Kristina Gemzell-Danielsson

Misoprostol: Pharmacokinetic profiles, effects on the uterus and side-effects

Misoprostol, a synthetic prostaglandin E1 analogue, is commonly used for medical abortion, cervical priming, the management of miscarriage, induction of labor and the management of postpartum hemorrhage. It can be given orally, vaginally, sublingually, buccally or rectally. Studies of misoprostols pharmacokinetics and effects on uterine activity have demonstrated the properties of the drug after various routes of administration. These studies can help to discover the optimal dose and route of administration of misoprostol for individual clinical applications. Misoprostol is a safe drug but serious complications and teratogenicity can occur with unsupervised use.

Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus

In mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. In this study, we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partner’s seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the periovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. A substantial influx of CD45+ cells mainly comprising CD14+ macrophages and CD1a+ dendritic cells expressing CD11a and MHC class II was evident in both the stratified epithelium and deeper stromal tissue after coitus. CD3+CD8+CD45RO+ T cells were also abundant and increased after coitus. Leukocyte recruitment did not occur without coitus or with condom-protected coitus. An accompanying increase in CSF2, IL6, IL8, and IL1A expression was detected by quantitative RT-PCR, and microarray analysis showed genes linked with inflammation, immune response, and related pathways are induced by seminal fluid in cervical tissues. We conclude that seminal fluid introduced at intercourse elicits expression of proinflammatory cytokines and chemokines, and a robust recruitment of macrophages, dendritic cells, and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens and potentially, susceptibility to cervical metaplasia.

Strategies to prevent unintended pregnancy: increasing use of long-acting reversible contraception

BACKGROUND Despite increasing contraceptive availability, unintended pregnancy remains a global problem, representing as many as 30% of all known pregnancies. Various strategies have been proposed to reverse this disturbing trend, especially increased use of long-acting reversible contraceptive (LARC) methods. In this review we aim to discuss the role of LARC methods and importance of contraceptive counseling in reducing unintended pregnancy rates. METHODS References/resources cited were identified based on searches of medical literature (MEDLINE, 1990-2009), bibliographies of relevant publications and the Internet. RESULTS AND CONCLUSIONS LARC methods-copper intrauterine devices (IUDs), progestogen-releasing intrauterine system and injectable and implantable contraceptives-are safe and effective contraceptive options (unintended pregnancy rates with typical versus perfect use: 0.05-3.0 versus 0.05-0.6%) that are appropriate for a wide range of women seeking to limit or space childbearing. Despite their safety and efficacy records, these methods remain underutilized; injectable and implantable methods are used by an estimated 3.4% and intrauterine methods by 15.5% of women worldwide. LARC methods require no daily or coital adherence and avoid the adverse events and health risks of estrogen-containing contraceptives. The copper IUD and progestin-only injections and implants have been shown to be more cost-effective than more commonly used methods, such as condoms and the pill (5-year savings:

Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial

13,373-

Emergency contraception — mechanisms of action

14,122, LARC;

Mechanism of action of emergency contraception

12,239, condoms;

Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model

12,879, pill). Women who are considering use of LARC methods should receive comprehensive contraceptive counseling, as women who receive counseling before use demonstrate higher rates of after-use method satisfaction, continuation and acceptance than those who do not.

Treatment of incomplete abortion and miscarriage with misoprostol

BACKGROUND Uterine leiomyomas are widely prevalent and frequently cause menorrhagia. The major therapeutic option today is hysterectomy. Medical options are of highest interest. METHODS A total of 30 women with uterine leiomyomas scheduled for surgical intervention were randomized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery. Uterine blood flow and leiomyoma volume were evaluated once a month until surgery. Endometrial biopsies were obtained prior to and at end of treatment. Relevant biochemistry, symptoms and bleeding were recorded. Primary outcome was reduction in uterine leiomyoma size. RESULTS There was a significant percentual decrease (P = 0.021) in the total leiomyoma volume in the mifepristone-treated group, -28 (-48, -8) % (mean +/- 0, 95 confidence interval), compared with the control group values 6 (-13, 25) %. Mifepristone treatment significantly reduced the bleeding days (P = 0.001) and increased serum haemoglobin values (P = 0.046). Serum cortisol levels remained unchanged, while a mild increase in serum androgens was noted. Endometrial biopsies showed no premalignant changes or changes in mitotic indices. CONCLUSION Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding. Clinical Trials identifier: www.clinicaltrials.gov: NCT00579475.

The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology

Concerns regarding the mechanisms of action of emergency contraception (EC) create major barriers to widespread use and could also lead to incorrect use of EC and overestimation of its effectiveness. While the copper intrauterine device (Cu-IUD) is the most effective method available for EC, the hormonal methods are frequently considered to be more convenient and acceptable. Today, the most commonly used method for hormonal EC is levonorgestrel (LNG). More recently, the progesterone receptor modulator ulipristal acetate (UPA) has been shown to be more effective than LNG to prevent an unwanted pregnancy. The main mechanism of action of both LNG and UPA for EC is delaying or inhibiting ovulation. However, UPA appears to have a direct inhibitory effect on follicular rupture which allows it to be effective even when administered shortly before ovulation, a time period when use of LNG is no longer effective. The main mechanism of action of the Cu-IUD is to prevent fertilization through the effect of Cu ions on sperm function. In addition, if fertilization has already occurred, Cu ions influence the female reproductive tract and prevent endometrial receptivity. Based on this review of the published literature, it can be concluded that existing methods used today for EC act mainly through inhibition of ovulation or prevention of fertilization. An additional effect on the endometrium as occurs for the Cu-IUD, but not for the hormonal alternatives, seems to increase the efficacy of the method.

Endometrial Receptivity and Human Embryo Implantation

A major barrier to the widespread acceptability and use of emergency contraception (EC) are concerns regarding the mechanisms of action of EC methods. Today, levonorgestrel (LNG) in a single dose of 1.5 mg taken within 120 h of an unprotected intercourse is the most widely used EC method worldwide. It has been demonstrated that LNG-EC acts through an effect on follicular development to delay or inhibit ovulation but has no effect once luteinizing hormone has started to increase. Thereafter, LNG-EC cannot prevent ovulation and it does not prevent fertilization or affect the human fallopian tube. LNG-EC has no effect on endometrial development or function. In an in vitro model, it was demonstrated that LNG did not interfere with blastocyst function or implantation.