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Safety studies of sperm agglutinating factor produced by Staphylococcus aureus as a vaginal contraceptive: in vivo studies.
Gynecological Endocrinology. 2011 Nov; 27(11):956-960.Sperm agglutinating factor (SAF) isolated from Staphylococcus aureus when applied at concentration 10 mug before mating completely prevented conception in the mouse. The objective of the present study was to evaluate its safety, as safety is an important concern to be addressed before a compound is selected for contraceptive use. Our results showed that SAF has a very high safety profile. Vaginal application of SAF at 10 mug to the mouse for 14 consecutive days caused no systemic toxicity and vaginal irritation as indicated by lack of effect on organ weights and histology. Moreover, no adverse effect was observed on the subsequent reproductive capability, peritnatal outcome and growth and development of the offspring. SAF (10 mug) did not irritate the skin or penile mucosa. Oral administration of 2 mg/kg body weight of SAF did not show any toxicity to reproductive and non-reproductive organs. Therefore, SAF with spermicidal activity and lack of toxicity may have the potential to become the active ingredient of a vaginal contraceptive.
Evaluation of the potential of synthetic peptides of 80 kDa human sperm antigen (80 kDaHSA) for the development of contraceptive vaccine for male.
Vaccine. 2008 Jul 4; 26(29-30):3711-3718.80 kDaHSA has been demonstrated to be responsible for inducing immunoinfertility. Synthetic peptides NT, 1, 2 and 4 of 80 kDaHSA are immunogenic and immunobiologically mimic the native protein. Peptides 1 and NT being highly immunogenic their potential for contraceptive vaccine developmentwas evaluated. Active immunization of male rabbits with peptide-1 and -NT induced reversible infertility in 100% and 60% of animals, respectively and subsequently active immunization of non-human primate model, male marmosets with peptide-1 induced reversible infertility in six out of seven high antibody titer animals. The present study suggests the potential of peptide-1 of 80 kDaHSA for the development of contraceptive vaccine. (author's)
Reproductive Biology and Endocrinology. 2004 Mar 18; 2: p..Antisperm antibodies (ASA) may be a reason of infertility in some individuals. They may affect pre- as well as post-fertilization stages of the reproductive process. There is ongoing progress in the identification of sperm antigens related to fertilization. The employed methods for this purpose include recombinant DNA technology and the most advanced proteomic analysis. This paper enlists the different approaches undertaken in order to identify and characterize the immunoreactive sperm antigens. We have mainly focused on those, which have been already studied in regard of their immunocontraceptive potential, although it has been impossible to include all published data concerning the topic in a single article. Few novel sperm auto- and isoantigens, discovered recently, have also been reviewed even if their role in fertilization has not been yet established. (author's)
RASA, a recombinant single-chain variable fragment (scFv) antibody directed against the human sperm surface: implications for novel contraceptives.
Human Reproduction. 2001; 16(9):1854-1860.Background: A recombinant single-chain variable fragment (scFv) antibody was engineered to a tissue-specific carbohydrate epitope located on human sperm agglutination antigen-1 (SAGA-1), a sperm glycoform of CD52. Methods and Results: cDNAs encoding the variable regions of the S19 [IgG(-1)?] monoclonal antibody (mAb) were identified, linked, and cloned into the pCANTAB 5E vector. The recombinant anti-sperm antibody (RASA) was expressed in E. coli HB2151 cells as a 29 kDa monomer and, remarkably, also formed multimers of ~60 and 90 kDa. RASA reacted with the endogenous SAGA-1 antigen by Western blot analysis, labelled the entire human sperm surface by indirect immunofluorescence, and aggregated human spermatozoa in a tangled (head-to-head, head-to-tail, tail-to-tail) pattern of agglutination, as was also observed with the native S19 mAb. Conclusions: These results demonstrate that active recombinant antibodies can be produced to a tissue-specific carbohydrate epitope on the human sperm surface, thereby opening opportunities for novel contraceptive agents. (author's)
Human Reproduction. 2000; 15(2):231-233.The purpose of a debate contribution is to stir up controversy and discussion, and a recent paper (Helmerhorst et al., 1999) has done exactly that. However, aside from several criticisms already highlighted (Bronson, 1999), it seems that the view-point of Helmerhorst et al. (1999) is biased, among other things by the selection of references. Both Helmerhorst et al. (1999) and Bronson (1999) fail to mention to mixed agglutination reaction (MAR) test using latex beads instead of red blood cells (SpermMar test; Fertipro, Beernem, Belgium); (Jager et al., 1978; Vermeulen and Comhaire, 1983). In contrast to the polyacrylamide beads used in the immunobead test (MacMillan and Baker, 1987), the latex particles have a uniform diameter of 2 µm. In the SpermMar test for immunoglobulin (Ig)G, the particles are coated with IgG, and they do attach to the region of the spermatozoa where the antisperm antibodies are located. This attachment is obtained by adding strong and highly specific anti-IgG to the mixture of fresh, untreated spermatozoa and latex beads (Rasanen et al., 1994). There are also SpermMar tests for IgA and IgM. (excerpt)
Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features.
