Spermatogenesis In Patients Research Articles

Effects of surgery, medical therapy and combined therapeutical approach on spermatogenesis in patients suffering from varicocele: a prospective and comparative analysis

The definite mechanisms through which varicocele affects spermatogenesis are still not completely understood, and consequently the exact role of the various approaches available for its treatment is still under debate. In this study a comparison of medical treatment, surgery and combined approach is reported. Material and Methods. The study was conducted as a prospective evaluation of 189 patients suffering from varicocele and oligoasthenospermia. Patients were randomized in three groups on the basis of the different therapeutic approach: group A, treated only with varicocelectomy; group B, treated with varicocelectomy associated with hormonal therapy; group C, treated only with hormonal therapy. Randomization criteria were based on patient's preference. Spermiogram tests were carried out at baseline and after 3, 6 and 12 months from therapy. Results. Our results show that patients undergoing a combined therapeutical approach (surgery associated with hormonal therapy) and medical therapy alone achieve a greater improvement of seminal parameters than patients treated by surgery only. Conclusion. Data reported in this study are in accordance with Literature review. Furthermore, the association between varicocelectomy and early use of hormonal therapy seems to improve testis functional rehabilitation with a early evidence of sperm parameters improvement. In the light of these results of ours, we should conclude that surgical treatment is not effective for the spermatogenesis improvement.

Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients

The aims of our study were to investigate the short- and long-term effects of chemo- or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy (RT group; n = 95). For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A, <40 x 10(6)/ejaculate; B, >or=40 x 10(6)/ejaculate). At t(24), subgroup A of both the CH and RT groups showed improved sperm parameters over the baseline, whereas subgroup B for both CH and RT groups showed a return of sperm parameters to those of baseline values. In conclusion, the recovery of spermatogenesis after chemo- or radiotherapy in our group of testicular cancer patients was not a function of pre-therapy sperm parameter quality. Cryopreservation of sperm before performing such therapy is therefore imperative.

Induktion der Spermiogenese nach antegrader Varikozelensklerosierung bei Patienten mit nicht-obstruktiver Azoospermie

The aim of this study was to prove the efficacy of antegrade sclerotherapy for varicocele testis in patients with azoospermia and in patients with cryptozoospermia (less than 0.1 million spermatozoons/mL ejaculate). We have investigated the induction of spermatogenesis in patients with non-obstructive azoospermia after antegrade sclerotherapy. 20 consecutive patients who had been trying to beget a child over a period of one year or longer were chosen for this study. All patients suffered from non-obstructive azoospermia or from cryptozoospermia. We produced a control spermiogram for each patient before, 3 and 6 months after antegrade sclerotherapy. The postoperative spermiogram was done according to WHO criteria and was then compared to the preoperative data. 15 patients (75 %) were found to suffer from azoospermia preoperatively and 5 patients (25 %) from cryptozoospermia. Out of the 15 patients with initial azoospermia 8 (53 %) showed cryptozoospermia (OAT/OT syndrome) after antegrade sclerotherapy. Out of the 5 patients with the initial cryptozoospermia 3 (60 %) showed an improvement in the sperm count and motility criteria. Antegrade sclerotherapy for varicocele testis is a valid treatment option to isolate the spermatozoons from the ejaculate for extracorporeal fertilisation in patients with non-obstructive azoospermia. Complete normalisation of the spermiogram parameters, i.e., sufficient for natural child conception, cannot safely be achieved by this method.

Disruption of Spermatogenesis by the Cancer Disease Process

In the past, cancer survivors tended to be most concerned about disease recurrence and treatment side effects. As survival rates have increased, however, patients are now also concerned about quality-of-life issues such as preserving fertility potential. It is well known that cancer treatment adversely affects male fertility via direct effects on the testis and/or through the endocrine glands. Evidence also suggests that the disease process itself may affect a man's fertility by influencing spermatogenesis. However, the causes of poor semen quality in cancer patients are not well understood. Multiple factors are likely involved, including preexisting defects in germ cells, systemic effects of cancer, and endocrine and immunological disturbances. This paper will summarize available evidence on different factors involved in impaired spermatogenesis in patients with various cancers with emphasis on testicular cancer and Hodgkin lymphoma. Cryopreservation of spermatozoa is a simple and practical approach available to all patients with cancer who wish to preserve their fertilizing potential before cancer therapy.

