Littérature scientifique sur le sujet « Non-obstructive azoospermia, male infertility »

Over the past 20 years, there has been a clear trend to increase in the number of infertile men in Ukraine, their percentage reaches 50% in infertile couples. There is a significant percentage of male infertility caused by azoospermia – the lack of sperm in the ejaculate. In male infertility, azoospermia is found in 10–15% of patients, among other forms of pathospermia. Given the ambiguity of ideas about the etiology, pathogenesis and treatment and diagnostic approaches for various types of infertility, it remains important to clarify the relationship of urogenital infections with the regulatory systems of cells, including the state of the pro- and antioxidant system and the search for additional markers. 119 patients with various forms of azoospermia were examined. All patients underwent the following studies: spermogram, infectious screening, inhibin B, lipid peroxidation, activity of enzymes of the glutathione antioxidant system in sperm plasma and blood serum. Infectious screening included analysis of urethral secretions, bacteriological examination of sperm or prostate secretion, assessment of the species and quantitative composition of the microflora of the male urogenital tract. According to the results of spermogram and other diagnostic methods, a non-obstructive form of azoospermia was detected in 69 patients. In obstructive azoospermia, ejaculate as such was absent. It is suggested that inhibin B may be an important medical diagnostic test for azoospermia. As a result of the conducted researches the importance of determining the concentration of inhibin B as a marker of azoospermia was demonstrated and a negative correlation of moderate strength between the content of inhibin B and testosterone level in the plasma of men with non-obstructive azoospermia was revealed. It was found that Ureaplasma pervum and Ureaplasma urealyticum infect the male genitourinary system to the greatest extent among a number of microorganisms, both in non-obstructive and obstructive forms of azoospermia. Enterococcus faecalis is more pronounced in the sperm fluid in the non-obstructive form of azoospermia and prostate secreton in the obstructive form of azoospermia. In the non-obstructive form of azoospermia in the seminal plasma and serum, the processes of lipid peroxidation intensify, the concentration of reduced glutathione decreases and the activities of the enzymes of the glutathione antioxidant system (glutathione peroxidase and glutathione transferase) decrease. It can be considered that an important diagnostic test for the nonobstructive form of azoospermia is the ratio of reduced glutathione to oxidized glutathione in sperm plasma.

Objective. The aim of this study was to evaluate the prevalence of most common mutations and intron 8 5T (IVS8-5T) polymorphism of CFTR gene in Italian: a) azoospermic males; b) non azoospermic subjects, male partners of infertile couples enrolled in assisted reproductive technology (ART) programs. Material and methods. We studied 242 subjects attending our Andrology Unit (44 azoospermic subjects and 198 non azoospermic subjects, male partners of infertile couples enrolled in ART programs). Semen analysis, molecular analysis for CFTR gene mutations and genomic variant of IVS8-5T polymorphic tract, karyotype and chromosome Y microdeletions, hormonal profile (LH, FSH, Testosterone) and seminal biochemical markers (fructose, citric acid and L-carnitine) were carried out. Results. The prevalence of the common CFTR mutations and/or the IVS8-5T polymorphism was 12.9% (4/31 cases) in secretory azoospermia, while in obstructive azoospermia was 84.6% (11/13 cases; in these, the most frequent mutations were the F508del, R117H and W1282X). Regarding the non azoospermic subjects, the prevalence of the CFTR and/or the IVS8-5T polymorphism was 11.1% (11/99 cases) in severe dyspermia, 8.1% (6/74 cases) in moderate dyspermia and finally 4.0% (1/25 cases) in normospermic subjects. Conclusions. This study confirms the highly significant prevalence of CFTR mutations in males with bilateral absence of the vas deferens or ejaculatory ducts obstruction compared with subjects with secretory azoospermia. Moreover, the significant prevalence of mutations in severely dyspermic subjects may suggest the possible involvement of CFTR even in the spermatogenic process. This could explain the unsatisfactory recovery of sperm from testicular fine needle aspiration in patients affected by genital tract blockage.

Approximately 30–40% of couples seeking fertility treatments have male factor infertility. Their dysfunctions include azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. Those with azoospermia represent about 25% of the total, and of these about 30% have an obstructive process while the remaining have either primary or secondary testicular failure. In the obstructive azoospermia group, 25% of males have congenital bilateral absence of the vas deferens (CBAVD).

