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PREDICTORS OF FERTILITY IN PATIENTS TREATED FOR GERM-CELL TESTICULAR CANCER
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THE JOURNAL OF UROLOGY®
2171 REDEFINING ABNORMAL FSH IN THE MALE INFERTILITY POPULATION Jennifer B Gordetsky*, Edwin van Wijngaarden, Jeanne O’Brien, Rochester, NY INTRODUCTION AND OBJECTIVE: FSH is important in the regulation of sertoli cell function and ultimately spermatogenesis. The normal range for FSH in the post-pubescent male is commonly defined as 1.4-18.1 mIU/ml, which is uninformative in determining the etiology of male factor infertility since nearly all patients would be considered to have “normal” FSH levels. We examined the correlation of FSH and testosterone/FSH level with semen analysis parameters to evaluate whether the range for judging normal FSH levels should be reconsidered. METHODS: A retrospective chart review was performed on 610 male infertility patients from a single urologist’s practice from 20042008. Patients (n=153) excluded had used steroids or failed to complete blood work or semen analysis testing. Abnormal semen analysis values were based on the WHO 1999 criteria. We performed t-tests, analysis of variance, chi-square tests and logistic regression, to statistically examine the association between FSH (or testosterone/FSH ratio) level and semen parameters. RESULTS: FSH level showed statistically significant associations (p<0.0001), with evidence of a dose response, with abnormal motility, sperm concentration, and morphology but not with semen volume (p=0.9). In men with FSH levels greater than 7.5, the risk of abnormal semen quality was 5-13 times that of men with FSH levels < 2.8 depending on the specific semen parameter. Similarly, semen parameters were more likely to be abnormal with decreasing testosterone/FSH ratios. CONCLUSIONS: A significantly increased risk of abnormal semen analyses among men with FSH > 4.5 and decreasing testosterone/ FSH ratios suggests that redefining normal FSH in infertile men would be valuable. Source of Funding: None
2172 INTRA-OPERATIVE DOPPLER PHASE SHIFT TO LOCALIZE THE PRESENCE OF SPERM DURING TESTIS BIOPSY IN AZOOSPERMIC MEN Sijo J Parekattil*, Marc S. Cohen, Johannes W Vieweg, Gainesville, FL INTRODUCTION AND OBJECTIVE: Testis biopsy is a diagnostic procedure performed in men with possible non-obstructive azoospermia (NOA). Recent studies have illustrated that it is likely to find active spermatogenesis in areas with good blood supply within the testicle. These studies utilized detailed color Doppler ultrasonography and needle guidance techniques to localize possible areas of spermatogenesis within the testicle. Our goal was to assess the efficacy of percutaneous hand-held Doppler phase shift measurements of the testicle at the time of biopsy to localize areas of spermatogenesis. METHODS: Prospective blinded control trial of 5 patients who underwent testis biopsy for NOA from Sept’08 to Nov’08. Percutaneous hand-held Doppler (Vascular Technology Inc, Nashua, NH) blood flow shift measurements were taken from 12 different marked regions of one testicle (one testicle scanned on each patient - the testicle that was larger was chosen). The surgeon then obtained 12 biopsies from the same testicle in these marked regions (blinded to the Doppler analysis). The findings from the biopsies were then compared to the pre-biopsy Doppler phase shift mapping to assess if the Doppler readings had any predictive value in detecting spermatogenesis. RESULTS: The Doppler phase shift readings were analyzed and an algorithm developed to identify areas of the testicle with specific flow patterns. These flow patterns were then analyzed to assess for any correlation with spermatogenesis. A predictive model optimized to identify areas of sperm production was then created. The model was 92% accurate (ROC 0.9) in identifying areas within the testicle that had sperm based of Doppler phase shift readings.
Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009
CONCLUSIONS: Our preliminary evaluation of hand-held Doppler phase shift flow mapping of the testicle at the time of biopsy appears to have promise in detecting areas of spermatogenesis. Further evaluation and testing will reveal its potential in this role.
