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PubMed1999

Inhibin B is a more sensitive marker of spermatogenetic damage than FSH in the irradiated non-human primate model.

This study evaluated the effect of bilateral testicular irradiation (2 Gy) on reproductive hormones, testicular volume (TV) and sperm parameters in six adult cynomolgus monkeys. Hormone levels (FSH, inhibin B and testosterone (T)) were determined to find the most valuable endocrine marker of irradiation-induced damage. All parameters were analysed at weekly intervals for 14 weeks. Histological evaluation of both testes was performed at week 14 after irradiation when one monkey was castrated and at week 27 when the remaining five monkeys were bilaterally biopsied. A decrease in body weight, TV (30% of the pre-treatment size) and sperm count was observed after irradiation. Severe oligozoospermia was achieved throughout the study but azoospermia was recorded only occasionally. Histological evaluation revealed a heterogeneous picture with patchy arrangement of seminiferous tubules containing advanced germ cell types. An increase (P<0.05) in FSH levels and, to a lesser degree also in T levels, occurred several weeks after irradiation. Inhibin B levels showed a sharp decline (P<0.001) as soon as 1 week after irradiation. FSH and inhibin B did not return to baseline levels during the observation period. A negative correlation was found between FSH and inhibin B values (r=-0.35, P<0.001). Inhibin B correlated positively with testis volume (r=0.73, P<0.001) and sperm counts (r=0.55, P<0.01). In conclusion, this study shows that inhibin B represents an early and more sensitive marker of testicular damage than FSH. Furthermore, the rapid fall of inhibin B after irradiation suggests that this hormone is a direct parameter of premeiotic germ cell proliferation.

Animals↗
PubMed1975

The semen of fertile men: statistical analysis of 1300 men.

The prevasectomy semen analyses of 1300 men who had fathered at least two children were studied. The ages of the men ranged from 23 to 64 years, with a mean age of 39.6 years; 84% of the men were Caucasian, 5% were black, and 5% were of other ethnic groups; 32% of the men were Roman Catholic, 26% Jewish, 22% Protestant, and 11% professed no religion; in 9% religion was not recorded. The number of children ranged from 2 (48%) and 3 (30.6%) to 10 (0.1%). The volume of the ejaculate ranged from 0.1 to 11.0 ml, with a mean of 3.2 ml plus or minus 1.4 SD. Sperm density ranged from 1.5 to 375 million/ml, with an arithmetic mean of 79 million/ml plus or minus 57 SD; however, the logarithmic or geometric mean was chosen as being more representative of the asymmetric distribution under study. The geometric mean was 65 million/ml, with standard deviation limits of 30 to 142 million/ml, figures that correspond to the 16th and 84th percentiles. The percentage of motile sperm ranged from 5 to 95%, with a mean of 65% plus or minus 22 SD. The grade of sperm motility, according to MacLeod and Gold's classification (Fertil Steril 2:187, 1951) of 0 to 4, ranged from 1 to 4, with a mean grade of 3. There were 25 men (2%) with a sperm count below 10 million/ml and 26 (2%) in whom the percentage of motile sperm was less than 20%. Polyzoospermy (count greater than 250 million/ml) was found in 15 men (1.2%); one or more spontaneous abortions had occurred in six of the spouses of these men (40%), whereas the over-all spontaneous abortion rate was 7% and the spontaneous abortion rate for wives of men with sperm counts below 10 million/ml was 4%. A positive relationship was found between sperm density and percentage of motile sperm; the relationship between motility and the logarithm of sperm density was represented by a straight line (a 10-fold increase in sperm count was accompanied by an increase of 20.4% in sperm motility); the slope of the line was highly significant, although the correlation coefficient was weak (0.27). A similarly positive relationship was found between sperm density and grade of motility; however, the correlation coefficient was also weak (0.22). The relationship between the grade of motility and the proportion of motile sperm also positive, was reasonably large (0.70), although its significance is questionable because of the crudeness of the scale utilized to assess the grade of sperm motility. A comparison of the findings with those of similar studies was made.