Background: Azoospermia is a highly upcoming subject in the last few decades. In the past, use of donor sperm was the only option providing a realistic chance of conception for couples affected by azoospermia. Introduction of sperm retrieval techniques and assisted reproductive technologies, especially intracytoplasmic sperm injection (ICSI), has provided these men a chance to father their genetically own child and changed the management approach significantly. The aim of this study was to compare the outcome of intracytoplasmic sperm injection (ICSI) of surgically retrieve sperms between couples with infertility due to male non-obstructive azoospermia (NOA) and obstructive azoospermia (OA).Methods: It was a retrospective observational study and data analysis was conducted at Centre for Infertility and Assisted Reproduction (CIMAR), Edappal, Kerala, India from January 2018 to December 2021. The selection of cases was based on detailed history, physical examination, husband’s semen analysis confirmed twice and hormone profile. During a period of four years, 754 azoospermic patients were diagnosed at our centre. In this study, female age <35 years considered as the inclusion criteria as female age plays a pivotal role for IVF/ICSI outcome, while patient in whom voluntary donor sperm used, patients in whom sperm retrieval failed, female age >35 years and female associated with any pathology which can alter the treatment outcome e.g., endometriosis, severe adenomyosis, diminished ovarian reserve, fibroid uterus were excluded from the study groups. On the basis of serum FSH, serum testosterone and testicular size and considering inclusion and exclusion criteria, patients were subdivided into two group as: group A (n=75) included patients with non-obstructive azoospermia and group B (n=75) included patients with obstructive azoospermia, underwent ICSI.Results: Clinical pregnancy rate, fertilization and implantation rate were found to be higher in OA cases in comparison to those of NOA cases. Grade A embryo formation rate and miscarriage rate showed no significant difference.Conclusions: As the cause of azoospermia is different in both the groups, the chances of achieving a successful outcome (fertilization rate, embryo formation rate, and clinical pregnancy rate) after ICSI are negatively affected by the type of azoospermia and are reduced in men with NOA in comparison to patients with OA.

The infertility affects about 15% of couples and male factors being responsible about 40-50%. In male infertility, genetic abnormalities of Y chromosome play crucial role in spermatogenesis defect. Y chromosome q arm having Azoospermia factor region (AZFa, AZFb, and AZFc) are most important for spermatogenesis. Here, we investigated the frequencies of Y-chromosome microdeletions using three sets of multiplex PCR in idiopathic cases of azoospermia. We studied a total of 110 infertile male with non-obstructive azoospermia subjects & 50 fertile control subjects. All DNA samples were used for Y chromosome microdeletions analysis by using 11 STS markers in three different multiplex PCR of AZF regions. Out of 110 infertile azoospermic males, 14 (12.72%) infertile males showed partial deletion of AZF regions using three sets of multiplex PCR group. In the AZF microdeletions of infertile males, individually AZFc region was the most deletions sites (10%) followed by AZFb (6.36%) and AZFa (1.81%). The sites and sizes of microdeletions differ in all infertile azoospermic males who showed at least two or more STS markers microdeletions. The frequency of Y chromosome microdeletions in our azoospermic infertile males is 12.72%. We conclude that Y chromosome microdeletions frequency in azoospermic infertile males is higher than other infertile group due to severe impairment in spermatogenesis. Multiplex PCR screening of microdeletions is very useful and time saving technique when used more number of STS markers. It will be great help to infertility clinics for genetic counseling and assisted reproduction.

Abstract Infertility, a global problem affecting up to 15% of couples, can have varied causes ranging from natural ageing to the pathological development or function of the reproductive organs. One form of female infertility is premature ovarian insufficiency (POI), affecting up to 1 in 100 women and characterised by amenorrhoea and elevated FSH before the age of 40. POI can have a genetic basis, with over 50 causative genes identified. Non-obstructive azoospermia (NOA), a form of male infertility characterised by the absence of sperm in semen, has an incidence of 1% and is similarly heterogeneous. The genetic basis of male and female infertility is poorly understood with the majority of cases having no known cause. Here, we study a case of familial infertility including a proband with POI and her brother with NOA. We performed whole-exome sequencing (WES) and identified a homozygous STAG3 missense variant that segregated with infertility. STAG3 encodes a component of the meiosis cohesin complex required for sister chromatid separation. We report the first pathogenic homozygous missense variant in STAG3 and the first STAG3 variant associated with both male and female infertility. We also demonstrate limitations of WES for the analysis of homologous DNA sequences, with this variant being ambiguous or missed by independent WES protocols and its homozygosity only being established via long-range nested PCR.

