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Clinical and Experimental Immunology. 1978 Aug; 33(2):360-375.Since guidelines for safety evaluation of antifertility vaccines do not exist, this WHO report attempts to define the parameters to be examined and the methodology which might be used for such a safety assessment. In principle, antifertility vaccines may: 1) prevent sperm transport and/or fertilization; 2) prevent or disrupt implantation; and 3) prevent blastocyst development. Potential advantages of this immunological approach to fertility regulation include: 1) possibility of infrequent administration, possibly by paramedicals; 2) use of antigens or antigen frangments that are not pharmacologically active; and 3) the possibility of large-scale synthesis and manufacture of vaccine at relatively low cost in the case of antigens of known chemical structure. To evaluate the efficacy and safety of placental antigen vaccines, placental antigens used should not possess significant immunological similarity with tissue other than placenta. Carriers or haptens may require structural remodifications of placental molecules to overcome natural immunological tolerance. Adjuvants may be needed to enhance the immune response required. Quality-control procedures for vaccine component production include tests for: 1) purity; 2) toxicity; 3) sterility; and 4) shelf-life. Acute, subacute, and chronic toxicity testing in animals is described for it must be performed separately for the haptenated antigen or conjugate and adjuvant. Such tests would include hematological parameters, blood chemistry, urinanaylsis, gross pathological and organ weight analysis, and ophthalmological tests. Animal models are suggested. Means of monitoring the immune reponse and potential hazards of immunization (e.g., allergy or autoimmune disease) are discussed. The rationale and protocol for safety and efficacy studies of human chorionic gonadotropin-peptide vaccine receive similar attention, with emphasis on tests to be performed before human clinical trials can start.
Geneva, World Health Organization, 1966. (Technical Report Series No. 334.) 21 p.A WHO Scientific Group on Immunological Aspects of Human Reproduction met in Geneva October 4-9, 1965. Topics of discussion included: 1) immunology of human gonadotropins; 2) sperm and seminal fluid; 3) blood group antigens and human reproduction; and 4) maternal-fetal immunological interactions. It was concluded that further investigations are required to study: 1) the correlation between physiocochemical, biological, and immunological criteria for the purity of antigens concerned in human reproduction; 2) the chemical structure of hormones concerned with reproduction, with special reference to the biologically active sites and the nature of antibodies against these active sites; 3) production of antibodies to the gonadotropins by the use of adjuvants and/or chemically modified gonadotropins; 4) modification of hormones from other species to render them active but non-antigenic in man; 5) the use of immunological methods for assisting in the detection of the time of ovulation: these could aid in the control of fertility and in the treatment of infertility; 6) the development of strains of animals of high immunological competence; 7) characterization of the male antigens responsible for various immunological phenomena in males; 8) characterization of male antigens responsible for inducing circulating antibodies and reducing the fertility of immunized females; 9) the nature and biological significance of the antagglutinins; 10) possible ways of interfering with the transmission of antibodies in man; and 11) the possible occurrence of specific antitrophoblastic antibodies in pre and postpartum. Other research needs are also outlined.
VACCINE WEEKLY. 1995 May 29 - Jun 5; 9-10.A priest, president of Human Life International (HLI) based in Maryland, has asked Congress to investigate reports of women in some developing countries unknowingly receiving a tetanus vaccine laced with the anti-fertility drug human chorionic gonadotropin (hCG). If it is true, he wants Congress to publicly condemn the mass vaccinations and to cut off funding to UN agencies and other involved organizations. The natural hormone hCG is needed to maintain pregnancy. The hormone would produce antibodies against hCG to prevent pregnancy. In the fall of 1994, the Pro Life Committee of Mexico was suspicious of the protocols for the tetanus toxoid campaign because they excluded all males and children and called for multiple injections of the vaccine in only women of reproductive age. Yet, one injection provides protection for at least 10 years. The Committee had vials of the tetanus vaccine analyzed for hCG. It informed HLI about the tetanus toxoid vaccine. HLI then told its World Council members and HLI affiliates in more than 60 countries. Similar tetanus vaccines laced with hCG have been uncovered in the Philippines and in Nicaragua. In addition to the World Health Organization (WHO), other organizations involved in the development of an anti-fertility vaccine using hCG include the UN Population Fund, the UN Development Programme, the World Bank, the Population Council, the Rockefeller Foundation, the US National Institute of Child Health and Human Development, the All India Institute of Medical Sciences, and Uppsala, Helsinki, and Ohio State universities. The priest objects that, if indeed the purpose of the mass vaccinations is to prevent pregnancies, women are uninformed, unsuspecting, and unconsenting victims.
