Patient experience in a randomized trial of a weekly progesterone vaginal ring versus a daily progesterone gel for luteal support after in vitro fertilization.

OBJECTIVE: To assess patient experience and convenience of using progesterone vaginal ring (VR) versus vaginal gel for women requiring luteal phase support during in vitro fertilization (IVF). DESIGN: Post hoc analysis of a prospective, randomized, single-blind, multicenter, phase 3 clinical trial. SETTING: Twenty-two U.S. IVF centers. PATIENT(S): Women undergoing IVF (N = 1,297). INTERVENTION(S): Randomization to weekly VR or daily gel the day after egg retrieval for up to 10 weeks, with fresh embryo transfer IVF per site-specific procedures. MAIN OUTCOME MEASURE(S): Patient satisfaction questionnaire completed at final study visit. RESULT(S): In the women who were taking ≥1 dose of either VR (n = 647) or gel (n = 650), >97% reported that learning to use the formulation, remembering to take it at the correct time, and using it as prescribed was "easy" or "somewhat easy." More VR than gel users reported noninterference with daily activity (93.3% vs. 74.7%, P<.001), sexual comfort (80.3% vs. 67.8%, P<.001), and sexual desire (73.8% vs. 61.8%, P<.001), as well as not being bothered during sexual intercourse (66.9% vs. 39.2%, P<.001). More gel than VR users reported no difficulty with application (97.4% vs. 80.9%, P<.001). Among women who had previously used progesterone during IVF, more VR users than gel users preferred their currently assigned treatment to their previous treatment (91.4% vs. 83.0%, P=.03). CONCLUSION(S): Weekly progesterone VR and daily progesterone gel were easy to use, with limited impact on quality of life. Overall, the VR appeared to interfere less with daily life, social activities, and sexual activity although the gel was less difficult or stressful to apply. CLINICAL TRIAL REGISTRATION NUMBER: NCT00615251.

Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer.

Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti-cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line.

Current status of contraceptive vaginal rings.

Contraceptive vaginal rings (CVR) offer a new, effective contraceptive option, expanding the available choices of hormonal contraception. Various ring prototypes have been evaluated: progestin-only rings and combined progestin-estrogen rings, as well as different combination of progestins and estrogens. The progestin-only ring is intended for continuous use, whereas the combined ring has been designed for cyclic 3-week in/1-week out use, although several studies have explored alternative schemes of extended use. However, only two ring designs have reached the market: NuvaRing, a 1-month combined ring that releases etonogestrel and ethinylestradiol, and Progering, a 3-month progesterone-releasing ring for use in lactating women. A one year Nestorone/ethinyl estradiol CVR is approaching the final stages of development, as the Population Council is preparing to submit a new drug application to the Food and Drug Administration. The main advantages of CVRs are their effectiveness (similar or slightly better than the pill), ease of use without the need of remembering a daily routine, user ability to control initiation and discontinuation, nearly constant release rate allowing for lower doses, greater bioavailability and good cycle control with the combined ring, in comparison with oral contraceptives. Current prototypes in development include rings releasing progesterone receptor modulators, which would provide estrogen-free contraception, as well as combined rings releasing estradiol, instead of ethinyl-estradiol, providing a safer profile. Furthermore, intensive efforts towards developing dual protection rings, providing both contraception and protection against reproductive tract infections, offer hope that this greatly needed technology will soon undergo clinical testing and will be in the hands of women worldwide in the near future.

The contraceptive vaginal ring, NuvaRing(®), a decade after its introduction.

