Is there a specific abnormality of sperm morphology in men with varicoceles?

With the use of a case-control design, we have studied seminal cytology in 53 infertile men with large left varicoceles to determine whether they had a specific morphologic pattern. An equal number of infertile controls without varicoceles were matched for characteristics such as left testicular size, serum follicle-stimulating hormone levels, and sperm concentration to ensure similar degrees of testicular dysfunction. No significant difference in the morphologic patterns was observed, especially in the hallmarks of the "stress pattern": increased percentages of spermatozoa with tapering heads (1.8 +/- 2.6:1.9 +/- 4.0) and immature forms (8.1 +/- 5.4:6.4 +/- 2.9) in the varicocele and control groups, respectively. Assessment of morphologic characteristics was associated with wide errors (approximately 20% to 80%) among technicians working in the same laboratory. There does not appear to be a characteristic morphologic stress pattern in infertile men with large left varicoceles.     

Semen profile, testicular volume, and hormonal levels in infertile patients with varicoceles compared with fertile men with and without varicoceles

OBJECTIVE: To assess semen analysis, testicular volume, and hormone levels in fertile and infertile patients with varicoceles and fertile men without varicoceles. DESIGN: Retrospective study. SETTING: Academic medical center. PATIENT(S): Patients were divided into three groups: fertile men with varicoceles (n = 79), infertile men with varicoceles (n = 71), and fertile men without varicoceles (n = 217). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of LH, FSH, and total T and testicular volume in fertile and infertile men with varicoceles and fertile controls without varicoceles. RESULT(S): LH (IU/L) and T (ng/dl) levels were not statistically different across the three groups. FSH levels were significantly higher in infertile men with varicoceles (7.8 +/- 7.6 IU/L) than in the fertile men with varicoceles (3.5 +/- 2.1 IU/L) or in fertile men without varicoceles (3.5 +/- 1.9 IU/L). The right testicle was smaller in infertile patients with varicoceles (18.7 +/- 8.3 cm(3)) than in fertile men with varicoceles (25.2 +/- 13 cm(3)) or in fertile men without varicoceles (24.9 +/- 10.7 cm(3)). In addition, the left testicle was smaller in infertile men with varioceles (17.6 +/- 8.9 cm(3)) than in fertile men with varicoceles (21.6 +/- 7.8 cm(3)) or in fertile men without varicoceles (23.4 +/- 8.3 cm(3)). Sperm concentration was lower in infertile men with varicoceles (33.7 +/- 23.3 x 10(6)/mL) than in fertile men with varicoceles (101.8 +/- 76.6 x 10(6)/mL) or in fertile men without varicoceles (111.8 +/- 74.2 x 10(6)/mL). In addition, sperm motility was lower in infertile men with varicoceles (37.2% +/- 23.9%) than in fertile men with varicoceles (53.9% +/- 17.4%) or fertile men without varicoceles (58.9% +/- 15.8%). CONCLUSION(S): Infertile patients with varicoceles have higher levels of FSH, smaller testes, and lower sperm concentration and motility compared with controls with or without varicoceles. No statistical differences were seen in the variables evaluated among the fertile men with incidental varicoceles detected at physical examination and those without varicoceles.     

Association of scrotal hyperthermia with impaired spermatogenesis in infertile men

Scrotal temperatures, testicular volumes, and sperm characteristics were studied in 150 infertile, nonazoospermic men and in 37 fertile men, used as a control group. The mean scrotal temperature values of the infertile men were significantly greater than those observed in the fertile men (+0.4 degrees C for the right; +0.5 degrees C for the left). In the infertile men, it was found that the higher the scrotal temperature, the more alterated the sperm characteristics. The only clinical element that seemed to be linked to the existence of scrotal hyperthermia in the infertile men was testicular hypotrophy. Although the scrotal temperatures of the infertile men with varicocele were significantly higher than those of the fertile men, they did not significantly differ from those of the infertile men without varicocele. No other specific pathologic factor, infectious or surgical urogenital history was found to be responsible for the scrotal hyperthermia observed in the infertile men.     

