Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial.

BACKGROUND: Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). METHODS: This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. FINDINGS: Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per µL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per µL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial.

BACKGROUND: Doravirine and islatravir is an investigational, once-daily regimen with high antiviral potency, favourable safety and tolerability, and a low propensity for resistance. We investigated a switch from bictegravir, emtricitabine, and tenofovir alafenamide to doravirine (100 mg) and islatravir (0·75 mg) in virologically suppressed adults with HIV-1. METHODS: We conducted a phase 3, multicentre, randomised, active-controlled, double-blind, double-dummy, non-inferiority trial at 89 research, community, and hospital-based clinics in 11 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL for at least 3 months on bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation allocation schedule, with block randomisation based on a block size of four, to switch to doravirine (100 mg) and islatravir (0·75 mg) or continue bictegravir, emtricitabine, and tenofovir alafenamide orally once daily, with matching placebos taken by all participants. Participants, investigators, study staff, and sponsor personnel involved in study drug administration or clinical evaluation of participants were masked to treatment assignment until week 48. Participants were instructed at each visit to take one tablet from each of the two bottles received, one of study drug and one of placebo, once daily, and participants were assessed at baseline and weeks 4, 12, 24, 36, and 48. The primary endpoint was the proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug; US Food and Drug Administration snapshot; prespecified non-inferiority margin 4%). The study is ongoing, with all remaining participants in post-treatment follow-up, and is registered with ClinicalTrials.gov, NCT04223791. FINDINGS: We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88·6%) participants were randomly assigned to a treatment group (183 [28·5%] women and 460 [71·5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0·75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021. At week 48, two (0·6%) of 322 participants in the doravirine and islatravir group compared with one (0·3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0·3%, 95% CI -1·2 to 2·0). The per-protocol analysis showed consistent results. 25 (7·8%) participants in the doravirine and islatravir group had headache compared with 23 [7·2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31·4%) compared with 98 (30·7%) had infections; and eight (2·5%) participants in each group discontinued therapy due to adverse events. 32 (9·9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11·9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group. In the islatravir and doravirine group, CD4 cell counts (mean change -19·7 cells per µL) and total lymphocyte counts (mean change -0·20 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Corifollitropin Alfa Combined With Human Chorionic Gonadotropin in Adolescent Boys With Hypogonadotropic Hypogonadism.

CONTEXT: Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization. OBJECTIVE: We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH. METHODS: This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 µg if weight ≤ 60 kg, or 150 µg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. RESULTS: After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. CONCLUSION: Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18).

Neurovascular anatomy of the adult female medial arm in relationship to potential sites for insertion of the etonogestrel contraceptive implant.

OBJECTIVE: Anatomic assessment of the medial upper arm to identify potential sites for insertion of the etonogestrel (ENG) implant. STUDY DESIGN: Forty female cadaveric arms were dissected. Two rows of 1×2-cm dissection windows were created in the inner arm overlying the triceps approximately 2-3 and 4-5 cm posterior to the bicipital sulcus (sulcus). The primary window was 8-10 cm proximal to the medial epicondyle and approximately 2-3 cm posterior to the sulcus. Neurovascular structures within each window were identified. The entire medial upper arm was dissected to visualize underlying structures. RESULTS: Mean age (± SD) of cadavers at death was 72.0±11.0 years. Arm measurements at the primary window were circumference 28.2±4.8 cm [range: 21-41], skin thickness 0.6±0.2 mm [0.3-1.0] and subcutaneous tissue thickness: 12.3±4.9 mm [4.7-21]. The basilic vein and the medial brachial cutaneous, ulnar and medial antebrachial cutaneous nerves were located in 40%, 58%, 40% and 18% of the primary windows, respectively. No major neurovascular structures were located 3-5 cm posterior to the sulcus. More neurovascular structures were identified overlying the biceps than triceps. Elbow flexion with the hand underneath the head displaced the ulnar nerve anteriorly towards the sulcus. CONCLUSION: As no major neurovascular structures were identified overlying the triceps 8-10 cm proximal to the medial epicondyle and 3-5 cm posterior to the sulcus, ENG implant insertion at this location may minimize risk of injury associated with improper deep insertion. Elbow flexion deflects the ulnar nerve away from this area and may further decrease risk of injury secondary to inadvertent deep insertion. IMPLICATIONS: Although a limited cadaver study, this anatomic assessment provides rationale for insertion of the ENG implant overlying the triceps 8-10 cm proximal to the medial epicondyle and 3-5 cm posterior to the sulcus. This area is theoretically safer for insertion of the ENG implant than areas of the inner arm where major neurovascular structures are commonly located.

