Azoospermia is usually detected in the course of an infertility investigation. It is established on the basis of two semen analysis evaluations done at separate occasions (when the seminal specimen after centrifugation shows no sperm under the microscope) and requires a further work-up.

The investigation includes a history, a physical examination including a thorough evaluation of the scrotum and testes, laboratory tests, and possibly imaging. History includes the general health, sexual health, past fertility, libido, and sexual activity. Past exposure to a number of agents needs to be queried including medical agents like hormone/steroid therapy, antibiotics, 5-ASA inhibitors (sulfasalazine), alpha-blockers, 5 alpha-reductase inhibitors, chemotherapeutic agents, pesticides, recreational drugs (marijuana, excessive alcohol), and heat exposure of the testes. A history of surgical procedures of the genital system needs to be elicited. The family history needs to be assessed to look for genetic abnormalities.

Congenital absence of the vas deferens may be detectable on physical examination and can be confirmed by a transrectal ultrasound (TRUS). If confirmed genetic testing for cystic fibrosis is in order. Transrectal ultrasound can also assess azoospermia caused by obstruction, or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.

Retrograde ejaculation is diagnosed by examining a postejaculatory urine for presence of sperm after making it alkaline and centifuging it.

Low levels of LH and FSH with low or normal testosterone levels are indicative of pretesticular problems, while high levels of gonadotropins indicate testicular problems. However, often this distinction is not clear and the differentiation between obstructive versus non-obstructive azoospermia may require a testicular biopsy. On the other hand, "In azoospermic men with a normal ejaculate volume, FSH serum level greater than two times the upper limit of the normal range is reliably diagnostic of dysfunctional spermatogenesis and, when found, a diagnostic testicular biopsy is usually unnecessary, although no consensus exists in this matter." But also, extremely high levels of FSH (>45 ID/mL) have been correlated with successful microdissection testicular sperm extraction.

Serum inhibin-B weakly indicates presence of sperm cells in the testes, raising chances for successfully achieving pregnancy through testicular sperm extraction (TESE), although the association is not very substantial, having a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for prediction the presence of sperm in the testes in non-obstructive azoospermia.

Seminal plasma proteins TEX101 and ECM1 were recently proposed for the differential diagnosis of azoospermia forms and subtypes, and for prediction of TESE outcome. Mount Sinai Hospital, Canada started clinical trial to test this hypothesis in 2016.

It is recommended that men primary hypopituitarism may be linked to a genetic cause, a genetic evaluation is indicated in men with azoospermia due to primary hypopituitarism. Azoospermic men with testicular failure are advised to undergo karyotype and Y-micro-deletion testing.

MAIS is only diagnosed in normal phenotypic males, and is not typically investigated except in cases of male infertility. MAIS has a mild presentation that often goes unnoticed and untreated; even with semenological, clinical and laboratory data, it can be difficult to distinguish between men with and without MAIS, and thus a diagnosis of MAIS is not usually made without confirmation of an AR gene mutation. The androgen sensitivity index (ASI), defined as the product of luteinizing hormone (LH) and testosterone (T), is frequently raised in individuals with all forms of AIS, including MAIS, although many individuals with MAIS have an ASI in the normal range. Testosterone levels may be elevated despite normal levels of luteinizing hormone. Conversion of testosterone (T) to dihydrotestosterone (DHT) may be impaired, although to a lesser extent than is seen in 5α-reductase deficiency. A high ASI in a normal phenotypic male, especially when combined with azoospermia or oligospermia, decreased secondary terminal hair, and/or impaired conversion of T to DHT, can be indicative of MAIS, and may warrant genetic testing.

Pre- and post-testicular azoospermia are frequently correctible, while testicular azoospermia is usually permanent. In the former the cause of the azoospermia needs to be considered and it opens up possibilities to manage this situation directly. Thus men with azoospermia due to hyperprolactinemia may resume sperm production after treatment of hyperprolactinemia or men whose sperm production is suppressed by exogenous androgens are expected to produce sperm after cessation of androgen intake. In situations where the testes are normal but unstimulated, gonadotropin therapy can be expected to induce sperm production.

