Assessment of immunological mechanism in infertility of the rat after experimental testicular torsion

Summary A necrotic torted testis left in the scrotum affects the contralateral testis, resulting in depressed fertility. It was suggested that testicular torsion provoked a systemic response of an immunologic nature. In order to prove this theory, 56 rats were operated. Ten had a sham operation, in 17 a testis was torted and excised after 24 h, and in 29 a testis was torted and excised after 24 h, and in 29 a testis was torted but left in situ till the sacrifice. Antisperm-antibodies were not found in any phase of the experiment in the sham group. Using indirect immunofluorescence, antisperm-antibodies were found in the sera of 8/17 rats of the orchiectomy group and in 24/29 of the detorted group. In the direct immunofluorescence study, all the antibodies were localized in the tail of the spermatozoid. The antisperm-antibodies dissappeared after 3 to 6 months.     

Spermatogenesis and hormonal status after orchiectomy for cancer and before supplementary treatment

Low numbers of sperm cells (less than 20 million/ml), low motility indices (less than 40) and/or a high percentage of abnormal sperm cells (greater than 80%) were found in about half of 60 patients with testicular cancer after orchiectomy and before further treatment. There was no correlation between these findings and the patient's age, tumor histology or clinical stage. Relatively low serum testosterone values in the majority of patients and increased serum LH and FSH in some patients also indicated disturbed gonadal function at the time of fertility evaluation. The clinical significance of cryopreservation of sperm cells is therefore questionable in the majority of these patients. The demonstrated hypofertility after orchiectomy and before further treatment for testicular cancer may, however, be reversible at least in some patients. In patients with testicular cancer every attempt should be made to preserve the patients' fertility during the necessary diagnostic and therapeutic procedures, without a reduction in the high cure rate which is obtained by modern multimodal treatment of testicular cancer.     

Antispermatozoal autoantibodies and genital infection

The aim of this study was to evaluate why high levels of antispermatozoa autoantibodies (SPZAA) in seminal fluid represent a particularly detrimental factor in male fertility. We studied a population of 219 patients consulting us on conjugal sterility associated with an initial asthenospermia. We looked in each case for the presence of SPZAA at the surface of spermatozoa in the seminal fluid and in the serum. We found 31 patients positive for surface SPZAA, 26 of whom had urogenital infections. We also demonstrated statistically significant correlations between high levels of SPZAA in seminal fluid and both a reduction in ejaculate volume and a tendency to oligospermia. A similar correlation was found between the reduction in ejaculate volume and oligospermia. These results suggest that urogenital infection is at present the main cause of SPZAA production, that testicular damage is frequently associated with apparently isolated glandular damage, and above all that a high level of SPZAA in seminal fluid has a more detrimental effect on male fertility due to more severe genital (glandular and testicular) damage.     

Testicular sperm extraction in azoospermic patients with gonadal germ cell tumors prior to chemotherapy--a new therapy option

BACKGROUND: In view of the high cure rates in patients with testicular germ cell tumors (TGCT), increasing clinical importance is attached to protection of fertility. Long-term infertility due to cytostatic therapy may be expected in more than 50% of the patients at a cumulative dose of cisplatin > 0.6 g/m2. The standard procedure for fertility protection in cancer patients includes cryopreservation of ejaculated spermatozoa. Considering that some patients have tumor-induced azoospermia, we examined the usefulness of testicular sperm extraction before therapy. METHOD: A survey of the literature served as a basis for investigating biological and clinical aspects of the impact of chemotherapy on male fertility. A study of our patient population also enabled us to explore the option of extracting sperm from the contralateral healthy testis prior to treatment in 14 azoospermic patients with testicular germ cell tumors. RESULTS: We were able to successfully recover haploid germ cells in 6/14 testicular biopsies from azoospermic patients with testicular germ cell cancer prior to treatment. Maturation arrest was found in 3/14 cases and Sertoli-cell-only syndrome in the rest. None of the patients had secondary healing or a treatment delay because of the testicular biopsy. CONCLUSION: Since the post-therapeutic fertility status is difficult to predict in cancer patients, we think that TESE should be regarded as a general option prior to cancer treatment and offered to azoospermic cancer patients. New guidelines should be established in this connection.     