Immunopharmacology and Immunotoxicology. 2003 Nov; 25(4):627-643.Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group; the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters. (author's)
ADVANCES IN REPRODUCTION. 2001; 5(4): p..Steroid contraceptives are used worldwide and are the primary choice in contraception. However, and despite its efficacy, several papers are reporting the relationship between their use and some physiological alterations, ranging from gain of body weight to some types of cancer, mainly cervical and breast cancer. Efforts have been conducted to develop alternative, safe contraceptives. Researchers have developed both synthetic and hormone-derived abortive strategies, such as in the case of the beta-chain human gonadotrophin hormone-based effort of Indian investigators and the French RU-486 abortive pill that acts probably regulating the MUC1 expression in the uterus. Gamete-specific targets have also been investigated, such as the LDH-X, hyaluronidase, acrosin, sorbitol dehydrogenase from the sperm, the oocyte zona pellucida components, or even the embryo-specific fertilization antigen FA-1. WHO has shown a preferential use of traditional, almost home-made preparations for fertility control and some success have been achieved, as is the case of gossypol derived from the Gossypium seeds, which is capable of inducing a reversible oligospermic state. Some other plant groups have also been studied. In Mexico, a water extract from Kalanchoe sp. and an alcoholic extract from Sedum oxipetalum immobilize sperm. We report the sperm-agglutinating activity from two Bursera species that are commonly used in religious services due to their sweet smell after burning the whole plant, known as "copal" in many Central America countries. Some plants have more than the common utility value, as is the case of some members of the Bursera species such as the Mexican copal, a plant used for worship. Water extracts of several plants have vaginal contraceptive properties. We evaluated the sperm agglutinating activity of two Bursera species on human boar sperm. Extracts from stems and leaves were obtained. Capacitated sperm samples were used in all cases. There were different agglutinating capacities, which were not observes in the vehicle-only samples. The most frequent sperm agglutination response was that involving the heads. Agglutinating activity was higher from stem-than leaf-derived extracts. The results indicate that proteins present in the extracts are responsible for the aggregation of sperm heads. (full text)
NETWORK. 1998 Spring; 18(3):16-9, 31.Despite years of research, the development of new male methods of contraception is proceeding very slowly and no modern contraceptive drug exists for men. The most effective contraceptive options for men remain condom use or vasectomy and even the more promising experimental male methods are still at least one decade away from general use. A lack of commercial interest and funding has frustrated research. Progress has also been slow because of the difficulty involved in regulating the human male reproductive system. It is easier to interrupt a woman's ovulation than it is to interrupt sperm production. However, despite the challenge, research continues on a number of projects to identify new modern contraceptive methods for men. Current experimental prototypes typically either attempt to suppress sperm production by hormonal or nonhormonal means, or attempt to inhibit the fertilizing ability of sperm, usually by disrupting a key step in the conception process. Most research, however, is focused upon suppressing sperm production. Hormonal approaches, testosterone derivatives, nonhormonal suppression, and disrupting sperm function are discussed.
