randomized in a 1:1:1:1 ratio. The primary outcome was the number of uterine bleeding and spotting days over a 90-day reference (treatment) period. Secondary outcomes were the number of women showing endometrial histology expected for intrauterine levonorgestrel application and the frequency of treatment-emergent adverse events. Point estimates and 2-sided 90% credible intervals were calculated for mean and median differences between treatment groups and the levonorgestrel-releasing intrauterine system without indomethacin. Point and interval estimates were determined using a Bayesian analysis. RESULTS: A total of 174 healthy, premenopausal women, aged 18 to 45 years, were randomized, with 160 women eligible for the per-protocol analysis set. Fewer bleeding and spotting days were observed in the 90-day reference period for the 3 indomethacin/levonorgestrel-releasing intrauterine system dose groups than for the levonorgestrel-releasing intrauterine system without indomethacin group. The largest reduction in bleeding and spotting days was achieved with low-dose indomethacin/levonorgestrel-releasing intrauterine system, which demonstrated a point estimate difference of -32% (90% credible interval, -45% to -19%) compared with levonorgestrel-releasing intrauterine system without indomethacin. Differences for high- and middle-dose indomethacin/levonorgestrel-releasing intrauterine system groups relative to levonorgestrel-releasing intrauterine system without indomethacin were -19% and -16%, respectively. Overall, 97 women (58.1%) experienced a treatment-emergent adverse event considered related to the study drug, with similar incidence across all treatment groups including the unmodified levonorgestrel-releasing intrauterine system. These were all mild or moderate in intensity, with 6 leading to discontinuation. Endometrial biopsy findings were consistent with effects expected for the levonorgestrel-releasing intrauterine system. CONCLUSION: All 3 doses of indomethacin substantially reduced the number of bleeding and spotting days in the first 90 days after placement of the levonorgestrel-releasing intrauterine system, thus providing proof of concept. Adding indomethacin to the levonorgestrel-releasing intrauterine system can reduce the number of bleeding and spotting days in the initial 90 days postplacement, without affecting the safety profile, and potentially improving patient acceptability and satisfaction.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

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.

Intrauterine device use, sexually transmitted infections, and fertility: a prospective cohort study.

BACKGROUND: In the 1970s, numerous medical reports, media coverage, and litigation around the Dalkon Shield intrauterine device led to a perception that all intrauterine devices cause upper genital tract infection and infertility. OBJECTIVE: This study aimed to assess the association between intrauterine device use and time to conception. STUDY DESIGN: The Fertility After Contraceptive Termination Study is a multicenter, prospective cohort study of women stopping their contraceptive method to attempt conception. We recruited participants between 2011 and 2017. Participants were a convenience sample of women recruited from academic centers in Philadelphia, PA; Los Angeles, CA; St. Louis, MO; Indianapolis, IN; Aurora, CO; and Salt Lake City, UT. Women were eligible if they stopped their contraceptive method within the past 120 days before enrollment, were between 18 and 35 years of age, had no history of infertility or sterilization, and had at least 6 months of follow-up. Baseline data included demographic and reproductive characteristics, past contraceptive use, nucleic acid amplification testing for sexually transmitted infections, and serology for past infection with Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. The primary exposure was intrauterine device use (ever); the primary outcome was time to conception. All participants were observed longitudinally for up to 24 months. We used piecewise exponential proportional hazards models with multiple imputation to provide hazard ratios and their respective 95% confidence intervals. RESULTS: Of the 461 participants, mean age was 28.2 years, 178 (38.7%) were Black, 157 (34.1%) were considered as low socioeconomic status, and 275 (59.7%) had a history of intrauterine device use. Without adjusting for any covariates, the median time to conception was shorter for participants who had a history of intrauterine device use (5.1 months) than participants who never used an intrauterine device (7.5 months). After controlling for potential confounders, the association of past intrauterine device use with time to conception was not statistically significant (adjusted hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). In our multivariable model, age, nulligravidity, Black race, low socioeconomic status, and past Mycoplasma genitalium infection were associated with longer times to conception (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). Conception by 12 months was lower in participants with past Mycoplasma genitalium infection (68% vs 80% without past infection; P=.019). CONCLUSION: We found no impairment of fertility with ever use of an intrauterine device. Serologic evidence of past Mycoplasma genitalium infection was associated with longer times to conception and higher rates of infertility. Mycoplasma genitalium infection is a potential modifiable cause of infertility.

Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study.

BACKGROUND: Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. OBJECTIVE: We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. STUDY DESIGN: APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. RESULTS: The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. CONCLUSION: Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Women's satisfaction with and ongoing use of hormonal long-acting methods compared to the oral contraceptive pill: Findings from an Australian general practice cluster randomised trial (ACCORd).

BACKGROUND: The Australian Contraceptive ChOice pRoject (ACCORd) aimed to assess the impact of a complex general practice intervention on the uptake of long-acting reversible contraceptives (LARC). AIMS: Using survey data from enrolled women, we aimed to compare the ongoing use and satisfaction of women who chose one of the hormonal LARC methods including the levonorgestrel intrauterine system (LNG-IUS) or levonorgestrel implant compared to the oral contraceptive pill (OCP). MATERIALS AND METHODS: We used the data from participants' baseline, six and 12-month surveys to identify new users of implants, LNG-IUS or OCP. We included demographic information, ongoing use of the contraceptive method, reasons for dissatisfaction and discontinuation and experience of side-effects. Proportions were compared using χ2 tests. RESULTS: Of the 740 women enrolled in ACCORd, 176 started using a hormonal LARC or OCP in the study's first six months with 76 using the IUS (43%), 60 the implant (34%) and 40 (23%) the OCP. Twelve-month continuation rates for the LNG-IUS, implant and OCP were 93, 83 and 65% respectively (P < 0.001). Satisfaction was highest among the LNG-IUS users; 86% were very/somewhat satisfied compared to 75% of implant users and 61% of OCP users (P < 0.001). Main reasons for method dissatisfaction were irregular bleeding and mood changes which were similar for all methods. CONCLUSIONS: This study provides further evidence that hormonal LARC methods have higher continuation and satisfaction rates compared to the OCP with similar side-effects. Since hormonal LARC methods have the highest contraceptive efficacy, these should be offered first-line to women.

Noncandidal vaginitis: a comprehensive approach to diagnosis and management.

Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear diagnosis or experience recurrent symptoms despite treatment. The 3 most common etiologies of vaginitis are trichomonas, bacterial vaginosis, and vulvovaginal candidiasis, which account for an estimated 70% of cases. The remaining 30% may be related to other causes of vaginitis, including atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal erosive disease. The purpose of this review is to describe the noncandidal causes of acute and recurrent vaginitis, with the goal of improving the likelihood of accurate diagnosis as well as efficient and effective therapy. We excluded candidal vaginitis from our review because there was a recently published review on this topic in the Journal. The clinical presentation and evaluation of patients with symptoms of vaginitis can be triaged into 1 of 2 diagnostic pathways: noninflammatory and inflammatory vaginitis. The most common noninflammatory cause is bacterial vaginosis. Features such as irritation, purulent discharge, and the presence of polymorphonuclear neutrophils are more suggestive of an inflammatory process. Trichomoniasis is the most common cause of inflammatory vaginitis. Other well-described forms of inflammatory vaginitis include atrophic vaginitis, desquamative inflammatory vaginitis, and erosive disease. We present a review of the pathogenesis, symptoms, examination findings, diagnostic testing, and treatment for each of these causes of noncandidal vaginitis.

Increasing long-acting reversible contraceptives: the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomized trial.