A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17ß-estradiol in the treatment of women with primary dysmenorrhea.

OBJECTIVE: To evaluate the effect of investigational vaginal rings containing nomegestrol acetate (NOMAC) plus 17ß-estradiol (E2) or etonogestrel (ENG) plus E2 in women with moderate to severe primary dysmenorrhea. STUDY DESIGN: This was a Phase 2b randomized, placebo-controlled, multicenter, double-blind study. We randomized participants to one of five treatment groups: four hormonal rings and one placebo ring. The investigational vaginal rings released 300 µg of E2 daily along with 700 µg or 900 µg of NOMAC or 100 µg or 125 µg of ENG. Each participant received 2 identical rings and was to insert each for 21 days followed by a 7-day ring-free period. The primary endpoint, as assessed by a daily electronic diary (e-Diary), was the change in menstrual pain score from baseline to the second in-treatment withdrawal bleeding episode (Cycle 2). The pain score was the mean of the three highest scores for menstrual cramping pain (0-4 point scale) recorded from the day before menses to the third day of bleeding. The primary hypothesis was that at least one investigational vaginal ring would demonstrate a statistically significant larger reduction from baseline in pain score compared to placebo. Secondary endpoints included total mean impact score (which assessed the negative impact on work/school, physical activities, leisure/social activities) and the amount and days of rescue medication (ibuprofen) used. CLINICAL TRIAL REGISTRATION NUMBER: NCT01670656. RESULTS: We randomized 439 participants. The mean pain score decreased from baseline to Cycle 2 in all groups; the decrease in all four treatment groups compared to placebo was statistically significant (p-values ≤0.002). All treatment groups had greater reductions than placebo in ibuprofen intake and greater improvement in impact scores; these differences were statistically significant for both endpoints for the ENG-E2 100/300 µg/day group, while the other groups were not statistically significant for one or both endpoints. CONCLUSION: All four investigational rings produced a statistically significantly larger reduction from baseline in mean menstrual pain score compared to placebo while pain medication use decreased. IMPLICATIONS: This placebo-controlled study provides evidence that vaginal contraceptive rings containing NOMAC-E2 or ENG-E2 improve moderate to severe dysmenorrhea, across all of doses studied. This adds to the evidence that hormonal contraceptives are effective treatments for dysmenorrhea.

Safety and efficacy of the NuvaRing® Applicator in healthy females: a multicenter, open-label, randomized, 2-period crossover study.

INTRODUCTION: We assessed performance and safety of the NuvaRing® Applicator. METHODS: We randomized women (18-45 years) to insert a placebo ring using the applicator or fingers-only and then vice versa. We assessed outcomes post-insertion and then 24-72 h later. RESULTS: Insertion was 100% successful using both methods (applicator, n=163; fingers-only, n=162). A total of 8.6% (applicator) and 4.3% (fingers-only) of subjects reported at least 1 treatment-related adverse event (AE); all were mild. Subjects reported 5 applicator-related AEs (vulvovaginal pain, 4; abdominal cramping, 1). There was no vaginal bleeding within 15 h post-applicator use. Ring expulsions were rare (applicator, 1; fingers-only, 2). CONCLUSION: NuvaRing Applicator is effective and well-tolerated (NCT02275546).

Six-month and 1-year continuation rates following postpartum insertion of implants and intrauterine devices.

OBJECTIVE: Studies show immediate postpartum (PP) insertion increases use of contraceptive implants and intrauterine devices (IUDs). Our objective was to compare the satisfaction and continuation rates of the two types of devices at 6 months and 1 year following PP insertion. STUDY DESIGN: We enrolled 133 women in a prospective cohort study following immediate PP insertion of an implant or IUD at two academic hospitals during 8 months of 2011. Subjects completed an enrollment survey during hospital admission and a follow-up phone survey 6 months and 1 year PP. RESULTS: At 6 months PP, 72% of subjects provided follow-up information. Implant users were more likely to be using the originally-placed device (40/41, 98% vs. 45/55, 82%, p=0.02); nine women reported IUD expulsions. When accounting for replacement of expelled IUDs, IUD continuation at 6 months was 89% yielding similar continuation rates between groups (p=0.12). At 1 year PP, 51% provided follow-up. Of those, 82% still had a LARC method in place with similar continuation by device type (84% for implants, 81% for IUDs, p=0.96). Overall, satisfaction was similarly high in both groups. CONCLUSION: Due to IUD expulsion, implants had a higher continuation rate than IUDs six months following immediate PP insertion. After replacement of expelled IUDs, continuation and satisfaction were similar for both devices at 6 months and 1 year. IMPLICATIONS: Placement of implants and IUDs immediately PP can lead to high satisfaction. Despite early IUD expulsions, continuation rates were similar to those placed outside of the immediate PP period.