Male infertility is a major health problem affecting about 8–12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

The aim of the study: to analyze the results of the program ІМSI as one of the methods of VRT to ensure in vitro fertilization. Materials and methods. The basis of the study consisted of 100 couples with male factor infertility. Pair was examined and treated at the Institute of reproductive medicine (Kiev) in 2013-2015. The Diagnosis verified, assistance was provided in the framework of standard clinical protocols. The 51 men were diagnosed oligoasthenozoospermia, obstructive and non-obstructive azoospermia - in 28 and 21 men, respectively. Results. There were identified features according to the results of cycles. When native - biochemical pregnancy achieved almost equally often oligoasthenozoospermia and obstructive azoospermia (53.0±6.9% and 53.4±9.4%), whereas non-obstructive in two times less (28.6±9.8%). When critical the difference in results is not traced with obstructive and non-obstructive azoospermia and was 16% lower in cases of oligoasthenozoospermia. Biochemical pregnancies occurred in 63 of the 100 pairs (63.0±4.8%), with oligoasthenozoospermia and 37 of 51 (72.5 per cent), obstructive azoospermia – in 19 of 28 (67.8 per cent), non-obstructive – 7 of 21 (33.3 percent). After reproductive losses (5 of 63, 7.9% as) the end result was lower – 58.0±4.9 per cent. The number of births in total in the group with oligoasthenozoospermia was 35 of 51 (68.6%), obstructive and non-obstructive azoospermia - 17 of 28 (60.7 per cent) and 6 of 21 (28.6 per cent), respectively. Conclusion. The data motivate the need of finding opportunities to improve program performance ІМSI. Promising in this regard is the preparation of the pair to her conduct, which goes beyond the limits of the medical, carried out according to the protocols. An important point should be the identification and leveling of risk factors for general medicine and a social plan. Key words: male infertility, the program ІМSI, results.

Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques. Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the “omics” perspective. Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated. After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis. These datasets were classified into groups according to the disease or cause of male infertility. The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion. Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups. Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3). These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes. Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility. Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.

Background: Globally, the prevalence of infertility is around 10% of the total population. 30% of these have male factor infertility. Azoospermia is found in 1% of men, in 20% of which, the etiology is a bilateral obstruction of the male genital tract while others have non obstructive azoospermia. In azoospermic men sperms are microsurgically retrieved from epididymis and testes by TESA and PESA respectively. The aim of this study was to evaluate the outcomes of intracytoplasmic sperm injection ICSI using surgically retrieved sperm of azoospermic men either obstructive or nonobstructive and to compare it with ejaculated sperms in men having severe oligospermia.Methods: This was retrospective cohort study conducted based on the data collected from our reproductive endocrinology and infertility unit, 126 ICSI cycles performed during the period of 5 years were taken and divided into two groups, one with patients having ejaculated sperms with oligospermia and other group with patients who had surgically retrieved normal sperms due to azoospermia. Outcome of these ICSI cycles included fertilization, cleavage, biochemical and clinical pregnancy was assessed.Results: In present study it was found that ICSI outcome was comparable in both the groups with ejaculated sperm and surgically retrieved sperm as fertilization rate (72% vs 65%), Implantation Rate (58 vs 51%), clinical pregnancy rate (CPR) (51% vs 44.82%) observed with ejaculated or retrieved sperm group respectively showed no statistical difference.Conclusions: Present study shows that minimally invasive techniques of PESA and TESA can be successfully performed to retrieve sperm for ICSI in the treatment of azoospermic men which gives them the chance to father their biological child. The result of this study indicates that treatment outcomes of PESA/TESA-ICSI cycles compare favourably with that of ICSI using ejaculated sperm.

