Male infertility refers to a

sexually mature Sexual maturity is the capability of an organism to reproduce. In humans it might be considered synonymous with adulthood, but here puberty is the name for the process of biological sexual maturation, while adulthood is based on cultural definiti ...

male's inability to

impregnate Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the

semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...

, and

semen quality Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality Cryptorchidism, hypospadias, testicular cancer and poor semen quali ...

is used as a surrogate measure of male fecundity. More recently, advance sperm analyses that examine intracellular sperm components are being developed.

Age considerations

There is a decrease in sperm concentration as men age: 90% of

seminiferous tubule Seminiferous tubules are located within the testes, and are the specific location of meiosis, and the subsequent creation of male gametes, namely spermatozoa. Structure The epithelium of the tubule consists of a type of sustentacular cells known ...

s in men in their 20s and 30s contain

spermatid The spermatid is the haploid male gametid that results from division of secondary spermatocytes. As a result of meiosis, each spermatid contains only half of the genetic material present in the original primary spermatocyte. Spermatids are co ...

s, whereas men in their 40s and 50s have spermatids in 50% of their seminiferous tubules, and only 10% of seminiferous tubules from men aged > 80 years contain spermatids. In a random international sample of 11,548 men confirmed to be biological fathers by DNA paternity testing, the oldest father was found to be 66 years old at the birth of his child; the ratio of DNA-confirmed versus DNA-rejected paternity tests around that age is in agreement with the notion of general male infertility above age 65–66.

Causes

Factors relating to male infertility include:

Immune infertility

Antisperm antibodies Antisperm antibodies (ASA) are antibodies produced against sperm antigens. Types Antisperm antibodies are immunoglobulins of IgG, IgA, and/or IgM, which are directed against sperm antigens. ASA can be detected in ejaculate, cervical muc ...

(ASA) have been considered as infertility cause in around 10–30% of infertile couples. ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and

acrosome reaction During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg cell to fertilize it. Fusing to the egg cell usually causes little problem, whereas penetrating through the egg's hard shell or extracellular ...

, impaired

fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

, influence on the implantation process, and impaired growth and development of the embryo. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis,

varicocele varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. This plexus of veins drains blood from the testicles back to the heart. The vessels originate in the abdomen and course down through the inguinal canal as p ...

, infections,

prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an ...

, failure of immunosuppression and unprotected receptive anal or oral sex with men.

Genetics

Chromosomal anomalies and genetic mutations account for nearly 10–15% of all male infertility cases.

Klinefelter syndrome

One of the most commonly known causes of infertility is

Klinefelter syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are sub ...

, which affects one in 500–1000 newborn males. Klinefelter syndrome is a chromosomal defect that occurs during gamete formation due to a non-disjunction error during cell division. Resulting in males having smaller testes, reducing the amount of testosterone and sperm production. Males with this syndrome carry an extra

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...

(XXY), meaning they have 47 chromosomes compared to the normal 46 in each cell. This extra chromosome directly affects sexual development before birth and during puberty. A variation of Klinefelter syndrome is when some cells in an individual have the extra X chromosome but others do not, referred to as mosaic Klinefelter syndrome. The reduction of testosterone in the male body normally results in an overall decrease in the production of viable sperm for these individuals thereby forcing them to turn to fertility treatments to father children.

Y chromosome deletions

Y chromosomal infertility is a direct cause of male infertility due to its effects on sperm production, occurring in approximately one in 2000 males. Usually, affected men show no symptoms, although they may have smaller testes. Men with this condition may exhibit azoospermia (no sperm production),

oligozoospermia Terms oligospermia, oligozoospermia, and low sperm count refer to semen with a low concentration of sperm and is a common finding in male infertility. Often semen with a decreased sperm concentration may also show significant abnormalities in sperm ...

(small number of sperm production), or they may produce abnormally shaped sperm (

teratozoospermia Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males. Causes The causes of teratozoospermia are unknown in most cases. However, Hodgkin's disease, coelia ...

). This case of infertility occurs during the development of gametes in the male. Where a normal healthy male will have both an X and a Y chromosome, affected males have genetic deletions in the Y chromosome. These deletions affect protein production that is vital for spermatogenesis. Studies have shown that this is an inherited trait; if a male is fathered by a man who also exhibited Y chromosome deletions then this trait will be passed down. These individuals are thereby "

Y-linked Y linkage, also known as holandric inheritance (from Ancient Greek ὅλος ''hólos'', "whole" + ἀνδρός ''andrós'', "male"), describes traits that are produced by genes located on the Y chromosome. It is a form of sex linkage. Y&nbs ...