The gonadotropin response of men with varicoceles to a four-hour infusion of gonadotropin-releasing hormone

The serum gonadotropin, testosterone, and estradiol responses to a 4-hour intravenous infusion of gonadotropin-releasing hormone (GnRH) were studied in four groups of men: severely oligospermic men with varicoceles and sperm densities less than 1 X 10(7)/ml, men with varicoceles and sperm densities between 1.1 X 10(7) and 3 X 10(7)/ml, men with varicoceles and sperm densities greater than 3 X 10(7)/ml, and men of normal fertility. Each group had similar preinfusion luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels. Both the severely oligospermic men and the men with sperm densities between 1.1 X 10(7)/ml and 3 X 10(7)/ml had excessive gonadotropin responses to the GnRH infusion. The gonadotropin responses of the men with sperm densities greater than 3 X 10(7)/ml were not different from normal. These results demonstrate that men with varicoceles and sperm densities less than 3 X 10(7)/ml have an altered integrity of their hypothalamic-pituitary-testicular axes, which can be demonstrated by their responses to GnRH.     

Predictive indicators of successful varicocele repair in men with infertility

OBJECTIVE: We sought predictive indicators of functionally successful repair in 168 infertile Japanese males who underwent high ligation of a varicocele via a retroperitoneal approach. METHODS: Possible indicators evaluated included age at marriage, duration of infertility, testicular volume, varicocele grade, seminal analysis findings, and serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone. All patients had palpable or visible unilateral left varicoceles. Success in conception was evaluated in all subjects 1 year after varicocele repair. RESULTS: No associations were observed between outcome and mean age at marriage, infertility duration, varicocele grade, seminal volume, or serum PRL and testosterone concentrations, but testicular volume, sperm count, percentage of motile sperm, and serum FSH and LH concentrations were significantly associated with outcome. Multiple regression analysis of dependence of outcome revealed testicular volume and serum FSH concentrations to be independent predictors. CONCLUSIONS: Varicocele repair is likely to accomplish fertility in patients with a combined testicular volume of at least 30 mL or serum FSH concentrations lower than 11.7 mIU/mL.     

Hormonal parameters in incidental varicoceles and those causing infertility

The gonadotropin responses to a 4-hour infusion of gonadotropin-releasing hormone (GnRH), the prolactin (PRL) responses to a bolus injection of thyrotropin-releasing hormone (TRH), and seminal plasma dihydrotestosterone (DHT) levels were assessed before and 6 to 12 months after varicocelectomy was performed in 56 infertile men with varicoceles and sperm densities less than 30 X 10(6)/ml. The men were divided into four groups, determined by their sperm densities and hormonal parameters. Groups I (18 men) and II (12 men) had sperm densities less than 10 X 10(6)/ml, and groups III (16 men) and IV (10 men) had sperm densities of 11 to 30 X 10(6)/ml. The men from groups I and III had excessive preoperative gonadotropin and PRL responses, and lower-than-normal seminal plasma DHT levels. The men in groups II and IV had normal hormonal values. After operation, 12 of the men from group I and 11 from group II had improvements in seminal and hormonal parameters. The other men in these two groups and all of the men in groups II and IV had no changes in seminal and hormonal parameters after operation. This study indicates that an assessment of these hormonal parameters may be useful in predicting which men with varicoceles are likely to have an improvement in sperm density after varicocele repair.     

An examination of blood steroid and gonadotropin concentrations in relation to fertility status and testicular function in men

Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17 beta-estradiol (E2) have been measured in men complaining of infertility in comparison with men of proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm or by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between the groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm count grouping but were significantly less than those found for the infertile men with sperm. Azoospermic patients with high testicular scores had FSH levels indistinguishable from those of the fertile men. The results are discussed in terms of testicular abnormalities and on the interrelationship between the hormones examined.     

