Cornell University

NEW YORK
CORNELL		Cornell University
Weill Medical College
Cornell Institute for Reproductive Medicine

Center for Male Reproductive Medicine and Microsurgery

"State-of-the-Art Compassionate Care for the Infertile Couple"

What's New at 2000 AUA Meeting (Infertility Topics)

2000 American Urologic Association Meeting
Atlanta, GA. May 2000

  1. Urology Times Report: Azoospermic men suitable for TESE-ICSI post-chemotherapy. (Cheryl Guttman, Urology Times Correspondent, reported this article. Urology Times, Vol.28, No.5. May 2000)

  2. Abstract: ICSI AS A TREATMENT FOR MEN WITH PERSISTENT AZOOSPERMIA POST-CHEMOTHERAPY

  3. Urology Times Report: Epididymostomy good for pre-epididymal obstruction. (Cheryl Guttman, Urology Times Correspondent, reported this article. Urology Times, Vol.28, No.5. May 2000)

  4. ABSTRACT: MICROSURGICAL RECONSTRUCTION OF PRE-EPIDIDYMAL OBSTRUCTIVE AZOOSPERMIA

1. Urology Times Report: Azoospermic men suitable for TESE-ICSI post-chemotherapy. (Cheryl Guttman, Urology Times Correspondent, reported this article. Urology Times, Vol.28, No.5. May 2000)

“The study results (20% of pregnancy rate) show that TESE is as effective in men with long-standing azoospermia after chemotherapy as it is in those with other non-obstructive etiologies.”

Atlanta---In the modem era of assisted reproduction techniques, men with long-standing azoospermia after chemotherapy should not be automatically given a diagnosis of sterility, say investigators from Weill Medical College of Cornell University, New York.

In the study's series of 12 patients with azoospermia post-chemotherapy, seven of 15 attempts at testicular sperm extraction (TESE) were successful, the group led by Peter Schlegel, MD, Marc Goldstein, MD and Peter T.K. Chan, MD, reported at the AUA annual meeting here. The research team, from the Cornell Institute for Reproductive Medicine and the department of urology, also reported that while using intracytoplasmic sperm injection (ICSI), biochemical pregnancy was achieved in three of the seven couples. Two went on to deliver three healthy children.

An additional patient, in whom no sperm were retrieved with an initial TESE attempt had sperm return to his ejaculate after varicocele repair, said Dr. Goldstein, professor of reproductive medicine and urology at the New York Hospital-Cornell Medical Center. Sperm from this patient's ejaculate were used for ICSI that resulted in successful initiation of pregnancy and culminated in a live birth.

The Cornell team previously reported on TESE results in sperm retrieval from men with non-obstructive azoospermia (Urology 1997; 49:435-40).

"However, it was not known what the success rate would be among post-chemotherapy patients because of their risk for treatment-induced destruction of all tes-ticular foci of sperm production:' said Dr. Goldstein.“ The results of the present study show that TESE is as effective in men with long-standing azoospermia after chemo-therapy as it is in patients with other non-ob-structive etiologies."

Dr Goldstein recommends that the repair of any existing varicocele should be first attempted in men who are azoospermic after chemotherapy.

"Two years earlier, we reported that about 50% of azoospermic men who under-go microsurgical varicocelectomy will experience return of sperm to the semen. That study did not specifically evaluate the success of this surgery in men with azoo-spermia secondary to chemotherapy," he said. "However, the experience with the individual in the current series indicates microsurgical varicocele repair can be ben-eficial in these men as well."

If varicocele repair surgery does not lead to the appearance of sperm in the semen, Dr. Goldstein said TESE can be performed.

TESE-ICSI for azoospermia

The 12 post-chemotherapy patients in this study represented a subset of 142 patients who underwent TESE-ICSI for azoosper-mia between 1995 and 1999. TESE was performed microscopically using the tech-nique pioneered by Dr. Schlegel, associate professor of urology and reproductive medicine, Weill Medical College of Cornell University.

Patients ranged in age from 29 to 54 years with a mean age of about 39 years. Ages of their female partners ranged from 28 to 43 years. The indications for chemo-therapy among the 12 men included Hodgkin's lymphoma (five patients), tes-ticular neoplasm (three), non-Hodgkin's lymphoma (two), leukemia (one), and nephrotic syndrome (one).

Time elapsed between chemotherapy and TESE ranged from 4 to 18 years. No relationships were identified between the prognosis for sperm retrieval and either chemotherapy regimen received or disease treated.

Histological examination of biopsy spec-imens yielded findings consistent with the expected effects of chemotherapy. A Sertoli cell-only pattern was present in 90% of men while a single patient had hyposper-matogenesis as the most advanced sper-matogenic pattern.

Dr. Goldstein noted that in a recent paper from the Cornell group correlating histo-logic findings with the chance of retriev-ing sperm through TESE, the extraction procedure was successful in 24% of men with a Sertoli cell-only pattern (J Urol 1999; 161:112-6).

"Based on that rate and the even greater success we observed in the present series of patients, it seems entirely reasonable to recommend performing TESE in these chemotherapy patients, even if the biopsy shows a Sertoli cell-only pattern:' noted Dr. Goldstein.

