Serum inhibin B and follicle-stimulating hormone levels as markers in the evaluation of azoospermic men: a comparison

Inhibin B is a glycoprotein hormone produced mainly by Sertoli cells of the testes in the adult male. It selectively suppresses the secretion of pituitary follicle-stimulating hormone (FSH) and has local paracrine actions in the testes. Its measurement is useful for investigating the role of inhibin B in male gonadal dysfunction. The objective of this study was to investigate the efficacy of serum inhibin B in men with nonobstructive azoospermia in comparison with FSH. Serum concentration of FSH was measured using microparticle enzyme immunoassay, inhibin B by specific solid phase sandwich enzyme-linked immunosorbent assay in men with nonobstructive azoospermia (n = 46) and control fertile men (n = 5). Mean inhibin B and FSH level was 104.6 pg ml(-1) and 4.0 mIU ml(-1) in control men whereas the value for nonobstructive azoospermic men was 17.06 pg ml(-1) and 31.1 mIU ml(-1) respectively. Inhibin B and FSH levels were significantly different in azoospermia than controls (P < 0.0001). There were six cases of nonobstructive azoospermia with normal inhibin B. Testicular histology did not find any evidence of spermatogenesis in three cases with normal inhibin B. This demonstrated that inhibin B was not a superior predictor for testicular function in our study.     

Prospective analysis of outcomes after microsurgical intussusception vasoepididymostomy

OBJECTIVE: To prospectively analyse the outcomes of microsurgical vasoepididymostomy using the intussusception technique, as vasoepididymostomy is considered the most challenging reconstructive microsurgery in urology. PATIENTS AND METHODS: From 1998 to 2003, of 324 men with obstructive azoospermia who had undergone microsurgical reconstruction of the reproductive tracts, 68 (21%) had intussusception vasoepididymostomy bilaterally or unilaterally in a functionally solitary testis. The outcomes of these patients were analysed prospectively. RESULTS: The mean age was 39.8 years for the men and 31.8 years for their partners. The causes of obstruction were after vasectomy in 31%, infection in 22%, iatrogenic in 19%, trauma in 1.5%, and idiopathic in 27%. The median duration of obstruction was 18.8 years; 37% of patients had had previous failed attempts at reconstruction. The mean (range) follow-up was 15.2 (1-36) months. The overall patency (>10 000 sperm/mL) rate was 84% (53/63). Patency was achieved in 60% (38/63) of men at 1 month after surgery. The mean best sperm count was 12.8 (0.01-80) x 10(6)/mL, with a 21 (0-30)% motility. Among patients with a follow-up of > 1 year, the natural paternity rate was 40%. The median time to achieve a natural pregnancy was 14.3 (3-30) months. Pregnancy was achieved with in vitro fertilization or intracytoplasmic sperm injection in 31% of cases, all using fresh ejaculated sperm. CONCLUSIONS: A favourable patency and pregnancy rate can be achieved using microsurgical intussusception vasoepididymostomy. Even when assisted-reproductive technology is needed, fresh ejaculated sperm can be used without requiring a subsequent sperm retrieval procedure. Thus, microsurgical reconstruction of the reproductive tract should be primary therapeutic method in cases of azoospermia from epididymal obstruction.     

Robotic microsurgical vasovasostomy and vasoepididymostomy in rats

Robotic and robotic assisted procedures are rapidly increasing in popularity amongst practicing surgeons and urologists. Robotic techniques are now commonly used to perform radical prostatectomies for prostate cancer and pyeloplasties for uretero-pelvic junction obstruction. Other robotic procedures include robotic assisted coronary artery bypass and partial nephrectomies. We initially studied the da Vinci surgical robot in order to determine the feasibility of adapting the robot to microsurgical vasovasostomy and vasoepididymostomy. In this paper, we describe our experience in developing a set of practice exercises using the da Vinci robot to prepare for these microsurgical procedures. We also review the design and results of our studies of robotic microsurgical vasovasostomy and vasoepididymostomy in rats.Finally, we discuss the potential future roles of robotic microsurgery in urology and surgery.     

Comparison of the outcome of intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia in the first cycle: a report of case series and meta-analysis

To investigate the outcome of intracytoplasmic sperm injection with fresh and cryopreserved-thawed testicular spermatozoa in the first cycle in patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), a total of 90 cases, 48 OA and 42 NOA were studied. All patients underwent sperm retrieval by testicular sperm extraction (TESE) while their wives received conventional ovarian hyperstimulation. The hormone levels, testicular histology, the rates of sperm retrieval, fertilization, implantation and pregnancy were analysed and evaluated. This study and other four similar studies were subjected to meta-analysis. Sperm retrieval was successful in 100% OA and 61% NOA. Fresh spermatozoa were used in 87.5% and 92.4% of OA and NOA cases respectively; while cryopreserved-thawed spermatozoa were used in 12.5% and 7.6% of OA and NOA, respectively. The fertilization, implantation and clinical pregnancy rates were 65.5%, 15% and 25% respectively in OA group, and 54.2%, 5% and 23.1% respectively in NOA group. Sperm status (fresh or thawed), male partner's age, female age and male serum follicle-stimulating hormone had no significant effect upon fertilization rate, implantation rate, or pregnancy rate per embryo transfer. The results of meta-analysis indicate that there is no statistically significant difference in clinical pregnancy rates between the two groups. There was a significantly higher fertilization rate among OA patients in all analysed studies (95% CI = 14.29-15.71, d.f. 832, T = 1.96). In conclusion, although the fertilization rate was significantly higher in the OA group in our study and from the given meta-analysis, there were some differences as regards pregnancy rates. Although the overall effect was more or less similar pregnancy rates in both subtypes of azoospermia, this may not be true if non-male infertility variables were controlled for in all studies.     

