Approaching the next millennium: how should we manage andrology diagnosis in the intracytoplasmic sperm injection era?
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Biomedical subjects
Publications and source records attributed to T Kruger.
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OBJECTIVE: To assess the relationship between sperm morphology and motion parameters and sperm-zona pellucida (ZP) binding capacity under hemizona assay (HZA) conditions and to determine the discriminatory power of the HZA for the prediction of in vitro sperm fertilizing ability. DESIGN: Prospectively designed study. SETTING: Academic tertiary centers. PATIENT(S): One hundred ninety-six couples undergoing IVF therapy participated in this study. INTERVENTION(S): Hemizona assay and IVF results were determined for each couple. MAIN OUTCOME MEASURE(S): Computerized sperm motion analysis, sperm morphology (strict) criteria), and HZA results were correlated with fertilization outcome. RESULT(S): Among sperm parameters from the original ejaculates, morphology was the best predictor of sperm-ZP binding ability; hyperactivated motility was the best predictor of HZA results after swim-up separation of the motile sperm fractions. The HZA index provided the highest discriminatory power for fertilization success/failure, with an overall accuracy of 86%. CONCLUSION(S): Sperm morphology and hyperactivated motility showed a high correlation with the capacity of sperm to achieve tight binding to the ZP. The excellent positive and negative predictive values of the HZA for fertilization outcome provide additional support for the use of this functional bioassay in the decision-making process within the assisted reproduction setting.
This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non-bacterial cultures turned out to be of little prognostic value.
This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants who are mechanically ventilated due to respiratory distress. The disease consists of an initial inflammatory influx of neutrophils to the lungs, followed by long-term chronic fibrosis of the lung tissue. The antigenic repertoire that initiates the inflammatory component of BPD has not been defined. Furthermore, the repertoire of cytokines responsible for attracting neutrophils to the lung and the mediators of pathogenesis in BPD have not been characterized. Mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum have been isolated from the lungs of infants that developed BPD and yet have not been widely recognized as potential initiators of the inflammatory component of BPD. In the studies described here, we examined the ability of both viable and heat-killed Mycoplasma hominis to elicit type II epithelial cell production of cytokines that are chemotactic for polymorphonuclear leukocytes (PMNs), particularly interleukin-8 (IL-8) and epithelial cell-derived neutrophil-activating peptide (ENA-78). The results of these studies demonstrate that M. hominis and M. hominis antigen are potent stimulators of type II epithelial cell-derived IL-8 and ENA-78. Thus, these data strongly suggest that the presence of M. hominis in the lungs of premature infants may initiate the inflammatory component of BPD by inducing epithelial cell production of cytokines chemotactic for PMNs. Furthermore, these data suggest that the onset of the inflammatory component of BPD likely precedes, and is independent of, the recruitment and activation of alveolar macrophages.
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A prospective randomized study was conducted to assess the prognostic value of sperm morphology in an in-vitro fertilization (IVF) programme, using strict criteria. The first group (T, teratozoospermic) included 32 couples with an isolated teratozoospermia in the male partner (morphology < 9% normal). The second group (C, control) contained 36 couples with normal semen parameters, including morphology (> 9% normal, strict criteria). In both groups, 50 IVF cycles were performed. Patients were matched for indication for IVF. There was no difference between the two groups regarding age, duration of infertility, stimulation protocol, catheter used for embryo transfer and different sperm parameters. A statistically significant difference between the T and C groups respectively was observed regarding the fertilization rate (69.2 and 79.4%, P < 0.05), pregnancy rate per cycle (12.0 and 42%, P < 0.001), the pregnancy rate per transfer (13.9 and 42.0%, P < 0.01) and per embryo transferred (6.1 and 14.8%, P < 0.05). No pregnancy occurred in the poor prognosis group (morphology < 5% normal). In cases of moderate teratozoospermia, the fertilization rate appeared normal (78.6%) but the conception rate remained low. We concluded that the use of strict criteria in the assessment of sperm morphology is useful in predicting fertilization and pregnancy rate in the human in-vitro model.