Abortion, Spontaneous↗
PubMed1985

Hormonal effects of GnRH agonist in the human male: an approach to male contraception using combined androgen and GnRH agonist treatment.

Observations that hypophysectomized men demonstrate predictable azoospermia have led to attempts to suppress gonadotropin secretion with drugs for contraceptive purposes. Testosterone enanthate, given on a weekly or bimonthly basis, failed to predictably induce azoospermia in men. Treatment with agonist analogs of GnRH significantly suppressed spermatogenesis, but led to concomitant decline in serum testosterone concentrations. To prevent GnRH agonist induced changes in libido and potency we tested regimens employing daily subcutaneous injections of 200 micrograms of D(Nal2)6GnRH in combination with 200 mg testosterone enanthate every 2 weeks. This regiment led to 86% decline in mean sperm count over the 16-week treatment period, but azoospermia was not achieved in any subject. Basal or 24 h integrated serum LH or 24 h urinary LH concentrations were not significantly suppressed by combined treatment. In order to assess whether constant infusion of GnRH agonist will lead to greater suppression of gonadal function than its intermittent administration, we administered either 20 or 200 micrograms of D(Nal2)6GnRH to 2 groups of normal male volunteers for 28 days either by single daily injection or by constant subcutaneous infusion. Serum testosterone, LH and FSH responses were not significantly different between the two modes of agonist delivery either at 20 or 200 micrograms dose. Marked decrease in serum testosterone and sperm counts in these studies occurred in the face of little or no change in immunoreactive LH, indicating that the antigonadal actions of GnRH agonist in the human male cannot be fully explained on the basis of downregulation of pituitary LH secretion alone. GnRH agonist treatment however, led to marked decrease in bioassayable LH concentrations suggesting secretion of a molecularly altered LH species with diminished biologic activity.

Animals↗
PubMed2002

How work-place conditions, environmental toxicants and lifestyle affect male reproductive function.

Major temporal and geographical shifts in male reproductive function is presently an issue worldwide. The hormonal disruption hypothesis has achieved considerable attention but epidemiological evidence in support of the theory is lacking. Several occupational hazards to male reproductive function are known but exposure prevalences are hardly sufficient to play a role for reduced sperm count in the general male population. Sedentary work may be an exception. Perhaps prolonged time in the sedentary position exhausts the testicular heat regulation. But so far studies addressing implications of the heat hypothesis in the general population are few. Neither change of sexual behaviour nor reduced period of sexual continence seems to be a likely explanation. Tobacco smoking and consumption of caffeine and alcoholic beverages in adulthood have a rather marginal impact on spermatogenesis and can hardly explain major shifts or regional differences in male reproductive health. However, prenatal effects following smoking during pregnancy might play a role because we have witnessed a smoking epidemic among fertile women in some countries during the second half of the twentieth century. Moreover, if genetic factors play more than a marginal role for testicular function and sperm count, pregnancy planning resulting in reduced family size during the past 100 years could possibly explain a decline in semen quality because the most fertile part of the population reproduce less while the subfertile probably continue to get a limited number of children.

Body Temperature Regulation↗
PubMed2004

Effectiveness of vasectomy using cautery.

BACKGROUND: Little evidence supports the use of any one vas occlusion method. Data from a number of studies now suggest that there are differences in effectiveness among different occlusion methods. The main objectives of this study were to estimate the effectiveness of vasectomy by cautery and to describe the trends in sperm counts after cautery vasectomy. Other objectives were to estimate time and number of ejaculations to success and to determine the predictive value of success at 12 weeks for final status at 24 weeks. METHODS: A prospective, non-comparative observational study was conducted between November 2001 and June 2002 at 4 centers in Brazil, Canada, the UK, and the US. Four hundred men who chose vasectomy were enrolled and followed for 6 months. Sites used their usual cautery vasectomy technique. Earlier and more frequent than normal semen analyses (2, 5, 8, 12, 16, 20, and 24 weeks after vasectomy) were performed. Planned outcomes included effectiveness (early failure based on semen analysis), trends in sperm counts, time and number of ejaculations to success, predictive value of success at 12 weeks for the outcome at 24 weeks, and safety evaluation. RESULTS: A total of 364 (91%) participants completed follow-up. The overall failure rate based on semen analysis was 0.8% (95% confidence interval 0.2, 2.3). By 12 weeks 96.4% of participants showed azoospermia or severe oligozoospermia (< 100,000 sperm/mL). The predictive value of a single severely oligozoospermia sample at 12 weeks for vasectomy success at the end of the study was 99.7%. One serious unrelated adverse event and no pregnancies were reported. CONCLUSION: Cautery is a very effective method for occluding the vas. Failure based on semen analysis is rare. In settings where semen analysis is not practical, using 12 weeks as a guideline for when men can rely on their vasectomy should lessen the risk of failure compared to using a guideline of 20 ejaculations after vasectomy.

