The presence of symptoms significantly depends on the underlying condition, but couples usually report prolonged attempts of conception without success. Some obvious features include the appearance of very small testes or a reduction in testicular volume [10], which can point to hypogonadism. Sometimes pain or edema of the testicles may be reported, which can be distinctive for tumors. Accompanying gynecomastia can suggest a pituitary adenoma, most likely prolactinoma. Behavioral changes may suggest substance abuse. Because numerous diseases may be responsible for oligospermia, a detailed diagnostic workup should be performed.

• Neglect

  While not knowing the cause can be very frustrating, medicine still has a lot to study and understand about male infertility, which is a relatively neglected field today. The major cause of male infertility usually is a sperm problem. [web.archive.org]

• Testicular Disease

  Testicular causes They are caused by testicular diseases, including cryptorchidism, hydrocele, trauma in the genitalia, varicocele … Also, some genetic abnormalities, such as Y chromosome microdeletions (YCM), can have a negative impact on the testicular [oligospermia.info]

  CAUSES (Caused by testicular diseases) POST-TESTICULAR OLIGOZOOSPERMIC CAUSES (Refers to ejaculation problems, sperm production function works properly, but problem appears during the time of ejaculation) Medical treatment which affects sperm production [medicoverfertility.in]

Prior to performing laboratory and imaging studies, a detailed patient history is vital in infertile males. Information regarding puberty, recent trauma, illnesses or surgical procedures may provide key details for the physician in further evaluation [6]. History of previous attempts of conception with partners is also important.

To make the diagnosis, semen analysis is performed, which will show various characteristics, including volume, viscosity, pH, motility, presence of fructose and most importantly, sperm count. A sperm count of < 15 million/mL is the diagnostic criteria for oligospermia [11]. Testing should be repeated at least 2 more times to confirm that sperm count is below the threshold value. Once the diagnosis is made, the workup should include evaluation of hormones, including androgens and genetic testing. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone should be evaluated, while karyotyping, detection of Y chromosome deletions and identification of CFTR gene mutations should be performed in all patients with confirmed oligospermia.

Surgery may provide relief in case of tumors such as prolactinoma and seminoma, while endocrine and genitourinary disorders may be treated accordingly. However, the mainstay of therapy is the attempt to increase the sperm production rate via clomiphene, which belongs to the group of anti-estrogens. Because it competes with estrogen for receptors, thus reducing estrogenic effects, FSH and LH rise and stimulate the production of sperm directly. Clomiphene citrate is usually given in doses of 25-50 mg PO q24h for 25 days in one month for 3-4 months [1]. Alternatively, in vitro fertilization is a method that "bypasses" the defect that caused infertility in these patients, with the principal method being injection of a single sperm cell into an egg, known as intracytoplasmic sperm injection [12], while alternative strategies include intrauterine insemination or the use of donor sperm.

The prognosis of patients with oligospermia depends on the underlying cause. If the condition is transient (i.e. infection or trauma) and can be adequately managed, spermatogenesis may be restored to normal. However, if the causes are genetic, the prognosis is fairly poor, sometimes even with adequate pharmacologic therapy. For these reasons, it is important to establish the cause of oligospermia. However, the cause often remains unknown.

Oligospermia may be caused by numerous conditions, including [6]:

• Chromosomal mutations - Translocations, inversions, deletions, as well as structural and numerical abnormalities have been identified in much higher rates among infertile men in comparison to the general population. Some of the most commonly encountered anomalies include Klinefelter syndrome (47, XXY) [8], microdeletions of AZF on the Y chromosome and CFTR mutations. It is estimated that more than 75% of infertile males have an underlying chromosomal error [3].
• Infections - Viral orchitis, caused by mumps virus, but also hepatitis and human immunodeficiency virus (HIV) infection have shown to be a potential cause of oligospermia.
• Endocrine disorders - Various diseases that affect the hypothalamic-pituitary-gonadal axis may be responsible for low sperm count, including hypogonadism, hypothyroidism, hyperprolactinemia (usually as a result of a pituitary prolactinoma), acromegaly and adrenal hyperplasia.
• Iatrogenic causes - Various drugs have shown to interfere with spermatogenesis, including chemotherapeutic agents, sulfasalazine, corticosteroids, estrogens, antimalarials, nicotine, cimetidine, ethanol, opioids, methotrexate and many other [1].
• Testicular and endocrine tumors, as well as trauma with subsequent orchidectomy, are also described as potential causes.

Oligospermia is one of the most common causes of male infertility, which is estimated to affect 1 in 20 men. Moreover, a male factor is responsible for infertility in approximately 50% of couples [3]. Studies across the world suggest that the contribution of genetic factors significantly varies between countries, but between 2-20% of males have some abnormality that influences the process of spermatogenesis [4]. Gender and ethnic predilection have not been established, but isolated studies show higher prevalence among Caucasians [9].

