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Objective To investigate the applicability of phospholipase C zeta (PLCζ) analysis in assisting the clinical decision-making process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology. Design Fifty-six males (43 infertile/13 fertile) were screened using our PLCζ assay. Setting Fertility unit/university laboratory. Patient(s) Infertile males with abnormal sperm morphology or total fertilization failure, low fertilization rate ( Intervention(s) We analyzed PLCζ levels in sperm from fertile and infertile males. Eligible patients subsequently underwent intracytoplasmic sperm injection (ICSI)/artificial oocyte activation (AOA) with calcimycin (GM508). Main Outcome Measure(s) PLCζ localization and level and the proportion of sperm expressing PLCζ. Thresholds of PLCζ deficiency, fertilization rates, pregnancy rates, and live birth rates of AOA and non-AOA cycles. Result(s) Compared with 13 fertile controls, 34 of the 43 infertile males had significantly lower levels of PLCζ and/or a significantly lower proportion of sperm exhibiting PLCζ. Of these 34 patients, 15 showed a significant PLCζ reduction in both parameters, which we termed “PLCζ deficiency.” Five PLCζ-deficient patients opted for AOA; all five achieved fertilization, and four achieved clinical pregnancies and live births. The fertilization rate improved significantly from 18.6% (ICSI) to 56.8% (ICSI/AOA). The clinical pregnancy rate and live birth rate with AOA were both 40% per initiated cycle. Youden index analysis revealed that the cutoffs below which infertile males were likely to benefit from AOA were 71% for the proportion of sperm expressing PLCζ and 15.57 arbitrary units for mean PLCζ level. Conclusion(s) PLCζ analysis is a useful diagnostic tool to determine patient eligibility for subsequent AOA treatment.

Objective To determine differences and frequency of excessive (≥50%) sperm DNA damage between ejaculated and motile sperm. Design Sperm DNA damage was assessed by acridine orange fluorescence and the results of ejaculated and motile sperm were compared. Setting Public and private clinical assisted reproduction centers. Patient(s) A total of 272 subfertile men were studied. Intervention(s) None. Main Outcome Measure(s) Semen analysis and sperm DNA damage. Result(s) Sperm DNA damage was negatively correlated with sperm motility and normal morphology. Overall, 39.7% (108 of 272) of semen samples had excessive sperm DNA damage. In contrast, only 15% (41 of 272) of motile sperm fractions had excessive DNA damage. Based on DNA results of motile sperm and semen characteristics, the proportion of men with excessive sperm DNA damage was 26% in severe teratozoospermia, 17.5% in oligozoospermia, 12.5% in moderate teratozoospermia, and 4.6% in normozoospermia. Severe teratozoospermia had five times more frequent excessive DNA damage than normozoospermia. Conclusion(s) Abnormal sperm morphology is highly associated with sperm DNA damage. Results of DNA damage of ejaculated sperm do not accurately reflect DNA status of motile sperm. Therefore, sperm DNA damage should be assessed in motile sperm fraction rather than whole ejaculated sperm.

Objective To study the changes in semen parameters, gonadotropic and sex hormones, and serum leptin in obese fertile and infertile oligozoospermic men. Design Prospective. Setting University hospital. Patient(s) Forty-two obese fertile and 80 obese infertile oligozoospermic men (body mass index [BMI] >30). Intervention(s) The BMI calculation, semen analysis, and serum FSH, LH, T, E 2 , PRL, and leptin estimation. Main Outcome Measure(s) Semen and hormonal profiles. Result(s) Obese oligozoospermic patients had significant increase in mean BMI, serum FSH, LH, E 2 , PRL, and leptin compared with obese fertile controls. The BMI had significant positive correlation with abnormal sperm morphology, LH, serum leptin and significant negative correlation with sperm concentration, sperm motility, serum T. Serum leptin demonstrated significant positive correlation with patients' age, abnormal sperm morphology, serum FSH, LH, PRL and significant negative correlation with sperm concentration, sperm motility, and serum T. Conclusion(s) Serum leptin mediates a link between obesity and male infertility.

Objective To assess the effect of the Lebanese civil war on sperm parameters. Design Retrospective review of patient records. Setting Males providing semen samples at a university laboratory. Semen samples collected 1985–1989 (during the war) were compared with those obtained 1991–1995 (postwar). Patient(s) Males with or without a history of infertility providing semen samples at a university central laboratory. Intervention(s) None. Main Outcome Measure(s) Standard clinical semen analysis. Result(s) The sperm concentration was significantly lower during the war compared with the postwar period. However, the percentage of abnormal sperm morphology increased in the postwar period. War had no significant effect on volume and motility. Postwar, the percent azospermic and those 20 million). Conclusion(s) There was a significant decline in sperm concentration during the Lebanese civil war. Increased stress level during the war is believed to be one of the main factors leading to this finding.