A major advancement in recent years has been the introduction of IVF with ICSI which allows successful fertilization even with immature sperm or sperm obtained directly from testicular tissue. IVF-ICSI allows for pregnancy in couples where the man has irreversible testicular azoospermia as long as it is possible to recover sperm material from the testes. Thus men with non-mosaic Klinefelter's syndrome have fathered children using IVF-ICSI. Pregnancies have been achieved in situations where azoospermia was associated with cryptorchism and sperm where obtained by testicular sperm extraction (TESE).

In men with posttesticular azoospermia a number of approaches are available. For obstructive azoospermia IVF-ICSI or surgery can be used and individual factors need to be considered for the choice of treatment. Medication may be helpful for retrograde ejaculation.

Due to its mild presentation, MAIS often goes unnoticed and untreated. Management of MAIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Treatment includes surgical correction of mild gynecomastia, minor hypospadias repair, and testosterone supplementation. Supraphysiological doses of testosterone have been shown to correct diminished secondary sexual characteristics in men with MAIS, as well as to reverse infertility due to low sperm count. As is the case with PAIS, men with MAIS will experience side effects from androgen therapy (such as the suppression of the hypothalamic-pituitary-gonadal axis) at a higher dosage than unaffected men. Careful monitoring is required to ensure the safety and efficacy of treatment. Regular breast and prostate examinations may be necessary due to comorbid association with breast and prostate cancers.

Pre-implantation genetic diagnosis (PGD or PIGD) is a technique used to identify genetically normal embryos and is useful for couples who have a family history of genetic disorders. This is an option for people choosing to procreate through IVF. PGD is considered difficult due to it being both time consuming and having success rates only comparable to routine IVF.

Blastomere biopsy is a technique in which blastomeres are removed from the zona pellucida. It is commonly used to detect aneuploidy. Genetic analysis is conducted once the procedure is complete. Additional studies are needed to assess the risk associated with the procedure.

The most common diagnostic dilemma in otherwise normal boys is distinguishing a retractile testis from a testis that will not descend spontaneously into the scrotum. Retractile testes are more common than truly undescended testes and do not need to be operated on. In normal males, as the cremaster muscle relaxes or contracts, the testis moves lower or higher ("retracts") in the scrotum. This cremasteric reflex is much more active in infant boys than older men. A retractile testis high in the scrotum can be difficult to distinguish from a position in the lower inguinal canal. Though there are various maneuvers used to do so, such as using a cross-legged position, soaping the examiner's fingers, or examining in a warm bath, the benefit of surgery in these cases can be a matter of clinical judgment.

In the minority of cases with bilaterally non-palpable testes, further testing to locate the testes, assess their function, and exclude additional problems is often useful. Pelvic ultrasound or magnetic resonance imaging performed and interpreted by a radiologist can often, but not invariably, locate the testes while confirming absence of a uterus. A karyotype can confirm or exclude forms of dysgenetic primary hypogonadism, such as Klinefelter syndrome or mixed gonadal dysgenesis.

Hormone levels (especially gonadotropins and AMH) can help confirm that there are hormonally functional testes worth attempting to rescue, as can stimulation with a few injections of human chorionic gonadotropin to elicit a rise of the testosterone level. Occasionally these tests reveal an unsuspected and more complicated intersex condition.

In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitalia, further testing is crucial and has a high likelihood of detecting an intersex condition or other anatomic anomalies. Ambiguity can indicate either impaired androgen synthesis or reduced sensitivity. The presence of a uterus by pelvic ultrasound suggests either persistent Müllerian duct syndrome (AMH deficiency or insensitivity) or a severely virilized genetic female with congenital adrenal hyperplasia. An unambiguous micropenis, especially accompanied by hypoglycemia or jaundice, suggests congenital hypopituitarism.

