Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele

BACKGROUND: To evaluate the improvement in semen quality and pregnancy rate after internal spermatic vein (ISV) embolization in men with nonobstructive azoospermia virtual azoospermia, or extremely severe oligoteratoasthenoazoospermia (OTA). METHODS: A prospective cohort of 101 azoospermic or severe oligoteratoasthenospermic men of mean (+/-SD) age 34.1+/-7.7 years who underwent ISV between September 1998 and June 2003 were evaluated for semen characteristics, endocrinology profile, and conception rate. RESULTS: Significant improvement was noted in mean sperm concentration, motility, and morphology in 83 men (82%). Mean sperm concentration increased from 0.22+/-0.30 x 10(6)/ml total sperm in the ejaculate to 9.28+/-1.2 x 10(6)/ml after embolization (P < 0.001); mean sperm motility rose from 8.78+/-1.59 to 29.56+/-2.0% (P < 0.001), and mean sperm morphology rose from 3.79+/-0.74 to 13.72+/-1.37% (P < 0.005). Pregnancy was achieved in 34 cases (34%), 20 (20%) unassisted and 14 (14%) assisted. CONCLUSIONS: Based on our findings, the following statements can be made: (i) Varicocele may cause any variation of severity in OTA, including azoospermia. (ii) Since male fertility is preserved with only one testis, OTA, azoospermia or virtual azoospermia represent bilateral testicular dysfunction. (iii) Treatment of bilateral varicocele may reverse testicular dysfunction and improve spermatognesis and testosterone production in men with extremely severe OTA and induce sperm production in men with azoospermia and virtual azoospermia. (iv) If azoospermia is not too long-standing, the treatment of varicocele may significantly improve spermatogenesis and renew sperm production. (v) Adequate treatment may spare in > 50% of azoospermic patients the need for testicular sperm extraction as preparation for ICSI. (vi) Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele (bilateral) is an effective medical adjunct for the IVF units prior to the treatment. We recommend that infertile men with azoospermia or virtual azoospermia or extremely severe OTA be evaluated for varicocele, with special attention to its bilateral nature.     

Ultrasonic texture and volume of testicles in infertile men

Ultrasound scanning of the testes and surgical biopsy were performedin 95 infertile men to evaluate the use of ultrasound In maleinfertility. Ultrasonic testicular volume was calculated usingthree measurements and the formula of an ellipsoid, and theultrasonic texture was evaluated and given a score from 1 to5, indicating increasing degrees of irregularity. The medianscore was 3 (range 1–5), which was higher than previouslyfound in nonnal men (median score 2; range 1–5; P <0.0001). The ultrasonic texture score was lower in testes witha uniform pattern of 100% spermatogenic tubules compared withthe rest, both for the right (P < 0.001) and for the left(P < 0.0005) testis. Texture score was correlated with thenumber of obliterated tubules for both testes (P <0.001).The mean ultrasonic testicular volume of the right testis was10.30 ml, and that of the left 10.26 ml. Both were smaller comparedwith the findings in normal men (P <0.0001). Ultrasonic testicularvolume was negatively correlated with texture score (P <0.001). A positive correlation between ultrasonic volume andsperm count was seen (P < 0.001). Sperm count was negativelycorrelated with texture score if calculated together with datafrom 119 men from the general population (P < 0.001). Thestudy shows that ultrasonic volume and texture are valuableparameters in the evaluation of infertile men.     

Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele

BACKGROUND: Varicoceles are associated with venous flux that may cause increased heat and interstitial pressure within the testes, but these effects are variable. Some men with varicocele have infertility, but others do not. We question whether other factors contribute to the infertility, and whether these other factors could be identified by specific molecular/genetic markers. Can such markers predict the outcome of varicocele repair? Can these markers be demonstrated bilaterally in unilateral left varicocele? METHODS: Limited bilateral testes biopsies were obtained by ultrasonically guided percutaneous aspiration at the time of varicocelectomy. In each specimen, cadmium levels were determined by atomic absorption and the percentage apoptosis within the seminiferous tubules was quantified. RESULTS: The percentage of apoptotic nuclei and cadmium levels were high in some men with varicocele. There was a concordance of these values in both testes despite the presence of left-sided varicocele only. These values were inversely related to an increase in sperm concentration after varicocelectomy. CONCLUSIONS: Cadmium, a metal ion inducer of apoptosis, may contribute to this form of male infertility. Apoptosis may deplete the sperm concentration among men with varicocele and infertility. Pre-operative measurements of apoptosis and cadmium content may predict the outcome of varicocele repair.     

