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1.
Active immunization of proven fertile adult male bonnet monkeys (Macaca radiata) with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific peptides from the extracellular domain resulted in a progressive drop in sperm count with all animals becoming azoospermic by day 100. However, serum testosterone concentrations were unaltered during the entire course of study and animals exhibited normal mating behaviour. Breeding studies with proven fertile female monkeys revealed that all the immunized males were infertile. Following interruption of immunization on day 225, sperm counts returned to normal with restoration of fertility. These results indicate that infertility can be induced in adult male monkeys by interfering with the action of FSH using specific peptides of the extracellular domain of FSHR as antigens, without the risk of producing cross-reacting antibodies to the other glycoprotein hormones.  相似文献   

2.
Immunointerruption of pregnancy consists of preventing pregnancy or terminating it at an early stage through antibodies. The antibodies may be obtained after administration of vaccine to induce their formation through active immunization, or by direct injection through passive immunization. Antigens that could potentially be used are found in sperm, the zona pellucida, and reproductive hormones, especially the chorionic gonadotropins. The sperm antigens are basically enzymes such as hyaluronidase and accrosine. 3 glucoproteins have been identified in the zona pellucida of mice and pigs. In vitro studies have shown that fertilization can be prevented if eggs are exposed to antizona-pellucida antibodies along with sperm. Active immunization could give longer term results, but ovarian function could also be affected if the antigens weren't purified. Much research has been devoted to identifying human embryonic antigens through analysis of the proteins of the cells of embryonic teratocarcinoma. Among placental antigens, the glucoprotein SP1 synthesized by the trophoblast is under study. Anti-SP1 antibodies appear to cause abortion in monkeys, but knowledge of these antigens is still fragmentary. Various reproductive hormones have been studied, but too many undesirable effects could result from the use of luteinizing hormone, luteinizing hormone releasing hormone, follicle stimulation hormone, or steroids. Human chorionic gonadotropin (hCG), however, is more promising. It is a glucoprotein formed of alpha and beta subunits, both of which are needed for hCG to interact with its receptor. The alpha subunit has the same sequence as that of other hormones of the same species, but the beta subunit is specific to each hormone. Studies are underway to determine the site of amino acids and peptide sequences capable of inducing an anti-hCG response which would inactivate the biological activity of hCG. Different teams have used synthetic peptides analogous to sequences of beta-hCG or fragments obtained by enzymatic cleavage of natural hCG to block pregnancy in rats and baboons. The presence of antibodies can block pregnancy without disturbing ovulation or modifying menstrual regularity. No toxic or secondary effect has been observed in animals. A multicenter phase 1 test using beta-hCG coupled with tetanus antitoxin caused almost all the women participating to develop antibeta-hCG and antitetanus anatoxin antibodies, but titres of antibodies varied greatly between different women, required 5-6 months to develop, and declined rapidly thereafter. Several pregnancies were observed, especially in women with low titres of antibodies. The approach of passive immunization through direct injection of antibodies has met with numerous obstacles, including lack of success in producing human monoclonal antibodies. Although a 2nd generation of vaccines in under study, the potential role of immunointerruption of pregnancy in fertility regulation remains to be clarified.  相似文献   

3.
IntroductionClomiphene citrate is employed off‐label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism.AimOur aim was to compare oral enclomiphene citrate as an alternative to topical testosterone.Main Outcome MeasuresBlood levels of total testosterone (TT), estradiol, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin‐like growth factor 1 IGF‐1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated.MethodsThis was a proof‐of‐principle, randomized, open‐label, fixed dose, active‐control, two‐center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone.ResultsAfter discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 106/mL range. The gel was ineffective in raising sperm counts above 20 × 106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow‐up, only enclomiphene citrate treatment was associated with elevated sperm counts.ConclusionsEnclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.  相似文献   

4.
The effects of an oral contraceptive, Etinodiene .5 (reduced dose), were studied in 233 women during 2812 cycles. In addition to clinical examinations, the urine pregnanediol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations during therapy were also measured. The use of the drug did not produce any significant changes in blood pressure, body weight, and blood counts. LH and FSH tests revealed blocking of the pituitary gonadotropic hormone release and inhibition of ovulation. The drug proved to be an effective contraceptive, without any case of pregnancy in the group observed, and side effects caused by the treatment were slightly milder than those reported with other estrogen-progestogen combinations.  相似文献   

