2292 MEDICAL TESTOSTERONE CAUSES IATROGENIC MALE INFERTILITY - A GROWING PROBLEM

2292 MEDICAL TESTOSTERONE CAUSES IATROGENIC MALE INFERTILITY - A GROWING PROBLEM

Vol. 189, No. 4S, Supplement, Wednesday, May 8, 2013 16.7 expected (SIR 1.7, 95% CI 1.2-2.5). When stratifying by azoospermia status, only azoospermi...

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Vol. 189, No. 4S, Supplement, Wednesday, May 8, 2013

16.7 expected (SIR 1.7, 95% CI 1.2-2.5). When stratifying by azoospermia status, only azoospermic men had a significantly elevated risk of cancer (SIR 2.9, 95% CI 1.4-5.4). Infertile men without azoospermia had a trend toward a higher rate of cancer to the general Texas population (SIR 1.4, 95% CI 0.9-2.2). The Cox regression model revealed that azoospermic men had 2.2 fold higher risk compared to non azoospermic men (HR 2.2, 95% CI 1.0-4.8) after adjusting for age and year of evaluation. CONCLUSIONS: Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Source of Funding: None

2290 THE SEMEN ANALYSIS OUTCOMES OF TESTIS CANCER PATIENTS WITH AZOOSPERMIA PRIOR TO ORCHIECTOMY Patrick Teloken*, Darren Katz, Boback Berookhim, John Mulhall, New York, NY INTRODUCTION AND OBJECTIVES: Testis cancer (TC) patients are at increased risk of sub-fertility prior to any intervention. Evidence suggests that improvement in semen parameters may occur after orchiectomy (O). This analysis was undertaken to assess the effects of orchiectomy in the semen analysis of men with TC who were diagnosed with azoospermia (AZ). METHODS: A review of records of patients meeting the following criteria was conducted: (i) documented AZ prior to orchiectomy for the management of TC (ii) no prior paternity (iii) no TESE performed at time of O and (iv) semen analysis after O but prior to any further intervention. For patients with post-O AZ and with ⱕ1 million (M) sperm/ml, testis sperm extraction (TESE) was performed. Testis cancer histopathology, hormonal profile (total testosterone, TT; follicle stimulating hormone, FSH), semen and TESE data were recorded. Multivariable analysis was performed in an attempt to identify predictors of sperm return the ejaculate or retrieval on TESE after O. Factors included in the model were: patient age, serum T and FSH levels, testis volume, type of TC. RESULTS: Thirty-six patients were included. Mean age ⫽ 34⫾16 years. Mean volume of unaffected testis ⫽ 16⫾8 ml. Sixty-eight percent of men had a seminoma while the remainder had a nonseminomatous germ cell tumor (NSGCT). Mean post-O TT was 364⫾168 ng/dl and FSH 11⫾4 IU/ml. Twenty-wo (61%) patients remained AZ after O, but 14 (39%) had return of some sperm to their semen; 22% ⱕ1M/ml and 17% ⬎1M/ml (mean 4.2⫾3.6, range 1.6-8). Thirty men underwent TESE; 16/22 (73%) AZ patients had sperm found (mean vial number cryopreserved ⫽ 4); 8/8 (100%) men with near-AZ had sperm found (mean vial number 11). Mean FSH for these two TESE groups ⫽ 9 and 6 respectively (p⫽0.08). No predictors of sperm return or sperm retrieval on TESE were identified. CONCLUSIONS: More than one third of men with pre-O AZ had sperm return to their semen after O. Sperm concentration was sufficient to avoid TESE in almost 20% of men. Overall, more than 80% of patients with testicular cancer and azoospermia prior to any intervention had sperm available for banking prior to adjuvant treatment. Source of Funding: None

2291 TESTOSTERONE PRESCRIBING PATTERNS IN THE MALE INFERTILITY POPULATION Mary Samplaski*, Yasir Loai, Kirk Lo, Ethan Grober, Keith Jarvi, Toronto, Canada INTRODUCTION AND OBJECTIVES: Over the last decade there has been a gradual increase in testosterone (T) prescribing. We sought to analyze patterns of T prescribing in men presenting for infertility evaluation.

