Mitchell D. Creinin

Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system

OBJECTIVE To assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive (LNG20) designed for up to 7 years use. STUDY DESIGN Nulliparous and parous women aged 16-45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label, partially randomized trial to evaluate LNG20. The primary outcome was pregnancy rate for women aged 16-35 years calculated as the Pearl Index. Women aged 36-45 years received LNG20 for safety evaluation only. All participants had in-person or phone follow-up approximately every 3 months during the study. RESULTS A total of 1600 women aged 16-35 years and 151 women aged 36-45 years agreed to LNG20 placement, including 1011 (57.7%) nulliparous and 438 (25.1%) obese women. Successful placement occurred in 1714 (97.9%) women. Six pregnancies occurred, four of which were ectopic. The Pearl Index for LNG20 was 0.15 (95% CI 0.02-0.55) through Year 1, 0.26 (95% CI 0.10-0.57) through Year 2, and 0.22 (95% CI 0.08-0.49) through Year 3. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24-1.23) through 3 years. Expulsion was reported in 62 (3.5%) participants, most (50 [80.6%]) during the first year of use. Of women who discontinued LNG20 and desired pregnancy, 86.8% conceived spontaneously within 12 months. Pelvic infection was diagnosed in 10 (0.6%) women. Only 26 (1.5%) LNG20 users discontinued due to bleeding complaints. CONCLUSION The LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women. IMPLICATIONS STATEMENT A new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years.

Prophylactic ibuprofen does not improve pain with IUD insertion: a randomized trial

OBJECTIVE To evaluate if ibuprofen 800mg reduces pain with intrauterine device (IUD) insertion among U.S. women. STUDY DESIGN We conducted a randomized, double-blind, placebo-controlled trial of women undergoing IUD insertion approximately 2-6weeks following first-trimester uterine aspiration. Subjects were randomized to receive ibuprofen 800mg or placebo 30-45min prior to IUD insertion. A 100-mm visual analog scale (VAS) was administered to measure pain after speculum insertion (baseline) and immediately following IUD insertion. RESULTS A total of 202 women were enrolled, with 101 randomized to each group (ibuprofen or placebo). Sociodemographic characteristics and baseline VAS scores were similar between groups. The median pain score with IUD insertion was 41.5mm in the placebo group and 38.0mm in the ibuprofen group (p=.50). Mean and median pain scores did not differ between placebo and ibuprofen when nulliparous and parous women were analyzed independently. Overall, median pain scores were 17.5mm higher in nulliparous women than parous women (p=.004). Median pain scores did not differ by age, IUD-type, history of dysmenorrhea or time since aspiration. CONCLUSIONS Administration of ibuprofen 800mg prior to IUD insertion does not reduce pain associated with the procedure for U.S. women. Overall, nulliparous women report more pain with IUD insertion than multiparous women.

Understanding women's desires for contraceptive counseling at the time of first-trimester surgical abortion.

OBJECTIVE The objective was to investigate whether or not women presenting for a first-trimester surgical abortion want to discuss contraception on the day of their procedure. STUDY DESIGN Between October 2012 and January 2013, an anonymous self-administered survey was distributed to women receiving first-trimester surgical abortions at four northern California family planning clinics. The survey obtained demographic information about each woman and inquired about her desire for contraceptive counseling during her appointment. Results were analyzed using both univariate and multivariable regression analyses to assess trends in responses related to desire for contraceptive counseling based on demographic and other variables. RESULTS Of the 199 respondents, 64% reported that they did not want to talk to a counselor or doctor about contraception on the day of their abortion. About half of the women (52%) who did not want to discuss contraception indicated they already knew what they wanted for pregnancy prevention. Of the 25% who reported that they did want to discuss contraception, the most important topic desired from the counseling was identification of methods that were easier to use than what they used previously. CONCLUSION The majority of women seeking first-trimester surgical abortion may not desire additional information about contraception on the day of the procedure. IMPLICATIONS STATEMENT This study demonstrates that a significant proportion of women may not want contraceptive counseling on the day of a planned surgical abortion.

