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Geneva, WHO, 1973. (WHO Technical Report Series No. 520) 34 p.After summarizing current WHO research directed at the control of male fertility focusing on 1) gametogenesis and ultrastructure of the testis; 2) cytogenetic aspects; 3) hormonal regulation; 4) epididymal function (the maturation and preservation of spermatozoa); 5) vas deferens; and 6) semen analysis; recommendations for further research in the area are made. Studies are required on the following aspects of reproductive function in the male: 1) structural and cytochemical organization of the various classes of germ cells in humans and nonhuman primates; 2) interstitial tissues and the components of the blood-testis barrier and their role in the regulation of gametogenic function of the testis; 3) structural and functional state of the testis during growth and development, during aging, and in most histopathological conditions leading to partial or complete sterility; 4) the role of meiotic chromosome aberration in degeneration of germ cells; 5) role of abnormal chromosomes as an etiological factor in male infertility; 6) binding and metabolism of androgens and their effects on the seminiferous tubule; 7) role of gonadotropins, particularly follicle stimulating hormone (FSH), in regulation of spermatogenesis; 8) identification of tubular factors involved in regulation of FSH secretion; 9) elucidation of epididymal function in a number of species; 10) characteristics of sperm surface; 11) nature of epididymal plasma and the factors that control it; 12) anatomy, physiology, and functional role of human vas deferens, with emphasis on blood supply; 13) effect of vasectomy on male reproductive function and possible immunological sequelae of this operation; 14) relationship between fertility and such characteristics of sperm as number, motility, and morphology; 15) biochemical characteristics of the nucleus, acrosome, and midpiece of sperm, and their relationship to sperm motility and fertility; 16) chemical nature of substances secreted specifically in different accessory sex organs; 17) the possible relationship between autoimmune phenomenoa and testicular disease; and 18) immunological sequelae of vasectomy. In addition, studies on the cryobiology of human and animal sperm are expected to yield information on the biology of sperm.
Geneva, Switzerland, WHO, 1965. 19 p. (WHO Technical Report Series No. 304)This WHO technical report focuses on the 1) psychosomatic factors in human reproduction; 2) hypothalamo-hypophyseal system; 3) mechanism of sexual rhythm; 4) nervous influences on the hypothalamus; 5) hormonal influences on the hypothalamus; 6) neuroendocrine aspects of sexual behavior; and 7) effects of drugs on reproduction. After summarizing current research status on the above-mentioned topics, the following research needs are suggested: 1) assays of individual human endogenous gonadotropins, suitable for clinical application; 2) autoradiography, fluorescent-antibody, spectrophometric interference and histochemical and biochemical techniques for studying cells that supply axons to the primary capillary plexus of the hypophyseal portal system and for studying effects of different hormonal status on hypothalmic structure and function; 3) computer techniques for evaluating electrophysiological data; 4) improved lesioning techniques; 5) comparative studies of reproductive activity patterns, exteroceptive factors, neuroendocrine factors in sexual and related social behavior, and long-term or delayed effects of drugs administered during gestation on subsequent sexual development; 6) studies of synaptic connections of hypothalamic neurones; 7) studies of endogenous gonadal and gonadotropin production in prepuberal animals; 8) functional significance of regional distribution of hypophyseal portal system; 9) mechanisms involved in selective uptake of labeled hormones; 10) hypothalamic lesions in species with spontaneous ovulation and active luteal function; 11) direct effect of gonadal hormones on single hypothalamic neurones studied with combination of microinjection and unit recording devices; 12) studies of the possibility of a direct feedback of gonadotropic hormones on the hypothalamus; 13) studies of the receptor mechanisms involved in neuroendocrine reflexes; 14) wider exploration of brain structures, with regard to feedback action of gonadal hormones; 15) studies of pineal function; 16) further investigation of a possible role of the peripheral autonomic pathways in reproductive processes; and 17) research on the application of tissue culture techniques for studying problems of the origin and metabolic effects of neurohormonal mediators and the biochemcial and morphological changes induced by sex hormones.
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.
Social Science and Medicine. 1995 Sep; 41(5):657-71.One aim of providing fertility-regulating vaccines is to prevent pregnancy in an individual by inducing reversible contraception. The recipient population of both types of vaccines can be children and adults. The biological bases and immunological targets of traditional vaccines mean that immunity can be antibody-mediated and cell-mediated. Fertility-regulating vaccines are directed against the immunologically accessible molecules involved in reproduction. These may be molecules on the surface of mature gametes (sperm and ova), or the hormones involved in the reproductive process. Several anti-gamete vaccines under development generate immune responses that react directly on intact, mature sperm and ova. The prototype anti-hormone vaccines are of two basic types, those against the hormones necessary for maturation and release of gametes and those against a placental hormone necessary to maintain the early stages of pregnancy. Pituitary and hypothalamic hormones consist of follicle-stimulating hormone and luteinizing hormone. Among placental hormones the most advanced contraceptive vaccines are those against human chorionic gonadotropin (hCG). Three prototype hCG vaccines have undergone limited clinical trials in women. Various perspectives concern developers and users. Since its inception in 1972, the WHO's Special Program of Research, Development and Research Training in Human Reproduction has played a central role in the development of contraceptive vaccines. The perspectives of women, as potential users, tend toward consideration of disadvantages, in contrast to the generally positive perspectives offered by the developers. With regard to the state vs. the rights of the individual, the topics include: restricted access to methods of contraception and to abortion; incentives or outright coercion as a means of imposing birth control; and the issues of parenthood, and individual and state responsibility raised by reproductive technologies.
