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-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.

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by "AR" gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

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.

Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.

In the UK, AIS appears on a list of serious genetic diseases that may be screened for via PGD. Some ethicists, clinicians, and intersex advocates have argued that screening embryos to specifically exclude intersex traits are based on social and cultural norms as opposed to medical necessity.

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.

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.

Conditions justifying newborn screening for any disorder include (1) a simple test with an acceptable sensitivity and specificity, (2) a dire consequence if not diagnosed early, (3) an effective treatment if diagnosed, and (4) a frequency in the population high enough to justify the expense. In the last decade more states and countries are adopting newborn screening for salt-wasting CAH due to 21-hydroxylase deficiency, which leads to death in the first month of life if not recognized.

The salt-wasting form of CAH has an incidence of 1 in 15,000 births and is potentially fatal within a month if untreated. Steroid replacement is a simple, effective treatment. However, the screening test itself is less than perfect. While the 17α-hydroxyprogesterone level is easy to measure and sensitive (rarely missing real cases), the test has a poorer specificity. Screening programs in the United States have reported that 99% of positive screens turn out to be false positives upon investigation of the infant. This is a higher rate of false positives than the screening tests for many other congenital metabolic diseases.

When a positive result is detected, the infant must be referred to a pediatric endocrinologist to confirm or disprove the diagnosis. Since most infants with salt-wasting CAH become critically ill by 2 weeks of age, the evaluation must be done rapidly despite the high false positive rate.

Levels of 17α-hydroxyprogesterone, androstenedione, and cortisol may play a role in screening.

Patients with a double uterus may need special attention during pregnancy as premature birth and malpresentation are common. Cesarean section was performed in 82% of patients reported by Heinonen.

Uterus didelphys, in certain studies, has also been found associated with higher rate of infertility, miscarriage, intrauterine growth retardation, and postpartum bleed.

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.

Since CAH is an autosomal recessive disease, most children with CAH are born to parents unaware of the risk and with no family history. Each child will have a 25% chance of being born with the disease. Families typically wish to minimize the degree of virilization of a girl. There is no known prenatal harm to a male fetus from CAH, so treatment can begin at birth.

Adrenal glands of female fetuses with CAH begin producing excess testosterone by the 9th week of gestation. The most important aspects of virilization (urogenital closure and phallic urethra) occur between 8 and 12 weeks. Theoretically, if enough glucocorticoid could be supplied to the fetus to reduce adrenal testosterone production by the 9th week, virilization could be prevented and the difficult decision about timing of surgery avoided.

The challenge of preventing severe virilization of girls is twofold: detection of CAH at the beginning of the pregnancy, and delivery of an effective amount of glucocorticoid to the fetus without causing harm to the mother.

The first problem has not yet been entirely solved, but it has been shown that if dexamethasone is taken by a pregnant woman, enough can cross the placenta to suppress fetal adrenal function.

At present no program screens for risk in families who have not yet had a child with CAH. For families desiring to avoid virilization of a second child, the current strategy is to start dexamethasone as soon as a pregnancy has been confirmed even though at that point the chance that the pregnancy is a girl with CAH is only 12.5%. Dexamethasone is taken by the mother each day until it can be safely determined whether she is carrying an affected girl.

Whether the fetus is an affected girl can be determined by chorionic villus sampling at 9–11 weeks of gestation, or by amniocentesis at 15–18 weeks gestation. In each case the fetal sex can be determined quickly, and if the fetus is a male the dexamethasone can be discontinued. If female, fetal DNA is analyzed to see if she carries one of the known abnormal alleles of the "CYP21" gene. If so, dexamethasone is continued for the remainder of the pregnancy at a dose of about 1 mg daily.

Most mothers who have followed this treatment plan have experienced at least mild cushingoid effects from the glucocorticoid but have borne daughters whose genitalia are much less virilized.

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.

A pelvic examination will typically reveal a double vagina and a double cervix. Investigations are usually prompted on the basis of such findings as well as when reproductive problems are encountered. Not all cases of uterus didelphys involve duplication of the cervix and vagina.

Helpful techniques to investigate the uterine structure are transvaginal ultrasonography and sonohysterography, hysterosalpingography, MRI, and hysteroscopy. More recently 3-D ultrasonography has been advocated as an excellent non-invasive method to evaluate uterine malformations.

Uterus didelphys is often confused with a complete uterine septum. Often more than one method of investigation is necessary to accurately diagnose the condition. Correct diagnosis is crucial as treatment for these two conditions is very different. Whereas most doctors recommend removal of a uterine septum, they generally concur that it is better not to operate on a uterus didelphys. In either case, a highly qualified reproductive endocrinologist should be consulted.

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.

Like the other forms of CAH, suspicion of severe 3β-HSD CAH is usually raised by the appearance of the genitalia at birth or by development of a salt-wasting crisis in the first month of life. The diagnosis is usually confirmed by the distinctive pattern of adrenal steroids: elevated pregnenolone, 17α-hydroxypregnenolone, DHEA, and renin. In clinical circumstances this form of CAH has sometimes been difficult to distinguish from the more common 21-hydroxylase deficient CAH because of the 17OHP elevation, or from simple premature adrenarche because of the DHEA elevation.