Cervical preparation for second-trimester surgical abortion prior to 20 weeks' gestation: SFP Guideline #2013-4.

For a dilation and evacuation (D&E) procedure, the cervix must be dilated sufficiently to allow passage of operative instruments and products of conception without injuring the uterus or cervical canal. Preoperative preparation of the cervix reduces the risk of cervical laceration and uterine perforation. The cervix may be prepared with osmotic dilators, pharmacologic agents or both. Dilapan-S™ and laminaria are the two osmotic dilators currently available in the United States. Laminaria tents, made from dehydrated seaweed, require 12-24 h to achieve maximum dilation. Dilapan-S™, made of synthetic hydrogel, achieves significant dilation within 4 h and is thus preferable for same-day procedures. A single set of one to several dilators is usually adequate for D&E before 20 weeks' gestation. Misoprostol, a prostaglandin E1 analogue, is sometimes used instead of osmotic dilators. It is generally regarded as safe and effective; however, misoprostol achieves less dilation than overnight osmotic tents. The literature supports same-day cervical preparation with misoprostol or Dilapan-S™ up to 18 weeks' gestation. As the evidence regarding alternative regimens increases, highly experienced D&E providers may consider same-day regimens at later gestations utilizing serial doses of misoprostol or a combination of osmotic and pharmacologic agents. Misoprostol use as an adjunct to overnight osmotic dilation is not significantly beneficial before 19 weeks' gestation. Limited data demonstrate the safety of misoprostol before D&E in patients with a prior cesarean delivery. Mifepristone, a progesterone receptor antagonist, is also effective for cervical preparation prior to D&E, although data to support its use are limited. The Society of Family Planning recommends preoperative cervical preparation to decrease the risk of complications when performing a D&E. Since no single protocol has been found to be superior in all situations, clinical judgment is warranted when selecting a method of cervical preparation.

Immediate placement of intrauterine devices after first and second trimester pregnancy termination.

BACKGROUND: We reviewed our experience with intrauterine device (IUD) placement after surgical abortion up to 20 weeks' gestation. STUDY DESIGN: Women presenting for elective abortion between January 2004 and March 2009 who requested an IUD were included in this retrospective review. RESULTS: Of 308 women requesting postabortion IUD placement, 221 (72%) planned insertion at the time of abortion (immediate group) and 87 (28%) planned insertion at their postoperative visit (interval group). IUDs were placed in 96% of the immediate group and in 23% of the interval group (212/221 vs. 20/87; p<.0001). Failure to return for placement was the most common reason for noninsertion in the interval group (60/87=69%). Follow-up information was obtained for 56% of patients and was documented a median of 137 days postabortion (range 3-1594 days). There was no difference in complication rates between groups. Expulsion rates were 3% and 0% in the immediate and interval groups, respectively (6/212 vs. 0/20; p=.4). Considering only those with documented follow-up after immediate insertion (119), there was a nonsignificant trend towards increased expulsion with placement after second vs. first trimester abortion (4/54=7% vs. 2/65=2%; p=.3). When analyzing the 172 subjects with documented follow-up, those planning immediate insertion were more likely to have an IUD in situ at the last contact than those planning later insertion (84/124=68% vs. 20/48=42%; p=.002). CONCLUSION: Immediate postabortion IUD insertion is safe and effective. Given the low rate of return for interval insertion, immediate placement may be preferable.

Postexposure prophylaxis for victims of sexual assault: treatments and attitudes of emergency department physicians.

