quantitative assessment of vascular flow in testes of infertility patients with varicocele using...

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we identified 69 non-azoospermic men with idiopathic infertility and 73 with clinical varicocele. Twenty consecutive fertile men presenting for vasectomy were used as controls. All men presenting for vasectomy had previously fathered at least 2 children. Standard semen parameters (density, motility and VMO morphology) were recorded. Residual sperm cytoplasm was detected by microscopic examination of Papanicolaou smears. A min- imum of 200 spermatozoa was examined per slide and the results were expressed as the percentage of sperm with retained cytoplasm. Results: Fertile controls had significantly greater mean percent sperm motility and normal morphology than infertile men, with no difference in semen parameters between men with idiopathic infertility and men with varicocele. The mean percentage of sperm with residual cytoplasm was significantly different in all three groups. Infertile men with varicocele had the highest percentage of sperm with residual cytoplasm, the next highest level being in men with idiopathic infertility and the lowest level in fertile controls (11.7 6 1.0, 8.1 6 0.9 and 3.2 6 0.4%, respectively, p,0.0001). Conclusions: Our data demonstrate that varicocele is associated with impaired disposal of sperm residual cytoplasm by the testis and/or epididymis. These data provide a possible mechanism for the observed semen abnormalities and reduced fertility potential associated with var- icocele. P-463 Quantitative Assessment of Vascular Flow in Testes of Infertility Pa- tients With Varicocele Using Power Doppler and Image Analysis. 1 L. Kaufman, 2 J. Drose, 1 L. S. Ross, 1 C. S. Niederberger, 2 R. Meacham. 1 Chicago, IL and 2 Denver, CO. Objectives: Varicoceles are the most often treated cause of male infertil- ity. Controversy remains, however, regarding the pathophysiological mech- anisms caused by varicocele. We sought to evaluate vascular flow using a highly sensitive ultrasonic device, power Doppler, and analyzed the images using programs we wrote in IDL (Interactive Data Language). Methods: 20 men with a history of male infertility were evaluated, as well as 4 normal controls. These men underwent a physical exam as well as a scrotal ultrasound to evaluate or rule out a varicocele. Using the IDL program we were able to analyze the blood flow of both the affected testicle as well as the contralateral unaffected testicle. Results: A decrease in blood flow recorded by IDL image analysis was noted in the testicle associated with the varicocele when compared to the unaffected testicle. The velocity and resistance to arterial flow in the af- fected testis were also not different than in the contralateral side or than in the normal controls. Conclusion: The current scientific consensus is that varicoceles cause male infertility. Many theories exist regarding the pathophysiological effect of varicoceles. By IDL image analysis of power Doppler images we de- tected decreased flow in the affected testis without an increase in resis- tance in the affected testicle. Thus, the use of the highly sensitive ul- trasonic technique of power Doppler combined with image analysis using IDL further supports the hypothesis that vascular compromise invokes the pathological changes of varicocele that are associated with male infertility. P-464 Characterizing the Clinical and Genetic Spectrum of Bilateral Vasal Agenesis in a Cohort of 168 Men. 1 T. J. McCallum, 1 J. M. Milunsky, 2 A. Nehra, 1 R. D. Oates. 1 Boston Medical Center, Boston, MA, 2 Mayo Clinic, Rochester, MN. Objective: A link between bilateral vasal agenesis and mutations in the cystic fibrosis (CF) genes is well established, but not all men have a gene anomaly. At one end of the phenotypic continuum is clinical CF while at the other is Congenital Bilateral Absence of the Vas Deferens (CBAVD) and no detectable mutation. A small percentage have unilateral renal agenesis (URA). The purpose of this study is to further enhance and define the phenotypic, radiologic, and genetic spectrum of the bilateral vasal agenesis syndromes. Design: Retrospective review of 168 men with bilateral vasal agenesis (1988 to 1999). Groups defined as: 1. clinical CF (CF), 2. CBAVD with CF gene mutations (CBAVD/CF), 3. CBAVD with URA (CBAVD/URA), 4. CBAVD—no CF mutations (CBAVD/--). Materials and Methods: History, physical exam, semen analysis, trans- rectal ultrasound (TRUS), and CFTR mutation, (up to 26 mutations, poly T tract assayed since 1997) were