Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis tissue with intracytoplasmic sperm injection.

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.

The effect of spinal cord level on sexual function in the spina bifida population.

INTRODUCTION: Sexual dysfunction and infertility are prevalent in the spina bifida (SB) population; however, the mechanism of how they affect a person with spina bifida is poorly understood. Additionally, the management of children with spina bifida becomes more difficult as they exit from pediatric institutes. OBJECTIVE: The present study sought to evaluate sexual health (using validated questionnaires) and fertility in adults with spina bifida and to correlate spinal cord level and ambulatory status with degree of sexual function. STUDY DESIGN: After institutional board review approval, 199 adult patients with SB, aged 18 and older and who were followed in one pediatric institution, were identified. Patients who were non-English speaking, cognitively and/or developmentally delayed, or unable to be contacted were excluded. Surveys regarding demographics, sexual health and infertility were mailed to the patients and administered in the clinic with the option to opt-out of the survey. Survey questions regarding sexual health were constructed using validated questionnaires: Female Sexual Function Index (FSFI) for females, and International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM) for males. Sexual dysfunction scores were correlated to the patients' spinal level and ambulatory status. RESULTS: Of the 121 eligible patients, 45 replied, with a response rate of 39%. For females, using a cut-off value of 26.5 for FSFI scoring, 25 out of 28 (89%) had sexual dysfunction. No association was seen between spinal level or ambulatory status and overall FSFI, satisfaction, or desire scores. For males, 10 out of 17 (59%) had severe erectile dysfunction (ED), and one out of 17 (6%) had no ED. No association was seen between ambulatory status and sexual function scores for the males. However, SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. People with spina bifida of both genders tended to have more severe dysfunction compared to those with sexual dysfunction of other etiologies, except with similar sexual desire scores. Regarding questions on fertility, no participant attempted to have children; thus, there was no infertility reported. DISCUSSION: Few studies have been conducted on sexual health and fertility in adults with SB. Three studies have utilized validated questionnaires and found varying degrees of sexual dysfunction in this subset of patients; however, only one study found sexual activity to be more likely in patients with more caudal levels of neurologic impairment. The present study also showed that SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. Limitations to this study primarily included the small sample size and low survey response rate. CONCLUSION: Limited information is known about adults with SB, and sexual function and fertility. While expressing sexual desire, adults with SB appear to experience high rates of sexual dysfunction. Fertility rates were inadequately assessed; this was possibly due to the high rate of sexual dysfunction. Sexual health in the SB population is an important component of the myriad of urologic care issues for these people. Due to the disparity in their care after reaching adulthood, it is prudent to follow these patients and understand their pathophysiology as they continue to mature through life.

Pulmonary function and clinical observations in men with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) was once thought to be a distinct clinical entity, but genetic similarities in men with cystic fibrosis (CF) and CBAVD are described increasingly. We evaluated the clinical status, growth and nutritional state, and respiratory function of 18 men with CBAVD to determine whether these men with different CF transmembrane regulator (CFTR) genotypes may have clinical evidence of mild CF. Following a thorough history and examination, pulmonary function tests, sweat test, and renal ultrasound were performed. Genetic evaluation for 50 known CF mutations, screening for private mutations (single-strand conformational polymorphism and direct sequencing), and assay of the length of the polypyrimidine tract in the splice site acceptor of intron 8 was performed. A history of pulmonary disease was present in three, and an additional man had some features suggestive of malabsorption. Results of general physical examination and anthropomorphic measurements were unremarkable in all patients, with a mean (SD) body mass index of 26 (3). Pulmonary function tests of large and small airway function as well as lung volumes were normal in all except one whose results were consistent with moderate asthma. Five men were compound heterozygotes for CFTR mutations, four of whom had positive sweat tests (sweat chloride > 60 mEq/L). Twelve men were heterozygotes for CFTR mutations while no mutations were identified in one man. Although putative etiologic factors may suggest that men with CBAVD and CFTR mutations could be considered within the spectrum of clinical CF, the authors suggest that in men with CBAVD without any other clinical features of CF, the diagnosis of CF may not be made.

Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes.