Adult↗
PubMed1991

[Inhibin, steroid hormone, and gonadotropin concentration in blood from fertile and infertile males and its relationship with testicular function].

The role of inhibin in the testicular function and its relation with other hormone regulation spermatogenesis have not been elucidated in the human, therefore we studied by RIA the serum concentrations of this testicular secretion product, as well as those of LH, FSH, T and E2 and their possible correlation with some parameters evaluated by spermatobioscopy (cell number, motility, morphology and immature germinal cells) in fertile, oligozoospermic and azoospermic men. We did not find significant differences in inhibin concentration between fertile and oligozoospermic males; however in the azoospermic group the mean inhibin concentration was significantly higher (722.9 +/- 137.9 U/l in the fertile men; 658.5 +/- 147.1 and 963.1 +/- 300.9 U/l in the oligozoospermic and azoospermic groups respectively), in spite of data dispersion in the 3 study groups. Among the fertile males we found a negative significant correlation between the inhibin and the LH and FSH concentrations (p less than 0.05), while in the oligozoospermic patients this negative correlation was observed with T concentration. In the fertile males inhibin also showed correlation with the sperm percentage with normal morphology and with the immature germinal cells in semen; in the oligozoospermic group this glycoprotein showed correlation with the sperm count and the germinal cells concentration. We also found correlation between testosterone and/or LH concentrations and sperm count in both groups. These results indicate modifications in the hormonal concentrations regulating the testicular function and in their relationship, in men with testicular damage, which can render a change in the mechanisms controlling this function.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMedDate not supplied

[Results of laparoscopic bilateral varicocelectomy].

Left varicocele (LV) is a common clinical condition that is present in approximately 15% of the general male population. Bilateral varicocele (BV) is an association of clinical LV and subclinical or ultrasound diagnosed right varicocele. Recent diagnostic technology suggests that BV is much more common than previously suspected varying from 15 to 57%. The laparoscopic technique offers the possibility of planning bilateral varix ligation but only a few reports are currently available. The aim of this study was to evaluate the outcome of contemporary bilateral correction of BV on spermatogenesis. From 1992 January to 1998 December a total of 207 patients with clinical left varicocele and a pathological sperm count were studied. Scrotal sonography was performed and in 96 patients (group A) subclinical right varicocele was diagnosed while 111 patients (group B) only had LV. 84 patients were married and had tried unsuccesfully for a pregnancy for at least one year before evaluation. All patients underwent laparoscopic varicocelectomy, performed under general anesthesia with a three trocar technique with application of clips to the spermatic vein and resection. Patients with right reflux received bilateral varix ligation. Operating time averaged 28 minutes for unilateral cases and 42 minutes for bilateral legatures. No significant differences were found in age distribution or preoperative seminal paramenters between the two groups. Postoperative hospital stay was 1.2 and 1.3 days respectively. 168 patients underwent sperm count four to six months after surgery. Both groups showed improvements in number (group A 41 millions, group b 27 millions), 2nd hour motility (group A 32%, group B 19%) and morphology (group A 52%, group B 51%). 95 patients achieved normalization of seminal parameters, 40 (63%) in group A and 37 (30%) in group B, and there was a statistically significant difference between the two groups. The pregnancy rate was calculated on married population after one year; it was 41% in total. The role of the subclinical right varicocele associated to clinical left varicocele is uncertain and there are few papers concerning this argument. In this serie normalization of seminal parameters and the pregnancy rate were significantly higher in patients with bilateral correction of reflux. In conclusion our data confirm that subclinical right reflux also has a detrimental effect on spermatogenesis and we suggest that it must be corrected contemporary when associated with clinical left varicocele.

