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Biomedical subjects

H Yavetz

Publications and source records attributed to H Yavetz.

At least 19 recordsLinked to original sources

Expression profile of AZF genes in testicular biopsies of azoospermic men.

BACKGROUND: The Y-chromosome AZF regions include genes whose functions and specific roles in spermatogenesis have not been fully clarified. This study investigated the expression of several AZF (USP9Y, DDX3Y/DDX3Yt1, EIF1AY and PRY) and USP9X transcripts in testicular biopsies of 89 azoospermic men who had been classified by histology and cytology assessments. METHODS: Expression was analysed by RT-PCR, and some biopsies were evaluated by multiplex RT-PCR. Quantitative PCR was performed in some biopsies to determine the ratio of the testis-specific transcript DDX3Yt1 to the total DDX3Y transcription. RESULTS: The expression of USP9Y, USP9X and DDX3Y was found in all the specimens tested, whereas DDX3Yt1 expression was diminished or undetectable in several biopsies with impaired spermatogenesis. EIF1AY was detected in all except two of the specimens. Noteworthy, PRY expression was detected mainly in biopsies with germ cells, and this association was significant (P < 0.001). An identical expression profile was obtained by either single or multiplex RT-PCR. CONCLUSIONS: These findings suggest that PRY is usually expressed in germ cells, whereas the other transcripts are also expressed in testicular somatic cells. The absence of EIF1AY expression might sporadically contribute to azoospermia. The decreased ratio of DDX3Yt1/DDX3Y transcript in impaired spermatogenesis suggests that the DDX3Yt1 transcript is under-expressed in impaired spermatogenesis. The findings contribute to the search and selection of the most valuable gene markers potentially useful as additional tools for predicting complete spermatogenesis by multiplex expression analysis.

Azoospermia↗

Seasonal variations in pre- and post-thaw donor sperm quality.

BACKGROUND: The present study was conducted to evaluate seasonal variability in the quality of pre- and post-thaw semen parameters among sperm bank donors. METHODS: The first two consecutive ejaculates during the months March (spring, 92 males), June (summer, 97 males), September (autumn, 81 males) and December (winter, 97 males) were analysed. A comparison was made between sperm parameters from the same sperm donor at different seasons. Only males who donated semen samples during at least two seasons were enrolled in the study group (n = 103). Sperm specimens were cryopreserved in aliquots with fixed range of 8-12 x 10(6)/ml of progressive motile sperm concentration after thawing. RESULTS: Differences between months were found in sperm concentration (P = 0.030) and normal morphology (P = 0.038); highest values were found in March and December, and the lowest in September. Mean specimen volume and percent of motile sperm cells did not vary throughout the seasons. The freezability of the donors' sperm dropped dramatically from March to September, as determined by the number of straws (fixed aliquots of 0.5 ml) and total thawed progressive motile sperm that were cryopreserved for each male (P = 0.017 and P = 0.002, respectively). CONCLUSIONS: Cryopreservation of donor sperm is more effective during winter and spring than during the rest of the year.

Adult↗

Y-chromosome haplotypes in azoospermic Israeli men.

Among azoospermic and severely oligozoospermic men, 7-15% present microdeletions of a region on the long arm of the Y chromosome that has been called AZF (azoospermia factor). Because these deletions present varying relative frequencies in different populations, we decided to ascertain whether their presence was correlated with specific Y-chromosome haplotypes. For that, we evaluated 51 infertile Israeli men, 9 of whom had microdeletions in AZF. Haplotypes were identified using a hierarchical system with eight biallelic DNA markers. We also checked for the presence of the deletion marker 50f2/C, which was absent in all seven patients with isolated AZFc deletion and also in the one patient with isolated AZFb deletion, suggesting that these microdeletions overlap. As expected, haplogroup J was the most common (47%), followed by equal frequencies of haplogroups Y* (xDE, J, K), P* (xR1a, R1b8), K* (xP), and E. In six patients with AZFc deficiencies of comparable size, three belonged to haplogroup J, two belonged to haplogroup P* (xR1a, R1b8), and one belonged to haplogroup R1a. Also, there were no significant differences in the haplotype frequencies between the groups with and without microdeletions. Thus we did not identify any association of a specific haplogroup with predisposition to de novo deletion of the AZF region in the Israeli population.

Chromosomes, Human, Y↗

Expression of CDY1 may identify complete spermatogenesis.