What is the incidence of varicocele in a fertile population?

One hundred men with proven fertility who presented for vasectomy consultation were examined for testicular size and presence of a varicocele, including examination with the Doppler stethoscope for the presence of subclinical varicocele. A diagnosis of varicocele was established in 61%. In 17 patients, the varicocele was evident clinically, whereas in 44 patients it was subclinical (8 bilateral). There was a discrepancy in testicular size in 22 patients, but this group included 8 men without varicoceles and 7 with subclinical varicoceles. It is apparent that varicoceles, especially subclinical varicoceles, are an extremely common finding, even in a group of fertile men. The results suggest that subclinical varicoceles have no role in male infertility.     

Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele

OBJECTIVE: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with varicocele. DESIGN: Prospective controlled study. SETTING: Male infertility clinic, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. PATIENT(S): Thirty-one infertility patients and 16 fertile controls. INTERVENTION(S): Sperm DNA fragmentation index (DFI), levels of seminal reactive oxygen species (ROS), and total antioxidant capacity (TAC) were assessed using the sperm chromatin structure assay, chemiluminescence assay, and enhanced chemiluminescence assay, respectively. ROS-TAC score was calculated as a measure of OS. MAIN OUTCOME MEASURE(S): Median (interquartile range) DFI and ROS-TAC scores. RESULT(S): Sixteen of the 31 patients had left varicocele [grade I (n = 3), grade II (n = 10), and grade III(n = 3)], and the remaining 15 had normal genital examination. Patients with varicoceles had significantly higher percent DFI than controls (25%, range: 20%-35%; vs. 15%, range: 10%-22%). Patients with varicoceles had significantly lower ROS-TAC scores (21, range: 9.5-31) than the infertile patients with normal genital examination (34, range: 28-42) or the controls (40.3, range: 38-44). CONCLUSION(S): Infertile men with varicoceles showed significantly increased spermatozoal DNA damage that appears to be related to high levels of OS in semen.     

Varicocele is associated with abnormal retention of cytoplasmic droplets by human spermatozoa

OBJECTIVE: To determine whether varicocele is associated with retention of sperm cytoplasmic droplets in infertile men. DESIGN: Retrospective study.Setting: University infertility clinic. PATIENT(S): Nonazoospermic men with idiopathic (n = 69) and varicocele-associated infertility (n = 73), and 20 fertile controls presenting for vasectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Standard semen parameters and percentage of spermatozoa with cytoplasmic droplets on Papanicolaou smears. RESULT(S): No statistically significant differences were found between the fertile and infertile groups with respect to semen volume. Fertile controls had significantly greater mean percent sperm motility and normal morphology than infertile men. The mean percentage of sperm with residual cytoplasm was statistically significantly different in all three groups. Infertile men with varicocele had the highest percentage of sperm with cytoplasmic droplets, the next highest level being in men with idiopathic infertility and the lowest level in fertile controls (11.7 +/- 1.0, 8.1 +/- 0.9 and 3.2 +/- 0.4%, respectively, P<.0001). CONCLUSION(S): Our data show that idiopathic and even moreso, varicocele-related male infertility are conditions associated with impaired disposal of residual sperm cytoplasm by the testis and/or epididymis. These data provide a possible mechanism for the observed semen abnormalities and reduced fertility potential associated with varicocele and idiopathic male infertility.     

Insemination data on men with varicoceles.

