Role of epididymis in sperm maturation

One hundred ninety patients with obstructive azoospermia caused by bilateral epididymal blockage have been followed up for four years or longer after undergoing "specific tubule" vasoepididymostomy. When anastomosis was required in the corpus epididymis, the "patency" rate was 78 percent, and the overall pregnancy rate was 56 percent. The pregnancy rate for "patent" cases was 72 percent, indicating that a high fertility rate can be obtained with sperm that have not transited the full length of corpus epididymis. By contrast, with vasoepididymostomy to the caput epididymis there was a 73 percent "patency" rate, but the overall pregnancy rate was only 31 percent. The pregnancy rate for "patent" cases was 43 percent. Sperm from the corpus epididymis have a higher rate of fertility than sperm from the caput epididymis, but sperm from proximal areas of the corpus have no less fertility than sperm from the distal corpus epididymis. The most remarkable observation is that in almost half the cases sperm that have never journeyed beyond the caput epididymis seem to be capable of causing pregnancy.     

附睾输精管吻合术治疗梗阻性无精子症

目的探讨附睾输精管吻合术在梗阻性无精子症治疗中的作用。方法选择23例确诊为梗阻性无精子症并初步怀疑为附睾水平梗阻的患者进行阴囊探查，观察睾丸、附睾及输精管情况，对其中19例确定为附睾水平梗阻并在附睾液中找到活精子的患者用8-0尼龙线施行双侧或单侧附睾输精管端侧吻合术，术后随访其疗效。结果19例获随访8～34个月，9例(47％)于术后3～9个月从精液中检出活精子，其中5例配偶受孕成功。结论阴囊探查简单、易行，有助于梗阻性无精子症的诊断和治疗，附睾输精管吻合术治疗梗阻性无精子症取得初步效果，值得进一步探讨。     

Expression and distribution of OCTN2 in mouse epididymis and its association with obstructive azoospermia in juvenile visceral steatosis mice

AIM: L-carnitine, an essential cofactor for mitochondrial, beta-oxidation of long-chain fatty acids, is known to play important roles in sperm maturation and metabolism when spermatozoa pass and acquire motility in the epididymis. We reported that obstructive azoospermia occurred in the epididymis in the juvenile visceral steatosis (JVS) mice, which are OCTN2 dysfunction mice caused by mutations in the gene encoding OCTN2, have been used for animal models of primary systemic carnitine deficiency. The aim of present study is to investigate the expression of OCTN2 protein in the mouse epididymis and its relation between the localization of OCTN2 and obstructive azoospermia in JVS mice as animal models for human male infertility. METHODS: Animals used in this study were wild-type (C57BL/6 J) mice (n = 4) and JVS mice (n = 4). We made a specific polyclonal antibody against OCTN2 and examined immunohistochemically the localization of OCTN2 in the mouse epididymis. RESULTS: OCTN2 was localized on the apical membrane of the principal cells of distal corpus and cauda epididymides. Immunocytochemistry demonstrated that OCTN2 was localized on the surface of microvillus upon the principal cells. In JVS mice, immunoreactivity started in a region immediately distal to where the sperm obstruction occurred. CONCLUSIONS: Our results suggest that OCTN2 functions as a carnitine transporter between the epithelium and the lumen in distal corpus and cauda epididymides and provides a clue as to why obstructive azoospermia is induced in distal parts of epididymis.     

显微外科技术治疗梗阻性无精子症的新进展

显微外科技术在最近 5～ 10年的生殖医学发展中扮演了重要角色。显微外科的睾丸取精技术和附睾取精技术 ,与体外受精和卵细胞内单精子注射技术的结合 ,使得过去一直被认为是难以治疗的因生精功能障碍所致的非梗阻性无精子症的治疗成为现实。与此同时 ,显微外科输精管吻合和输精管附睾吻合的技术革命使治疗梗阻性无精子症的效果显著地改善 ,成为治疗梗阻性无精子症的首选方法。本文着重介绍了显微外科输精管吻合术、输精管附睾吻合术、手术指征与手术成功的要素 ,预测了未来的发展方向 ,讨论了显微外科技术的优势 ,强调了显微外科培训对泌尿外科医生治疗男性不育患者的重要意义。     

