[Treatment of oligospermia/asthenozoospermia patients by three different Chinese medical principles: a randomized control clinical study].

OBJECTIVE: To assess the efficacy and safety of three different Chinese medical principles in treating patients with male infertility (oligospermia/asthenozoospermia). METHODS: Totally 128 patients with male infertility were classified into 3 groups, i.e., Shen-essence deficiency syndrome, Pi-Shen deficiency syndrome, Shen-deficiency blood-stasis syndrome. They were assigned to the Chinese medical treatment group (96 cases) and the Western medical treatment group (32 cases) by stratified randomization in the ratio of 3: 1. Those in the Chinese medical treatment group were treated with Chinese drugs for Shen invigorating and blood activating, Shen invigorating and Pi supplementing, Shen-qi benefiting. Those in the Western medical treatment group were treated with Clomifene (at the daily dose of 25 mg per day, once daily). Three months consisted of one therapeutic course. The parameters of semen, the pregnancy rate, and adverse reactions were observed. RESULTS: Totally 24 patients dropped out in the two group, 17 in the Chinese medical treatment group (9 patients of Shen deficiency blood stasis syndrome, 5 of Shen-Pi deficiency syndrome, and 3 of Shen-essence deficiency syndrome) and 7 in the Western medical treatment group. Compared with before treatment, there was no statistical difference in the improvement of semen amount at 3 months after treatment between the two groups (P > 0.05). There was statistical difference in the improvement of semen density, class A semen, class A +B semen, and 1-h activity ratio (P < 0.05). The improvement was most obvious in Shen deficiency blood stasis syndrome, followed by Shen-Pi deficiency syndrome and Shen-essence deficiency syndrome. The improvement was the weakest in the Western medical treatment group. There was no statistical difference in the improvement of semen amount, semen density, class A semen, or 1-h activity ratio at 3 months after treatment between the two groups (P > 0.05). Best effect was obtained in improving class A + B semen quality in patients of Shen deficiency blood stasis syndrome, showing statistical difference when compared with the other two syndrome types and the Western medical treatment group (P < 0.05, P < 0.01). No obvious adverse reaction occurred in the two groups during the treatment course. CONCLUSION: Shen invigorating and blood activating method could improve the semen density and semen activities, and it was superior to other therapeutic methods.

"Oligozoospermia," "azoospermia," and other semen-analysis terminology: the need for better science.

The Greek-based terms used to describe semen-analysis abnormalities (e.g., "oligozoospermia" and "azoospermia") are unscientific, have overlapping definitions, and are often misinterpreted. The best course is to abandon these vague and difficult labels and simply report semen analyses quantitatively.

The use of Data Mining in the categorization of patients with Azoospermia.

OBJECTIVE: Data Mining is a relatively new field of Medical Informatics. The aim of this study was to compare Data Mining diagnosis with clinical diagnosis by applying a Data Miner (DM) to a clinical dataset of infertile men with azoospermia. DESIGN: One hundred and forty-seven azoospermic men were clinically classified into four groups: a) obstructive azoospermia (n=63), b) non-obstructive azoospermia (n=71), c) hypergonadotropic hypogonadism (n=2), and d) hypogonadotropic hypogonadism (n=11). The DM (IBM's DB2/Intelligent Miner for Data 6.1) was asked to reproduce a four-cluster model. RESULTS: DM formed four groups of patients: a) eugonadal men with normal testicular volume and normal FSH levels (n=86), b) eugonadal men with significantly reduced testicular volume (median 6.5 cm3) and very high FSH levels (n=29), c) eugonadal men with moderately reduced testicular volume (median 14.5 cm3) and raised FSH levels (n=20), and d) hypogonadal men (n=12). Overall DM concordance rate in hypogonadal men was 92%, in obstructive azoospermia 73%, and in non-obstructive azoospermia 69%. CONCLUSIONS: Data Mining produces clinically meaningful results but different from those of the clinical diagnosis. It is possible that the use of large sets of structured and formalised data and continuous evaluation of DM results will generate a useful methodology for the Clinician.

[The management of azoospermic patient]. / La actitud ante el paciente azoospérmico: la visión del urólogo.