OBJECTIVES: To review the clinical experience with the contraceptive vaginal ring (CVR, NuvaRing(®)) since its introduction over ten years ago. METHODS: The literature was searched on efficacy, cycle control, safety, user preference and satisfaction of the CVR in comparison with combined oral contraceptives (COCs) and the patch, with special attention to recent developments. RESULTS: The ring has the same working mechanism and contraindications as COCs. Serum levels of steroids are steadier, whereas oestrogenic exposure is lower. Contraceptive efficacy is similar, as are metabolic changes. Cycle control is better, and compliance and continuation rates are equal or higher. Oestrogen-related adverse symptoms appear to be fewer, but reports on the incidence of venous thrombosis are conflicting. Expulsion of the ring is reported by 4% to 20% of women. Local adverse events are the main reason for discontinuation. Acceptability is as high as with COCs and, after structured counselling, the ring is preferred by many women to the pill or the patch. CONCLUSIONS: Efficacy of the CVR, and the metabolic changes and adverse events it elicits, are generally comparable to those of COCs, yet oestrogenic exposure is lower and cycle control superior. After counselling, the ring is preferred to the pill by many women.

The use of newer progestins for contraception.

The synthetic progestins used for contraception so far are structurally related either to testosterone (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor (GR) interactions. Dienogest (DNG) and drospirenone (DRSP) exhibit a partial antiandrogenic action, and DRSP has predominant anti-mineralocorticoid properties. The 19-norpregnanes include Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG), and possess a high specificity for binding to the progesterone receptor (PR) with no or little interaction with other steroid receptors. DRSP has been developed as combination oral pills with ethinyl estradiol (EE); DNG has been combined both with EE and, more recently, with estradiol valerate (E2V). NOMAc has been used as a progestin-only method and more recently combined with estradiol (E2). Nestorone is not active orally but proved to be the most active antiovulatory progestin when used parenterally. It has been developed in various formulations such as implants, vaginal rings or transdermal gel or spray. Risks and benefits of the new progestins depend upon the type of molecular structure, the type of estrogen associated in a combination and the route of administration.

The contraceptive vaginal ring.

The contraceptive vaginal ring offers effective contraception that is self-administered, requires less frequent dosing than many other forms of contraception, and provides low doses of hormones. NuvaRing (Organon, Oss, The Netherlands), the only contraceptive vaginal ring approved for use in the United States, contains etonogestrel and ethinyl estradiol. It is inserted into the vagina for 3 weeks, followed by a 1-week ring-free period, and works by inhibiting ovulation. Most women note a beneficial effect on bleeding profiles and are satisfied with NuvaRing. Commonly reported adverse events include vaginitis, leukorrhea, headaches, and device-related events such as discomfort. Serious adverse events are rare. In Chile and Peru, progesterone-only vaginal contraceptive rings are available for nursing women. Studies are ongoing examining new formulations of vaginal contraceptive rings.

Nuevo método de esterilización ambulatoria y permanente con técnica histeroscopia, essure / New method of permanent and ambulatory sterilization with histeroscopic technic, Essure

Objetivo: Presentamos nuestra experiencia en la inserción de un nuevo método de esterilización permanente vía histeroscópica, Essure. Se revisa el procedimiento de inserción, complicaciones, tolerancia, grado de satisfacción y aceptación de usuaria. Método: Entre enero y febrero de 2005 se realizaron 5 esterilizaciones con Essure en la Unidad de Ginecología y Obstetricia de Clínica Las Condes. Resultados: Se colocó el dispositivo en ambas trompas exitosamente en todas las pacientes. Rango de tiempo operatorio: 10-30 minutos. No hubo complicaciones intraoperatorias. Todas expresaron buena tolerancia y un alto grado de satisfacción frente al procedimiento de inserción histeroscópico. Lo recomendarían por su rapidez, carácter ambulatorio y ausencia de dolor. Durante el postoperatorio un caso presentó metrorragia leve y algia pélvica moderada. Conclusiones: Nuestra primera experiencia en la inserción del dispositivo intra tubario mostró ser un procedimiento bien tolerado y con buena aceptación por las pacientes.

Pelvis iatrógenica: dispositivo contraceptivo en localización intravesical

Paciente de 24 años de edad, sexo femenino, remitida al servicio de urología del Hospital Clínica San rafael, por cuadro de 6 años de evolución de infección de vías urinarias, interrecurrente crónica comprobada, y sispecha de localización extrauterina de dispositivo anticonceptivo

The diaphragm: barrier contraception has a new social role.

