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In most mammals, pituitary-testicular hormone secretion is very active during the perinatal period, but the physiological significance of this function for later pituitary-gonadal interactions and sexual maturation is largely unknown. Short-term neonatal treatment with gonadotropin-releasing hormone (GnRH) antagonist results in delayed sexual maturation and infertility in male rats. We have now extended our earlier findings and studied in more detail the pituitary-gonadal function in adult rats after such neonatal treatment. In this study, the pituitary-testicular activity of newborn male rats was temporarily blocked by treatment with a GnRH antagonist analogue (N-Ac-4-Cl-D-Phe1, 4-Cl-D-Phe2, D-Trp3, D-Phe6, des-Gly10-GnRH-D-alanylamide; Organon 30039; 2 mg/kg s.c. twice daily) on Days 1-5 of life. Timing of puberty was slightly delayed in the treated rats (average: 2 days, p less than 0.05), as determined by the age of the balano-preputial separation. In adult rats (90-110 days), only 3 of the 17 rats treated neonatally with GnRH antagonist were fertile (14 of 17 controls, p less than 0.01), despite normal circulating androgen levels. Pituitary and serum follicle-stimulating hormone (FSH) levels were slightly but consistently elevated (20-30%; p less than 0.05) in antagonist-treated animals, whereas luteinizing hormone (LH) levels (both immunoreactive and bioactive) were unaffected. The pituitary contents of GnRH receptors were increased in antagonist-treated animals 85 +/- 6.6 (mean +/- SEM, n = 19) vs. 58 +/- 4.1 fmol/gland in controls (n = 20; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neonatal treatment of male rats with a gonadotropin-releasing hormone antagonist results in altered function of the pituitary-testicular axis in adult age. 269 58

Daily concentrations of salivary progesterone (P) were measured from 32 women during a complete menstrual cycle. Seventeen of the subjects were university students and 15 were patients of an infertility clinic (a severe male-factor was verified as the cause of infertility in all of them). Commercially available reagents for radio-immunoassay of serum P were modified for salivary measurements, to yield acceptable precision and sensitivity (40 pmol/l). Good correlation (r = 0.93) was found between salivary and serum P concentrations in samples collected simultaneously. The follicular phase levels of salivary P were below 100 pmol/l, and those at the luteal peak were 390 +/- 45 pmol/l (mean +/- SEM, n = 24). From the menstrual salivary P concentration curves we identified the first day of significant elevation above mean follicular levels (T2) and thereafter calculated the cumulative sum of daily P concentrations until 95% of the luteal phase secretion had accumulated (C95). The time needed to reach C95 (designated T95) and logC95 were plotted in coordinates and used as the basis of evaluation of normal menstrual P secretion. The observations were distributed in two groups, one with clearly identifiable T2 and a distinct luteal-phase P (ovulation had occurred) and one with no identifiable T2 and absent luteal-phase P peak (indicative of anovulation). Interestingly, 47% of the student population had an abnormally low menstrual P profile while all the other subjects displayed a clear luteal-phase peak of salivary P. These data provide more evidence for applicability of salivary P measurements for diagnosis of corpus luteam function and highlight the difficulty of selecting representative reference populations in studies on female reproductive endocrinology.
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PMID:Daily measurements of salivary progesterone reveal a high rate of anovulation in healthy students. 274 Aug 29

In order to detect peritoneal abnormalities that could account for infertility associated with endometriosis, 122 infertile individuals were studied at the time of laparoscopy for diagnostic purposes or for in vitro fertilization. Four groups were defined: group 1, laparoscopy without endometriosis; group 2, laparoscopy with endometriosis; group 3, in vitro fertilization without endometriosis; and group 4, in vitro fertilization with endometriosis. Mean peritoneal fluid volume was greater, although not significantly so, in group 4 (29.0 +/- 6.6 ml, mean +/- SEM) than in group 3 (18.2 +/- 2 ml). The concentration and total number of pelvic macrophages were similar for groups 1 and 2. The total number of pelvic macrophages was increased in group 4 (16.9 +/- 4.2 x 10(6)) versus group 3 (10.0 +/- 1.8 x 10(6)) (p = 0.08). The mean sperm phagocytosis in vitro did not differ among the four groups studied. Interleukin 1 activity within the peritoneal fluid and the in vitro interleukin 1 production rate did not differ between individuals with and without endometriosis. Peritoneal fluid and macrophage supernatants from individuals with endometriosis were not embryotoxic when studied in an in vitro mouse embryo system.
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PMID:Local peritoneal factors: their role in infertility associated with endometriosis. 296 Dec 65