Adolescent↗
PubMed2000

Acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in pregnant Long Evans rats: association of measured tissue concentrations with developmental effects.

Prenatal exposure to TCDD interferes with fetal development at doses lower than those causing overt toxicity in adult animals. Exposure to TCDD during development produces alterations in the reproductive system of the developing pups- delayed puberty and reduced sperm counts in males and malformations in the external genitalia of females. The objectives of this study were to determine maternal and fetal tissue concentrations of TCDD after acute exposure and whether these tissue concentrations can be used to estimate the intensity of the developmental abnormalities reported by other laboratories. Pregnant Long Evans rats received a single, oral dose of 0.05, 0.20, 0.80, or 1.0 microg [3H]-TCDD/kg on gestation day (GD) 15, and maternal and fetal tissue concentrations of TCDD were measured on GD16 and GD21. On GD16, maternal liver contained the greatest amount of TCDD (30-47% administered dose). One day after administration of 0.20 microg TCDD/kg on GD15, there were 13.2 pg TCDD/g present in an individual fetus. This concentration is associated with delayed puberty and decreased epididymal sperm counts in male pups as well as malformations in the external genitalia of females. For the responses studied, tissue concentration measured during a critical period of gestation adequately predicts the intensity of the response. In addition, there was a strong correlation between fetal body burden and maternal body burden on GD16. A dose of 0.05 microg TCDD/kg resulted in maternal body burdens of 30.6+/-3.1 and 26.6+/-3.1 ng TCDD/kg on GD16 and GD21, respectively. In conclusion, low-level TCDD exposure during the perinatal stage of life can produce adverse effects within the developing pups and that tissue concentration measured during a critical period is the appropriate dose metric to predict adverse reproductive and developmental effects.

Animals↗
PubMed2001

Effects of neonatal exposure to a high-dose p-tert-octylphenol on the male reproductive tract in rats.

Time-course alterations in morphological changes of the reproductive tract including spermatogenesis as well as pituitary and gonadal hormones, reproductive ability, and the size of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were investigated in male rats neonatally exposed to 100 mg/kg p-tert-octylphenol (OP) subcutaneously. OP treatment affected hormone levels of follicle stimulating hormone (FSH) and testosterone, reproductive organ weights and sperm counts. Slightly depressed FSH levels at prepuberty and prolonged suppression of testosterone till 7 weeks of age were observed as two hormonal alterations. The lasting reduction in testosterone appeared to be associated with growth inhibition of male reproductive organs such as the testis, prostate and epididymis, these demonstrating low organ weights compared with those of age-matched controls till 7 weeks of age. The FSH concentrations after puberty showed a rise to values equal to or higher than those of the control group, suggesting recovery of maturation of the reproductive tract. No morphological abnormalities, even with morphometric stage analysis of spermatogenesis, were detected in the male reproductive tract throughout the study. Size of the SDN-POA and reproductive ability was comparable to those in controls. At the termination (18 weeks of age), however, a reduction in the sperm count in the epididymis of OP-treated animals demonstrated a possibility that the male reproductive system might be still affected by neonatal exposure to OP. The results observed demonstrate that neonatal exposure to a high-dose OP exerts estrogenic action directly or indirectly, resulting in slight but prolonged impairment of the male reproductive tract. The suppression of FSH caused by modulation of the hypothalamus-pituitary control system may be the trigger for the impairment, while the possibility of direct estrogenic action of OP is not ruled out. Our results also indicate that more sensitive endpoints should be established to detect the effects of neonatal exposure to estrogens or estrogenic compounds on the male reproductive tract.

Animals↗
PubMed1994

Case-control study of whether subfertility in men is familial.