Comparative analysis of the effects of nomegestrol acetate/17 β-estradiol and drospirenone/ethinylestradiol on premenstrual and menstrual symptoms and dysmenorrhea

Abstract Objectives To compare premenstrual and menstrual symptoms in healthy women using nomegestrol acetate/17β-estradiol (NOMAC/E2) and drospirenone/ethinylestradiol (DRSP/EE) via the Moos Menstrual Distress Questionnaire Form C (MDQ-C). Methods Women completed the MDQ-C at baseline and after completion of cycles 1, 3, 6 and 13, for the premenstrual (four days before most recent flow) and menstrual (most recent flow) phases in two randomized controlled trials. Treatment effects of NOMAC/E2 and DRSP/EE on the t-scores of eight MDQ-C symptom domains from 3522 women were examined, and the effects of both treatments on the score for cramps from 1779 women with moderate to severe cramps at baseline. Longitudinal data analysis methods were applied in both analyses. Results NOMAC/E2 users experienced a significant improvement in Pain, Water Retention, Negative Affect, Impaired Concentration and Behaviour Change domain scores in the menstrual phase compared with DRSP/EE users (p < 0.001 for all comparisons). However, Arousal (emotional and mental) scores worsened with NOMAC/E2 but not with DRSP/EE. Women with moderate to severe cramps experienced an improvement in the cramps score with NOMAC/E2 and DRSP/EE. Conclusions NOMAC/E2 was effective in reducing most premenstrual and menstrual symptoms, and was associated with significantly greater improvements in many MDQ-C domain scores compared with DRSP/EE. (ClinicalTrials.gov: NCT00413062 and NCT00511199). Chinese Abstract 摘要 目的 通过应用经期不适问卷C表格，调查使用醋酸诺美孕酮/17β雌二醇（NOMAC/E2）和屈螺酮/炔雌醇(DRSP/EE) 避孕的健康妇女， 了解其经前期和经期的不适及改善情况。 方法 在两个随机对照的临床试验中，受试妇女分别于基线，服药的第1、3、6、13个周期，从月经前期（指月经出血前4天）到月经期（月经出血第一天开始）完成经期不适问卷的C表格。3522名妇女在使用NOMAC/E2和DRSP/EE后，完成经期不适问卷所涉及的八大项相关症状调查。同时对1779名在基线时有中到重度痛经的妇女，对其服药后痛经的改善情况进行评估。在每一项分析中，均采用纵向数据分析法。 结果 NOMAC/E2使用者在月经期疼痛、水潴留、消极情绪、注意力不集中、行为改变等方面的评分，与DRSP/EE使用者相比较，均有显著的改善（p＜0.001）。然而，NOMAC/E2使用者身心健康感（不论是情绪还是精神）的评分是下降的。对于有着中到重度痛经的妇女，使用NOMAC/E2和DRSP/EE后，其疼痛都是改善的。 结论 NOMAC/E2对于改善经前期和经期的不适症状都是有效的，与DRSP/EE相比，对经期不适问卷C表格涉及的许多主要症状，均有较大的显著的改善作用。

Standardizing abortion research outcomes (STAR): a protocol for developing, disseminating and implementing a core outcome set for medical and surgical abortion

Author(s): Whitehouse, Katherine C; Kim, Caron R; Ganatra, Bela; Duffy, James MN; Blum, Jennifer; Brahmi, Dalia; Creinin, Mitchell D; DePineres, Teresa; Gemzell-Danielsson, Kristina; Grossman, Daniel; Winikoff, Beverly; Gulmezoglu, A Metin

Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation

Background A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora. Methods There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study. Results Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed. Conclusion Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem. Trial Registration ClinicalTrials.gov NCT00263341, NCT00455156

Transvaginal administration of intraamniotic digoxin prior to dilation and evacuation

BACKGROUND Transabdominal injection of digoxin into the amniotic fluid or fetus to induce fetal demise before dilation and evacuation (D&E) abortion has become common practice since the passage of the Partial-Birth Abortion Ban Act in 2007. STUDY DESIGN We performed a prospective study to assess the feasibility of transvaginal administration of intraamniotic digoxin the day before D&E. All women between 18 0/7 and 23 5/7 weeks of gestation seeking termination from December 2009 to May 2011 were approached for study participation. Women who declined participation were asked to identify their primary rationale. For women declining study participation, transection of the umbilical cord during D&E was performed to meet the requirements of the ban. RESULTS Over 18 months, 134 women met study entry criteria and 108 (81%) declined to participate. Of the 26 women who enrolled, 1.0 mg undiluted digoxin was successfully administered transvaginally in 24 (92%, 95% confidence interval 75%-99%). The most common reasons for declining participation were discomfort with preoperatively inducing fetal demise (37%) and desire to avoid a medically unnecessary medication (36%). CONCLUSIONS Transvaginal administration of digoxin is a feasible alternative to transabdominal administration to induce preoperative fetal demise. The majority of women decline digoxin administration when an alternative is available.