completed and the results for each group tabulated and subjected to Chi Square statistical analysis (Excel software package). Results: Classification: CF: 12; CBAVD/CF: 85; CBAVD/URA: 17; CBAVD/--: 54. There was no statistical difference seen between the 4 groups with regards to semen analysis volume or pH length of the epidid- ymal remnant or the presence or absence of seminal vesicles as determined by TRUS. Clinical CF was associated with a compound state more often than CBAVD/CF (p,.01). Table 1. CF CBAVD/CF CBAVD/URA CBAVD/-- Epididymides: Caput only 22 (92%) 120 (76%) 28 (82%) 61 (65%) Additional remnant present 2 (8%) 38 (24%) 6 (18%) 33 (35%) Seminal Vesicles: Agenesis 10 (50%) 52 (42%) 20 (62%) 44 (54%) Additional remnant present 72 (58% 12 (38%) 38 (46%) CFTR Status: Compound heterozygote 9 (75%) 6 (7%) 0 0 Simple heterozygote 1 (8%) 79 (94%) 2 (13%) 0 With 5T variant 1 25 0 0 Without 5T variant 0 32 2 0 Conclusions: There are at least 4 subtypes of bilateral vasal agenesis. CF and CBAVD/CF are genetic related but phenotypically different in terms of pulmonary and pancreatic disease. CBAVD/URA may have a completely different genetic etiology not secondary to anomalies of the CF genes. CBAVD/-- is of unclear etiology and may or may not be related to the either of the previous two groups. However, all appear to have the same ulti- mate phenotypic expression regarding the vasa, epididymides and sem- inal vesicles. P-465 Seminal Parameters in Men Over 40 Years Presenting to an In Vitro Fertilization (IVF) Facility. 1 O. Shah, 2 L. C. Krey, 1 A. R. McCullough. Departments of 1 Urology and 2 Obstetrics and Gynecology, New York University School of Medicine, New York, NY. Objectives: There have been conflicting reports regarding age-related changes in semen analysis parameters in both fertile and infertile men. Whereas several studies have shown that sperm count, motility, or mor- phology decrease in men older than 40 years of age, others have reported no changes in parameters with age. We undertook a study to look at the seminal parameters in this population of men presenting to an infertility center to establish mean values and to detect age-dependent changes. Design: A retrospective chart review was performed of all semen ana- lyzes in individuals $40 years of age presenting to an infertility center andrology lab in 1999. Materials and Methods: Fresh semen samples from 329 men were ana- lyzed manually by one of three andrology lab technicians. Semen analysis was performed according to the World Health Organization guidelines and sperm morphology was assessed by Kruger strict criteria. To evaluate the relationship between increasing age and semen characteristics, the men were divided into five groups: group A (n5181), 40 – 44 years; group B (n578), 45– 49; group C (n548), 50 –54; group D (n517), 55–59; group E (n55), .60. To evaluate the impact of strict morphology on other param- eters, the samples were divided into three groups: Group I ($14% normal sperm morphology); Group II (5–13%); Group III (#4%). Statistical anal- ysis was performed using SAS computer software. Results: Mean sperm concentration, motility, and strict morphology in men over the age of 40 undergoing semen analysis were 74.2 6 70.3 (standard deviation), 51.2 6 17.0, and 7.5 6 5.1, respectively. Correlation analysis of semen parameters vs. age did not reveal any significant differ- ences between groups A–E for concentration, motility, and head morphol- ogy. The only age-dependent difference was in tail morphology, where the appearance of coiled tails increased with age (p,0.01). Only 11.5% of men demonstrated 14% normal head morphology, Group I, while 57.2% were in Group II and 31.3% in Group III. As morphology improved, there was a significant improvement in count and motility: Group I (120.3, 61.9%), FERTILITY & STERILITYt S241

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Page 1: Quantitative Assessment of Vascular Flow in Testes of Infertility Patients With Varicocele Using Power Doppler and Image Analysis

we identified 69 non-azoospermic men with idiopathic infertility and 73with clinical varicocele. Twenty consecutive fertile men presenting forvasectomy were used as controls. All men presenting for vasectomy hadpreviously fathered at least 2 children. Standard semen parameters (density,motility and VMO morphology) were recorded. Residual sperm cytoplasmwas detected by microscopic examination of Papanicolaou smears. A min-imum of 200 spermatozoa was examined per slide and the results wereexpressed as the percentage of sperm with retained cytoplasm.