OBJECTIVE: To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause. DESIGN: Case-control study and segregation analysis. SETTING: Two teaching hospitals in Leeds. SUBJECTS: Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department. MAIN OUTCOME MEASURES: The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers. RESULTS: Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families. CONCLUSION: Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.

Adult↗
PubMed2003

Traffic pollutants affect fertility in men.

BACKGROUND: Given the lack of consensus about the effect of traffic-derived pollutants on male fertility, we evaluated semen quality in men occupationally exposed to traffic. METHODS: Semen quality was investigated in 85 men employed at motorway tollgates and in 85 age-matched men living in the same area. Semen, circulating sex hormones, methaemoglobin, sulphaemoglobin, carboxyhaemoglobin, lead (Pb) and zinc (Zn) protoporphyrin were assayed. Environmental carbonium oxide, nitrogen oxide, sulphur oxide and Pb were also measured. RESULTS: Sperm count, and serum levels of FSH, LH and testosterone were within normal range in both groups. Total motility, forward progression, functional tests and sperm kinetics were significantly lower in tollgate workers versus controls. In a subset of tollgate workers with motility below normal, methaemoglobin was inversely correlated with total motility, viability, the hypo-osmotic swelling test, the acridine orange test, the cervical mucus penetration test, linearity, and amplitude of lateral movement of the sperm head, whereas blood levels of Pb were inversely correlated with viability and sperm count. CONCLUSIONS: The finding that blood methaemoglobin and Pb were inversely correlated with sperm parameters indicates that nitrogen oxide and Pb adversely affect semen quality.

Adult↗
PubMed1995

Diagnosing testicular function using 31P magnetic resonance spectroscopy: a current review.

Patients with low sperm counts combined with normal concentrations of gonadotrophins, and in whom physical examination and post-ejaculatory urine analysis are normal, present a diagnostic dilemma. This situation can be caused by testicular failure or by ductal obstruction, which have very different clinical prognoses. Ductal obstruction might be correctable by microsurgical vasovaso/vasoepididymostomy, whereas this approach is of no use in primary testicular failure. A possible diagnostic step for these patients is a testicular biopsy to differentiate between hypospermatogenesis and a normal gonad. However, to date testicular biopsy is seldom performed because of its invasive character. An alternative accurate, non-invasive method to assess testicular function could be very helpful in the evaluation of idiopathic azoospermia or idiopathic oligozoospermia. During the past decade, magnetic resonance (MR) spectroscopy has been developed from a scientific tool into a non-invasive clinical diagnostic tool and has also been used to study testicular function. Recent studies have shown that 31P-MR spectroscopy, based upon differences in the ratio of peaks of phosphomonoester to beta-adenosinetriphosphate, is a non-invasive technique able to differentiate between groups of patients with testicular failure and ductal obstruction, and it correlates reasonably well with the averaged mean Johnsen score of testicular biopsy. The role for a non-invasive technique in the diagnosis of male infertility, such as 31P-MR spectroscopy, can be manifold. It serves not only as an alternative for biopsy but can also be used to assess obstruction as the cause of infertility in patients with subnormal sperm counts, and to predict the chances of pregnancy in patients planned for vasovasostomy to correct a prior vasectomy. However, the main limitation to MR spectroscopy becoming a universal clinical diagnostic technique is the limited availability of 1.5 Tesla MR scanners.

Biopsy↗
PubMedDate not supplied

Heterologous ovum penetration test and seminal parameters in fertile and infertile men.

Sperm penetration rates in the heterologous ovum penetration test were correlated with results of routine semen analysis in 30 fertile and 50 infertile men. There was no difference in penetration rates when comparing infertile men with normal and abnormal seminal parameters, nor was any difference seen between fertile (15-83%) and infertile men (8-83%). Of the 22 infertile men with normal seminal characteristics, seven had partners with no discernible reproductive dysfunction. The penetration rates of these men (38-81%) did not differ from those of fertile men. Stepwise regression analysis of seminal characteristics, with penetration as the dependent variable, indicated that sperm count and morphology are the most important seminal parameters for fertility assessment. Discrimination analysis revealed that sperm numbers and morphologic variables provide significant information for discriminating between fertile men and infertile men with normal or abnormal seminal characteristics. Sperm penetration and motility were not indicated as important factors. The present data suggest that, in unselected male patients seeking reproductive evaluation, the sperm penetration assay did not yield any additional information on the cause of infertility.