146例炎症梗阻性无精子症的临床评估和ICSI治疗结局分析

目的分析炎症梗阻性无精子症的临床评估和单精子卵胞浆内注射(ICSI)的治疗结局。方法前瞻性研究近5年间接受ICSI治疗的炎症性梗阻性无精子症的临床特征、精液和超声特点,经皮附睾穿刺精子抽吸术(PESA)或经皮睾丸穿刺取精术(TEFNA)结合ICSI治疗后观察受精、临床妊娠等结果。结果146例患者体检附睾均有增粗变硬或伴头尾部结节。82例患者曾有生育史、附睾炎症史或输精管附睾吻合手术史,其中72例PESA找到附睾精子;53例无上述病史者49例PESA找到附睾精子:另有精道远端梗阻11例。ICSI治疗146例167周期炎症性梗阻性无精子症的受精率、每周期临床妊娠率分别为81.1%和42.1%。结论炎症梗阻性无精子症具备典型的临床和超声特征,PESA附睾精子获取率高,ICSI治疗获得较高受精率和临床妊娠率。     

Epididymal microsurgery: current techniques and new horizons

Surgical treatment for obstructive azoospermia was introduced about 30 years ago with the development of Bayle's vasoepididymal fistula technique (Bayle: Enc Med Chir 41:435, 1966). More recently this has been replaced by single tubule end-to-end microvasoepididymal bypass procedures with improved success rates. We describe the use of animal models in the development and application of a modified end-to-end microanastomosis technique in which the vas deferens is attached to a single surface convolution of the ductus epididymidis. In comparison with other microvasoepididymostomy (micro-VE) procedures, this technique results in less postoperative scarring and allows for easier access to the epididymis in those patients requiring subsequent epididymal surgery. With this procedure 60% of patients produced spermatozoa after operation, and 10% of 102 patients have so far achieved pregnancies. For patients, such as those with congenital absence of the vasa deferentia, whose infertility cannot be corrected by microvasoepididymal surgery, we describe a microaspiration procedure that can be used to collect spermatozoa from the epididymis for use in in vitro fertilization (IVF). This procedure has a low success rate at present, with an 18% fertilization and 3% pregnancy rate per cycle. Improvements in treatment procedures for aspirated sperm samples, such as the use of motility stimulators and in vitro maturation by coculture with epididymal tubule segments before IVF, may enhance the success for this technique. Microinjection of sperm collected by epididymal microaspiration into oocytes may be an alternative method of treatment for these patients in the future. Two procedures (microepididymoepididymostomy and the vas bridge bypass) that are currently being modelled in the rabbit may provide new directions for epididymal microsurgery and for examining epididymal function. Although the two methods are technically more difficult than standard micro-VE procedures, preliminary studies are encouraging and suggest a future role for these techniques in treating obstructive azoospermia. Such techniques make use of the epididymis distal to the obstruction site and may be particularly important in improving the success of surgery for obstructive azoospermic patients with high-level obstructions in whom sperm quality following micro-VE surgery is often poor.     

Microsurgical side-to-end epididymovasostomy: surgical technique and outcomes

The surgical procedures and results of microsurgical epididymovasostomy for obstructive azoospermia at the epididymis are reported. These procedures include the separation of a single epididymal tubule, an incision in the side wall, and a side-to-end anastomosis to the mucosa of the vas deferens under microscopic view. The tunica of the epididymis and the muscle layer of the vas are sutured together to support the mucosal anastomosis. Ten patients with epididymal obstruction underwent the side-to-end epididymovasostomy. The group consisted of two with Young's syndrome, one with an epididymal blow-out after vasectomy, one unsuccessful epididymoepididymostomy, 4 after epididymitis and 2 cases of unknown origin. After the operation, sperm appeared in 9 patients, and semen quality was normalized in 4 patients, all of whom impregnated their wives. Microsurgical side-to-end epididymovasostomy is a much easier procedure than Silber's specific tubule method, and results in a high success rate.     

Microsurgical vasoepididymostomy with sperm cryopreservation for future assisted reproduction

BACKGROUND: Although obstructive azoospermia is treatable with microscopic seminal reconstruction, the number of patients who choose to undergo vasoepididymostomy is limited because of recent advances in assisted reproductive technology (ART). We attempted to define the outcome of surgical reconstruction in patients with suspected epididymal obstruction and no previous history of vasectomy. METHODS: We described 40 eligible end-to-side vasoepididymostomy procedures performed on 24 azoospermic patients who had either bilateral or unilateral epididymal obstruction. RESULTS: The overall patency rate following surgery was 54% (13/24) and for four patients (17%), natural intercourse resulted in pregnancy. Two pregnancies were initiated with intracytoplasmic sperm injections using frozen sperm collected during vasoepididymostomy. CONCLUSIONS: In the era of modern ART, microsurgical vasoepididymostomy with cryopreservation of sperm collected during the operation is recommended for patients with epididymal obstructions.     

