- Email: [email protected]
Fertility preservation: outcomes for Onco-TESE in male cancer patients prior to oncological therapy
MATERIALS AND METHODS: PESA was attempted in all cases and ICSI was performed with either fresh or frozen-thawed epididymal spermatozoa. TESE was performed in cases where no motile sperm were recovered from either the fresh or frozen-thawed PESA samples. Only fresh testicular sperm were used in ICSI cycles. We examined and compared the reproductive outcomes of three groups: (A) PESA-ICSI cycles (n ¼ 8) with ‘‘poor’’ quality sperm (%2% motility), (B) PESA-ICSI cycles (n ¼ 12) with ‘‘good’’ quality sperm (>2% motility) and (C) TESE-ICSI cycles (n ¼ 9). RESULTS: Spermatozoa were recovered in all 29 cycles. Male diagnosis (e.g. vasectomy, absent vas deferens), female age, day 3 serum FSH level, response to ovarian stimulation, fertilization rate and number of embryos transferred were not significantly different between the 3 groups. The ongoing pregnancy rates for groups A, B and C were 38%, 67% and 89%, respectively. The difference in ongoing clinical pregnancy rate between groups A (‘poor’ PESA) and C (TESE) was statistically significant (P<0.05). CONCLUSIONS: Our data indicate that PESA-ICSI outcomes may be influenced by epididymal sperm quality (motility). Taken together, the data suggest that in men with OA, TESE may be a better option than PESA when epididymal sperm motility is very poor. Supported by: None.
P-864 IS TESTICULAR SPERM EXTRACTION PERMITTED BY JEWISH LAW (HALACHAH)? G. R. Weitzman, H. J. Lieman. PUAH Institute, Jerusalem, Israel; Department of Obstetrics and Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: To investigate the different methods currently employed to extract sperm from the testicle in cases of obstructive or non-obstructive azospermia. To determine if any method would be acceptable by Jewish law and whether there is a preferred procedure. DESIGN: Three methods of sperm extraction will be reviewed and the relevant Jewish texts will be presented in an effort to arrive at an acceptable or even favored method according to the halachah. MATERIALS AND METHODS: The different methods of sperm extraction were investigated by reviewing the medical literature. The classic and more contemporary Jewish texts were reviewed. RESULTS: The three methods of sperm extraction evaluated were 1) testicular sperm extraction, TESE, 2) testicular fine-needle aspiration, TEFNA, and 3) microdissection TESE. It is clear much more tissue is removed during the standard TESE. Evidence suggests that TEFNA may cause atrophy. Microdissection TESE has been shown to produce better results than standard TESE. The Torah prohibits male castration and as per Talmudic explanation, even puncturing one of the testicles can be considered castration and all the described methods for sperm extraction would not be permissible. In modern times three halachic authorities permitted testicular biopsies despite this prohibition based on three separate assumptions. 1) The prohibition only applies when the puncturing is done in a destructive manner. If it is done in a controlled environment to correct the azospermia, it is permitted. 2) The prohibition refers to making a hole that does not heal. If the perforation heals completely, then it is permitted. 3) The prohibition of castration is only when it renders the man infertile but when it addresses his infertility it is permitted. According to the first two reasons the method that caused the least damage would be ideal. However, according to the last reason, the preferred method will be the one with the best success rates without regard to the amount of damage caused to the testicle. CONCLUSIONS: The medical literature suggests different methods for sperm extraction may yield better results than others or limit damage to the testicle. However, many halachic authorities do indeed allow testicular sperm extraction. The different reasoning employed to allow the procedure determines which method is favored. Supported by: The Puah Institute for Fertility and Gynecology in Accordance with the Halachah; JEWEL Program, Albert Einstein College of Medicine, Department of Obstetrics and Gynecology & Women’s Health.