OBJECTIVE: To investigate the expression of deleted in azoospermia (DAZ), RNA-binding motif (RBM), and chromodomain y1 (CDY1) genes in the testes of men with azoospermia with variable histopathologies. DESIGN: Prospective study. SETTING: Andrology laboratory of a university-affiliated maternity hospital. PATIENT(S): Sixty-six men with azoospermia. INTERVENTION(S): Testicular sperm extraction. MAIN OUTCOME MEASURE(S): The results of gene expression in testicular tissue tested by RT-PCR were correlated with those of histopathologically and microscopically examined minced testicular tissue. Y chromosome microdeletion testing and karyotyping were performed, as was direct sequencing of CDY1-PCR products. RESULT(S): CDY1-minor expression was detected in all biopsies in which mature spermatids/spermatozoa were observed by histological analysis and/or in the minced tissue. CDY1-minor expression was also detected in two biopsies with arrest at the spermatocyte stage during which no mature spermatids/spermatozoa were observed. A previously unreported CDY1-minor alternative splicing transcript was identified. DAZ and RBM gene expressions were detected in all biopsies in which at least a few germinal cells in early stages were found and in one biopsy histologically determined as Sertoli cell only. CONCLUSION(S): Our preliminary results suggest that CDY1-minor expression might increase the prospect for complete spermatogenesis, while RBM and DAZ expression can only be indicative of the presence of germinal cells.

Adult↗

Vascularity index distribution within the testis: a technique for guiding testicular sperm extraction.

Azoospermia is defined as the absence of spermatozoa in the ejaculate, although some foci of spermatogenesis may exist in the testes of these men. Currently, there are no clinical, seminal or hormonal parameters for identifying spermatogenesis within the testis sufficient for achieving genetic offspring. As a result, multiple biopsies are performed at several arbitrary sites of both testes in search of spermatozoa. We developed a power Doppler (PD) ultrasound (US) image-based technique that predicts sites with the greatest potential for spermatogenesis. PDUS images of the testes of azoospermic men were acquired at seven cross-sections to reconstruct a 3-D matrix for constructing a spatial map of preferential regions where spermatozoa are most likely to exist. This technique may obviate the need for arbitrary multiple biopsies that inflict some degree of damage upon testicular tissue, and may increase the success rate of identifying viable spermatozoa in testicular biopsies.

Biopsy↗

Donor insemination in Israel: sociodemographic aspects.

The paper describes the sociodemography of donor insemination recipients in Israel. Arab recipients are very few. Among the Jews, married recipients are generally younger than their single counterparts, and they are somewhat less educated and more religious. Ethnically, the percentage of Orientals among the married recipients is relatively higher; among the single women, Orientals are under-represented. On the whole, however, donor insemination seems to have reached Jewish Israelis of all segments of society.

Adult↗

Intrauterine insemination in male factor subfertility: significance of sperm motility and morphology assessed by strict criteria.

The study was conducted to evaluate the results of IUI treatment in a homogenous group with male factor infertility, and to assess the correlation of sperm variables, including sperm morphology by strict criteria, with pregnancy achievement after IUI. A total of 108 couples with no apparent female aetiology for infertility underwent 264 intrauterine insemination treatment cycles. A comparison was made between the sperm variables in two groups in which the achievement of pregnancy differed. The percentage of motile spermatozoa, degree of motility and normal morphology (by strict criteria) were significantly higher in the pregnant group compared with that of the nonpregnant group. A significant difference in pregnancy rates per couple after intrauterine insemination was demonstrated among three groups according to the percentage of sperm morphology, i.e. poor (< 4%), fair (4-14%) or good (> 14%) (11.1%; 36.1% and 50.0%, respectively). Intrauterine insemination is a valid mode of treatment in cases with male infertility, provided that normal morphology by strict criteria is higher than 4%.

Adult↗

Effect of freezing-thawing on the expression of mannose-ligand receptors on human spermatozoa: the impact on sperm capacitation and acrosome reaction.

The aim of this study was to evaluate the change in the expression of mannose-ligand receptors following a freezing-thawing procedure, in order to assess its impact on sperm capacitation and acrosome reaction. Twenty semen samples were obtained from fertile donors. Sperm samples were divided into two equal volumes. One aliquot was cryopreserved and the other aliquot was incubated at 32 degrees C. After 2 h the frozen sample was thawed and both samples were further incubated at 32 degrees C to allow capacitation. Mannose receptors were examined following 4 and 22 h of incubation using a mannosylated-BSA-FITC probe. The expression of mannose-ligand receptors on the sperm plasma membrane was determined according to the fluorescence pattern: pattern I represents pre-capacitation, pattern II represents capacitated spermatozoa and pattern III represents acrosome-reacted spermatozoa. After 4 h incubation in capacitating medium, the percentages of patterns I, II and III were 90, 7 and 3% for fresh spermatozoa and 89, 8 and 3% for frozen-thawed spermatozoa, respectively (P > 0.05). Following 22 h of incubation, the percentages of patterns I, II and III were 84, 11 and 5 for fresh spermatozoa and 83, 11 and 6% for frozen-thawed spermatozoa, respectively (not significant at P > 0.05). The percentages of patterns II and III in fresh and frozen-thawed spermatozoa were increased by the same magnitude with longer incubation in the capacitating conditions. It was concluded that the freezing-thawing procedure for human spermatozoa does not affect the expression of mannose-ligand receptors and the dynamics of sperm pre-fertilization processes.