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: 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. 72-87.Recent evidence has shown that spermatogenesis and steroidogenesis are not independent testicular functions, but rather represent a feedback mechanism. Spermatogenesis in mammals can be divided into 3 stages: 1) mitotic replication of stem cells, the spermatogonia; 2) the meiotic process involving primary and secondary spermatocytes; and 3) spermiogenesis--a complex series of cytological changes resulting in transition of conventional cell into a spermatozoon. These cytological changes include 1) elaboration of the acrosomal cap by the Golgi complex; 2) change in nuclear position from central to eccentric; 3) formation of axial filament and its associated organelles from Golgi-adjacent centrioles; and 4) rearrangement of the cytoplasm of spermatids toward the abaacrosomal pole of the spermatid. The kinetics of spermatogenesis show a biological constant for most species in duration of time for conversion from spermatogonia to sperm (64 days in humans). It is generally agreed that luteinizing hormone and follicle stimulating hormone are required for initiation of spermatogenesis at puberty in humans and rats, though controversy exists over whether both hormones are necessary for maintenance. The action of increasing doses of testosterone in suppressing and then stimulating spermatogenesis suggests that a high local concentration of testosterone is required for the spermatogenic process. Evidence supports high androgen concentration within the seminiferous tubules, but its entry route is still speculative. Relationship of Sertoli cell to spermatogenesis and hormonal interrelationship between the testis and hypothalamo-hypophyseal unit are discussed. Sperm maturation is attributed to: 1) inherent ability of sperm to mature, and 2) specialized environment of the epididymis.
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.
Cyproterone acetate (CPA) a potential male contraceptive: further studies on the interactions with endocrine parameters.
Berlin, Germany, WHO-CCCR, . 11 p.This unpublished paper is the transcript of a conference proceeding, but the figures referred to textually are not included in the document. This study evaluated the effects of medium dose cyproterone acetate (CPA), 10-30 mg/day, on gonadotropin and peripheral androgen levels. On the average, luteinizing hormone (LH) concentrations were about 35% lower during CPA administration; similar observations were made for follicle stimulating hormone (FSH). CPA medication resulted in a significant reduction of LH response to LH-releasing hormone (RH); FSH increments following LH-RH stimulation were considerably smaller than those of LH and were hardly distinguishable from spontaneous FSH fluctuations. LH-RH double stimulation resulted in a slow but continuous rise of T without distinct peaks of borderline significance. CPA administration caused a highly significant elevation of serum prolactin in 7/10 males. In summary, medium dose CPA exerted the following effects on the hypothalamo-pituitary-testicular axis during the 1st 12 weeks of administration: 1) suppression of basal LH, FSH, T, and dihydroT; 2) abolition of the spiking phenomenon of androgen secretion; 3) suppression of LH-RH mediated secretion of LH and FSH; and 4) elevation of basal prolactin.
In: Sciarra, J.J., Markland, C. and Speidel, J.J., eds. Control of male fertility. (Proceedings of a Workshop on the Control of Male Fertility, San Francisco, June 19-21, 1974). Hagerstown, Maryland, Harper and Row, 1975. p. 274-307Literature on research approaches to permanent and relatively reversible methods of male fertility control is reviewed. Sources and expenditures for research into male fertility control are noted. Permanent methods discussed include electrocautery of the vas, transcutaneous interruption of the vas, vasectomy clips, chemical occlusion of the vas, and passive immunization. Reversible methods reviewed include vasovasotomy, intravasal plugs, and vas valves. Current research into animal models, reversibility after vas occlusion, nonocclusive surgical techniques, pharmacological alteration of male reproductive function, including adrenergic blocking agents, steroidal compounds, inhibitors of gonadotropin secretion, clomiphene citrate, organosiloxanes, prostaglandins, alpha-chlorohydrin, heterocyclic agents, and alkylating agents, and delivery systems for antifertility agents is discussed. Research into semen storage and improved condoms is also reviewed. As a relatively low proportion of funds are committed to research in male fertility control, a greater investment in applied and clinical research is warranted.