OBJECTIVES: Since first pregnancy after ICSI was achieved in 1992, the treatment and prognosis of severe male factor, i.e azoospermia, has radically changed. The objective of this article is to review the issue from the urologist-andrologist point of view. METHODS: We perform a short revision of the two types of azoospermia and diagnostic tests, and show the algorithm used in our centre for the management of patients with azoospermia. We review the techniques for spermatozoid recovery and surgical treatment of obstructive azoospermia because the role of the urologist is maximum in these aspects. Genetic anomalies in azoospermic patients is one of the issues analyzed in more detail for being one of the most important and of maximum interest currently. RESULTS: Nearly 1% of pregnancies in developed countries are achieved by assisted reproduction techniques, and genetic anomalies among newborns from ICSI cycles have increased to 1.6%, three times normal population. Genetic anomalies are tenfold in azoospermic patients in comparison to general population. We analyze the importance of these studies in patients with secretory azoospermia. We review the most frequent genetic anomalies associated with azoospermia and diagnostic tests employed. Its importance is based on this diagnosis allowing genetic counselling and pre-implant or prenatal diagnosis with the aim of trying to minimize genetic anomalies and disease transmission to next generations. CONCLUSIONS: The diagnosis and treatment of azoospermia continues to be one of the most thrilling challenges in the field of infertility, with promising research lines such as in vitro spermatogenesis from stem cells and autotransplantation of criopreserved cells in patients undergoing radiotherapy and chemotherapy.

Cytogenetic and Y chromosome microdeletion screening of a random group of infertile males.

OBJECTIVE: To assess whether to perform routine cytogenetic and Y chromosome microdeletion screening on all infertile male patients. DESIGN: A cytogenetic and Y microdeletion study of a random group of infertile men. SETTING: University department. PATIENT(S): In total, 40 patients had azoospermia (21 nonidiopathic), 27 had severe oligozoospermia/oligoasthenozoospermia (

Predictive value of testicular histology in secretory azoospermic subgroups and clinical outcome after microinjection of fresh and frozen-thawed sperm and spermatids.

BACKGROUND: A retrospective study was carried out on 159 treatment cycles in 148 secretory azoospermic patients to determine whether histopathological secretory azoospermic subgroups were predictive for gamete retrieval, and to evaluate outcome of microinjection using fresh or frozen-thawed testicular sperm and spermatids. METHODS: Sperm and spermatids were recovered by open testicular biopsy and microinjected into oocytes. Fertilization and pregnancy rates were assessed. RESULTS: In hypoplasia, 97.7% of the 44 patients had late spermatids/sperm recovered. In maturation-arrest (MA; 47 patients), 31.9% had complete MA, and 68.1% incomplete MA due to a focus of early (36.2%) or late (31.9%) spermiogenesis. Gamete retrieval was achieved in 53.3, 41.2 and 93.3% of the cases respectively. In Sertoli cell-only syndrome (SCOS; 57 patients), 61.4% were complete SCOS, whereas incomplete SCOS cases showed one focus of MA (5.3%), or of early (29.8%) and late (3.5%) spermiogenesis. Only 29.8% of the patients had a successful gamete retrieval, 2.9% in complete and 77.3% in incomplete SCOS cases. In total, there were 87 ICSI, 39 elongated spermatid injection (ELSI) and 33 round spermatid injection (ROSI) treatment cycles, with mean values of fertilization rate of 71.4, 53.6 and 17%, and clinical pregnancy rates of 31.7, 26.3 and 0% respectively. CONCLUSIONS: Histopathological subgroups were positively correlated with successful gamete retrieval. No major outcome differences were observed between testicular sperm and elongated spermatids, either fresh or frozen-thawed. However, injection of intact round-spermatids showed very low rates of fertilization and no pregnancies.

Assisted conception in the azoospermic male.