Soluble Forms of Fas and Fas Ligand Concentrations in the Seminal Plasma of Infertile Men With Varicocele

The Fas system in the testis has been identified as a key physiological regulator of apoptosis, an ongoing physiological process that limits the size of the germ cell population so it can be supported. Recently it was reported that the soluble form of Fas blocks Fas dependent apoptosis. In the present study we measured soluble Fas (sFas) concentrations in seminal plasma of oligozoospermic men with and without varicocele, and in normal men, looking for an association between seminal sFas and sFas ligand with spermatogenesis. A total of 27 oligozoospermic men with varicocele, 59 oligozoospermic men without varicocele and 34 normal volunteers were included in this study. Patients were evaluated clinically according to the protocol of the World Health Organization. sFas and sFas ligand were measured using a commercially available double antibody enzyme linked immunoassay. Follicle-stimulating hormone, luteinizing hormone, testosterone and estradiol concentrations were determined by chemiluminescence assays. Seminal concentrations of sFas in oligozoospermic men with varicocele (3.6 +/- 2.4 ng/ml) were significantly lower than those in oligozoospermic men without varicocele (4.9 +/- 2.7 ng/ml, p = 0.0321) and normal men (5.1 +/- 2.4 ng/ml, p = 0.0201). The seminal sFas concentration significantly correlated with sperm concentration (r = 0.517, p = 0.0058). After varicocelectomy the increase in sperm concentration significantly correlated with an increase in sFas in seminal plasma (r = 0.555, p = 0.0026). The serum concentration of luteinizing hormone, follicle-stimulating hormone, testosterone or estradiol did not correlate significantly with the seminal sFas concentration. The sFas ligand concentration in seminal plasma was less than the limit of detection. The sFas concentration in seminal plasma shows a strong association with spermatogenesis. Subnormal levels of sFas may be responsible for increased apoptosis induced by the Fas system, resulting in impaired spermatogenesis in patients with varicocele.

Human chorionic gonadotropin beta subunit impaired spermatogenesis in patients with seminomaspermatogenesis in patients with seminoma

Human chorionic gonadotropin beta subunit impaired spermatogenesis in patients with seminomaspermatogenesis in patients with seminoma

Effect of Mesh and its Localisation on Testicular Flow and Spermatogenesis in Patients with Groin Hernia

In this study, the long-term effects of mesh and its localisation (i.e. anterior or posterior) on testicular perfusion and testicular function were evaluated in groin hernia patients.Testicular function has been evaluated with spermiogram and testicular perfusion with colour Doppler ultrasonography. Group I: consisted of 30 posterior preperitoneal mesh repair patients Group II: consisted of 30 anterior tension-free repair patients. The operation types were randomised with a systematic sampling method.There was no statistically significant difference between pre-operative and postoperative spermiogram results for both groups. No statistically significant difference was found between the two groups in terms of Doppler flow parameters (PSV, EDV, RI and PI) for pre-operative, early and late postoperative periods.When Doppler flow parameters were compared for group I, statistically significant differences were found between pre-operative and early postoperative values. No statistically significant difference was found between pre-operative and late postoperative values. This is also true for early postoperative values versus late postoperative values. When Doppler flow parameters were compared for group II, statistically significant differences were found between pre-operative and early postoperative values. No statistically significant difference was found between pre-operative and late postoperative values. This is also true for early postoperative values versus late postoperative values. These results support the idea that inguinal mesh application is still a safe procedure in patients with no children or who are undergoing infertility treatment, where testicular function is important.

Correlation between fluorescence in situ hybridization and testicular biopsy for the prediction of spermatogenesis in 37 patients with nonobstructive azoospermia

Objectives We applied interphase fluorescence in situ hybridization (FISH) to testis sections to examine the evidence of spermatogenesis in patients with nonobstructive azoospermia. This technique was evaluated and compared with conventional testicular histopathologic findings for the possibility of additional clinical applications. Methods Thirty-seven consecutive patients with nonobstructive azoospermia were carefully evaluated clinically. Testes were biopsied for both sperm extraction and histopathologic examination. FISH staining was performed with a CEP 18 SpectrumAqua/CEP X SpectrumGreen/CEP Y SpectrumOrange probe. Results Eight of 11 cases (sensitivity 73%) that were found to have spermatids on the histopathologic slides also were proven to produce haploid cells by FISH staining. On the other hand, 21 of the 26 cases (specificity 81%) for which no spermatids could be found on the histopathologic slides also had only diploid cells by FISH staining. On the basis of the good correlation between the FISH staining and conventional histopathologic findings, we could confirm the diagnosis of spermatogenesis using both methods. Conclusions FISH staining of testicular sections allows more reliable prediction of spermatogenesis and provides benefits for a patient’s decision regarding fertility counseling.