Adult↗
PubMed2002

Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism.

OBJECTIVE: To assess the efficacy and safety of recombinant human follicle-stimulating hormone (rhFSH; follitropin alpha) in increasing sperm concentration in 26 men with severe isolated hypogonadotropic hypogonadism (IHH). DESIGN: Clinical and endocrine studies using an open design. SETTING: Six university clinical sites in three European countries. PATIENT(S): Azoospermatic patients aged 16 to 48 years with IHH. INTERVENTION(S): Patients received hCG for up to 6 months before 18 months of treatment with rhFSH. Sperm count, motility, and morphology were assessed every 3 months. MAIN OUTCOME MEASURE(S): Achievement of a sperm concentration of 1.5 x 10(6)/mL. RESULT(S): Spermatogenesis was achieved in 15 of 19 patients who could be evaluated, 12 achieving a sperm concentration of > or =1.5 x 10(6)/mL. CONCLUSION(S): With hCG, rhFSH is effective in initiating spermatogenesis in patients with IHH, and is well tolerated.

Adolescent↗
PubMed1995

Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection.

OBJECTIVE: To describe the preparation of fresh or frozen-thawed epididymal and testicular sperm for intracytoplasmic single sperm injection and to compare the fertilization, embryo quality, and pregnancy rates (PRs) obtained after using these spermatozoa to the results when freshly ejaculated sperm was used for microinjection. DESIGN: Retrospective analysis of 1,034 consecutive microinjection cycles. Ejaculated (965 cycles), fresh epididymal (43 cycles), frozen-thawed epididymal (9 cycles), and testicular sperm (17 cycles) was used for intracytoplasmic sperm injection. SETTING: Procedures were performed in a tertiary IVF center coupled with an institutional research environment. MAIN OUTCOME MEASURES: Semen density and motility were judged by the World Health Organization criteria and sperm morphology was evaluated by the Tygerberg's strict criteria. After microinjection, oocyte intactness, fertilization, embryo cleavage, transfer, and PRs were evaluated and compared. RESULTS: The median values of total sperm count, total motility and normal morphology were 17.85 x 10(6), 37%, 8% for freshly ejaculated sperm; 46.20 x 10(6), 12%, 9% for fresh epididymal sperm; 0.15 x 10(6), 0%, 0% for frozen-thawed epididymal sperm; and 0.54 x 10(6), 0% for testicular sperm (morphology was not determined). The percentage of intact oocytes after microinjection ranged from 84% to 90%. Normal fertilization rates were high when fresh or frozen-thawed epididymal and testicular spermatozoa were used for the injection (56%, 56%, 48%, respectively) but were significantly lower than for ejaculated sperm (70%). There was a higher proportion of transferable embryos obtained after ejaculated sperm injection than after testicular sperm injection. Forty percent, 58%, 33%, and 46% of cycles had positive serum hCG using ejaculated, fresh, or frozen-thawed epididymal and testicular sperm. Initial pregnancy loss occurred in 26.3% of the conception cycles. CONCLUSION: Intracytoplasmic sperm injection can provide high normal fertilization, cleavage, and PRs when fresh or frozen-thawed epididymal and testicular spermatozoa are used, but normal fertilization rates are significantly lower than after microinjection with ejaculated sperm.

Adult↗
PubMed1987

Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann's syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis.