JOURNAL OF CLINICAL EPIDEMIOLOGY. 1993 Jan; 46(1):101-9.A comparative study of 69 vasectomized and 126 nonvasectomized men enrolled in the Portland (Oregon, US) Center for the Multiple Risk Factor Intervention Trial evaluated vasectomy as a risk factor for cardiovascular disease. In animal studies, atherosclerosis development has been linked to circulating anti-sperm antibodies and immune complexes formed in response to sperm breakdown products released in the body after vasectomy. Vasectomized men smoked more and had lower diastolic and systolic blood pressure than men in the control group. As expected, both sperm immobilization and sperm agglutination assays were significantly higher among vasectomized men than controls; 29.4% of vasectomized men compared with only 2.5% of nonvasectomized men had sperm immobilization values of 0.3 or less, while 54.1% of vasectomized men compared with 12.5% of nonvasectomized men had sperm agglutination values of 20.0 or above. These significant differences persisted even when a variety of coronary heart disease risk factors and treatments were controlled. Multivariate analysis showed that antibody development tended to decrease with age at vasectomy and increase with time since vasectomy. In the case of sperm agglutination, the antibodies clearly increased with time since vasectomy.
UROLOGIA INTERNATIONALIS. 1994; 53(3):143-6.In this series the authors present the results of a retrospective analysis of 66 vasovasostomy procedures performed between 1983 to 1991. Obstructive intervals and serum antisperm antibodies were correlated with pregnancy and patency rates. With obstructive intervals of less than 5 years a patency rate of 100% (31/31) was obtained. Even more than 10 years after reversal, pregnancy occurred in 25% (2/8) of the patients. Preoperative serum antisperm antibodies were correlated with pregnancy rates. Patients with a high agglutinin titer of 1/64 obtained a pregnancy rate of 23% (3/13). Those men who had no circulating antisperm antibodies in their blood had a significantly better chance in obtaining pregnancy (pregnancy rate 80%). In this study the authors accounted for an overall pregnancy rate of 51.5% (34/66) vs an overall patency rate of 84.8% (56/66). Neither long obstructive intervals nor high antisperm antibody titers should dissuade a surgeon from performing a vasovasostomy procedure. (author's)
REPRODUCTION, FERTILITY, AND DEVELOPMENT. 1993; 5(1):135-9.In Newcastle, New South Wales, Australia, health workers obtained sera and semen samples from 29 men requesting a vasectomy reversal to examine anti-sperm antibody profiles and their pregnancy induction rate after reanastomosis. The researchers also wanted to determine some preoperative parameters that predict postoperative success. The antisperm antibody titres of 329% of the men were clinically significant (gelatin agglutinin test titres > 1/40). Among the men who wanted to have children 42% were able to induce pregnancy. About 47% of men with no antisperm antibodies were able to induce pregnancy. No man with antisperm antibody titres of at least 160 were able to induce pregnancy. The exact probability of pregnancy occurring by chance in these men was just 0.14%, which was statistically significant. No association between prereversal serum antisperm antibody titres and postreversal semen quality existed. These findings led the researchers to recommend that any man with a serum antisperm antibody titre of at least 160 who wants to undergo vasectomy reversal should be about the low probability of postreversal infertility.
In: Fertility control. 2nd ed., edited by Stephen L. Corson, Richard J. Derman, Louise B. Tyrer. London, Canada, Goldin Publishers, 1994. 319-38.Men in all societies value vasectomy when their concern for family limitation surpasses their longing for more children and where there is concern for risks of maternal morbidity and female contraceptive method failure or risks. Vasectomies do not affect either the physical or mental health of men. In the US, 25% of all men at least age 35 have undergone a vasectomy. The farther a client is from a medical facility, the more important it is to screen for men at the highest risk of complications. They may be hemostasis, epididymitis, sperm granuloma, hematoma, and recanalization. Contraindications include local infections of the skin or lower genital tract and systemic blood disorders (e.g., hemophilia). Informed and written consent are required to obtain vasectomy. Preoperative counseling should inform the client that vasectomy does not assure sterility, about the physical effects of vasectomy, and about its possible long-term effects. Preoperative preparation should consist of a general history, a prostate exam, a system review, attention to previous genital surgery, and any adverse reactions to drugs. Vasectomy techniques include traditional vasectomy (occlusion of the vas via an incision through the scrotum and into the perivasal tissues) and no-scalpel vasectomy (occlusion of the vas through a puncture in the scrotal skin). No-scalpel vasectomy has a lower risk of bleeding and of local complications than the traditional technique. Sperm disappear in the semen after 6-10 postvasectomy ejaculations. Sperm agglutination often occurs in vasectomized men (about 50%). If azoospermia has not been reached after 20 ejaculations, men should submit another specimen after 10 more ejaculations. Any motile sperm after 30 ejaculations indicates vasectomy failure. Anywhere from 36% to 45% of recently vasectomized men do not return for follow-up. We do not know whether a reduction of mononuclear cells in semen after vasectomy reduces infectivity of the sexually active HIV-infected male.