BACKGROUND: Men with cystic fibrosis (CF) have bilateral absence of the vas deferens causing an obstructive azoospermia that is not amenable to surgical correction. Advances in the field of reproductive medicine allow for the procurement of viable sperm and facilitate fertilization and pregnancy in couples where the man has CF. OBJECTIVES: To describe patient anatomy and semen characteristics and to determine the pregnancy rates of couples in whom the male partner has CF and who have undergone microsurgical epididymal sperm aspiration coupled with in vitro technology, specifically intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis. SETTING: Clinical department of urology and two reproductive medicine units. PATIENTS: Thirteen married men with CF who were referred for infertility. INTERVENTIONS: History, physical examination, semen analysis, transrectal and renal ultrasonography, CF mutation analysis, and microsurgical sperm aspiration coupled with ICSI. RESULTS: All 13 men had low-volume azoospermia, absent vasa, and aplasia/hypoplasia of the seminal vesicles. CF mutation analysis was carried out in 11 of 13 men, and 9 of 11 were DeltaF508 homozygous. Eight men underwent microsurgical sperm aspiration, and their partners underwent one or more cycles of ICSI. Five couples (62.5%) achieved a pregnancy, with four couples delivering (three sets of twins and one singleton). CONCLUSIONS: CF in men is accompanied by bilateral vasal aplasia. The resultant obstructive azoospermia can be treated quite successfully with a combination of sperm aspiration and ICSI. It is important for physicians involved in the care of men with CF to convey the message that prospects for fatherhood are excellent with current technology.

Effect of level of anastomosis and quality of intraepididymal sperm on the outcome of end-to-side epididymovasostomy.

OBJECTIVES: Epididymovasostomy is commonly performed at the most distal site of the epididymis where whole sperm are present within the lumen, regardless of their motility status. Although more fresh and motile sperm can be found more proximally within the epididymis, it is believed that the outcome of epididymovasostomy is better more distally. Because the current results of epididymovasostomy are far from perfect, it would be ideal to be able to harvest motile sperm for cryopreservation at the time of surgery in case the patient remains azoospermic postoperatively. The objective of this study was to determine the effect of the level of epididymal anastomosis and quality of sperm on the outcome of surgery. METHODS: An end-to-side epididymovasostomy was performed on 131 azoospermic men with a mean age of 39 years and a mean obstructive interval of 18 years. The etiology of obstruction was vasectomy in 48%, infectious in 19%, congenital in 20%, and unknown in 13%. The average duration of follow-up was 32 months. The overall patency rate was 67% and pregnancy rate was 27%. Subgroups of patients with an anastomosis to the same level of the epididymis on all functional sides were identified as follows: caput (56), corpus (28), and cauda (13). These groups were compared in regard to the presence of motile sperm within the epididymal lumen at the time of surgery, patency rates, postoperative semen quality, and pregnancy rates. RESULTS: Motile sperm were present more often in both the caput (54%) and corpus (61%) than in the cauda epididymis (25%) (P < 0.05). The patency rates for the three subgroups were not significantly different. The postoperative total motile sperm count and pregnancy rate for the corpus epididymis (13 x 10(6) and 45%) was significantly (P < 0.05) better than for the caput (4.4 x 10(6) and 22%) but no different than that of the cauda (10 x 10(6) and 23%). The patency and pregnancy rates for anastomoses performed at levels demonstrating motile sperm were not significantly better than at sites with nonmotile sperm, but the postoperative total motile sperm count was better (P < 0.05). CONCLUSIONS: The results of this study suggest that the outcomes of epididymovasostomy to the corpus and cauda epididymis are roughly equivalent and superior to the caput. Therefore, it may be reasonable to move more proximally from the cauda to corpus in the search for motile sperm for cryopreservation during an end-to-side epididymovasostomy. In contrast, moving from the corpus to the caput epididymis has a significant adverse effect upon outcome; it is, therefore, not worthwhile to search for viable sperm for cryopreservation in this clinical setting.

Presence of mature sperm in testicular parenchyma of men with nonobstructive azoospermia: prevalence and predictive factors.