Results: Fertile controls had significantly greater mean percent spermmotility and normal morphology than infertile men, with no difference insemen parameters between men with idiopathic infertility and men withvaricocele. The mean percentage of sperm with residual cytoplasm wassignificantly different in all three groups. Infertile men with varicocele hadthe highest percentage of sperm with residual cytoplasm, the next highestlevel being in men with idiopathic infertility and the lowest level in fertilecontrols (11.76 1.0, 8.16 0.9 and 3.26 0.4%, respectively,p,0.0001).

Conclusions: Our data demonstrate that varicocele is associated withimpaired disposal of sperm residual cytoplasm by the testis and/orepididymis. These data provide a possible mechanism for the observedsemen abnormalities and reduced fertility potential associated with var-icocele.

P-463

Quantitative Assessment of Vascular Flow in Testes of Infertility Pa-tients With Varicocele Using Power Doppler and Image Analysis.1L. Kaufman,2J. Drose,1L. S. Ross,1C. S. Niederberger,2R. Meacham.1Chicago, IL and2Denver, CO.

Objectives: Varicoceles are the most often treated cause of male infertil-ity. Controversy remains, however, regarding the pathophysiological mech-anisms caused by varicocele. We sought to evaluate vascular flow using ahighly sensitive ultrasonic device, power Doppler, and analyzed the imagesusing programs we wrote in IDL (Interactive Data Language).

Methods: 20 men with a history of male infertility were evaluated, as wellas 4 normal controls. These men underwent a physical exam as well as ascrotal ultrasound to evaluate or rule out a varicocele. Using the IDLprogram we were able to analyze the blood flow of both the affected testicleas well as the contralateral unaffected testicle.

Results: A decrease in blood flow recorded by IDL image analysis wasnoted in the testicle associated with the varicocele when compared to theunaffected testicle. The velocity and resistance to arterial flow in the af-fected testis were also not different than in the contralateral side or than inthe normal controls.

Conclusion: The current scientific consensus is that varicoceles causemale infertility. Many theories exist regarding the pathophysiological effectof varicoceles. By IDL image analysis of power Doppler images we de-tected decreased flow in the affected testis without an increase in resis-tance in the affected testicle. Thus, the use of the highly sensitive ul-trasonic technique of power Doppler combined with image analysisusing IDL further supports the hypothesis that vascular compromiseinvokes the pathological changes of varicocele that are associated withmale infertility.

P-464

Characterizing the Clinical and Genetic Spectrum of Bilateral VasalAgenesis in a Cohort of 168 Men.1T. J. McCallum,1J. M. Milunsky,2A.Nehra,1R. D. Oates.1Boston Medical Center, Boston, MA,2Mayo Clinic,Rochester, MN.

Objective: A link between bilateral vasal agenesis and mutations in thecystic fibrosis (CF) genes is well established, but not all men have a geneanomaly. At one end of the phenotypic continuum is clinical CF while at theother is Congenital Bilateral Absence of the Vas Deferens (CBAVD) andno detectable mutation. A small percentage have unilateral renal agenesis(URA). The purpose of this study is to further enhance and define thephenotypic, radiologic, and genetic spectrum of the bilateral vasal agenesissyndromes.

Design: Retrospective review of 168 men with bilateral vasal agenesis(1988 to 1999). Groups defined as: 1. clinical CF (CF), 2. CBAVD with CFgene mutations (CBAVD/CF), 3. CBAVD with URA (CBAVD/URA), 4.CBAVD—no CF mutations (CBAVD/--).