5.
Twenty-five boys between 1 and 10 years of age with unilateral or bilateral cryptorchidism were treated with 200 microgram of gonadotropin-releasing hormone (GnRH) pernasally six times daily until descensus was completed, or for 10 weeks at most. Complete descent of the tests occurred in 16 patients, usually after 2 to 5 weeks of treatment. No adverse side effects have been observed. Radioimmunologic measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and prolactin, carried out before treatment, at the end of treatment, and 6 months after treatment, showed a transitory increase of the LH responsiveness to GnRH in only four of the patients and in the group as a whole a slight but significant decrease of FSH responsiveness. There were no signs of precocious puberty. GnRH antibodies were not found.  相似文献   

6.
Transplantation of a human testis for anorchia   总被引:6,自引:0,他引:6  
One of two genetically identical twins (30 years old) had been born with two normal testes and the other with none. In the anorchic twin, preoperative serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were extremely high, and the serum testosterone level was extremely low. In the twin with two testes, preoperative serum FSH, LH, and testosterone levels were normal. After successful transplantation of a testis from the twin with two testes to the twin with no testes, using the microvascular technique, the recipient twin developed a normal serum testosterone level within 2 hours of surgery; his FSH and LH levels came down toward a normal range more slowly over the ensuing 4 weeks. The donor's FSH level became mildly elevated 2 days postoperatively but returned to normal by 3 months. Thereafter, serum FSH, LH, and testosterone levels remained persistently normal in both twins. In the donor, pre- and postoperative sperm counts were normal. Preoperatively the recipient's semen had no sperm, but postoperatively the sperm content has slowly increased to normal levels.  相似文献   

7.
Serum follicle-stimulating hormone (FSH) levels measured by radioimmunoassay (RIA) usually correlate well with the rate of spermatogenesis. However, in certain cases this correlation does not exist. The purpose of this study was to establish a reliable bioassay of FSH for the andrological clinic. Follicle-stimulating hormone was measured by both standard RIA and bioassay in 98 men subgrouped into normospermic, oligospermic, and azoospermic. Bioactivity of FSH was determined using in vitro cultures of granulosa cells utilizing progesterone measurements for assessing FSH activity. Results of FSH levels obtained by both methods correlated well (r = 0.55, P less than 0.01) within themselves, and both correlated negatively and significantly with sperm concentration. The ratio between bioactivity and immunoreactivity of FSH did not correlate with sperm density. Thus, the decrease in sperm concentration and other sperm variables resulting from a germinal epithelial dysfunction was not mediated or associated with low biological activity of FSH. The application of this method can be of clinical value in cases where a discrepancy is found between serum RIA-FSH levels and sperm quality.  相似文献   

8.
OBJECTIVE: To identify, among patients with idiopathic normogonadotropic oligoasthenozoospermia, those with low bioactive follicle-stimulating hormone (FSH), possibly because of inadequate gonadotropin-releasing hormone (GnRH) pulsatility, whose bioactive FSH and sperm could be improved by GnRH treatment. DESIGN: Randomized, double-blind, placebo-controlled trial with intranasal (IN) GnRH, followed by open GnRH treatment. SETTING: Outpatient endocrinology clinic. PATIENTS: Twenty-eight infertile men with idiopathic normogonadotropic oligoasthenozoospermia. INTERVENTIONS: Gonadotropin-releasing hormone or placebo was self-administered IN every 2 hours. MAIN OUTCOME MEASURES: Serum immunoreactive and bioactive FSH and semen analyses. RESULTS: Ten men showed a low basal FSH bioactive/immunoreactive ratio, which increased in 5 of them under GnRH without parallel sperm modification. Sperm improvements were observed in 10 patients with no parallel evolution of FSH bioactive/immunoreactive ratio. Unpredicted by sperm changes, three pregnancies developed on placebo and 5 on GnRH. CONCLUSIONS: Low bioactive FSH was not the cause of idiopathic normogonadotropic oligoasthenozoospermia in our patients and could not predict response to GnRH. Pulsatile GnRH did not improve sperm beyond random fluctuations.  相似文献   

