- Email: [email protected]
Male Infertility
494
MALE INFERTILITY
agent are present in the tumor cells and the bladder at the time of the resection. In contrast, with postoperative topical chemotherapy treatment usually is delayed for at least 1 week following transurethral resection. At that time the tumor cells may already be established in the wound. Also, transurothelial absorption of the cy totoxic agents is unpredictable following a transurethral resection. In the clinical setting it is difficult to deter mine to what extent tumor recurrences are due to either incomplete resection of the primary lesion, missed syn chronous lesions, progression of multifocal areas of dys plasia or neoplasia, or tumor cell implantation. If im plantation can be eliminated with nontoxic doses of pre operative chemotherapy this approach may prove useful. William J. Catalona, M. D.
Single-Dose Cyclophosphamide for the Prevention of Bladder Tumor Implantation in F344 Rats: Site of Drug Activity W.
A.
SEE, S.
A.
CRIST AND
R. D.
WILLIAMS, Department of
Urology, University of Iowa, Iowa City, Iowa Cancer Res., 51: 1378-1383, 1991 Permission to Publish Abstract Not Granted
Editorial Comment: In the companion article the au thors demonstrated that single dose cyclophosphamide prevented bladder tumor implantation in F344 rats. In this article the authors show that the principal site of activity of cyclophosphamide is the site of implantation and it appears to be related to tissue levels of cyclophos phamide. The studies further demonstrate that periop erative low dose chemoprophylaxis may be effective treatment for application to other cancers in which sur gical manipulation may predispose to tumor cell implan tation. William J. Catalona, M. D.
Molecular Genetics of Human Bladder Carcinomas D. PERUCCA, P. SzEPETOWSKI, M.-P. SIMON AND P. GAUDRAY, LGMCH Faculte de Medecine, Nice, France Cancer Genet. Cytogenet., 49: 143-156, 1990 Bladder cancer corresponds to a tumor type whose clinical behavior is difficult to predict. A better understanding of this pathology is expected from molecular genetics, which brings together cytogenetics and molecular biology. Therefore, we have tried to overview correlations between chromosome ab normalities and the presence, in the vicinity of the altered loci, of genes (oncogenes and others) that could be involved in bladder oncogenesis and/or tumor progression. In addition to oncogene activation by point mutations, gene amplification, or deregulation of gene expression, several cytogenetic as well as molecular evidences point to genetic deletions (existence of "tumor suppressor genes") being involved in those processes.
Editorial Comment: This article from France provides an excellent overview of current studies on the molecu-
lar genetics of human bladder cancer. It is written in a straightforward fashion that allows a nonmolecular ge neticist to follow most of the information. The authors point out that cytogenetic studies have shown that 11 autosomes are frequently involved in bladder cancer, including chromosomes 1, 3, 5, 6, 7, 8, 9, 10, 11, 13 and 1 7. Some are of particular interest because they have been implicated as oncogenes or suppressor genes in other tumors. Most of the karyotypic abnormalities that have been observed involve losses of genetic material. From a cytogenetic viewpoint these could be primary changes involved in the early steps of malignant trans formation. The authors cite correlations between chromosome alterations and the location of genes that are believed to be involved with oncogenesis and tumor progression. For example, they state that deletions on chromosome 3 could affect the genes coding for receptor for retinoic acid. They point out that the absence of receptor for retinoic acid has been correlated with a poor prognosis and that retinoids inhibit the proliferation of neoplastic cells. Also, a trisomy could increase the receptor content for epidermal growth factor that has been demonstrated to be characteristic of poorly differentiated and invasive tumors. Another example cited is that monosomy of chromosome 9 could be involved in the disappearance of ABO blood group antigens on the surface of cancer cells and that abnormalities in chromosome 7 could result in the selection of drug resistance. On chromosome 10 a deletion could result in the loss of the suppressor gene that controls deoxyribonucleic acid replication or an other suppressor gene known to be involved in multiple endocrine neoplasia. The authors discuss results of molecular genetic analy sis with respect to oncogene activation by point muta tions. They emphasize that approximately 10 to 15% of bladder cancers have activated ras oncogenes. On the other hand, amplification of proto-oncogenes is a rare event in bladder cancer, and it is believed to be unlikely to be sufficient for oncogenesis and tumor progression. The authors include a discussion of tumor suppressor genes, particularly suppressor genes on chromosome 11 that have been associated with Wilms tumor, and sup pressor genes on chromosome 13 that have been associ ated with retinoblastoma and other tumors. They con clude that it is conceivable that loss of suppressor genes may represent primary targets for bladder cancer de velopment. The inactivation of these suppressor genes requires homozygous mutations, that is 2 hits, and the time needed to accumulate these 2 hits could be respon sible, at least in part, for the appearance of bladder cancer late in life. The article contains 76 references on the molecular genetics of bladder cancer, which are helpful to those interested. William J, Catalona, M. D.