Objective To evaluate the influence of morphology of individual spermatozoa on fertilization and pregnancy outcome. Design Retrospective analysis. Setting An IVF center in an institutional research environment. Patient(s) Fertilization and embryo quality according to individual sperm morphology were analyzed in 662 consecutive ICSI cycles. Pregnancy outcome was evaluated for these cycles and an additional 1005 consecutive ICSI cycles. Intervention(s) ICSI was performed using sperm cells of ejaculated, epididymal, or testicular origin. Observation through an inverted microscope was used to prospectively classify injected sperm cells as normal or morphologically abnormal. Main outcome measure(s) Oocyte fertilization, embryo morphology, and pregnancy outcome of unmixed embryo transfers. Result(s) Injection of morphologically abnormal spermatozoa (irrespective of origin) resulted in a lower fertilization rate (60.7%) than did injection of morphologically normal spermatozoa (71.7%). Embryo cleavage quality did not differ between groups. Higher pregnancy and implantation rates were obtained in patients with normal sperm morphology (36.7% and 18.7%, respectively) than in those with abnormal sperm morphology (20.2% and 9.6%). Conclusion(s) Individual sperm morphology assessed at the moment of ICSI correlated well with fertilization outcome but did not affect embryo development. The implantation rate was lower when only embryos resulting from injection of an abnormal spermatozoon were available.

Objective: To evaluate the impact of cigarette smoking on male factor subfertility and the semen parameters of sperm count, motility, and morphology by questionnaire and determination of the cotinine concentrations in blood and seminal plasma of fertile and subfertile males. Design: Case-control study of 107 fertile and 103 subfertile males who provided a standardized blood and semen specimen and completed a self-administered questionnaire about their smoking habits. Setting: Outpatient fertility clinic of the University Medical Centre St. Radboud, Nijmegen, The Netherlands. Patient(s): One hundred seven fertile and 103 subfertile males. Intervention(s): Vena puncture and semen collection. Main Outcome Measure(s): Blood and seminal plasma cotinine levels in relation to semen parameters. Result(s): A higher frequency of cigarette smoking was observed in subfertile males than in fertile males, with an odds ratio of 1.7 (95% confidence interval, 0.9–3.2). The self-reported number of cigarettes smoked per day correlated with the cotinine concentrations in blood and seminal plasma for both groups. A small but statistically significant correlation was found between cotinine concentrations in seminal plasma and the percentage of abnormal sperm morphology, but not for other semen parameters ( r s = 0.19). Conclusion(s): Although the mechanism of the toxicity of cotinine on sperm morphology is not clear, this study indicates only a minor effect of cigarette smoking on male factor subfertility, which is probably due to compounds in cigarette smoke other than nicotine (cotinine).

Male patients with chronic hepatitis C virus (HCV) infection (n = 57) demonstrated a statistically significant decrease in semen volume, sperm count, and progressive sperm motility and a statistically significant increase in abnormal sperm morphology compared with healthy controls (n = 40). The duration of the HCV infection was negatively correlated with semen volume and sperm motility where the HCV RNA viral load was negatively correlated with sperm count and sperm motility. Chronic HCV patients had statistically significantly lower total serum testosterone and higher serum E 2 and prolactin levels compared with healthy controls.

Objective To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. Design Cohort study. Setting Four regions in China where high exposure to BPA in the workplace existed. Patient(s) 218 men with and without BPA exposure in the workplace. Intervention(s) None. Main Outcome Measure(s) Semen parameters. Result(s) After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. Conclusion(s) These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.

Objective Sperm morphology classification was analyzed by the computer-assisted semen analysis equipped with the Morphologizer II (Cryo Resources Ltd., New York, NY) was compared with the traditional manual method. Design, Setting, Patients Fifty stained semen smears from men attending the infertility clinic of a tertiary referral institution were studied. Main Outcome Measures Sperm head morphology was classified by the two methods into the following forms: normal, small oval, big oval, taper, and amorphous. Results Overall, the classifications of mean percent normal, small, and amorphous head forms were similar in the two methods. However, the differences between paired values obtained by the two methods were highly variable (range from −20% to +20%). The large differences between the methods were related to the large coefficients of variations present when classifying abnormal sperm morphology even by the same experienced technician. Only the percent normal spermatozoa could be classified by both methods with acceptable precision. In contrast, the variations in the morphometric analyses between the different semen smears were very small. Conclusions There was no advantage of the morphologizer over the manual method in sperm morphology classification. The clinical value of morphometric parameters of spermatozoa has to be defined.