The advent of intracytoplasmic sperm injection (ICSI) has offered new solutions for the management of patients with azoospermia. Surgical sperm recovery combined with ICSI has allowed many men with azoospermia to father their own biological children. Azoospermia can be classified as obstructive and non-obstructive, with investigations, management and success rates varying markedly between the two forms. In certain cases of obstructive azoospermia surgical reconstruction remains a viable option, whereas cases with congenital obstruction need to be screened for mutations of the cystic fibrosis gene. In most cases of obstruction sperm can be retrieved from the epididymis using percutaneous epididymal sperm aspiration (PESA). If PESA is unsuccessful, testicular sperm extraction (TESE) is successful in all cases. With non-obstructive azoospermia, the genetic basis has been investigated intensely. Screening for karyotypic abnormalities as well as Y microdeletions is recommended. Irrespective of the histological diagnosis, focal spermatogenesis can be observed in 40-50% of cases using multiple testicular biopsies.

Morphology of testicular spermatozoa obtained by testicular sperm extraction in obstructive and nonobstructive azoospermic men and its relation to fertilization success in the in vitro fertilization-intracytoplasmic sperm injection system.

The aim of the present study was to evaluate the morphology of testicular spermatozoa by 3 different determinants. Sperm cells were obtained and their morphology was evaluated from 27 testicular sperm extraction (TESE) operations, of which 20 men had nonobstructive azoospermia and 7 had obstructive azoospermia. In 17 cases, 2 biopsies were obtained from 2 different locations of the testis. Only mature spermatozoa presenting full-grown tail (tail dimension about 10-fold greater than the head dimension) were counted. Three characteristics of sperm morphology were evaluated: head dimensions, and acrosome and midpiece irregularities. The percentage of sperm cells with normal morphology (considering the 3 characteristics) in specimens from patients with obstructive and nonobstructive azoospermia were 47% +/- 4.6% and 29 +/- 1.8%, respectively (P < .01). The percentage of spermatozoa with normal head dimensions were 76% +/- 3.2% and 63% +/- 2.6% (P > .05), those with normal acrosome were 58% +/- 4.6% and 41% +/- 3.4% (P < .05), and those with normal midpiece were 74% +/- 4.1% and 67% +/- 1.6% (P > .05), in obstructive and nonobstructive azoospermia, respectively. No significant differences were observed in sperm morphology between different locations of the testis. Sperm morphological characteristics were not associated with fertilization rate in intracytoplasmic sperm injection (ICSI). Follicle-stimulation hormone and luteinizing hormone were inversely correlated with normal morphology of testicular spermatozoa (r = -0.49 and r = -0.47, respectively; P < .05). It can be concluded that a relatively high portion of testicular sperm are morphologically normal. The higher rate of normal spermatozoa in obstructive azoospermia compared with nonobstructive spermatozoa suggests that the factors leading to azoospermia may affect testicular sperm morphology. The morphological characteristics of testicular sperm do not affect fertilization rate in ICSI.

Beyond the clinical classification of azoospermia: opinion.

There is an ongoing debate regarding the appropriate classification of azoospermia. This manuscript reviews the rationale for the current classification of azoospermia and how to effect a change if there is a need to do so. The current classification of azoospermia into obstructive and non-obstructive is because azoospermia due to ejaculatory duct dysfunction and hypogonadotrophism are extremely rare. Though the use of clinical protocols (defective spermatogenesis, genital tract obstruction, ejaculatory duct dysfunction, hypogonadotrophism or pre-testicular, testicular and post-testicular) may be useful in selecting patients for appropriate treatment, no study has shown that they provide a better method of classification of azoospermia than the current approach. There is increasing evidence of a genetic basis of male infertility as well as the evidence that men's fertility potential may be classified genetically. Moreover, genetic disorders may be transmitted to the offspring and their presence in infertile couples may affect treatment outcome. It is therefore useful to explore a genetic classification of azoospermia.

Azoospermia: incidence, and biochemical evaluation of seminal plasma by the differential pH method.