". Daughters are not affected and cannot be carriers due to their lack of a Y chromosome.

Other

* Age group 12–49 (

Paternal age effect The paternal age effect is the statistical relationship between the father's age at conception and biological effects on the child. Such effects can relate to birthweight, congenital disorders, life expectancy and psychological outcomes. A 2017 ...

) *

Aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...

, an abnormal number of chromosomes * Centriole *

Neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

, e.g.

seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in ...

Idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...

failure *

Cryptorchidism Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...

Trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...

* Hydrocele, particularly

hydrocele testis A hydrocele testis is an accumulation of clear fluid within the cavum vaginale, the potential space between the layers of the tunica vaginalis of the testicle. It is the most common form of hydrocele and is often referred to simply as a "hydrocele ...

Hypopituitarism Hypopituitarism is the decreased (''hypo'') secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is know ...

in adults, and hypopituitarism untreated in children (resulting in growth hormone deficiency and proportionate dwarfism.) * Mumps *

Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

Testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an ...

* Defects in

USP26 USP26 is a peptidase enzyme. The USP26 gene is an X-linked gene exclusively expressed in the testis and it codes for the ubiquitin-specific protease 26. The USP26 gene is found at Xq26.2 on the X-chromosome as a single exon. The enzyme that this g ...

in some cases *

Acrosomal The acrosome is an organelle that develops over the anterior (front) half of the head in the spermatozoa (sperm cells) of many animals including humans. It is a cap-like structure derived from the Golgi apparatus. In placental mammals the acrosome c ...

defects affecting egg penetration * Idiopathic oligospermia – unexplained sperm deficiencies account for 30% of male infertility.

Pre-testicular causes

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

Varicocele

Varicocele varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. This plexus of veins drains blood from the testicles back to the heart. The vessels originate in the abdomen and course down through the inguinal canal as p ...

is a condition of swollen testicle veins. It is present in 15% of normal men and in about 40% of infertile men. It is present in up to 35% of cases of primary infertility and 69–81% of secondary infertility. *

Hypogonadotropic hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis). Hypothalamic disorders result from a deficiency in the release of gonadotropic r ...

due to various causes **

Obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

increases the risk of hypogonadotropic hypogonadism. Animal models indicate that obesity causes leptin insensitivity in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, leading to decreased Kiss1 expression, which, in turn, alters the release of

gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and release ...

(GnRH). * Undiagnosed and untreated

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

(CD). Coeliac men may have reversible infertility. Nevertheless, CD can present with several non-gastrointestinal symptoms that can involve nearly any organ system, even in the absence of gastrointestinal symptoms. Thus, the diagnosis may be missed, leading to a risk of long-term complications. In men, CD can reduce

quality and cause immature

secondary sex characteristic Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...

hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estroge ...

and

hyperprolactinaemia Hyperprolactinaemia is the presence of abnormally high levels of prolactin in the blood. Reference ranges for common blood tests, Normal levels average to about 13 ng/mL in women, and 5 ng/mL in men, with an upper normal limit of serum ...

, which causes

impotence Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of mal ...

and loss of

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...

. The giving of gluten free diet and correction of deficient dietary elements can lead to a return of fertility. It is likely that an effective evaluation for infertility would best include assessment for underlying celiac disease, both in men and women. * Drugs, alcohol * Strenuous riding (

bicycle riding Cycling, also, when on a two-wheeled bicycle, called bicycling or biking, is the use of cycles for transport, recreation, exercise or sport. People engaged in cycling are referred to as "cyclists", "bicyclists", or "bikers". Apart from t ...

horseback riding Equestrianism (from Latin , , , 'horseman', 'horse'), commonly known as horse riding (Commonwealth English) or horseback riding (American English), includes the disciplines of riding, driving, and vaulting. This broad description includes the ...

) * Medications, including those that affect spermatogenesis such as

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

, fluoxetine, anabolic steroids, cimetidine,

spironolactone Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...