Parmi les couples avec un projet parental, le facteur masculin d’infertilité est responsable d’environ 20%. Malgré de longues années d’activités d’assistance médicale à la procréation, un nombre important de cas reste idiopathiques. Considérant le nombre élevé des gènes potentiellement impliqués dans la gamétogenèse, il est fort probable que la majorité des formes ‘idiopathiques’ sont d’origine génétique. Dans l'étude présente, nous avons d’identifier deux nouveaux gènes impliqués dans une infertilité masculine. Nos données suggèrent que la mutation dans TEX15 puisse corréler avec une diminution du nombre de spermatozoïdes au fil du temps. Un test diagnostique identifiant la mutation chez un patient pourrait fournir une indication d’organiser au plus tôt une cryopréservation du sperme. On a aussi identifié MAGEB4 liées à l’X comme un nouveau gène impliqué dans une infertilité masculine héritée. Cette étude fournit le premier indice sur la fonction physiologique d'une protéine MAGE
Among couples with a desire for a child, male factor is responsible approximately 20%. Despite long years of assisted reproductive activities, a significant number of cases remain idiopathic. Considering the high predicted number of genes involved in male gametogenesis, it is likely that most ‘idiopathic’ forms may have a genetic origin. In the present study, we have defined two new genes implicated in male infertility. Our data suggested that a nonsense mutation in TEX15 correlates with a decrease in sperm count over time. A diagnostic test identifying the mutation in man could provide an indication of spermatogenic failure and prompt patients to undertake sperm cryopreservation at an early age. We also identified MAGEB4 as a new X-linked gene involved in an inherited male infertility. This study provides the first clue on the physiological function of a MAGE protein