Under physiological circumstances, spermatogenesis is a continuous process that occurs in the testes under tight regulation by the hypothalamic-pituitary-gonadal axis and testosterone, which is secreted by Leydig cells in the testes. Various diseases at different stages of sperm maturation interfere with this process and can cause reduced sperm production. Presumably, infections, tumors or endocrine disorders interfere with both structural and functional aspects of spermatogenesis and impede this process significantly. Iatrogenic factors, particularly chemotherapeutic agents, have shown cytotoxic effects on cells involved in sperm production, while anabolic steroid abuse directly inhibits sperm production in testes [6]. CFTR gene mutations in cystic fibrosis, which is characterized by impaired chloride channel functions in epithelial cells, induce malformations in vas deferens, the duct through which sperm passes from the testes into the urethra, ultimately leading to reduced sperm output, but also reduced quantity that may be severe (azoospermia). Although several mutations have been discovered, including those occurring on CFTR genes, but also those involving various chromosomal aberrations, their exact pathogenic mechanisms remain unknown.

Preventive strategies include avoiding risky sexual contact because of various sexually transmitted diseases (STDs) that are known to be important causes of infertility, but also avoiding drugs and substances that have established effects on spermatogenesis, such as alcohol, especially during attempts of conception. However, the cause often remains unknown and preventive strategies under such circumstances are not possible.

Oligospermia is one of the most common causes of male infertility and it is defined as a low sperm count, mainly due to insufficient production. Various conditions may cause this disorder, including endocrine (hypogonadism, hypothyroidism, disruption of the hypothalamic-pituitary-gonadal axis) and genitourinary diseases (cryptorchidism, testicular infections), numerous drugs (including anabolic steroids, monoamine oxidase inhibitors and many other), while genetic mutations also possess a significant role in the pathogenesis [1]. Numerous mutations have been described, including aneuploidy of X chromosomes that leads to Klinefelter syndrome (47, XXY), deletions of azoospermia factor (AZF) located on the long arm of Y chromosome [2], mutations in the cystic fibrosis transmembrane regulator (CFTR) gene and various other [3]. Studies have estimated that somewhere between 2-20% of infertile men possess some genetic abnormality which directly influences spermatogenesis [4], but what is more worrisome is the fact that male infertility affects approximately 1 in 20 men and that such abnormalities in men are the cause in almost 50% of infertile couples [5]. Regardless of the etiology, the insufficient quantity of ejaculated sperm significantly reduces the chance of conception. Symptoms may not be apparent in the majority of males, apart from prolonged attempts to conceive a child, but for some conditions, such as hypogonadism, small testes, and a micropenis may be observed, while abuse of anabolic steroids can lead to reduced testicular volumes [6]. To make the diagnosis, semen analysis and genetic testing should be performed. Semen analysis comprises several morphological characteristics, but the focus is on sperm count if oligospermia is suspected. Less than 15 million sperm cells/mL confirm the diagnosis of oligospermia, which can be mild (between 10-15 million/mL), moderate (between 5-10 million/mL) or severe (< 5 million/mL) [7]. Genetic testing is usually performed once the diagnosis is made and includes karyotyping, as well as detection of potential mutations that are known to occur in these patients. Treatment is aimed at managing underlying conditions, when possible, but in the majority of patients, pharmacologic agents are used to inducing sperm production. Clomiphene is used as first-line therapy, which belongs to the group of antiestrogens. In cases where clomiphene is not effective, assisted reproduction therapy, such as in vitro fertilization may surpass the defect and achieve conception.

Oligospermia is a condition that demarcates insufficient production of sperm, which can occur due to various causes. Infections, trauma, numerous drugs, endocrine diseases, tumors, but also genetic abnormalities are shown to be involved, but in more than half of patients, the cause remains unknown. It is established that 1 in 20 men is infertile and that almost 50% of infertile couples are due to diseases in males, with oligospermia being one of the most common causes. Various theories have been proposed in the attempt to describe the exact disease mechanism, such as disturbances in normal hormonal production and regulation of spermatogenesis, together with genetic aberrations that lead to defective cellular functioning. However, further studies are required to determine the exact effects. Symptoms depend on the underlying condition, but males primarily report prolonged attempts to conceive a child with their partner without success. To make the diagnosis, evaluation of semen for sperm count is performed and a sperm count of < 15 million/mL is the diagnostic criteria. In patients with oligospermia, hormonal status should be determined, including levels of the follicular-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin levels should be determined. Genetic testing is usually performed in confirmed oligospermia, in the attempt to identify the cause. Karyotyping, which implies the numeric evaluation of chromosomes, is most commonly performed, together with the exclusion of several most common mutations encountered in these patients. Treatment principles aim to induce sperm cell production through the use of clomiphene, which possesses stimulating effects on hormones that increase production of sperm. If clomiphene is not successful, in vitro fertilization may be performed, which usually consists of the insertion of one sperm cell into an egg. This procedure is known as intracytoplasmic sperm injection, while other procedures such as insemination and donor sperm may be alternative means of conception. The prognosis of males with oligospermia depends on the underlying condition, which may often be undetermined, but a careful examination and thorough patient history obtained by the physician may reveal information that may be of great importance, such as recent exposure to certain drugs, prior procedures, and trauma.

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