腹腔镜精索静脉高位结扎术治疗亚临床型精索静脉曲张45例报告

目的探讨经腹腔镜精索静脉高位结扎术治疗亚临床型精索静脉曲张的疗效及安全性。方法回顾分析我院45例行腹腔镜精索静脉高位结扎术患者的临床资料。结果45例手术均获成功,平均手术时间35min,基本无出血,平均住院5d。随访3～6个月,无复发。结论腹腔镜下精索静脉高位结扎术具有视野清楚、创伤小、并发症少等优点,对治疗亚临床型精索静脉曲张具有显著临床价值。     

Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men

Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.     

Andrology: Clinical and biological characteristics of infertile men with a history of cryptorchidism

Out of 85 fertile and 1014 infertile men, two (2.4%) and 95(9.4%) respectively had a history of cryptorchidism. Thus cryptorchidismappears to be a risk factor for fertility since this differencewas significant. Further comparisons showed that the volumeof a former cryptorchid testis was smaller than the contralateralnormally descended one and that sperm output/concentration wasmore impaired in bilateral than in unilateral cryptorchidism.A retractile testis, defined as a testis reported by the patientto be spontaneously and regularly, i.e. at least once a week,ascending up into a supra-scrotal position, was more frequentin infertile men with a history of cryptorchidism than in fertilemen. Retractility was more frequent on the cryptorchid side,and was found more frequently after hormonal than after surgicaltreatment. Independently of all epidemiological and clinicalparameters studied, retractility was associated with a lowersperm output. Among the infertile men with a history of cryptorchidism,45% had an abnormally high scrotal temperature. This abnormaltemperature represented a pejorative risk factor for fertilityin this group, since it was associated with a more severelyimpaired spermatogenesis and a higher incidence of primary infertilitythan in infertile men with a history of cryptorchidism but normalscrotal temperatures.     

Andrology: Effect of growth hormone administration on circulating levels of luteinizing hormone, follicle stimulating hormone and testosterone in normal healthy men

A new area of growth hormone (GH) therapy in adults is the treatmentof infertility. The aim of this study was to evaluate the effectsof pharmacological GH administration on the secretion of pituitaryand gonadal hormones in normal men. Eight healthy men, 23–32years of age (mean 28.1 years), with a normal body mass indexwere studied in a double-blind, placebo-controlled crossoverdesign. All participants had a normal semen analysis beforeentering the study. Each participant was treated with placeboand GH (12/IU/day, Norditropin; Novo Nordisk, Denmark) duringtwo different 14-day periods, separated by a 6 week washoutperiod. Administration of GH for 14 days resulted in a significantincrease in serum insulin-like growth factor I (IGF-I; P <0.01) but no changes occurred in IGF-I values during placebotreatment. The concentrations of follicle stimulating hormoneand luteinizing hormone displayed no change during the two periodsand did not differ between the GH treatment period and the placeboperiod. The concentration of testosterone was unchanged duringthe placebo/GH periods and there was no difference between theGH treatment period and the placebo period. We conclude thatGH treatment for 14 days in normal healthy men does not affectgonadotrophin or testosterone patterns.     

Significance of serum inhibin B concentration for evaluating improvement in spermatogenesis after varicocelectomy