Nuclear receptor subfamily 5 group A member 1 (NR5A1), also known as SF1 or Ad4BP (MIM 184757), is located on the long arm of chromosome 9 (9q33.3). The NR5A1 is an orphan nuclear receptor that was first identified following the search for a common regulator of the cytochrome P450 steroid hydroxylase enzyme family. This receptor is a pivotal transcriptional regulator of an array of genes involved in reproduction, steroidogenesis and male sexual differentiation and also plays a crucial role in adrenal gland formation in both sexes. NR5A1 regulates the mullerian inhibitory substance by binding to a conserved upstream regulatory element and directly participates in the process of mammalian sex determination through mullerian duct regression. Targeted disruption of NR5A1 (Ftzf1) in mice results in gonadal and adrenal agenesis, persistence of Mullerian structures and abnormalities of the hypothalamus and pituitary gonadotropes. Heterozygous animals demonstrate a milder phenotype including an impaired adrenal stress response and reduced testicular size. In humans, NR5A1 mutations were first described in patients with 46, XY karyotype and disorders of sex development (DSD), Mullerian structures and primary adrenal failure (MIM 612965). After that, heterozygous NR5A1 mutations were described in seven patients showing 46, XY karyotype and ambiguous genitalia, gonadal dysgenesis, but no adrenal insufficiency. Since then, studies have confirmed that mutations in NR5A1 in patients with 46, XY karyotype cause severe underandrogenisation, but no adrenal insufficiency, establishing dynamic and dosage-dependent actions for NR5A1. Subsequent studies revealed that NR5A1 heterozygous mutations cause primary ovarian insufficiency (MIM 612964).

About 10–15% of human couples are infertile, unable to conceive. In approximately in half of these cases, the underlying cause is related to the male. The underlying causative factors in the male infertility can be attributed to environmental toxins, systemic disorders such as, hypothalamic–pituitary disease, testicular cancers and germ-cell aplasia. Genetic factors including aneuploidies and single-gene mutations are also contributed to the male infertility. Patients suffering from nonobstructive azoospermia or oligozoospermia show microdeletions in the long arm of the Y chromosome and/or chromosomal abnormalities, each with the respective frequency of 9.7% and 13%. A large percentage of human male infertility is estimated to be caused by mutations in genes involved in primary or secondary spermatogenesis and sperm quality and function. Single-gene defects are the focus of most research carried out in this field.

NR5A1 mutations are associated with male infertility, suggesting the possibility that these mutations cause the infertility. However, it is possible that these mutations individually have no major effect and only contribute to the male infertility by collaboration with other contributors such as environmental factors and other genomics variants. Vice versa, existence of the other alleles could reduce the phenotypic effects of impaired NR5A1 proteins and attenuate the expression of abnormal phenotypes and manifest male infertility solely.

About 10% of Klinefelter cases are found by prenatal diagnosis. The first clinical features may appear in early childhood or, more frequently, during puberty, such as lack of secondary sexual characteristics and aspermatogenesis. Despite the presence of small testes, only a quarter of the affected males are recognized as having Klinefelter syndrome at puberty. Another quarter receive their diagnosis in late adulthood. About 64% of affected individuals are never recognized. Often the diagnosis is made incidentally as a result of examinations and medical visits for reasons not linked to the condition.

The standard diagnostic method is the analysis of the chromosomes' karyotype on lymphocytes. In the past, the observation of the Barr body was common practice as well. To confirm mosaicism, it is also possible to analyze the karyotype using dermal fibroblasts or testicular tissue.

Other methods may be: research of high serum levels of gonadotropins (follicle-stimulating hormone and luteinizing hormone), presence of azoospermia, determination of the sex chromatin, and prenatally via chorionic villus sampling or amniocentesis. A 2002 literature review of elective abortion rates found that approximately 58% of pregnancies in the United States with a diagnosis of Klinefelter syndrome were terminated.

Children with XXY differ little from other children. Although they can face problems during adolescence, often emotional and behavioral, and difficulties at school, most of them can achieve full independence from their families in adulthood. Most can lead a normal, healthy life.

The results of a study carried out on 87 Australian adults with the syndrome shows that those who have had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to those who had been diagnosed in adulthood.

