Subdermal contraceptive implants

Subdermal contraceptive implants involve the delivery of a steroid progestin from polymer capsules or rods placed under the skin. The hormone diffuses out slowly at a stable rate, providing contraceptive effectiveness for 1–5 years. The period of protection depends upon the specific progestin and the type of polymer. Advantages of progestin implants include long term contraceptive action without requiring the user's or provider's attention, low dose of highly effective contraception without the use of estrogen, and fertility is readily reversible after the removal of implants. The levonorgestrel implant Norplant R system is the only one that has been approved for distribution. The contraceptive efficacy of Norplant is the highest observed amongst the most effective methods with an annual pregnancy rate of 0.2 during the first and second year and 1.1 on the fifth year. Menstrual problems are the main reason for the discontinuation of Norplant and 9% of women stopped using it during the first year of treatment. Other implants are still under development trying to simplify the method by reducing the number of units and to introduce other progestins that may minimize side effects. Norplant-2 was designed to release the same dose of progestin from only two covered rods. Evaluation of 1400 women enrolled, indicates that over 2 years the cumulative pregnancy rate is below 0.5 per 100 women. There are three single implants under development: Nestorone, 3-Keto-desogestrel and Uniplant that are expected to be effective for 1–2 years. Phase II clinical trials with Nestorone have been completed and no pregnancies have been observed in 1570 woman-months of use. Bleeding irregularities occurred in 20–30% of the women but there were only four terminations because of bleeding problems. A multricentric study is ongoing with a newly designed 3-keto-desogestrel implant named Implanon, which releases approx. 60 μg/day of the hormone. The objectives of this study are to assess contraceptive efficacy, safety and acceptability of Implanon. Another multricentric study is ongoing with Uniplant, which releases nomegestrol acetate with a duration of action for only 1 year. The objectives of the trial are to study the endocrine profile of Uniplant users and to evaluate the efficacy and acceptability of the method.     

Effects of delayed transfer and treatment with oestrogen on the transport of microspheres by the rat oviduct

Starch or dextran blue microspheres were transferred microsurgically to the infundibulum of the oviduct on Days 1, 2, or 3 of pregnancy of control and oestradiol-treated rats. The animals were killed a few hours to several days after transfer to assess the number and distribution of ova and microspheres in the tract. After transfer on Day 1 of pregnancy, microspheres and eggs crossed the ampullary-isthmic junction (AIJ) 18 h after ovulation. After transfer on Day 2 of pregnancy, more than 50% of microspheres were retained in the ampulla, indicating that the AIJ changes again 34 h after ovulation. Treatment with oestradiol did not advance the passage of eggs or microspheres across the AIJ but caused accelerated transport through the isthmus as soon as the eggs or microspheres reached this segment. Dextran blue microspheres were seen to move back and forth in the isthmus of control anaesthetized rats at a frequency of 5-6 times/min. Between 7 and 20 h after treatment with oestradiol the frequency of these movements was significantly augmented, indicating that increased frequency of contractions of the smooth muscle of the isthmus precedes and accompanies accelerated transport of ova through this segment.