9.
Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17 beta-estradiol (E2) have been measured in men complaining of infertility in comparison with men of proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm or by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between the groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm count grouping but were significantly less than those found for the infertile men with sperm. Azoospermic patients with high testicular scores had FSH levels indistinguishable from those of the fertile men. The results are discussed in terms of testicular abnormalities and on the interrelationship between the hormones examined.  相似文献   

10.
A new look at antifertility vaccines   总被引:2,自引:0,他引:2  
This article reviews new advances in biochemistry, biotechnology, and immunology relevant to antifertility vaccine development and evaluates the current status and future prospects of contraceptive vaccines and other immunologic approaches to fertility regulation. Contraceptive vaccine candidates include human chorionic gonadotropin, human luteinizing hormone and luteinizing hormone releasing hormone, and reproductive steroid hormones. Sperm enzymes are attractive for a contraceptive vaccine; among the sperm antigens studied are antibodies to hyaluronidase, acrosin, and lactate dehydrogenase-C4. Several laboratories have developed monoclonal antibodies to a variety of sperm antigens and are using them to identify and characterize new sperm proteins and their roles in fertility. Considerable progress has been made toward biochemical characterization of unique glycoproteins constituting the zona pellucida. Zona pellucida antigens are good candidates because antizona antibodies may block both fertilization and implantation, and low amounts of antibody would be sufficient because of the small number of mature eggs with zona present at any time. Studies are underway to identify human embryonic antigens through examination of the protein profile of human teratocarcinoma cell lines at various stages of differentiation and through analysis of antibodies in human pregnancy and infertility sera. Placental and extraembryonic membranes produce several tissue-specific antigens that have been considered for antifertility vaccines, but concern that they could produce late or incomplete abortion has prevented their serioud consideration. Because of possibly serious systemic side effects, presence of the blood-testis barrier, and large number of sperm produced daily, it is unlikely that sperm vaccines can be safely administered to men. Nautural protective mechanisms will probably render some immunocontraceptive approaches ineffective. The possibility of serious pathogenic side effects of contraceptive vaccines demands vaccines demands a cautious approach to their development.  相似文献   

11.
Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.  相似文献   

12.
Recently, a model for early pregnancy in the rhesus monkey was developed which involved administration of a 10-day treatment regimen of human chorionic gonadotropin (hCG). The current studies were designed to determine whether monkeys produced antibodies in response to this hCG regimen and, if so, to characterize the specificity of the antibodies and their effects on subsequent menstrual cycles. Based on Sephadex chromatography and immunoglobulin precipitation with protein A, serum collected from hCG-treated monkeys contained binding components for 125I-hCG. Binding was specific for human gonadotropins (hCG, human luteinizing hormone [LH], human follicle-stimulating hormone [FSH]) and did not cross-react with macaque LH/FSH. Shortening the hCG regimen to less than or equal to 6 days did not result in significant binding. The 10-day hCG regimen did not alter subsequent menstrual cycles, but attenuated 17 beta-estradiol production in response to human menopausal gonadotropin. In conclusion, the 10-day regimen of hCG treatments used to simulate early pregnancy in rhesus monkeys induced the production of serum components with characteristics of hCG antibodies. These antibodies did not alter the regulation of the menstrual cycle, but attenuated the response to exogenous human gonadotropins.  相似文献   

13.
To determine whether clomiphene citrate (CC) improves fertility in oligospermic men, 23 men with sperm concentrations between 0.5 and 20 million sperm per milliliter; normal serum gonadotropins and testosterone; and a presumptively fertile partner were enrolled in the study. After a 3-month control period, patients were randomly prescribed CC, 25 mg/day; or placebo, 1 tablet/day, for 12 months. The pregnancy rates for the CC group and the placebo group were 9.09% and 44.44%, respectively (not significant). During the treatment phase, the CC group had significantly higher levels of luteinizing hormone (LH) serum, follicle-stimulating hormone (FSH), testosterone (T), and estradiol than the placebo group. CC treatment also resulted in greater LH, FSH, and T responses to gonadotropin-releasing hormone (GnRH). There were no differences between the placebo and CC groups for the sperm penetration assay or semen parameters. The authors conclude that CC is not a useful drug in the treatment of male infertility.  相似文献   