to vasectomy, prostatectomy and herniorrhaphy. When diagnosed clinically, these relationships remain unclear. We investigated the clinical factors associated with clinically symptomatic vasitis in a series of affected men. DESIGN: We retrospectively reviewed the records of patients diagnosed with clinically symptomatic vasitis (scrotal pain and mass) in a single urologic practice from 2004–2007. No patient had undergone prior vasectomy. Vasitis was confirmed by palpable nodularity of the vas deferens on physical exam. MATERIALS AND METHODS: We analyzed the clinical characteristics of affected men in an attempt to identify associated characteristics, and reviewed clinical care patterns to assess the effectiveness of different treatments. RESULTS: Among 10 affected patients, the mean patient age at presentation was 44 years (range 29–60 years). All patients presented with groin and/ or scrotal pain and tenderness. The mean diameter of the vas deferens was 0.9 cm on examination. Seven men (70%) reported prior surgery near or on the vas deferens, including 4 patients with prior ipsilateral herniorrhaphy and 2 with radical prostatectomy. One patient had a prior perianal fistulectomy and another had epididymitis with congenital bilateral absence of the vas deferens. Three patients were HIV positive and 5 were active smokers. Seven of 9 patients with adequate follow-up improved with medical management that included nonsteroidal and steroidal anti-inflammatories and antibiotics. One patient was lost to follow-up. CONCLUSIONS: Similar to studies of pathologically detected vasitis, this study of clinical vasitis suggests that physical manipulation of the vas deferens, as with prior herniorrhaphy, prostatectomy and epididymitis as well as immunomodulating conditions such as HIV infection and smoking may be risk factors for its development. In addition, the use of anti-inflammatories and antibiotics warrants further investigation as potentially effective treatments for a disease that has previously and uniformly involved surgical excision. Supported by: None.
P-866 FERTILITY PRESERVATION: OUTCOMES FOR ONCO-TESE IN MALE CANCER PATIENTS PRIOR TO ONCOLOGICAL THERAPY. J. K. Modder, T. Kohler, R. E. Brannigan. Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL. OBJECTIVE: To describe outcomes of fertility preservation in our azoospermic/severe oligospermic male cancer patients prior to and during oncologic treatment. DESIGN: Retrospective chart review. Onco-TESE Outcomes Age No. at Dx 1
31
Marital Status/ Children Single/0
2
45
Married/0
3
30
Single/0
4
30
Single/0
P-865 CLINICALLY SYMPTOMATIC VASITIS CLINICAL CORRELATIONS IN A RARE CONDITION. J. Rose-Nussbaumer, J. L. Mehdizadeh, P. J. Turek. Department of Urology, University of California, San Francisco, San Francisco, CA. OBJECTIVE: Vasitis, or inflammation of the vas deferens, is a rare condition first described in 1943. When diagnosed pathologically, it has been linked
FERTILITY & STERILITYÒ
5
32
Single/0
6
40
Married/0
Pre-op SA Azoospermia
Tumor Markers Normal
Pathology
R seminoma, classic, GCIN (partial orchiectomy) L seminoma, classic, GCIN, invasion of rete testis Azoospermia Normal R seminoma, classic, GCIN, invasion of rete testis Azoospermia Normal R seminoma, classic, GCIN R seminoma, Severe Mild classic, Oligospermia LDH GCIN elevation L seminoma, classic, GCIN (partial orchiectomy) Severe Normal R seminoma, oligospermia classic Azoospermia Hodgkin’s lymphoma, bilateral fibrosclerotic parenchyma, no sem tubules
Stage
TESE Outcomes
T1N0M0 5 vials frozen
T1N0M0 4 vials frozen
T1N0M0 4 vials frozen
T1N0M0 5 vials frozen T1N0M0 7 vials frozen T1N0M0
T1N0M0 No sperm retrieved No sperm retrieved
Stage II
S393
MATERIALS AND METHODS: We reviewed the charts of patients referred to the male infertility clinic for sperm cryopreservation prior to cancer therapy from 2/2006 - 4/2007. Six patients were identified with azoospermia or severe oligospermia at the time of cancer diagnosis. Microdissection testicular sperm extraction was attempted in all six patients. RESULTS: The average age of the patients was 34.8 years (range 30–45). Five had testicular cancer, and one had Hodgkin’s lymphoma. Two had bilateral testicular tumors; one had a testicular tumor in a solitary testis. All testicular tumors were classic seminoma, stage T1N0M0, and all pre-operative tumor markers were normal. Sperm was retrieved in four out of five men with testicular cancer. The fifth (with severe oligospermia) cryopreserved one vial of sperm pre-operatively. No sperm was retrieved from the patient with lymphoma. CONCLUSIONS: Fertility preservation in male cancer patients with azoospermia or severe oligospermia at the time of cancer diagnosis can be augmented by testicular sperm extraction with cryopreservation prior to the initiation of oncological therapy. Supported by: None.