BACKGROUND: The study aim was to clarify the relationship of serum inhibin B concentrations to recovery of spermatogenic function after varicocelectomy, both as a predictor of improvement in the seminogram and as a means of monitoring hormonal function after surgery. METHODS: Fifty-two varicocele patients, including five with normal sperm concentrations, were studied. Changes in the seminogram, serum hormone concentrations and serum inhibin B were evaluated in the 47 oligozoospermic patients after surgery. Preoperative inhibin B concentrations correlated significantly with serum concentrations of FSH (r = 0.598, P < 0.0001) and testosterone (r = 0.380, P < 0.02). Inhibin B concentrations also correlated significantly with sperm concentration (r = 0.351, P < 0.02) and total testicular volume (r = 0.578, P < 0.0001). No significant correlation was seen between inhibin B and the Johnsen score. Preoperative concentrations of inhibin B were higher in patients who increased their sperm concentration after surgery (responders) than in those without improved concentrations (non-responders). No significant difference was observed between pre- and postoperative inhibin B concentrations in responders or non-responders. However, 15 of 25 (60%) patients with increased inhibin B showed improvement of the seminogram, while only five of 22 (23%) patients with no change or a decrease in inhibin B had any improvement (P < 0.05). CONCLUSIONS: Preoperative serum inhibin B concentration could not reliably predict a response to varicocelectomy. However, a change in serum inhibin B concentration after varicocelectomy might be helpful to evaluate the improvement of testicular function after varicocelectomy.     

Serum luteinzing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal fofficle stimulating hormone serum concentrations

The purpose of the study was to evaluate pulsatile luteinizinghormone (L release and intratesticular concentrations of testosteroneand oestradlol in infertile men, to determine if alterationsin gonadotrophin secretion are associated with changes in thetesticular concentrations of steroids. Patients with idiopathicoligo/azoospermia were divided into a high follicle stimulatinghormone (FSH) group (n=5) and a normal FSH group (n = 6). Bloodsamples were taken every 15 mm for 6 h to determine LH, FSH,testosterone, oestradiol, sex hormone binding globulin, bioactiveLH and bioavailable testosterone. The patients underwent a bilateraltesticular biopsy for histological assessment and to determinetestosterone and oestradiol concentrations. Serum measure mentswere compared with those of seven fertile men. The high FSHgroup had a higher concentration of serum UI and oestradiolthan normal men (P < 0.01) and showed a lower frequency ofLII pulses than the normal FSH group and control men (P <0.01). Intratesticular oestradiol was higher in the high FSHgroup (P < 0.001), with a lower testosterone/oestradlol ratio(P < 0.01). Patients showed a negative correlation betweenthe serum testosterone/LH ratio and FSH (r = -–0.75; P< 0.01) and a positive correlation between the testicularoestradiol concentration and serum FSH (r=0.86; P<0.01).The histopathological examination only showed a smaller tubediameter in the high FSll group (P < 0.05). These data seemto indicate that a higher intratesticular concentration of oestradiolwith a lower testosterone/oestradiol ratio in the high FSH groupcould have a deleterious effect on spermatogenesis.     

睾丸静脉与腹壁浅静脉分流治疗小儿精索静脉曲张的应用解剖

目的：为临床行睾丸静脉分流术治疗小儿精索静脉曲张症提供应用解剖学资料。方法：在３４侧小儿标本上，解剖观测了睾丸静脉、腹壁浅静脉的起始、位置、外径及分离长度。结果：腹壁浅静脉由脐下浅静脉汇成，以腹股沟为标志线，静脉在距前正中线３．５±０．８ｃｍ处，位于浅筋膜内几乎垂直下行注入大隐静脉，分离长度６．０±１．７ｃｍ，中１／３外径２．０±０．３ｍｍ。结论：腹壁浅静脉是治疗小儿精索静脉曲张症较为理想的分流血管。     

The peritubular myoid cells in the testes from men with varicocele: an ultrastructural, immunohistochemical and quantitative study

Ultrastructural and some immunophenotypic features of the peritubular myoid cells of testes from normal men and from men with varicocele were studied. The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In normal testes only type a and b tubules were found, whereas the testes from men with varicocele showed type b-e tubules. Myoid cells in tubule types a and b showed slender cytoplasmic projections with abundant, parallel arranged microfilament bundles and electron-dense bodies. In c tubules, the myoid cells showed the same ultrastructure. The myoid cells of tubules with advanced (type d) or complete (type e) sclerosis showed irregularly outlined nuclei, scant microfilament bundles and absence of electron-dense bodies. Immunostaining of myoid cells with anti-actin antibodies was intense in types a-c tubules and scant in types d and e. Immunostaining with anti-desmin antibodies was intense in tubules types a-d, but the immunoreactive cells in types c and d tubules were irregularly shaped and distributed and were scanty in tubule type e. Immunostaining with anti-vimentin antibodies was weak in types a-c tubules and intense in types d and e tubules. Quantitative studies revealed that, with the progression of sclerosis, the numbers of both actin- and desmin-immunoreactive cells per cross-sectioned tubule, and the surface area occupied by the immunostained portion of these cells, decreases while the number of vimentin-immunoreactive cells and their immunostained surface area increases.     

Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men

A light microscopical study on a total of 812 consecutive testicular biopsies from 555 infertile men revealed intratubular changes in germ cells compatible with a carcinoma in situ pattern in six oligospermic patients (I.I%); the changes were found in both testes in two of these men. Four of the six patients developed an invasive germ cell tumour within follow-up period of 1.3 to 4.5 years. The results confirm the malignant nature of these intratubular atypical germ cells. It is concluded that testicular biopsy may be useful for early detection and cure of germ cell carcinoma in patients at risk, i.e. patients with cryptorchidism, infertile men or patients with previous cancer of one testis.     

Response of serum inhibin B and pro-alphaC levels to gonadotrophic stimulation in normal men before and after steroidal contraceptive treatment

BACKGROUND: Testicular regulation of inhibin B may be influenced by the germ cell complement. METHODS: We examined the effects of gonadotrophin stimulation on serum inhibin B and pro-alphaC in 25 normal men at (i) control (stimulation test 1), (ii) after spermatogenic suppression induced by testosterone plus progestin treatment (stimulation test 2), and (iii) during spermatogenic recovery induced by FSH and/or hCG treatment (stimulation test 3). For each test, subjects received a single injection of 1200 IU FSH or 5000 IU hCG or both. RESULTS: Inhibin B and pro-alphaC fell with spermatogenic suppression (75 and 51% of pre-treatment baseline respectively, P < 0.05). Inhibin B response to FSH (130-144%) was similar in controls and after germ cell suppression. Pro-alphaC response after germ cell suppression compared with control was significantly increased (P < 0.05) with both FSH (210-229% versus 140-185%) and hCG (254-261% versus 145%). All treatments partially restored spermatogenesis with no clear relationship apparent between inhibin B and sperm count. CONCLUSIONS: We conclude that: (i) serum inhibin B and pro-alphaC are only partially gonadotrophin dependent, (ii) spermatogenic suppression does not modify inhibin B response to FSH but enhances pro-alphaC response to both FSH and hCG, and (iii) inhibin B is a poor marker of spermatogenesis in this model of gonadotrophic manipulation in normal men.     

Impaired spermatogenesis in men with congenital absence of the vas deferens

It is generally assumed that men with congenital bilateral absence of the vas deferens (CBAVD) have azoospermia because of obstruction and that sperm production is normal. This study examines spermatogenesis in men with CBAVD to assess the validity of this assumption. We identified all men with CBAVD who had undergone either a diagnostic or therapeutic fertility procedure. Procedures included diagnostic biopsy, testis fine needle aspiration (FNA) mapping, microscopic epididymal sperm aspiration (MESA), and testis sperm extraction (TESE). Among 33 CBAVD men, 18 underwent testis biopsy, 27 had MESA/TESE, and 10 had FNA mapping. On evaluation of these procedures, normal spermatogenesis was present in 29 men. Four men (12%) demonstrated impaired spermatogenesis. One patient had FNA testis cytology consistent with late maturation arrest, another demonstrated hypospermatogenesis on biopsy and low sperm yield by MESA, and two patients had pure Sertoli cell only histology on biopsy. Aetiologies for impaired spermatogenesis included varicocele and underlying genetic abnormalities. Although patients with CBAVD are assumed to have normal spermatogenesis and infertility due simply to obstruction, the potential for concomitant defects in sperm production exists. A clinical suspicion of testis failure should prompt further diagnostic evaluation of spermatogenesis prior to sperm retrieval. In addition, genetic counselling should be offered and testing for genetic lesions, including cystic fibrosis gene mutations and/or variants, Y chromosome microdeletions, and karyotype abnormalities, should be considered.     