BACKGROUND: Long-active reversible contraceptives reduce unintended pregnancy and abortions, but uptake is low. Interventions to increase uptake in family medicine settings are untested. OBJECTIVE: The Australian Contraceptive ChOice pRoject, which was adapted from the successful US Contraceptive CHOICE study, aimed to evaluate whether a complex intervention in family medicine practices resulted in increased long-active reversible contraceptive uptake. STUDY DESIGN: This cluster randomized controlled trial was set in family practices in metropolitan Melbourne, Australia. From April 2016 to January 2017, we recruited 57 family physicians by mail invitation. Each family physician aimed to recruit at least 14 female patients. Eligible family physicians worked ≥3 sessions per week in computerized practices. Eligible women were English-speaking, sexually active, not pregnant, not planning a pregnancy in the next year, 16-45 years old, and interested in discussing contraception or in starting a new, reversible method. With the use of a randomization sequence with permuted blocks that were stratified by whether the family physician performed long-active reversible contraceptive insertion or not, family physicians were assigned randomly to a complex intervention that involved training to provide structured effectiveness-based contraceptive counselling and access to rapid referral to long-active reversible contraceptive insertion clinics. The 6-hour, online educational intervention was based on the US Contraceptive CHOICE Project and adapted for the Australian context. The control family physicians received neither the educational intervention nor access to the long-active reversible contraceptive rapid referral clinics and conducted their usual contraception counselling. We used the chi-square test, which was adjusted for clustering and stratification by whether the family physician inserted long-active reversible contraceptives, and binary regression models with generalized estimating equations and robust standard errors to compare, between the intervention and control groups, the proportions of women who had a long-active reversible contraceptive inserted. The primary outcome was the proportion of women with long-active reversible contraceptives that were inserted at 4 weeks. Secondary outcomes included women's choice of contraceptive method, quality of life, and long-active reversible contraceptive use at 6 and 12 months. Analyses were performed according to intention-to-treat. RESULTS: A total of 25 intervention and 32 control family physicians recruited 307 and 433 women, respectively (N=740). Within 4 weeks, 19.3% of women in the intervention group and 12.9% of women in the control group had long-active reversible contraceptive inserted (relative risk, 2.0; 95% confidence interval, 1.1-3.9; P=.033). By 6 months, this number had risen to 44.4% and 29.3%, respectively (relative risk, 1.6; 95% confidence interval, 1.2-2.17; P=.001); by 12 months, it had risen to 46.6% and 32.8%, respectively (relative risk, 1.5; 95% confidence interval, 1.2-2.0; P=.0015). The levonorgestrel intrauterine system was the most commonly chosen long-active reversible contraceptive by women in the intervention group at all time points. Differences between intervention and control groups in mean quality-of-life scores across all domains at 6 and 12 months were small. CONCLUSION: A complex intervention combination of family physician training on contraceptive effectiveness counselling and rapid access to long-active reversible contraceptive insertion clinics resulted in greater long-active reversible contraceptive uptake and has the potential to reduce unintended pregnancies.

Associations between the vaginal microbiome and Candida colonization in women of reproductive age.

BACKGROUND: The composition of bacteria within the vaginal microbiome has garnered a lot of recent attention and has been associated with reproductive health and disease. Despite the common occurrence of yeast (primarily Candida) within the vaginal microbiome, there is still an incomplete picture of relationships between yeast and bacteria (especially lactobacilli), as well as how such associations are governed. Such relationships could be important to a more holistic understanding of the vaginal microbiome and its connection to reproductive health. OBJECTIVE: The objective of the study was to perform molecular characterization of clinical specimens to define associations between vaginal bacteria (especially Lactobacillus species) and Candida colonization. In vitro studies were conducted to test the 2 most common dominant Lactobacillus species (Lactobacillus crispatus and Lactobacillus iners) in their ability to inhibit Candida growth and to examine the basis for such inhibition. STUDY DESIGN: A nested cross-sectional study of reproductive-age women from the Contraceptive CHOICE Project was conducted. Vaginal swabs from 299 women were selected to balance race and bacterial vaginosis status, resulting in a similar representation of black and white women in each of the 3 Nugent score categories (normal [0-3], intermediate [4-6], and bacterial vaginosis [7-10]). Sequencing of the 16S ribosomal gene (V4 region) was used to determine the dominant Lactobacillus species present (primarily Lactobacillus iners and Lactobacillus crispatus), defined as >50% of the community. Subjects without dominance by a single Lactobacillus species were classified as Diverse. A Candida-specific quantitative polymerase chain reaction targeting the internally transcribed spacer 1 was validated using vaginal samples collected from a second cohort of women and used to assess Candida colonization. Two hundred fifty-five nonpregnant women with sufficient bacterial biomass for analysis were included in the final analysis. Generalized linear models were used to evaluate associations between Lactobacillus dominance, sociodemographic and risk characteristics, and vaginal Candida colonization. In separate in vitro studies, the potential of cell-free supernatants from Lactobacillus crispatus and Lactobacillus iners cultures to inhibit Candida growth was evaluated. RESULTS: Forty-two women (16%) were vaginally colonized with Candida. Microbiomes characterized as Diverse (38%), Lactobacillus iners-dominant (39%), and Lactobacillus crispatus-dominant (20%) were the most common. The microbiome, race, and Candida colonization co-varied with a higher prevalence of Candida among black women and Lactobacillus iners-dominant communities compared with white women and Lactobacillus crispatus-dominant communities. Lactobacillus iners-dominant communities were more likely to harbor Candida than Lactobacillus crispatus-dominant communities (odds ratio, 2.85, 95% confidence interval, 1.03-7.21; Fisher exact test, P = .048). In vitro, Lactobacillus crispatus produced greater concentrations of lactic acid and exhibited significantly more pH-dependent growth inhibition of Candida albicans, suggesting a potential mechanism for the clinical observations. CONCLUSION: In nonpregnant women, Lactobacillus iners-dominant communities were significantly more likely to harbor Candida than Lactobacillus crispatus-dominant communities, suggesting that Lactobacillus species have different relationships with Candida. In vitro experiments indicate that Lactobacillus crispatus may impede Candida colonization more effectively than Lactobacillus iners through a greater production of lactic acid.