Objective To evaluate the impact of abnormal sperm morphology on the rates of aneuploidy, implantation, and clinical pregnancy. Design Retrospective cohort study. Setting University-based IVF center. Patient(s) Fifty-two patients undergoing their first IVF–preimplantation genetic diagnosis (PGD) cycle. Intervention(s) The PGD analysis of embryos. Main Outcome Measure(s) Patients were divided into two groups based on sperm morphology: teratospermic group (TSG) and normal sperm group (NSG). The primary outcome measures of rates of aneuploidy, implantation, clinical pregnancy rate (PR) per cycle, and clinical PR per embryo transfer were compared between TSG and NSG according to PGD analysis results. Results A higher percentage of normal embryos was seen in the NSG (32%) versus the TSG (20%). Overall, 30% of IVF–PGD cycles had no normal embryos for transfer. The clinical PR per cycle was 44% in the NSG compared to 14% in the TSG (relative risk [RR] = 3.19; 95% confidence interval [CI] 1.1–9.0). A similar trend was noted with the clinical PR per embryo transfer with 57% patients becoming pregnant in the NSG versus 20% patients in the TSG (RR = 2.76; 95% CI 1.2–7.2). Implantation was twice as likely to occur in the NSG as compared to TSG (RR = 2.5; 95% CI 1.1–7.2). Conclusion(s) Rates of euploidy, implantation, clinical PR per cycle, and clinical PR per embryo transfer were higher in the NSG compared to the TSG, suggesting that sperm morphology plays an important role in the outcome of IVF–PGD cycles.

Objective To evaluate the performance of the automated semen quality analyzer system for assessing sperm quality. Design Double-blind prospective study. Setting Tertiary care hospital. Patient(s) Fifty healthy men donated semen samples. Intervention(s) None. Main Outcome Measure(s) Precision, accuracy and agreement between automated and manual semen analysis methods was assessed for sperm concentration, motility, morphology, and known concentrations of latex bead quality control media. Result(s) A good agreement was seen between the results of sperm concentration reported by the SQA-V automated analyzer (Spermalite/SQA-V; Medical Electronic Systems Ltd, Caesarea Industrial Park, Israel) and those obtained manually. A similar linearity was seen when the SQA-V results were compared with the manual data and also when the manual results of individual operators were compared with each other. The automated assessment of morphology showed high sensitivity (89.9%) for identifying percent normal morphology, and the precision of the SQA-V was considerably higher when compared with the manual method. The interoperator variability for manual assessment was significant. The automated analysis was quick compared with the manual method. Conclusion(s) The SQA-V can be used interchangeably with manual semen analysis methods for examining sperm concentration and motility. The automated SQA-V analyzer is more precise and shows the ability to accurately classify normal versus abnormal sperm morphology.

In 98 men whose partners experienced three or more spontaneous abortions, there were no significant differences in ejaculate volume, concentration of sperm, the percentage of total abnormal sperm, or the percentage of individual sperm defects as compared with normal WHO standards and 17 men fathering successful pregnancies. These data indicate that neither abnormal sperm concentration nor abnormal sperm morphology are significantly associated with recurrent spontaneous abortion.

Objective: To evaluate sperm morphology assessment using the IVOS (Hamilton-Thorne Research Version 3 Dimension Program, Beverly, MA) system in prediction of fertilization rate in vitro after intracytoplasmic sperm injection (ICSI). Design: A prospective clinical study. Setting: Diagnostic andrology laboratory and assisted conception service. Patient(s): Thirty-five patients from the ICSI program were evaluated. Semen samples were analyzed using a computerized system for conventional semen parameters, sperm movement characteristics, and sperm morphology. Only patients with three or more metaphase II (MII) oocytes available were studied. Intervention(s): None. Main Outcome Measure(s): Fertilization rates in vitro after ICSI were compared according to the sperm morphology obtained from the IVOS system. Result(s): Linear regression analysis of fertilization rates against the sperm parameters assessed by computer (IVOS), which included conventional semen parameters, sperm movement characteristics, percentage of normal sperm morphology, and percentage of each specific abnormal sperm morphology, did not reveal any significant correlations. The mean (±SEM) fertilization rates in the healthy prognosis group (normal sperm morphology ≥4%) and poor prognosis group (normal sperm morphology ≤4%) were 82.4 ± 4.0% and 75.0 ± 3.8%, respectively. There was no statistically significant difference in the mean fertilization rate between both groups. Moreover, no statistically significant difference was found in overall fertilization rates in vitro between the two prognosis categories (79.6% versus 78.0%). Conclusion(s): Sperm morphology obtained from the IVOS system is not related to the outcome of ICSI and cannot be used for prediction of fertilization rate in vitro after ICSI.