Role of varicocelectomy in men with nonobstructive azoospermia

OBJECTIVE: To evaluate the benefits of varicocelectomy in men with nonobstructive azoospermia. DESIGN: Retrospective review of effect of prior varicocelectomy on sperm retrieval rates in men with nonobstructive azoospermia. Chart review of men with nonobstructive azoospermia who underwent microsurgical varicocelectomy to determine the effect of the procedure on the need for testicular sperm extraction (TESE). SETTING: Tertiary, university-based referral center. PATIENT(S): Men with clinical varicoceles and nonobstructive azoospermia. INTERVENTION(S): Microsurgical varicocelectomy, TESE. MAIN OUTCOME MEASURE(S): Return of sperm to the ejaculate and need for TESE after varicocele repair, ability to find sperm using microdissection TESE. RESULT(S): Of 31 men who underwent varicocele repair at one institution for documented nonobstructive azoospermia, 7/31 (22%) had sperm reported on at least one semen analysis postoperatively. However, only 3/31 (9.6%) men after varicocele repair had adequate motile sperm in the ejaculate for ICSI, without TESE. Sperm retrieval rates for men with varicoceles were not affected by a history of prior varicocelectomy. CONCLUSION(S): Men with clinical varicoceles that are associated with nonobstructive azoospermia will rarely have adequate sperm in the ejaculate after varicocele repair to avoid TESE. A history of prior varicocele repair does not appear to affect the chance of sperm retrieval by TESE for men with clinical varicoceles and nonobstructive azoospermia. The benefits of varicocelectomy in men with nonobstructive azoospermia may be less than previously reported.     

Sertoli cell inactivation by cytotoxic damage to the human testis after cancer chemotherapy

OBJECTIVE: To assess Sertoli cell involvement in postchemotherapy azoospermia. DESIGN: Case report. SETTING: Teaching hospital. PATIENT(S): A 31-year-old azoospermic man who underwent cancer cytotoxic chemotherapy for non-Hodgkin's lymphoma at 13 years of age. INTERVENTION(S): Testicular biopsy specimens were obtained for sperm recovery in preparation for intracytoplasmic sperm injection. The biopsy specimens were evaluated by quantitative immunohistochemistry for the immature Sertoli cell markers cytokeratin 18 (CK-18) and D2-40. MAIN OUTCOME MEASURE(S): Extent of immature Sertoli cells. RESULT(S): A fraction of Sertoli cells (13%) in the atrophic tubules of this patient reexpressed the intermediate filament protein CK-18, which is normally absent after puberty, but not the D2-40 antigen, an Mr 40,000 a-linked membrane glycoprotein, whose loss of expression at puberty marks an irreversible step in Sertoli cell maturation. Tubules with normal spermatogenic progression lined by Sertoli cells negative for CK-18 were also observed. CONCLUSION(S): A fraction of Sertoli cells of this patient initially progressed to full maturation at puberty and reverted to a dedifferentiated state marked by reexpression of CK-18 as a consequence of chemotherapy. This inactivation of Sertoli cells caused by the cytotoxicity of the chemotherapeutic drugs may have contributed to the spermatogenic impairment and resulting infertility.     

Superior outcomes of microsurgical vasectomy reversal in men with the same female partners

OBJECTIVE: To evaluate the outcomes of vasectomy reversals in men with the same female partners. DESIGN: Retrospective analysis with comparison with a historical cohort. SETTING: University hospital. PATIENT(S): Among 1,048 patients who underwent microsurgical vasectomy reversal from 1986 to 2002, 27 men (2.6%) were identified who had the same partners as before their vasectomy. INTERVENTION(S): Microsurgical vasovasostomy or vasoepididymostomy. MAIN OUTCOME MEASURE(S): Semen parameters, clinical pregnancy, and live birth rates. RESULT(S): The mean age of the men was 38.5 years, and 37.2 years for their female partners. The reasons for vasectomy reversal were death of a child in 33% of cases and desire for more children in 66% of cases. The overall patency rate was 100% at 1 month postoperatively, with an average sperm concentration of 30 million/mL and 24% motility. Among patients with follow-up beyond 1 year, the natural pregnancy rate was 86%, which was achieved at 8.3 months postoperatively, with a live birth rate of 82%. The live birth rate in couples with the death of a child was 100%. CONCLUSION(S): The outcomes of vasectomy reversal in men with the same female partners are better than for men with new partners. Possible reasons for these superior results are previous proven fecundity as a couple, shorter time interval since vasectomy, and emotional dedication.     