Association between obesity and bacterial vaginosis as assessed by Nugent score.

BACKGROUND: Bacterial vaginosis is 1 of the most common vaginal conditions in the United States. Recent studies have suggested that obese women have an abnormal microbiota reminiscent of bacterial vaginosis; however, few studies have investigated the prevalence of bacterial vaginosis in overweight and obese populations. Moreover, despite the increased prevalence of obesity and bacterial vaginosis in black women, it is not known whether racial disparities exist in the relationship between obesity and bacterial vaginosis. OBJECTIVE: The objective of this study was to examine the relationship between body mass index and bacterial vaginosis as determined by Nugent score and to determine the influence of race in this context. STUDY DESIGN: We performed a cross-sectional study using patient data and vaginal smears from 5918 participants of the Contraceptive CHOICE Project. Gram-stained vaginal smears were scored with the Nugent method and categorized as bacterial vaginosis-negative (Nugent score, 0-3), bacterial vaginosis-intermediate (Nugent score, 4-6), or bacterial vaginosis-positive (Nugent score, 7-10). Body mass index was determined with Centers for Disease Control and Prevention guidelines, and obese individuals were categorized as class I, II, or III obese based on National Institutes of Health and World Health Organization body mass index parameters. Linear regression was used to model mean differences in Nugent scores; Poisson regression with robust error variance was used to model prevalence of bacterial vaginosis. RESULTS: In our cohort, 50.7% of participants were black; 41.5% were white, and 5.1% were of Hispanic ethnicity; the average age of 25.3 years old. Overall, 28.1% of participants were bacterial vaginosis-positive. Bacterial vaginosis was prevalent in 21.3% of lean, 30.4% of overweight, and 34.5% of obese women (P<.001). The distribution of bacterial vaginosis-intermediate individuals was similar across all body mass index categories. Compared with the scores of lean women, Nugent scores were highest among overweight and obese class I women (adjusted mean difference: overweight women, 0.33 [95% confidence interval, 0.14-0.51] and obese women, 0.51 [95% confidence interval, 0.29-0.72]). Consistent with this, overweight and obese women had a higher frequency of bacterial vaginosis compared with lean women, even after adjustment for variables that included race. Among white women, the prevalence of bacterial vaginosis was higher for overweight and class I and class II/III obese white women compared with lean white women, which is a phenomenon not observed among black women and suggests an effect modification. CONCLUSION: Overweight and obese women have higher Nugent scores and a greater occurrence of bacterial vaginosis compared with lean women. Black women have a greater prevalence of bacterial vaginosis independent of their body mass index compared with white women.

Effect of baseline menstrual bleeding pattern on copper intrauterine device continuation.