机器人辅助输精管吻合术治疗梗阻性无精子症初步经验分析

目的:探讨机器人辅助下输精管-输精管吻合术(RAVV)及机器人辅助下输精管-附睾管吻合术(RAVE)的可行性及手术技巧。方法:2013年5月和7月我院收治2例梗阻性无精子症患者,1例为输精管结扎患者,行RAVV术;1例为双侧附睾梗阻患者,行RAVE术。结果:2例手术均顺利完成,术后共随访9个月,2例患者均于术后6个月时在精液中发现精子,精子浓度分别为2.0×106/ml、66.0×106/ml。结论:RAVV及RAVE具有吻合确切、视野清楚等优点,可以选择作为治疗梗阻性无精子症的手术方式。     

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.     

显微外科技术下梗阻性无精子症术前诊断及治疗方式探讨

目的:探讨梗阻性无精子症(OA)在显微外科技术下术前诊断及其治疗策略。方法:57例不育症患者确诊为OA并初步怀疑为附睾梗阻,行阴囊探查术观察附睾及输精管梗阻情况;术中对确定为附睾梗阻并在附睾液中找到活精子的患者施行附睾输精管端侧吻合术,同时对探查至附睾头部才发现精子或术中发现双侧附睾以远输精管梗阻、缺如的患者留取精子冷冻以备卵细胞胞质内单精子注射(ICSI);术后随访其疗效。结果:53例(92.9%,53/57)行阴囊探查术确诊为附睾水平OA,47例(82.5%,47/57)完成显微手术,10例(17.5%,10/57)术中留取精子冷冻。22例(46.8%,22/47)于显微手术后1～18个月从精液中检出活动精子;5例(10.6%,5/47)配偶自然受孕成功,6例(18.5%,6/32)留取精子行ICSI后配偶怀孕。结论:在显微外科技术日益成熟下,OA的术前诊断应尽量采取无创的手段,在手术探查中进行梗阻部位的确诊及决定治疗方式。     

Vasoepididymostomy for Vasectomy Reversal: A Critical Assessment in the Era of Intracytoplasmic Sperm Injection

Purpose

We compared vasoepididymostomy to microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection for treatment of epididymal obstruction secondary to vasectomy.

Materials and Methods

Results in patients who underwent vasoepididymostomy for vasectomy reversal at our institution were compared to those reported previously for microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection performed for obstructive azoospermia. The pregnancy rates, delivery rates, complications, cost per procedure and cost per delivery were compared. A cost per newborn analysis was performed using pregnancy and delivery rates, and reported cost estimates for the complications of assisted reproductive techniques.

Results

A total of 55 men underwent 58 vasoepididymostomies in an attempt to restore fertility after vasectomy. Median followup was 19 months (range 0 to 115). Median obstructive interval was 12 years. There were no major complications. The patency rate after 6 months was 85%. Of the couples 20 achieved 24 pregnancies and 16 had 17 live births. The pregnancy rate at 1 year was 44%. There were 4 miscarriages and there are 3 ongoing pregnancies. The live delivery rate was 36%. Assuming a 29% delivery rate for microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection, the cost per newborn was $51,024, compared to $31,099 for vasoepididymostomy.

Conclusions

Vasoepididymostomy is more successful and more cost-effective than microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection for vasectomy reversal. It does not expose the women to complications in the treatment of a male problem and it is indicated for treatment of epididymal obstruction secondary to vasectomy. Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection should be reserved for cases not amenable to surgical reconstruction.     