There is research suggesting Klinefelter syndrome substantially decreases life expectancy among affected individuals, though the evidence is not definitive. A 1985 publication identified a greater mortality mainly due to diseases of the aortic valve, development of tumors and possible subarachnoid hemorrhages, reducing life expectancy by about 5 years. Later studies have reduced this estimated reduction to an average of 2.1 years. These results are still questioned data, are not absolute, and will need further testing.

The primary management of cryptorchidism is watchful waiting, due to the high likelihood of self-resolution. Where this fails, a surgery, called orchiopexy, is effective if inguinal testes have not descended after 4–6 months. Surgery is often performed by a pediatric urologist or pediatric surgeon, but in many communities still by a general urologist or surgeon.

When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and very occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin (HCG). A series of hCG injections (10 injections over 5 weeks is common) is given and the status of the testis/testes is reassessed at the end. Although many trials have been published, the reported success rates range widely, from roughly 5 to 50%, probably reflecting the varying criteria for distinguishing retractile testes from low inguinal testes. Hormone treatment does have the occasional incidental benefits of allowing confirmation of Leydig cell responsiveness (proven by a rise of the testosterone by the end of the injections) or inducing additional growth of a small penis (via the testosterone rise). Some surgeons have reported facilitation of surgery, perhaps by enhancing the size, vascularity, or healing of the tissue. A newer hormonal intervention used in Europe is the use of GnRH analogs such as nafarelin or buserelin; the success rates and putative mechanism of action are similar to hCG, but some surgeons have combined the two treatments and reported higher descent rates. Limited evidence suggests that germ cell count is slightly better after hormone treatment; whether this translates into better sperm counts and fertility rates at maturity has not been established. The cost of either type of hormone treatment is less than that of surgery and the chance of complications at appropriate doses is minimal. Nevertheless, despite the potential advantages of a trial of hormonal therapy, many surgeons do not consider the success rates high enough to be worth the trouble since the surgery itself is usually simple and uncomplicated.

In cases where the testes are identified preoperatively in the inguinal canal, orchiopexy is often performed as an outpatient and has a very low complication rate. An incision is made over the inguinal canal. The testis with accompanying cord structure and blood supply is exposed, partially separated from the surrounding tissues ("mobilized"), and brought into the scrotum. It is sutured to the scrotal tissue or enclosed in a "subdartos pouch." The associated passage back into the inguinal canal, an inguinal hernia, is closed to prevent re-ascent.

In patients with intraabdominal maldescended testis, laparoscopy is useful to see for oneself the pelvic structures, position of the testis and decide upon surgery ( single or staged procedure ).

Surgery becomes more complicated if the blood supply is not ample and elastic enough to be stretched into the scrotum. In these cases, the supply may be divided, some vessels sacrificed with expectation of adequate collateral circulation. In the worst case, the testis must be "auto-transplanted" into the scrotum, with all connecting blood vessels cut and reconnected ("anastomosed").

When the testis is in the abdomen, the first stage of surgery is exploration to locate it, assess its viability, and determine the safest way to maintain or establish the blood supply. Multi-stage surgeries, or autotransplantation and anastomosis, are more often necessary in these situations. Just as often, intra-abdominal exploration discovers that the testis is non-existent ("vanished"), or dysplastic and not salvageable.

The principal major complication of all types of orchiopexy is a loss of the blood supply to the testis, resulting in loss of the testis due to ischemic atrophy or fibrosis.

To some extent, it is possible to change testicular size. Short of direct injury or subjecting them to adverse conditions, e.g., higher temperature than they are normally accustomed to, they can be shrunk by competing against their intrinsic hormonal function through the use of externally administered steroidal hormones. Steroids taken for muscle enhancement (especially anabolic steroids) often have the undesired side effect of testicular shrinkage.

Similarly, stimulation of testicular functions via gonadotropic-like hormones may enlarge their size. Testes may shrink or atrophy during hormone replacement therapy or through chemical castration.

In all cases, the loss in testes volume corresponds with a loss of spermatogenesis.