Serum follicle stimulating hormone--predictor of cancer in the remaining testis in patients with unilateral testicular cancer

In 10 of 13 patients with unilateral testicular cancer and subsequent invasive cancer or carcinoma in situ in the remaining testis, the follicle stimulating hormone (FSH) level was elevated after the first orchiectomy and before further treatment. In only 4 of 26 comparable control patients was the FSH level raised. This may be because elevated serum FSH often reflects disturbances in spermatogenesis and fertility, the latter being a known risk factor for testicular cancer. An elevated FSH level that occurs after orchiectomy for unilateral testicular cancer and before further treatment identifies patients at high risk of developing a tumour in the remaining testis.     

Testicular Trauma: Potential Impact on Reproductive Function

Purpose

The long-term effects of testicular trauma on reproductive function are unknown. In an effort to define the relationship between testicular injury and fertility in humans, we identified patients with a history of testicular trauma and assessed parameters commonly associated with fertility.

Materials and Methods

We reviewed 15 patients 23 to 59 years old who underwent immediate exploration after testicular trauma between 1972 and 1991. Of the patients 11 were contacted and 8 returned for prospective followup. Reproductive and sexual histories, physical examination, measurements of serum hormones and antisperm antibodies, semen analysis and scrotal ultrasound were done.

Results

Of the 8 patients 1 (13 percent) achieved and 7 (87 percent) did not attempt conception. Hormonal status was normal in all 8 patients. Six men had objective evidence of subfertility by semen analysis only, although none had severe oligospermia or asthenospermia and only 1 had severe teratospermia. Five of 9 traumatized testes were atrophic. Interestingly, only 1 patient had antisperm antibodies, the levels of which were probably low enough to be clinically insignificant.

Conclusions

There was definite evidence of subfertility as assessed by abnormal semen analyses and atrophic testes following testicular trauma. However, the subfertility did not appear to be immune mediated nor did the patients present with infertility. Since only 1 patient had severely compromised fertility according to semen analysis we conclude that early repair can help preserve hormonal function as well as fertility.     

Fertility considerations in nerve-sparing retroperitoneal lymph-node dissection

Summary Nerve-sparing retroperitoneal lymph-node dissection (RPLND) maintains the patient's ability to ejaculate postoperatively. However, since testicular cancer patients sometimes have diminished spermatogenesis, questions have been raised as to the advisability of nerve preservation relative to ultimate fertility. Fertility status was assessed in clinical stage A patients by two methods. These included standard semen analysis and a post-RPLND survey. The results show that approximately 75% of nonseminomatous testicular cancer patients who present in clinical stage A have fertility potential as based on semen analysis. Additionally, of those patients responding to the post-RPLND survey who had attempted pregnancy following RPLND, 76% reported attainment of pregnancy. Nerve-sparing RPLND maintains fertility potential in clinical stage I patients; furthermore, this fertility potential appears to be worth preserving as many patients will be capable of impregnating their partners.     

Can serum Inhibin B and FSH levels, testicular histology and volume predict the outcome of testicular sperm extraction in patients with non-obstructive azoospermia?

Introduction In our study, we evaluated the diagnostic accuracy of serum follicle stimulating hormone (FSH), Inhibin B, testicular volumes and distribution of testicular sperm extraction (TESE) outcome according to the histological diagnosis in men with non-obstructive azoospermia. Materials and methods Between February 2001 and April 2002, 66 men presenting with infertility of at least 1 year were found to have non-obstructive azoospermia. Serum FSH and Inhibin B levels, testicular volumes and pathological analysis were reviewed retrospectively using medical records of these patients. Results Of 66 patients, 52 were enrolled into the study and sperm extraction was successful in 31 of 52 patients (59.6%). There was no statistically significant difference between the patients who had successful and unsuccessful TESE in terms of mean serum Inhibin B, FSH levels and testicular volumes (P > 0.05). The area under ROC analysis for serum Inhibin, serum FSH and testicular volume was 0.557, 0.523 and 0.479, respectively. For Inhibin B, the best cut-off value for discriminating between successful and failed TESE at 90% sensitivity was 6.25 with a very low level of specificity (14%) and diagnostic accuracy that was 53.8. Conclusion Besides the controversies about the direct marker role of serum Inhibin B in determination of spermatogenesis, it does not seem to give a clue about the prediction of sperm presence before TESE. Because of the conflicting results in the literature, the potential role of serum Inhibin B as a marker for prediction of sperm presence in testis is yet to be determined.     