ABSTRACT The severest form of male factor infertility is non-obstructive azoospermia (NOA), which occurs in approximately 1% of all men in reproductive age. It is common knowledge that Klinefelter Syndrome (47, XXY) and Y-chromosome microdeletions are direct causes of NOA, but in the majority of patients the etiology of this spermatogenic alteration is still unknown. The global aim of the present thesis was to enhance our understanding on genetic factors involved in non-obstructive azoospermia. The first part of the thesis focuses on the search of X-linked “AZF-like” regions. The Y-linked AZF deletions, which arise through Non-Allelic Homologous Recombination (NAHR), are the first example in andrology of functionally relevant Copy Number Variations (CNVs) causing spermatogenic failure. In analogy to the Y chromosome, the X chromosome is enriched in genes involved in spermatogenesis and its hemizygous state in males implies a direct effect of a damaging deletion making it a promising target for the discovery of new genetic factors leading to male infertility. To this purpose, we performed a multi-step bioinformatic analysis starting from all X-linked CNVs reported in UCSC Genome Browser in order to select X-linked recurrent CNVs: i) flanked by segmental duplications (SDs) and thus possibly generated by the NAHR ii) containing genes that are probably under negative selection i.e. with an inverted ratio of deletions/duplications. Following the above analysis we identified 12 X-linked CNVs (candidate “AZF-like” regions) of which 10 CNVs contained genes with a predicted role during spermatogenesis. Screening for deletions was performed in 82 idiopathic NOA patients with different testis phenotypes from pure Sertoli Cell Only Syndrome (SCOS) to partial spermatid arrest. The analysis revealed a single deletion in a patient affected by pure spermatocytic arrest removing part of the members of the Opsin gene family and possibly affecting the expression of a testis specific gene, TEX28. qPCR analysis revealed that the Opsin gene family is not expressed in germ cells and the analysis of the carrier’ testis biopsy did not reveal any impairment of TEX28 expression. Therefore, no cause-effect relationship between deletion and the testis phenotype can be established. We hypothesize that the lack of deletions in our NOA cohort may be partially due to the strictly selected testicular phenotype. Hence, we cannot exclude deletions in these regions may cause a less severe impairment of spermatogenesis. On the other hand, for the regions containing ubiquitously expressed genes, the removal of one or more of these genes may cause a more complex phenotype. Our is the first study that, through a multi-step bioinformatic analysis, provides information about potential X-linked “AZF-like” regions and represents a starting point for future large scale investigations involving patients with crypto-or oligozoospermia. The second part of the thesis focuses on the sequencing of >160.000 coding exons in NOA patients and proven normozoospermic fertile controls. We performed a Whole Exome Sequencig (WES) in a set of 18 men affected by SCOS, Spermatogenic Arrest (SGA) and normozoospermic fertile controls. We studied patients with consanguineous parents and sporadic azoospermic cases. We have identified more than 22,000 variants/subject in the exons and splice sites. Concerning patients with consanguineous parents we adopted the recessive model by selecting rare (MAF≤0.01), predicted as pathogenic, homozygous variants in genes with a putative role during early spermatogenic stages. This analytic approach allowed the identification of 3 candidate genes for male infertility: FANCA, ADAD2 and MRO. The most relevant finding concerns the patient who carried the mutation p.Arg880Gln in the FANCA gene (a functionally damaging mutation) since it is the first time that Fanconi Anemia (FA) is diagnosed following an exome analysis for idiopathic NOA. Interestingly enough, the patient’s brother, also affected by NOA, was homozygous carrier of the same mutation. Although the two brothers were not aware about having Fanconi anemia, the discovery of this genetic anomaly prompted us to perform the chromosome breakage test, through which a mosaic FA was diagnosed in both subjects. Therefore, besides diagnosing the cause of NOA, we made an important incidental finding of Fanconi Anemia (chromosome instability/cancer-prone condition), providing benefit to the siblings’ future health by allowing preventive measures. For patients with unrelated parents we applied four models: i) search for hemyzigous rare X-linked pathogenic mutations (MAF≤0.01); ii) oligogenic inheritance of low-frequency/rare mutations in genes with a putative role during early spermatogenic stages; iii) synergistic effect of genes containing low-frequency/rare mutations belonging to the same biological pathway; iv) combined effect of validated genetic risk factors for NOA (common SNPs). Finally, we also performed a high resolution X-chromosome array-CGH in sporadic patients in order to complete WES data. The first model allowed us to indentify RBBP7 as a novel X-linked candidate gene for early spermatogenic stages. So far RBBP7 has been only proposed as a key regulator during oocyte meiosis, but the expression analysis performed in our laboratory in different testis biopsies showed that the encoded protein is also overexpressed in the spermatogonial cells. Concerning the X-chromosome specific array-CGH we could not identify any relevant X-linked CNV. The second model (oligogenic inheritance) allowed the identification of three patients with single heterozygous variants and three controls with multiple heterozygous mutations. Since no patients presented more than one mutation we exclude the possibility that the azoospermic phenotype is due to digenic/oligogenic inheritance. The fact that more than one mutation in these genes has been found in three normozoospermic men suggests that it is an unlikely model for NOA. Regarding the third model (Synergistic effect of multiple low frequency mutations), the enrichment analysis in NOA patients allowed the identification of an overrepresentation of genes belonging to 19 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. After filtering out the pathways enriched in the control group, we could define enrichment in the “regulation of actin cytoskeleton” pathway as a candidate for impaired spermatogenesis. One patient presented multiple mutations in genes forming part of this pathway suggesting a potential pathogenic mechanism for the NOA phenotype. Concerning the disease enrichment analysis we identified an overrepresentation of genes associated with neoplasms, urogenital neoplasms and Fanconi anemia/syndrome in the patient group and not in the control group. Finally, regarding the combined effect of validated genetic risk factors (common SNPs) reported in previous GWAS we did not observe differences between patients and controls. The work presented in this thesis provides further advancement in the understanding of the genomic basis of idiopathic NOA. On one hand, our bioinformatic analysis identified 12 AZF-like regions along the X-chromosome that are candidates for further large scale screening in less severe forms of male infertility. Our WES experiments proved that this approach is able to identify novel candidate genes and to provide a genetic diagnosis in patients with consanguineous parents (FANCA mutation). We provided a clear example on how WES might lead to important incidental findings and thus to diagnose a chromosome instability/cancer-prone condition with implication on general health and disease prevention. Concerning the sporadic cases, WES allowed the identification of a novel X-linked candidate gene for impaired spermatogenesis indicating that the X-chromosome remains a highly interesting target.

Surgical treatment of male infertility is indicated in men with obstructive azoospermia due to epididymal and vassal blockage, in infertile men with a varicocele and oligozoospermia, and to harvest spermatozoa for future intracytoplasmic sperm injection (ICSI). Testis biopsy may be performed in men with normal testis volume and normal gonadotrophins to confirm the diagnosis of obstructive azoospermia. Furthermore, testis biopsies are indicated in men with risk factors for testis cancer, such as infertility and ultrasonograhic abnormalities.Varicocele repair seems effective in case of an infertility duration of at least 2 years, oligozoospermia, and otherwise unexplained infertility in a couple. The advantages of surgery in these couples are a fair chance of spontaneous pregnancies at relative low cost and with less obstetric problems and birth defect compared to pregnancies from IVF procedures.

