the gr/gr polymorphism is clinically irrelevant

2
594 THE JOURNAL OF UROLOGY ® Vol. 179, No. 4, Supplement, Wednesday, May 21, 2008 respectively. The differences between KFS and NOA, KFS and OA, NOA in FSH, LH, and free T level. CONCLUSIONS: We provided the important message of the metabolic syndrome in KFS. Hypogonadism in KFS may cause an unfavorable change in body composition and metabolic syndrome. Hypogonadism is frequent in KFS, and we recommend that patients in KFS with low testosterone level should be treated properly with testosterone replacement. Source of Funding: None 1734 THE ASSESSMENT OF SERUM HORMONE LEVELS IN PATIENTS WITH NON-OBSTRUCTIVE AZOOSPERMIA AFTER MICRODISSECTION TESTICULAR SPERM EXTRACTION Yutaka Kondo*, Tomomoto Ishikawa, Kohei Yamaguchi, Atsushi Takenaka, Masato Fujisawa. Kobe, Japan. INTRODUCTION AND OBJECTIVE: Testicular sperm extraction (TESE), in combination with intracytoplasmic sperm injection, microdissection TESE (MD-TESE), which is less invasive and results in high sperm retrieval rate, is preferred. Even in patients with Klinefelter syndrome (KS), who usually present small testis and hypogonadism, MD- TESE has been successfully performed. Although recent studies reported that MD-TESE procedures might impair testosterone production, little studies compared postoperative serum hormone levels between 46XY males with NOA and KS have been reported. In this study, we assayed serum hormone levels after MD-TESE and compared postoperative testicular damage between 46XY males with NOA and KS. METHODS: The records were retrospectively evaluated for KS) who were underwent MD-TESE from January 2001 to November 2006 in Kobe University Hospital. Karyotyping test was performed on a sample of blood to all patients. Serum follicle-stimulating hormone were evaluated before and at 6 and 12 months after surgery. For rate- of-change analysis, these hormone levels at 6 and 12 months after MD-TESE in each patient were expressed as arbitrary units relative to baseline concentration, set as a value of “1.” RESULTS: In 46XY males with NOA, serum levels of FSH at increased from baseline concentrations (p = .001, .01, and .003, of LH at 12 months and T at 6 and 12 months compared to baseline concentrations at all time after surgery (0.79-fold at 6 months, p = .007, and 0.77-fold at 12 months, p = .003). FSH and LH concentrations in rate of change of T concentrations (p = .02 at 6 months and .03 at 12 months, respectively). CONCLUSIONS: Long term hormonal follow up is recommended after MD-TESE, particularly in patients with KS. We recommend that patients in KS with low T level after MD- TESE may be treated properly to prevent the long-term deleterious consequences of hypogonadism. Source of Funding: None 1735 SIGNIFICANT INCIDENCE OF HYPOANDROGENISM IN INFERTILE MEN Beneranda S Ford*, Lawrence S Ross, Craig S Niederberger. Chicago, IL. INTRODUCTION AND OBJECTIVE: In 1997, Sigman and Jarow observed that the incidence of endocrinopathy in men with > 10 million sperm/ml was low enough to recommend an endocrine study unnecessary if this threshold was met. In the present era, increasing men sperm may be extracted for ICSI. We sought to determine the incidence < 300 ng/dl in a modern infertile male population undergoing evaluation, and verify the results in a subset analysis as calculated by bioavailable testosterone by the free testosterone index (FTI). METHODS: Patient records for men presenting with infertility ml (oligospermia) and sperm density > 20 million/ml (normospermia). Incidence of total T < 300 ng/dl was determined in each group and calculated using the FTI with total testosterone, albumin and sex hormone binding globulin (SHBG). incidence of hypoandrogenism by FDA criteria in men with OA was similar to the general population at 16.7%. 45.0% of men with NOA had total T < 300 ng/dl. Interestingly, 42.9% men with oligospermia and 35.3% of men with sperm density > 20 million/ml but presenting with infertility had total T < 300 ng/dl. Comparing incidence of hypoandrogenism in the infertile non-obstructive groups to that of OA, the difference was of 16 men were available with total T, SHBG and albumin to calculate bioavailable T by the FTI. 83.3% of men with NOA had bioavailable T < 200 ng/dl. CONCLUSIONS: The incidence of hypoandrogenism by FDA criteria for men with NOA is high at 45.0%. Subset analysis calculating incidence of hypoandrogenism in men with OA (with an incidence expected to be similar to the general population) to men with NOA, oligospermia and sperm density > 20 million/ml but presenting with 1990s, but the widespread use of the FDA criteria for hypoandrogenism and an increasing presentation of men with NOA may account for the term follow-up. Source of Funding: None 1736 THE GR/GR POLYMORPHISM IS CLINICALLY IRRELEVANT Peter J Stahl*, Anna Mielnik, Michael B Marean, Peter N Schlegel, Darius A Paduch. New York, NY. INTRODUCTION AND OBJECTIVE: Y chromosome microdeletion (YCM) screening provides prognostic information that guides the management of infertile men. Patients with classic YCMs are at risk for spermatogenic failure and have predictably altered outcomes of microsurgical testicular sperm extraction (microTESE). With more widespread genetic diagnostics, increasing numbers of clinical sequelae of the gr/gr deletion are unclear. Studies have been limited by small ethnically homogenous patient populations and have men, the largest to date. METHODS: We screened 1997 men for YCMs from 1997-2007 by PCR of sequence tagged sites (STS). Prior to 2004 patients were not initially screened for the gr/gr polymorphism. In all possible cases, these patients were re-screened using our DNA repository. 258 patients without available semen analyses and 329 patients without banked testicular ultrasounds, and microTESE outcomes were retrospectively the sy1291 STS. We have previously published our detailed screening methods. Frequency of the gr/gr polymorphism in the screened population Sperm Concentration (million per mL) Number Screened Number of gr/gr Deletions Detected gr/gr Frequency 989 43 4.3% <1 197 6 3.0% 1 - <5 120 12 10.0% 5 - <20 61 6 9.8% 20+ 43 6 14% Total 1410 73 5.2%