OBJECTIVE: To determine possible benefits of sperm processing and intrauterine insemination (IUI) for a group of men with a varicocele history who had not achieved a pregnancy by natural coitus (mean duration of infertility 42.2 months). DESIGN: A retrospective study including infertile men with varicoceles who were classified by their semen analyses and sperm penetration assays (SPAs). SETTING: Private practice of infertility. PATIENTS: Seventy-one infertile couples. The husbands had a varicocele history and were grouped into four clinical categories (14 untreated, 5 medical treatment, 34 varicocelectomies, and 18 varicocelectomies plus medical treatment). The wives were studied or treated before IUI. INTERVENTIONS: Varicocelectomies were performed on the males when indicated. Female studies included laparoscopies as indicated intrauterine insemination with Tomcat catheter (Sherwood Medical, St. Louis, MO) was performed in all cases. MAIN OUTCOME MEASURES: Overall pregnancy rates (PRs) and fecundity rates with sperm processing and IUI. RESULTS: Six pregnancies occurred with 66 cycles of sperm processing and IUI among 28 men with normal SPAs (PR 21%, fecundity rate = 0.09). In contrast, there were no pregnancies with 121 cycles among 43 varicocele patients with abnormal SPA results or with low values for all three semen parameters. CONCLUSIONS: Sperm processing and IUI may be beneficial for selected patients with varicoceles who had not achieved a pregnancy by coitus.     

The role of varicocele repair in nonobstructive azoospermia must be evaluated with controlled trials rather than observational studies

Certainly, varicoceles can have a substantive effect on sperm production in infertile males. In addition, varicocele repair may optimize sperm production. However, additional studies and evaluation of the role of varicocele repair in men with this condition (nonobstructive azoospermia) are warranted.     

Hyperprolactinemic male infertility.

Serum prolactin was studied in 25 fertile and 127 infertile men. The latter included 91 oligospermic, 27 azoospermic, and 9 hypogonadotropic hypogonadal men. The mean prolactin level in all three groups of infertile men was significantly above that of the fertile group. There was no correlation among serum levels of follicle-stimulating hormone, luteinizing hormone, sperm count, and serum prolactin values. Hyperprolactinemia was found in five patients (two oligospermic, one azoospermic, and two hypogonadotropic hypogonadal men). Bromocriptine, 2.5 mg twice daily, suppressed hyperprolactinemia. In one man with hyperprolactinemic oligospermia, treatment with bromocriptine yielded significant improvement in sperm count (to normal values).     

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.     

Deoxyribonucleic acid polymerase activity in the testes of infertile men with varicocele

Activities of deoxyribonucleic acid (DNA) polymerase alpha, beta, and gamma were measured in extracts of testicular biopsy specimen obtained from 37 cases of male infertility with left varicocele and compared with those of 6 normal controls. It was observed that levels of DNA polymerase alpha, beta, and gamma were significantly lower in infertile men than normal controls on both sides of testes. Among three DNA polymerases, the level of DNA polymerase beta activity well correlated with the histological findings (Johnsen's score), i.e., the extent of differentiation of germinal cells. DNA polymerase beta activity appeared to be the lowest in the patients whose sperm density was less than 5 X 10(6)/ml. On the other hand, no correlation was apparent between levels of DNA polymerases and other clinical parameters, e.g., testicular volume, sperm motility, grade of varicocele, and serum hormone levels. These results suggest that the combined decrease in the DNA polymerase activities may be one of the factors that have deleterious effects on spermatogenesis in varicocele patients.     

Hormonal parameters of men with varicoceles before and after varicocelectomy

The gonadotropin responses to a 4-hour infusion of gonadotropin-releasing hormone (GnRH) and seminal plasma dihydrotestosterone (DHT) and testosterone levels were assessed before and 6 to 12 months after varicocelectomy in 22 men with varicoceles. Twelve men were severely oligozoospermic (sperm densities less than 10 X 10(6)/ml), whereas 10 men had sperm densities between 11 and 30 X 10(6)/ml. Each man had excessive gonadotropin responses to GnRH and lower than normal seminal plasma DHT levels preoperatively. Eight of the 12 severely oligozoospermic men and 6 of the other 10 men had postoperative improvements in sperm density. These men (responders) had normalization of gonadotropin response and seminal plasma DHT levels. The nonresponders had identical hormonal parameters before and after surgery. These results indicate that the pantesticular defect in hormonal synthesis and spermatogenesis, seen in some men with varicoceles, can be reversible.     