; those that decrease FSH levels such as

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

; those that decrease sperm motility such as

sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...

and

nitrofurantoin Nitrofurantoin is an antibacterial medication used to treat urinary tract infections, but it is not as effective for kidney infections. It is taken by mouth. Common side effects include nausea, loss of appetite, diarrhea, and headaches. Rarely ...

* Genetic abnormalities such as a Robertsonian translocation

Tobacco smoking

There is increasing evidence that the harmful products of tobacco smoking may damage the testicles and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.

DNA damage

Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility. As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage. The damage manifests by

DNA fragmentation DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be done intentionally by laboratory personnel or by cells, or can occur spontaneously. Spontaneous or accidental DNA fragmentation is fragmentation that gradually a ...

and by the increased susceptibility to denaturation upon exposure to heat or acid, the features characteristic of apoptosis of somatic cells. These findings suggest that DNA damage is an important factor in male infertility.

Epigenetic

An increasing amount of recent evidence has been recorded documenting abnormal sperm DNA methylation in association with abnormal semen parameters and male infertility. Until recently, scientists have thought that epigenetic markers only affect the individual and are not passed down due to not changing the DNA. New studies suggest that environmental factors that changed an individual's epigenetic markers can be seen in their grandchildren, one such study demonstrating this through rats and fertility disruptors. Another study bred rats exposed to an endocrine disruptor, observing effects up to generation F5 including decreased sperm motility and decreased sperm count. These studies suggest that environmental factors that influence fertility can be felt for generations even without changing the DNA.

Post-testicular causes

Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in

ejaculation Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential compone ...

: *

Vas deferens The vas deferens or ductus deferens is part of the male reproductive system of many vertebrates. The ducts transport sperm from the epididymis to the ejaculatory ducts in anticipation of ejaculation. The vas deferens is a partially coiled tube ...

obstruction * Lack of

, often related to genetic markers for cystic fibrosis *

Infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

, e.g.

, male accessory gland infection *

Retrograde ejaculation Retrograde ejaculation occurs when semen which would be ejaculated via the urethra is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation, sealing the bladder which besides inhibiting the relea ...

Ejaculatory duct obstruction Ejaculatory duct obstruction (EDO) is a pathological condition which is characterized by the obstruction of one or both ejaculatory ducts. Thus, the efflux of (most constituents of) semen is not possible. It can be congenital or acquired. It is ...

Hypospadias Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location in the head of the penis. It is the second-most common birth abnormality of the male reproductive system, affecting abou ...

Impotence Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of mal ...

Diagnostic evaluations

The diagnosis of infertility begins with a medical history and physical exam by a

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

, physician assistant, or

nurse practitioner A nurse practitioner (NP) is an advanced practice registered nurse and a type of mid-level practitioner. NPs are trained to assess patient needs, order and interpret diagnostic and laboratory tests, diagnose disease, formulate and prescribe ...

. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.

Medical history

The history should include prior testicular or penile insults (

torsion Torsion may refer to: Science * Torsion (mechanics), the twisting of an object due to an applied torque * Torsion of spacetime, the field used in Einstein–Cartan theory and ** Alternatives to general relativity * Torsion angle, in chemistry Bi ...

cryptorchidism Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...

trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...

infections An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

( mumps

orchitis Orchitis is inflammation of the testes. It can also involve swelling, pains and frequent infection, particularly of the epididymis, as in epididymitis. The term is from the Ancient Greek ὄρχις meaning "testicle"; same root as ''orchid''. S ...

epididymitis Epididymitis is a medical condition characterized by inflammation of the epididymis, a curved structure at the back of the testicle. Onset of pain is typically over a day or two. The pain may improve with raising the testicle. Other symptoms may i ...

), environmental factors, excessive heat, radiation, medications, and drug use ( anabolic steroids, alcohol, smoking).Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.Loss of

and

headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

visual disturbances A vision disorder is an impairment of the sense of vision. Vision disorder is not the same as an eye disease. Although many vision disorders do have their immediate cause in the eye, there are many other causes that may occur at other locations in ...

may indicate a

pituitary tumor Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.diabetic neuropathy (

retrograde ejaculation Retrograde ejaculation occurs when semen which would be ejaculated via the urethra is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation, sealing the bladder which besides inhibiting the relea ...