Possible relationship between seminal plasma inhibin B and spermatogenesis in patients with azoospermia.

Inhibin B is bidirectionally secreted by Sertoli cells, basal secretion into the circulation exerts negative feedback on follicle-stimulating hormone secretion, and serum inhibin B is considered a marker of spermatogenesis. The precise role of apical secretion is unknown. The objective of our work was to study the relationship between seminal inhibin B and spermatogenesis. Dimeric inhibin B was measured by immunoassay in seminal plasma of volunteers with normozoospermia (n = 10, group 1), in men after vasectomy (n = 10, group 2), and in men with azoospermia (n = 50, group 3). Testicular biopsy and testicular sperm extraction were performed in men with azoospermia. Seminal inhibin B levels were higher in men in group 1 than in men in groups 2 and 3 (P <.0001). In seminal plasma, inhibin B presents a positive correlation with alpha glucosidase activity (r =.37, P =.002). Seminal inhibin B is inversely related with serum FSH (r = -.58, P <.001), and presents a weak positive correlation with serum testosterone concentration (r =.29, P =.03). No difference was found between inhibin B levels in seminal plasma of patients with nonobstructive or obstructive azoospermia, and between positive or negative outcome of TESE. We conclude that inhibin B secretion by Sertoli cells is differentially regulated. The contribution of accessory sex glands limits the use of seminal plasma inhibin B as a marker of spermatogenesis.

Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy

Objective: To characterize clinical and laboratory findings in nonmosaic 47,XXY patients that may help to predict spermatogenetic activity in their testicles. Design: Prospective study. Setting: Assisted reproductive technology program. Patient(s): Twenty patients with nonmosaic Klinefelter syndrome who underwent testicular sperm retrieval for IVF. Main Outcome Measure(s): The correlation between basal FSH, LH and testosterone levels, mean testicular volume, and results of the hCG test and presence or absence of sperm after testicular sperm extraction (TESE). Result(s): Sperm was found in nine patients (45%). The mean testicular volume was 7.8 ± 2.5 mL in men with sperm after TESE and 5.6 ± 1.2 mL in those without sperm after TESE; corresponding testosterone levels were 3.5 ± 1.2 ng/mL and 1.7 ± 0.8 ng/mL. Serum levels of FSH and LH did not significantly differ between groups. After the hCG test, the mean serum testosterone level was 16.0 ± 6.3 ng/mL in men with sperm after TESE and 6.7 ± 5.6 ng/mL in those without sperm. Conclusion(s): Testicular volume, testosterone levels, and results of the hCG test are important predictive factors of spermatogenesis in patients with nonmosaic Klinefelter syndrome.

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 × 10 6/mL. Result(s): Spermatogenesis was achieved in 15 of 19 patients who could be evaluated, 12 achieving a sperm concentration of ≥ 1.5 × 10 6/mL. Conclusion(s): With hCG, rhFSH is effective in initiating spermatogenesis in patients with IHH, and is well tolerated.

Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility

Objective: To determine whether expansion of CAG repeats in exon 1 of the androgen receptor is correlated with impaired spermatogenesis in patients with male idiopathic infertility.Design: A retrospective study.Setting: Medical school in Besançon, France.Participant(s): Thirty-seven infertile patients with azoospermia or oligospermia and 50 fertile controls.Intervention(s): History, physical, hormonal assays, semen analysis, and collection of blood samples in order to study the androgen receptor’s gene.Main Outcome Measure(s): Blood samples were collected from each infertile patient and control. The length of the CAG repeat segment was evaluated by using polymerase chain reaction (PCR) electrophoresis in exon 1 and PCR single-strand conformation polymorphism in exons 2–8.Result(s): The mean length of the CAG repeats was significantly different between infertile and fertile patients (23.91 ± 0.5 vs. 22.20 ± 0.4). No mutation was detected in exons 2–8 of the androgen receptor gene in infertile patients.Conclusion(s): Expansion of the CAG repeat segment of the androgen receptor is correlated with male idiopathic infertility. The number of CAG repeats may therefore have a modulatory effect on normal androgen receptor function.

CAG repeat length analysis and mutation screening of the androgen receptor gene in Japanese men with idiopathic azoospermia.