MALE INFERTILITY Diagnostic Value of Scrotal Sonography in Infertile Men: Report on 658 Cases
MALE INFERTILITY
D. NASHAN, H. M. BEHRE, J. H. GRUNERT AND E. NIESCHLAG, Institute of Reproductive Medicine of the University and Max Planck Clinical Research Unit for Reproductive Medicine, Munster, Germany Andrologia, 22: 387-395, 1990 Scrotal sonography with a 7.5 MHz sector scanner was performed on 658 consecutive patients of our infertility clinic. The incidence of pathological findings was unexpectedly high. Forty per cent of the patients revealed pathological structures such as varicoceles (21%), hydroceles (7%), epididymal abnor malities ( 6%), spermatoceles (6% ), intratesticular hyper- and hyp oechoic changes (4.5%), intratesticular cysts (1%) and tu mours or carcinoma in situ (CIS) (0.6%). Sonographic evaluation and measurement of the caput epi didymidis was compared with palpation. Sonography distin guished size ranges of "normal" and "thickened" epididymides as diagnosed b;y palpation. Cystic structures were proven in 56% of cases with "thickened" epididymides. The sonographi cally determined diameters of doppler-negative blood vessels were significantly smaller than those of doppler-positive ves sels. Sonography revealed a higher occurrence of varicoceles than diagnosed by palpation (76% by palpation). Only 58% of sonographically identified hydroceles and only 67% of sono graphically detected spermatoceles were detected by palpation. One testicular tumour and one case with CIS were only seen by sonography and not suspected on palpation. The results demonstrate that sonography represents a valu able tool in the routine diagnosis of andrological patients.
Editorial Comment: Scrotal sonography is being used increasingly to evaluate male infertility. In this large prospective study from Germany 40% of 658 patients with male infertility were found to have a testicular pathological condition on sonography. A variety of the findings reported in this study, including hydrocele and testicular cysts, are of questionable significance in subfertile men. The authors found that 12% of subfertile patients had epididymal cysts or other abnormalities. Unfortunately, there is no control population to deter mine what the incidence of epididymal cyst is in age matched fertile controls. Of the patients 21% had vari coceles noted on Doppler ultrasound, of which only 76% were palpable. However, there remains a "gold stand ard" argument in this type of study. The presence of a varicocele by Doppler ultrasound was considered to be a true positive. In fact, 1 diagnostic test should not serve as the "gold standard" to evaluate the accuracy of an other diagnostic test. Since repair of varicoceles diag nosed only by Doppler ultrasound has not been conclu sively shown to improve pregnancy outcome, routine application of scrotal ultrasound for men in a fertility evaluation should be viewed as investigational. Cer tainly, scrotal sonography can provide an accurate as sessment of testicular volume but it remains to be seen whether routine scrotal sonography will provide sub stantial information to aid in the diagnosis and treat ment of the subfertile man. John D. McConnell, M. D.
Computer-Assisted Assessment of Human Sperm Mor phology: Usefulness in Predicting Fertilizing Capacity of Human Spermatozoa
C. WANG, V. NG, A. LEUNG, K.-F. LEE, W.-L. TSOI, S. Y. W. CHAN AND J. LEUNG, University of Hong Kong, Hong Kong, and Cedars-Sinai Medical Center, Los Angeles, California Fertil. Steril., 55: 989-993, 1991 Objective: The usefulness of sperm morphology to predict the outcome of human sperm fertilizing capacity was examined. Design, Setting, Patients: Semen samples from 50 male pa tients attending the infertility clinic of a tertiary referral insti tution were studied. Main Outcome Measures: Sperm morphology was classified both by visual assessment and computer-assisted image analy sis. In addition, morphometric analysis of the spermatozoa was measured by the morphologizer. Multivariate discriminant analysis was used to evaluate the usefulness of these morphol ogy parameters for predicting the outcome of the zona-free hamster oocyte sperm penetration assay. Results: The manually derived percent of spermatozoa with normal and small head were selected to be of discriminating value in predicting the outcome of the zona-free hamster oocyte penetration test. The accuracy of correctly classifying the out come of zona-free hamster oocyte penetration test by these two parameters in combination was 84%, whereas assessment of sperm morphology with morphometric analysis by the mor phologizer selected a total of eight variables, which together predicted sperm fertilizing capacity with 74% accuracy. Addi tion of the morphologizer-derived parameters to those derived manually did not significantly improve the predictive value. Conclusion: We conclude that the results of the zona-free hamster egg penetration test could be predicted using manual assessment of sperm morphology and computer-assisted mor phometric analysis did not add further information.
Computer-Assisted Assessment of Human Sperm Mor phology: Comparison With Visual Assessment
w.
