Intrauterine implantations

Number and distribution of intrauterine implantations classified as follows ... 

Some subcutaneous and intrauterine implants of progesterone have also been used which are prepared in biodegradable polymeric matrices. 

As of 1994, there were approximately 47 progestin-containing contraceptive dmg formulations sold in the United States for use as oral contraceptives (Table 3). In addition, there are three nonoral contraceptive formulations containing progestins ie, one injectable (Depo-Provera), one as an intrauterine device (lUD) (Progestasert), and one implantable (Norplant). Of the oral formulations, all but two also contain an estrogen component, ethynylestradiol. 

After insertion of an lUD, polymorphonuclear leukocytes and macrophages accumulate in the uterine cavity. These cells appear to phagocytize sperm and Hberate a blastotoxic toxin (92,93). Intrauterine devices also may create a hostile environment, perhaps because antibodies are produced that interfere with implantation of the fertilized ovum (93). 

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

IUDs cause low-grade, intrauterine inflammation and increased prostaglandin formation. In addition, endometrial suppression is caused by the progestin-releasing IUD. They are spermicidal and also interfere with implantation of the fertilized ovum. Efficacy rates are greater than 99% with both perfect use and typical use. 

It is through the local generation of eicosanoids that intrauterine contraceptive devices are effective, since they stimulate production of prostaglandins by the myometrium which increases its contractility, preventing implantation. 

Rule 14 deals with devices used for contraception or the prevention of transmission of sexually transmitted diseases - Class 11b, for example, condoms, contraceptive diaphragms and if they are implantable or long-term invasive Class 111, for example, intrauterine devices. 

Only one implantable contraceptive preparation is available at present in the USA. Etonogestrel, also used in some oral contraceptives, is available in the subcutaneous implant form listed in Table 40-3. Several hormonal contraceptives are available as vaginal rings or intrauterine devices. Intramuscular injection of large doses of medroxyprogesterone also provides contraception of long duration. 

Small doses of progestins administered orally or by implantation under the skin can be used for contraception. They are particularly suited for use in patients for whom estrogen administration is undesirable. They are about as effective as intrauterine devices or combination pills containing 20-30 meg of ethinyl estradiol. There is a high incidence of abnormal bleeding. 

Kit for subcutaneous implant 6 capsules of 36 mg each Intrauterine system 52 mg Medroxyprogesterone acetate (generic, Provera)... 

French RS, Cowan FM, Mansour DJ, Morris S, Procter T, Hughes D, Robinson A, Guillebaud J. Implantable contraceptives (subdermal implants and hormonally impregnated intrauterine systems) versus other forms of reversible contraceptives two systematic reviews to assess relative effectiveness, acceptability, tolerability and cost-effectiveness. Health Technol Assess 2000 4(7) 1-107. 

Meirik O, Farley TM, Sivin I. Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization. Obstet Gynecol 2001 97(4) 539-47. 

Wildemeersch, D., et al. 1999. GyneFIX. The frameless intrauterine contraceptive implant—An update for interval, emergency and postabortal contraception. Br J Fam Plan 24. 

Prenatal developmental toxicity studies (e.g. OECD Test Guideline 414) are very suitable for the demonstration of intrauterine death resorption after implantation. In studies where dosing is started before implantation, preimplantation loss may also be assessed by comparing the number of corpora lutea in the ovaries of the pregnant animals with the number of implantations. Uteri that appear non-gravid should be further examined. 

An unpublished USSR study analyzed by the U.S. Army Research Institute of Chemical Defense (Solana, 1992) provided data indicating that preconception maternal exposure of rats to 0.045 or 0.002 mg lewisite/cm, 4 hours/day, 5 days/week for 4 months did not affect numbers of corpora lutea or implantations, number and physical dimensions of fetuses, increased intrauterine mortality or ossification of long bones. Approximately 140 litters of rats were used in this study. 

Copper intrauterine devices are widely used and highly effective (> 99% at one year) for 5 and some for 10 years. They are especially useful in the over-40s in whom oral contraceptives may become progressively contraindicated and for whom one lUD will last into the menopause. The lUD prevents implantation of the fertilised ovum, and has an additional antifertilisation effect enhanced by the toxic effect of copper ions on the gametes. 

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