Source of Funding: None
2173 PREDICTORS OF FERTILITY IN PATIENTS TREATED FOR GERMCELL TESTICULAR CANCER Andrea Salonia*, Matteo Ferrari, Lorenzo Rocchini, Andrea Gallina, Rayan Matloob, Antonino Saccà, Giuseppe Zanni, Renzo Colombo, Nazareno Suardi, Luigi F Da Pozzo, Patrizio Rigatti, Francesco Montorsi, Milan, Italy INTRODUCTION AND OBJECTIVE: To assess rate and predictors of fertility in patients treated for germ-cell testicular cancer. METHODS: A cohort of 345 consecutive patients who underwent unilateral or bilateral orchiectomy for germ-cell testicular cancer at a single Institution was used. Patients were comprehensively assessed with a detailed medical history and a semi-structured interview regarding fertility after any oncologic treatment. Fertility was defined as at least one live birth after orchiectomy. Patients’ comorbidities were scored with the age-corrected Charlson Comorbidity Index (CCI) according to the ICD9-CM codes. Logistic regression models tested the association between various clinical predictors [including age at surgery, educational status, CCI, previous fatherhood, adjuvant chemotherapy, adjuvant radiotherapy, and retroperitoneal lymph node dissection (RPLND)] and fertility. RESULTS: At a median (mean) 73 (85.5) mo follow-up (range: 1-312) complete data collection was available for 270 (78.3%) patients. Fertility rate was 15.9% (43/270). Fertile men were younger at surgery (31.3±4.2 yr vs. 36.0±12.1 yr; P=0.013), and had a lower CCI (0.5±1.02 vs. 0.02±0.15; P=0.002). Conversely, no differences were recorded according to educational status and any adjuvant treatment (all P>0.1). At univariate analysis, age at surgery was the only significant predictor of subsequent fertility (O.R.=0.96; P=0.013). At multivariate analysis, age confirmed its reverse association with fertility (O.R.=0.93; P=0.005), after adjusting for all other predictors. Previous fatherhood (O.R.=2.40; P=0.061) and adjuvant chemotherapy (O.R.=0.46; P=0.059) reached a borderline significant association with fertility. Conversely, all other predictors did no reach an independent predictor status. CONCLUSIONS: These data show that age at surgery is an independent predictor of subsequent fertility in patients with testicular germ cell cancer undergoing orchiectomy. At the mean 7-yr follow up, adjuvant treatments did not have a significant negative impact toward fertility. Source of Funding: None
2174 LEYDIG CELL FAILURE FREQUENTLY ASSOCIATED WITH SPERMATOGENIC FAILURE John W Weedin*, Jon A Rumohr, Richard C Bennett, Mohit Khera, Larry I Lipshultz, Houston, TX INTRODUCTION AND OBJECTIVE: The prevalence and role of hypogonadism in patients with nonobstructive azoospermia (NOA) is uncertain. We hypothesized that hypogonadism is highly prevalent in men with NOA and that men with lower levels of testosterone have less
THE JOURNAL OF UROLOGY®
2171 REDEFINING ABNORMAL FSH IN THE MALE INFERTILITY POPULATION Jennifer B Gordetsky*, Edwin van Wijngaarden, Jeanne O’Brien, Rochester, NY INTRODUCTION AND OBJECTIVE: FSH is important in the regulation of sertoli cell function and ultimately spermatogenesis. The normal range for FSH in the post-pubescent male is commonly defined as 1.4-18.1 mIU/ml, which is uninformative in determining the etiology of male factor infertility since nearly all patients would be considered to have “normal” FSH levels. We examined the correlation of FSH and testosterone/FSH level with semen analysis parameters to evaluate whether the range for judging normal FSH levels should be reconsidered. METHODS: A retrospective chart review was performed on 610 male infertility patients from a single urologist’s practice from 20042008. Patients (n=153) excluded had used steroids or failed to complete blood work or semen analysis testing. Abnormal semen analysis values were based on the WHO 1999 criteria. We performed t-tests, analysis of variance, chi-square tests and logistic regression, to statistically examine the association between FSH (or testosterone/FSH ratio) level and semen parameters. RESULTS: FSH level showed statistically significant associations (p<0.0001), with evidence of a dose response, with abnormal motility, sperm concentration, and morphology but not with semen volume (p=0.9). In men with FSH levels greater than 7.5, the risk of abnormal semen quality was 5-13 times that of men with FSH levels < 2.8 depending on the specific semen parameter. Similarly, semen parameters were more likely to be abnormal with decreasing testosterone/FSH ratios. CONCLUSIONS: A significantly increased risk of abnormal semen analyses among men with FSH > 4.5 and decreasing testosterone/ FSH ratios suggests that redefining normal FSH in infertile men would be valuable. Source of Funding: None
2172 INTRA-OPERATIVE DOPPLER PHASE SHIFT TO LOCALIZE THE PRESENCE OF SPERM DURING TESTIS BIOPSY IN AZOOSPERMIC MEN Sijo J Parekattil*, Marc S. Cohen, Johannes W Vieweg, Gainesville, FL INTRODUCTION AND OBJECTIVE: Testis biopsy is a diagnostic procedure performed in men with possible non-obstructive azoospermia (NOA). Recent studies have illustrated that it is likely to find active spermatogenesis in areas with good blood supply within the testicle. These studies utilized detailed color Doppler ultrasonography and needle guidance techniques to localize possible areas of spermatogenesis within the testicle. Our goal was to assess the efficacy of percutaneous hand-held Doppler phase shift measurements of the testicle at the time of biopsy to localize areas of spermatogenesis. METHODS: Prospective blinded control trial of 5 patients who underwent testis biopsy for NOA from Sept’08 to Nov’08. Percutaneous hand-held Doppler (Vascular Technology Inc, Nashua, NH) blood flow shift measurements were taken from 12 different marked regions of one testicle (one testicle scanned on each patient - the testicle that was larger was chosen). The surgeon then obtained 12 biopsies from the same testicle in these marked regions (blinded to the Doppler analysis). The findings from the biopsies were then compared to the pre-biopsy Doppler phase shift mapping to assess if the Doppler readings had any predictive value in detecting spermatogenesis. RESULTS: The Doppler phase shift readings were analyzed and an algorithm developed to identify areas of the testicle with specific flow patterns. These flow patterns were then analyzed to assess for any correlation with spermatogenesis. A predictive model optimized to identify areas of sperm production was then created. The model was 92% accurate (ROC 0.9) in identifying areas within the testicle that had sperm based of Doppler phase shift readings.
Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009
CONCLUSIONS: Our preliminary evaluation of hand-held Doppler phase shift flow mapping of the testicle at the time of biopsy appears to have promise in detecting areas of spermatogenesis. Further evaluation and testing will reveal its potential in this role.
Source of Funding: None
2173 PREDICTORS OF FERTILITY IN PATIENTS TREATED FOR GERMCELL TESTICULAR CANCER Andrea Salonia*, Matteo Ferrari, Lorenzo Rocchini, Andrea Gallina, Rayan Matloob, Antonino Saccà, Giuseppe Zanni, Renzo Colombo, Nazareno Suardi, Luigi F Da Pozzo, Patrizio Rigatti, Francesco Montorsi, Milan, Italy INTRODUCTION AND OBJECTIVE: To assess rate and predictors of fertility in patients treated for germ-cell testicular cancer. METHODS: A cohort of 345 consecutive patients who underwent unilateral or bilateral orchiectomy for germ-cell testicular cancer at a single Institution was used. Patients were comprehensively assessed with a detailed medical history and a semi-structured interview regarding fertility after any oncologic treatment. Fertility was defined as at least one live birth after orchiectomy. Patients’ comorbidities were scored with the age-corrected Charlson Comorbidity Index (CCI) according to the ICD9-CM codes. Logistic regression models tested the association between various clinical predictors [including age at surgery, educational status, CCI, previous fatherhood, adjuvant chemotherapy, adjuvant radiotherapy, and retroperitoneal lymph node dissection (RPLND)] and fertility. RESULTS: At a median (mean) 73 (85.5) mo follow-up (range: 1-312) complete data collection was available for 270 (78.3%) patients. Fertility rate was 15.9% (43/270). Fertile men were younger at surgery (31.3±4.2 yr vs. 36.0±12.1 yr; P=0.013), and had a lower CCI (0.5±1.02 vs. 0.02±0.15; P=0.002). Conversely, no differences were recorded according to educational status and any adjuvant treatment (all P>0.1). At univariate analysis, age at surgery was the only significant predictor of subsequent fertility (O.R.=0.96; P=0.013). At multivariate analysis, age confirmed its reverse association with fertility (O.R.=0.93; P=0.005), after adjusting for all other predictors. Previous fatherhood (O.R.=2.40; P=0.061) and adjuvant chemotherapy (O.R.=0.46; P=0.059) reached a borderline significant association with fertility. Conversely, all other predictors did no reach an independent predictor status. CONCLUSIONS: These data show that age at surgery is an independent predictor of subsequent fertility in patients with testicular germ cell cancer undergoing orchiectomy. At the mean 7-yr follow up, adjuvant treatments did not have a significant negative impact toward fertility. Source of Funding: None
2174 LEYDIG CELL FAILURE FREQUENTLY ASSOCIATED WITH SPERMATOGENIC FAILURE John W Weedin*, Jon A Rumohr, Richard C Bennett, Mohit Khera, Larry I Lipshultz, Houston, TX INTRODUCTION AND OBJECTIVE: The prevalence and role of hypogonadism in patients with nonobstructive azoospermia (NOA) is uncertain. We hypothesized that hypogonadism is highly prevalent in men with NOA and that men with lower levels of testosterone have less