Using a diaphragm as a barrier contraceptive has received little attention in recent literature. A discussion of the role of the diaphragm to prevent pregnancy, as well as sexually transmitted diseases, is presented. A procedure for properly fitting the diaphragm is described. To ensure compliance, a review of a plan for education and practice by users is outlined.

PIP: The vaginal diaphragm, while designed for contraception, provides important additional benefits as a barrier to the transmission of sexually transmitted diseases (STDs). For centuries women have used various forms of the diaphragm to prevent pregnancy (e.g., cups molded of opium or oiled silky paper or halves of squeezed lemons). The modern diaphragm was brought to the US from Europe by Margaret Sanger in the 1920s. Today, three types are available: arcing, coil, and flat spring. Typical use of the diaphragm may provide greater efficacy than other barrier methods. The spermicidal agent used in conjunction with the diaphragm, nonoxynol-9, is active against a wide range of bacterial and parasite-associated STDs (but no data prove that spermicides are active against HIV in vivo). Thus, women using barrier contraceptives have lower prevalence rates of STDs and are less likely to develop cervical cancer or its precursors. The diaphragm also has no systemic side effects. However, diaphragm use has been associated with increased incidence of candidal infections, urinary tract infections, and bacterial vaginosis. Diaphragm use increased between 1973 and 1982, and efficacy is determined by the user's knowledge and consistency of use. First-year failure rates have been noted in 18% of those who exhibit typical use and 6% in cases of perfect use. Failure rates determine acceptance as does cost, which in the case of the diaphragm ranges from $18 to $30 in the US with spermicidal jelly costing $6-13 per tube. Diaphragms must be prescribed and fitted by a health care provider. They can be inserted 6 hours before intercourse and must remain in place for 6 hours thereafter. The only absolute contraindication to diaphragm use occurs in women in whom pregnancy would be life-threatening. Women depending on hormonal methods for contraception should consider use of the diaphragm for prevention of STDs. Diaphragm sizes range from 50 to 95 mm, and fit is determined by the distance between the posterior fornix and the pubic bone. Clients must be taught proper insertion and use techniques through an initial 30-minute visit and, ideally, in a follow-up visit 2 weeks later. Diaphragms should be replaced every 3 years or immediately should the diaphragm become punctured.

Condón femenino: nuevo dispositivo de barrera

Es posible que próximamente las mujeres tengan su propio condón: un nuevo dispositivo anticonceptivo que también podría ofrecer protección contra las enfermedades de transmisión sexual (ETS). El "condón femenino" es una funda desechable de látex o plástico blando, que se coloca dentro de la vagina. Muchos de los métodos eficaces para el control de la natalidad son controlados por los mujeres, pero el principal método para la protección contra las ETS (el condón masculino) no lo está. En la estela de la pandemia del SIDA, el brindar a las mujeres el potencial de proteger su salud sexual tiene mayor urgencia que nunca

Contraceptives: a look at the future.

PIP: Some future contraceptives promise new reliability and convenience. The Silastic vaginal ring is expected to be available worldwide in the mid-1990s. The ring releases 250 to 280 mcg of levonorgestrel and 180 mcg of estradiol, a combination that virtually eliminates ovulation. A low-dose ring is also being investigated. Contraceptive implants of Silastic polymer-based rods or capsules are inserted under the skin; these slowly release progestogen that suppresses ovulation. These implants are currently available in Scandinavian countries, Indonesia, and South America. The cervical cap has recently returned to the US market. The woman applies a spermicidal cream or jelly in the cap and places it over her cervix. It can be left in place for up to 36 hours. At present, 80 countries use various injectable drugs that inhibit ovulation for 2-3 months, but they are not yet approved in the USA because of their potential side effects. Under investigation in the US and elsewhere are antispermatogenic agents that create temporary infertility by interfering either with spermatogenesis or with the sperm's ability to fertilize ova. The agents can be given by injection or taken orally. Developed in France and undergoing clinical trials in the US, RU-486 is a pill that disrupts gestation by interfering with progesterone receptors in the inner lining of the uterus. RU-486 can be used to induce early nonsurgical abortions or routinely each month just before menstruation is due.^ieng