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METHODS: Men presenting for fertility evaluation from 20082012 on T were identified via a prospective database. Data were analyzed for prevalence, prescriber, formulation, dosage and indication. RESULTS: 4400 men were evaluated for male infertility, and 56 (1.3%) were on T at presentation. Prescribers included: Endocrinologists (10, 17.9%), General Practitioners (5, 8.9%), Urologists (3, 5.3%), and independently obtained (4, 7.1%). Formulations and dosages included: Gel (26, 46.4%): most commonly 5mg every other day (QOD), range: 5mg QOD to 10mg daily; Intramuscular injection (25, 44.6%), most commonly 200mg every 2 weeks, range: 50-300mg every 2 weeks; Oral (1, 1.8%), 80mg QOD; Pellet (1, 1.7%), dose unknown; and unknown formulation and dose (5, 8.9%). Indications for T included: symptoms of hypogonadism (27, 48.2%), symptoms ⫹ low serum T (21, 37.5%), low serum T (4, 7.1%), athletic purposes (3, 5.4%), and subfertility (1, 1.8%). Co-existing conditions included: Klinefelters syndrome (8, 14.3%), history of bilateral undescended testicles (7, 12.5%), Kallmans syndrome (5, 8.9%), Sertoli only syndrome (2, 3.6%), chemotherapy induced testicular failure (2, 3.6%), prolactinoma (2, 3.6%), anejaculation (1, 1.8%), and opioid induced testicular failure (1, 1.8%). CONCLUSIONS: At our infertility center, T was not commonly used by men presenting for infertility investigation. Most men on T were being treated for appropriate conditions, with appropriate routes and dosages. Endocrinologists and General Practitioners were the most common prescribers, and educational efforts to emphasize the negative impacts of T on spermatogenesis should be focused on these groups. There are a group of men that obtain their T independently, and a group that uses T for athletic purposes. While this was a small fraction of the men in our population of infertile men, as the use of T increases, this fraction will undoubtedly grow. Source of Funding: None

2292 MEDICAL TESTOSTERONE CAUSES IATROGENIC MALE INFERTILITY - A GROWING PROBLEM Matthew Lane Purcell*, Birmingham, AL; William Parker, Kansas City, KS; Tyler Poston, Birmingham, AL; Ajay K. Nangia, Kansas City, KS; Peter N. Kolettis, Birmingham, AL INTRODUCTION AND OBJECTIVES: An increasing number of men in their reproductive years are on supplemental testosterone (T) for low T levels, decreased energy, or low libido. It is well known that testosterone can decrease sperm count. We have observed many men coming in for infertility work up have been on supplemental T. The objective of the study was to determine the prevalence of testosterone usage in an infertility practice and to see the recovery of semen parameters with treatment. METHODS: A retrospective chart review was performed for all male infertility patients for two providers from separate institutions from 1/2005 to 3/2011 (N⫽1540). Strict inclusion criteria were supplemental T usage at the time of initial visit, stopping testosterone usage, and semen analysis both while on T and after stopping. Patients who were also started on a recovery treatment (clomiphene, human chorionic gonadotropin and/or follicle stimulating hormone) at the same time as stopping the testosterone were also included. Comparisons were made based on sperm concentration before stopping testosterone and after stopping testosterone. RESULTS: 110 of the 1540 patients (7.1%) we looked at were on supplemental T. 34 patients met the inclusion criteria. 17 of 34 (50%) were started on recovery treatment. Overall, a statistically significant increase in average sperm concentration from 1.8 million/ml to 34 million/ml (p⬍0.0001) was seen after T cessation. 6 of the 34 patients (17.6%) did not have any recovery after cessation. 5 of 6 of these patients were tried on recovery treatment. Semen values were collected at an average of 97.6 days after discontinuing T. There was a significant increase in sperm concentration when the groups were stratified between those started on a recovery treatment (p⫽0.0011)

