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DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT. 1989 Jan 13; 114(2):78.The Special Program of Research Development and Research Training in Human Reproduction of WHO has been supporting new and improved methods of contraception since the 1970s for about 600 million couples in reproductive age in developing countries. A new approach is the immunological influencing of fertility by vaccine. In man spermatozoa surface antigens, gonadotropin-releasing hormone (GnRH), gonadotropin, and sexual steroids serve as target antigens. In women the potential antigens are more spermatozoa surface antigens, zona-pellucida antigens, trophoblast surface antigens, and embryonal antigens as well as human chorionic gonadotropin (HCG), GnRH, gonadotropins, and sexual steroids. Most of these produced untoward side effects. The most promising is the immunization against spermatozoa surface antigens and against HCG. Anti-HCG antibodies bound to tetanus toxin carrier produced contraception in primates, but its drawback was the cross reaction of the beta chain of the HCG molecule with luteinizing hormone (LH). This was avoided by using a synthetic peptide bound to diphtheria toxin. 43 women aged 26-43, who had been sterilized, were injected with this vaccine. In all 30 women who remained in the study dose-dependent antibody levels increased to provide contraception within 6 weeks that lasted 6 months. Side effects included mild myalgia, pruritus exanthem (2 cases), plasma cortisone increase (1 case), and menstrual disorder (5 cases). Outstanding questions remain: reversibility, allergic reactions, cross reaction with other organ systems, failure at the time of implantation, or immune reaction developing during pregnancy. These will preclude their universal introduction for some time to come.
[Immunocontraception -- current research status] Immunkontrazeption -- jetziger Stand der Forschung.
GYNAKOLOGE. 1990 Jun; 23(3):178-83.In 1972, WHO advanced the idea of a safe and reversible birth control vaccine lasting 1-2 years. This contraceptive could utilize the connection of sperm antibodies and sterility by active immunization (foreign antigens) and passive immunization (monoclonal antibodies). After long experimentation, a vaccine was introduced in 1984 based on the carboxyl-terminal peptide (CTP) of the beta subunit of human chorionic gonadotropic (HCG) couples with a diphtheria toxoid (DT) and mixed with a muranyldipeptide (MDP) adjuvant called 109-145-CPT-beta- HCG:DT mixed with MDP. When given to baboons, the pregnancy rate fell to 4.6% vs. the 70% rate in untreated animals. Out of 15 women with previous tubal ligations, 14 showed production of specific antibodies: in Group A, 80 ug beta-HCG antigen was injected 4 times 2 weeks apart, while Group B received 240 ug only twice, 1 month apart. Side effects included edema, adnexal pain, DNA-antibody increase, plasmacortisone fluctuations, and liver enzyme changes. Later refinements eliminated blood chemistry changes, and injection 4 times produced specific antibody formation after 500 days. Immunization against follicle stimulating hormone (FSH) produced reversible sterility in rhesus monkeys after 4 and 1/2 years; however, the controversial role of testosterone in spermatogenesis terminated this approach. The inactivation of LDH-C4-lactatedehydrogenase produced only reduction of fertility in rabbits and baboons. However, 25 guinea pigs immunized twice, 1 month apart, with PH 20, a sperm-coating antigen, exhibited 100% infertility compared to the fact that 94% of untreated controls had a litter. Zona-pellucida antigens affected not only the egg cells but also the ovarian follicles. Among embryonal antigens, F-9-oncofetal antigens reduced fertility in mice but produced teratocarcinoma. Passive immunization by mono- and polyclonal antibodies against early- pregnancy factor terminated pregnancy in mice, suggesting another possible avenue for immunocontraception.