BACKGROUND: Recent artificial reproductive technologies (ART) have enabled even azoospermic subjects to take part in "in vitro fertilization" programs. The aim of the present study was: a) to evaluate the incidence of azoospermic male partners of infertile couples; b) to determine whether biochemical evaluation of such azoospermic males can help to discriminate between obstructive and secretory azoospermia. METHODS: Semen samples (n. 28,339; period 1990-1997) were analyzed according to WHO guidelines. In addition, in 108 azoospermic subjects, fructose, citric acid and L-carnitine (taken respectively as markers of seminal vesicle, prostate and epididymal function) were assayed using a new, faster technique, the differential pH method. RESULTS: The incidence of azoospermic semen samples was 4.76%. The biochemical analyses were indicative diagnostically, especially with regard to obstructive azoospermia. However, in secretory azoospermia, biochemical analysis of seminal plasma did not offer particularly helpful indications, except in cases of hypogonadism. CONCLUSIONS: Azoospermia accounts for a relatively high number of cases and justifies detailed attention to the diagnostic and therapeutic approach. Biochemical analysis of the seminal markers is a valid support for differential diagnosis between secretory obstructive azoospermia. It can therefore help in the correct recruitment of such patients for ART programs.

Y chromosome microdeletions in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome.

The objective of this study was to elucidate the cause of the spermatogenic defect in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Genomic DNAs from 9 cases of Korean idiopathic azoospermia and 6 of Korean non-mosaic type of Klinefelter syndrome were used for the detection of Y chromosome microdeletions by polymerase chain reaction using 60 primers. Microdeletions of the Y chromosome were found in 1 of 9 (11.1%) patients with idiopathic azoospermia, whereas none was deleted in non-mosaic type of Klinefelter syndrome. This result suggests that Y chromosome microdeletions could be one of the etiologic factors in idiopathic azoospermia.

Y chromosome microdeletions in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome

The objective of this study was to elucidate the cause of the spermatogenic defect in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Genomic DNAs from 9 cases of Korean idiopathic azoospermia and 6 of Korean non-mosaic type of Klinefelter syndrome were used for the detection of Y chromosome microdeletions by polymerase chain reaction using 60 primers. Microdeletions of the Y chromosome were found in 1 of 9 (11.1%) patients with idiopathic azoospermia, whereas none was deleted in non-mosaic type of Klinefelter syndrome. This result suggests that Y chromosome microdeletions could be one of the etiologic factors in idiopathic azoospermia.

[Etiology and treatment of sterility due to azoospermia]. / Etiologie et traitement de la stérilité due à une azoospermie.

Azoospermia can be classified according to the serum level of FSH into obstructive (OA) or non-obstructive (NOA) azoospermia. It can also be due to a lack of gonadotrophins. In the latter case the administration of FSH and HCG can normalize the sperm production. In the other cases ICSI must be performed. In OA sperm can be retrieved using percutaneous epididymal aspiration or testicular fine needle aspiration in case of failure of vasovasostomy or epididymovasostomy. In NOA or spermatogenic arrest, focal spermatogenesis can be observed in 40 to 50% of cases using repeated testis biopsies, allowing to perform ICSI. Although the risk of malformation in children born after ICSI is not increased there is an increased risk to transmit genetic abnormalities in case of NOA (such as the rate of sex chromosome, or microdeletions of the Y chromosome) and in case of congenital OA (mutations of the cystic fibrosis gene).

[Are testes in oligo/azoospermia homogenous or heterogenous?].

We determined whether a single testicular specimen is sufficient to represent qualitatively the spermatogenic process within the testes of azoospermic or severely oligospermic infertile men. In 191 testes of azoospermic patients and in 26 of those with severe oligospermia, fine needle aspirations at 3 different sites of each testis were performed. Aspirated material from each puncture was stained and in each smear all spermatogenic cells, as well as Sertoli cells, were identified. Testes were classified according to the most mature spermatogenic cell type present, or the presence of only Sertoli cells. The homogeneity of the testicular spermatogenic process was then evaluated. There was an overall intratesticular difference between aspirates in 14.1% of azoospermic testes and in 26.9% of severely oligospermic testes with regard to the most mature spermatogenic cell type. When spermatozoa were the most mature cell type, they were detected in all of the 3 aspirates in 71.4% of the testes. In 18.4% or 10.2% of this group of testes they were retrieved in only 1 or 2 of the aspirates, respectively. In testes in which spermatids or spermatocytes were the most mature spermatogenic stage, these cell types were detected in all 3 aspirates in only 36.4% and 68.0%, respectively. In azoospermic patients with full testicular spermatogenesis, the likelihood of retrieving spermatozoa from the testes was 84.3%, 92.7% and 100% in 1, 2 and 3 specimens, respectively. The following conclusions were drawn: There is a wide range of testicular heterogeneity in azoospermia or very severe oligospermia for diagnosing the testicular spermatogenic pattern. In azoospermia, specimens from several testicular sites are required. It is strongly recommended that no assisted fertilization be offered to azoospermic patients unless prior evaluation of the spermatogenic pattern in the seminiferous tubules is determined.