Surgical sperm retrieval combined with the advent of in vitro fertilization and intracytoplasmic sperm injection has enabled many men with obstructive and non-obstructive azoospermia to father their own biological children. Several sperm retrieval techniques have been described to obtain sperm from the vas deferens, epididymis, and testicular parenchyma for use in assisted reproduction technologies. The current techniques have variable success rates but have not been subjected to randomized control trials hence the paucity of good evidence to inform the choice of one technique over the others. In experienced hands, sufficient and good quality sperm can usually be harvested for treatment and/or cryopreservation. This chapter summarizes the current techniques of surgical sperm retrieval, sperm retrieval success rate, and the role of adjuvant therapies in increasing chance of successful sperm retrieval.

The adult testis performs two principle functions: the synthesis and secretion of androgens, and the production of male germ cells, the spermatozoa. Testosterone is essential for male sexual differentiation, growth, and function of the male genital tract, secondary sexual characteristics, sexual potency, and production of spermatozoa. Hypogonadism may be due to disorders of the pituitary/hypothalamus (secondary or hypogonadotropic hypogonadism) or testes (primary or hypergonadotropic hypogonadism). Its symptoms and signs depend on the age of onset of androgen deficiency. Prepubertal presentation is with sexual infantilism, delayed puberty, and eunuchoidal body proportions. Male infertility may affect 5% of men of reproductive age and is caused by a heterogeneous group of disorders. The commonest cause (60% of cases) is ‘idiopathic’ azoo/oligozoospermia, although many cases are now recognized as due to discrete gene defects associated with impaired spermatogenesis. Other causes include cryptorchidism, testicular tumours, genital tract infection, obstructive azoospermia, and sperm autoimmunity.

Gamete cryobanking has been widely incorporated in present assisted reproductive technology (ART). Preserving male gametes for future fertility is considered to be an easy and accessible way to insure one’s reproduction. Despite the fact that the method could not secure success, sperm freezing could be the only chance to father biological offspring. In cases when severe male factor (SMF) infertility is diagnosed (retrograde ejaculation, virtual azoospermia, obstructive azoospermia, cryptozoospermia) and providing fresh semen samples for assisted reproduction may alter chances to achieve pregnancy, rare sperm cryopreservation could contribute for conceiving. Isolation, selection and cryopreservation of single sperm cells from semen samples is a challenging procedure. Different approaches and devices could be used in order to extract utmost spermatozoa. Aiming to highest cryosurvival rates sperm freezing protocols should be carefully considered. For some men, rare sperm cryopreservation might be the only alternative for parenting biological offspring. Thus, the latter technique should be widely discussed, developed and practiced in assisted reproduction.

One of the major concerns of the world health community is the infertility. The definition of infertility according to the World Health Organization (WHO) and the American Society for Reproductive Medicine (ASRM) is the inability of a healthy couple to achieve a conception after one year of regular, unprotected intercourse. Fertility complications affect seven percent of the male. The causes of infertility were divided to non-obstructive and obstructive. But, in almost 75% of male infertility cases are idiopathic with predominance of the genetic abnormalities. Numerical or structural chromosomal abnormalities are considered as genetic abnormalities that occur during the meiotic division in spermatogenesis. These abnormalities get transferred to the Offspring, which affects the normal and even the artificial conception. In the human reproduction, sperm cells are considered as a delivery vehicle for the male genetic material packed in chromosomes, which are composed of nearly 2-meter Deoxyribonucleic acid (DNA) molecule and their packaging proteins. This chapter points to grant a summarized description of individual components of the male reproductive system: the seminiferous tubule and spermatogenesis. Here, we describe step by step the structure of the testis seminiferous tubule and what occurs inside these tubules like cell communication and germ cell development from spermatogonia until spermatozoon. This book chapter is very useful for the biologists and physicians working in Assisted reproduction field to understand the physiology and pathology of spermatogenesis.