14.
Synthetic LH-RH was given to 15 healthy men divided into 3 groups of 5 each. A dose of 250 mug LH-RH was injected as a single intravenous bolus for 1 day, every other day for 3 days or for 7 consecutive days respectively. Antibody formation against this synthetic hormone was measured by testing for binding with 125I labeled LH-RH. No antibody formation was detected in any group during the seven day period. Sperm counts were done 1 week before and immediately after the administration of LH-RH, as well as 3 months later. Changes in sperm counts could not be related to the number of injections received. Gonadotropins (FSH and LH) were measured by RIA. There was a significant rise in plasma levels of both gonadotropins, but no signigicant changes in their basal level or percent response resulted from the repetitive administration of LH-RH. Plasma testosterone was also measured by RIA. There was no significant channge in either baseline or percent response in any of the groups after 1, 3 or 7 injections. Some individuals did show a significant rise in plasma testosterone levels, but this was not consistent and was not related to the number of injections administered. Thus, in this study, the repetitive administration of LH-RH did not alter pituitary responsiveness or result in antibody formation.  相似文献   

15.
Semen characteristics, antisperm antibodies, and cervical mucus penetration studies were analyzed in 754 couples and 95 men undergoing infertility evaluation. The means for the different semen/sperm variables were within ranges published for fertile men. Ages of the men ranged from 22 to 55 years and accounted for a small amount of variation. Sperm counts were lowest in September, December, and January, and highest in April, May, October, and November. Of the sperm characteristics, morphology appeared to be associated with the most other variables. Specimens with more than 50% abnormal sperm forms were overall of significantly poorer quality in terms of sperm counts, motility, forward progression, and ability to penetrate cervical mucus. Antisperm antibodies (agglutinating and immobilizing) were detected in the serum samples of 19.0% of the men, 20.4% of the women, and 32.8% of the couples where one or both partners were positive. Agglutinating antibody titers were significantly correlated between partners. Serum titers of antisperm antibodies were associated with decreased sperm counts, motility, forward progression, and normal forms (immobilizing antibodies). Multiple correlation analysis indicated significant independent effects of sperm concentration, motility, forward progression, and antibodies on sperm-cervical mucus penetration scores of the men. In women, cervical mucus penetration was adversely affected by the presence in the serum of sperm agglutinating antibodies and of immobilizing activity in the cervical mucus.  相似文献   

16.
The administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). However, whereas Clomid produced a decrease in the LH response to LH-releasing hormone (LHRH), no such effect was seen after the administration of tamoxifen. In fact, prolonged treatment (6 weeks) with tamoxifen significantly increased the LH response to LHRL. Treatment of patients with "idiopathic" oligospermia for 6 to 9 months resulted in a significant increase in gonadotropin, testosterone, and estradiol levels. A significant increase in sperm density was observed only in subjects with oligospermia below 20 X 10(6)/ml and normal basal FSH levels. When basal FSH levels were increased or oligospermia was moderate (greater than 20 X 10(6)/ml); no effect on sperm density was seen. As sperm density increased, FSH levels decreased, suggesting an inhibin effect. Sperm motility was not improved by tamoxifen treatment. In five boys with delayed puberty, tamoxifen treatment appeared to activate the pituitary-gonadal axis and pubertal development.  相似文献   

