A possible association of a human tektin-t gene mutation (A229V) with isolated non-syndromic asthenozoospermia: case report.

Asthenozoospermia (AZS), characterized by grade A + B sperm motility (as in World Health Organization Guidelines) < or =50% or A <25% in fresh ejaculate, may exist as an isolated disorder, in combination with other sperm anomalies or as part of syndromic association. The majority of syndromic patients can be ascribed to mutations in dynein genes, while, to date, no genes have been described to be associated in humans with non-syndromic, isolated AZS. An interesting family of axonemal proteins, the tektins, has been recently identified in various mammals and they are thought to play a fundamental role in ciliary movement. Recently, the human tektin-t (or h-tekB1 or Tektin-2) gene has been cloned, showing specific expression in flagella of mature sperm. We report the screening of tektin-t gene in 90 isolated non-syndromic AZS patients. We found a heterozygous mutation (A229V) in one patient. Ultrastructural analysis showed anomalies in > or =80% of examined spermatozoa involving axoneme microtubules and mitochondria. Moreover, the viability and mitochondrial function of sperm were altered in the patient with the A229V mutation. This is the first description of human pathology linked to a tektin-family gene, since only murine models are available for these genes.

High-power microscopy for selecting spermatozoa for ICSI by physiological status.

Sperm selection for intracytoplasmic sperm injection (ICSI), based on standard morphology, can fail to select normal cells, and actual methods to evaluate their physiological status do not allow their later use for ICSI. Some authors have demonstrated that sperm selection based on high-magnification morphology is associated with a better ICSI outcome, above all in subjects with severe testicular failure. In this study there was an evaluation of mitochondrial function, chromatin structure and sperm aneuploidies on whole sperm samples from 30 subjects: 10 normozoospermic controls and 20 patients that were severely oligozoospermic due to testicular damage or partial obstruction of the seminal ducts. All severely oligozoospermic patients showed worse mitochondrial function and chromatin status, while sperm aneuploidies were significantly increased only in those subjects with severe testicular damage (P < 0.001). In the latter patients the analysis of a single spermatozoon, performed after morphological selection by high-magnification microscopy, showed significantly better mitochondrial function, chromatin status and aneuploidy rate than observed in unselected cells (all P < 0.001). Interestingly, these parameters were further improved when nuclear vacuoles were lacking. These results suggest a strong relationship between high-magnification morphology and the status of spermatozoa, and they may explain the better results of ICSI obtained using spermatozoa selected by high-magnification microscopy.

Clinical and prognostic significance of human papillomavirus DNA in the sperm or exfoliated cells of infertile patients and subjects with risk factors.

OBJECTIVE: To evaluate human papillomavirus (HPV) sperm infection and its correlation with sperm parameters in infertile patients and subjects with risk factors. DESIGN: Cross-sectional clinical study. SETTING: Andrology and microbiology sections at a university hospital. PATIENT(S): A cohort of 290 subjects: 26 with genital warts, 66 with HPV positive partners, 108 infertile patients, and 90 fertile controls. INTERVENTION(S): Semen analysis, sperm culture, polymerase chain reaction, and fluorescence in situ hybridization (FISH) for HPV detection. Statistical analysis was performed with a two-tailed Student's t-test. RESULT(S): The prevalence of HPV semen infection found in all groups was as follows: patients with genital warts, 53.8%; infected partners, 40.9%; infertile patients, 10.2%, fertile controls, 2.2%. Infertile patients had a higher HPV DNA prevalence in sperm cells than the other groups. The results of HPV investigation were compared with sperm parameters and the results of FISH analysis. Sperm motility was more frequently reduced in infected samples and in particular when the infection was present in the sperm. CONCLUSION(S): This study demonstrated a very high prevalence of infection in the semen of patients with risk factors for HPV. In each group of subjects, HPV seems to be preferentially located in sperm or exfoliated cells, with different effects on sperm motility.

Human papillomavirus found in sperm head of young adult males affects the progressive motility.

OBJECTIVE: To evaluate the prevalence of human papillomavirus (HPV) sperm infection and its correlation with sperm parameters in a cohort of young adult males. DESIGN: Cross-sectional clinical study. SETTING: Andrology and Microbiology sections at a university hospital. PATIENT(S): A cohort of 200 young adult male volunteers (18 years old), 100 with previous sexual intercourse and 100 without previous sexual intercourse. MAIN OUTCOME MEASURE(S): Seminal parameters, sperm culture for HPV and fluorescence in situ hybridization (FISH) analysis for HPV detection in the sperm head. Statistical analysis was performed with a two-tailed Student's t-test. RESULT(S): Results of HPV investigation were compared to sperm parameters and results of FISH analysis. HPV infection was present in sperm cells of 10 subjects among those 100 young adults who already had unprotected intercourse and its presence was associated with reduced sperm motility. Furthermore, infected samples showed that about 25% of sperm had an HPV DNA positivity at the head site, but it is unclear whether it was integrated in the nucleus or not. CONCLUSION(S): This is the first report estimating the percentage of HPV-positive sperm in infected subjects and the association between HPV infection and sperm motility.

Gonadotropin administration after gonadotropin-releasing-hormone agonist: a therapeutic option in severe testiculopathies.

OBJECTIVE: To evaluate the effect of recombinant human follicle-stimulating hormone (FSH) plus human chorionic gonadotropin (hCG) on seminal parameters and pregnancy rate in severe testiculopathies after high FSH plasma concentrations have been suppressed. DESIGN: Prospective, controlled, randomized clinical study. SETTING: Infertility center at a university hospital. PATIENT(S): Eighty-seven men affected by severe testiculopathy. INTERVENTION(S): We treated 57 men with a gonadotropin-releasing hormone agonist (GnRH-a) and then with recombinant human FSH and hCG, and 30 patients did not receive any treatment. Seminal parameters and sperm aneuploidies were evaluated during and after the treatment period. Couples did not achieve a spontaneous pregnancy received assisted reproduction treatment. MAIN OUTCOME MEASURE(S): Seminal parameters, sperm aneuploidies, testicular cytologic analysis, FSH, luteinizing hormone, testosterone, inhibin B concentrations, and pregnancy rate. RESULT(S): After the therapy period, the treated group showed statistically significant improvement in sperm parameters and sperm aneuploidies. No changes were observed in the untreated group. A trend toward an increase in pregnancy rate also was observed among treated couples (cumulative pregnancy rates 31.6% treated vs. 20.0% untreated), although the increase was not statistically significant. The improvement of seminal parameters in the treated group allowed some patients to undergo in vitro fertilization-embryo transfer instead of intracytoplasmic sperm injection. CONCLUSION(S): Results from this controlled, randomized clinical trial show that FSH therapy improves sperm parameters in severe male factor infertility when endogenous high FSH plasma levels are suppressed. In cases of severely impaired testicles, a rational treatment of male infertility is mandatory to improve the outcome of assisted reproduction techniques.