P-867 ASSOCIATION OF SPERM MORPHOLOGY ASSESSED BY SPERM DEFORMITY INDEX (SDI) WITH POLY (ADP-RIBOSE) POLYMERASE (PARP) CLEAVAGE INHIBITION. N. Aziz, R. Mahfouz, R. Jha, R. Sharma, M. Bykova, A. Agarwal. Reproductive Research Center, Glickman Urological Institute and Department of Obstetrics & Gynecology, Cleveland Clinic, Cleveland, OH; Department of Obs/Gyn, Liverpool Women’s Hospital, Liverpool, United Kingdom. OBJECTIVE: The sperm deformity index (SDI) is a novel expression of sperm morphology that has been shown to be a powerful predictor of the fertility potential of a semen sample both in vivo and in vitro. We have previously demonstrated a position correlation between the SDI and late markers of sperm apoptosis. Cleavage of Poly (ADP-Ribose) polymerase (cPARP) has been shown to be stimulated by any DNA damage and so it is considered to be an early apoptosis marker. The association of cPARP with sperm morphology as assessed by the SDI has not been studied before. The aim of our study was to evaluate the relationship between the SDI and cPARP. DESIGN: Prospective study. MATERIALS AND METHODS: Semen samples were collected from 10 donors and prepared by sperm density gradient separation. The resultant mature and immature sperm fractions were examined for sperm motility applying the WHO 1999 standards. Sperm morphology was assessed using the strict criteria of morphology. A multiple entry technique was utilized to calculate the SDI scores. Two aliquots of each of the mature and the immature fraction were used to induce sperm apoptosis by adding staurosporine 2.5 uM final concentration, with and without PARP inhibitor (3-aminobenzoate; 3ABA, final concentration 0.3 mM). Aliquots were examined for cPARP using flow cytometry. Paired Mann-Whittney test was utilized to compare different variables in different sperm fractions. Spearman’s rank correlation was used to examine relationships between variables. P<0.05 was considered significant. RESULTS: The mature sperm fractions had significantly lower mean SDI score and significantly higher mean percentage sperm with normal morphology compared to the immature fractions (normal morphology%: CI ¼ 5 to 10, P<0.0001; SDI: CI ¼ 0.39 to 0.14, P¼0.0006). When the data was considered collectively there was a significant positive interdependence between the SDI scores and cPARP positive sperm in the treated sperm with PARP inhibitor (r ¼ 0.5, P¼0.039). On the other hand, there was no correlation between percentage sperm with normal morphology and cPARP positive sperm in the treated sperm with PARP inhibitor (r ¼ 0.02, P¼0.9518). CONCLUSIONS: The sperm deformity index scores are associated with PARP cleavage as an early marker of apoptosis. PARP inhibition in sperm samples with high SDI score promotes induced apoptosis reflecting an inbuilt susceptibility to apoptotic stimuli. Supported by: None.