Testicular Sperm Extraction (TESE) and Intracytoplasmic Sperm Injection (ICSI) in Hypogonadotropic Hypogonadism with Persistent Azoospermia After Hormonal Therapy

PURPOSE: We aimed to retrieve testicular sperm to be employed on intracytoplasmic sperm injection (ICSI) cycles on a male affected of hypogonadotropic hypogonadism (HH) that remained azoospermic after long-time hormonal treatment. METHODS: Design. We initially performed hormonal therapy using gonadotropins to achieve spermatogenesis. After several semen analyses, we weighed the possibility of looking for testicular spermatozoa for ICSI. Setting. A private university-affiliated setting. Patient. A 30-years-old man diagnosed 10 years ago to suffer from idiopathic, prepubertal HH. Interventions. Gonadotrophin treatment was initiated with hCG and follicle stimulating hormone (FSH). Testicular sperm extraction was carried out when repeated spermiograms were negative. Motile testicular spermatozoa were cryopreserved and were subsequently employed for ICSI. Multiple follicular development was stimulated with gonadotropins after a downregulation with gonadotropin-releasing hormone (GnRH) antagonists in the woman. Main Outcome Measures. Seminal analyses were performed after 3, 6, and 12 months of treatment and serum FSH, luteinizing hormone (LH) and testosterone levels were also measured. RESULTS: Seminal analysis showed always azoospermia. Serum FSH was 2.9 mIU/mL, serum LH >1 mIU/mL and serum testosterone 7.9 ng/mL (12 months after treatment). Nine oocytes were collected by ultrasound-guided transvaginal route and eight of them were microinjected with motile, frozen-thawed testicular spermatozoa. Four oocytes were fertilized. Three embryos were transferred without pregnancy. CONCLUSIONS: The case report here presented shows that the currently available assisted reproduction techniques may be of value in patients with HH not responding to conventional hormonal treatments.     

Relation between the anatomical genital phenotype and cystic fibrosis transmembrane conductance regulator gene mutations in the absence of the vas deferens

OBJECTIVE: To study the correlation between genital phenotype and cystic fibrosis genotype in men lacking at least one vas deferens. DESIGN: Prospective study. SETTING: Institut Rh?nalpin pour la Reproduction Humaine, Lyon-Bron, France. PATIENT(S): Forty-seven infertile men lacking at least one vas deferens. INTERVENTION(S): All patients were screened for the 13 most common CFTR gene mutations and for the 5-thymidine variant of intron 8. Renal, scrotal, and transrectal ultrasonography were systematically performed. MAIN OUTCOME MEASURE(S): Epididymal and seminal vesicular abnormalities and testicular volume were compared among men with two, one, or no CFTR gene mutation, with or without the 5T allele. RESULTS: Seminal vesicles and the symmetry of epididymal and vesicular abnormalities did not differ between patients with and those without the CFTR gene mutation. Epididymal abnormalities were more frequent in men without the mutation. Testicular volumes were significantly lower in men without the mutation and those with the 5T allele only. CONCLUSION: Men with the CFTR mutation, the 5T allele only, and those without CFTR mutation have few differences in genital phenotype. Low testicular volume is observed in men without the CFTR mutation and those with the 5T allele only.     

Application of seminal germ cell morphology and semen biochemistry in the diagnosis and management of azoospermic subjects

Aim: To evaluate whether the study of seminal germ cell morphology (SGCM) and semen biochemistry could be fruitfully utilized for the diagnosis and management of azoospermic subjects. Methods: In the semen, mature and immature germ cells are contributed by the testes, 70% of glycerylphosphoryl choline (GPC) by the epididymis, fructose mostly or solely by the seminal vesicles and acid phosphate (ACP) by the prostate. In 16 normal volunteers, 12 vasectomized subjects and 186 azoospermic subjects, these parameters have been studied and the data have been analyzed. Results: Both mature and immature germ cells are absent in the semen of vasectomized subjects as well as in obstructive azoospermia; GPC level is also significantly decreased in both these groups. In cases with non-obstructive azoospermia immature germ cells are present and seminal GPC, ACP and fructose levels are normal. The diagnosis of obstructive and non-obstructive azoospermia based on these parameters correlated well with “correct” testicular biopsy findings. In some cases of azoospermia due to hypospermatogenesis or spermatogenic developmental arrest, the SGCM studies were very helpful in objectively monitoring the response of the germinal tissue to specific treatments. Conclusion: SGCM and semen biochemical parameters are very valuable non-invasive markers for differentiating obstructive from non-obstructive azoospermia. The SGCM findings serve as a dependable non-invasive testicular marker with high predictive value.