C. WANG, V. NG, A. LEUNG, K.-F. LEE, W.-L. Tsor, S. Y. CHAN AND J. LEUNG, University of Hong Kong, Hong Kong, and Cedars-Sinai Medical Center, Los Angeles, California Fertil. Steril., 55: 983-998, 1991
Objective: Sperm morphology classification was analyzed by the computer-assisted semen analysis equipped with the Mor phologizer II (Cryo Resources Ltd., New York, NY) was com pared with the traditional manual method. Design, Setting, Patients: Fifty stained semen smears from men attending the infertility clinic of a tertiary referral insti tution were studied. Main Outcome Measures: Sperm head morphology was clas sified 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 ob tained 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 ex perienced technician. Only the percent normal spermatozoa could be classified by both methods with acceptable precision. In contrast, the variations in the morphometric analyses be tween the different semen smears were very small. Conclusions: There was no advantage of the morphologizer
496
MALE INFERTILITY
over the manual method in sperm morphology classification. The clinical value of morphometric parameters of spermatozoa has to be defined. Editorial Comment: Of the routine semen parameters sperm morphology is viewed as the most useful in dis criminating infertile from fertile men. Presumably, nor mal head morphology, an indirect indicator of head function, reflects to some degree the fertilization capac ity of the sperm. Classification of mid piece and tail defects may provide additional predictive value con cerning sperm motility. Recently, computer assisted sperm morphology units have been developed in an at tempt to improve the accuracy and predictive value of morphological analysis. Since manual assessment of sperm morphology is known to be subject to a large measurement variation, it was reasoned that computer assisted analysis would be superior. In the first study the predictive value of computer assisted morphometric measurements was determined by comparing the results of the morphometric assess ment with results of the zona-free hamster egg penetra tion assay. Although the penetration assay certainly has its own problems with predictive value (especially neg ative predictive value), it does correlate well with the results of in vitro fertilization. The authors found a reasonable correlation between the results of the sperm penetration assay and assessment of sperm morphology. However, there was no additional discriminatory value of the computer assisted morphometric analysis over the manual assessment. It is also interesting that the manual assessment of serum morphology classified the results of the zona-free hamster egg test with 8 4% accuracy, suggesting that simple assessment of morphology may indirectly provide roughly the same predictive value as the more expensive penetration assay. In the second study, the authors found that the com puter assisted morphology unit was not able to discrim inate accurately abnormal sperm forms. Only the per centage of normal sperm could be assessed accurately by manual and computer assisted methods. However, there was no advantage of the computer assisted system over manual morphology assessment. Since the com puter assisted method requires significantly more time than the manual assessment and a substantial invest ment in equipment, for the present time computer as sisted morphological analysis does not appear to be of clinical value. John D. McConnell, M. D.
Placebo-Controlled Trial of High-Dose Mesterolone Treatment of Idiopathic Male Infertility J. GERRIS, K. PEETERS, F. COMHAIRE, F. SCHOONJANS AND P. HELLEMANS, Middelheim General Hospital, Antwerp Uni
versity, Antwerp, and State University Hospital, Ghent, Bel gium
Fertil. Steril., 55: 603-607, 1991 The possible effect of Mesterolone (Schering N.V., Brussels, Belgium) (fo-methyl-5-a-androstane-17/3-ol-3-one) on semen quality and fertility of men with idiopathic oligoasthenospermia
and/or teratozoospermia has been evaluated in a double-blind trial. The study included 52 patients who were treated during 12 months with either 150 mg/d of Mesterolone or placebo. The overall pregnancy rate was similar in the Mesterolone treated cases (26%) and in the placebo control cases (48%), although a significant increase in motility and in the proportion of spermatozoa with normal morphology was recorded in the Mesterolone-treated cases. Because similar semen improve ment also occurred in the placebo controls, our findings cast doubt on the possible usefulness of high-dose Mesterolone treatment of idiopathic male infertility. Editorial Comment: Androgenic compounds have long been used for the empirical treatment of male subfertil ity. The previous rationale was that since spermatogen esis required a critical level of testosterone to proceed, exogenously administered androgenic hormones may improve sperm production. However, there is mounting evidence that this therapeutic approach lacks clinical efficacy. Moreover, it is clear that the administration of exogenous androgens is not rational from a physiologi cal point of view, since they do not increase the level of androgen in either the testis or the epididymal fluid. In this double-blind study men were treated with Mes terolone, an androgen derivative, and semen parameters and pregnancy rates were assessed. Although the over all pregnancy rates were not statistically different be tween the 2 groups, the trend was toward a lower pregnancy rate in the drug-treated group. The authors conclude that Mesterolone treatment does not have sig nificant value in the treatment of oligospermia. Based upon reproductive physiology studies that demonstrate that exogenous androgens do not increase intratesticu lar or intraepididymal androgen levels, and the failure to improve pregnancy rates, the empirical use of testos terone for the treatment of male infertility should be abandoned. John D. McConnell, M. D.
Variation in Sperm Penetration Assay Related to Viral Illness J.P. BUCH AND S. K. HAVLOVEC, Division of Urologic Surgery,
University of Nebraska School of Medicine, Omaha, Nebraska
Fertil. Steril., 55: 844-846, 1991 No Abstract Editorial Comment: Febrile illness has been known to affect sperm production for varying periods following the acute insult. In this case report a longitudinal fol lowup of a single donor documents the effect of a viral illness on spermatogenesis. The sperm density in the patient, which started at levels of approximately 100 million per ml., decreased to a low of 17 million per ml. 6 to 7 weeks after the illness. Recovery of sperm density did not occur until 14 to 15 weeks after the initial episode. In contrast, egg penetration ability, as assessed by the hamster egg sperm penetration assay, reached a nadir at 5 to 6 weeks but recovered more quickly than the sperm density, reaching control values 8 to 9 weeks
497 after the initial. ""..,,,,,,,...,;;. this is a ca§e report, it provide§ clinically useful information concern ing the response of sperm density and function to a brief viral mness. John D. McConneH, M. D.
