Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.

Background: Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation.

Study Design: This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring.

Severity of infection following the introduction of new infection control measures for medical abortion.

Background: In response to concerns about serious infections following medical abortion, in early 2006 the Planned Parenthood Federation of America changed the route of misoprostol administration from vaginal to buccal and required either routine antibiotic coverage or universal screening and treatment for chlamydia; in July 2007, the Planned Parenthood Federation of America began requiring routine antibiotic coverage for all medical abortions. We previously reported a pronounced drop in the rate of serious infections following the adoption of these new infection control measures. Our objective in this study was to assess whether the degree of severity of the serious infections differed in the three infection control groups (vaginal misoprostol and no antibiotics; buccal misoprostol and screen-and-treat method; buccal misoprostol and routine antibiotics) or, equivalently, to assess whether the declines in rates of serious infections after the adoption of new infection control measures differed across the degree of severity categories.

State-of-the-art of non-hormonal methods of contraception: III. Intrauterine devices.

Since the 1959 revival of the IUD, non-hormonal devices have become the most widely used of all reversible contraceptives. Pregnancy rates of copper-releasing IUDs in current use range from approximately 0.5 to 1.

State-of-the-art of non-hormonal methods of contraception: I. Mechanical barrier contraception.

Mechanical barriers, specifically male condoms, command renewed interest and are used today by more people. The worldwide prevalence rate of male condoms was about 6% in 2007 corresponding to 65 million cohabiting couples. The prevalence of female barrier methods, including diaphragms, cervical caps and female condoms has declined to less than 1% of women in North America and in north-west Europe.

State-of-the-art of non-hormonal methods of contraception: IV. Natural family planning.

Despite the popularity of 'modern' contraceptives, natural family planning (NFP), including fertility awareness-based (FAB) methods and withdrawal, are practised in most countries. Worldwide FAB methods and withdrawal are used, respectively, by about 3.6% and 2.

Unexpected heaping in reported gestational age for women undergoing medical abortion.

Background: In August 2006, the Planned Parenthood Federation of America (Planned Parenthood) conducted an extensive audit of first-trimester medical abortions with oral mifepristone plus buccal misoprostol through 56 days of gestation so that patients could be given accurate information about the success rate of the new regimen.

Objectives: We sought to evaluate the effectiveness of this buccal misoprostol regimen and to examine correlates of its success during routine service delivery.

Methods: Audits in 10 large urban service points were conducted in 2006 to estimate the success rates of the buccal regimen.

Effectiveness of medical abortion with mifepristone and buccal misoprostol through 59 gestational days.

Background: From 2001 to March 2006, Planned Parenthood Federation of America (Planned Parenthood) health centers throughout the United States provided medical abortions principally by a regimen of oral mifepristone, followed 24-48 h later by vaginal misoprostol. In late March 2006, analyses of serious uterine infections following medical abortions led Planned Parenthood to change the route of misoprostol administration and to employ additional measures to minimize subsequent serious uterine infections. In August 2006, we conducted an extensive audit of medical abortions with the new buccal misoprostol regimen so that patients could be given accurate information about the success rate of the new regimen.

Rates of serious infection after changes in regimens for medical abortion.

Background: From 2001 through March 2006, Planned Parenthood health centers throughout the United States provided medical abortion (abortion by means of medication) principally by a regimen of oral mifepristone followed 24 to 48 hours later by vaginal misoprostol. In response to concern about serious infections, in early 2006 Planned Parenthood changed the route of misoprostol administration from vaginal to buccal and required either routine provision of antibiotics or universal screening and treatment for chlamydia; in July 2007, Planned Parenthood began requiring routine treatment with antibiotics for all medical abortions.

Methods: We performed a retrospective analysis assessing the rates of serious infection after medical abortion during a time when misoprostol was administered vaginally (through March 2006), as compared with rates after a change to buccal administration of misoprostol and after initiation of additional infection-reduction measures.

Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard gel: a randomized, cross-over, pharmacokinetic study.

Background: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner.

Study Design: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application.

A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells.

Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4(+) T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4(+), not CD8(+), T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites.

Utility and drawbacks of continuous use of a copper T IUD for 20 years.

This article examines interrelated questions concerning the extent of need for contraception in women 40 years and older and the degree to which that need can be served when use of collared T IUDs is initiated in women aged 25-35 years. Differentials in the impacts of intrauterine device (IUD) use on health issues in the second decade of contraception are also addressed. Although fertility of all women aged 40-44 years is below 100 per 1000 in all regions of the world today, the risk of pregnancy among married or cohabiting women who do not use contraception is estimated at 270-300 per 1000 or 27-30% per year.

Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen.

Objective: We evaluated the effects of a new combined hormonal contraceptive vaginal ring (CVR) delivering the nonandrogenic progestin Nestorone (NES) and ethinyl estradiol (EE) on several key estrogen-sensitive hepatic proteins that may be markers for the risk of arterial or venous disease events and on blood pressure (BP). Because the pharmacologic androgenicity of the progestin in these formulations influences the hepatic impact of EE, we selected an oral contraceptive (OC) delivering the androgenic progestin levonorgestrel (LNG) and EE as the comparator. We also investigated the effect of delivery route, which is known to modify the hepatic effects of estradiol, but has not been widely studied with EE.

Local and systemic effects of intranodally injected CpG-C immunostimulatory-oligodeoxyribonucleotides in macaques.

Immunostimulatory CpG-C oligodeoxyribonucleotides (ISS-ODNs) represent a promising strategy to enhance vaccine efficacy. We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-gamma responses in vitro. To further explore the potential of C274 for future vaccine studies, we assessed the in vivo effects of locally administered C274 (in naive and healthy infected macaques).

Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables.

Objective: This study aimed to compare the effects on hemostasis variables of a contraceptive vaginal ring with those of an oral contraceptive.

Study Design: Twenty-three and 22 healthy premenopausal women were randomized to the contraceptive vaginal ring (150 microg Nestorone and 15 microg ethinyl estradiol) or Stediril 30 during 3 cycles. Analysis of covariance was performed with baseline values as covariate.

CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques.

Cytosine-phosphate-guanine class C (CpG-C) immunostimulatory sequence oligodeoxynucleotides (ISS-ODNs) activate human B cells and dendritic cells (DCs), properties that suggest potential use as a novel adjuvant to enhance vaccine efficacy. After demonstrating that the CpG-C ISS-ODN C274 activates macaque DCs, we examined in vitro activation of macaque B cells by C274 as a prelude to evaluation of this molecule as an adjuvant in the testing of candidate human immunodeficiency virus vaccines in the rhesus macaque-simian immunodeficiency virus (SIV) model. C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN.

Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.

Objective: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated.

Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.

Objectives: This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days.

Methods: Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding.

Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial.

In a multicenter 1-year trial of contraceptive vaginal rings (rings) involving 150 women, three dose combinations of the progestin Nestorone (NES) and ethinylestradiol (EE) were compared with respect to effectiveness, safety and acceptability. Mean in vitro drug release rates for the three doses were 150 and 15, 150 and 20 and 200 and 15 microg/day of NES and EE, respectively. Each ring remained in situ for 21 days, removed for 7 days and then reinserted for a total of 13 cycles of use.

Two-year performance of a Nestorone-releasing contraceptive implant: a three-center study of 300 women.

A 2-year trial of a single Nestorone (NES) rod implant was conducted at three Latin American centers, each enrolling 100 women. We studied the safety, effectiveness and acceptability of this progestin-releasing contraceptive implant. Three pregnancies occurred, the last at 18 months of use.