[Management of testicular biopsies in secretory azoospermias]. / Stratégie des prélèvements testiculaires dans les azoospermies sécrétoires.

Management of testicular biopsies in non-obstructive azoospermia is unclear: there is non-factors that are predictive of eventual sperm presence or absence and there is no consensus neither for open testicular biopsy versus percutaneous testis biopsy nor for fresh testicular sperm extract ion and synchronous ICSI versus frozen samples for a later sample.

[Clinical elements for the diagnosis of secretory azoospermia]. / Eléments cliniques du diagnostic d'azoospermie sécrétoire.

Secretory azoospermia is defined by the existence of azoospermia, normal epididymis and vesicular markers and often high but sometimes low FSH levels. Study of the past history often reveals the cause of azoospermia, which is often toxic or a side effect of medication. Clinical investigation includes assessment of the genital organs in particular the volume of the testicles. The clinical investigation must always be accompanied by a general examination. When anamnesis and clinical examination are completed, secretory azoospermia will be classed in one of the following categories: high FSH azoospermia, law FSH azoospermia, normal FSH azoospermia.

Sperm motility and morphology as changing parameters linked to sperm count variations.

Variations in semen analyses of 177 males over a 1 year period were assessed. The average means of total counts, motility, morphology, total motile count and non-motile % were determined for 5 classes of patients ranging from azoospermic to normospermic. Positive relationships between a falling sperm count, a decrease in motility and total motile counts were seen. Also, increasingly, abnormal forms were found with lower sperm counts.

Biophysical and biochemical analysis of semen in infertile Nigerian males.

Biophysical analysis of semen was performed in fifty-eight Nigerian male partners of infertile marriages. Sperm count concentration was significantly higher (P < 0.001) in oligospermics compared to normospermics as expected. However, there was no significant difference in sperm volume or motility percentage between the normospermics and the oligospermics; of course, no sperms were seen in the azoospermics. Biochemical analyses of serum zinc, copper, magnesium, and manganese by atomic absorption spectrophotometry [8] were further correlated in fifty-two patients. There were no statistically significant differences observed in the serum levels of zinc, magnesium, and copper among the normospermics, oligospermics, and azoospermics. The normospermic infertile patients, however, exhibited higher serum manganese when compared with oligospermics and azoospermics (P < 0.001). This finding suggests a potential role for manganese in the evaluation of infertile males.

High implantation and pregnancy rates with testicular sperm extraction and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia.

Thirty-two infertile couples with obstructive and non-obstructive azoospermia were included in this study. Testicular sperm extraction (TESE) was performed in 16 obstructive azoospermic cases where microsurgical sperm aspiration (MESA) or percutaneous sperm aspiration (PESA) were impossible because of totally destroyed epididymis and 16 non-obstructive azoospermia cases with severe spermatogenetic defect where the testicles were the only source of sperm cells. A total of 288 oocytes was obtained from 32 females and 84% were injected. The fertilization rates (FR) with 2 pronuclei (PN) and cleavage rate were 50.8 and 68.2% respectively. A total of 15 pregnancies was achieved (53% per embryo transfer), nine from the obstructive and six from the non-obstructive group. Four pregnancies resulted in clinical abortion (26.6%). The ongoing pregnancy rate was 39.2% per embryo transfer (ET) and 34.3% per started cycle. A high implantation rate was also achieved (26.6% in non-obstructive and 30% in obstructive azoospermia group). Using testicular spermatozoa in combination with ICSI in both obstructive and non-obstructive azoospermic groups, high implantation and pregnancy rates can be achieved.