In: Immunology of pregnancy, edited by Gerard Chaouat. Boca Raton, Florida, CRC Press, 1993. 245-61.Evidence shows that immunologic means can control fertility. Researchers first targeted the human chorionic gonadotropin (hCG) antigen which is in the most advanced stages of testing and development. Preimmunization with a carrier (e.g., tetanus toxoid [TT]) sometimes inhibits production of antibodies to new epitopes or ligands linked to the same protein. Use of an alternate carrier (e.g., diphtheria toxoid [DT]) bypasses this carrier-induced suppression. Extended phase I clinical trials of an alternate carrier hCG vaccine (TT or DT) show that all the women developed anti-hCG antibodies and no one developed adverse effects on clinical parameters, ovulation, or pathology. hCG is needed to maintain pregnancy, pregnancy specific, and produced very early in pregnancy in amounts that antibodies can easily neutralize. A recombinant hCG vaccine (vaccinia virus) has induced high levels of antibody production in monkeys. Gonadotropin releasing hormone (GnRH) launches a series of events which maintain fertility in males and females. It also needs to be linked to a foreign carrier. Phase I/II clinical trials show that as GnRH antibodies increase, levels of luteinizing hormone, follicle stimulating hormone (FSH), and testosterone levels fall concurrently. No adverse effects have developed. FSH is needed for spermatogenesis. Passive immunization with anti-FSH and active immunization with FSH induces either acute oligospermia or azoospermia. The earliest demonstration of deliberate immunization against sperm occurred 100 years ago. Animal research with sperm antigen vaccines has used purified sperm antigens, some of which produce antibodies causing sperm agglutination. Egg antigens target the zona pellucida which surrounds the oocyte and the preimplantation embryo and have sperm binding functions. The most promising zona pellucida antigen is the ZP3 macromolecules. Future attention will focus on cell mediated immune mechanisms to achieve infertility.
COMPREHENSIVE THERAPY. 1993 Jan; 19(1):37-41.About 500,000 men undergo vasectomy in the US yearly. 2-6% seek surgical reversal. Divorce is the main reason for vasectomy reversal in the US, while death of a child is in developing countries. Microsurgical techniques result in sperm's return to the ejaculate in more than 90% of reversal cases and in pregnancy in more than 50%. The clinician should conduct a complete physical examination and patient history to determine the prevasectomy fertility status of men wanting reversal, the surgical approach to use, and the success of reversal based on the location of the obstructed segment and the amount of vas removed. He/she should request a semen analysis, including serum and semen antisperm antibody assays. The surgeon should perform vas reanastomosis under general anesthesia or epidural anesthesia with sedation. Microsurgical vas reanastomosis requires considerable skill and 2-4 hours. Serial transection of the epididymis at high levels avoids rupture of the epididymis and secondary obstruction. The surgeon can usually discharge the patient the same day of the reversal. The patient can resume intercourse and normal activities in 3 weeks. The longer the time period between vasectomy and reversal, the less likely the reversal will be successful. Sperm granuloma at the vasectomy site increases the likelihood of successful vasectomy reversal, while sperm granuloma at the level of the epididymis or rete testis is linked to secondary obstruction and less successful reversal. As little as 50% of vasectomized men develop antisperm antibodies which may adversely affect the outcome of vasectomy reversal. If vas fluid samples from the testicular side have normal sperm, the possibility of a return to fertility is good; otherwise, it is less than 25%. A vasoepididymostomy may be needed in these cases. The most important factors in bringing about successful reversal surgery are the microsurgical technique and intraoperative judgment. In successful reversal cases, pregnancy usually does not occur until 6-18 months postoperatively.
