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International Journal of Gynecology and Obstetrics. 1999 Dec; 67 Suppl 2:S111-6.By building on the successful past and ongoing partnership with the Research Training in Human Reproduction in supporting researches relevant to reproduction and reproductive health, the Rockefeller Foundation and the World Health Organization are pushing another joint research initiative in the area of implantation. Issues addressed include the implantation process, options for the development of anti-implantation agents, and the rationale for using these agents as method of fertility regulation. This paper concerns the scientific and logistical objectives and focus of the initiative. The following are the proposed foci of the research: 1) the implantation window at the endometrial level in a primate; 2) the development and demise of the primate corpus luteum; and 3) the pre-implantation embryo-uterus-corpus luteum interaction. Six proposals were selected and recommended for support, including in vitro and in vivo basic research, mainly at the molecular level, research in appropriate animal models, and clinical trial in mechanisms of action of alleged anti-implantation and menses-inducing agents and infertility caused by endometrial or ovarian factors. The six centers are located in developed and developing countries. The principal investigators and areas of work of the selected proposals are outlined and offer a future direction of the initiative.
ENTRE NOUS. 1991 Dec; (19):15.About 8 million women use the long acting injectable contraceptive depot-medroxy-progesterone acetate (DMPA) and norethisterone enanthate (NET-EN). These progesterone only injectables are not dependent on sexual activity and are easy to administer. Yet they are not always well accepted since they can interfere with menstrual bleeding and often induce amenorrhea. Researchers find that adding estrogen to DMPA and NET-EN treats these irregularities. They must use esters with limited action to protect the endometrium from constant estrogens, however, which requires monthly injections. Thus bleeding occurs once a month just like the normal menstrual cycle. Clinical trials in China of Injectable No. 1 (250 mg 17-alpha-hydroxyprogesterone caproate and 5 mg estradiol valerate) show that it has few side effects and is acceptable. Other trials in China are evaluating monthly injectables with NET-EN or megestrol acetate. Numerous developing countries often as WHO's Special Programme of Research in Human Reproduction for effective, safe, and fully studied monthly injectables. WHO operates under a 2 part strategy: optimum improvement of HPR 102 (50 m NET-EN and 5 mg estradiol valerate) and Cyclofem (25 mg DMPA and 5 mg estradiol cypionate) resulting in a reduction of the dose of at least 1 of the hormones and results of a study of the efficacy and side effects of these 2 injectables. It hopes the study provides the impetus to introduce them into national family planning programs. It demonstrates that they are indeed efficacious, effect fewer changes in the menstrual cycle than the progesterone only injectables, and are well accepted, even though women must go to a clinic every 27-33 days for an injection. Other studies are determining their effects on lipid and glucose metabolism, coagulation, and fibrinolysis. They are also looking at the time needed for ovulation to return. 1 study shows that menstruation returned in all women by the 3rd cycle.
In: Zatuchni GI, Goldsmith A, Shelton JD, Sciarra JJ, ed. Long-acting contraceptive delivery systems. Philadelphia, Pa., Harper and Row, 1984. 621-7. (PARFR Series on Fertility Regulation)Progestasert (Alza Corporation, Palo Alto, California) achieves relatively high rates of contraceptive effectiveness through the release of a sex hormone--progesterone. Currently, it is recommended that Progestaserts be replaces every 12 months and most copper-bearing IUDs, every 3 years. To improve on Progestasert's 1-year replacement interval, Alza Corporation modified the Progestasert by increasing the amount of pregesterone contained in the IUD (from 38 to 52 mg) without changing the average daily release of 65mg. This long-acting progestasert, called the Intrauterine Progesterone Contraceptive System (IPCS), was designed to have a useful life of 3 years before replacement was required. The IPCS is identical in appearance to the Progestasert, and its contraceptive action in the same as that of the Progestasert. The effectiveness of either is through the effects of an intrauterine foreign body and through the effects of the progesterone on the encometrium. The IPCS system was designed to provide maximum contraceptive protection over a 3-year period and to reduce IUD-related bleeding, pain, and expulsion problems. Results from Alza monitored trials of the IPCS in the US and Mexico indicate that the cumulative life-table pregnancy rate increased from 3.6/100 women after 25 to 30 months of use to 10.6/100 women after 30 to 36 months of use. Laboratory evaluations of removed IPCS devices indicates that after 30 months of IPCS use the release rate of progesterone may not be adequate to prevent pregnancy effectively. The World Health Organization (WHO) evaluated the IPCS in 2 multiclinic studies. Postinsertion complications and complaints for the IPCS and T Cu-200 are shown. The include cervical perforation, ectopic pregnancy, pelvic inflammatory disease, dysmenorrhea, bleeding, spotting, and pelvic pain. The IPCS seemingly offers no particular advantages for use in developing countries.