Because androgens are required for normal spermatogenesis, we are investigating abnormalities in the androgen receptor as a possible cause of impaired spermatogenesis in patients with idiopathic male infertility. The CAG repeat length in exon 1 and mutations of the androgen receptor gene were studied in 30 men with idiopathic azoospermia and in 51 fertile men. In men with azoospermia, plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were measured and testicular biopsies were performed. The CAG repeat length ranged from 19 to 30 (mean 23.4 +/- 2.9) and from 17 to 28 (mean 23.7 +/- 3.2) in men with azoospermia and in controls, respectively. There was no significant difference between the 2 groups. In men with azoospermia, the Johnsen testicular biopsy score negatively correlated with plasma FSH (P < .01). However, the Johnsen testicular biopsy score did not correlate with plasma LH and testosterone levels. The CAG repeat length did not correlate with the Johnsen testicular biopsy score, or with plasma concentrations of LH, FSH, and testosterone. No abnormalities in the androgen receptor gene were detected. These facts suggest that the CAG repeat length and alterations in the androgen receptor gene are not associated with the etiology of idiopathic azoospermia.

ZNF214: a candidate gene for impaired spermatogenesis.

Objective: The aim of this study was to investigate whether the ZNF214 gene is a candidate gene in male factor subfertility due to impaired spermatogenesis. Design: Case-control association-study and mutation-analysis. Materials/Methods: DNA was collected from 77 men of infertile couples with idiopathic oligo- or azoospermia defined as a total sperm count of less than 20 × 106 in at least two semen analyses. 65 men with a total sperm count over 40 × 106 with a propulsive motility and normal morphology of at least 40%, in two consecutive semen analyses were included as controls. The patients were subdivided in two groups based on the presence or absence of cryptorchidism in their medical history. An association study was performed using 6 Single Nucleotide Polymorphism’s (SNP’s) in the ZNF 214 gene. Haplotypes were constructed on the basis of the individual genotype scores. Subsequently this gene was screened for mutations by SSCP analysis in both patient groups. Results: In the patient group with a medical history of cryptorchidism, a significantly different allele frequency was found for the 197 A→G (p < 0.02) and the 383 T→G (p < 0.04) variant in the ZNF214 gene. In the patient group without cryptorchidism no significant differences were found. The six SNP’s observed segregate as 6 haplotypes in the total population. In both subgroups of patients there was a difference in haplotype frequencies when compared to the control group. Subsequently all coding and flanking intron sequences of ZNF214 were screened for the presence of mutations by SSCP analysis. In three patients three new mutations were identified, all resulting in an amino acid change. These mutations were not present among the controls. In two of the patients DNA of the parents was available and in both cases the mutation was inherited from the mother. All three patients were phenotypically normal, especially no BWS symptoms were present. They all were primary subfertile for at least three years. Semen analysis revealed severe oligozoospermia. Only one patient carrying a mutation had a medical history of cryptorchidism. Conclusions: ZNF 214 is associated with impaired spermatogenesis in patients with cryptorchidism in their medical history. We have identified three new mutations in three patients with impaired spermatogenesis. Further research is necessary to explain the functional role of the ZNF 214 gene in spermatogenesis. Supported by: Center for Reproductive Medicine. Academic Medical Center. Dept. Obstetrics and Gynecology. Meibergdreef 9. 1105AZ Amsterdam. The Netherlands.

Suppression of spermatogenesis in ipsilateral and contralateral testicular tissues in patients with seminoma by human chorionic gonadotropin beta subunit

Objectives. The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. Methods. Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen’s score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. Results. A significant linear relationship ( r = −0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. Conclusions. A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.

Histopathological mapping of open testicular biopsies in patients with unobstructive azoospermia.

To evaluate, in patients with unobstructive azoospermia, the heterogeneity of spermatogenesis within the testes and thus whether there is any region of advanced spermatogenesis. Patients and methods Seventy infertile men (mean age 34 years, SD 5.01) with no varicoceles or testicular atrophy had bilateral open testicular biopsies taken from six different sites. For each biopsy specimen the number of seminiferous tubules and of tubules with sperm maturation were counted (by light microscopy at x 400). The ratio of tubules with active spermatogenesis to the total number was calculated for each biopsy sample. The mean (SD) right and left testicular volumes were 19.82 (7.8) and 18.84 (7.89) mL, respectively; the patients' follicle-stimulating hormone level was 8.34 (1.17) IU/mL. On sextant biopsy spermatozoa were detected in 42 of the 70 patients (60%). The mean (SD) ratio of tubules with spermatozoa was 5.23 (0.8)% for the right and 5.37 (0.76)% for the left testes. There was no statistically significant difference in the ratio of seminiferous tubules positive for spermatozoa at the different biopsy sites in either the right or left testis. Spermatozoa were identified in only one to three biopsy sites in almost half of those with maturation arrest; this ratio increased to 74% in patients diagnosed as having Sertoli-cell-only syndrome with focal spermatogenesis. Conclusion There is no region of the testis that is rich or advanced in spermatogenesis in patients with unobstructive azoospermia. Without multiple testicular biopsy it is possible to miss advanced spermatogenesis in some unobstructed patients. The sextant testis biopsy is a reliable method for detecting the presence and exact location of seminiferous tubules with spermatozoa in patients with unobstructive azoospermia.