The study was presented at the AUA meeting by Dr. Chan, a fellow at the Cornell Institute for Reproductive Medicine and department of urology.
(Cheryl Guttman, Urology Times Correspondent, reported this article. Urology Times, Vol.28, No.5. May 2000)


2. Abstract:

ICSI AS A TREATMENT FOR MEN WITH PERSISTENT AZOOSPERMIA POST-CHEMOTHERAPY. Peter T K. Chan, Gianpiero D. Palermo, Lucinda L. Veeck, Deborah Liotta, Carol Ann Cook, Peggy King, Marc Goldstein, Zev Rosenwaks, Peter N. Schlegel.

Center for Male Reproductive Medicine and Microsurgery; Center for Reproductive Medicine and Infertility, Cornell Institute for Reproductive Medicine, and Department of Urology, The New York Presbyterian Hospital-Weill Medical College of Cornell University. New York, NY.

INTRODUCTION AND OBJECTIVES: Men who remain azoospermic long after chemotherapy are generally considered sterile. We hereby report our experience of testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection (ICSI) applied to azoospermic men who previously received chemotherapy for a variety of indications.

METHODS: Among 142 patients who underwent TESE-ICSI for azoospermia from 1995 to 1999, 15 TESE procedures in 12 patients who previously received chemotherapy were identified. All TESE was performed microscopically under local anesthesia with sedation or general anesthesia. The hormonal profile, histology of testicular biopsies, and the outcome of TESE-ICSI of this subgroup of patients were analyzed.

RESULTS: Patients mean age was 38.9 (29-54) yr and the mean FSH was 21.2 (7.1-43) mIU/ml. Female partners mean age was 36.2 (28-43) yr. Five patients had chemotherapy for Hodgkin lymphoma (42%), 3 for testicular neoplasm (25%),2 for non-Hodgkin lymphoma (17%), 1 for leukemia (8%) and I for nephrotic syndrome (8%). The interval from chemotherapy to TESE was 4-18 years. All patients had at least 2 semen analyses to confirm azoospermia. A total of 15 attempts of TESE-ICS1 were performed (mean 1.3 attempts per patient). Histology revealed Sertoli cell only pattern in 90% of cases. One patient (10%) had hypospermatogenesis as the most advanced spermatogenic pattern. Sperm retrieval was accomplished in 7/15 (47%) attempts, with biochemical pregnancy after sperm retrieval in 3n couples (43%). Live deliveries were achieved in 2/7 couples (29%). Two healthy boys and one girl were delivered. An additional patient who failed to have sperm retrieved with TESE had sperm return to his ejaculate after varicocele repair. He initiated a pregnancy and delivery with ICS1 alone. No correlation was noted between the outcome of TESE-ICSI and the underlying conditions treated with chemotherapy.

CONCLUSIONS: Using TESE-ICSI, sperm retrieval leading to pregnancy and delivery of healthy children is possible for men with long-standing azoospermia after chemotherapy. The prognosis for sperm retrieval was not clearly influenced by the chemotherapy regimen or disease treated. Despite their prolonged azoospermia after chemotherapy, these men should no longer be considered sterile in the era of TESE-ICSI.

Support: Brady Urology Foundation

This abstract ( #1520) was presented at American Urological Annual Meeting, Atlanta, GA. May 3, 2000
(J. of Urol. ,vol.163, No. 4, Supplement, Wednesday, May 3, 2000)


3. Urology Times Report: Epididymostomy good for pre-epididymal obstruction. (Cheryl Guttman, Urology Times Correspondent, reported this article, Urology Times, Vol.28, NO 5, May 2000)

Atlanta --- Microsurgical reconstruction of pre-epididymal obstructive azoospermia has a surprisingly high patency rate, according to results of a study presented by researchers from the Weill Medical College of Cornell University, New York. They presented their findings at the AUA annual meeting here.

In a retrospective review of 14 men who underwent only vasoefferent ductule anastomosis for obstructive azoospermia, 13 (93%) had return of sperm in semen analysis. Sperm counts were generally good, averaging 27 million/ml, (range: 0 to 77 million/ml). However, motility was low, with a mean of 17% and range of 0 to 40%.

In addition, appearance of sperm in the semen was delayed postoperatively, averaging 6.2 months until appearance (range: 2 to 16 months). Because of the generally low sperm motility of the group, only one patient was successful in achieving pregnancy through sexual intercourse. "In the past, repair of pre-epididymal obstruction was considered not worthwhile. First, it was believed that the tubules are too tiny to successfully repair. And, even if the operation was technically successful, it was considered to be of no value, since the sperm, with no opportunity for epididymal maturation, would not acquire the ability to swim:' said Marc Goldstein, MD, professor pf reproduc-tive medicine and urology, New York Hospital-Cornell Medical Center. "Based on these considerations, it was assumed that outcomes of these operations were very poor. But nobody had really looked at a series of such attempted reconstructions to actually define the results."