Beta-endorphin concentration in the femoral and spermatic venous blood of males affected by varicocele.

Several studies in the rat indicate that opioid peptides produced in the testicular interstitial compartment can affect events in the tubular compartment. For example, it is thought that some specific functions of Sertoli cells, such as androgen-binding protein production are decreased by a paracrine mechanism. In this study ACTH beta-endorphin and cortisol were measured in the femoral and spermatic venous blood drawn from 18 patients affected by varicocele during catheterization for venous occlusion. The results showed the absence of a significant secretory gradient of beta-endorphin in the human testis and also demonstrated that this opioid is circulating at picomolar concentrations within human testis under stress conditions.     

Abnormalities for chromosomes 13 and 21 detected in spermatozoa from infertile men

Sperm samples from infertile men with oligozoospermia or teratozoospermiawere studied by multicolour fluorescence in-situ hybridization(FISH) using DNA probes for chromosomes 13 and 21. A total of90 809 sperm nuclei from nine infertile men and 182 799 spermnuclei from 18 control donors were analysed. There was a highlysignificant increase in the frequency of spermatozoa disomicfor chromosome 13 in infertile patients (0.28%) compared tocontrol donors (0.13%) (two-tailed Z statistic P <0.0001and for chromosome 21 (0.48% in infertile men versus 0.37% incontrols, P <0.0001). Also there was a significantly increasedfrequency of diploid spermatozoa in infertile men (0.85%) comparedto control donors (0.66%) (P <0.0001). Our previous studieson these same infertile patients demonstrated increased frequenciesof sperm disomy for chromosomes 1 and XY. This suggests thatinfertile men, who are prime candidates for intracytoplasmicsperm injection, may be at a very small increased risk of aneuploidoffspring.     

Facilitators and obstacles to sperm banking in young men receiving gonadotoxic chemotherapy for cancer: the perspective of survivors and health care professionals

BACKGROUND: Testicular cancer and Hodgkin's disease are among the most common malignancies to affect young men of reproductive age. Although both are associated with high rates of infertility, sperm banking (SB) remains underutilized by both diagnostic groups. Reasons for this remain elusive. METHODS: This study used a qualitative design. In-depth interviews were conducted with 20 cancer survivors and 18 health care professionals (HCPs) to examine their perspectives on factors that facilitate or hinder SB. Interview data were analysed using a mixed approach and a three-step process of data reduction, data display and conclusion drawing and verification. RESULTS: Eight factors were identified as having an impact on SB, and findings suggest that effective promotion of SB involves adequate communication around the severity and personal risk for infertility, assessing the importance of patients place on having children, emphasizing the benefits of SB and addressing possible obstacles such as cost, misperceptions or cultural and other factors. In addition, the communicator should be perceived as appealing. CONCLUSIONS: These results are conceptually consistent with both the Health Belief Model and the Elaboration Likelihood Model of health promotion and are useful in informing HCPs on how to better promote SB.     

A simple,low cost and non-invasive method for screening Y-chromosome microdeletions in infertile men

BACKGROUND: Recent investigations emphasized a high prevalence of Y-chromosome microdeletions in men having severely impaired spermatogenesis. Screening of these men is recommended prior to assisted reproduction techniques. METHODS: The aim of this study was to define a reliable and efficient method to detect Y-chromosome deletions in infertile men. At first the feasibility of using a cytobrush to collect buccal cells as a source of DNA was tested. Then, a multiplex PCR in accordance with European recommendations (European Andrology Academia: EAA) was compared with a commercial kit. The test population consisted of 18 infertile male patients (with a known Y-deletion). Both buccal and blood cells were used for DNA extraction. A specific DNA extraction protocol was carried out on the buccal cells. RESULTS: Between 4-10 micro g of DNA were retrieved per brush, allowing for several PCR attempts. The commercial kit failed to detect an AZFa deletion. Furthermore, markers sY130, sY133 and sY153, included in the kit, are not reliable. Both false negative and false positive results were generated by the commercial kit. CONCLUSION: A multiplex PCR performed pursuant to EAA recommendations is proposed. When the testing is conducted with DNA extracted from buccal cells, this protocol is simple, accurate and affordable.