Intranasal (in) GnRH spray caused induction and maintenance of spermatogenesis and biological paternity in a 28-yr-old man with Kallmann's syndrome. Prior treatment had included GnRH analog administration, which failed to induce puberty, and testosterone (T) enanthate weekly. Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased. The patient had then received 250 mg T enanthate/month for 2 yr and 7 months; it was discontinued 7 weeks before the in GnRH study began. At its start (July 1984) the subject's testis size was 7 mL, and he had azoospermia, low serum LH and FSH levels, and a serum T of 74 ng/dL (2.6 nmol/L). GnRH was administered in a dose of 200 micrograms (20-120 ng/kg were absorbed into the circulation) every 2 h, seven to nine times a day, between 0700 and 2400 h for 242 days. After 12 days of treatment, serum T had increased to 519 ng/dL (18.0 nmol/L). After 70 days, the patient's sperm count was 11.5 million/mL (4.5 mL ejaculate volume; 70% motility; 36% normal morphology); on day 185, sperm count was 31 million/mL (4 mL ejaculate volume; 54% motility; 36% normal morphology). His spouse conceived on day 162 and delivered a fullterm daughter 265 days later. The probability of paternity was 99.9994%. Our results suggest that induction and maintenance of spermatogenesis as well as fertility in hypothalamic hypogonadism can be achieved with in GnRH therapy if pituitary and testicular function are intact. Spermatogenesis induced by in GnRH has the same quality as spermatogenesis induced by hCG/human menopausal gonadotropin therapy. Patient compliance is probably the most important factor for the success of in GnRH therapy.

Adult↗
PubMed1983

Reproductive hazards in the workplace. Development of epidemiologic research.

Application of the techniques of epidemiology and clinical toxicology has accelerated study of the reproductive effects of toxic chemical and physical exposures in the workplace. Three examples of work in progress are included in the present communication. The first concerns 1,2-dibromo-3-chloropropane, a known cause of male sterility, which continues to be used as a nematocide in Hawaii. Occupational exposures of Hawaiian agricultural workers to airborne 1,2-dibromo-3-chloropropane are mainly in the range of parts per billion. A prospective study of pineapple field workers has been undertaken to evaluate sperm counts and morphology before, during, and after 1,2-dibromo-3-chloropropane application. To date, no sperm count depression is evident at this level of exposure. The second example involves a cluster of seven spontaneous abortions in female office workers exposed to video display terminals. The cluster has been analyzed with the use of fetal life tables. Excess incidence was confirmed (p = 0.0045), but no etiology was determined. The findings may have been due to chance. The third example pertains to male chemical workers manufacturing diaminostilbene, an optical brightener, and the workers' reported sexual impotence. Impotence was confirmed in 7 of 29 workers by questionnaire and suggested for another 7. Serum testosterone analyses found depressed values (less than 300 mg/ml) in 8 of 28 exposed workers. The luteinizing hormone and follicular stimulating hormone levels were generally normal.

Abortion, Spontaneous↗
PubMed1985

Failure of high-dose sustained release luteinizing hormone releasing hormone agonist (buserelin) plus oral testosterone to suppress male fertility.

Previously we have demonstrated that sperm counts of normal young men decreased during constant subcutaneous infusion of the LHRH agonist buserelin (118 or 230 micrograms/d). In order to test whether azoospermia can be achieved with higher doses, seven young men received 450 micrograms buserelin subcutaneously daily for 12 weeks via extracorporeal osmotic minipumps. To avoid symptoms of androgen deficiency, oral supplementation with 80 mg/d testosterone undecanoate (TU) was initiated in week 5 and was increased to 120 mg/d by week 8. Follow-up after treatment lasted for another 12 weeks. In order to evaluate possible psychotropic effects of treatment-related endocrine changes, continuous psychometric testing was performed focusing on personality, emotions and sexuality. After an initial rise, both serum LH and FSH returned to normal. FSH was below normal during the 3rd-5th week following treatment. LHRH stimulation tests performed at the end of treatment showed pituitary desensitization. Serum T (always measured between 0800 and 1300 h at least 12 h after last TU) tended to decrease by week 7 and remained slightly depressed until the end of treatment while libido, potency and emotional well-being remained unchanged. While testicular volumes showed a reduction from week 7 of treatment to week 10 post-treatment, sperm counts decreased only insignificantly from 65 +/- 10 to 44 +/- 14 million per ml in week 12 post-treatment. Severe oligo- or azoospermia was not observed in any of the seven men. It is concluded that full androgen substitution by TU can drastically delay if not abolish the antifertility effect of LHRH-induced pituitary desensitization.

Administration, Oral↗