Contraceptive Efficacy of Testosterone-Induced Azo ospermia in NormaJ Men
and prostatic cancer, a:re un known, If elevation of the plasma testosterone leads to elevation of intraprosta:tic testosterone and dihydrotes terone, then acceleration of benign prostati.c hyperplasia would be possible. Animal studies have afao raised the of high dose testosterone acting as a tumor promoter. Until these ism1es are resolved the use of testosterone as a contraceptive should remain investi gationaL John D. McConneH, M. D,
WORLD HEALTH ORGANISATION TASK FORCE ON METHODS FOR THE REGULATION OF MALE FERTILITY
Lancet, 336: 955-959, 1990 A multicentre study (ten centres) in seven countries was done to assess the contraceptive efficacy of hormonally-induced azoospermia in 271 healthy fertile men. Each subject received 200 mg testosterone enanthate weekly by intramuscular injec tion. 157 men (cumulative rate at 6 months 65%) became azoospermic in three consecutive semen samples. These men entered a 12-month efficacy phase during which continuing testosterone injections were the only form of contraception. There was 1 pregnancy during 1486 months of the efficacy phase (0.8 conceptions [95% confidence interval 0.02-4.5] per 100 person-years). Discontinuations from the study were mainly because azoospermia was not achieved within 6 months and because of dislike of the injection schedule. The mean time to become azoospermic was 120 days (SD 40); reappearance of spermatozoa was detected in 11 men and in no case led to discontinuation from the study or to pregnancy. After the testosterone injections had been stopped, the estimated median time from azoospermia to recovery (sperm concentration of at least 20 million/ml) was 3.7 months (3.6-3.9) and to the sub ject's mean baseline sperm concentration was 6.7 months (6.28.7). Hormonal regimens that induce azoospermia can provide highly effective, sustained, and reversible male contraception with minimum side-effects. Editorial Comment: This is a weH designed multicen ten�d study to assess the contraceptive effectiveness of testosterone-induced azoospermia in 271 fertile men, Each patient received 200 mg, testosterone enanthate weekly by intramuscular injection. Of the patients 85% became azoospermic at 6 months, which was docu mented 3 consecutive gamples. In the men rendered azoospermic there was patient-monthB, or 0.8 ""'""·"'P,'""'"'"' per 100 pernon yea:rs, There were no §ignificant side effects noted other than the inconvenience and discomfort of ....,�'""'�·· The mean time to become azoospermic was 120 days. In 11 men spermatozoa appeared after initial azoospermia. No pregnancy occurred in this group of patients. After ther apy was withdrawn all patients with a:wospermi.c levels experienced return to baseline sperm concentration within 6 to 7 months. It seems unlikely that injectable fo:rms of testosterone would ever achieve acceptance as a male contraceptive simply because of the inconvenience of delivery. Even with the development of more sophisticated delivery vehicles, such as implantable slow release capsules, there are questions about the safety of hormonal suppression. The effects of high levels of testosterone on prostatic growth, specifically on the development of be-
SEXUAL FUNCTION AND DYSFUNCTION Glans Ischemia After Penis Revascularization: Thera peutic EmboHzation G. WILMS, R. OYEN, L. CLAES, W. BOECKX, A. L. BAERT AND L. BAERT, Departments of Radiology, Urology and Surgery, University Hospitals KU Leuven, Belgium
Cardiovasc. Intervent. Rad., 13: 304-305, 1990 A case of hyp ervascularization of the penis with glans ische mia after venous leakage procedure followed by revascularization of the penis is reported. The venous byp ass between the inferior epigastric artery and the dorsal penile artery was mis placed on the deep dorsal vein leading to venous hyp ertension of the glans. Transcatheter embolization of the venous byp ass cured this complication. Editorial Comment: This case report describes an at tempt at penile revascularization for presumed vascu logenic impotence that resulted in hyperemia of the glans penis postoperatively. The authors report success ful treatment by embolization of the arterial graft. Two important points are made: 1) arte:ri.ographic evaluation of the penile arterial tree must be performed after injec tion of intracavernou.s vasodilators to avoid a false pos itive reading and when performing an anastomosis of the epigastric artery to deep dorsal vein it is imperative to tie off the distal deep dorsal vein and tributaries to prevent glanular hyperemia. If this results after a small branch is missed, therapeutic approaches include re operation with ligation of the open channel and the:ra peuti.c embolization. Tom F. Lue, M. D.
Controlled Vacuum Ch.amber for Standardized Photo graphic Documentation of Penile Erectile Deformity M. K.