P-868 NATURAL HISTORY OF VARICOCELE MANAGEMENT IN THE ERA OF ASSISTED REPRODUCTIVE TECHNOLOGIES (ART): LESSONS FROM A CONTROLLED TRIAL OF MICROSURGICAL VARICOCELECTOMY FOR MALE FACTOR INFERTILITY. J. M. Boman, J. Libman, K. Jarvi, A. Zini. Urology, McGill University, Montreal, QC, Canada; Urology, Mount Sinai Hospital, Toronto, ON, Canada.
S394
Abstracts
OBJECTIVE: Varicocele represents the most common cause of male infertility and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. However, assisted reproductive technologies are a viable alternative to varicocelectomy in couples with infertility. We sought to evaluate and compare the clinical characteristics of infertile couples with varicocele who chose or not to undergo varicocelectomy. DESIGN: Retrospective review of 610 consecutive infertile couples in whom the man presented with a clinical varicocele. MATERIALS AND METHODS: At the time of presentation, all couples were presented with their clinical information and possible treatment options (observation, varicocelectomy, assisted reproductive technologies). The clinical characteristics of two subgroups of men (those who elected to undergo varicocelectomy [n ¼ 363] and those who did no [n ¼ 247]) were examined and compared. RESULTS: Sixty percent men opted for varicocele repair. The surgical and non-surgical groups had comparable ages, partner ages, and duration of infertility. However, both sperm concentration (19.8 24.6 106/ml vs. 27.6 33.9 106/ml; P¼0.001) and motility (25.5 17.1% vs. 32.8 21.2%; P<0.001) were significantly lower in the surgical group compared to the observation group. As well, the surgical group had a significantly higher prevalence of primary infertility (80% vs. 71%), and significantly smaller testicles bilaterally. ART utilization rates were significantly higher in the observation group compared to the surgical group (56% vs. 29%). Overall pregnancy rates (spontaneous þ assisted) were not statistically significant between the two groups, despite differences in baseline characteristics. CONCLUSIONS: This study on the natural history of infertile men with varicocele suggests that men with poorer baseline characteristics are more likely to opt for varicocele repair. Furthermore, couples electing to observe the varicocele are more likely to undergo ART procedures in order to conceive. Supported by: None.
P-869 PROPECIA MAY INDUCE SPERMATOGENIC FAILURE. K. E. Liu, S. Binsaleh, K. C. Lo, K. Jarvi. Dept of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Division of Urology, Dept of Surgery, Murray Koffler Urologic Wellness Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. OBJECTIVE: To describe two cases of azoospermia and severe oligospermia with significant improvements in sperm concentration after discontinuation of finasteride 1 mg. DESIGN: Case Report. MATERIALS AND METHODS: Charts from patients presenting to a tertiary care referral centre for male infertility were reviewed. RESULTS: Case 1- DH is a 34 yo with 3 years of primary infertility. Several semen analysis over a one-year period had shown azoospermia with occasional rare sperm seen. FSH was 3 IU/L, LH 3.3 IU/L and total testosterone 23 nmol/L. Examination confirmed normal testicular volume, and bilateral vas deferens present. His history was significant for 4 years use of finasteride 1mg for hair loss- he was advised to discontinue this medication. A preliminary diagnosis of obstructive azoospermia was made, and the patient was booked for a testicular biopsy. 3 months after stopping the medication, testing showed sperm concentration of 0.9 106/mL. Six months after discontinuing finasteride, the patient’s sperm concentration improved to 5.5 106/mL. The patient was adviced to proceed with other fertility treatments. Case 2- KS is a 32 yo male with severe oligospermia by semen analysis: volume 1.4 mL, concentration 4 106/mL, motility 14%, 5% normal forms. Examination showed normal testicular size. On history, he was taking finasteride 1mg for hair loss. After stopping finasteride, sperm concentration improved after three months (6.6 106/mL) and 6 months (18.7 106/mL). CONCLUSIONS: Finasteride is a 5-alpha reductase inhibitor used for benign prostatic hyperplasia. However, the 1mg dose is now marketed under the name ‘propecia’ and is used to treat hair loss. Although finasteride 5 mg has been shown to decrease semen volume and total sperm counts, the lower dose did not show any effect on semen parameters in a study on young, healthy men. We have reported two cases of infertile patients with azoospermia or severe oligospermia who showed significant improvements in sperm concentration 6 months after the discontinuation of finasteride. In one case the improvement in semen parameters prevented the need for testicular biopsy and corrected the azoospermia. Stopping finasteride in the infertility population may improve semen parameters and may allow for less invasive fertility treatments. Supported by: None.