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and those who were just taken off supplemental T (p⫽0.0003). 15 of the patients had a second semen analysis at an average of 237.1 days after stopping T. These concentrations maintained a significantly higher level than the samples on T (p⫽0.0023). CONCLUSIONS: Medical testosterone is an increasing problem, causing iatrogenic decrease in semen parameters in an infertility practice. These effects may seem to be transient, but a portion of men did not recover. Source of Funding: None

2293 IMPACT OF THE 2012 AUA VASECTOMY GUIDELINES ON POST-VASECTOMY OUTCOMES Niraj Badhiwala*, Robert Coward, Ryan Smith, Jason Kovac, Tung-Chin Hsieh, Matthew McIntyre, Lata Murthy, Dolores Lamb, Larry Lipshultz, Houston, TX INTRODUCTION AND OBJECTIVES: The 2012 AUA Vasectomy Guidelines have proposed the inclusion of rare, non-motile sperm (RNMS), in addition to azoospermia, as endpoints of post-vasectomy success. Our institution, and many others, have previously defined success as two sequential centrifuged semen pellets demonstrating azoospermia. Inclusion of RNMS, defined as the presence of ⱕ 100,000 non-motile sperm/mL, has the potential to reduce the number of repeat semen analyses and diminish the time to determination of a successful vasectomy. Using post-vasectomy semen analysis (PVSA) data, we examined our previous outcomes within the context of the new 2012 AUA Vasectomy Guidelines. METHODS: All men undergoing vasectomy (n⫽1415) with subsequent PVSA between November 1999 and June 2012 were retrospectively reviewed. The majority (n⫽1009, 71%) had vasectomies performed by a single surgeon. Demographics and PVSA were obtained from an IRB-approved institutional database. Total number of PVSA, success rate, need for repeat vasectomy, and compliance with scheduled follow-up were reviewed and re-analyzed using the 2012 AUA Vasectomy Guidelines. RESULTS: A total of 2468 PVSAs were obtained in 1415 patients with a mean age of 39.3 ⫾ 6.8 years. Vasectomy success, defined as azoospermia after two sequential pellet analyses, was identified in 388 patients (27.4%). Of the remaining patients, 793 (56.0%) had only one PVSA and were then lost to follow-up, while 622 patients (44.0%) underwent 2 or more PVSA due to lack of pelleted azoospermia. Of those, 556 (70.1%) ultimately had azoospermia, 192 (24.2%) had RNMS, 12 (1.5%) had ⬎ 100,000/mL non-motile sperm, and 33 (4.1%) had motile sperm. Four patients underwent repeat vasectomy for persistent RNMS. Upon re-analysis using the 2012 AUA Vasectomy Guidelines, success rates would have been 96.4% (n⫽1364; p ⬍ 0.05). Since all four repeat vasectomies were done for the continued presence of RNMS, they would have been deemed unnecessary using the new guidelines. Moreover, 994 PVSAs would have been avoided using the 2012 AUA Vasectomy Guidelines. Compliance would have improved to 96.4% from the 56.0% that did not return for their second PVSA. CONCLUSIONS: The 2012 AUA Vasectomy Guidelines provide clear, evidence-based criteria for vasectomy success. The Guidelines simplify follow-up protocols, improve patient compliance, and help avoid unnecessary PVSAs and repeat vasectomies. Source of Funding: None

2294 CLINICAL CHARACTERIZATION AND REPRODUCTIVE OUTCOMES IN MEN WITH COMPLETE AZFC DELETIONS: A 17-YEAR EXPERIENCE Akanksha Mehta*, Ali Dabaja, Peggy King, Anna Mielnik, Darius Paduch, Peter Schlegel, New York, NY INTRODUCTION AND OBJECTIVES: Deletions of the AZFc region of the Y-chromosome are the most common genetic cause of