), radical pelvic or

retroperitoneal The retroperitoneal space (retroperitoneum) is the anatomical space (sometimes a potential space) behind (''retro'') the peritoneum. It has no specific delineating anatomical structures. Organs are retroperitoneal if they have peritoneum on thei ...

surgery (absent seminal emission secondary to sympathetic nerve injury), or

hernia repair Hernia repair refers to a surgical operation for the correction of a hernia—a bulging of internal organs or tissues through the wall that contains it. It can be of two different types: herniorrhaphy; or hernioplasty. This operation may be pe ...

(damage to the vas deferens or testicular blood supply). A

family history Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kin ...

may reveal genetic problems.

Physical examination

Usually, the patient disrobes completely and puts on a gown. The physician, physician assistant, or nurse practitioner will perform a thorough examination of the

penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males d ...

scrotum The scrotum or scrotal sac is an anatomical male reproductive structure located at the base of the penis that consists of a suspended dual-chambered sac of skin and smooth muscle. It is present in most terrestrial male mammals. The scrotum co ...

testicles A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...

, I

vas deferens The vas deferens or ductus deferens is part of the male reproductive system of many vertebrates. The ducts transport sperm from the epididymis to the ejaculatory ducts in anticipation of ejaculation. The vas deferens is a partially coiled tube ...

spermatic cord The spermatic cord is the cord-like structure in males formed by the vas deferens (''ductus deferens'') and surrounding tissue that runs from the deep inguinal ring down to each testicle. Its serosal covering, the tunica vaginalis, is an exten ...

ejaculatory ducts The ejaculatory ducts (''ductus ejaculatorii'') are paired structures in male anatomy. Each ejaculatory duct is formed by the union of the vas deferens with the duct of the seminal vesicle. They pass through the prostate, and open into the ureth ...

urethra The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra c ...

urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine ente ...

, anus and rectum. An

orchidometer An orchidometer (or orchiometer) is a medical instrument used to measure the volume of the testicles. The orchidometer was introduced in 1966 by Swiss pediatric endocrinologist Andrea Prader of the University of Zurich. It consists of a string of ...

can measure testicular volume, which in turn is tightly associated with both sperm and hormonal parameters. A physical exam of the scrotum can reveal a

, but the impact of detecting and surgically correct a varicocele on sperm parameters or overall male fertility is debated.

Sperm sample

Semen sample obtaining

Semen sample obtaining is the first step in spermiogram. The optimal sexual abstinence for semen sample obtaining is of 2–7 days. The first way to obtain the semen sample is through masturbation, and the best place to obtain it is in the same clinic, as this way temperature changes during transport can be avoided, which can be lethal for some spermatozoa. A single semen sample is not determining for disease diagnosis, so two different samples have to be analyzed with an interval between them of seven days to three months, as sperm production is a cyclic process. It is prudent to ask about possible sample loss, as that could mask true results of spermiogram. To obtain the sample, a sterile plastic recipient is put directly inside, always no more than one hour before being studied. Conventional preservatives shouldn't be used, as they have chemical substances as lubricants or spermicides that could damage the sample. If preservatives have to be used, for cases of religious ethics in which masturbation is forbidden, a preservative with holes is used. In case of paraplegia it is possible to use mechanic tools or electroejaculation. The sample should never be obtained through coitus interruptus for several reasons: * Some part of ejaculation could be lost. * Bacterial contamination could happen. * The acid vaginal pH could be deleterious for sperm motility. Also is very important to label the sample correctly the recipient with patient identification, date, hour, abstinence days, among other data required to be known. The volume of the semen sample (must be more than 1.5 ml), approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. It is possible to have hyperspermia (high volume more than 6 ml) or Hypospermia (low volume less than 0.5 ml). This is the most common type of fertility testing. Semen deficiencies are often labeled as follows: *

Oligospermia Terms oligospermia, oligozoospermia, and low sperm count refer to semen with a low concentration of sperm and is a common finding in male infertility. Often semen with a decreased sperm concentration may also show significant abnormalities in spe ...

– decreased number of spermatozoa in semen *

Aspermia Aspermia is the complete lack of semen with ejaculation (not to be confused with azoospermia, the lack of sperm cells in the semen). It is associated with infertility. One of the causes of aspermia is retrograde ejaculation, because of that the s ...

– complete lack of semen *

Hypospermia Hypospermia is a condition in which a man has an unusually low ejaculate (or semen) volume, less than 1.5 mL. It is the opposite of hyperspermia, which is a semen volume of more than 5.5 mL. It should not be confused with oligospermia, which mea ...