GELBARD, Division of Urology, Clinical Faculty, UCLA School of Medicine, Los Angeles, California
Urology, 36: 367-369, 1990 No Abstract Editorial Comment: The author describes a technique in which a t:ransparent chamber and vacuum gauge are used to document the degree of penile curvature in pa tients with Peyronie's disease. The results are standard ized and reproducible. In my practice the degree of curvature can also be well characterized preoperatively
MALE INFERTILITY
agent are present in the tumor cells and the bladder at the time of the resection. In contrast, with postoperative topical chemotherapy treatment usually is delayed for at least 1 week following transurethral resection. At that time the tumor cells may already be established in the wound. Also, transurothelial absorption of the cy totoxic agents is unpredictable following a transurethral resection. In the clinical setting it is difficult to deter mine to what extent tumor recurrences are due to either incomplete resection of the primary lesion, missed syn chronous lesions, progression of multifocal areas of dys plasia or neoplasia, or tumor cell implantation. If im plantation can be eliminated with nontoxic doses of pre operative chemotherapy this approach may prove useful. William J. Catalona, M. D.
Single-Dose Cyclophosphamide for the Prevention of Bladder Tumor Implantation in F344 Rats: Site of Drug Activity W.
A.
SEE, S.
A.
CRIST AND
R. D.
WILLIAMS, Department of
Urology, University of Iowa, Iowa City, Iowa Cancer Res., 51: 1378-1383, 1991 Permission to Publish Abstract Not Granted
Editorial Comment: In the companion article the au thors demonstrated that single dose cyclophosphamide prevented bladder tumor implantation in F344 rats. In this article the authors show that the principal site of activity of cyclophosphamide is the site of implantation and it appears to be related to tissue levels of cyclophos phamide. The studies further demonstrate that periop erative low dose chemoprophylaxis may be effective treatment for application to other cancers in which sur gical manipulation may predispose to tumor cell implan tation. William J. Catalona, M. D.
Molecular Genetics of Human Bladder Carcinomas D. PERUCCA, P. SzEPETOWSKI, M.-P. SIMON AND P. GAUDRAY, LGMCH Faculte de Medecine, Nice, France Cancer Genet. Cytogenet., 49: 143-156, 1990 Bladder cancer corresponds to a tumor type whose clinical behavior is difficult to predict. A better understanding of this pathology is expected from molecular genetics, which brings together cytogenetics and molecular biology. Therefore, we have tried to overview correlations between chromosome ab normalities and the presence, in the vicinity of the altered loci, of genes (oncogenes and others) that could be involved in bladder oncogenesis and/or tumor progression. In addition to oncogene activation by point mutations, gene amplification, or deregulation of gene expression, several cytogenetic as well as molecular evidences point to genetic deletions (existence of "tumor suppressor genes") being involved in those processes.
Editorial Comment: This article from France provides an excellent overview of current studies on the molecu-
lar genetics of human bladder cancer. It is written in a straightforward fashion that allows a nonmolecular ge neticist to follow most of the information. The authors point out that cytogenetic studies have shown that 11 autosomes are frequently involved in bladder cancer, including chromosomes 1, 3, 5, 6, 7, 8, 9, 10, 11, 13 and 1 7. Some are of particular interest because they have been implicated as oncogenes or suppressor genes in other tumors. Most of the karyotypic abnormalities that have been observed involve losses of genetic material. From a cytogenetic viewpoint these could be primary changes involved in the early steps of malignant trans formation. The authors cite correlations between chromosome alterations and the location of genes that are believed to be involved with oncogenesis and tumor progression. For example, they state that deletions on chromosome 3 could affect the genes coding for receptor for retinoic acid. They point out that the absence of receptor for retinoic acid has been correlated with a poor prognosis and that retinoids inhibit the proliferation of neoplastic cells. Also, a trisomy could increase the receptor content for epidermal growth factor that has been demonstrated to be characteristic of poorly differentiated and invasive tumors. Another example cited is that monosomy of chromosome 9 could be involved in the disappearance of ABO blood group antigens on the surface of cancer cells and that abnormalities in chromosome 7 could result in the selection of drug resistance. On chromosome 10 a deletion could result in the loss of the suppressor gene that controls deoxyribonucleic acid replication or an other suppressor gene known to be involved in multiple endocrine neoplasia. The authors discuss results of molecular genetic analy sis with respect to oncogene activation by point muta tions. They emphasize that approximately 10 to 15% of bladder cancers have activated ras oncogenes. On the other hand, amplification of proto-oncogenes is a rare event in bladder cancer, and it is believed to be unlikely to be sufficient for oncogenesis and tumor progression. The authors include a discussion of tumor suppressor genes, particularly suppressor genes on chromosome 11 that have been associated with Wilms tumor, and sup pressor genes on chromosome 13 that have been associ ated with retinoblastoma and other tumors. They con clude that it is conceivable that loss of suppressor genes may represent primary targets for bladder cancer de velopment. The inactivation of these suppressor genes requires homozygous mutations, that is 2 hits, and the time needed to accumulate these 2 hits could be respon sible, at least in part, for the appearance of bladder cancer late in life. The article contains 76 references on the molecular genetics of bladder cancer, which are helpful to those interested. William J, Catalona, M. D.
