High-resolution array-CGH analysis on 46,XX patients affected by early onset primary ovarian insufficiency discloses new genes involved in ovarian function.

STUDY QUESTION: Can high resolution array-CGH analysis on a cohort of women showing a primary ovarian insufficiency (POI) phenotype in young age identify copy number variants (CNVs) with a deleterious effect on ovarian function? SUMMARY ANSWER: This approach has proved effective to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms. WHAT IS KNOWN ALREADY: POI describes the progression toward the cessation of ovarian function before the age of 40 years. Genetic causes are highly heterogeneous and despite several genes being associated with ovarian failure, most of genetic basis of POI still needs to be elucidated. STUDY DESIGN, SIZE, DURATION: The current study included 67 46,XX patients with early onset POI (<19 years) and 134 control females recruited between 2012 and 2016 at the Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano. PARTICIPANTS/MATERIALS, SETTING, METHODS: High resolution array-CGH analysis was carried out on POI patients' DNA. Results of patients and female controls were analyzed to search for rare CNVs. All variants were validated and subjected to a gene content analysis and disease gene prioritization based on the present literature to find out new ovary candidate genes. Case-control study with statistical analysis was carried out to validate our approach and evaluate any ovary CNVs/gene enrichment. Characterization of particular CNVs with molecular and functional studies was performed to assess their pathogenic involvement in POI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 37 ovary-related CNVs involving 44 genes with a role in ovary in 32 patients. All except one of the selected CNVs were not observed in the control group. Possible involvement of the CNVs in POI pathogenesis was further corroborated by a case-control analysis that showed a significant enrichment of ovary-related CNVs/genes in patients (P = 0.0132; P = 0.0126). Disease gene prioritization identified both previously reported POI genes (e.g. BMP15, DIAPH2, CPEB1, BNC1) and new candidates supported by transcript and functional studies, such as TP63 with a role in oocyte genomic integrity and VLDLR which is involved in steroidogenesis. LARGE SCALE DATA: ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/); accession numbers SCV000787656 to SCV000787743. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis for almost all of the CNVs identified. Inheritance studies of CNVs in some non-familial sporadic cases was not performed as the parents' DNA samples were not available. Addionally, RT-qPCR analyses were carried out in few cases as RNA samples were not always available and the genes were not expressed in blood. WIDER IMPLICATIONS OF THE FINDINGS: Our array-CGH screening turned out to be efficient in identifying different CNVs possibly implicated in disease onset, thus supporting the extremely wide genetic heterogeneity of POI. Since almost 50% of cases are negative rare ovary-related CNVs, array-CGH together with next generation sequencing might represent the most suitable approach to obtain a comprehensive genetic characterization of POI patients. STUDY FUNDING/COMPETING INTEREST(S): Supported by Italian Ministry of Health grants 'Ricerca Corrente' (08C203_2012) and 'Ricerca Finalizzata' (GR-2011-02351636, BIOEFFECT) to IRCCS Istituto Auxologico Italiano.

Genetics of primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is characterized by a loss of ovarian function before the age of 40 and account for one major cause of female infertility. POI relevance is continuously growing because of the increasing number of women desiring conception beyond 30 years of age, when POI prevalence is >1%. POI is highly heterogeneous and can present with ovarian dysgenesis and primary amenorrhea, or with secondary amenorrhea, and it can be associated with other congenital or acquired abnormalities. In most cases POI remains classified as idiopathic. However, the age of menopause is an inheritable trait and POI has a strong genetic component. This is confirmed by the existence of several candidate genes, experimental and natural models. The variable expressivity of POI defect may indicate that, this disease may frequently be considered as a multifactorial or oligogenic defect. The most common genetic contributors to POI are the X chromosome-linked defects. Here, we review the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI with the expectation that this list will soon be upgraded, thus allowing the possibility to predict the risk of an early age at menopause in families with POI.

Genetic defects of ovarian TGF-ß-like factors and premature ovarian failure.

Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles; POF affects approximately 1-2% of women under the age of 40 yr, thus representing one major cause of female infertility. POF relevance is continuously growing because women tend to conceive always more frequently beyond 30 yr. Frequently, POF is the end-stage of an occult process [primary ovarian insufficiency (POI)]. POI is a heterogeneous disease caused by a variety of mechanisms. Though the underlying cause remains unexplained in the majority of cases, several data indicate that POI has a strong genetic component. These data include the existence of several causal genetic defects in human, experimental, and natural models, as well as the frequent familiarity. The candidate genes are numerous, but POF remains unexplained in most of the cases. Several recent evidences have driven the attention of researchers on the possible involvement of various elements belonging to the transforming growth factor ß family, which includes bone morphogenetic proteins, growth/differentiation factors, and inhibins. These peptides are produced by either the oocyte or granulosa cells to constitute a complex paracrine network within the ovarian follicle. Here, we review the studies reporting the genetic alterations of these factors in human and animal defects of ovarian folliculogenesis which support the fundamental roles played by these signals in ovarian morphogenesis and function.

Open partial nephrectomy with no clamping of the pedicule: a good surgical option in treatment of renal cancer.

AIM: The aim of the present work was to describe authors' surgical experience using the partial nephrectomy technique without intraoperatory pedicle clamping for masses even up to 4 cm of size. METHODS: The study enrolled 96 patients with an average age of 59.7 years, who underwent partial nephrectomy without pedicle clamping. The average dimensions of the masses treated were 3.7x3x3.8. In preoperative and in postoperative time creatinine, hemoglobine, hematocrit and platelets were monitored. The follow-up was of 1-3-6 months. At the third month postoperatively a renal US scan was performed, together with a control CT scan and at the sixth month of follow-up the patients underwent also a control Tc99/DMSA renal scintigraphy in back, front, oblique and right posterior oblique left rear projections. RESULTS: Surgery and anesthesia time have been respectively of 1 h 51 min e 2 h 30 min. In the postoperative time the average values were: creatinine 1.46 ng/mL (±0.45), hemoglobin: 11.25 g/dL (±1.6), hematocrit: 36.4 % (±3), platelets: 205 x 103 (±45 x 103). At follow-up at 1-3-6 months the average values were: creatinine 1.16 ng/dL (±0.66), hemoglobin 14.13 g/dL (±0.13), hematocrit 42.43% (±1.03), platelets 204 x 103 U/L (±1.66 x103). After six months the renal function demonstrated intraparenchymal homogeneous distribution of the drug in all the patients, with a 7% of difference of relative uptake by the operated kidney than the healthy controlateral one. CONCLUSION: The partial nephrectomy without intraoperative pedicle clamping can be a good therapeutic option for the treatment of kidney cancer for masses even up to 4 cm of size. The follow-up should be longer to assess oncological results.

Renin secretion by the spontaneously diabetic rat.

Renal function studies and measurements of in vivo plasma renin activity (PRA), kidney renin content, and renin secretion by isolated, perfused kidneys were performed in spontaneously diabetic and nondiabetic BioBreeding/Worcester (BB/W) rats. Diabetic animals evidenced hyperglycemia, glycosuria, and plasma volume expansion. After dietary sodium deprivation, plasma volume fell to levels equivalent to those of sodium-deprived, nondiabetic rats. Dietary sodium deprivation evoked a larger proportional increase in PRA among diabetic than nondiabetic animals, although PRA before sodium restriction was equivalent in the two groups. Basal renin release (RR) was higher from isolated, perfused kidneys from diabetic rats than from nondiabetic kidneys. Diabetic kidneys, moreover, displayed increased kidney renin content (KRC). By contrast, while isoproterenol (10(-5) M) stimulated a nearly fivefold increment in RR from nondiabetic, perfused kidneys, a negligible effect was observed in diabetic kidneys. The dose-response curve of renin secretion (as a proportion of total renal content) in response to isoproterenol was shifted downward. Hence, while KRC and spontaneous RR by isolated, perfused kidneys were increased, the increment in PRA with salt depletion and the renin-secretory response to isoproterenol in vitro were impaired. We propose that specific defects in renin secretion, in particular, the response to beta-adrenergic stimulation, may be operative in diabetes.