BACKGROUND: Heavy menstrual bleeding is a leading cause of copper intrauterine device discontinuation. Thus, girls and women with heavy baseline menstrual bleeding may be at increased risk for early copper intrauterine device discontinuation. OBJECTIVE: Our objective was to assess if there was an association between baseline menstrual bleeding pattern prior to intrauterine device insertion and discontinuation rate at 12 months among study participants who chose copper intrauterine device at baseline. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project, a prospective observational cohort study of 9256 girls and women offered no-cost contraception for 2-3 years. Included in our study were participants who chose copper intrauterine device for contraception and for whom method continuation data at 12 months were available. Prior to contraception initiation, participants were asked to qualify their menstrual bleeding over the past year as: light, moderate, moderately heavy, or heavy. Light bleeding corresponded to using ≤10 pads/tampons per period. Moderate, moderately heavy, and heavy bleeding corresponded to 11-20 pads/tampons, 21-30 pads/tampons, and >30 pads/tampons per period, respectively. Subjects were then categorized into either a "heavy" baseline group (those reporting moderately heavy or heavy bleeding at baseline), or a "not heavy" group (those reporting light or moderate bleeding). The 12-month continuation rate for each group was then calculated using Kaplan-Meier survival function, and hazard ratio for risk of discontinuation was evaluated using a Cox proportional hazard model to determine if moderately heavy or heavy bleeding at baseline was associated with early discontinuation. RESULTS: Of the 918 girls and women meeting the inclusion criteria for this analysis, 165 were in the heavy baseline bleeding group, while 753 were in the not heavy bleeding group. The 12-month continuation rates for groups were similar: 80.2% (heavy) and 85.0% (not heavy; P = .24). Patients reporting either moderately heavy or heavy baseline bleeding were not at increased risk for early discontinuation of copper intrauterine device (hazard ratio, 1.21; 95% confidence interval, 0.88-1.66). Our sample size provided >90% power to detect a clinically important difference of 15% (assuming 20% discontinuation rate in not heavy bleeding group and a 35% discontinuation rate in the heavy bleeding group). CONCLUSION: We did not find that girls and women who reported baseline moderately heavy or heavy menstrual bleeding were at increased risk for early discontinuation. Thus, we do not believe that girls and women with heavy menstrual bleeding should be discouraged from using this safe and highly effective form of contraception.

Anticipated pain as a predictor of discomfort with intrauterine device placement.

BACKGROUND: Intrauterine devices have been gaining popularity for the past 2 decades. Current data report that >10% of women who use contraception are using an intrauterine device. With <1% failure rates, the intrauterine device is one of the most effective forms of long-acting reversible contraception, yet evidence shows that fear of pain during intrauterine device placement deters women from choosing an intrauterine device as their contraceptive method. OBJECTIVES: The objective of this analysis was to estimate the association between anticipated pain with intrauterine device placement and experienced pain. We also assessed other factors associated with increased discomfort during intrauterine device placement. We hypothesized that patients with higher levels of anticipated pain would report a higher level of discomfort during placement. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project. There were 9256 patients enrolled in Contraceptive CHOICE Project from the St. Louis region from 2007-2011; data for 1149 subjects who came for their first placement of either the original 52-mg levonorgestrel intrauterine system or the copper intrauterine device were analyzed in this study. Patients were asked to report their anticipated pain before intrauterine device placement and experienced pain during placement on a 10-point visual analog scale. We assessed the association of anticipated pain, patient demographics, reproductive characteristics, and intrauterine device type with experienced pain with intrauterine device placement. RESULTS: The mean age of Contraceptive CHOICE Project participants in this subanalysis was 26 years. Of these 1149 study subjects, 44% were black, and 53% were of low socioeconomic status. The median expected pain score was 5 for both the levonorgestrel intrauterine system and the copper intrauterine device; the median experienced pain score was 5 for the levonorgestrel intrauterine system and 4 for the copper intrauterine device. After we controlled for parity, history of dysmenorrhea, and type of intrauterine device, higher anticipated pain was associated with increased experienced pain (adjusted relative risk for 1 unit increase in anticipated pain, 1.19; 95% confidence interval, 1.14-1.25). Nulliparity, history of dysmenorrhea, and the hormonal intrauterine device (compared with copper) also were associated with increased pain with intrauterine device placement. CONCLUSION: High levels of anticipated pain correlated with high levels of experienced pain during intrauterine device placement. Nulliparity and a history of dysmenorrhea were also associated with greater discomfort during placement. This information may help guide and treat patients as they consider intrauterine device placement. Future research should focus on interventions to reduce preprocedural anxiety and anticipated pain to potentially decrease discomfort with intrauterine device placement.

Medicaid savings from the Contraceptive CHOICE Project: a cost-savings analysis.