FERTILITY OUTCOME AFTER REPEAT VASOEPIDIDYMOSTOMY

PURPOSE: Historically, epididymal obstruction has been treated with surgical reconstruction. We determine whether it is worthwhile for patients to undergo repeat surgical reconstruction after failed vasoepididymostomy or whether they should be advised only to undergo sperm acquisition for assisted reproductive technique. MATERIALS AND METHODS: A total of 18 patients underwent repeat vasoepididymostomy performed by a single urologist (A. J. T.). Cases were divided based on the etiology of obstruction into groups 1--prior vasectomy (4), 2--congenital (7) and 3--inflammatory (7). Data were available regarding time of obstruction between initial and repeat vasoepididymostomy, quality of epididymal fluid, levels of anastomoses, semen analyses at least 12 months after surgery for all 18 men and pregnancy rates based on more than 18 months of followup in 12. RESULTS: Mean patient age at repeat vasoepididymostomy was 40.6 years (50.5, 36 and 39.4 years for groups 1, 2 and 3, respectively). Mean interval between vasectomy and initial vasoepididymostomy was 12.3 years (range 10 to 18). Mean interval between initial and repeat vasoepididymostomy was 19 months (range 12 to 41). Of the patients 10 underwent unilateral and 8 bilateral anastomoses, for a total of 26 repeat anastomoses. Overall patency rate was 66.7% (12 of 18) with sperm in the ejaculate in 75, 85 and 43% of patients in groups 1, 2 and 3, respectively. The patency rates according to the levels of the anastomosis were 66.7, 62.5 and 100% in the caput, corpus and cauda, respectively. Natural conception occurred in 3 of 12 couples (25%, 2 caput and 1 caudal anastomosis) during a mean followup of 23 months (range 13 to 34). All 3 cases had congenital obstruction. Pregnancy was achieved in 2 group 1 cases with cryopreserved sperm extracted at repeat vasoepididymostomy, and in 1 case each in groups 1 and 2 with microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection. CONCLUSIONS: After repeat vasoepididymostomy two-thirds of men have sperm in the semen. Natural conception occurred in 25% of patients (3 of 12) followed for more than 18 months. Inability to establish pregnancy in the remaining 7 of 9 patients with sperm in the semen with a followup longer than 18 months may be due to epididymal dysfunction or partial obstruction and subsequent poor sperm quality. Aspiration of motile sperm and cryopreservation were possible in 11 of 18 cases at repeat vasoepididymostomy and should be recommended in case azoospermia remains or occurs after surgery. It appears worthwhile to offer patients repeat vasoepididymostomy after a failed initial procedure.     

Treatment of azoospermic patient with genitourinary tuberculosis: a case report]

A case of azoospermia due to genitourinary tuberculosis is reported with discussion on the treatment of infertility in such a case. A 38-year-old man visited us complaining of 4-year sterility. We suspected obstructive azoospermia due to previous genitourinary tuberculosis because of his treatment history, calcifications in the seminal vesicles and nodules in the right epididymis. After microsurgical epididymal sperm aspiration (MESA) was performed twice without success, we extracted sperm from his testis (testicular sperm extraction, TESE) and fertilized his wife's egg by intracytoplasmic sperm injection.     

Prognostic factors in the surgical treatment of azoospermia

Surgery for male obstructive infertility is not always successful. A number of clinical and operative findings, not previously reported, may influence the outcome. We have studied 182 patients with azoospermia who underwent vasoepididymostomy. The pre-operative and operative findings which adversely affected the function of the anastomosis were identified. The presence of spermatozoa in the semen sample was taken to mean a successful anastomosis. Abnormal testicular histology was an adverse pre-operative finding. Adverse operative findings included non-canalisation of the epididymal tubules and hypoplasia of the epididymis; both factors were associated with a high failure rate (almost 100%). The anastomosis was a failure in 78% of the patients when no fluid was seen on sectioning the epididymis. In the absence of adverse findings the success rate of vasoepididymostomy was 59%. Pre-operative testicular biopsy, together with careful observation and recording of findings before and during surgery, are recommended to avoid needless exploration and anastomosis.     

Clinical observation of loupe-assisted intussusception vasoepididymostomy in the treatment of obstructive azoospermia (analysis of 49 case reports)

To evaluate the clinical outcomes of loupe-assisted intussusception vasoepididymostomy (VE) in the treatment of epididymal obstructive azoospermia (EOA), we retrospectively analyzed data from 49 patients with EOA who underwent two-suture longitudinal intussusception vasoepididymostomy (LIVE) between 2000 and 2007. The data included the surgical method, postoperative motile sperm count per ejaculation, percentage of progressive motile sperm and patency and pregnancy outcomes. There were a total of 49 men undergoing scrotal exploration, and epididymal obstruction was found in all cases. Bilateral or unilateral anastomoses were performed in 40 and 6 men, respectively. The postoperative courses of 42 patients were followed up for more than 6 months, and the courses of 38 patients were followed up for more than 1 year. The overall patency and pregnancy rates were 71.4% and 26.3%, respectively. Moreover, progressive motile sperm was more frequently present in those patients who had undergone anastomosis at cauda than at corpus or caput. Pregnancy was achieved only in those patients who had undergone anastomosis at least on one side of the cauda epididymis. We think that the loupe-assisted method, with a lower overall cost and a simplified surgical procedure, can achieve satisfactory patency outcomes and pregnancy results. Data from this paper also suggest that paternity outcomes occur more frequently after anastomoses at cauda than at corpus or caput.     