– reduced seminal volume * Azoospermia – absence of sperm cells in semen *

Teratospermia Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males. Causes The causes of teratozoospermia are unknown in most cases. However, Hodgkin's disease, coeliac ...

– increase in sperm with abnormal morphology * Asthenozoospermia – reduced sperm motility * Necrozoospermia – all sperm in the ejaculate are dead * Leucospermia – a high level of white blood cells in semen * Normozoospermia or normospermia – It is a result of semen analysis that shows normal values of all ejaculate parameters by WHO but still there are chances of being infertile. This is also called as unexplained Infertility There are various combinations of these as well, e.g. ''Teratoasthenozoospermia'', which is reduced sperm morphology and motility. Low sperm counts are often associated with decreased sperm motility and increased abnormal morphology, thus the terms "oligoasthenoteratozoospermia" or "oligospermia" can be used as a catch-all.

Special obtaining

Psychological inhibition Social inhibition is a conscious or subconscious avoidance of a situation or social interaction. With a high level of social inhibition, situations are avoided because of the possibility of others disapproving of their feelings or expressions. Soc ...

– Psychotherapy – Intercourses with special preservatives without lubricants or spermicides. In case of religion limitations we should use a SCD, or Seminal Collection Device, such as preservatives with holes. – Drug stimulation – Percutaneous spermatozoa obtaining directly from epididymis, testes, etc. *

Neurological injury A neurological disorder is any Disorder (medicine)#Disorder, disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms incl ...

– Vibro-stimulation – Electro-stimulation *

This type of ejaculation happens when there is a defect on prostate, so the sample is not ejaculated outside but to the bladder. So, in that case, what we have to do to obtain the sample is: – Intake bicarbonate, about 25 grams, the night before and the morning of the sample obtaining. This will neutralize acidic urine and will turn it alkaline, near semen's pH, so spermatozoa can survive. – Before masturbation we have to urinate to empty the bladder. This must go to the first recipient. – Just after that, the subject has to masturbate and ejaculate, obtaining then a new urine sample with ejaculation that will be stored on the second recipient. – Finally we have to obtain the next urine, 2nd urine, for potential ejaculation fraction, which will be stored in the third recipient. This may contain the most important fraction.

Blood sample

Common hormonal test include determination of FSH and

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

levels. A blood sample can reveal genetic causes of infertility, e.g.

, a Y chromosome microdeletion, or cystic fibrosis.

Ultrasonography

Scrotal ultrasonography Scrotal (or transscrotal) ultrasound is a medical ultrasound examination of the scrotum. It is used in the evaluation of testicular pain, and can help identify solid masses. Indications Although the development of new imaging modalities such as c ...

is useful when there is a suspicion of some particular diseases. It may detect signs of

testicular dysgenesis Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system in the male or female. It is the atypical development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous ti ...

, which is often related to an impaired spermatogenesis and to a higher risk of

. Scrotum ultrasonography may also detect testicular lesions suggestive of malignancy. A decreased testicular vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions such as

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

and

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

Doppler ultrasonography Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to perform imaging of the movement of tissues and body fluids (usually blood), and their relative velocity to the probe. By calculating the frequency shift of ...

useful in assessing

venous reflux Varicose veins, also known as varicoses, are a medical condition in which superficial veins become enlarged and twisted. These veins typically develop in the legs, just under the skin. Varicose veins usually cause few symptoms. However, some indi ...

in case of a

, when palpation is unreliable or in detecting recurrence or persistence after surgery, although the impact of its detection and surgical correction on sperm parameters and overall fertility is debated. Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract. Such abnormalities are associated with abnormalities in sperm parameters, as are abnormalities in the texture of the epididymis. Scrotal and

transrectal ultrasonography Transrectal ultrasonography, or TRUS in short, is a method of creating an image of organs in the pelvis, most commonly used to perform an ultrasound-guided needle biopsy evaluation of the prostate gland in men with elevated prostate-specific ant ...

(TRUS) are useful in detecting uni- or bilateral

congenital absence of the vas deferens Congenital absence of the vas deferens (CAVD) is a condition in which the vasa deferentia reproductive organs fail to form properly prior to birth. It may either be unilateral (CUAVD) or bilateral (CBAVD). Signs and symptoms The vas deferens con ...