BACKGROUND: Forty-five percent of births in the United States are unintended, and the costs of unintended pregnancy and birth are substantial. Clinical and policy interventions that increase access to the most effective reversible contraceptive methods (intrauterine devices and contraceptive implants) have potential to generate significant cost savings. Evidence of cost savings for these interventions is needed. OBJECTIVE: The purpose of this study was to conduct a cost-savings analysis of the Contraceptive CHOICE Project, which provided counseling and no-cost contraception, to demonstrate the value of investment in enhanced contraceptive care to the Missouri Medicaid program. STUDY DESIGN: The Contraceptive CHOICE Project was a prospective cohort study of 9256 reproductive-age women who were enrolled between 2007 and 2011. Study follow-up was completed October 2013. This analysis includes 5061 Contraceptive CHOICE Project participants who were current Missouri Medicaid beneficiaries or were uninsured and reported household incomes <201% of the federal poverty line. We created a simulated comparison group of women who were receiving care through the Missouri Title X program and modeled the contraception and pregnancy outcomes that would have occurred in the absence of the Contraceptive CHOICE Project. Data about contraceptive use for the comparison group (N=5061) were obtained from the Missouri Title X program and adjusted based on age, race, ethnicity, and income. To make an accurate comparison that would account for the difference in the 2 populations, we used our simulation model to estimate total Contraceptive CHOICE Project costs and total comparison group costs. We reported all costs in 2013 dollars to account for inflation. RESULTS: Among the Contraceptive CHOICE Project participants who were included, the uptake of intrauterine devices and implants was 76.1% compared with 4.8% among the comparison group. The estimated contraceptive cost for the simulated Contraceptive CHOICE Project group was $4.0 million vs $2.3 million for the comparison group. The estimated numbers of unintended pregnancies and births averted among the simulated Contraceptive CHOICE Project group compared with the comparison group were 927 and 483, respectively, which represented a savings in pregnancy and maternity care of $6.7 million. We estimated that the total cost savings for the state of Missouri attributable to the Contraceptive CHOICE Project was $5.0 million (40.7%) over the project duration. CONCLUSION: A program providing counseling and no-cost contraception yields substantial cost savings because of the increased uptake of highly effective contraception and consequent averted unintended pregnancy and birth.

Dual method use among long-acting reversible contraceptive users.

OBJECTIVE: To compare rates of dual method use (concurrent use of condoms and an effective method of contraception) in long-acting reversible contraceptive (LARC) and non-LARC hormonal contraceptive users, and to determine factors associated with dual method use. METHODS: We conducted a secondary analysis of the Contraceptive CHOICE Project, an observational, prospective cohort study of 9256 women in St. Louis, MO, USA. Our sample included 6744 women who initiated a contraceptive method within 3 months of enrollment, continued use at 6 months post-enrollment, and responded regarding dual method use. Our primary outcome was the rate of dual method use at 6 months post-enrollment. RESULTS: Dual method use was reported by 32% of LARC and 45% of non-LARC hormonal contraceptive users (p < .01). After adjusting for other covariates and comparing to non-LARC hormonal contraceptive users, LARC users were less likely to report dual method use (RRadj 0.76, 95% CI 0.70-0.83). Factors associated with dual method use in our multivariable analysis were age <25 years, black race, lower education, single relationship status, baseline dual method use, baseline diagnosis of sexually transmitted infection (STI), greater partner willingness to use a condom, and higher condom self-efficacy score. CONCLUSIONS: LARC users are less likely to report dual method use compared to non-LARC hormonal contraceptive users, but other factors also impact dual method use. Further studies should be performed to determine whether this lower dual method use increases the risk of STI. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov Identifier NCT01986439.

Provision of no-cost, long-acting contraception and teenage pregnancy.

BACKGROUND: The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential. METHODS: The Contraceptive CHOICE Project was a large prospective cohort study designed to promote the use of long-acting, reversible contraceptive (LARC) methods to reduce unintended pregnancy in the St. Louis region. Participants were educated about reversible contraception, with an emphasis on the benefits of LARC methods, were provided with their choice of reversible contraception at no cost, and were followed for 2 to 3 years. We analyzed pregnancy, birth, and induced-abortion rates among teenage girls and women 15 to 19 years of age in this cohort and compared them with those observed nationally among U.S. teens in the same age group. RESULTS: Of the 1404 teenage girls and women enrolled in CHOICE, 72% chose an intrauterine device or implant (LARC methods); the remaining 28% chose another method. During the 2008-2013 period, the mean annual rates of pregnancy, birth, and abortion among CHOICE participants were 34.0, 19.4, and 9.7 per 1000 teens, respectively. In comparison, rates of pregnancy, birth, and abortion among sexually experienced U.S. teens in 2008 were 158.5, 94.0, and 41.5 per 1000, respectively. CONCLUSIONS: Teenage girls and women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC methods had rates of pregnancy, birth, and abortion that were much lower than the national rates for sexually experienced teens. (Funded by the Susan Thompson Buffett Foundation and others.).