BACKGROUND: Emergency departments (EDs) are the primary source of care for victims of sexual assault (SA). Provision of emergency contraception (EC) to these women has previously been noted to be sporadic. Completeness of care for victims of SA and the barriers to complete care are further investigated in this study. STUDY DESIGN: All ED attending physicians in Maryland, Virginia and the District of Columbia were identified and contacted for participation; 35% completed the survey. Practice patterns were analyzed for the 67% of physicians who do not refer SA victims to other hospitals. RESULTS: We found that 83% of physicians "always" or "usually" offer EC, but only half prescribe EC more than 48 h postassault. While most (89%) typically offer prophylaxis for STDs other than HIV, only 45% offer or counsel on HIV prophylaxis. Physician attitudes and hospital protocols were significant modifiers. CONCLUSION: Sexual assault victims are often not offered comprehensive care including prophylaxis against pregnancy and all STDs including HIV. Additional research is warranted to determine why physicians do not routinely offer HIV prophylaxis after SA.

MicroRNA miR-125a controls hematopoietic stem cell number.

MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size.

Cervical dilation in second-trimester abortion.

Dilation and evacuation, the most common method performed for second-trimester abortion in the United States, requires sufficient cervical dilation to reduce the risk of complications such as cervical laceration or uterine perforation. The cervix may be prepared with osmotic dilators such as laminaria, Lamicel, or Dilapan-S, or with pharmacologic agents such as misoprostol. Dilapan-S and Lamicel achieve their maximum dilation faster than laminaria, making same-day procedures possible. Misoprostol has limited data supporting its use in this setting. Decisions regarding which method is best are clinician-dependent, and factors such as gestational age and time allowed for preparation should be considered.

Cervical preparation for second-trimester surgical abortion prior to 20 weeks of gestation.

Roughly 11% of induced abortions in the United States are performed after 14 weeks of gestation, most commonly by dilation and evacuation (D&E). For a D&E procedure, the cervix must be dilated sufficiently to allow passage of operative instruments and products of conception without injuring the uterus or cervical canal. Preoperative preparation of the cervix reduces the risk of cervical laceration and uterine perforation. The cervix may be prepared with osmotic dilators, prostaglandin analogues, or both. Osmotic dilators currently available in the United States include Dilapan-S, Lamicel, and laminaria. Laminaria tents are made from dehydrated seaweed and require 12-24 h to achieve greatest dilation. The synthetic products, Dilapan-S and Lamicel, achieve maximum effect within 6 h. Dilapan-S achieves greater dilation than the others and, thus, requires fewer dilators to be placed but may be more difficult to remove. For same day procedures, Dilapan-S and Lamicel are preferable to laminaria. A single set of one to several dilators is usually adequate for D&E before 20 weeks of gestation. Additional sets over 1-2 days may be needed in challenging cases. Misoprostol, a prostaglandin analogue, is sometimes used instead of osmotic dilators; however, the data to support such use are limited. Misoprostol is inferior to overnight dilation with laminaria for cervical priming prior to D&E. Misoprostol use as an adjunct to overnight osmotic dilation is only marginally beneficial for priming beyond 16 weeks and does not truly demonstrate any benefit before 19 weeks of gestation. Limited data demonstrate the safety of misoprostol prior to D&E in patients with a uterine scar. The Society of Family Planning recommends preoperative cervical preparation to decrease the risk of complications when performing a D&E prior to 20 weeks of gestation. The three currently available osmotic dilators (laminaria, Lamicel, and Dilapan-S) are safe and effective for this use. Since no single protocol has been found to be superior, clinical judgment is warranted when selecting a method of preoperative cervical preparation.

A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion.

OBJECTIVE: To demonstrate equivalence between mifepristone 200 mg followed 6 to 8 hours later and 24 hours later by misoprostol 800 microg vaginally for abortion in women up to 63 days of gestation. METHODS: Mifepristone 200 mg was swallowed by 1,080 women after which they were randomly assigned to self-administer misoprostol intravaginally 6 to 8 hours later (group 1) or 23 to 25 hours later (group 2) at home. Participants returned for an evaluation, including transvaginal ultrasonography, 7 +/- 1 days after initiating treatment. Subjects who had not aborted were offered a second dose of misoprostol. All participants returned approximately 2 weeks after receiving mifepristone. Telephone contact was also attempted approximately 5 weeks after treatment. Treatment was considered a failure if a suction aspiration was performed for any indication. RESULTS: Complete abortion rates for groups 1 and 2 were 503 of 525 (95.8%, 95% confidence interval 93.7%, 97.3%) and 521 of 531 (98.1%, 95% confidence interval 96.6%, 99.1%), respectively, which were statistically equivalent. Side effects were significantly more common after mifepristone administration for women in group 2. Nausea, vomiting, and heavy bleeding were also significantly greater for women in group 2 after misoprostol treatment. Pain and subject acceptability were similar between groups. CONCLUSION: Mifepristone 200 mg followed 6 to 8 hours later by misoprostol 800 microg vaginally is as effective for abortion and has significantly fewer side effects as compared with regimens using a 24-hour dosing interval. Women receiving mifepristone and vaginal misoprostol for abortion can have the flexibility to administer the misoprostol as soon as 6 hours after using the mifepristone.