Objective: To evaluate in a prospective randomized study the outcome of subzonal insemination (SUZI) in patients with male subfertility. Design: In a period of 7 months, 48 patients underwent IVF treatment for male subfertility reasons. Normal insemination and SUZI were performed on sibling oocytes. Patients were divided into three groups depending on the sperm morphology (strict criteria): group 1, 10% to 14%; group 2, 5% to 10%; group 3, 0% to 5%. Setting: Private fertility center in Leuven, Belgium. Main Outcome Measures: The fertilization rates, cleavage rates, implantation rates, and pregnancy rates between the normally inseminated and the SUZI-treated group were compared. Results: The fertilization rate with SUZI was significantly higher (32%) than after normal insemination (7%). The difference was striking in groups 2 and 3 (35% and 33% versus 11% and 4%). Conclusion: This study indicates that SUZI increases the fertility outcome in patients with male subfertility and that there is a marked difference in fertilization rate when morphology, using strict criteria, is

Sperm chromosomes from 15 fertile men were analyzed after fusion of their spermatozoa with zona-free hamster eggs. The total proportion of abnormal metaphases as well as the proportions of aneuploidy and structural aberrations were calculated for every man and examined for linear correlations with [1] sperm morphology and [2] the age of the persons studied. A positive correlation between the cytogenetic parameters and the percentage of abnormal sperm morphology was not evident, suggesting that assessment of sperm morphology cannot be used as an indicator of chromosomal damage in human spermatozoa. In contrast, there was a more distinct positive correlation between the age of donors and the three cytogenetic parameters studied.

This study aimed: (1) to evaluate the zona-binding capacity of patients with abnormal sperm morphology, using standard hemizona assay (HZA) conditions and increasing sperm insemination concentration during the assay and (2) to determine the insemination concentration needed to obtain equality in the number of tightly bound sperm to matching hemizonae, using sperm from teratozoospermic patients versus proven fertile controls. The minimum concentration of motile sperm from fertile controls necessary to validate HZA results was 250,000/mL (35.4 +/- 5.6 tightly bound sperm; mean +/- SE). The "effective number of sperm" (morphologically normal with high motility) was 60,750/mL. Each teratozoospermic patient had a unique, (higher) sperm insemination concentration (range: 0.5 X 10(6) to 2.0 X 10(6) motile sperm/mL) necessary to equal the number of tightly bound sperm representing the lower 95% confidence interval for the control sample (at 0.5 X 10(6) motile sperm/mL) with the matching hemizona. These results suggest that the HZA may be used as an indicator of the sperm insemination concentration during in vitro fertilization in patients with teratozoospermia.

NN1-bis(dichloroacetyl)18-octanediamine Cl2CHCONH(CH2)8NHCOCHCl2 was tested. Cytologically the semen of some infertile males show low sperm count poor motility abnormal sperm morphology with a high percentage of tapering forms and the presence of many immature cells of the germinal line. Since this seminal picture can be produced experimentally by the antispermatogenic compounds tested in these experiments and may be induced temporarily by illness the author reasons that the apparently spontaneous appearance of the combination of exfoliated cells and tapering form in individuals lacking overt clinical symptoms may be due to a disturbance in hormone distribution or to an abnormal metabolite. Evidence was sought of excessive or abnormal steroid excretion in 6 individuals presenting the required seminal picture. The data though scant point in the expected direction.

Sperm morphology evaluated by new, strict criteria is a good predictor of outcome in in vitro fertilization (IVF). This study aimed (1) to determine whether the fertilization rate of preovulatory oocytes in patients with abnormal morphology can be improved by increasing insemination concentration at the time of IVF and (2) to evaluate the pregnancy outcome in patients with abnormal sperm morphology. Three groups were studied: (1) normal morphology, (2) good prognosis pattern, and (3) poor prognosis pattern. All other sperm parameters were normal. Group 3 had a lower overall fertilization rate, lower pregnancy rate/cycle, and lower ongoing pregnancy rate/cycle. Groups 2 and 3 showed a higher miscarriage rate, although not significantly different from group 1. By increasing insemination concentration from 2- to 10-fold, the fertilization rate in group 3 increased from 14.5% to 62.6%. However, pregnancy outcome did not improve. We conclude that patients with severe sperm head abnormalities have a lower ability to establish successful pregnancies, even though fertilization may be achieved.

In patients with acceptable sperm count and motility, two patterns of abnormal morphology, judged with strict criteria, were identified and described. Patients with less than 4% normal forms and less than 30% morphology index (summation of normal and slightly amorphous forms) had a fertilization rate of 7.6% of the oocytes (P pattern, poor prognosis). Patients with normal morphology between 4 and 14% had a significantly better fertilization rate of 63.9% of the oocytes (P less than 0.0001). Cases with greater than 14% normal forms fertilized within the normal range for the laboratory. By evaluating sperm morphology with the proposed strict criteria, its predictive value in in vitro fertilization is enhanced.