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  1. 1
    310566

    WHO grade "a" sperm motility and zona pellucida-binding test predict IVF outcome [letter] [reply]

    Sifer C; Poncelet C; Porcher R; Wolf JP

    Human Reproduction. 2007 Jan; 22(1):311-312.

    We thank Professor Evers for his interest in our preliminary work. We agree that a positive likelihood ratio (LR+) of 1.67 will change the likelihood of disease in a clinically not very relevant way. Indeed, we have moderated our purpose saying that an LR+ of 1.67 indicated a small impact on the post-test probability of successful IVF. However, this change was statistically significant as our study showed. Thus, we believe that in the lack of other predictive tests that could be performed routinely, this new combined test is helpful to decrease the risk of fertilization failure during IVF therapy in the case of unexplained infertility. Concerning male factor, we have found an LR+ of 6.0, which indicated a better, though moderate, post-test impact, as we have said in our study and accordingly to Professor Evers' letter. However, we effectively did not include the 95% confidence interval (CI) of this LR in our study, and we agree that this could lead to misinterpretation. We thought that this CI is calculated using an approximate formula, which could not be considered as valid on such a small sample. (excerpt)
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  2. 2
    310565

    WHO grade "a" sperm motility and zona pellucida-binding test predict IVF outcome [letter]

    Evers JL

    Human Reproduction. 2007 Jan; 22(1):311.

    I have read with great interest the article by Sifer et al. (2005) on the combination of a newly developed sperm-zona pellucida-binding assay and WHO grade 'a' sperm motility to predict sperm fertilizing ability in IVF. The authors have to be commended for developing a--theoretically very appealing--new sperm function test, and it is easy to understand how they could get carried away by their enthusiasm about the clinical applicability of this new test. In fact, the authors are so positive about the results of their combination test that they consider it 'an excellent predictor of sperm fertilizing potential in cases of mild male-factor infertility', and they recommend that it 'should be incorporated as a functional test to direct patients to IVF or ICSI at their first attempt'. They continue by stating that 'the positive LR of 1.67 (95% CI 1.07-2.59) allowed us to use this test in these cases' (i.e. in patients with unexplained infertility). (excerpt)
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  3. 3
    736034

    Reproductive function in the human male.

    World Health Organization [WHO]. Scientific Group

    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.
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  4. 4
    660150

    Immunological aspects of human reproduction: report of a WHO Scientific Group.

    WHO SCIENTIFIC GROUP

    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.
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  5. 5
    640030

    Biology of human reproduction.

    WHO SCIENTIFIC GROUP

    Geneva, World Health Organization, 1964. (Technical Report Series No. 280.) 30 p.

    A WHO Scientific Group on the Biology of Human Reproduction was convened in Geneva from April 2-8, 1963, for the purpose of advising the Director-General on developments and major research needs in that field. The biology of human reproduction is an extremely broad scientific topic, which impinges to some degree on virtually all the basic medical disciplines. Major topics included in the report are: 1) comparative aspects of reproduction; 2) neuroendocrine aspects of reproduction; 3) biology of the gonads and gametes; 4) gestation; 5) biochemistry of the sex steroids; 6) immunological aspects of reproduction; and 7) pharmacological aspects of reproduction. The Group recommends: 1) that WHO assist in the development of fundamental knowledge of the biology of human reproduction and of other fields on which that knowledge is based and 2) that WHO convene meetings of appropriate specialist groups to consider practical methods of implementing certain proposals concerning organization of surveys, provision of services, and promotion of relevant research.
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  6. 6
    083775

    WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 3rd ed.

    World Health Organization [WHO]. Special Programme of Research, Development and Research Training in Human Reproduction

    Cambridge, England, Cambridge University Press, 1992. viii, 107 p.

    In 1992, WHO's special program of research, development and research training in human reproduction updated its laboratory manual for the examination of human semen and sperm-cervical mucus interaction because the field of andrology continues to progress quickly and there is heightened realization of the need for standardized measurement of all semen variables. This manual is designed to mainly serve the needs of researchers and clinicians in developing countries. Chapter 2 addresses laboratory procedures that are minimal essential steps for semen evaluation, optional procedures, and procedures needing additional evaluation, such as computer-aided sperm analysis used to measure sperm motion (i.e., research tools). The Shorr stain has replaced the Papanicolaou stain. Measurements of acid phosphatase and neutral alpha-glucosidase were added, while the measurement of adenosine triphosphatase was excluded. Few changes between the 2nd and 3rd editions occurred in Chapter 3. Chapters 4 and 5 are rather brief but discuss interlaboratory and technical standardization procedures. New appendices present safety guidelines and basic requirements for the andrology laboratory.
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  7. 7
    082842
    Peer Reviewed

    Contraceptive vaccines.