Feasibility study of the use of a daily electronic mail reminder to improve oral contraceptive compliance.

Women who ingest their oral contraceptive pill (OCP) as part of a daily routine are more likely use their OCPs correctly. This trial examines the feasibility of an electronic-mail (e-mail) reminder system to improve OCP compliance. An e-mail reminder was sent to 50 new OCP users daily for 3 months. Subjects sent an e-mail reply to confirm receipt. OCP compliance was recorded on diaries. Four subjects were discontinued for not checking their e-mail. Active participants missed a median of 18% of the e-mail reminders (range: 0-65%). A follow-up visit was scheduled after completion of three OCP cycles. Of the 40 subjects returning completed diaries, 50% missed no active pills at all and 20% missed at least one in each cycle. Most found the daily e-mail somewhat (65%) or very helpful (19%) for OCP compliance. Of those continuing OCPs, 64% wanted to continue receiving e-mail reminders at the completion of the study. Because inconsistent OCP use is a significant cause of unplanned conception, the use of e-mail to improve OCP compliance has the potential to decrease unintended pregnancies.

Mifepristone and vaginal misoprostol on the same day for abortion from 50 to 63 days' gestation.

In a previous study of 40 women up to 49 days' gestation, our research center demonstrated that mifepristone 200 mg followed on the same day by misoprostol 800 microg vaginally produced abortion at rates similar to standard regimens which administer the two drugs 24 or 48 h apart. We performed this study to evaluate the same regimen in women with pregnancies at 50 to 63 days' gestation. Forty women from 50 to 56 days' gestation (Group 1) and 40 women from 57 to 63 days' gestation (Group 2) inserted misoprostol vaginally 6 to 8 h after taking mifepristone. Participants were instructed to return 24 +/- 1 h after using misoprostol for an evaluation that included transvaginal ultrasonography. Subjects who had not aborted received a second dose of misoprostol to administer 48 h after the mifepristone. All participants were to return 2 weeks later. Ultrasound examinations were performed in those who required a second dose of misoprostol to confirm the abortion was successful. At 24 h after receiving misoprostol, 37/40 (93%, 95% CI 80, 98%) and 36/40 (90%, 95% CI 76, 97%) women from Groups 1 and 2, respectively, had expelled the pregnancy. By follow-up 2 weeks after taking mifepristone, all 40 women in Group 1 (100%, 95% CI 91,100%) and 39/40 women in Group 2 (98%, 95% CI 87,100%) had complete abortions. One woman in the latter group who aborted within the first 24 h had an incomplete abortion treated by suction curettage. This pilot study suggests that mifepristone 200 mg, followed on the same day by misoprostol 800 microg vaginally, effects abortion in women 50 to 63 days' gestation at rates comparable to regimens using longer dosing intervals between medications. Though this regimen is promising, larger randomized trials comparing it to standard regimens are needed before widespread use.

Early surgical abortion: efficacy and safety.

OBJECTIVE: Because of concern over the higher rates of failed abortion, many clinicians defer surgical abortion until 7 menstrual weeks or later. We conducted this study to evaluate the efficacy and safety of early surgical abortions that are performed by numerous physicians in a community-based setting. STUDY DESIGN: We prospectively gathered data on all eligible patients who had surgical abortions at <6 weeks of gestation at 3 Planned Parenthood clinics from January 1, 1998, to August 31, 2000. Outcomes were evaluated with the use of proportions with 95% CI and chi(2) analysis. RESULTS: A total of 1132 women had early surgical abortions during the study interval, and follow-up was available for 750 of those women (66%). Seventeen women (2.3%; 95% CI, 1.4%, 3.7%) had failed attempted abortions. Other complications occurred in 13 women. CONCLUSION: Early surgical abortion is safe and effective. In this series, the frequency of complications that required curettage was similar to that reported with mifepristone and vaginal misoprostol.