Glomerulopathy in spontaneously diabetic rat. Impact of glycemic control.

The spontaneously diabetic BioBreeding/Worcester (BB/W) rat was used to examine the role of glycemic control in the pathogenesis of diabetic glomerulopathy and proteinuria. Nondiabetic BB/W rats (group 1) were compared with moderately (group 2) and severely (group 3) hyperglycemic diabetic animals of similar age. Urinary protein excretion and morphometric measurements of glomerular basement membrane (GBM) width and mesangial area were performed after 4, 8, and 12 mo of study. At 4 mo, urinary protein excretion both in group 2 (9.3 +/- 0.7 mg/24 h) and group 3 (24.8 +/- 1.98 mg/24 h) exceeded that in group 1 (5.4 +/- 0.6 mg/24 h; P less than .05). Moreover, proteinuria in group 3 was significantly greater than in group 2 (P less than .05). In addition, proteinuria increased in group 3 animals between 4 and 12 mo of study but did not advance in groups 1 or 2. GBM width in both diabetic groups (168.8 +/- 2.4 and 165.7 +/- 2.2 nm, groups 2 and 3, respectively) exceeded that in group 1 (148.3 +/- 3.8 nm; P less than .01) by 4 mo. At 12 mo, severely hyperglycemic group 3 animals had significantly greater GBM thickening than group 2. GBM width increased in all three groups over the course of study, but the rate of growth did not differ between groups 1 and 2. However, the rate of growth in group 3 was greater than in either group 1 or group 2. Urinary protein excretion correlated significantly with GBM width in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation.

Oils enriched in certain polyunsaturated fatty acids suppress joint pain and swelling in rheumatoid arthritis (RA) patients. Because T lymphocyte activation is important to propagation of joint tissue injury in patients with RA, we examined the effects of fatty acids administered by mouth in vivo on proliferation of human lymphocytes activated through the T cell receptor complex. T cell proliferation was reduced after oral administration of 2.4 g gammalinolenic acid in capsules of borage seed oil. Oral administration of oils enriched in linoleic acid, the parent n-6 fatty acid, and alpha linolenic acid, the parent n-3 fatty acid, did not influence growth of stimulated cells. Fatty acid analyses indicated that suppression of lymphocyte proliferation after gammalinolenic acid administration was associated with increased plasma and peripheral blood mononuclear cell concentrations of gammalinolenic acid and dihomogammalinolenic acid.

B cells expressing IL-10 mRNA modulate memory T cells after DNA-Hsp65 immunization.

In DNA vaccines, the gene of interest is cloned into a bacterial plasmid that is engineered to induce protein production for long periods in eukaryotic cells. Previous research has shown that the intramuscular immunization of BALB/c mice with a naked plasmid DNA fragment encoding the Mycobacterium leprae 65-kDa heat-shock protein (pcDNA3-Hsp65) induces protection against M. tuberculosis challenge. A key stage in the protective immune response after immunization is the generation of memory T cells. Previously, we have shown that B cells capture plasmid DNA-Hsp65 and thereby modulate the formation of CD8+ memory T cells after M. tuberculosis challenge in mice. Therefore, clarifying how B cells act as part of the protective immune response after DNA immunization is important for the development of more-effective vaccines. The aim of this study was to investigate the mechanisms by which B cells modulate memory T cells after DNA-Hsp65 immunization. C57BL/6 and BKO mice were injected three times, at 15-day intervals, with 100 µg naked pcDNA-Hsp65 per mouse. Thirty days after immunization, the percentages of effector memory T (TEM) cells (CD4+ and CD8+/CD44high/CD62Llow) and memory CD8+ T cells (CD8+/CD44high/CD62Llow/CD127+) were measured with flow cytometry. Interferon γ, interleukin 12 (IL-12), and IL-10 mRNAs were also quantified in whole spleen cells and purified B cells (CD43-) with real-time qPCR. Our data suggest that a B-cell subpopulation expressing IL-10 downregulated proinflammatory cytokine expression in the spleen, increasing the survival of CD4+ TEM cells and CD8+ TEM/CD127+ cells.

Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain.

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

High-dose chemotherapy with bone marrow transplantation for advanced colorectal cancer.

A chemotherapy regimen based on high doses of BCNU and mitomycin C with autologous bone marrow transplantation was used in 18 patients with advanced colorectal carcinoma. Haematological toxicity was manageable, with a short nadir for white blood cells and platelets. The response rate was 33%, with a prevalence in peritoneal lesions compared to liver or lung metastases. Extra-haematological toxicity appeared in 16% of cases: a case of veno-occlusive disease of the liver and two cases of lung impairment are discussed. Although the response rate obtained with the regimen was satisfactory, the more extensive use of high-dose chemotherapy followed by autologous bone marrow transplantation requires the identification of less toxic protocols.

A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer.

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids.

Oils enriched in certain polyunsaturated fatty acids suppress joint pain and swelling in rheumatoid arthritis patients with active synovitis. Because T lymphocyte activation is important for propagation of joint tissue injury in patients with rheumatoid arthritis, we examined the effects of fatty acids added in vitro on proliferation of human T lymphocytes stimulated with monoclonal antibodies to CD3 and CD4. Unsaturated fatty acids reduced T cell proliferation in a dose dependent manner (dihomogammalinolenic acid > gammalinolenic acid > eicosapentaenoic acid > arachidonic acid). Removal of fatty acids from cultures before cell stimulation did not change the effects, but addition of fatty acids after cell stimulation failed to reduce T cell responses. The saturated palmitic acid did not influence T cell growth. These studies indicate that small changes in cellular fatty acids can have profound effects on early events in T cell signaling and on T cell function.

Oxidative metabolism of anandamide.

In addition to the well studied hydrolytic metabolism of anandamide, a number of oxidative processes are also possible. Several routes somewhat analogous to the metabolism of free arachidonic acid have been reported. These involve mediation by various lipoxygenases and COX-2 and lead to ethanolamide analogs of the prostaglandins and HETES. The physiological significance of these products is not well understood at this time. There are also preliminary data suggesting a pathway involving oxidation of the hydroxy group of anandamide to a putative metabolite, N-arachidonyl glycine (AA-gly). This molecule displays activities in experimental models that suggest that it may play a role in some of the activities attributed to its precursor, anandamide.

Application of the Spherical Harmonic Model to the Study of the Terminal nu(CO) Spectra of Transition Metal Carbonyl Clusters.

The application of the spherical harmonic model to the interpretation of the terminal nu(CO) spectra of transition metal carbonyl clusters is explored. Unless there is strong spectral evidence to the contrary (when the tensor harmonic model is applicable), the coupling between CO vibrators at each metal atom is to be ignored when these vibrators are symmetry-related. The overwhelming majority of carbonyl clusters conform to the spherical harmonic model, either in its simplest form-in which only a single infrared band is observed in the solution infrared spectrum-or in its more elaborate form. In the latter, bands of lower intensity are observed on the low-frequency side of the intense band. The greater the separation from the intense band, the weaker the additional band, indicating an intensity stealing mechanism. The observations have been interpreted in terms of a "cluster selection rule" analogous to the "surface selection rule" of metal surface spectroscopy and the implications of this rule are discussed.

Effects of gammalinolenic acid on interleukin-1 beta and tumor necrosis factor-alpha secretion by stimulated human peripheral blood monocytes: studies in vitro and in vivo.