Functional and immunological relevance of the COOH-terminal extension of human chorionic gonadotropin Beta: implications for the WHO birth control vaccine.
FASEB JOURNAL. 1993 Nov; 7(14):1381-5.The WHO Task Force on Birth Control Vaccines has selected the pregnancy hormone human chorionic gonadotropin (hCG) and a target molecule for a contraceptive vaccine. A synthetic peptide antigen corresponding to the amino acid sequence 109-145 of the carboxyl-terminal portion of the hCGbetaCTP, which is supposed to elicit hCG-immunoneutralizing antibodies, has been submitted to clinical trials. Recent findings suggest that hCGbetaCTP does not play a role in the biological activity of hCG. This raises the question concerning the assumed mechanism of action of the hCGbetaCTP-based birth control vaccine. The authors therefore investigated the immunoneutralizing capacity of antibodies directed against hCGbetaCTP. Although it is possible to generate specific monoclonal and polyclonal antibodies for hCG by using hCGbetaCTP as an immunogen, it appeared that the biological response to hCG was not affected by such antibodies. The reason for this is that the hCG-antibody-complex is still able to bind to target cell receptors and therefore the intended contraceptive effect should not occur. In addition, there is a risk of hazardous possible side effects such as an autoimmune reaction against the ovary because the authors found that at least 1 epitope is still accessible for antibody binding on receptor-bound hCG. They conclude from their results that both the efficacy and safety of the WHO vaccine are not yet ensured. (author's)
WORLD HEALTH FORUM. 1993; 14(1):90-1.The WHO Special Program of Research, Development, and Research Training in Human Reproduction has developed a prototype antifertility vaccine. The vaccine is directed against human chorionic gonadotrophin (hCG) and consists of a conjugate immunogen, formed from a synthetic fragment of the beta subunit of hCG joined to diphtheria toxoid and mixed with an immunostimulant. After 4 years of extensive preclinical safety and efficacy studies, the Program conducted a Phase I clinical trial between 1986 and 1988, using the vaccine in sterilized women to assess its safety. Teratology studies were carried out in rats and rabbits in case it failed to prevent pregnancy; the results showed that the WHO prototype vaccine had no adverse effects either on the pregnant animals or on the fetuses. The Program is now planning to conduct Phase II clinical trials to assess the effectiveness of the vaccine. The studies done so far have shown that the prototype anti-hCG vaccine is well tolerated, safe, and immunogenic in humans, but this version requires at least 2 injections, at an interval of several weeks, to elicit an anti-hCG immune response lasting for 3-6 months. Therefore, the Program has been developing an advanced prototype vaccine designed to elicit effective levels of immunity which will last for 12-18 months following a single injection. The advanced prototype anti-hCG vaccine consists of the same immunogen conjugate and immunostimulant used in the prototype version, but they are incorporated into a polymer designed to release the vaccine slowly over an extended and predetermined period of time. Dose-response and toxicity studies are currently under way in rabbits and baboons to determine the optimal dose of the vaccine and to see if this vaccine is safe for testing in humans.
BRITISH MEDICAL BULLETIN. 1993 Jan; 49(1):88-99.The 3 primary candidates for the development of a contraceptive vaccine are: a) human chorionic gonadotropin (hCG), b) the zona pellucida, and c) the sperm surface. The most advanced approach involves the induction of immunity against hCG. Completed Phase I clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. Phase 2 studies are about to commence. Vaccines are being engineered based on conjugates which incorporate tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centered on the beta-subunit of this molecule. However, the longterm safety of efficacy of such immunity is unknown. The remaining 2 vaccine development approaches aim to prevent conception by interfering with the interactive events that characterize the union of male and female gametes of fertilization. The zona glycoprotein, ZP3, is a prime candidate for such a vaccine, in the view of its important role in the recognition and activation of spermatozoa and its unique antigenic composition. A major problem with this approach involves the loss of primordial follicles observed in the many in vivo studies in which active immunity against this protein has been induced. The possibility that this problem can be overcome by identifying B-cell epitopes that will avoid the T-cell responses thought to be responsible for the appearance of ovarian dysfunction is now being actively investigated. Disruption of fertilization through the induction of immunity against sperm surface antigens is a third approach, for which there is clinical support as patients have exhibited infertility associated with the appearance of spontaneous immunity against sperm antigens. Potential targets are constrained by considerations of immunogenicity, specificity, antigen density, and location.