The 14 men included in the analysis had a mean age of 33 years and were identified from a series of 230 patients who underwent vasoepididymostomy for obstruc-tive azoospermia between 1983 and 1999-Diagnosis of pre-epididymal obstruction was based on the finding that sperm were absent in the cauda, corpus, or caput epididymis, but present in the efferent ducts. The etiology of the obstruction varied. It was considered idiopathic in eight men, while four men had a history of epididymo-orchitis and two cases were thought to be iatrogenic related to orchiopexy.

Before surgery, semen analysis was performed to confirm azoospermia, and testicular biopsies were taken to establish spermatogenesis. Vasoefferent duct anastomosis was performed bilaterally or unilaterally in men with a single functioning testis. A variety of surgical techniques were used in this series, including an end-to-end anastomosis in three men, an end-to-side anastomosis in two men, and an end-to-side intussusception technique in nine men.

End-to-side recommended

Dr. Goldstein noted that he recommends performing the repair with an end-to-side, two- or three-stitch intussusception technique as described by Richard Berger, MD, University of Washington, Seattle.

"Compared with other alternatives, that approach yields the highest patency rate and lowest rate of sperm leakage. In addition, it is technically easier to perform since suturing is done before opening the tubules, affording the advantage of placing the stitches in a distended tubule.” he explained.

To determine which of the efferent ducts to use for anastomosis, Dr. Goldstein identifies the one that is most enlarged. "All of the efferent ductules communicate with each other. So, conceptually, all of the sperm will travel through the one that is unblocked:' he said.

"From our findings, we would recommend performing anastomosis of the vas to the efferent duct in men with a pre-epididymal obstruction, because it is likely to result in return of sperm to the semen,” said Dr. Goldstein. "While these men have a low chance of achieving pregnancy naturally, they will at least become candidates for assisted reproductive techniques, includ-ing insemination or in vitro fertilization using the sperm from the semen."

The study was presented at the meeting by Peter T.K. Chan, MD, a fellow in the department of reproductive medicine and urology at New York-Cornell. (Cheryl Guttman, Urology Times Correspondent, reported this article, Urology Times, Vol.28, NO 5, May 2000)


4. Abstract:

MICROSURGICAL RECONSTRUCTION OF PRE-EPIDIDYMAL OBSTRUCTIVE AZOOSPERMIA.

Peter T K. Chan, Marc Goldstein

Center for Male Reproductive Medicine and Microsurgery, Cornell Institute for Reproductive Medicine, and Department of Urology, The New York Presbyterian Hospital-Weill Medical College of Cornell University. New York, NY.

INTRODUCTION AND OBJECTIVES: Obstructive azoospermia can be managed with microsurgical vasovasostomy or vasoepididymostomy for epididymal obstruction. Sometimes obstruction is very proximal, at the level of the efferent ducuiles. While sperm retrieval for IVF/ICSI is an established and successful treatment option, the value of microsurgical reconstruction to the efferent ductules is not established. We report, for the first time, the results of microsurgical reconstruction of efferent ductule obstruction.

METHODS: Among 230 patients who underwent vasoepididymostomy from 1983 to 1999 for obstructive azoospermia, 14 patients (6% incidence) who intra-operatively had no sperm in the cauda, corpus and caput epididymis, but had sperm in efferent ductules underwent vaso-efferent duct anastomosis bilaterally or, in cases of solitary testis, unilaterally. Three patients (22%) had an end-end anastomosis, 2 (14%) had an end-side anastomosis and 9 (64%) had an end-side triangulation technique anastomosis. The etiology, hormonal profile, post-operative semen analysis and outcomes were analyzed.

RESULTS: The mean age of the patients was 33 ± 7 yr. (21-47 yr). Four men had a history of epididymo-orchitis (30%), 2 cases (14%) were probably iatrogenic from orchiopexy (I torsion and I cryptorchidism), and the etiology of the remaining 8 patients (57%) was idiopathic. All patients had a preoperative semen analysis to confirm azoospermia, and testicular biopsies to confirm spermatogenesis. The mean serum testosterone level was 297 ± 105 ng/dI, mean FSH was 6.2 ± 4.1 mIU/ml, mean LH was 4.9 ± 4.3 mIUlml. Post-operatively, 13 patients (93%) had sperm in the semen analysis. The mean of the best sperm concentration post-operatively was 27 million/ml (0-77 million/ml) with 17% (0-40%) motility. Among patients who had sperm in the semen, the mean post- operative time to sperm appearance was 6.2 months (2-16 months). One case of natural pregnancy was achieved in this group.

CONCLUSIONS: Microsurgical reconstruction of pre-epididymal obstructive azoospermia yields a surprisingly high patency rate of 90%. Sperm motility is low. as expected in the absence of epididymal maturation. Although intra-operative sperm retrieval for future IVF should be performed routinely for these patients, micro-reconstruction with anastomosis of the vas to the efferent duct is a feasible option and worth performing in addition to sperm retrieval.

This abstract ( #1146) was presented at American Urological Annual Meeting, Atlanta, GA. May 2, 2000
( J. of Urol. ,vol.163, No. 4, Supplement, Tuesday, May 2, 2000)

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