OBJECTIVES: Hitherto, patients with testicular dysfunction and azoospermia had to resort to adoption, donor sperm insemination, or child-free living. The realization that a proportion of such men harbor spermatozoa in their testicular parenchyma, combined with the ability of intracytoplasmic sperm injection (ICSI) to effect pregnancy with single sperm, has prompted male infertility clinicians to explore testicular sperm extraction (TESE) in this patient population. We sought to investigate the likelihood of finding spermatozoa during TESE from men presenting with nonobstructive azoospermia and to define if any factors existed that were predictive of eventual sperm presence or absence. METHODS: Thirty patients with nonobstructive azoospermia underwent TESE and simultaneous formal testis biopsy, cytologic analysis, and wet preparation analysis. Tissue obtained from TESE was analyzed according to a rigorous protocol, followed by exhaustive searching by trained embryologists. RESULTS: Twenty-one patients (70%) had spermatozoa found on testicular tissue analysis. Neither patient age nor follicle-stimulating hormone (FSH) level was predictive of the ability to find sperm. With regard to histologic pattern, 50% of men with Sertoli cell-only, 75% of patients with maturation arrest, and 100% of patients with spermatids seen on histologic analysis had sperm retrieved from their testicular tissue during TESE. Absence of sperm on cytologic smear and wet preparation analysis failed to predict the presence of sperm on formal testicular tissue analysis in 40% of patients. CONCLUSIONS: Men with nonobstructive azoospermia may have mature spermatozoa present within their testicular parenchyma. Relying on these data, patients should not be excluded from TESE based on serum FSH level, age, prior histopathologic pattern, or cytology/wet preparation results. These figures will allow clinicians to counsel patients with nonobstructive azoospermia informatively regarding TESE and their chances of having testicular sperm retrieved.

Testicular tissue extraction in a young male with 47,XXY Klinefelter's syndrome: potential strategy for preservation of fertility.

OBJECTIVE: To describe a case involving the cryopreservation of testis tissue retrieved from a 15-year-old male teenager with Klinefelter's syndrome. DESIGN: Case report. SETTING: An academic medical center. PATIENT(S): A 15-year-old boy with Klinefelter's syndrome. INTERVENTION(S): Microsurgical testis sperm extraction with cryopreservation of harvested tissue. MAIN OUTCOME MEASURE(S): Spermatozoa within testis tissue. RESULT(S): Successful extraction and cryopreservation of three vials of sperm-containing testis tissue. No effect on subsequent testosterone levels. CONCLUSION(S): Testis tissue extraction in the adequately virilized but azoospermic young male with 47, XXY Klinefelter's syndrome may be a strategy to preserve future biological paternity.

The achievement of pregnancies using assisted reproductive technologies for male factor infertility after retroperitoneal lymph node dissection for testicular carcinoma.

OBJECTIVE: To evaluate the success of electroejaculation with assisted reproductive technologies (ART) in anejaculate men after retroperitoneal lymph node dissection (RPLND) for testicular cancer. DESIGN: Retrospective clinical study. SETTING: Tertiary care, university-affiliated IVF program. PATIENTS: Anejaculate men after RPLND, spouses. INTERVENTIONS: Electroejaculation, microsurgical sperm aspiration, various assisted reproductive technologies. MAIN OUTCOME MEASURES: Sperm density and motility, fertilization rate, pregnancy rate (PR). RESULTS: Compared with patients not receiving chemotherapy, patients who received chemotherapy had diminished average sperm densities and motilities (63 x 10(6) and 20% versus 101 x 10(6) 32%, respectively); decreased fertilization rates per cycle for IVF and intracytoplasmic sperm injection (ICSI) (11% versus 26%, respectively); lower PRs per cycle of hMG-IUI and IVF (14% versus 60% and 8% versus 50%, respectively). No pregnancies were achieved with natural cycle-IUI, clomiphene citrate-IUI, or GIFT. Two couples progressed to intracytoplasmic sperm injection with one achieving the successful delivery of healthy twins. The overall PR per cycle was 22%. CONCLUSIONS: Patients receiving chemotherapy had decreased sperm densities, motilities, fertilization, and PRs for each modality used. Rectal probe electroejaculation with ART can help anejaculate men after RPLND achieve biologic paternity. An early move to the more aggressive therapies (hMG-IUI, IVF, ICSI) is supported.