Levonorgestrel release rates over 5 years with the Liletta® 52-mg intrauterine system

OBJECTIVE To understand the potential duration of action for Liletta®, we conducted this study to estimate levonorgestrel (LNG) release rates over approximately 5½years of product use. METHODS Clinical sites in the U.S. Phase 3 study of Liletta collected the LNG intrauterine systems (IUSs) from women who discontinued the study. We randomly selected samples within 90-day intervals after discontinuation of IUS use through 900days (approximately 2.5years) and 180-day intervals for the remaining duration through 5.4years (1980days) to evaluate residual LNG content. We also performed an initial LNG content analysis using 10 randomly selected samples from a single lot. We calculated the average ex vivo release rate using the residual LNG content over the duration of the analysis. RESULTS We analyzed 64 samples within 90-day intervals (range 6-10 samples per interval) through 900days and 36 samples within 180-day intervals (6 samples per interval) for the remaining duration. The initial content analysis averaged 52.0±1.8mg. We calculated an average initial release rate of 19.5mcg/day that decreased to 17.0, 14.8, 12.9, 11.3 and 9.8mcg/day after 1, 2, 3, 4 and 5years, respectively. The 5-year average release rate is 14.7mcg/day. CONCLUSION The estimated initial LNG release rate and gradual decay of the estimated release rate are consistent with the target design and function of the product. The calculated LNG content and release rate curves support the continued evaluation of Liletta as a contraceptive for 5 or more years of use. IMPLICATIONS STATEMENT Liletta LNG content and release rates are comparable to published data for another LNG 52-mg IUS. The release rate at 5years is more than double the published release rate at 3years with an LNG 13.5-mg IUS, suggesting continued efficacy of Liletta beyond 5years.

Federally Funded Sterilization: Time to Rethink Policy?

In the 1970s, concern about coercive sterilization of low-income and minority women in the United States led the US Department of Health, Education, and Welfare to create strict regulations for federally funded sterilization procedures. Although these policies were instituted to secure informed consent and protect women from involuntary sterilization, there are significant data indicating that these policies may not, in fact, ensure that consent is truly informed and, further, may prevent many low-income women from getting a desired sterilization procedure. Given the alarmingly high rates of unintended pregnancy in the United States, especially among low-income populations, we feel that restrictive federal sterilization policies should be reexamined and modified to simultaneously ensure informed decision-making and honor womens reproductive choices.

Factors influencing women's satisfaction with surgical abortion

Abstract Objective Investigate which specific factors of abortion-related healthcare influence the overall satisfaction of women undergoing surgical abortion. Study Design Between May and December 2014, we invited women undergoing first-trimester surgical abortion without sedation at six Northern California reproductive health clinics from two clinic systems (four clinics in System A and two clinics in System B) to complete an anonymous survey in the recovery room. The survey obtained demographic information and inquired about the womens level of satisfaction with different aspects of care (very satisfied, somewhat satisfied, not satisfied or dissatisfied, somewhat dissatisfied or very dissatisfied). The survey asked women to rank the three most important factors that contributed to their level of satisfaction. We analyzed the results using univariate and descriptive analyses to assess trends in responses related to level of satisfaction based on demographic and other variables. Results A high percentage of women were very satisfied with their overall experience in both systems (A=79%, B=84%, p=0.34). Only 2% of women in System A and 1% in System B responded that they were neutral or not satisfied. The top three aspects of care ranked as most important were the same from both systems: ability to get an appointment in a timely manner, courtesy of staff and being informed as much as they wanted to know. Women were very satisfied or somewhat satisfied with these features of their care within both systems. Conclusion Women are generally very satisfied by the first-trimester surgical abortion care they receive in different clinics. Although each clinic and system provides unique care, the factors contributing to womens level of satisfaction are consistent. Implications Statement The most important factors that contribute to womens satisfaction with their first-trimester surgical abortion experience include the ability to get an appointment quickly, courtesy of the staff and being provided with information and responses to their questions.