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Page 1: THE GR/GR POLYMORPHISM IS CLINICALLY IRRELEVANT

594 THE JOURNAL OF UROLOGY® Vol. 179, No. 4, Supplement, Wednesday, May 21, 2008

respectively. The differences between KFS and NOA, KFS and OA, NOA

in FSH, LH, and free T level. CONCLUSIONS: We provided the important message of

the metabolic syndrome in KFS. Hypogonadism in KFS may cause an unfavorable change in body composition and metabolic syndrome. Hypogonadism is frequent in KFS, and we recommend that patients in KFS with low testosterone level should be treated properly with testosterone replacement.

Source of Funding: None

1734THE ASSESSMENT OF SERUM HORMONE LEVELS IN PATIENTS WITH NON-OBSTRUCTIVE AZOOSPERMIA AFTER MICRODISSECTION TESTICULAR SPERM EXTRACTIONYutaka Kondo*, Tomomoto Ishikawa, Kohei Yamaguchi, Atsushi Takenaka, Masato Fujisawa. Kobe, Japan.

INTRODUCTION AND OBJECTIVE: Testicular sperm extraction (TESE), in combination with intracytoplasmic sperm injection,

microdissection TESE (MD-TESE), which is less invasive and results in high sperm retrieval rate, is preferred. Even in patients with Klinefelter syndrome (KS), who usually present small testis and hypogonadism, MD-TESE has been successfully performed. Although recent studies reported that MD-TESE procedures might impair testosterone production, little studies compared postoperative serum hormone levels between 46XYmales with NOA and KS have been reported. In this study, we assayed serum hormone levels after MD-TESE and compared postoperative testicular damage between 46XY males with NOA and KS.

METHODS: The records were retrospectively evaluated for

KS) who were underwent MD-TESE from January 2001 to November 2006 in Kobe University Hospital. Karyotyping test was performed on a sample of blood to all patients. Serum follicle-stimulating hormone

were evaluated before and at 6 and 12 months after surgery. For rate-of-change analysis, these hormone levels at 6 and 12 months after MD-TESE in each patient were expressed as arbitrary units relative to baseline concentration, set as a value of “1.”

RESULTS: In 46XY males with NOA, serum levels of FSH at

increased from baseline concentrations (p = .001, .01, and .003,

of LH at 12 months and T at 6 and 12 months compared to baseline

concentrations at all time after surgery (0.79-fold at 6 months, p = .007, and 0.77-fold at 12 months, p = .003). FSH and LH concentrations in

rate of change of T concentrations (p = .02 at 6 months and .03 at 12 months, respectively).

CONCLUSIONS: Long term hormonal follow up is recommended after MD-TESE, particularly in patients with KS. We recommend that patients in KS with low T level after MD- TESE may be treated properly to prevent the long-term deleterious consequences of hypogonadism.

Source of Funding: None

1735SIGNIFICANT INCIDENCE OF HYPOANDROGENISM IN INFERTILE MENBeneranda S Ford*, Lawrence S Ross, Craig S Niederberger. Chicago, IL.