SYMPOSIA OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY. 1989; 43:325-36.After a brief review of the molecular structure of cervical mucus, the data are presented on inhibition of sperm transport through cervical mucus by polyanions and on enhancement of sperm penetration in cases of infertility due to antisperm antibodies. Cervical mucus is a gel made up of large, unbranched, glycosylated glycoprotein with highly glycosylated domains separated by hydrophobic peptide chains. Spermatozoa probably traverse the unbound water phase rather than the water bound to the macromolecules. Since mucin is a polyanion, polycations were investigated as potential vaginal spermicides. The two biguanides studies, chlorhexidine and Vantocil were both spermicidal in concentrations of 1-10 mg/ml. Their rate of entry into mucin in capillary tubes differed. Vantocil penetrated superficially and set up a barrier of inspissated mucus. Chlorhexidine entered further, with dept inversely proportional to concentration. Both biguanides increased the thickness of cervical mucus in a dose-dependent manner, as judged by dynamic storage modules, by sedimentation in analytical ultracentrifugation, and by solubility in 0.22 M thiocyanate. It was speculated that these biguanides act by altering the molecular configuration of mucin. In the presence of anti-sperm antibodies, spermatozoa observed in cervical mucus in vitro may show non-progressive mobility or immobility. The presence of auto-antibodies can be shown with Immunobeads. Binding of secretory IgA to sperm can be cleaved with bacterial protease as can binding of IgG with trypsin. By assaying the blockage of sperm by antibodies with Immunobeads and measuring penetration of sperm in donor cervical mucus, displacement of sperm antibodies could be demonstrated in 9 infertile subjects. Therefore, it might be possible to treat the ejaculate with proteases, and achieve conception by either a gamete intrafallopian tube transfer or an in vitro fertilization procedure.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1993; 71(3-4):413-9.About 42 million couples worldwide, most of whom live in developing countries, have chosen vasectomy as their family planning (FP) method. There has been considerable research on the short and longterm safety of vasectomy. In the 1970s, research on rhesus monkeys indicated an increased risk of atherosclerosis, possible due to an increased level of antisperm antibodies. Later research on vasectomized men in developed and developing countries did not support these animal studies. Epidemiological studies in the US and Scotland showed an increased risk of testicular cancer in vasectomized men. A WHO meeting reviewed these studies and found no logical mechanism for this association. Later research found that vasectomy does not cause testicular tumors or accelerate the development of existing neoplasms. 2 studies in the US in 1990 suggested that vasectomy increases the risk of prostate cancer many years after the procedure. No studies since then have substantiated these findings. Besides, no known biological mechanism or hypothesis can explain the association. Vasectomy and prostate cancer specialists at a meeting of the US National Institutes of Health in March, 1993, agreed that physicians should continue to perform vasectomies and need not change clinical practice. Extrapolation of the US results to other countries is not logical, particularly to countries where prostate cancer is rare. Nevertheless, these recent reports will probably affect FP programs and acceptance of vasectomy in countries where vasectomy is common. Still, the evidence does not justify changes pertaining to vasectomy in national FP programs. Research on the longterm safety of vasectomy should be conducted. In conclusion, vasectomy is still a simple, safe, and very effective FP method.
WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 3rd ed.
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.
High-titer protamine-specific IgG antibody associated with anaphylaxis: report of a case and quantitative analysis of antibody in vasectomized men.
ANESTHESIOLOGY. 1993 Feb; 78(2):368-72.A vasectomized man reacted to intravenous protamine with shock; IgG and IgE antibodies against protamine were then measured in a group of 55 vasectomized men and compared to 55 age-matched controls. The index case was a 63-year old vasectomized man who, while having mitral valve repair and cardiopulmonary bypass, reacted to intravenous protamine with severe hypotension and pulmonary hypertension. protamine is the standard drug given to reverse the anticoagulatory effects of heparin used in cardiac procedures. He had another episode of bradycardia and hypotension 2 weeks later during heparin and protamine infusion as part of a follow-up studies. To document the presence of antibodies against protamine, a solid phase radioimmunoassay of protamine-IgG and -IgE was developed and performed on the subject's serum. This test was also applied to vasectomized men aged 21-45 years and 50 age-matched controls. The subject had a protamine-specific IgG level of 53 mcg/ml at the time of the 1st reaction, 667 at the 2nd, and 79 mcg/ml 3 months later. 16 (29%) of the vasectomized men also had protamine-specific IgG. None of the controls had protamine IgG. None of the men studies showed protamine-specific IgE in their sera. Before this case, diabetics receiving protamine-insulin were considered at risk for reactions to iv protamine, but only one other case of a vasectomized man succumbing to shock after protamine infusion has been reported.