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spermatogenic failure. Unlike complete AZFa and AZFb deletions, paternity is possible in the setting of complete AZFc deletions. This study investigated the clinical characteristics, surgical sperm retrieval rates, and pregnancy outcomes in a large cohort of patients with complete AZFc deletions screened at a specialized academic center. METHODS: Medical records of consecutive male infertility patients undergoing Y-chromosome microdeletion (YCMD) testing between 1995 and 2012 were reviewed. Only patients with a complete AZFc deletion were included. All available data on serum hormone levels, sperm concentration, karyotype analysis, testicular size and histology, sperm retrieval rates (SRR), and pregnancy outcomes was collected. Student’s t-test and Fisher’s exact test were used to compare baseline characteristics with respect to SRR and pregnancy outcomes. A p-value ⬍0.05 was considered statistically significant. RESULTS: Of 2780 men screened for YCMD, 118 patients with complete AZFc deletions were identified. Mean age was 34 yrs. Mean concentrations of serum testosterone, FSH, LH, and estradiol were 400 ng/mL, 15.9 mIU/mL, 6.6 mIU/mL, and 32.9 pg/mL, respectively. Bilateral testicular volumes averaged 12.4 mL. Of 100 men for whom semen analysis data was available, 59 were azoospermic, 33 had sperm ¨ 1 million/ml, and two had concentrations of 5 and 21 concentration ¡U million/ml, respectively. The majority (96%) had a normal 46,XY karyotype. The overall SRR, using microsurgical testicular sperm extraction (TESE) for azoospermic men, was 73% (41/56). Clinical pregnancy occurred in 59% (33/56) of treatment cycles. Four spontaneous miscarriages were reported. There was no difference maternal or paternal age, FSH levels, or testicular size between cycles where sperm were and were not retrieved. However, the chance of finding sperm with TESE was affected by the predominant histologic pattern on random testis biopsy (58 vs. 76 vs. 100% for Sertoli-only vs. maturation arrest vs. hypospermatogenesis, p⬍0.001). CONCLUSIONS: While the majority of patients with AZFc deletions have sperm concentrations ⬍1 million/mL, higher concentrations are possible in a small fraction of men. Surgical sperm retrieval using TESE is successful in 73% of patients with AZFc deletion, with pregnancy rates of approximately 50% at our center. As with other patients, focal areas of hypospermatogenesis on testicular histology may predict a higher chance of sperm retrieval in AZFc-deleted men. Source of Funding: None

2295 COMMON CLINICAL AND LABORATORY PARAMETERS IMPROVE ABILITY TO PREDICT POSITIVE GENETIC TESTING IN MEN WITH AZOOSPERMIA AND SEVERE OLIGOSPERMIA Kiranpreet Khurana*, Karen Baker, Tianming Gao, Edmund Sabanegh, Cleveland, OH INTRODUCTION AND OBJECTIVES: Chromosome and Y microdeletion testing is recommended for men presenting with nonobstructive azoospermia (NOA) and severe oligospermia, but the prevalence of a positive test is only 10-12%. The expense of genetic tests ($2,500 at our institution) is high, and not always covered by insurance. Given the expense of genetic testing and the rarity of abnormalities, we sought to develop a model that would better predict the chance of a positive genetic test in the infertile male. METHODS: Retrospective chart review was performed for men who sought consultation for infertility from 2007 to 2011 and underwent both Y microdeletion and karyotype testing. The semen parameters, total testicular volume by physical exam, testosterone, luteinizing hormone, follicular stimulating hormone, and the presence of a varicocele were extracted from the electronic medical record. Logistic regression was fitted to all relevant predictors. Model selection was based on concordance index (C-index), which was calculated by internal bootstrap sampling. Calibration of the model was assessed. RESULTS: Of 325 patients, 211 completed all ordered tests. The median age of the population was 33 years old (range 20-55 years old), median testosterone was 328 ng/dL (range 45-875 ng/dL), median sperm concentration was zero (range 0-113 million/mL), and average