Vol. 88, Suppl 1, September 2007
P-864 IS TESTICULAR SPERM EXTRACTION PERMITTED BY JEWISH LAW (HALACHAH)? G. R. Weitzman, H. J. Lieman. PUAH Institute, Jerusalem, Israel; Department of Obstetrics and Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: To investigate the different methods currently employed to extract sperm from the testicle in cases of obstructive or non-obstructive azospermia. To determine if any method would be acceptable by Jewish law and whether there is a preferred procedure. DESIGN: Three methods of sperm extraction will be reviewed and the relevant Jewish texts will be presented in an effort to arrive at an acceptable or even favored method according to the halachah. MATERIALS AND METHODS: The different methods of sperm extraction were investigated by reviewing the medical literature. The classic and more contemporary Jewish texts were reviewed. RESULTS: The three methods of sperm extraction evaluated were 1) testicular sperm extraction, TESE, 2) testicular fine-needle aspiration, TEFNA, and 3) microdissection TESE. It is clear much more tissue is removed during the standard TESE. Evidence suggests that TEFNA may cause atrophy. Microdissection TESE has been shown to produce better results than standard TESE. The Torah prohibits male castration and as per Talmudic explanation, even puncturing one of the testicles can be considered castration and all the described methods for sperm extraction would not be permissible. In modern times three halachic authorities permitted testicular biopsies despite this prohibition based on three separate assumptions. 1) The prohibition only applies when the puncturing is done in a destructive manner. If it is done in a controlled environment to correct the azospermia, it is permitted. 2) The prohibition refers to making a hole that does not heal. If the perforation heals completely, then it is permitted. 3) The prohibition of castration is only when it renders the man infertile but when it addresses his infertility it is permitted. According to the first two reasons the method that caused the least damage would be ideal. However, according to the last reason, the preferred method will be the one with the best success rates without regard to the amount of damage caused to the testicle. CONCLUSIONS: The medical literature suggests different methods for sperm extraction may yield better results than others or limit damage to the testicle. However, many halachic authorities do indeed allow testicular sperm extraction. The different reasoning employed to allow the procedure determines which method is favored. Supported by: The Puah Institute for Fertility and Gynecology in Accordance with the Halachah; JEWEL Program, Albert Einstein College of Medicine, Department of Obstetrics and Gynecology & Women’s Health.