(CBAVD), which may be associated with abnormalities or

agenesis In medicine, agenesis () refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue. Many forms of agenesis are referred to by individual names, depending on the organ affected: * A ...

of the epididymis,

seminal vesicles The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen. The vesicles are 5� ...

or kidneys, and indicate the need for

testicular sperm extraction Testicular sperm extraction (TESE) is a surgical procedure in which a small portion of tissue is removed from the testicle and any viable sperm cells from that tissue are extracted for use in further procedures, most commonly intracytoplasmic sperm ...

. TRUS plays a key role in assessing azoospermia caused by obstruction, and detecting distal CBAVD 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.

Prevention

Some strategies suggested or proposed for avoiding male infertility include the following: * Avoiding smoking as it damages sperm DNA * Avoiding heavy marijuana and alcohol use. * Avoiding excessive heat to the testes. * Maintaining optimal frequency of coital activity: sperm counts can be depressed by daily coital activity and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more). * Wearing a

protective cup A jockstrap, also a jock (male), jill (female), strap, cup, groin guard, pelvic protector (female), supporter, or athletic supporter, is an undergarment for protecting the testes and penis or vulva during contact sports or other vigorous physi ...

and

jockstrap A jockstrap, also a jock (male), jill (female), strap, cup, groin guard, pelvic protector (female), supporter, or athletic supporter, is an undergarment for protecting the testes and penis or vulva during contact sports or other vigorous physic ...

to protect the testicles, in any sport such as

baseball Baseball is a bat-and-ball sport played between two teams of nine players each, taking turns batting and fielding. The game occurs over the course of several plays, with each play generally beginning when a player on the fielding t ...

, football,

cricket Cricket is a bat-and-ball game played between two teams of eleven players on a field at the centre of which is a pitch with a wicket at each end, each comprising two bails balanced on three stumps. The batting side scores runs by str ...

lacrosse Lacrosse is a team sport played with a lacrosse stick and a lacrosse ball. It is the oldest organized sport in North America, with its origins with the indigenous people of North America as early as the 12th century. The game was extensiv ...

hockey Hockey is a term used to denote a family of various types of both summer and winter team sports which originated on either an outdoor field, sheet of ice, or dry floor such as in a gymnasium. While these sports vary in specific rules, numbers o ...

softball Softball is a game similar to baseball played with a larger ball on a smaller field. Softball is played competitively at club levels, the college level, and the professional level. The game was first created in 1887 in Chicago by George Hanc ...

paintball Paintball is a competitive team shooting sport in which players eliminate opponents from play by hitting them with spherical dye-filled gelatin capsules called paintballs that break upon impact. Paintballs are usually shot using low-energy a ...

, rodeo,

motorcross Motocross is a form of off-road motorcycle racing held on enclosed off-road circuits. The sport evolved from motorcycle trials competitions held in the United Kingdom. History Motocross first evolved in Britain from motorcycle trials competiti ...

wrestling Wrestling is a series of combat sports involving grappling-type techniques such as clinch fighting, throws and takedowns, joint locks, pins and other grappling holds. Wrestling techniques have been incorporated into martial arts, combat ...

, soccer, karate or other martial arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin. * Diet: Healthy diets (i.e. the Mediterranean diet) rich in such nutrients as omega-3 fatty acids, some antioxidants and vitamins, and low in saturated fatty acids (SFAs) and trans-fatty acids (TFAs) are inversely associated with low semen quality parameters. In terms of food groups, fish, shellfish and seafood, poultry, cereals, vegetables and fruits, and low-fat dairy products have been positively related to sperm quality. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy products, coffee, alcohol and sugar-sweetened beverages and sweets have been inversely associated with the quality of semen in some studies. The few studies relating male nutrient or food intake and fecundability also suggest that diets rich in red meat, processed meat, tea and caffeine are associated with a lower rate of fecundability. This association is only controversial in the case of alcohol. The potential biological mechanisms linking diet with sperm function and fertility are largely unknown and require further study.

Treatment

Treatments vary according to the underlying disease and the degree of the impairment of the male's fertility. Further, in an infertility situation, the fertility of the female needs to be considered. Pre-testicular conditions can often be addressed by medical means or interventions. Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for

intrauterine insemination Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatm ...

(IUI),

in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) f ...

(IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved. Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF.

Vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...

helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility. A hormone-antioxidant combination may improve sperm count and motility. Giving oral antioxidants to men in couples undergoing in vitro fertilisation for male factor or unexplained subfertility may lead to an increase in the

live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simpl ...

but overall the risk of adverse effects is unclear.

Hormonal therapy

Administration of

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...

(LH) (or

human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...

) and follicle-stimulating hormone (FSH) is very effective in the treatment of male infertility due to

hypogonadotropic hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis). Hypothalamic disorders result from a deficiency in the release of gonadotropic r ...

. Although controversial, off-label clomiphene citrate, an

antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or ...

, may also be effective by elevating

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...

levels. Though androgens are absolutely essential for spermatogenesis and therefore male fertility, exogenous testosterone therapy has been found to be ineffective in benefiting men with low sperm count. This is thought to be because very high local levels of testosterone in the testes (concentrations in the

s are 20- to 100-fold greater than circulating levels) are required to mediate spermatogenesis, and exogenous testosterone therapy (which is administered systemically) cannot achieve these required high local concentrations (at least not without extremely supraphysiological dosages). Moreover, exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

, as seen in users of androgens/ anabolic steroids (who often have partially or completely suppressed sperm production). This is because suppression of gonadotropin levels results in decreased testicular androgen production (causing diminished local concentrations in the testes) and because FSH is independently critical for spermatogenesis. In contrast to FSH, LH has little role in male fertility outside of inducing gonadal testosterone production.

Estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

, at some concentration, has been found to be essential for male fertility/spermatogenesis. However, estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels. As such, clomiphene citrate (an

) and

aromatase inhibitor Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone ex ...

s such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis. Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men, including in men with severe oligospermia.

Research

Researchers at University of Münster, Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation. If reproduced in humans, this could potentially enable infertile men to father children with their own sperm. Researchers from Montana State University developed precursors of sperm from skin cells of infertile men. Sharpe ''et al.'' comment on the success of intracytoplasmic sperm injection (ICSI) in women saying, "[t]hus, the woman carries the treatment burden for male infertility, a fairly unique scenario in medical practice. Ironically, ICSI's success has effectively diverted attention from identifying what causes male infertility and focused research onto the female, to optimize the provision of eggs and a receptive endometrium, on which ICSI's success depends."

Prevalence

Currently, there are no solid numbers on how many couples worldwide experience infertility, but the World Health Organization estimates between 60 and 80 million couples are affected. The population in different regions have varying amounts of infertility. Starting in the late 20th century, scientists have expressed concerns about the declining semen quality in men. A study was done in 1992 with men who had never experienced infertility showed that the amount of sperm in semen had declined by 1% per year since 1938. Further research a few years later also confirmed the decline in sperm count and also seminal volume. Various studies in Finland, Southern Tunisia, and Argentina also showed a decline in sperm count, motility, morphology, and seminal volume. Males from India had a 30.3% decline in sperm count, 22.9% decline in sperm motility, and a 51% decrease in morphology over a span of a decade. Doctors in India disclosed that the sperm count of a fertile Indian male had decreased by a third over a span of three decades. Some factors may include exposure to high temperatures at places such as factories. A 1 degree increase in temperature will reduce 14% of spermatogenesis. Researchers in Calcutta conducted a study between 1981 and 1985 that also showed a decrease in sperm motility and seminal volume, but no change in sperm concentration.

Society and culture

There are a variety of social stigmas that surround male infertility throughout the world. A lot of research has pointed to the relationship between infertility and emasculation. This association has led to infertility being less studied and diagnosed in men over time. In places like Egypt, Zimbabwe, and Mexico, erectile dysfunction also known as impotence, is considered a determinant of infertility. When stereotypical ideals of manhood are virility and strength, men sharing problems of infertility can face feelings of inadequacy, unworthiness, and have thoughts of suicide. In many cases, a variety of socio-economic interventions come in play to determine penile activity. For the Shona people, since impotence is linked to infertility, an examination to check on the penile function spans from infancy to post marriage. At infancy, there are daily check-ups by the mothers on the son's erection and urine quality. When the son reaches puberty, they are asked to ejaculate in river banks and for their male elders to examine sperm quality. The traditions last until post-marriage, when the family of the bride take part to check on consummation and the groom's sperm quality.

Crisis

References

External links

{{DEFAULTSORT:Male Infertility Male infertility, Fertility medicine Fertility Male genital disorders