The incidence of ovarian remnant syndrome is difficult to determine. The available data are limited to case reports or to retrospective case series. The best available data are from a study describing the frequency and outcome of laparoscopy in women with chronic pelvic pain and/or a pelvic mass who were found to have ovarian remnants. In 119 women who underwent hysterectomy and oophorectomy by laparoscopy, ovarian remnants were known in 5 and were found during surgery in 21 patients (18%).[2] However, this was a small study and the participants were only symptomatic women. Therefore, it is not known whether the data can be extrapolated to include all women who have undergone oophorectomy.

Testicular size as a proportion of body weight varies widely. In the mammalian kingdom, there is a tendency for testicular size to correspond with multiple mates (e.g., harems, polygamy). Production of testicular output sperm and spermatic fluid is also larger in polygamous animals, possibly a spermatogenic competition for survival. The testes of the right whale are likely to be the largest of any animal, each weighing around 500 kg (1,100 lb).

Among the Hominidae, gorillas have little female promiscuity and sperm competition and the testes are small compared to body weight (0.03%). Chimpanzees have high promiscuity and large testes compared to body weight (0.3%). Human testicular size falls between these extremes (0.08%).

Testis weight also varies in seasonal breeders like deer and horses. The change is related to changes in testosterone production.

Human testicles are smaller than chimpanzee testicles but larger than gorilla testicles.

Surgical exploration and of possible ovarian tissue is required for the definitive diagnosis of ORS, and treatment by excision of the remnant ovarian tissue may be performed during the same procedure. For women who are not candidates for surgery, a clinical diagnosis can be made based on the symptoms and levels (follicle-stimulating hormone and estradiol, after bilateral oophorectomy) and/or findings consistent with the presence of residual ovarian tissue. Laparoscopy and histological assessment can aid in diagnosis.

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.

Currently, in the United States and over 40 other countries, every child born is screened for 21-hydroxylaase CAH at birth. This test will detect elevated levels of 17-hydroxy-progesterone (17-OHP). Detecting high levels of 17-OHP enables early detection of CAH. Newborns detected early enough can be placed on medication and live a relatively normal life.

The screening process, however, is characterized by a high false positive rate. In one study, CAH screening had the lowest positive predictive value (111 true-positive cases among 20,647 abnormal screening results in a 2-year period, or 0.53%, compared with 6.36% for biotinidase deficiency, 1.84% for congenital hypo-thyroidism, 0.56% for classic galactosemia, and 2.9% for phenylketonuria). According to this estimate, 200 unaffected newborns required clinical and laboratory follow-up for every true case of CAH.

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. In the United States, termination rates are around 67%, but this rate varied from 61% to 93% among different populations evaluated. When nonpregnant people are asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.

Genetic analysis can be helpful to confirm a diagnosis of CAH but it is not necessary if classic clinical and laboratory findings are present.

In classic 21-hydroxylase deficiency, laboratory studies will show:

Classic 21-hydroxylase deficiency typically causes 17α-hydroxyprogesterone blood levels >242 nmol/L. (For comparison, a full-term infant at three days of age should have <3 nmol/L. Many neonatal screening programs have specific reference ranges by weight and gestational age because high levels may be seen in premature infants without CAH.) Salt-wasting patients tend to have higher 17α-hydroxyprogesterone levels than non-salt-wasting patients. In mild cases, 17α-hydroxyprogesterone may not be elevated in a particular random blood sample, but it will rise during a corticotropin stimulation test.

A complete physical evaluation should be done prior to initiating more extensive studies, the examiner should differentiate between widespread body hair increase and male pattern virilization. One method of evaluating hirsutism is the Ferriman-Gallwey Score which gives a score based on the amount and location of hair growth on a woman. After the physical examination, laboratory studies and imaging studies can be done to rule out further causes.

Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound, due to the high prevalence of polycystic ovary syndrome (PCOS), as well as 17α-hydroxyprogesterone (because of the possibility of finding nonclassic 21-hydroxylase deficiency). Many women present with an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level. Levels greater than 700 μg/dL are indicative of adrenal gland dysfunction, particularly congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, PCOS and idiopathic hirsutism make up 90% of cases.

Other blood value that may be evaluated in the workup of hirsutism include:

- androgens; androstenedione, testosterone

- thyroid function panel; thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4)

- prolactin

If no underlying cause can be identified, the condition is considered idiopathic.

When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis. If Down syndrome occurs in one in 500 pregnancies and the test used has a 5% false-positive rate, this means, of 26 women who test positive on screening, only one will have Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means one of eleven who test positive on screening have a fetus with DS. Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of miscarriage between 0.5 and 1%. The risk of limb problems is increased in the offspring due to the procedure. The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.