UNILATERAL TESTICULAR INJURY FROM EXTERNAL TRAUMA: EVALUATION OF SEMEN QUALITY AND ENDOCRINE PARAMETERS

Purpose

Because few studies have described the impact of unilateral testicular trauma on fertility parameters, we review the experience at the Ben Taub General Hospital during a 16-year period. Semen and endocrine profiles were analyzed to evaluate the influence on the outcomes of orchiectomy versus testicular salvage.

Materials and Methods

From 1979 to 1995, 67 patients were identified who sustained unilateral testicular trauma. Of these patients 12 were located and 10 agreed to be evaluated. Injuries included gunshot wounds, stab wounds and blunt trauma, and treatment consisted of unilateral orchiectomy or testicular repair. The study protocol comprised a history and physical examination, routine semen analysis, determination of semen and serum antisperm antibody titers (Immunobead* assay) and a modified gonadotropin stimulation test. Results were compared with a group of semen donors with proved fertility.Biorad, Seattle, Washington.

Results

In the 7 patients who underwent unilateral orchiectomy mean sperm density was normal but significantly decreased compared with that of the fertile controls (81.6 versus 132.6 × 10⁶/ml., p = 0.04). Sperm motility was not significantly affected. Baseline follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and post-stimulation LH were significantly increased in this group compared with controls (p <0.01). In the group that underwent testicular repair sperm density, motility, and baseline and post-stimulation FSH and LH levels were not significantly different from controls. In all patients in both groups testosterone levels and contralateral testicular size were normal. Only 1 patient in the repair group had an elevated serum and semen antisperm titer.

Conclusions

While the testicular salvage group had no significant seminal or endocrine abnormality, the orchiectomy group had a significant decrease in sperm density and elevation of baseline FSH and LH. These preliminary data suggest that testicular salvage is more protective of overall testicular function than orchiectomy.     

Repeated testicular infarction in a patient with sickle cell disease: a possible mechanism for testicular failure

We report a case of repeated testicular infarction in a 39-year-old man with sickle cell disease. The patient presented with a 2-week history of testicular pain and was found clinically and sonographically to have a testicular mass, suspicious for a testicular tumor. The pathologic examination of the orchiectomy specimen revealed multiple infarcts, showing temporal variation ranging from acute (several days old) to recent (2 to 3 weeks old) to remote. This is the fifth case of segmental testicular infarction reported in patients with sickle cell disease/trait. We propose repeated testicular infarction as a probable mechanism of testicular failure and impaired fertility in patients with sickle cell disease.     

Klinefelter syndrome and fertility—Impact of X‐chromosomal inheritance on spermatogenesis

With the use of testicular sperm extraction (TESE), spermatozoa can be retrieved in about 30%‐50% of men with Klinefelter syndrome (KS). The reason for the absence or presence of spermatozoa in half of the men with KS remains unknown. Therefore, the search for an objective marker for a positive prediction in finding spermatozoa is of significant clinical value to avoid unnecessary testicular biopsies in males with (mostly) low testicular volume and impaired testosterone. The objective of this study was to determine whether paternal or maternal inheritance of the additional X‐chromosome can predict the absence or presence of spermatogenesis in men with KS. Men with KS who have had a testicular biopsy for diagnostic fertility workup TESE were eligible for inclusion. Buccal swabs from nine KS patients and parents (trios) were taken to compare X‐chromosomal inheritance to determine the parental origin of both X‐chromosomes in the males with KS. Spermatozoa were found in TESE biopsies 8 of 35 (23%) patients after performing a unilateral or bilateral TESE. Different levels of spermatogenesis (from the only presence of spermatogonia, up to maturation arrest or hypospermatogenesis) appeared to be present in 19 of 35 (54%) men, meaning that the presence of spermatogenesis not always yields mature spermatozoa. From the nine KS‐trios that were genetically analysed for X‐chromosomal inheritance origin, no evidence of a correlation between the maternal or paternal origin of the additional X‐chromosome and the presence of spermatogenesis was found. In conclusion, the maternal or paternal origin of the additional X‐chromosome in men with KS does not predict the presence or absence of spermatogenesis.     