INTRODUCTION AND OBJECTIVE: In 1997, Sigman and Jarow observed that the incidence of endocrinopathy in men with > 10 million sperm/ml was low enough to recommend an endocrine study unnecessary if this threshold was met. In the present era, increasing men

sperm may be extracted for ICSI. We sought to determine the incidence

< 300 ng/dl in a modern infertile male population undergoing evaluation, and verify the results in a subset analysis as calculated by bioavailable testosterone by the free testosterone index (FTI).

METHODS: Patient records for men presenting with infertility

ml (oligospermia) and sperm density > 20 million/ml (normospermia). Incidence of total T < 300 ng/dl was determined in each group and

calculated using the FTI with total testosterone, albumin and sex hormone binding globulin (SHBG).

incidence of hypoandrogenism by FDA criteria in men with OA was similar to the general population at 16.7%. 45.0% of men with NOA had total T < 300 ng/dl. Interestingly, 42.9% men with oligospermia and 35.3% of men with sperm density > 20 million/ml but presenting with infertility had total T < 300 ng/dl. Comparing incidence of hypoandrogenism in the infertile non-obstructive groups to that of OA, the difference was

of 16 men were available with total T, SHBG and albumin to calculate bioavailable T by the FTI. 83.3% of men with NOA had bioavailable T < 200 ng/dl.

CONCLUSIONS: The incidence of hypoandrogenism by FDAcriteria for men with NOA is high at 45.0%. Subset analysis calculating

incidence of hypoandrogenism in men with OA (with an incidence expected to be similar to the general population) to men with NOA,oligospermia and sperm density > 20 million/ml but presenting with

1990s, but the widespread use of the FDA criteria for hypoandrogenism and an increasing presentation of men with NOA may account for the

term follow-up.Source of Funding: None

1736THE GR/GR POLYMORPHISM IS CLINICALLY IRRELEVANTPeter J Stahl*, Anna Mielnik, Michael B Marean, Peter N Schlegel, Darius A Paduch. New York, NY.

INTRODUCTION AND OBJECTIVE: Y chromosome microdeletion (YCM) screening provides prognostic information that guides the management of infertile men. Patients with classic YCMsare at risk for spermatogenic failure and have predictably altered outcomes of microsurgical testicular sperm extraction (microTESE). With more widespread genetic diagnostics, increasing numbers of

clinical sequelae of the gr/gr deletion are unclear. Studies have been limited by small ethnically homogenous patient populations and have

men, the largest to date. METHODS: We screened 1997 men for YCMs from 1997-2007

by PCR of sequence tagged sites (STS). Prior to 2004 patients were not initially screened for the gr/gr polymorphism. In all possible cases, these patients were re-screened using our DNA repository. 258 patients without available semen analyses and 329 patients without banked

testicular ultrasounds, and microTESE outcomes were retrospectively

the sy1291 STS. We have previously published our detailed screening methods.

Frequency of the gr/gr polymorphism in the screened populationSperm Concentration(million per mL)

NumberScreened

Number of gr/gr Deletions Detected gr/gr Frequency

989 43 4.3%<1 197 6 3.0%1 - <5 120 12 10.0%5 - <20 61 6 9.8%20+ 43 6 14%Total 1410 73 5.2%

Page 2: THE GR/GR POLYMORPHISM IS CLINICALLY IRRELEVANT

Vol. 179, No. 4, Supplement, Wednesday, May 21, 2008 THE JOURNAL OF UROLOGY® 595

infertile men (5.2%) (Table). Presence of the polymorphism was negatively correlated (Fisher exact test) with the risks of oligospermia (< 20 million sperm/mL, p=.006) and severe oligospermia (< 5 million

in bitesticular volume, serum testosterone, FSH, or LH levels in gr/gr deleted patients compared to infertile men without YCMs. Sperm retrieval was successful in 14 of 22 gr/gr deleted patients who underwent microTESE (63.6%). This did not differ from the 53.2% retrieval rate for nondeleted men (Fisher exact test, p=.230).

CONCLUSIONS: The gr/gr polymorphism is not associated with spermatogenic failure and has no bearing on microTESE outcome. Affected patients are phenotypically indistinguishable from infertile men with intact Y chromosomes. Routine screening for the gr/gr polymorphism is unnecessary in the clinical setting.

Source of Funding: Generous support provided by Mr. Paul Ostling.

1737POSTVASECTOMY SA: RISK FACTORS FOR NONCOMPLIANCE

Stony Brook, NY.INTRODUCTION AND OBJECTIVE: Vasectomy is a popular

method of permanent contraception. Since failure of vasectomy may result in unwanted pregnancy and litigations, postvasectomy semen analysis( PVSA) is critical to establish the success of the procedure. While number and timing of PVSA are still debated, up to 90% of

and practical reasons for such noncompliance have been evaluated from patient’s perspective using questionnaire studies. The goal of our study was to investigate patients demographic characteristics as possible objective preoperative risk factors associated with higher noncompliance rate.

