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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)
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)
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.
Geneva, World Health Organization, 1966. (Technical Report Series NO. 332).The value and possible hazards of IUDs are discussed. Grafenberg developed a metal ring IUD in 1928. There was initial enthusiasm about the device, but it became discredited and interest was not revived in the method until 1959. Today, various shapes, sizes, and materials are employed in making IUD'S. No single cause or mechanism of action of an IUD has so far come to light. In sub-human primates the IUD causes accelerated passage of ova through the tube and the rest of the reproductive tract appears to be the major, but not necessarily the only, mechanism, of action. In ruminants, the contraceptive action of the IUD is exerted, at least in part, at the ovarian level. In rats, mice, rabbits, and ferrets, the main effect of the IUD is suppression of the implantation. It is concluded that the action of the IUDs in the human species is exerted before the stage of implantation. The most effective devices are associated with an incidence of 1.8 to 2.9 pregnancies per 100 insertions during the first year of use. The frequency of spontaneous expulsion ranges from about 5% to over 20% depending on the type of device. About one half of all expulsions occur in the first 3 months and comparatively few after the first year. The incidence of removal for medical reasons ranges from approximately 10% to 25% of first insertions during the first year. The method can be used successfully by almost 3 out of every 4 women who adopt it. Side effect and complications include bleeding and pain and less frequently pelvic inflammatory disease and perforation. The only absolute contraindications to the use of IUDs are: (1) active pelvic inflammatory disease, and (2) pregnancy, proven or suspected. Research needs are noted.
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.
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: Hankinson, R.K.B., Kleinman, R.L., and Ekstein, P., eds. Proceedings of the Eighth International Planned Parenthood, Santiago, Chile, April 9-15, 1967. London, International Planned Parenthood Federation, 1967. 501-506.Control of fertility in the male, ovum transport and fertilization, and the endocrinology and pharmacology of implantation are cited as areas of future study in contraception. In summarizing the proceedings of the Basic Science Sessions of the 8th International Conference of the International Planned Parenthood Federation, it is stated that 1) little has been developed in the immunological control of fertility, 2) the mechanism of IUD action is undetermined, and 3) 19-nor steroids do not appear to act directly on the ovary.