Materials and Methods: History, physical exam, semen analysis, trans-rectal ultrasound (TRUS), and CFTR mutation, (up to 26 mutations, poly Ttract assayed since 1997) were completed and the results for each grouptabulated and subjected to Chi Square statistical analysis (Excel softwarepackage).

Results: Classification: CF: 12; CBAVD/CF: 85; CBAVD/URA: 17;CBAVD/--: 54. There was no statistical difference seen between the 4groups with regards to semen analysis volume or pH length of the epidid-ymal remnant or the presence or absence of seminal vesicles as determinedby TRUS. Clinical CF was associated with a compound state more oftenthan CBAVD/CF (p,.01).

Table 1.

CF CBAVD/CF CBAVD/URA CBAVD/--

Epididymides:Caput only 22 (92%) 120 (76%) 28 (82%) 61 (65%)Additional remnant present 2 (8%) 38 (24%) 6 (18%) 33 (35%)

Seminal Vesicles:Agenesis 10 (50%) 52 (42%) 20 (62%) 44 (54%)Additional remnant present 72 (58% 12 (38%) 38 (46%)

CFTR Status:Compound heterozygote 9 (75%) 6 (7%) 0 0Simple heterozygote 1 (8%) 79 (94%) 2 (13%) 0

With 5T variant 1 25 0 0Without 5T variant 0 32 2 0

Conclusions: There are at least 4 subtypes of bilateral vasal agenesis. CFand CBAVD/CF are genetic related but phenotypically different in terms ofpulmonary and pancreatic disease. CBAVD/URA may have a completelydifferent genetic etiology not secondary to anomalies of the CF genes.CBAVD/-- is of unclear etiology and may or may not be related to the eitherof the previous two groups. However, all appear to have the same ulti-mate phenotypic expression regarding the vasa, epididymides and sem-inal vesicles.

P-465

Seminal Parameters in Men Over 40 Years Presenting to an In VitroFertilization (IVF) Facility. 1O. Shah,2L. C. Krey, 1A. R. McCullough.Departments of1Urology and 2Obstetrics and Gynecology, New YorkUniversity School of Medicine, New York, NY.

Objectives: There have been conflicting reports regarding age-relatedchanges in semen analysis parameters in both fertile and infertile men.Whereas several studies have shown that sperm count, motility, or mor-phology decrease in men older than 40 years of age, others have reported nochanges in parameters with age. We undertook a study to look at the seminalparameters in this population of men presenting to an infertility center toestablish mean values and to detect age-dependent changes.

Design: A retrospective chart review was performed of all semen ana-lyzes in individuals$40 years of age presenting to an infertility centerandrology lab in 1999.

Materials and Methods: Fresh semen samples from 329 men were ana-lyzed manually by one of three andrology lab technicians. Semen analysiswas performed according to the World Health Organization guidelines andsperm morphology was assessed by Kruger strict criteria. To evaluate therelationship between increasing age and semen characteristics, the menwere divided into five groups: group A (n5181), 40–44 years; group B(n578), 45–49; group C (n548), 50–54; group D (n517), 55–59; group E(n55), .60. To evaluate the impact of strict morphology on other param-eters, the samples were divided into three groups: Group I ($14% normalsperm morphology); Group II (5–13%); Group III (#4%). Statistical anal-ysis was performed using SAS computer software.

Results: Mean sperm concentration, motility, and strict morphology inmen over the age of 40 undergoing semen analysis were 74.26 70.3(standard deviation), 51.26 17.0, and 7.56 5.1, respectively. Correlationanalysis of semen parameters vs. age did not reveal any significant differ-ences between groups A–E for concentration, motility, and head morphol-ogy. The only age-dependent difference was in tail morphology, where theappearance of coiled tails increased with age (p,0.01). Only 11.5% of mendemonstrated 14% normal head morphology, Group I, while 57.2% were inGroup II and 31.3% in Group III. As morphology improved, there was asignificant improvement in count and motility: Group I (120.3, 61.9%),

FERTILITY & STERILITY t S241