Acrosome Reaction↗

High levels of catecholamines in human semen: a preliminary study.

The objective of this study was to determine the seminal concentrations of four different catecholamines and their association with semen quality. Seminal concentrations of adrenaline, noradrenaline, 3,4-dihydroxy-phenylalanine (DOPA), and 3,4-dihydroxy-phenyl acetic acid (DOPAC) were determined in 13 healthy volunteers, using high-performance liquid chromatography with an electrochemical detector. In addition, semen analysis was performed. Noradrenaline and DOPA were present in all specimens with a concentration of 15 181+/- 2951 pg ml(-1) and 4023 +/- 429 pg ml(-1) (mean +/- SE), respectively. These concentrations are respectively 19 times (range: 3-44) and twice (range: 1-3) as high as the maximal normal concentration in plasma. Adrenaline was present in 10 and DOPAC in seven of 13 specimens. No correlation was found between the concentration of any of the catecholamines evaluated and semen characteristics. In conclusion, noradrenaline and DOPA are present in human semen at concentrations that are much higher than maximal normal values in plasma. Adrenaline and DOPAC were also found in some of the samples. The concentrations of catecholamines in semen are not associated with semen quality.

Adult↗

The contribution of RNA-binding motif (RBM) antibody to the histopathologic evaluation of testicular biopsies from infertile men.

Testicular biopsies of infertile men are often characterized by mixed histologic patterns, with different types of spermatogenic impairments being found in adjacent seminiferous tubules. RNA-binding motif (RBM) is a nuclear protein expressed exclusively in the male germ cell line. We reasoned that RBM might be a useful marker to identify germ cells in testicular sections, particularly in biopsies with mixed histologic phenotype and small focal concentrations of spermatogenesis. Testicular biopsies from azoospermic men were immunohistochemically evaluated for RBM expression. RBM expression was detectable in spermatogonia, spermatocytes, and round spermatids in biopsies of men with obstructive azoospermia and normal spermatogenesis. No specific cell staining was shown in cases of Sertoli-cell-only (SCO) syndrome. In biopsies of patients with spermatogenic disorders, all the germ cells were stained up to and including the stage level of the arrest in spermatogenesis. This approach enabled identification of small focal concentrations of spermatogenesis in a biopsy previously classified as being SCO by hematoxylin and eosin staining. Thus, RBM can be a useful immunohistochemical marker for the specific identification of germ cells and provide greater accuracy in the histopathologic evaluation of testicular biopsies.

Antibodies↗

Results of 6139 artificial insemination cycles with donor spermatozoa.

BACKGROUND: Artificial insemination by donor spermatozoa (AID) can prove a valuable treatment for a number of male factor disorders, although its success rate is variable. METHODS: Retrospective analysis of the results of 6139 cycles performed in 1001 women during an 18 year period is presented. Pregnancy rates per cycle are presented as a function of: female fertility history, treatment modalities, medication used for induction of ovulation, female age, year of treatment, consecutive cycle effect and the use of fresh versus frozen-thawed spermatozoa. RESULTS: Overall pregnancy rate of 12.6% and cumulative pregnancy rate after 12 months of treatment of 75% were achieved. Age was found to be the most important determinant for success rate. CONCLUSIONS: Since the establishment of AID treatments, the mean age of the population of women receiving treatment has increased each year. Consequently, success rate did not improve, even with the use of more sophisticated medical modalities.

Abortion, Spontaneous↗

The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells.

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.

Cellular Senescence↗

High deletion frequency of the complete AZFa sequence in men with Sertoli-cell-only syndrome.