SPERMATOGENESIS AFTER UNILATERAL ORCHIECTOMY FOR TESTICULAR CANCER IN PATIENTS FOLLOWING SURVEILLANCE POLICY

Only limited information is available on the natural course of spermatogenesis in patients with testicular cancer who underwent unilateral orchiectomy and surveillance. We analyze long-term exocrine function of the remaining testicle in patients following surveillance policy. Sperm counts and serum follicle-stimulating hormone (FSH) levels were available in 60 nonrelapsing cases approximately 3 weeks (baseline), 1 year and 2 years or greater after orchiectomy. Contralateral testicular cancer subsequently developed in 2 men. At baseline 36 patients were normospermic (10 or greater x 106/ml.), 7 were azoospermic and 17 were oligospermic. After 1 year 45 patients were normospermic. Mean sperm concentrations increased significantly from 26 to 39 x 106/ml. during year 1 after orchiectomy. Elevated serum FSH at baseline was associated with incomplete recovery of spermatogenesis, although sperm counts improved in 3 of 7 patients. Furthermore, in the 2 initially oligospermic patients with subsequent contralateral testicle cancer transient normospermia was observed after 1 year. After orchiectomy fatherhood was recorded in 28 men and was assisted by fertilization using fresh semen in 2. In nonrelapsing testicular cancer cases on surveillance, initially reduced spermatogenesis recovers during year 1 after orchiectomy especially if baseline serum FSH is normal. Transient recovery also occurs in patients in whom contralateral testicular cancer subsequently develops. In high risk patients and in initially oligospermic patients with plans for future fatherhood, the period of improved spermatogenesis may be used for multiple semen cryopreservations enabling subsequent assisted fertilization.

Microdeletion of the DAZ (deleted in azoospermia) gene or the YRRM (Y chromosome ribonucleic acid recognition motif) gene does not occur in patients with Klinefelter’s syndrome with and without spermatogenesis

Objective: To evaluate the occurrence of microdeletions of the Y chromosome involving the DAZ and YRRM genes in patients with Klinefelter’s syndrome with and without spermatogenesis. Design: Controlled clinical study. Setting: Yamagata University Hospital, Yamagata, Japan. Patient(s): Patients with Klinefelter’s syndrome with spermatogenesis (n = 1) and without spermatogenesis (n = 20) and a control group of men of proven fertility (n = 10). Intervention(s): Blood and semen sampling and testicular biopsy. Main Outcome Measure(s): Semen analysis, polymerase chain reaction amplification of 32 DNA loci on the long arm of the Y chromosome involving the DAZ (deleted in azoospermia) and YRRM (Y chromosome ribonucleic acid recognition motif) genes, and measurement of plasma FSH, LH, and testosterone levels. Result(s): No microdeletions of 32 loci were found in any of the patients with Klinefelter’s syndrome, either with or without spermatogenesis. Plasma LH and FSH levels were abnormally high and testosterone levels were reduced in all the patients with Klinefelter’s syndrome. Conclusion(s): Severe impairment of spermatogenesis in patients with Klinefelter’s syndrome is not caused by microdeletions of the Y chromosome involving the DAZ and YRRM genes.

Prediction of Posttreatment Spermatogenesis in Patients With Testicular Cancer by Flow Cytometric Sperm Chromatin Structure Assay

Prediction of Posttreatment Spermatogenesis in Patients With Testicular Cancer by Flow Cytometric Sperm Chromatin Structure Assay

Prediction of Posttreatment Spermatogenesis in Patients With Testicular Cancer by Flow Cytometric Sperm Chromatin Structure Assay

Prediction of Posttreatment Spermatogenesis in Patients With Testicular Cancer by Flow Cytometric Sperm Chromatin Structure Assay