PROGRESS IN HUMAN REPRODUCTION RESEARCH. 1992; (22):4-5.During 1986-1988, the WHO Special Programme of Research, Development and Research Training in Human Reproduction used the diphtheria toxoid as a carrier for a fragment of the human chorionic gonadotropin (hCG) molecule (a conjugate immunogen) and an immunostimulant in a phase I clinical trial of this prototype antifertility vaccine in sterilized women. Between 1990 and 1991, it conducted teratology studies in rats and rabbits to determine whether the vaccine causes fetal abnormalities. The vaccine did not adversely affect either the animals or their fetuses. Clinical trials of the vaccine's effectiveness (phase II trials) are scheduled for 1992. At least 2 injections several weeks apart, are needed to produce an anti-hCG immune response which is only effective for 3-6 months, however. So the same components of the original vaccine were placed in a polymer to deliver the vaccine slowly over a prolonged and predetermined time frame. WHO hoped that this advanced vaccine would raise effective immunity levels long enough to last for at least 1 year after 1 injection. WHO is conducting dose-response and toxicity studies of this prototype vaccine in rabbits and baboons to identify the optimal dose which would elicit an effective immunity level over a desired period of time and would be safe for testing in humans. WHO hopes to begin a phase I clinical trial with this advanced anti-hCG vaccine in late 1992. WHO anticipates that the preclinical and clinical trials will reveal a need for further modifications and improvements. WHO is supported multicenter research on antitrophoblast vaccines which target membrane cells of the preimplantation embryo since 1985. It uses monoclonal antibodies (MABs) and recombinant DNA technology to identify and isolate surface molecules. So far this research has tested 15,000 MABs but is centering on 9 MAbs. A study in baboons showed that 1 MAB reduced fertility, even though researchers could only use minute amounts of the protein in the injection.
In: Vaccines for fertility regulation: the assessment of their safety and efficacy. Proceedings of a Symposium on Assessing the Safety and Efficacy of Vaccines to Regulate Fertility, convened by the WHO Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, June 1989, edited by G.L. Ada, P.D. Griffin. Cambridge, England, Cambridge University Press, 1991. 5-11. (Scientific Basis of Fertility Regulation)The predecessor of the WHO Task Force on Vaccines for Fertility Regulation chose to commit most of its resources to research and development of a vaccine directed against human chorionic gonadotropin (hCG). Task force members made this choice in 1978 because scientists tended to already know the amino acid sequence and general structure of hCG and a vaccine against hCG would prevent implantation of the fertilized ovum. Specifically they focused on the unique sequence of C-terminal 37 amino acid peptide of the beta chain of hCG because this method would not allow production of antibodies cross reacting with human luteinizing hormone and would reduce the risk of autoimmune pathology and other effects of cross reactivity of antibodies. They also defined the various parameters and the methodology to assess the safety of the approach which still is a useful guide to development of hCG and other antifertility vaccines. The Task Force strongly recommended that target antigens should be temporary and in relatively low amounts and limited to gametes and/or early products of fertilization. A Phase I clinical trial in sterilized women has already been conducted and a limited efficacy trial in fertile women is planned. In June 1989, WHO hosted a symposium in Geneva, Switzerland to review the safety and efficacy of antifertility vaccines based on past and current research and development. This symposium focused much attention on immunological and endocrine considerations. WHO forecasted that recommendations coming from the symposium would not only guide future research on vaccines against self-antigens but maybe even antitumor vaccines.
In: Vaccines for fertility regulation: the assessment of their safety and efficacy. Proceedings of a Symposium on Assessing the Safety and Efficacy of Vaccines to Regulate Fertility, convened by the WHO Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, June 1989, edited by G.L. Ada, P.D. Griffin. Cambridge, England, Cambridge University Press, 1991. 247-50. (Scientific Basis of Fertility Regulation)The 3 human chorionic gonadotropin (hCG) vaccines have shown the most potential for stimulating antibody production, but clinical trials have not yet tested for fertility reduction. Antifertility vaccine research began 20 years ago and it has taken this long to et this far because investigators have had to deal with the interaction of 2 complex systems--the immune system and the endocrine system. An example of this complexity is that no one understands why exogenous whole hCG does not induce a booster effect in hCG immunized women. Antifertility vaccines require much more effort than conventional antidisease vaccines because they will probably be used more often and more extensively than other vaccines. WHO should coordinate the trials of the 3 different vaccines to assure that researchers can designate the optimum preparation for particular cases. Other research indicates that cells and cell products may be vaccine candidates. Researchers may even try immunizing against other hormones beside hCG, gametes or their products, or the trophoblast. They may soon develop a T-cell vaccine which would be against the trophoblast. They speculate that eventually a composite vaccine will emerge which would have several targets therefore providing effective contraception and minimizing the immunological activity needed from each individual component. Biotechnology has allowed researchers to screen for many proteins such as those on the surface of spermatozoa which it can produce in great numbers. It may even be able to also screen for and manufacture carbohydrates making the zona pellucida to be a vaccine target. Potential areas of conflict once a vaccine is available are issues of ethics, national priorities, foreseeable abuse, and balance between individual rights and needs of future generations. Already contrasting points of view exist about an antifertility vaccine. Nevertheless the gravity of the demographic crisis calls for effective family planning technologies.