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Because methylene blue exhibits germicidal, oxidation, and reduction properties, the authors asked whether this agent causes adverse effects on gametes, embryos, and/or secretions of the reproductive tract. Time- and dose-dependent inhibition of human sperm motility by methylene blue was observed, as was growth inhibition of 2-cell mouse embryos. Furthermore, the presence of methylene blue in uterine, fallopian tube, and peritoneal fluids altered protein mobility in polyacrylamide gels, and yielded apparent values of follicle-stimulating hormone and estradiol up to 260% of actual values (P less than 0.05). These data suggest that the presence of methylene blue in reproductive tract fluids may provide a false impression of their biochemical and biophysical compositions, and that the use of methylene blue as a chromopertubation agent be conducted with appropriate awareness.
Failure of fertilization in patients undergoing in vitro fertilization (IVF) deserves extensive analysis for better prediction of the success or failure of this therapeutic modality. Consequently, we retrospectively studied the 52 couples in whom fertilization failed during Norfolk series 18 to 25, in an effort to establish the precise causes of failure. In the initial evaluation, pure oocyte abnormalities were identified in 19.2% of the cases; 32.6% showed sperm abnormalities, and a combination of oocyte and sperm anomalies was found in 7.7%. In 40.4% of the cases, failure of fertilization could not be explained. Reassessment of sperm morphology by new, strict criteria increased the identification of sperm abnormalities to 61.5% and of combined sperm and oocyte anomalies to 13.4%, for a total of 74.9% of sperm factors involved, as opposed to 40.3% in the original evaluation. The incidence of unexplained failed fertilization was substantially reduced, to 11.5%. In a control group (tubal infertility) matched by age, date, and stimulation, in whom fertilization occurred, 83.3% had normal sperm parameters as judged by the new criteria for morphology evaluation. This paper emphasizes the need for a more accurate diagnosis of sperm abnormalities to establish the true incidence of this factor in failed fertilization and to obtain information of prognostic value to patients and clinicians.
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The present investigation relates the results obtained by the indirect immunobead test (IBT) to those found during the tray-agglutination test (TAT) and sperm immobilization test (SIT) performed on 16 positive blood sera samples. An IB binding of greater than 50% can be regarded as significantly positive (p less than 0.05), since 77% of the positive IB samples with an IB binding of greater than 50% also revealed a TAT titer of greater than 1:8. The IBT is an excellent test for the detection of sperm antibodies during routine screening procedures.
Spermatozoal autoantibodies have been associated with reduced fertilization by natural coital methods. Nine subfertile men were evaluated who repeatedly tested positive for spermatozoal autoantibodies as characterized by direct immunobead test. Using the hemizona assay, we determined whether tight binding of spermatozoa to the zona pellucida was reduced in these test males as compared to a fertile male whose semen had been cryopreserved and thawed immediately prior to testing. The average number of spermatozoa tightly bound to the zona pellucida from the subfertile male was significantly reduced compared to the fertile male (mean +/- SD, P less than or equal to 0.01) 19.5 +/- 8 versus 77.1 +/- 49. Seven of the nine couples eventually had successful fertilization using intrauterine insemination or gamete intrafallopian tube transfer and one couple conceived with natural coital insemination. Our findings, albeit limited, suggest that greater caution should be used in implicating associations of spermatozoal autoantibodies with absolute infertility, because novel assisted reproductive technologies often may obviate conventional encumbrances on opportunities for pregnancy.
The hemizona assay (HZA) has facilitated investigations of sperm function in relation to zona pellucida binding. In this study, the authors examined: 1) the association between hyperactivated sperm motility and HZA binding; 2) the binding kinetics and efficiency of sperm from subfertile men; and 3) the influence of sperm freezing and thawing on binding capacity. For each HZA, a nonviable human oocyte was cut into equal zona hemispheres. The mean number of bound sperm and the incidence of hyperactivation were significantly greater for samples of sperm from fertile men compared with sperm from subfertile men (P less than 0.05). Subfertile sperm had a binding curve that paralleled the curve for fertile sperm, although the magnitude of binding was markedly reduced. Freezing and thawing of sperm from fertile samples impaired their capacity to bind to the zona pellucida. The HZA binding efficiency was reduced by 30%, although the binding curves for fresh versus frozen samples remained parallel.