Spermatogenesis arrest is a complex process of interruption in the differentiation of germinal cells of specific cellular type, which elicits an altered spermatozoa formation. Spermatogenic arrest is usually due to genetic factors resulting in irreversible azoospermia. However some cases may be consecutive to hormonal, thermic, or toxic factors and may be reversible either spontaneously or after a specific treatment.

Deafness is a feature of MDP syndrome as a result of the nerves not working well and people often have difficulty getting hearing aids because of the small size of their ears. Digital hearing aids can be helpful and audiometry follow up will be needed.

Many people with MDP syndrome are high achievers intellectually following careers in law, medicine and computing. A crucial point is that they do not have progeria and there is no evidence of accelerated intellectual decline with age in these patients. Equally life expectancy has not been shown to be reduced. Patients of 65 have been described in the literature and none of the patients are known to have malignancy. Therefore, there are many crucial differences with progeria and the name of progeroid in the title is confusing as this really refers to the lack of fat in the face and taut skin and not any intellectual or other age associated features.

The testicle or testis is the male reproductive gland in all animals, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testosterone. Testosterone release is controlled by the anterior pituitary luteinizing hormone; whereas sperm production is controlled both by the anterior pituitary follicle-stimulating hormone and gonadal testosterone.

Microscopic analysis of the hair shows twisted hairs of unequal size and different shapes (pili torti, aniso- and poikilotrichosis), longitudinal breaks and breaks located at nodes (trichorrhexis nodosa). Scanning electron microscopy might reveal hair budding (trichorrhexis blastysis). Biochemical analysis may reveal sulfur-deficient brittle hair (trichothiodystrophy; note that disulfide bonds determine hair waviness).

Immunodeficiency is a consistent feature with low serum concentrations of immunoglobulins which may improve with age and a poor immunological response to childhood vaccination. T cell dysfunction and abnormal antibody generation have been reported.

Diagnosis is usually based on clinical findings, although fetal chromosome testing will show trisomy 13. While many of the physical findings are similar to Edwards syndrome there are a few unique traits, such as polydactyly. However, unlike Edwards syndrome and Down syndrome, the quad screen does not provide a reliable means of screening for this disorder. This is due to the variability of the results seen in fetuses with Patau.

Different features of the dysostosis are significant. Radiological imaging helps confirm the diagnosis. During gestation (pregnancy), clavicular size can be calculated using available nomograms. Wormian bones can sometimes be observed in the skull.

Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1).

Partial monosomy of chromosome 13q is a monosomy that results from the loss of all or part of the long arm of chromosome 13 in human beings. It is a rare genetic disorder which results in severe congenital abnormalities which are frequently fatal at an early age. Up until 2003, more than 125 cases had been documented in medical literature.

Symptoms vary from case to case, and may correlate to how much of the chromosome is missing. Symptoms that are frequently observed with the condition include:

- Low birth weight

- Malformations of the head

- Eye abnormalities

- Defects of the hands and feet, polydactyly

- Reproductive abnormalities (males)

- Psychological and motor retardation

An omphalocele is often detected through AFP screening or a detailed fetal ultrasound. Genetic counseling and genetic testing such as amniocentesis are usually offered during the pregnancy.

The most accurate method of diagnosis is prenatal screening through real-time fetal images. However, since maternal body habitus leads to diagnostic difficulties using this method, MRI and sonography are the most commonly used technique since there is no exposure to ionizing radiation. At the beginning of the second trimester, the central nervous system (CNS) and anatomic structures of the fetus can be clearly visualized and the characteristic malformations of iniencephaly, such as a shortened trunk, marked lordosis in the cervicothoracic vertebrae, absence or partial absence of the occipital squama, abnoramal fusion of vertebrae, closed vertebral arches, formation of an encephalocele (for iniencephaly apertus), and dorsiflexion of the head in respect to the spine, can be precisely diagnosed as well as the severity and location established. Once established, further decisions can be made with regard to terminating the pregnancy or providing a plan of adequate postnatal care.