Androgen insensitivity has been reported to be present in as many as 40% of patients with severe oligospermia. In order to evaluate further the role of androgen resistance in male infertility we studied 24 men with severe oligospermia. Plasma T and LH were measured by RIA and the T X LH product was calculated. Fibroblasts were grown from genital skin obtained during testicular biopsies and androgen receptor maximal binding capacity (BMAX) and affinity (KD) were measured in fibroblast monolayers. Pubic skin 5 alpha-reductase activity, an androgen-dependent enzyme, was measured in skin homogenates. Plasma T values were in the upper normal range [7.0 +/- 1.7 (SEM) ng ml-1] whereas the T X LH product was high (greater than 50) in only six patients. Mean BMAX and KD values for the androgen receptor were normal [BMAX: 788 +/- 259 fmol mg DNA-1 (patients, n = 20), 726 +/- 227 (normal men, n = 20), and KD: 0.27 +/- 0.24 (patients, n = 20), 0.18 +/- 0.09 (normal men, n = 15), respectively]. However, four men had supranormal KD values. The mean BMAX was also normal when the group of men with sperm densities below 10(6) per ejaculate was considered separately. Public skin 5 alpha-reductase activity was normal in all but four patients (patients: 177.1 +/- 91 fmol/mg skin/h, n = 30, normal men: 210 +/- 45, n = 20 patients). In conclusion, androgen receptor BMAX levels were normal in all patients studied, regardless of the sperm density and the T X LH product. Pubic skin 5 alpha-reductase activity was also normal in all but four patients. In these four patients, a qualitative defect of the androgen receptor cannot be excluded. In this group of patients with severe oligospermia, infertility did not seem to be related to quantitative abnormality of the androgen receptor as was previously reported.
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PMID:Androgen insensitivity in oligospermic men: a reappraisal. 309 23

The presence of a varicocele in adult men has been correlated with infertility. This study documents the effect of an experimentally induced unilateral varicocele in 21-day-old juvenile prepubertal and 51-day-old adult rats (n = 10 per group) on subsequent adult testicular function. Varicoceles were induced by partial occlusion of the spermatic vein. There were ten sham-operated and five nonoperated control rats in each age group. The rats were sacrificed 1 month after surgery. Intrascrotal temperatures were elevated in both groups with varicoceles. Histologically, the ipsilateral testes of rats in both age groups demonstrated a decrease in the numbers of functioning seminiferous tubules and germ cells, but the decrease was significantly greater in the juveniles than in the adult rats. No changes were seen in the contralateral testes. Significant titers of cytotoxic sperm antibodies were present in all animals with varicoceles, which is in contrast to controls. The juveniles had significantly lower antibody titers (mean log2 +/- SEM; 3.2 +/- 0.09 vs. 8.5 +/- 1.1, P less than 0.001) than the adults. The induction of a unilateral varicocele damaged spermatogenesis and testicular function to a greater extent in juveniles than in adult rats. This damage may be immune complex-mediated.
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PMID:Pathological and immunological effects of surgically induced varicocele in juvenile and adult rats. 320 38

To investigate ultrastructural modifications in the endometrium of women receiving clomiphene citrate (CC) treatment, we performed endometrial biopsies in the preovulatory phase in 17 patients with anovulatory infertility and 16 normo-ovulating women with tubal or male sterility. Histology, scanning and transmission electron microscopy (SEM and TEM) revealed midproliferative phase aspects in 11.7% of the treated group and 6% of the controls, late proliferative aspects in 76.4% and 82%, and postovulation days 1-3 characteristics in 11.7% and 12% respectively. No significant differences were observed between the patients and controls; our data indicate that CC taken in a dose not exceeding 100 mg/day from day 3 of the cycle can induce endometrial maturation that is almost identical with that of a spontaneous preovulatory phase. This type of endometrium should therefore allow implantation of a fertilized egg and maintain unmodified the complex biohumoral relations with the embryo.
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PMID:Structural and ultrastructural patterns of the human preovulatory endometrium following clomiphene citrate treatment. 324 35