Condom use and incident sexually transmitted infection after initiation of long-acting reversible contraception.

BACKGROUND: Use of more effective contraception may lead to less condom use and increased incidence of sexually transmitted infection. OBJECTIVE: The objective of this study was to compare changes in condom use and incidence of sexually transmitted infection acquisition among new initiators of long-acting reversible contraceptives to those initiating non-long-acting reversible contraceptive methods. STUDY DESIGN: This is a secondary analysis of the Contraceptive CHOICE Project. We included 2 sample populations of 12-month continuous contraceptive users. The first included users with complete condom data (baseline, and 3, 6, and 12 months) (long-acting reversible contraceptive users: N = 2371; other methods: N = 575). The second included users with 12-month sexually transmitted infection data (long-acting reversible contraceptive users: N = 2102; other methods: N = 592). Self-reported condom use was assessed at baseline and at 3, 6, and 12 months following enrollment. Changes in condom use and incident sexually transmitted infection rates were compared using χ2 tests. Risk factors for sexually transmitted infection acquisition were identified using multivariable logistic regression. RESULTS: Few participants in either group reported consistent condom use across all survey time points and with all partners (long-acting reversible contraceptive users: 5.2%; other methods: 11.3%; P < .001). There was no difference in change of condom use at 3, 6, and 12 months compared to baseline condom use regardless of method type (P = .65). A total of 94 incident sexually transmitted infections were documented, with long-acting reversible contraceptive users accounting for a higher proportion (3.9% vs 2.0%; P = .03). Initiation of a long-acting reversible contraceptive method was associated with increased sexually transmitted infection incidence (odds ratio, 2.0; 95% confidence ratio, 1.07-3.72). CONCLUSION: Long-acting reversible contraceptive initiators reported lower rates of consistent condom use, but did not demonstrate a change in condom use when compared to preinitiation behaviors. Long-acting reversible contraceptive users were more likely to acquire a sexually transmitted infection in the 12 months following initiation.

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

BACKGROUND: The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. OBJECTIVE: We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the current Food and Drug Administration-approved duration. STUDY DESIGN: We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel intrauterine device for a minimum of 3 and 5 years, respectively (started intrauterine device in ≥2007 or implant in ≥2009). Demographic and reproductive health histories, as well as objective body mass index, were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rate, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using χ2 test and Fisher exact test, and compared serum etonogestrel levels stratified by body mass index using the Kruskal-Wallis test. RESULTS: Implant users (n = 291) have contributed 444.0 woman-years of follow-up. There have been no documented pregnancies in implant users during the 2 years of postexpiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (1-sided 97.5% confidence interval, 0-1.48) per 100 woman-years at 4 years and 0 (1-sided 97.5% confidence interval, 0-2.65) per 100 woman-years at 5 years. Among 496 levonorgestrel intrauterine device users, 696.9 woman-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the levonorgestrel intrauterine device is calculated as 0.25 (95% confidence interval, 0.04-1.42) per 100 woman-years; failure rate during the seventh year is 0.43 (95% confidence interval, 0.08-2.39) per 100 woman-years. Among implant users with serum etonogestrel results, the median etonogestrel level was 207.7 pg/mL (range 63.8-802.6 pg/mL) at the time of method expiration, 166.1 pg/mL (range 67.9 25.0-470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1-538.8 pg/mL) at the end of the fifth year. Median etonogestrel levels were compared by body mass index at each time point and a statistical difference was noted at the end of 4 years of use with overweight women having the highest serum etonogestrel (195.9; range 25.0-450.5 pg/mL) when compared to normal (178.9; range 87.0-463.7 pg/mL) and obese (137.9; range 66.0-470.5 pg/mL) women (P = .04). CONCLUSION: This study indicates that the contraceptive implant and 52-mg hormonal intrauterine device continue to be highly effective for at least 2 additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90 pg/mL for women in all body mass index classes.