In: Practice of fertility control: a comprehensive textbook. 3rd ed., [edited by] S.K. Chaudhuri. New Delhi, India, B.I. Churchill Livingstone, 1992. 229-38.A surgeon must consider various factors before deciding to rejoin the vas deferens of a vasectomized man. For example, was this man able to impregnate a woman before the vasectomy? If not, perhaps he was already infertile or subfertile or even the wife may be infertile. Further, perhaps too much of the vas was removed during the vasectomy making it impossible to rejoin the vas ends. Moreover, vasectomized men with high sperm antibody titers in semen tend to be infertile. Other possible drawbacks include epididymal obstructions and spermatic granuloma. A surgeon must interview a patient and be willing to answer any questions upon determining that the patient is a good candidate for vasectomy reversal. A subcutaneous injection of Demerol sedates the patient for several hours. Lidocaine without epinephrine is often used to bring about total regional anesthesia. After transection of the vas, the surgeon removes some spermatic fluid to detect sperms and sperm heads. If they are present, the surgeon performs the vasovasostomy. The surgeon can use either a microscope or loupes. Inert polyester sutures are superior for rejoining the vas. The patient should wear a suspensory for 2 weeks after the procedure and can recommence sexual intercourse in 7-10 days. Experienced surgeons can achieve patency rates of at least 80%. Pregnancy rates after vas reanastomosis tend not to be greater than 50%. Patency and pregnancy rates are usually 50% lower after epididymovasostomy than after vasovasostomy because there is a fistula between epididymis and vas instead of a watertight mucosa to mucosa anastomosis. Postoperative complications are minimal, but may include infection, bleeding, and minimal pain.
WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed.
Cambridge, England, Cambridge University Press, 1987. , 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.
Inhibition of sperm-zona pellucida tight binding by sperm immobilizing antibodies as assessed by the hemizona assay (HZA).
NIPPON SANKA FUJINKA GAKKAI ZASSHI. ACTA OBSTETRICA ET GYNAECOLOGICA JAPONICA. 1991 Feb; 43(2):237-8.Researchers collected serum samples from 23 infertile patients with sperm immobilizing antibodies (SI-Ab) and 1 pregnant patient from the Department of Obstetrics and Gynecology at the Hyogo Medical College in Japan to screen sera to determine whether they contained factors to inhibit sperm-zona pellucida tight binding. They used the recently developed hemizona assay (HZA) to test for this binding. The HZA assay showed that all 23 serum samples inhibited sperm-zona pellucida tight binding. The hemizona index (HZI) ranged from 3-53 with a mean of 18.1 (standard deviation of = or - 12) compared to a normal (HZI) of 100. Serum samples with titers >10 of SI50 inhibited sperm-zona binding as well as those with titers -or= 10 of SI50 (HZIs=17.3 vs. 18.9; p>.1). All 23 serum samples bound to the surface of sperm plasma membrane after 1 hour coincubation as evidenced by the fact that they all demonstrated >50% IgG beads bound. Further the results of the indirect immunobead test (I-IBT) showed that positive sera (+or= 20% IgG beads) significantly inhibited binding more than negative sera (<20% IgG beads bound) (HZIs=12.4 vs. 24.4; p<.05). Yet serum with positive I-IBT for IgM did not affect sperm-zona binding (HZIs=17.1 vs. 19.4; p>.1). No association existed between HZI and site of IB binding. The researchers interpreted theses results to mean that sera with both SI-Ab and antibodies recognized I-IBT for IgG and IgA may play a significant role to inhibit the sperm-zona pellucida tight binding. In conclusion, physicians should expect patients with low HZI to have more problems conceiving than those with normal HZI. In vitro fertilization using heat inactivated human cord serum or donor serum may help them to conceive.