Flow cytometric DNA analysis demonstrates contralateral testicular deterioration in experimental unilateral testicular torsion of prepubertal rats

Summary. It has been postulated that unilateral testicular torsion causes damage to the contralateral testis and reduces fertility. However, in animal studies such an effect has not been fully proven by histopathologic examination or other conventional assays of spermatogenesis. We investigated the effect of unilateral testicular torsion on contralateral spermatogenesis in prepubertal rats using quantitative flow cytometric DNA analysis. Male rats were divided into three groups which underwent sham-operation, simple hemiorchiectomy or unilateral testicular torsion. Five weeks after these operations, fertility and spermatogenesis by flow cytometry were evaluated. No significant differences were observed in body weight, contralateral testicular weight or serum testosterone concentration among the three experimental groups. In the torsion group, mean seminiferous tubular diameter, number of foetuses, fertility rate and percentage of haploid cells were all significantly decreased compared to the other two groups. These results suggest that unilateral testicular torsion causes damage to the contralateral testis and consequently can reduce the future fertility of prepubertal rats.     

Onco‐testicular sperm extraction: birth of a healthy baby after fertility preservation in synchronous bilateral testicular cancer and azoospermia

Testicular germ cell tumours (TGCT) represent 1%–1.5% of all male neoplasms, and they have the highest prevalence among men between 15 and 35 years old. Synchronous bilateral disease is a rare presentation, and the ratio of metachronous to synchronous bilateral disease is about 4 : 1. Several studies have suggested a correlation between male infertility and testicular cancer, with a 20‐fold increase in the incidence of testicular cancer in infertile patients compared with the general population. At the time of diagnosis, 50%–75% of patients with unilateral TGCT present with subfertility; almost 13% of the patients are azoospermic before treatment, and up to two‐thirds of patients become azoospermic following adjuvant cancer therapies. Therefore, fertility preservation should be considered in all oncological treatments. The only available option to preserve the reproductive potential in azoospermic patients with testicular cancer is to perform an onco‐testicular sperm extraction (onco‐TESE) before cancer treatment. In this paper, we describe a rare case of a patient with synchronous bilateral testicular cancer and azoospermia who was submitted to onco‐TESE, sperm cryopreservation, and which was followed by the delivery of a healthy baby after intracytoplasmic sperm injection (ICSI), emphasising the importance of fertility preservation in oncology patients.     

Cryptorchidism and infertility

Although the maldescended or dystopic testis is one of the most common congenital anomalies in man, proper treatment remains a subject of much discussion and confusion. Certainly, in light of the previously described findings, the future fertility of the patient with unilateral cryptorchidism, regardless of age of correction, should be a realistic concern. Hormonal treatment should be recognized as a good diagnostic test for defining the retractile testes and should not be considered therapy. The pediatrician or family practitioner should be encouraged to examine the scrotal contents thoroughly in the neonatal period and to document findings. Earlier surgical intervention may benefit these patients since a prolonged extrascrotal location may add further insult to an intrinsic abnormality in the dystopic gonad. The cryptorchid testis may be smaller and have decreased consistency with or without surgery and usually signals significant testicular pathology. Synthesis of androgens and serum concentrations of LH should not be affected; thus, secondary sex characteristics will appear normal. Basal levels of FSH are usually elevated but do not necessarily imply overwhelming testicular damage. Current evidence clearly shows a variable degree of primary intrinsic gonadal dysgenesis with a frequent impairment of fertility in the cryptorchid testis, regardless of the time of treatment. Early surgery may decrease the ultimate loss of testicular function superimposed on the congenital dystrophy, thus diminishing the ultimate loss of effective spermatogenesis.     

Newer ideas about fertility in patients with testicular cancer

Summary The outlook for fertility among patients who are treated for testicular cancer is one of guarded optimism. Although some of these men are subfertile before the onset of their disease, it is probable that the majority, although temporarily subfertile because of their tumors, have a potential for normal fertility. Lymphadenectomy probably can be performed effectively while preserving ejaculation in most patients. Likewise, the effects of platinum-based chemotherapy appear to be reversible in many patients, and there is hope that spermatogenesis can be protected during chemotherapy by endocrine manipulation. During the next decade, the preservation of fertility will become an increasingly important issue in the management of testicular cancer as investigators consolidate therapeutic gains.     