to vasectomy, prostatectomy and herniorrhaphy. When diagnosed clinically, these relationships remain unclear. We investigated the clinical factors associated with clinically symptomatic vasitis in a series of affected men. DESIGN: We retrospectively reviewed the records of patients diagnosed with clinically symptomatic vasitis (scrotal pain and mass) in a single urologic practice from 2004–2007. No patient had undergone prior vasectomy. Vasitis was confirmed by palpable nodularity of the vas deferens on physical exam. MATERIALS AND METHODS: We analyzed the clinical characteristics of affected men in an attempt to identify associated characteristics, and reviewed clinical care patterns to assess the effectiveness of different treatments. RESULTS: Among 10 affected patients, the mean patient age at presentation was 44 years (range 29–60 years). All patients presented with groin and/ or scrotal pain and tenderness. The mean diameter of the vas deferens was 0.9 cm on examination. Seven men (70%) reported prior surgery near or on the vas deferens, including 4 patients with prior ipsilateral herniorrhaphy and 2 with radical prostatectomy. One patient had a prior perianal fistulectomy and another had epididymitis with congenital bilateral absence of the vas deferens. Three patients were HIV positive and 5 were active smokers. Seven of 9 patients with adequate follow-up improved with medical management that included nonsteroidal and steroidal anti-inflammatories and antibiotics. One patient was lost to follow-up. CONCLUSIONS: Similar to studies of pathologically detected vasitis, this study of clinical vasitis suggests that physical manipulation of the vas deferens, as with prior herniorrhaphy, prostatectomy and epididymitis as well as immunomodulating conditions such as HIV infection and smoking may be risk factors for its development. In addition, the use of anti-inflammatories and antibiotics warrants further investigation as potentially effective treatments for a disease that has previously and uniformly involved surgical excision. Supported by: None.
P-866 FERTILITY PRESERVATION: OUTCOMES FOR ONCO-TESE IN MALE CANCER PATIENTS PRIOR TO ONCOLOGICAL THERAPY. J. K. Modder, T. Kohler, R. E. Brannigan. Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL. OBJECTIVE: To describe outcomes of fertility preservation in our azoospermic/severe oligospermic male cancer patients prior to and during oncologic treatment. DESIGN: Retrospective chart review. Onco-TESE Outcomes Age No. at Dx 1
31
Marital Status/ Children Single/0
2
45
Married/0
3
30
Single/0
4
30
Single/0
P-865 CLINICALLY SYMPTOMATIC VASITIS CLINICAL CORRELATIONS IN A RARE CONDITION. J. Rose-Nussbaumer, J. L. Mehdizadeh, P. J. Turek. Department of Urology, University of California, San Francisco, San Francisco, CA. OBJECTIVE: Vasitis, or inflammation of the vas deferens, is a rare condition first described in 1943. When diagnosed pathologically, it has been linked
FERTILITY & STERILITYÒ
5
32
Single/0
6
40
Married/0
Pre-op SA Azoospermia
Tumor Markers Normal
Pathology
R seminoma, classic, GCIN (partial orchiectomy) L seminoma, classic, GCIN, invasion of rete testis Azoospermia Normal R seminoma, classic, GCIN, invasion of rete testis Azoospermia Normal R seminoma, classic, GCIN R seminoma, Severe Mild classic, Oligospermia LDH GCIN elevation L seminoma, classic, GCIN (partial orchiectomy) Severe Normal R seminoma, oligospermia classic Azoospermia Hodgkin’s lymphoma, bilateral fibrosclerotic parenchyma, no sem tubules
Stage
TESE Outcomes
T1N0M0 5 vials frozen
T1N0M0 4 vials frozen
T1N0M0 4 vials frozen
T1N0M0 5 vials frozen T1N0M0 7 vials frozen T1N0M0
T1N0M0 No sperm retrieved No sperm retrieved
Stage II
S393
MATERIALS AND METHODS: We reviewed the charts of patients referred to the male infertility clinic for sperm cryopreservation prior to cancer therapy from 2/2006 - 4/2007. Six patients were identified with azoospermia or severe oligospermia at the time of cancer diagnosis. Microdissection testicular sperm extraction was attempted in all six patients. RESULTS: The average age of the patients was 34.8 years (range 30–45). Five had testicular cancer, and one had Hodgkin’s lymphoma. Two had bilateral testicular tumors; one had a testicular tumor in a solitary testis. All testicular tumors were classic seminoma, stage T1N0M0, and all pre-operative tumor markers were normal. Sperm was retrieved in four out of five men with testicular cancer. The fifth (with severe oligospermia) cryopreserved one vial of sperm pre-operatively. No sperm was retrieved from the patient with lymphoma. CONCLUSIONS: Fertility preservation in male cancer patients with azoospermia or severe oligospermia at the time of cancer diagnosis can be augmented by testicular sperm extraction with cryopreservation prior to the initiation of oncological therapy. Supported by: None.