MALE INFERTILITY Diagnostic Value of Scrotal Sonography in Infertile Men: Report on 658 Cases
MALE INFERTILITY
D. NASHAN, H. M. BEHRE, J. H. GRUNERT AND E. NIESCHLAG, Institute of Reproductive Medicine of the University and Max Planck Clinical Research Unit for Reproductive Medicine, Munster, Germany Andrologia, 22: 387-395, 1990 Scrotal sonography with a 7.5 MHz sector scanner was performed on 658 consecutive patients of our infertility clinic. The incidence of pathological findings was unexpectedly high. Forty per cent of the patients revealed pathological structures such as varicoceles (21%), hydroceles (7%), epididymal abnor malities ( 6%), spermatoceles (6% ), intratesticular hyper- and hyp oechoic changes (4.5%), intratesticular cysts (1%) and tu mours or carcinoma in situ (CIS) (0.6%). Sonographic evaluation and measurement of the caput epi didymidis was compared with palpation. Sonography distin guished size ranges of "normal" and "thickened" epididymides as diagnosed b;y palpation. Cystic structures were proven in 56% of cases with "thickened" epididymides. The sonographi cally determined diameters of doppler-negative blood vessels were significantly smaller than those of doppler-positive ves sels. Sonography revealed a higher occurrence of varicoceles than diagnosed by palpation (76% by palpation). Only 58% of sonographically identified hydroceles and only 67% of sono graphically detected spermatoceles were detected by palpation. One testicular tumour and one case with CIS were only seen by sonography and not suspected on palpation. The results demonstrate that sonography represents a valu able tool in the routine diagnosis of andrological patients.
Editorial Comment: Scrotal sonography is being used increasingly to evaluate male infertility. In this large prospective study from Germany 40% of 658 patients with male infertility were found to have a testicular pathological condition on sonography. A variety of the findings reported in this study, including hydrocele and testicular cysts, are of questionable significance in subfertile men. The authors found that 12% of subfertile patients had epididymal cysts or other abnormalities. Unfortunately, there is no control population to deter mine what the incidence of epididymal cyst is in age matched fertile controls. Of the patients 21% had vari coceles noted on Doppler ultrasound, of which only 76% were palpable. However, there remains a "gold stand ard" argument in this type of study. The presence of a varicocele by Doppler ultrasound was considered to be a true positive. In fact, 1 diagnostic test should not serve as the "gold standard" to evaluate the accuracy of an other diagnostic test. Since repair of varicoceles diag nosed only by Doppler ultrasound has not been conclu sively shown to improve pregnancy outcome, routine application of scrotal ultrasound for men in a fertility evaluation should be viewed as investigational. Cer tainly, scrotal sonography can provide an accurate as sessment of testicular volume but it remains to be seen whether routine scrotal sonography will provide sub stantial information to aid in the diagnosis and treat ment of the subfertile man. John D. McConnell, M. D.
Computer-Assisted Assessment of Human Sperm Mor phology: Usefulness in Predicting Fertilizing Capacity of Human Spermatozoa
C. WANG, V. NG, A. LEUNG, K.-F. LEE, W.-L. TSOI, S. Y. W. CHAN AND J. LEUNG, University of Hong Kong, Hong Kong, and Cedars-Sinai Medical Center, Los Angeles, California Fertil. Steril., 55: 989-993, 1991 Objective: The usefulness of sperm morphology to predict the outcome of human sperm fertilizing capacity was examined. Design, Setting, Patients: Semen samples from 50 male pa tients attending the infertility clinic of a tertiary referral insti tution were studied. Main Outcome Measures: Sperm morphology was classified both by visual assessment and computer-assisted image analy sis. In addition, morphometric analysis of the spermatozoa was measured by the morphologizer. Multivariate discriminant analysis was used to evaluate the usefulness of these morphol ogy parameters for predicting the outcome of the zona-free hamster oocyte sperm penetration assay. Results: The manually derived percent of spermatozoa with normal and small head were selected to be of discriminating value in predicting the outcome of the zona-free hamster oocyte penetration test. The accuracy of correctly classifying the out come of zona-free hamster oocyte penetration test by these two parameters in combination was 84%, whereas assessment of sperm morphology with morphometric analysis by the mor phologizer selected a total of eight variables, which together predicted sperm fertilizing capacity with 74% accuracy. Addi tion of the morphologizer-derived parameters to those derived manually did not significantly improve the predictive value. Conclusion: We conclude that the results of the zona-free hamster egg penetration test could be predicted using manual assessment of sperm morphology and computer-assisted mor phometric analysis did not add further information.
Computer-Assisted Assessment of Human Sperm Mor phology: Comparison With Visual Assessment
w.