Future treatment strategies for cryptorchidism to improve spermatogenesis

Orchiopexy is one of the most frequently used surgical procedures for cryptorchidism and has been shown to have a beneficial effect on fertility. However, orchiopexy, especially for bilateral cryptorchidism, does not always guarantee subsequent fertility and paternity. Compared with a control group, paternity was significantly compromised in men with previous bilateral, but not unilateral cryptorchidism. Recent techniques of assisted reproductive technology, especially testicular sperm extraction with intracytoplasmic sperm injection (TESE-ICSI), have brought revolutionary changes in clinical therapy for infertiliy. If spermatozoa exists in testis of infertile men, logically there is a possibility of paternity. However, our study demonstrated that about 20% of pubertal boys who had had orchiopexy, were predicted to have lost their future paternity potential even if TESE-ICSI were conducted, because they were predicted to have no spermatozoa in the testis. To prevent or reverse the damage of spermatogenesis at prepuberty or puberty, we should not take a wait-and-see attitude but should consider a countermeasure for the pubertal boys who had had bilateral orchiopexy in childhood, especially when the serum follicle stimulating hormone level is elevated and testicular volume is lowered, before paternity is lost. In this review, we discuss the potential approaches including epidermal growth facter therapy, gene therapy and stem-cell therapy for cryptorchid patients in the future.     

Histology of testicular biopsies taken at operation for bilateral maldescended testes in relation to fertility in adulthood.

A total of 91 boys underwent bilateral orchiopexy with testicular biopsy. The percentage of tubular transverse sections containing spermatogonia, the fertility index (FI) and the number of spermatogonia per tubular transverse section (S/T) were measured and expressed as a percentage of the minimum normal value (FI% and S/T%, respectively). The maximum and mean of the 2 FI% and S/T% values were noted for each patient. At follow-up, testicular volume was measured in 73 men; 71 of these gave a blood sample for FSH and 67 provided specimens of semen for analysis. The maximum and the mean FI% and S/T% values of the patients were positively correlated to maximal sperm density and to volume of pair of testes and negatively correlated to serum FSH. It seems reasonable to use these histological parameters as prognostic indices of fertility potential. In adulthood only 11 patients had sperm density greater than or equal to 20 million/ml, 37 had normal serum FSH and 29 had bilateral testicular volume greater than or equal to 15 ml. Patients with both testes originally placed in the superficial inguinal pouch at surgical exploration had a higher maximal sperm density than the rest of the study group.     

Androgenic effect of Mondia whitei roots in male rats

Aim: To determine the effect of the aqueous extract of Mondia whitei (Periplocaceae) roots on testosterone production and fertility of male rats. Methods: Adult male Wistar rats were used. In the acute study, 20 rats were randomly divided into 5 groups of 4 animals each. Four treated groups were administered orally a single dose of Mondia whitei (400 mg/kg) and the controls received a similar amount of distilled water. One group of animals were sacrificed by cervical dislocation 1,2,4 and 6 h after treatment, respectively. The controls were sacrificed at 6 h. Testicular testosterone was determined by radioimmunoassay. In the chronic study, 28 rats were divided at random into 4 groups of 7 animals each: Groups 1, 2 and 3 were given orally the plant extract (400 mg·kg-1·day-1) for 2, 4 and 8 days, respectively. The animals of Groups 1 and 2 were sacrificed 24 hours after the last dosing. The controls (Group 4) received the same amount of distilled water for 8 days. The fertility was assessed only in Grou     

Orchidectomy alone versus orchidectomy plus radiotherapy in stage I nonseminomatous testicular cancer: a randomized study by the Danish Testicular Carcinoma Study Group

All Danish patients with stage I nonseminomatous testicular cancer diagnosed between December 1980 and January 1984 entered a randomized study comparing irradiation of retroperitoneal lymph nodes with surveillance only after orchidectomy. Twenty-four of the seventy-nine patients in the observation-only group have relapsed, three patients relapsing more than 2 years after orchidectomy. Ten of the seventy-three patients receiving irradiation have relapsed, all within 10 months after orchidectomy. The median time to relapse in both groups was 4.5 months. Irradiation prevented retroperitoneal relapses. Thirty-three of the relapsed patients were rendered disease free with chemotherapy, and one is still being treated. Four deaths have occurred, all unrelated to testicular cancer or antineoplastic treatment. Absence of embryonal carcinoma and presence of teratocarcinoma correlated with improved relapse-free survival. Patients with increased serum concentrations of tumour markers before orchidectomy had an increased risk of relapse. Surveillance-only is a reasonable treatment strategy in clinical stage I nonseminomatous testicular cancer. Preferably control and treatment of relapses should take place in specialized centres.