The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.
HUMAN REPRODUCTION. 1991 Jan; 6(1):166-72.The WHO Task Force on Vaccines for Fertility Regulation is one of several Task Forces, consisting of international, multidisciplinary groups of scientists and clinicians collaborating in research on specific goals, established in 1972. Its accomplishments are reviewed here. The Task Force convened a meeting in 1974 to select criteria for tissues and molecules capable of mounting antifertility responses. These molecules had to be restricted to the target tissue, sequestered in the reproductive tract, present transiently, and chemically characterized. Some of the antigens considered were sperm enzymes and membranes, as well as a data bank of sera naturally immunized against sperm. Other were anti-ovum and placenta molecules such as zona pellucida, the SP-1 placental antigen, and the placental hormones chorionic somatotrophin and human chorionic gonadotropin (hCH). Trophoblast-derived monoclonal antibodies and gene libraries are being screened. Anti-hCH is the vaccine composed of a portion of the beta subunit complexed to a carrier antigen, diphtheria toxoid, in a water- oil emulsion with an adjuvant has been tested in a phase I clinical trial in 1986-1988. A Phase II trial is being planned to see if the immune response in women is large enough to be capable of preventing pregnancy. Further improvements in the vaccine are being envisioned, such as incorporation of the peptide carrier conjugate and immune stimulant into biodegradable microspheres, hopefully to produce a longer-lasting immunity and a more stable vaccine. While the WHO Task Force on Vaccines for Fertility Regulation has been forced to cut back on some avenues of research, its success has stimulated other centers to take up several important projects, e.g. the sperm LDH and zona pellucida vaccines.
INDIAN JOURNAL OF EXPERIMENTAL BIOLOGY. 1988 Apr; 26(4):243-51.A comprehensive review of the immunobiology of human chorionic gonadotropin (hCG), including the structure of both alpha and beta chains, immunogenicity of various segments and epitopes of each, secretion and function of the hormone, determinants of receptor recognition, and finally, clinical studies of possible contraceptive beta-hCG-based vaccines, is presented. hCG is composed of 2 glycosylated peptides. The alpha subunit is identical to that found in hLH, hFSH and hTSH. The beta subunit, which is limiting in the sense that it is secreted in smaller amounts, defines the biological activity of hCG. hCG is secreted throughout pregnancy from 170 hours after fertilization to a peak at 8-10 weeks of and is essential for maintenance of early pregnancy by progesterone secreted by the corpus luteum. Although native hCG evokes antibodies, they cross react with LH, so such a vaccine would not be useful for contraception. Beta-hCG has been purified and also produced by monoclonal antibodies, and shown to produce antibodies and infertility in baboons. Phase I clinical trials of immunologically purified beta-hCG complexed to tetanus toxoid were conducted on 63 women in an international study in the mid-1970s, but results were mixed in terms of antibody titer and duration. New vaccines have been designed based on more sophisticated adjuvants, beta- hCG-terminal peptides, and polyvalent vaccines and are being tested in 4 Phase I trials currently, sponsored by the Population Council, the Indian government-sponsored program, and the WHO.