C. WANG, V. NG, A. LEUNG, K.-F. LEE, W.-L. Tsor, S. Y. CHAN AND J. LEUNG, University of Hong Kong, Hong Kong, and Cedars-Sinai Medical Center, Los Angeles, California Fertil. Steril., 55: 983-998, 1991
Objective: Sperm morphology classification was analyzed by the computer-assisted semen analysis equipped with the Mor phologizer II (Cryo Resources Ltd., New York, NY) was com pared with the traditional manual method. Design, Setting, Patients: Fifty stained semen smears from men attending the infertility clinic of a tertiary referral insti tution were studied. Main Outcome Measures: Sperm head morphology was clas sified 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 ob tained 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 ex perienced technician. Only the percent normal spermatozoa could be classified by both methods with acceptable precision. In contrast, the variations in the morphometric analyses be tween the different semen smears were very small. Conclusions: There was no advantage of the morphologizer
496
MALE INFERTILITY
over the manual method in sperm morphology classification. The clinical value of morphometric parameters of spermatozoa has to be defined. Editorial Comment: Of the routine semen parameters sperm morphology is viewed as the most useful in dis criminating infertile from fertile men. Presumably, nor mal head morphology, an indirect indicator of head function, reflects to some degree the fertilization capac ity of the sperm. Classification of mid piece and tail defects may provide additional predictive value con cerning sperm motility. Recently, computer assisted sperm morphology units have been developed in an at tempt to improve the accuracy and predictive value of morphological analysis. Since manual assessment of sperm morphology is known to be subject to a large measurement variation, it was reasoned that computer assisted analysis would be superior. In the first study the predictive value of computer assisted morphometric measurements was determined by comparing the results of the morphometric assess ment with results of the zona-free hamster egg penetra tion assay. Although the penetration assay certainly has its own problems with predictive value (especially neg ative predictive value), it does correlate well with the results of in vitro fertilization. The authors found a reasonable correlation between the results of the sperm penetration assay and assessment of sperm morphology. However, there was no additional discriminatory value of the computer assisted morphometric analysis over the manual assessment. It is also interesting that the manual assessment of serum morphology classified the results of the zona-free hamster egg test with 8 4% accuracy, suggesting that simple assessment of morphology may indirectly provide roughly the same predictive value as the more expensive penetration assay. In the second study, the authors found that the com puter assisted morphology unit was not able to discrim inate accurately abnormal sperm forms. Only the per centage of normal sperm could be assessed accurately by manual and computer assisted methods. However, there was no advantage of the computer assisted system over manual morphology assessment. Since the com puter assisted method requires significantly more time than the manual assessment and a substantial invest ment in equipment, for the present time computer as sisted morphological analysis does not appear to be of clinical value. John D. McConnell, M. D.
Placebo-Controlled Trial of High-Dose Mesterolone Treatment of Idiopathic Male Infertility J. GERRIS, K. PEETERS, F. COMHAIRE, F. SCHOONJANS AND P. HELLEMANS, Middelheim General Hospital, Antwerp Uni
versity, Antwerp, and State University Hospital, Ghent, Bel gium
Fertil. Steril., 55: 603-607, 1991 The possible effect of Mesterolone (Schering N.V., Brussels, Belgium) (fo-methyl-5-a-androstane-17/3-ol-3-one) on semen quality and fertility of men with idiopathic oligoasthenospermia
and/or teratozoospermia has been evaluated in a double-blind trial. The study included 52 patients who were treated during 12 months with either 150 mg/d of Mesterolone or placebo. The overall pregnancy rate was similar in the Mesterolone treated cases (26%) and in the placebo control cases (48%), although a significant increase in motility and in the proportion of spermatozoa with normal morphology was recorded in the Mesterolone-treated cases. Because similar semen improve ment also occurred in the placebo controls, our findings cast doubt on the possible usefulness of high-dose Mesterolone treatment of idiopathic male infertility. Editorial Comment: Androgenic compounds have long been used for the empirical treatment of male subfertil ity. The previous rationale was that since spermatogen esis required a critical level of testosterone to proceed, exogenously administered androgenic hormones may improve sperm production. However, there is mounting evidence that this therapeutic approach lacks clinical efficacy. Moreover, it is clear that the administration of exogenous androgens is not rational from a physiologi cal point of view, since they do not increase the level of androgen in either the testis or the epididymal fluid. In this double-blind study men were treated with Mes terolone, an androgen derivative, and semen parameters and pregnancy rates were assessed. Although the over all pregnancy rates were not statistically different be tween the 2 groups, the trend was toward a lower pregnancy rate in the drug-treated group. The authors conclude that Mesterolone treatment does not have sig nificant value in the treatment of oligospermia. Based upon reproductive physiology studies that demonstrate that exogenous androgens do not increase intratesticu lar or intraepididymal androgen levels, and the failure to improve pregnancy rates, the empirical use of testos terone for the treatment of male infertility should be abandoned. John D. McConnell, M. D.
Variation in Sperm Penetration Assay Related to Viral Illness J.P. BUCH AND S. K. HAVLOVEC, Division of Urologic Surgery,
University of Nebraska School of Medicine, Omaha, Nebraska
Fertil. Steril., 55: 844-846, 1991 No Abstract Editorial Comment: Febrile illness has been known to affect sperm production for varying periods following the acute insult. In this case report a longitudinal fol lowup of a single donor documents the effect of a viral illness on spermatogenesis. The sperm density in the patient, which started at levels of approximately 100 million per ml., decreased to a low of 17 million per ml. 6 to 7 weeks after the illness. Recovery of sperm density did not occur until 14 to 15 weeks after the initial episode. In contrast, egg penetration ability, as assessed by the hamster egg sperm penetration assay, reached a nadir at 5 to 6 weeks but recovered more quickly than the sperm density, reaching control values 8 to 9 weeks
497 after the initial. ""..,,,,,,,...,;;. this is a ca§e report, it provide§ clinically useful information concern ing the response of sperm density and function to a brief viral mness. John D. McConneH, M. D.