Fertility and the use of assisted reproductive techniques in the adult male exstrophy/epispadias patient.

These three cases exemplify, in increasing order of complexity, how the common sense application of already successful techniques might be applied to augment the chance of pregnancy in this group of patients. We believe this to be the first report specifically outlining measures that may assist this group in their goal of pregnancy achievement. To our knowledge, vasal sperm aspiration has never been used for this indication.

Genetic abnormalities and reproductive failure.

Adequate male development and spermatogenesis involve a complex array of events, all prescribed by numerous gene products in an orderly temporal and spatial sequence. A single defect in any portion of these myriad steps may lead to total failure of testicular development or simply subtle spermatogenic deficiency. As emphasis continues to be placed upon elucidation of the molecular and genetic basis underlying clinical and phenotypic human failings, knowledge will slowly accumulate to explain these failings and, it is hoped, to suggest treatment strategies for some.

Disturbed sexual function in patients with spinal cord disease.

The normal neural pathways involved in erection and ejaculation and the various spinal cord and central nervous system disorders that can adversely affect these functions are reviewed in this article. Also outlined are treatment strategies currently being employed.

Unilateral absence of the scrotal vas deferens associated with contralateral mesonephric duct anomalies resulting in infertility: laboratory, physical and radiographic findings, and therapeutic alternatives.

Ten patients who presented for infertility had unilateral absence of the scrotal vas deferens and a contralateral mesonephric duct anomaly, including contralateral ejaculatory duct or epididymal/vasal obstruction. The details of the physical examination, semen analysis and transrectal ultrasound led to an accurate preoperative diagnosis in each case. Therapeutic manipulations appropriate in this group included transurethral resection of the ejaculatory duct, microscopic vasoepididymostomy and microsurgical sperm aspiration coupled with in vitro fertilization. Only 3 patients had ipsilateral renal agenesis or ectopia (30%), which is well below the stated percentage for patients with unilateral vasal agenesis (90%). An aberration in the proper sequence of mesonephric embryological development may partly explain this bilateral constellation of abnormalities.

Congenital bilateral absence of the vas deferens and cystic fibrosis. A genetic commonality.

CF and CBAVD are really just ends of a clinical spectrum. The type and nature of the mutations in the CF gene probably determine the phenotypic expression of the patient. Perhaps all patients homozygous for delta F508, for example, will have severe pulmonary and pancreatic disease as well as absent vasa, whereas those with other combinations, such as delta F508/D1270N, will be unaffected in terms of pulmonary and pancreatic function but will have absent vasa. Besides contributing to a better understanding of the nature of CBAVD, this linkage of CF and CBAVD most importantly mandates genetic screening and counseling for appropriate family members and even the patient's spouse. In addition, a broader understanding of CF is now at hand, as this brings a whole new cohort of patients under the CF umbrella. Many of these will have at least one, if not two, rare or novel CF gene mutations. Once all of these mutations have been detected and defined, our knowledge of the CF gene, its mutations, and their implications will be dramatically expanded.

Use of a polytetrafluoroethylene tube graft as a circumferential neotunica during placement of a penile prosthesis.

Various techniques have evolved for augmentation of the tunica albuginea in cases when tunical tissue has been found deficient during penile prosthesis implantation. An intraoperative situation occurred in which the size of the tunical defect did not permit primary tunical closure or allow for approximation by placement of a tunical patch graft. In this case, to ensure satisfactory insertion of a penile prosthesis a polytetrafluoroethylene (Gore-Tex) tube graft was used as a circumferential neotunica.

Male infertility: role of transrectal US in diagnosis and management.