    Aitken RJ; Paterson M; Koothan PT

    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.
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  8. 8
    077662

    WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed.

    World Health Organization [WHO]. Special Programme of Research, Development and Research Training in Human Reproduction

    Cambridge, England, Cambridge University Press, 1987. [7], 67 p.

    The WHO Special Programme of Research, Development and Research Training in Human Reproduction has revised its manual designed to standardize procedures for the examination of human semen. This revised manual, for instance, describes a simplified method for screening the morphology of cellular elements other than spermatozoa; the previous method now appears in the section on optional procedures. WHO has also included methods to determine the presence of spermatozoa antibodies. The manual has guidelines on measurement of biochemical components of seminal plasma to evaluate the secretory function of accessory glands (e.g., fructose indicates secretory function of the seminal vesicles). Even though these biochemical tests may not mark a man's fertility, they demonstrate the functional state of these glands. Besides, someday they may even help assess the possible effects of xenobiotic factors and of disease. Some researchers believe adenosine triphosphate levels are linked to spermatozoal function and that the zona free hamster oocyte test can determine the ability of human spermatozoa to join with the oocyte; so WHO has listed protocols for these 2 tests. The manual also has protocols to assess the ability of spermatozoa to penetrate cervical mucus in vitro: the microscopic method and the capillary tube test. WHO believes that determining this ability is important when evaluating the fertility of a couple. The Standard Procedures section on collection and examination of human semen considers appearance, volume, consistency, pH, motility, preparation and grading, agglutination, sperm viability, sperm count, and testing for antibody-coating of spermatozoa. The section on sperm cervical mucus interaction examines volume, consistency, ferning, spinnbarkeit, cellularity, pH, and in vivo and in vitro tests. It hopes that researchers will adapt the standard procedures presented in this manual to improve quality control between laboratories and allow aggregation of data from several sources for analysis.
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  9. 9
    067857

    The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.

    Griffin PD

    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.
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  10. 10
    049081

    Male pill: some reasons for cautious optimism.

    PROGRESS. 1988; (5):1, 6.

    Despite more than a decade of intense research effort, no acceptable antifertility drug for men has been produced. No drug regimen has been able to completely suppress sperm in the ejaculate, and some men who have achieved azoospermia show a spontaneous return of sperm in the ejaculate. On the other hand, there is some evidence that the residual sperm produced by men whose sperm production is only partially suppressed are incapable of fertilizing ova. Preliminary results of research conducted by the World Health Organization's Special Program of Research, Development, and Research Training in Hum Reproduction indicate that an androgenic steroid administered in 200-mg doses at 21-day intervals induces azoospermia in 65% of male volunteers, moderately low levels of sperm in 11%, and severely low levels of sperm in 24%. Also encouraging is the finding that residual sperm in men who reach severely low levels of sperm production after treatment with depot-medroxyprogesterone acetate plus testosterone enanthate are functionally impaired when tested in the hamster oocyte penetration assay. If such results can be produced in field trials, the development of new, more effective drugs for the regulation of male fertility may be forthcoming. At the same time, a considerable amount of research remains to be done before a male fertility regulating pill will be available on the market.
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  11. 11
    765514

    Techniques of male sterilization.

    MORRIS N; ARTHURE H

    In: Morris, N. and Arthure, H. Sterilization as a means of birth control in men and women. London, Peter Owen, 1976. p. 80-100

    Vasectomy was 1st used at the start of the 20th century and became prominent in the 1950s in family planning programs in Asian countries. The secondary sex characteristics do not change after vasectomy, and there is normal erectile power, libido, orgasm, and ejaculatory volume. Spermatogenesis continues normally in men following vasectomy, and plasma testosterone levels remain unchanged. Vasectomy involves cutting both vasa deferentes through an incision in the scrotum which is usually performed with local anesthesia without hospitalization. Preliminary counseling is necessary so that both partners understand the nature and effects of the operation. Semen banks may be used when available for men undergoing vasectomy. There is no evidence for the greater efficiency of 1 technique over the other. Patients must submit sperm samples for examination after 8-12 weeks and then every 4 weeks until 2 consecutive specimens are negative. Possible complications include: 1) a vasovagal reaction; 2) skin discoloration; 3) edema of the scrotal skin, 4) postoperative pain, 5) infection; 6) ulceration and gangrene of the scrotal skin, and 7) hydrocele or epididymo-orchitis. Successful reanastamosis of the vas deferens with reappearance of sperm can be accomplished in 50-80% of the patients, and the semen is not of quality to insure impregnation in 1/4 of these cases.
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  12. 12
    753685

    Task force on immunological methods for the regulation of fertility.

    World Health Organization [WHO]

    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.
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