P-867 ASSOCIATION OF SPERM MORPHOLOGY ASSESSED BY SPERM DEFORMITY INDEX (SDI) WITH POLY (ADP-RIBOSE) POLYMERASE (PARP) CLEAVAGE INHIBITION. N. Aziz, R. Mahfouz, R. Jha, R. Sharma, M. Bykova, A. Agarwal. Reproductive Research Center, Glickman Urological Institute and Department of Obstetrics & Gynecology, Cleveland Clinic, Cleveland, OH; Department of Obs/Gyn, Liverpool Women’s Hospital, Liverpool, United Kingdom. OBJECTIVE: The sperm deformity index (SDI) is a novel expression of sperm morphology that has been shown to be a powerful predictor of the fertility potential of a semen sample both in vivo and in vitro. We have previously demonstrated a position correlation between the SDI and late markers of sperm apoptosis. Cleavage of Poly (ADP-Ribose) polymerase (cPARP) has been shown to be stimulated by any DNA damage and so it is considered to be an early apoptosis marker. The association of cPARP with sperm morphology as assessed by the SDI has not been studied before. The aim of our study was to evaluate the relationship between the SDI and cPARP. DESIGN: Prospective study. MATERIALS AND METHODS: Semen samples were collected from 10 donors and prepared by sperm density gradient separation. The resultant mature and immature sperm fractions were examined for sperm motility applying the WHO 1999 standards. Sperm morphology was assessed using the strict criteria of morphology. A multiple entry technique was utilized to calculate the SDI scores. Two aliquots of each of the mature and the immature fraction were used to induce sperm apoptosis by adding staurosporine 2.5 uM final concentration, with and without PARP inhibitor (3-aminobenzoate; 3ABA, final concentration 0.3 mM). Aliquots were examined for cPARP using flow cytometry. Paired Mann-Whittney test was utilized to compare different variables in different sperm fractions. Spearman’s rank correlation was used to examine relationships between variables. P<0.05 was considered significant. RESULTS: The mature sperm fractions had significantly lower mean SDI score and significantly higher mean percentage sperm with normal morphology compared to the immature fractions (normal morphology%: CI ¼ 5 to 10, P<0.0001; SDI: CI ¼ 0.39 to 0.14, P¼0.0006). When the data was considered collectively there was a significant positive interdependence between the SDI scores and cPARP positive sperm in the treated sperm with PARP inhibitor (r ¼ 0.5, P¼0.039). On the other hand, there was no correlation between percentage sperm with normal morphology and cPARP positive sperm in the treated sperm with PARP inhibitor (r ¼ 0.02, P¼0.9518). CONCLUSIONS: The sperm deformity index scores are associated with PARP cleavage as an early marker of apoptosis. PARP inhibition in sperm samples with high SDI score promotes induced apoptosis reflecting an inbuilt susceptibility to apoptotic stimuli. Supported by: None.
P-868 NATURAL HISTORY OF VARICOCELE MANAGEMENT IN THE ERA OF ASSISTED REPRODUCTIVE TECHNOLOGIES (ART): LESSONS FROM A CONTROLLED TRIAL OF MICROSURGICAL VARICOCELECTOMY FOR MALE FACTOR INFERTILITY. J. M. Boman, J. Libman, K. Jarvi, A. Zini. Urology, McGill University, Montreal, QC, Canada; Urology, Mount Sinai Hospital, Toronto, ON, Canada.