METHODS: Retrospective random chart review of 214 patients who have undergone vasectomy by one surgeon was performed. All men had similar detailed preoperative consultation with written instruction to provide two PVSA two and four months after vasectomy. Noncompliance

data including age, marital status, number of children, level of education

and 95% CI were also calculated to describe the odds of compliance for each demographic parameter

RESULTS: Of 214 patients 99 (46.2%) provided no PVSA.Rate of noncompliance was higher in men younger than 35 years, with four or more children, smokers, and those with lower educational level. Marital status had no impact on postoperative compliance ( Table1)

CONCLUSIONS: While real reasons for low PVSA compliance remain unclear, objective risk factors including age, number of children, level of education and smoking history may help to anticipate postoperative noncompliance. A more thorough approach to vasectomy counseling and timely reminder of upcoming SA in these patients may help to improve compliance and prevent possible medical and legal repercussions.

Table1Number of Patients

Noncompliant(no PVSA) Compliant p

valueOdd ratio ( CI-95%)

Total 214 99 (46.2%) 115(53.8%)

SmokersNonsmokers

42 (19.6%)172 (80.4%)

29(69.0%)70 (40.1%)

13 (30.1%)102(59.3%)

0.001 3.251 ( 1.593-6.622)

SingleMarried

14 (6.50%)200 (93.5%)

6 (42.9%)93 (46.5%)

8 (57.1%)107(53.5%)

1 0.863 ( 0.301-2.475

No college educationCollege education

98 (45.8%)116 (54.2%)

57 (58.2%)42 (36.2%)

41 (41.8%)74 (63.8%) 0.002 2.449 (1.413-

4.246)Four or more children Three or less children

31 (14.5%)183 (85.5%)

21 (67.7%)78(42.6%)

10(32.3%)105(57.4%)

0.011 2.827(1.277-6.224)

Younger than 33Age 33 and older

27 (12.6%)187 (87.4%)

19 (70.3%)80 (42.8%)

8 (47.0%)107(57.2%)

0.012 3.177(1.348-7.464

Source of Funding: None

1738ANALYSIS OF 2,967 SEMEN RETRIEVAL TRIALS IN 481 MEN WITH SPINAL CORD INJURY (SCI)Emad Ibrahim*, Nancy L Brackett, Teodoro C Aballa, Charles M Lynne. Miami, FL.

INTRODUCTION AND OBJECTIVE: Men with SCI comprise the largest group of patients with neurogenic anejaculation. The purpose of this study was to review ejaculation success rates and semen quality in a large cohort of men with SCI.

METHODS: Data were collected for a period of 16 years (1991 - 2007). Outcomes of 2,967 semen retrieval trials were reviewed from 481 men with SCI who were participants in the Male Fertility ResearchProgram of the Miami Project to Cure Paralysis.

RESULTS: Subjects’ level of injury was: cervical (n=193), T1-T6 (119), T7-T12 (146), L1 and lower (19), unknown (4). Of the 481 men, 42 (9%) could ejaculate by masturbation and did not have penile vibratory stimulation (PVS) or electroejaculation (EEJ) procedures. PVS was attempted 1,929 times on the remaining 439 men with SCI (average

injury T10 or higher responded to PVS, versus only 15% of men whose level of injury was T11 or lower. EEJ was performed 911 times on a total of 200 men with SCI (average 4.6 procedures per patient). EEJ was performed mostly in cases of PVS failure. Of the 200 men, 189 (95%) could ejaculate with EEJ. Of the 5% who did not ejaculate with EEJ, most were men with retained pelvic sensation who experienced pain at low

further trials under sedation or general anesthesia. Of the PVS and EEJtrials that resulted in ejaculation, sperm were present in the ejaculate on 91% of trials. A total of 3,694 semen analyses were performed, including antegrade and retrograde fractions. Figure 1 shows the total motile sperm (TMS) obtained by all methods (open bars), including PVS, EEJ, antegrade and retrograde fractions, and the TMS obtained by the more simple semen retrieval method of antegrade fractions produced by PVS only (closed bars).

CONCLUSIONS: In this review of one of the largest databases of its kind, we conclude that semen can be easily obtained from the majority of men with SCI. Most of these men have reasonable yields of total motile sperm in their ejaculates. It is recommended that centers continue to examine the ejaculate, rather than proceeding directly to surgical sperm retrieval, as a source of sperm for assisted conception in couples with SCI male partners.

Source of Funding:Appropriations and the Miami Project to Cure Paralysis.