NATURE. 1985 Sep 26 - Oct 2; 317(6035):288-9.A fertility-regulating vaccine could provide an efficient, safe, and inexpensive contraceptive method. The antigens selected for such vaccines must be present transiently and in low amounts relative to the predicted antibody response, specific, chemically well characterized to facilitate manufacture, and restricted to gametes or the early products of fertilization. To be acceptable, the vaccine should have an efficacy rate of at least 90%. Over the past decade, the World Health Organization (WHO) has sponsored research on the development of a vaccine based on a polypeptide of the beta subunit of human chorionic gonadotropin (hCG). A prototype vaccine on which preclinical toxicity and safety evaluations have been completed is now ready for clinical testing. WHO plans to carry out a clinical trial to assess the immunologic efficacy and safety of the vaccine as soon as approval from regulatory agencies has been obtained. Significant progress has also been made in the search for other vaccine candidates. Sperm antigens comprise one such possibility for both males and females. Of the sperm antigens identified to date, only lactate dehydrogenase (LDH-4) has been well defined. Immunization with well characterized zona pellucida antigens can inhibit fertility in many species; however, there is an unacceptable alteration in ovarian function. Trophoblast surface antigens have the advantage of being expressed at only 1 anatomic site after fertilization and of being in intimate contact with maternal blood at a very early stage of pregnancy. The search for an appropriate iso-immunogen has been facilitated by the use of recombinant DNA technology and other techniques of molecular biology.
Bulletin of the World Health Organization. 1978; 56(2):179-192.Strong evidence that specific immunogenic components of the reproductive system exist that are not represented in other body systems has led to efforts to develop an acceptable vaccine for fertility regulation. The aim is to create a vaccine administered infrequently by trained technicians outside the clinical environment. For safety and practical reasons, an approach using active immunization with a vaccine is preferred to passive immunization with antibodies. In current research with sperm antigens, a lactate dehydrogenase isoenzyme (LDH-X), an enzyme normally present on the sperm surface, reduced fertility in mice and rabbits. However, significant embryo mortality occurred. Other sperm antigens have been tested and rejected. Most of the research on ovum antigens is directed toward the zona pellucida, and work is in progress to isolate experimental quantities of specific zona pellucida antigens. Antibodies to human zona are reported to react with pig zona and vice versa, providing a model system. Antibodies to whole-placenta homogenates reportedly disrupt pregnancy in several laboratory animal species, and 2 placenta-specific proteins are potential antigens since antibodies to them do not react with any other tissue so far tested. Of 3 protein hormones isolated from placental tissue, 2 are potential antigens. The possible hazards of antifertility vaccines can be divided into 2 categories: problems related to immunization and problems caused by antibodies produced.
British Medical Bulletin. 1979 May; 35(2):199-204.Contraceptive research and development is primarily performed at universities and research councils due to the cost and time involved for industry and philanthropic organizations to bring drugs to market. Promising fundamental research includes immunization of women against chorionic gonadotrophin in order to disrupt the embryo in early pregnancy. Post-coital drugs, such as Anordrin, are also being developed for situations involving low-coital frequency. Once-a-month formulas are being developed to 1) exert a direct luteolytic effect on the corpus luteum; 2) interfere with the luteotrophic action of the implanting blastocyst; 3) inhibit the progestational development of the endometrium during the luteal phase of the cycle; or 4) exert a specific toxic effect on the early embryo. Methods for detecting ovulation incuding urine and saliva tests as well as electronic devices to measure the blood flow or temperature associated with ovulation are also being explored. Reversible fertility control for men which suppress the pituitary function is under investigation. Applied research includes the design and assessment of alternate delivery systems such as intranasal sprays, intracervical devices, paper pills, vaginal rings, and biodegradable subdermal implants. In addition, long-acting injectable progestins, improved IUDs, and improved sterilization techniques are all being tested. With future funds, the comparative safety, efficacy, and acceptability of various fertility methods can be established.
Design of studies for the assessment of drugs and hormones used in the treatment of endocrine forms of female infertility.
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagen, Denmark, Scriptor, 1977. p. 135-154The lack of uniformity in diagnostic selection of women for treatment of infertility, in choice of therapy, in monitoring of therapy, and in follow-up, frequently does not allow a meaningful comparison of results reported from different centers. To design studies assessing effectiveness of therapy of endocrine forms of female infertility, it is essential to consider: 1) mechanism controlling reproductive functions (e.g., process of ovulation); 2) cause(s) responsible for infertility (mechanical factors, ovarian failure, and pituitary failure); and 3) the mechanism of action of agents used for therapy (e.g., gonadotropins stimulate gonadal function, clomiphene stimulates gonadotropin secretion, and ergoline derivatives inhibit prolactin secretion). Patients selected for therapy should be grouped according to etiology: 1) hypothalamic-pituitary failure; 2) hypothalamic-pituitary dysfunction; 3) ovarian failure; 4) congenital or acquired genital tract disorder; 5) hyperprolactinemic patients with a space-occupying lesion in the hypothalamic-pituitary region; 6) hyperprolactinemic patients with no space-occupying lesion; and 7) amenorrheic women with space-occupying lesion. Ideally, an infertile couple should be diagnosed and treated as a unit.