Ultrasound (US) has become crucial in the assessment of infertility of couples, in 50% of whom the male partner is responsible. Male infertility is caused by many diverse conditions, from reparable obstructive disorders to noncorrectable intrinsic testicular failure. During the past 4 years, a select group of 70 young infertile men with azoospermia or oligospermia and low ejaculate volume were examined with transrectal US. Twenty-six patients had congenital bilateral absence of the vas deferens, 11 had congenital unilateral absence of the vas deferens and contralateral obstructive pathology, 15 had additional abnormalities thought to be directly related to semen deficiencies, and 18 patients with other causes for semen deficiency and infertility had findings that were either normal or showed minor abnormalities. The delineation of congenital and obstructive abnormalities of the distal urogenital tract with transrectal US enables an accurate diagnosis of certain cases of male infertility and helps guide appropriate clinical and surgical management.

Granulomatous prostatitis following bacillus Calmette-Guerin immunotherapy of bladder cancer.

Granulomatous prostatitis is a recognized complication of intravesical bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. Of 32 patients receiving such therapy 13 underwent prostatic core biopsy and/or fine needle aspiration for clinical indications. Prostatic induration or nodularity developed in 12 patients and 1 underwent biopsy for staging of known prostatic carcinoma. Granulomatous prostatitis was found in 100 per cent of those patients who underwent biopsy or aspiration, indicating that the incidence of this finding is at least 41 per cent following bacillus Calmette-Guerin immunotherapy. Acid-fast bacilli were demonstrated within the prostate of 3 patients with granulomatous prostatitis. The mean interval between the initiation of therapy and diagnosis of granulomatous prostatitis was 11.5 months. Bacillus Calmette-Guerin related granulomas of the prostate may be differentiated histologically from nonspecific granulomatous prostatitis, allergic prostatitis and postoperative granulomas. The clinical implications of these findings are discussed.

Fertilization and pregnancy using intentionally cryopreserved testicular tissue as the sperm source for intracytoplasmic sperm injection in 10 men with non-obstructive azoospermia.

Testicular tissue extraction (TESE) to obtain spermatozoa for use with intracytoplasmic sperm injection (ICSI) has recently been employed in patients with non-obstructive azoospermia. Standard protocol is to retrieve a new sample of testis tissue on the day of oocyte recovery. Unfortunately, approximately 30% of men will possess no spermatozoa in their tissue, making ICSI an impossibility. We investigated whether testicular tissue that was intentionally obtained well before any planned ICSI cycle and cryopreserved could then serve as an efficacious sperm source in a subsequent ICSI cycle. This study reports on 10 men with non-obstructive azoospermia who did have spermatozoa found within their testis tissue at the time of TESE and who chose to use their frozen samples as the source of spermatozoa for a later cycle of ICSI. In 19 cycles the overall fertilization rate was 48%. Embryo transfer occurred in 89% of cycles. Two couples have achieved pregnancy (one ongoing, one delivered). All patients except one had multiple vials of frozen tissue remaining following their first cycle. This approach is offered as an alternative to repeated testicular tissue sampling, as the availability of spermatozoa is assured prior to the initiation of ovulation induction. This tissue can be harvested at the same time as diagnostic biopsy, thereby minimizing the number of surgical procedures.

Microscopic epididymal sperm aspiration (MESA): a new option for treatment of the obstructive azoospermia associated with cystic fibrosis.

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.

Congenital unilateral absence of the vas deferens: a heterogeneous disorder with two distinct subpopulations based upon aetiology and mutational status of the cystic fibrosis gene.

A total of 21 infertile men with congenital unilateral absence of the vas deferens (CUAVD) were studied to determine if this disorder involves mutations in the cystic fibrosis (CF) gene. This hypothesis derives from previous work which has established the genetic commonality of CF and congenital bilateral absence of the vas deferens (CBAVD). Both CF and CBAVD may result from compound heterozygosity for CF mutations. In our patients with unilateral vasal aplasia, 12 had anatomically complete and patent vasa deferentia on the contralateral side, i.e. side of the scrotally palpable vas. No CF mutations were detected in this subgroup. The remaining nine patients had a non-iatrogenic occlusion of the contralateral vas at either the inguinal or pelvic level. In this subgroup, eight out of nine (89%) had a mutation detected in one of their two CF genes. This is the first study to define accurately the clinically and anatomically heterogeneous nature of CUAVD and to begin to clarify the genetic basis of unilateral absence of the vas deferens.