BACKGROUND: Oils enriched in gammalinolenic acid, an unsaturated fatty acid, reduce joint pain and swelling in patients with rheumatoid arthritis. The cytokines interleukin-1 beta and tumor necrosis factor-alpha appear to contribute directly to joint tissue damage in patients with rheumatoid arthritis. Agents designed to interfere with the actions of interleukin-1 beta and tumor necrosis factor-alpha are being used to treat rheumatoid arthritis. METHODS: We examined the influence of gammalinolenic acid added to cells in vitro and administered orally in vivo on interleukin-1 beta and tumor necrosis factor-alpha secretion from activated human peripheral blood monocytes. Secretion of both cytokines was reduced by gammalinolenic acid. Administration of safflower oil as a polyunsaturated fatty acid control devoid of gammalinolenic acid did not change secretion of either cytokine. CONCLUSION: Suppression of IL-beta and TNF-alpha secretion by activated cells may be one mechanism whereby gammalinolenic acid suppresses synovitis in patients with rheumatoid arthritis.

Chemotherapy with cis-platin, doxorubicin, and cyclophosphamide (CAP) in patients with metastatic breast cancer.

Thirty-three evaluable patients with metastatic breast cancer (12 previously treated with adjuvant chemotherapy) were treated with a combination of cis-platin, doxorubicin, and cyclophosphamide (CAP). cis-Platin was given intravenously, 20 mg/m2, on days 1-3, doxorubicin, 40 mg/m2 i.v., on day 1, and cyclophosphamide, 200 mg/m2 i.v., on days 1-3. Cycles were repeated every 3 weeks. A complete response (CR) was obtained in 3 patients (9%) and a partial response (PR) in 18 (54%). The highest response rate was observed in soft tissue and in liver metastases. Median response duration was 48 weeks and median survival 93 weeks. Toxicity was moderate and consisted of alopecia (100%), gastrointestinal toxicity (86%), and myelosuppression (60%). We conclude that this regimen is active in the treatment of advanced breast carcinoma, with a generally acceptable tolerance, but further evaluations in Phase III studies are required.

Neoadjuvant cisplatin and etoposide for stage IIIA (clinical N2) non-small cell lung cancer.

In an attempt to improve the curative potential of surgery, 46 patients with unresectable Stage IIIA (Clinical N2) non-small cell lung cancer received neoadjuvant chemotherapy with cisplatin and etoposide. After 2 or 3 cycles, 45 patients were evaluable for response; the overall response rate was 82% (37/45) with 3 complete and 34 partial responses. Toxicity was primarily hematologic. Surgical exploration was performed on 35 patients, but resection was possible in only 33 (73%). Of these, 28 resections were complete (62%). Four patients (2CR, 2PR; 9%) had no tumor in biopsy specimen. Three deaths were surgery-related. Median survival of the entire 46 patients was 24.5 months with a 2-year survival of 53%. Cisplatin and etoposide is an effective chemotherapeutic regimen for regionally advanced non-small cell lung cancer; the resection and survival rates justify further trials to compare this approach to other treatment modalities.

Evaluation of the degree of susceptibility of Streptococcus pyogenes erythromycin-resistant strains to rokitamycin (a 16-membered macrolide) using the Epsilometer test.

Routine hospital screening of the resistance of Streptococcus pyogenes to macrolides is usually done using the erythromycin, clarithromycin or azithromycin disk diffusion technique. When a strain is found to be resistant to one of these macrolides, it is generally assumed to be resistant to the whole class. However this approach gives only partial qualitative information because S. pyogenes strains with inducible and M phenotype resistance are still susceptible to 16-membered ring macrolides such as rokitamycin. Seventy-four erythromycin-resistant (22 inducible and 52 M phenotype) strains of S. pyogenes were tested for their susceptibility to rokitamycin and clindamycin (control) by means of the agar disk diffusion test and the results were compared with those obtained using the Epsilometer test, a quantitative technique for measuring bacterial susceptibility and minimal inhibitory concentrations (MIC). Epsilometer testing of erythromycin in comparison with rokitamycin is useful for measuring the real degree of susceptibility of macrolide-resistant strains quickly and simply. This is important because strains with the same disk diffusion diameter do not necessarily have the same MIC, but a scattered distribution of susceptibility.

Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study.

AIMS AND BACKGROUND: In 1990 the National Institutes of Health Consensus Conference recommended adjuvant combined therapy for patients with radically resected rectal cancer at high risk for relapse (ie, stage II-III). The purpose of our prospective non-randomized study was to verify the feasibility and effectiveness of postoperative radiochemotherapy in terms of improvement in disease-free and overall survival in this patient subgroup. STUDY DESIGN: From January 1990 to October 1998, 191 consecutive patients with radically resected stage II-III rectal cancer were treated. A total of 159 patients with a 24-month follow-up were assessable for toxicity and survival. Anterior resection was performed in 129 (81%) and abdomino-perineal resection in 30 (19%) patients. Fifty-four (34%) stage II and 105 (66%) stage III patients entered the study. Within 45-60 days of surgery, all patients received 5-fluorouracil chemotherapy at the dose of 500 mg/m2 as an i.v. bolus on days 1-5, every 4 weeks, for 6 cycles. Chemotherapy cycles III and IV were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy consisted of 45 Gy/25 fractions plus a boost dose of 5.4 Gy. RESULTS: After a median follow-up of 57 months (range, 25-123), overall recurrent disease was reported in 58 (36%) patients: local, systemic, and both local and systemic relapses in 12 (8%), 37 (23%) and 9 (6%) cases, respectively. According to local extension, recurrence rates were 15% and 48% in stage II and III, respectively. Five-year overall and disease-free survival were 71% and 66%, respectively. Overall survival was 87% in stage II and 62% in stage III patients, and disease-free survival was 84% and 56% in stage II and III disease, respectively. According to univariate and multivariate analyses, significant prognostic factors for better tumor control were: stage (II vs III, P <0.001), the number of involved nodes (< or = 3 vs > 3, P <0.0001), and no extracapsular node invasion (P <0.0001). The recommended dose of the combined radiochemotherapy regimen was generally well tolerated. The incidence of any > or = grade 3 acute toxicity (according to the WHO scale) was 13% diarrhea, 11% proctitis, 5% perineal dermatitis and 4% myelosuppression. Four (3%) patients had radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: The study provided recurrence rates and survival similar to other adjuvant radiochemotherapy regimens published in the literature. However, in view of the low 5-year survival rate recorded in stage III patients, a different approach should be investigated.

[The neuroendocrinological and histopathological assessment of normogonadotropic azoospermic patients: the usefulness of the GnRH stimulation test]. / Evaluación neuroendocrinológica e histopatológica de pacientes azoospérmicos normogonadotrópicos: utilidad de la prueba de estimulación con GnRH.

This study evaluates the effect of gonadotropin releasing hormone (GnRH) administration on serum levels of FSH and LH. Also, relate those results with histopathologic findings of testicular biopsies. This was a prospective, clinical trial with a control group. It was done at Department of Reproductive Biology "20 de Noviembre" Hospital, ISSSTE, México City. Fifteen azoospermic, normogonadotropic patients without testicular atrophy and ten normal men use as control group. A GnRH challenge test was made in both groups, two days after we perform a testicular biopsy in patients with azoospermia. There was no significant difference in serum LH concentrations between the two groups, neither before or after GnRH challenge test. There was a statistical difference between serum FSH values of azoospermic patients, than those of control group, the former with higher values than those of the latter. As worst testicular damage was, we found also a higher FSH value on the GnRH challenge test. The GnRH challenge test perform in azoospermic, normogonadotropic patients is very helpful to detect those patients with gonadal damage. As higher the FSH values were, we found that an abnormal testicular biopsy was also more common.