Contraceptive Efficacy of Testosterone-Induced Azo ospermia in NormaJ Men
and prostatic cancer, a:re un known, If elevation of the plasma testosterone leads to elevation of intraprosta:tic testosterone and dihydrotes terone, then acceleration of benign prostati.c hyperplasia would be possible. Animal studies have afao raised the of high dose testosterone acting as a tumor promoter. Until these ism1es are resolved the use of testosterone as a contraceptive should remain investi gationaL John D. McConneH, M. D,
WORLD HEALTH ORGANISATION TASK FORCE ON METHODS FOR THE REGULATION OF MALE FERTILITY
Lancet, 336: 955-959, 1990 A multicentre study (ten centres) in seven countries was done to assess the contraceptive efficacy of hormonally-induced azoospermia in 271 healthy fertile men. Each subject received 200 mg testosterone enanthate weekly by intramuscular injec tion. 157 men (cumulative rate at 6 months 65%) became azoospermic in three consecutive semen samples. These men entered a 12-month efficacy phase during which continuing testosterone injections were the only form of contraception. There was 1 pregnancy during 1486 months of the efficacy phase (0.8 conceptions [95% confidence interval 0.02-4.5] per 100 person-years). Discontinuations from the study were mainly because azoospermia was not achieved within 6 months and because of dislike of the injection schedule. The mean time to become azoospermic was 120 days (SD 40); reappearance of spermatozoa was detected in 11 men and in no case led to discontinuation from the study or to pregnancy. After the testosterone injections had been stopped, the estimated median time from azoospermia to recovery (sperm concentration of at least 20 million/ml) was 3.7 months (3.6-3.9) and to the sub ject's mean baseline sperm concentration was 6.7 months (6.28.7). Hormonal regimens that induce azoospermia can provide highly effective, sustained, and reversible male contraception with minimum side-effects. Editorial Comment: This is a weH designed multicen ten�d study to assess the contraceptive effectiveness of testosterone-induced azoospermia in 271 fertile men, Each patient received 200 mg, testosterone enanthate weekly by intramuscular injection. Of the patients 85% became azoospermic at 6 months, which was docu mented 3 consecutive gamples. In the men rendered azoospermic there was patient-monthB, or 0.8 ""'""·"'P,'""'"'"' per 100 pernon yea:rs, There were no §ignificant side effects noted other than the inconvenience and discomfort of ....,�'""'�·· The mean time to become azoospermic was 120 days. In 11 men spermatozoa appeared after initial azoospermia. No pregnancy occurred in this group of patients. After ther apy was withdrawn all patients with a:wospermi.c levels experienced return to baseline sperm concentration within 6 to 7 months. It seems unlikely that injectable fo:rms of testosterone would ever achieve acceptance as a male contraceptive simply because of the inconvenience of delivery. Even with the development of more sophisticated delivery vehicles, such as implantable slow release capsules, there are questions about the safety of hormonal suppression. The effects of high levels of testosterone on prostatic growth, specifically on the development of be-
SEXUAL FUNCTION AND DYSFUNCTION Glans Ischemia After Penis Revascularization: Thera peutic EmboHzation G. WILMS, R. OYEN, L. CLAES, W. BOECKX, A. L. BAERT AND L. BAERT, Departments of Radiology, Urology and Surgery, University Hospitals KU Leuven, Belgium
Cardiovasc. Intervent. Rad., 13: 304-305, 1990 A case of hyp ervascularization of the penis with glans ische mia after venous leakage procedure followed by revascularization of the penis is reported. The venous byp ass between the inferior epigastric artery and the dorsal penile artery was mis placed on the deep dorsal vein leading to venous hyp ertension of the glans. Transcatheter embolization of the venous byp ass cured this complication. Editorial Comment: This case report describes an at tempt at penile revascularization for presumed vascu logenic impotence that resulted in hyperemia of the glans penis postoperatively. The authors report success ful treatment by embolization of the arterial graft. Two important points are made: 1) arte:ri.ographic evaluation of the penile arterial tree must be performed after injec tion of intracavernou.s vasodilators to avoid a false pos itive reading and when performing an anastomosis of the epigastric artery to deep dorsal vein it is imperative to tie off the distal deep dorsal vein and tributaries to prevent glanular hyperemia. If this results after a small branch is missed, therapeutic approaches include re operation with ligation of the open channel and the:ra peuti.c embolization. Tom F. Lue, M. D.
Controlled Vacuum Ch.amber for Standardized Photo graphic Documentation of Penile Erectile Deformity M. K.
GELBARD, Division of Urology, Clinical Faculty, UCLA School of Medicine, Los Angeles, California
Urology, 36: 367-369, 1990 No Abstract Editorial Comment: The author describes a technique in which a t:ransparent chamber and vacuum gauge are used to document the degree of penile curvature in pa tients with Peyronie's disease. The results are standard ized and reproducible. In my practice the degree of curvature can also be well characterized preoperatively