CRP Population Research. 1978 Nov; 33-34.The Contraceptive Development Branch (CDB) program conducts research in 2 areas: 1) reproductive processes and 2) product development. Research on reproductive processes improved the understanding of gamete transport and has better identified corpus luteum functions and the role of prostaglandins. The biology and biochemistry of the ovum has been studied, and in vitro fertilization investigated. The mechanism of spermatogenesis, sperm maturation, and subsequent fertilization have been observed. Moreover, CDB has participated in the distribution of a variety of reagents to the scientific community, to stimulate research on the antipregnancy vaccine. In the area of product development, the CDB continues experimenting with the synthesis of new chemicals to regulate human fertility, the issue of safety being the primary motivation of the program. Approximately 1100 new chemicals have been synthesized and tested on laboratory animals. A drug testing program was initiated in 1972, providing feedback of biological data, and representing the major drug testing effort in the U.S. Considerable progress has been made in the area of implantable and oral contraceptives, and in the area of devices for fertility regulation, and for sexual sterilization. Clinical studies sponsored by CDB are ongoing.
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagan, Denmark, Scriptor, 1977. p. 21-71This chapter reviews the hormonal changes which occur during the menstrual cycle. During the last days of the preceeding menstrual cycle, plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) increase. Follicular phase is characterized by gradually increasing estrogens. A few days preceding the LH surge, some little understood changes in estradiol, LH, and 17-hydroxyprogesterone, on one hand, and ACTH, cortisol, and aldosterone, on the other, occur. Evidence indicates that the estradiol peak occurs first, followed by a simultaneous rise and fall in LH and 17-hydroxyprogesterone values. The peak period of LH is about 32-44 hours long, during which time a rise in progesterone levels takes place. Other pituitary and steroid hormones (human chorionic gonadotropin, ACTH, prolactin, testosterine, androstenedione, cortisol, and aldosterone) show elevated levels during the periovulatory period. Ovulation occurs 16-48 hours after LH peak. The period following LH surge is characterized by rapidly increasing levels of progesterone, 17-hydroxyprogesterone, and 20-alpha-dihydroprogesterone, accompanied by moderately increasing estrogen levels to form the typical luteal-phase hormonal pattern. A luteal increase occurs also in levels of several other hormones, ranging from renin activity to angiotension, or from pregninolone to aldosterone. The last part of the luteal phase is characterized by rapidly declining levels of peripheral hormones. The perimenstrual phase around onset of heavy bleeding is characterized by gradually decreasing levels of progesterone, 20-alpha-hydroprogesterone, estradiol, and testosterone, associated with an incipient rise in LH and FSH levels.
In: World Health Organization (WHO). World Health Organization expanded programme of research, development, and research training in human reproduction: fourth annual report. Geneva, Switzerland, WHO, November 1975. 51-5. (HRP/75.3)2 years ago an exploratory program of possible vaccines for birth control was initiated. The approach is totally new and it is impossible to predict the outcome. Research on placental antigens has focused on the beta subunit of human chorionic gonadotropin (HCG), a placental-specific protein called SP1, a placental-specific glycoprotein called PP5, and several protein conjugates and adjuvants which use the beta chain of insulin with carrier proteins to synthesize beta-HCG. Details of this research are given. Considerable data suggest that antibodies to several substances in spermatozoa may immobilize, agglutinate, or destroy their biological activity. Sperm enzyme antigens being investigated include lactic dehydrogenase-X, hyaluronidase, and acrosin. These are given to the female; tests have shown fertility reductions up to 50%. Sperm membrane antigens are difficult to isolate but may be more suitable immunogens since they are membrane bound and would not have the problems of circulating immune complexes or nonspecific tissue cross-reactivity. These include "T" and "S" antigens, sperm immobilizing antigen, and carbohydrate antigens. Various antigen/carrier/adjuvant combinations will also be evaluated. Zona pellucida antigens are another research target, especially zone surface antigens. A workshop was organized to consider the production of local immunity in the female genital tract. Since infertility in humans attributed to immunological factors may hold useful information, a bank of sera from infertile men and women has been established in Arhus, Denmark. A symposium on immunological methods of fertility regulation was held in Bulgaria and the papers published as a monograph.