CFTR gene mutations and male infertility

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are a relatively frequent cause of male infertility. Depending on their molecular consequences, CFTR mutations may either result in typical cystic fibrosis (CF), one of the most common autosomal recessive disorders, which is characterized by chronic lung disease, pancreatic exocrine insufficiency, an increase in the concentration of sweat electrolytes and male infertility, due to obstructive azoospermia, or in atypical (often monosymptomatic) forms of CF such as congenital absence of the vas deferens (bi- or unilateral), bilateral ejaculatory duct obstruction or bilateral obstructions within the epididymides. All males with idiopathic obstructive azoospermia bear an increased risk for CF offspring. Couples requesting microsurgical epididymal sperm aspiration and in vitro fertilization, e.g. intracytoplasmic sperm injection, should be offered genetic counselling and molecular genetic analysis of the CFTR gene, if male infertility due to obstructive azoospermia is the underlying cause.     

Microsurgical vasoepididymostomy to corpus epididymidis in treatment of inflammatory obstructive azoospermia

A unilateral microsurgical vasoepididymostomy utilizing 35 mm of epididymis was performed in a patient with postinflammatory epididymal obstruction. Success was verified with multiple semen analyses, the hamster egg penetration test, and a pregnancy. These results demonstrate that surgical bypass of inflammatory tubal obstruction in the distal epididymis can result in the return of normal epididymal function and fertility.     

Outcomes for vasovasostomy with bilateral intravasal azoospermia

We conducted an evaluation of outcomes for microsurgical vasectomy reversal in which sperm are absent from the vas fluid in order to determine a threshold obstructive interval when vasoepididymostomy (VE) may be indicated. Vasectomy reversal was performed for 32 patients with intravasal azoospermia: 25 received bilateral vasovasostomy (VV), 1 had a bilateral VV, 5 underwent VV/VE, and 1 had bilateral VE. Overall, the patency rate was 50% (14 of 28). Five pregnancies (20%) and 3 live births (12%) occurred in 25 patients with sufficient follow-up. One pregnancy was electively terminated and the other is ongoing, for an ongoing or delivered rate of 16%. The patency rate for VV (either bilateral or unilateral) was 55% (12 of 22). Median obstructive interval was 7 years in patent and 15 years in nonpatent cases, respectively, (P =.0027). Sperm were not observed after VV in any case n which the obstructive interval was greater than 11 years. If VV was limited to obstructive intervals of 11 years or less, then the patency rate was 80% (12 of 15) and the pregnancy rate was 38% (5 of 13). The patency rate for bilateral VV was 67% (8 of 12) if clear fluid was observed on at least one side. We conclude that VE is not required in every case of intravasal azoospermia, but it could improve success rates in this setting. Based on our experience, VE may be indicated for intravasal azoospermia if the obstructive interval is more than 11 years.     

显微镜下输精管附睾吻合术治疗梗阻性无精子症的初步效果

目的 探讨显微镜下输精管附睾吻合术的技术及应用价值. 方法梗阻性无精子症患者98例,平均年龄31(20～43)岁,平均梗阻时间4年.术前至少2次精液常规检查未见精子,性激素水平正常,睾丸活检证实睾丸生精功能正常.经阴囊探查发现附睾发育异常22例,输精管梗阻18例,附睾体或尾部梗阻58例.对58例附睾体尾部梗阻患者行显微镜下输精管附睾吻合术.术后3个月复查精液常规,精子密度＞1×104个/ml证实为精道复通,随访至配偶怀孕. 结果58例患者术后失访8例.50例随访3～29个月,其中精液中可见精子36例,精f密度(4×104)～(2×108)个/ml,精子活力2%～70%.4例随访12个月仍无精子,建议辅助生殖.10例无精子者继续随访至少12个月.配偶自然受孕14例.术后总体复通率72%(36例),自然受孕率28%(14例),平均受孕时间为6.6(4.0～10.0)个月. 结论显微镜卜输精管附睾吻合术治疗部分梗阻性无精子患者,可提高复通率.