IUD self-removal: A randomized controlled trial of a self-removal guide in clinical and nonclinical settings.

OBJECTIVES: Intrauterine device (IUD) users often encounter barriers to desired removal. Self-removal, while previously found to be successful only 19% of the time, may mitigate these obstacles. Our primary objective was to evaluate the effectiveness of our previously developed IUD self-removal guide. Our secondary objectives were to evaluate the acceptability of the guide and characterize the self-removal process. STUDY DESIGN: This was a randomized controlled trial comparing IUD self-removal success rates with and without a guide. Participants selected a clinical or nonclinical setting for self-removal. The primary outcome was the rate of successful IUD self-removal. Covariates of interest included demographic characteristics, parity, body mass index, and attempted removal setting. RESULTS: Of the 116 participants, 35 (30%) successfully removed their IUDs, 20 (32%) randomized to the guide, and 15 (28%) randomized to no guide (p = 0.7). While our guide was not associated with increased successful self-removal, the majority (97%) of those randomized to it reported it to be helpful. Those who selected a nonclinical setting (80%) were more successful at self-removal (35% vs 9%, p = 0.01). Most participants would recommend IUD self-removal to a friend (68%) and attempt again with a future IUD (80%). CONCLUSIONS: The proportion of participants who successfully removed their IUDs was higher than previously shown, with or without the use of our guide. Our inclusion of a nonclinical setting was novel, in which the proportion of successful self-removal was significantly higher. Providers should consider discussion of IUD self-removal, with a reasonable expectation about the likelihood of success, as a means of increasing reproductive autonomy. IMPLICATIONS: IUD self-removal was feasible and acceptable.

A UPLC-MS/MS method for therapeutic drug monitoring of etonogestrel.

INTRODUCTION: Etonogestrel (ENG) is a progestin used in the contraceptive vaginal ring NuvaRing and the subdermal implant Implanon. A sensitive method for measuring ENG is useful for further investigating the progestin's pharmacokinetics with these alternative contraceptive formulations and generating important information about possible continued efficacy or potential failure to remove the subdermal implant. METHODS: Standards and serum samples were spiked with D8-progesterone (internal standard) and subsequently extracted with dichloromethane, dried, and reconstituted in 25% methanol with formic acid. ENG was analyzed by positive electrospray ionization in multiple reaction monitoring mode with a run time of 5.5 minutes using a C18 BEH column. The mobile phase was a gradient of water:acetonitrile, with 0.1% formic acid. The method was applied successfully to study the pharmacokinetics of ENG during vaginal ring use. The method was also used in routine patient care to assess ENG levels. RESULTS: The method is linear from 50 to 2000 pg/mL. The limits of detection and quantification are 25 and 50 pg/mL, respectively. There was no observed ionization suppression within the linear range of the assay, and the average recovery was 87%. Serum ENG levels of n = 3 subjects were all within the linear range of the assay for a total study period of 42 days after insertion of the ring. Of n = 20 patients with nonpalpable subdermal implants, n = 13 had ENG levels >25 pg/mL, whereas n = 7 had levels <25 pg/mL. CONCLUSIONS: We developed a rapid, sensitive, and robust ultra performance liquid chromatography-tandem mass spectometry (UPLC-MS/MS) method for the quantification of ENG in serum that is useful to study the progestin's pharmacokinetics and inform physicians about successful implantation or potential failure to remove a subdermal device.

Human Papillomavirus Vaccine: The Cancer Prevention Moonshot.

Cervical cancer is the fourth most common cancer in women worldwide with immense associated morbidity and mortality. Although most of the cervical cancer cases are caused by the human papillomavirus (HPV) and can effectively be prevented by HPV vaccination, vaccination unfortunately remains underused on a global scale with vast inequities in distribution. A vaccine as a tool to prevent cancer, cervical and others, is largely unprecedented. Then why do HPV vaccination rates globally remain so low? This article explores the burden of disease, development of the vaccine and its subsequent uptake, cost-effectiveness, and associated equity issues.

Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women.

OBJECTIVE: Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiologic studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring performance in obese women are needed. STUDY DESIGN: Twenty normal weight (body mass index [BMI] 19.0-24.9; median, 21.65) and 20 obese (BMI 30.0-39.9; median, 33.7) women enrolled in a prospective study of ethinyl estradiol (EE(2)) and etonorgestrel pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of contraceptive vaginal ring use. RESULTS: Thirty-seven women completed follow-up. Mean day 0-21 EE(2) concentrations were lower among obese vs normal weight women (15.0 vs 22.0 pg/mL, respectively, P = .004), whereas etonorgestrel concentrations were similar (1138 vs 1256 pg/mL, respectively, P = .39). Follicular development was minimal in both groups, with only 5 women achieving a maximum follicle diameter >13 mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels <1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 vs 1.4 days, respectively, P = .01). CONCLUSION: Although obese women had lower EE(2) levels during contraceptive vaginal ring use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that contraceptive vaginal ring effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE(2) levels in the obese women may explain the greater reported bleeding or spotting days.

Developing an intrauterine device self-removal guide: a mixed methods qualitative and small pilot study.