17.
To evaluate the predictive power for sperm retrieval in testicular sperm extraction of inhibin B and FSH levels in the peripheral blood in association with the testicular histology.Clinical study.Departments of andrology and urology at a university hospital.Fifty-two patients with azoospermia.Determination of serum levels of FSH and inhibin B in men with azoospermia. Testicular incision and histological investigation as well as testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection were performed.Comparison of hormone levels with different histological features of seminiferous tubules (normospermatogenesis, hypospermatogenesis, and Sertoli cell-only syndrome) and TESE outcome.With respect to the histological proof of spermatozoa, the sensitivity of the FSH levels >10 mU/mL was 82%, and of inhibin B levels, <79 pg/mL, 78%; the specificity was 80% for both hormone levels. With respect to the successful sperm extraction in the TESE procedure, the sensitivity of the FSH levels was 58% and the specificity was 50%; and the sensitivity of inhibin B levels was 52.5% and the specificity was 60%.Inhibin B and FSH levels are correlated with spermatogenetic activity. The combination of the two parameters is currently the best predictor for the presence of sperm, which may be found in TESE. However, the prediction is not absolutely reliable: TESE can be also successful when both hormone levels are outside the threshold levels.  相似文献   

18.
PURPOSE: To present various treatment options for male subfertility. METHODS: Surgical therapy for varicocele, hormonal therapy, mechanical therapy, e.g., intrauterine insemination, special treatment for antisperm antibodies and low hypoosmotic swelling test scores with protein digestive enzymes, and in vitro fertilization (IVF) with and without intracytoplasmic sperm injection are discussed. RESULTS: Questions have been raised as to the efficacy of varicocelectomy. Perhaps only a minority of the best of males respond to this therapy. Clomiphene citrate or gonadotropins or hCG may be effective but usually only when serum FSH, LH and/or testosterone levels are low or are in the low normal range. Intrauterine insemination is helpful for oligoasthenozoospermia but is not so beneficial for antisperm antibodies or low hypoosmotic swelling test scores unless first pretreated with chymotrypsin. CONCLUSIONS: Obstructive or non-obstructive azoospermia requires sperm aspiration from the testes or testicular biopsy followed by IVF with intracytoplasmic sperm injection (ICSI). In vitro fertilization with ICSI is needed for extremely low counts or motility. Otherwise less costly or invasive therapy can be tried first but IVF with ICSI can eventually be performed if more conservative therapy fails to achieve a pregnancy.  相似文献   

19.
The aim of the study was to analyze the distribution of the follicle-stimulating hormone (FSH) receptor (FSHR) Ala307Thr and Asn680Ser polymorphisms in infertile Brazilian men and evaluate the possible role of these polymorphisms on the serum levels of FSH and in sperm count. A case-control study was performed comprising138 infertile men with nonobstructive azoospermia (n = 53) or severe oligozoospermia (n = 85), and 217 fertile men as controls. Genotyping of FSHR polymorphisms was performed by real-time polymerase chain reaction (PCR). The results were analyzed statistically and a P value <.05 was considered significant. According to the sperm count, relatively similar FSHR polymorphisms genotype and allele frequencies were found among the groups, and combined genotypes of 2 polymorphisms did not identify a haplotype associated with sperm count. Considering FSH serum level according to genotypes of the Ala307Thr and Asn680Ser polymorphisms individually, statistical analysis showed no difference among the groups. When the combined genotypes of the FSHR polymorphisms were compared to FSH serum levels, no difference was also found among the groups. In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, Asn680Ser and Thr307Ala, of the FSHR gene are not correlated with serum FSH levels or sperm count in male infertility.  相似文献   

20.
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone were measured by radioimmunoassay in blood and seminal plasma of normo-spermic and oligospermic men. These parameters were correlated with sperm cell concentration as well as sperm motility. Average motility in the oligospermic group was significantly decreased as compared with the normospermic group (P less than .001). A significant reciprocal correlation was demonstrated between blood LH concentrations and sperm cell concentrations (P less than .05) as well as sperm motility (P less than .02). In contrast, a significant positive correlation was demonstrated between seminal LH concentrations and sperm cell count and motility (P less than .001). Seminal FSH and testosterone concentrations were positively correlated with sperm output but not sperm motility (P less than .05). The increased concentrations of LH in circulation accompanying idiopathic oligospermia suggests that LH secretion may be linked to the factors regulating spermatogenesis. The significant correlation between seminal testosterone and sperm concentration demonstrated in this study offers further support to this hypothesis. The significance of the correlation between the levels of LH and FSH in seminal plasma and sperm cell concentration and sperm motility is unknown.  相似文献   

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