We have developed a rapid screening protocol for deletion analysis of the complete AZFa sequence (i.e. 792 kb) on the Y chromosome of patients with idiopathic Sertoli-cell-only (SCO) syndrome. This Y deletion was mapped earlier in proximal Yq11 and first found in the Y chromosome of the SCO patient JOLAR, now designated as the AZFa reference patient. We now show that similar AZFa deletions occur with a frequency of 9% in the SCO patient group. In two multiplex polymerase chain reaction experiments, deletions of the complete AZFa sequence were identified by a typical deletion pattern of four new sequence-tagged sites (STS): AZFa-prox1, positive; AZFa-prox2, negative; AZFa-dist1, negative; AZFa-dist2, positive. The STS were established in the proximal and distal neighbourhoods of the two retroviral sequence blocks (HERV15yq1 and HERV15yq2) which encompass the break-point sites for AZFa deletions of the human Y chromosome. We have found deletions of the complete AZFa sequence always associated with a uniform SCO pattern on testicular biopsies. Patients with other testicular histologies as described in the literature and in this paper have only partial AZFa deletions. The current AZFa screening protocols can therefore be improved by analysing the extension of AZFa deletions. This may provide a valuable prognostic tool for infertility clinics performing testicular sperm extraction, as it would enable the exclusion of AZFa patients with a complete SCO syndrome.

Chromosomes, Artificial, Bacterial↗

Zona pellucida binding improvement effect of different sperm preparation techniques is not related to changes in sperm motility characterizations.

OBJECTIVE: To study the relation between changes in sperm motion characteristics and sperm binding capacity to the zona pellucida (ZP) after different sperm preparation techniques. DESIGN: Prospective study. SETTING: Andrology laboratory at the Lis Maternity Hospital. PATIENT(S): Sixty-three infertile men. INTERVENTION(S): In vitro preparation of 57 sperm samples by pentoxifylline (PTX), 38 samples by SpermPrep I (SP1), and 27 samples by mini-Percoll (mPER). Sperm preparation was evaluated in comparison with the control washing technique. MAIN OUTCOME MEASURE(S): Motility variables and binding capacity. RESULT(S): Binding capacity after PTX, SP1, and mPER preparation methods was significantly higher compared with the control medium preparation. Computer-assisted sperm analysis (CASA) of sperm motility revealed a significant increase in a number of variables after the different treatments. A statistically significant but low correlation was observed between sperm binding capacity after control swim-up preparation and VAP (r = 0.27) as well as with VSL (r = 0.30). No significant correlations were found between the changes in the CASA and the improved sperm binding to the ZP. CONCLUSION(S): The two biologic effects of binding capacity enhancement and motility features improvement are not related. Furthermore, because the binding assay is highly correlated with fertilization capacity, these alterations in motility, as evidenced by CASA, probably have a minor effect on fertilization in vitro.

Electronic Data Processing↗

Evaluation of meiotic impairment of azoospermic men by fluorescence in situ hybridization.

OBJECTIVE: To identify predictive criteria for the existence of spermatogenesis in nonobstructive azoospermic men. DESIGN: Prospective study. SETTING: Andrology laboratory at a teaching hospital. PATIENT(S): Twenty-two azoospermic men were divided into three groups by qualitative testicular histopathology and the presence of spermatozoa in minced biopsies. INTERVENTION(S): Testicular biopsies evaluation. MAIN OUTCOME MEASURE(S): The presence of spermatozoa and/or mature spermatids, the percentage of sex vesicle formation (X and Y chromosomes in proximity), and the pairing of the two 18 homologous chromosomes. RESULT(S): Spermatozoa and mature spermatids were found in 17 study patients. Whenever few mature spermatids and/or spermatozoa were found, the rates of X-Y and 18 bivalents were significantly higher (mean +/- SD, 73% +/- 13. 3% and 91% +/- 7.1%) than those in cases of spermatocyte maturation arrest (23% +/- 8.0% and 60% +/- 11.8%, respectively). CONCLUSION(S): Pairing of chromosomes during meiosis is apparently related to the progression of spermatogenesis. Consequently, high rates of bivalent formation increase the prospect of focal spermatogenesis in the testis, despite the failure to identify mature spermatids in the specific testicular biopsy under examination.

Adult↗

Secrecy among Israeli recipients of donor insemination.

Patterns of discretion and disclosure of fertility-related information among Israeli recipients of donor insemination (DI) are explored. Based on questionnaires completed by recipients in four sperm banks, we studied differences between married women and men. We found that most Israeli recipients conceal the treatment from their friends and relatives. Women and men, however, differ in their disclosure patterns: women are somewhat more open about the general fertility problem, but conceal the male factor; men are more discreet. However, men who disclose the fertility problem also tell about their own impairment. DI appears to be the most secretive issue in this context. Recipients who confided in anyone about their problem restricted it mostly to family relatives. The results are interpreted in terms of Israeli pronatalism, traditional concepts of the natural family, as well as elements of macho culture. Public education is highly recommended in order to open and "normalize" DI in Israel.

Attitude↗