S394
Abstracts
OBJECTIVE: Varicocele represents the most common cause of male infertility and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. However, assisted reproductive technologies are a viable alternative to varicocelectomy in couples with infertility. We sought to evaluate and compare the clinical characteristics of infertile couples with varicocele who chose or not to undergo varicocelectomy. DESIGN: Retrospective review of 610 consecutive infertile couples in whom the man presented with a clinical varicocele. MATERIALS AND METHODS: At the time of presentation, all couples were presented with their clinical information and possible treatment options (observation, varicocelectomy, assisted reproductive technologies). The clinical characteristics of two subgroups of men (those who elected to undergo varicocelectomy [n ¼ 363] and those who did no [n ¼ 247]) were examined and compared. RESULTS: Sixty percent men opted for varicocele repair. The surgical and non-surgical groups had comparable ages, partner ages, and duration of infertility. However, both sperm concentration (19.8 24.6 106/ml vs. 27.6 33.9 106/ml; P¼0.001) and motility (25.5 17.1% vs. 32.8 21.2%; P<0.001) were significantly lower in the surgical group compared to the observation group. As well, the surgical group had a significantly higher prevalence of primary infertility (80% vs. 71%), and significantly smaller testicles bilaterally. ART utilization rates were significantly higher in the observation group compared to the surgical group (56% vs. 29%). Overall pregnancy rates (spontaneous þ assisted) were not statistically significant between the two groups, despite differences in baseline characteristics. CONCLUSIONS: This study on the natural history of infertile men with varicocele suggests that men with poorer baseline characteristics are more likely to opt for varicocele repair. Furthermore, couples electing to observe the varicocele are more likely to undergo ART procedures in order to conceive. Supported by: None.
P-869 PROPECIA MAY INDUCE SPERMATOGENIC FAILURE. K. E. Liu, S. Binsaleh, K. C. Lo, K. Jarvi. Dept of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Division of Urology, Dept of Surgery, Murray Koffler Urologic Wellness Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. OBJECTIVE: To describe two cases of azoospermia and severe oligospermia with significant improvements in sperm concentration after discontinuation of finasteride 1 mg. DESIGN: Case Report. MATERIALS AND METHODS: Charts from patients presenting to a tertiary care referral centre for male infertility were reviewed. RESULTS: Case 1- DH is a 34 yo with 3 years of primary infertility. Several semen analysis over a one-year period had shown azoospermia with occasional rare sperm seen. FSH was 3 IU/L, LH 3.3 IU/L and total testosterone 23 nmol/L. Examination confirmed normal testicular volume, and bilateral vas deferens present. His history was significant for 4 years use of finasteride 1mg for hair loss- he was advised to discontinue this medication. A preliminary diagnosis of obstructive azoospermia was made, and the patient was booked for a testicular biopsy. 3 months after stopping the medication, testing showed sperm concentration of 0.9 106/mL. Six months after discontinuing finasteride, the patient’s sperm concentration improved to 5.5 106/mL. The patient was adviced to proceed with other fertility treatments. Case 2- KS is a 32 yo male with severe oligospermia by semen analysis: volume 1.4 mL, concentration 4 106/mL, motility 14%, 5% normal forms. Examination showed normal testicular size. On history, he was taking finasteride 1mg for hair loss. After stopping finasteride, sperm concentration improved after three months (6.6 106/mL) and 6 months (18.7 106/mL). CONCLUSIONS: Finasteride is a 5-alpha reductase inhibitor used for benign prostatic hyperplasia. However, the 1mg dose is now marketed under the name ‘propecia’ and is used to treat hair loss. Although finasteride 5 mg has been shown to decrease semen volume and total sperm counts, the lower dose did not show any effect on semen parameters in a study on young, healthy men. We have reported two cases of infertile patients with azoospermia or severe oligospermia who showed significant improvements in sperm concentration 6 months after the discontinuation of finasteride. In one case the improvement in semen parameters prevented the need for testicular biopsy and corrected the azoospermia. Stopping finasteride in the infertility population may improve semen parameters and may allow for less invasive fertility treatments. Supported by: None.
Vol. 88, Suppl 1, September 2007