BACKGROUND: The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception (LARC) with few contraindications. Users, however, often encounter barriers to desired removal. IUD self-removal may mitigate these obstacles. We sought to develop a guide for IUD self-removal with the aim of increasing user control over the method. METHODS: This was a two-phase mixed-methods qualitative and small pilot study with the aim of developing an IUD self-removal guide. We conducted an online content analysis of advice for IUD self-removal as well as interviews with expert key informants to develop an IUD self-removal guide. We next recruited IUD-users who had previously attempted self-removal to participate in focus group discussion and individual interviews to further refine the guide. In the second phase of the study, we piloted the guide among eight IUD-users seeking removal interested in attempting self-removal. RESULTS: Expert key informants agreed that IUD self-removal was safe and low risk. The primary components of successful IUD self-removal elicited were ability to feel and grasp the strings, a crouched down position, and multiple attempts. A preference for presenting IUD self-removal as safe was emphasized. In the second phase, participants in the clinical pilot suggested more information for non-palpable strings, but liked the style and information provided. One participant successfully removed their IUD. CONCLUSIONS: IUD-users reported satisfaction with our guide. In our small pilot, the majority were unable to remove their own IUD. A larger study is needed to assess acceptability, feasibility, and efficacy in increasing successful self-removal.

Using changes in binding globulins to assess oral contraceptive compliance.

BACKGROUND: Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguish noncompliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid-, sex-hormone- and thyroxine-binding globulins (CBG, SHBG and TBG, respectively) as measures of OCP compliance. METHODS: We used frozen serum from a trial that compared ovarian suppression between normal-weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were noncompliant. We matched noncompliant participants with compliant participants by age, body mass index, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels and compared change from baseline to 3-month follow-up between the noncompliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. RESULTS: Changes in CBG and TBG distinguished OCP noncompliant users from compliant users [area under the ROC curve (AUROC), 0.86 and 0.89, p<.01]. Changes in SHBG were less discriminating (AUROC 0.69) CONCLUSIONS: EE2-induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP.

Contraceptive vaginal ring effectiveness is maintained during 6 weeks of use: a prospective study of normal BMI and obese women.

BACKGROUND: A single study shows that contraceptive vaginal ring (CVR) use for up to 35 days in women with a normal body mass index (BMI) maintains serum hormone levels sufficient to suppress ovulation. This study is intended to confirm those results and to evaluate prolonged CVR use up to 42 days in both normal BMI and obese women. STUDY DESIGN: Twenty women with a normal BMI and 20 obese women enrolled in a prospective open label clinical study of ethinyl estradiol (EE) and etonogestrel (ENG) pharmacokinetics during six weeks of use of a single CVR. Participants underwent twice-weekly evaluations to determine serum hormone concentrations, ovarian follicle development, endometrial thickness and bleeding patterns. RESULTS: Thirty-seven women completed follow-up including eighteen women with a normal BMI and nineteen obese women. EE and ENG concentrations remained in therapeutic range for all women. Follicular development and endometrial proliferation were minimal. By the sixth week, 30% of participants reported spotting or bleeding. CONCLUSIONS: A single CVR used for 6 weeks demonstrates therapeutic serum levels of EE and ENG among women with normal and obese BMI. Women who forget to remove the CVR at day 21 may well have continued contraceptive protection during the next 3 weeks.

Matched-pairs analysis of ovarian suppression during oral vs. vaginal hormonal contraceptive use.

BACKGROUND: This study was conducted to compare ovarian suppression during oral vs. vaginal hormonal contraceptive use. Secondary aims included comparison of endometrial thickness and bleeding patterns. METHODS: In two open-label trials assessing ovarian suppression, 33 compliant women completed both studies. They first used oral contraceptive pills (OCs) [randomized to either 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) or 30 mcg EE/150 mcg LNG] and subsequently used contraceptive vaginal rings (CVRs) (daily release of 15 mcg EE/120 mcg etonogestrel), all 21/7-day regimens. Participants had at least one run-in cycle using each contraceptive method prior to evaluation. During one cycle of each method, women underwent biweekly transvaginal sonography to measure ovarian follicular diameters and endometrial thickness. We also noted presence of a corpus luteum or a ruptured follicle as a marker of ovulation. Participants recorded bleeding days on paper calendars. We used matched-pairs analyses as appropriate. RESULTS: During follow-up, we identified at least one ovarian follicle ≥8 mm in 20/33 (61%) OC users and 12/33 (36%) CVR users (matched-pairs analysis, p=.02). Similar trends were seen for larger follicles; however, we had limited statistical power to evaluate these differences. Median follicular diameter among OC users was larger than median follicular diameter among CVR users (p=.01). We did not observe a corpus luteum or ruptured follicle in any participant during either study. Endometrial thickness was similar during OC and CVR use (mean 4.1±1.4 vs. 4.1±1.6 mm, p=.9), as was the number of bleeding or spotting days (mean 2.1±2.4 vs. 1.9±2.1, p=.8). Oral contraceptive pill dose was unrelated to follicle diameter, endometrial thickness or bleeding. CONCLUSIONS: Ovarian follicles ≥8 mm were more common in 33 compliant women during OC use than during CVR use, indicating that CVR use results in greater ovarian suppression than OC use.