Multidisciplinary andrology deals with clinical application and modern technology for the evaluation and differential diagnosis of male infertility with emphasis on morphological, anatomical, biochemical, immunological, hereditary, and microbiological parameters. Little is known about the effects of diet, disease, stress, environmental, and drugs on male-related unexplained infertility of couples. Regional, national, and international centers of multidisciplinary andrology should provide (1) extensive and unique clinical services; (2) a computerized "patient referral center," (3) self-learning packages (slides/tape programs) for patients; and (4) a computer link to the National Library of Medicine and the Drug Information Center. Specialized laboratories and clinics can be served by expert consultants, visiting professors, bilingual and well-trained clinicians, nurses, laboratory technologists, computer operators, and related allied health personnel. Patient education pamphlets, updated every few years, can be distributed during training workshops when an extensive network of remote teleprinters can be utilized. Qualified client location may install a printer to allow on-site printing of reports in the shortest possible time. Special mailing containers are provided to clients who wish to mail their laboratory specimens. Other clinical services may include the following: 1. Central source of communication and information in andrology; 2. International roster of multidisciplinary andrology centers; 3. Patient referral to centers and consultations for developing countries; 4. Screening of husbands and wives for in vitro fertilization/embryo transfer (IVF/ET); 5. Screening of couples with unexplained infertility for sexually transmitted diseases (STDs) including AIDS; 6. Exchange of research material and methodology; 7. Coordination of multicenter research; 8. Organizing training workshops for clinicians, nurses, and laboratory technicians; 9. Establishing a repository of films, video tapes, slides, catalogs, instrumentation, books, SEM photos, and atlases; 10. Publication and editorial assistance; 11. Consultation for the appropriate selection, purchase, and quality control of instrumentation (all on one computer system); 12. Evaluation of new diagnostic tools for idiopathic infertility and fertility regulation; 13.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interdisciplinary andrology. STDs. AIDS research. 330 63

We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis.
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PMID:Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study. 335 15

Semen samples from 55 fertile nonautoimmune and 44 infertile sperm autoimmune men were evaluated by computerized sperm cell motion analysis. Sperm counts (mean +/- SEM, 59.6 +/- 10.3 X 10(6) per ml), motility (39.0 +/- 4.6%), mean swimming speed (micron/sec, 26.5 +/- 0.9), mean linearity (straight line distance of the cell track divided by the actual track length and multiplied by 10, 6.5 +/- 0.2), and motility index (% motility X mean speed, 10.7 +/- 1.4) in 23 men with significant titers of cytotoxic sperm antibodies in their serum and seminal plasma were less (p less than 0.0001) than those in the fertile controls. However, these parameters were comparable in 18 men with sperm antibodies in their seminal plasma but not in their serum, and the control group. Infertile men with serum cytotoxic sperm antibodies had more sperm cells swimming at 11-30 micron/sec, and fewer moving at 31 micron or higher; this was in contrast to results obtained from fertile men (p less than 0.05). The percentages of sperm cells moving at 21-30 micron/sec were increased, while those moving at 51-60 microns/sec were decreased in men with seminal plasma sperm antibodies, versus controls. Spermatozoa with low linearities (less than or equal to 6) were higher (p less than 0.05) in men with serum and seminal plasma cytotoxic sperm antibodies than in the fertile group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Motion characteristics of spermatozoa from men with cytotoxic sperm antibodies. 381 56

Sperm morphology and motility are believed to be important prognostic factors for fertility. Results of a group of 67 men investigated for primary infertility who had mean sperm concentrations greater than 5 million per ml and who later produced pregnancies, were compared with those of 67 matched controls who remained infertile. All female partners were potentially fertile. The groups were matched for other known prognostic factors for fertility, namely, wife's age, the duration of infertility, sperm concentration and varicocele size. There were no significant differences between the two groups overall in the (mean +/- SEM)% of sperm with normal morphology (58.3 +/- 2.1; 58.5 +/- 2.2), or motility (40.6 +/- 1.8; 37.0 +/- 2.0). However, among oligospermic men from the two groups, sperm motility was significantly higher (P less than 0.05) in the subsequently fertile group (43.1 +/- 2.6%) than in the persistently infertile group (33.3 +/- 3.7). These results indicate that sperm morphology as currently assessed may not be important in predicting fertility in subfertile men with a mean sperm concentration over 5 million/ml and the % sperm motility may only be a relevant predictor in oligospermic men.
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PMID:Are conventional sperm morphology and motility assessments of predictive value in subfertile men? 383 60


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