Acta Obstetricia et Gynecologica Scandinavica. 1991; 70(6):483-5.Health workers at the National Health Centre Laboratories in Izmir, Turkey took blood samples from 109 prostitutes to test for antisperm antibodies (ASA) and for Treponema pallidum (the causative agent for syphilis). Researchers analyzed the results to determine the role of ASA incidence in reproductive failure. 40 fertile women who were not prostitutes comprised the control group. Significantly more prostitutes (43.1%) tested positive for ASA than did the controls (5%) (p<.01). 53 prostitutes tested positive for T. pallidum. T. pallidum positive women were slightly more likely to also be ASA positive women were slightly more likely to also be ASA positive than T. pallidum negative women (49.1% vs. 37.5%) (p<.05). 27 (51%) prostitutes did not use any contraception. ASA incidence for these women stood at 61.31% compared to only 28.3% for the control group (p<.01). 23 of these women had had children, but the last birth occurred on average 9.3 years prior to the study. It was significant that these 23 women had not used any contraception since the last birth. Mean length of prostitution stood at 9.6 years. Of the prostitutes who did use contraception, most (24.5% of all prostitutes) used oral contraceptives. The researchers could not determine if the prostitutes who used contraception would have also become infertile if they did not use contraception. In conclusion, repeated exposure to multiple sperm antigens and/or microorganisms may explain the high incidence of ASA and reproductive failure among prostitutes.
INTERNATIONAL JOURNAL OF FERTILITY. 1991 Nov-Dec; 36(6):352-7.This report provides current facts about vasectomy reversal, hoping to inform non-urologists, who are often the first physicians consulted by patients seeking the procedure. The author explain that an increasing number of men are requesting vasectomy reversals, and unless non-urologists are informed about the subtleties involved in the procedure, they may provide patients with confusing and frustrating information. The article begins by discussing patient selection, operative choices, scheduling and anesthesia. Since all men continue to produce sperm in the testes after a vasectomy, they are all potential candidates for reversal. The procedure, however, involves thoughtful intraoperative evaluation, as well as the use of improved microsurgical techniques in some cases. The old vasectomy site may not be the only place of obstruction, since over time there may be engorgement, leaking, or scarring in the epididymis. The 2 operative procedures available are vasovasostomy and vasoepididymostomy. The decision of which procedure is required is made only at the time of the surgery, based upon certain intraoperative findings. The article goes on to explain the intraoperative findings that influence the operative choice, and discusses the success ratios of reversals. In 61 vasovasostomies performed by the author, more than 80% were considered successful, with 31 (50.8%) pregnancies reported. And in 16 vasoepididymostomies performed, 62.5% achieved patency and resulted in a pregnancy rate of 25%. The author then addresses the possible causes of postoperative failure, including sperm antibodies. Finally, the author briefly mentions options other than reconstructive microsurgery, such as intraoperative sperm aspiration and micromanipulation.
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.
CURRENT OPINION IN IMMUNOLOGY. 1989 Aug; 1(6):1125-30.Given the observation that naturally occurring antibodies to eggs and sperm can cause infertility, it seems feasible to pursue development of an infertility vaccine based on the induction of a specific immune response to gamete or early embryo antigens. Antibodies directed to the zona pellucida have been researched, but at current levels of purification, result in reduced ovarian hormone production. Of the numerous sperm antigens, LDH-C4 appears most promising for use in a vaccine. In the past decade, antisperm antibody investigations have focused on surface antibodies and sperm mixed agglutination reactions. It appears that antibodies in accessory fluids bind to sperm during ejaculation and/or antisperm antibodies enter the male tract at the epididymal level or higher. Antibodies directed against egg or sperm may prevent or modify the normal process of capacitation in which sperm undergo a series of biochemical and morphological transformations. Antisperm antibodies can suppress fertility by preventing sperm transport through cervical mucus or impeding the sperm-egg interaction during fertilization. The definition of sperm antigens associated with infertility--essential for development of a contraceptive vaccine--is being facilitated by monoclonal antibody techniques and DNA technology. Since the sperm surface is organized into highly specialized and distinct regions, cell recognition is an important research area. Most salient to the recognition and regulation of cell interaction are the components of the sperm plasma membrane and the zona pellucida.