Interrelationships of cigarette smoking, testicular varicoceles, and seminal fluid indexes

Data on cigarette smoking, testicular varicoceles, seminal fluid indexes, and oligospermia were examined in 160 young men without known disease and in 94 husbands in infertile couples. The combination of smoking and testicular varicoceles is strongly related to the incidence of oligospermia, defined as sperm count less than or equal to 20 X 10(6)/ml, in each sample. Smokers with testicular varicoceles, in each sample, had a disproportionately high incidence of oligospermia. In the combined sample of 254 men, the smokers with testicular varicoceles had an incidence of oligospermia approximately ten times greater than that in nonsmokers with testicular varicoceles and approximately five times greater than that in men who smoked but were without testicular varicoceles. This relationship of cigarette smoking and testicular varicoceles to oligospermia has not been previously reported. The pathophysiologic basis of the interaction between smoking and varicoceles was theorized to be due to an increased secretion of catecholamines from the adrenal medulla, induced by cigarette smoking. The elevated catecholamine concentrations in the renal vein would then reach the testes via retrograde flow down the internal spermatic vein in men with testicular varicoceles, resulting in seminiferous tubule damage.     

Clinical and subclinical varicocele: a useful distinction?

Objective: The purpose of the study was to establish whether it is useful to make a distinction between clinical and subclinical varicoceles with a view to deciding for treatment or not. Therefore, we compared our results of treatment of clinical vs. subclinical varicoceles. Study design: The changes of semen parameters and the occurrence of pregnancies in 40 infertile men treated for clinical varicocele were compared with those in 46 infertile men treated for subclinical varicocele. The significance of individual semen changes was analysed by paired t-test in both groups and the results of both groups were compared by analysis of covariance. The pregnancy rates were calculated and the life table curves of pregnancy of both groups were compared. Results: There were statistically significant increments in sperm density, motility and morphology both after treatment of clinical and subclinical varicoceles, and these increments did not differ significantly between both groups. The cumulative pregnancy rates after a mean follow-up period of 6.6 years amounted to 42.5% for clinical varicoceles and to 39.1% for subclinical varicoceles and the life table curves of pregnancy ran a rather similar course in both groups. Conclusion: We conclude that there is no reason to emphasize the palpatory findings in infertile men with varicocele.     

Testicular hormone concentration in men with varicoceles: immediate effects of varicocelectomy

As part of an investigation of the role of gonadal steroid concentrations and testicular function, testosterone (T), estradiol (E2) and dehydroepiandrosterone sulfate (DHEA-S) were measured in bilateral testicular biopsies from infertile men with varicoceles. The biopsies were performed randomly either immediately before or 1 hour after varicocelectomy in an effort to detect acute changes in testicular hormone concentrations. No significant differences were noted between these two groups nor was there consistent evidence of disturbed in vivo Leydig cell function. A wide range of testicular hormone concentrations was found in these biopsies, which did not correlate well with morphologic findings. This suggests that many different pathophysiologic conditions may exist in association with the presence of a varicocele.     

Measurement of human testicular consistency by tonometry

A tonometer was used for objective assessment of testicular consistency in a group of 83 men. Testicular measurements in three dimensions were also obtained using calipers. The testicular tonometry value was found to be significantly correlated with the clinical impression of testicular consistency and with testicular size. The testicular tonometry value for the right testicle was significantly larger than the tonometry value for the left testicle in all men except those with azoospermia. The difference in tonometry values between the right and left testicles was most significant in the group of men with left varicocele. The men with varicoceles also had left testicles which were significantly smaller than the paired right testicle in two of three dimensions. In the group with varicocele there was a significant positive correlation between the tonometry value and sperm concentration in the semen. In men with no history of varicocele there was a significant positive correlation between the tonometry value and the percentage of oval sperm.